The Theory of Endobiogeny: Volume 3: Advanced Concepts for the Treatment of Complex Clinical Conditions 0128169648, 9780128169643

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The Theory of Endobiogeny

The Theory of Endobiogeny

Volume 3: Advanced Concepts for the Treatment of Complex Clinical Conditions

Kamyar M. Hedayat Jean-Claude Lapraz

Academic Press is an imprint of Elsevier 125 London Wall, London EC2Y 5AS, United Kingdom 525 B Street, Suite 1650, San Diego, CA 92101, United States 50 Hampshire Street, 5th Floor, Cambridge, MA 02139, United States The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, United Kingdom © 2019 Elsevier Inc. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher. Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions. This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein). Notices Knowledge and best practice in this field are constantly changing. As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary. Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein. In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility. To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein. Library of Congress Cataloging-in-Publication Data A catalog record for this book is available from the Library of Congress British Library Cataloguing-in-Publication Data A catalogue record for this book is available from the British Library ISBN 978-0-12-816964-3 For information on all Academic Press publications visit our website at https://www.elsevier.com/books-and-journals

Publisher: Stacy Masucci Acquisition Editor: Rafael Teixeria Editorial Project Manager: Sandra Harron Production Project Manager: Sreejith Viswanathan Cover Designer: Matthew Limbert Typeset by SPi Global, India

Dedication This book is dedicated to our patients: fortuitous teachers whose confidence in us, and challenges to find better methods of care have served as a daily inspiration. They have nourished our research in a permanent trust and sharing which allowed the emergence of this new approach to Life that represents Endobiogeny.

Chapter 1

Allergic disorders Introduction The immune system is key to the survival of the organism. It is responsible for recognizing self vs nonself. Vigilance and defense are preferred to attack (The Theory of Endobiogeny, Volume 2, Chapter 3). When the immune system is hyperfunctioning, it is at risk of favoring attack over other roles. Allergies and autoimmune diseases are both disorders of immune hyperfunctioning. Because of the rising prevalence of these disorders around the world, understanding the underlying Endobiogenic terrain allows for the approach to therapy to be restorative and even curative, rather than merely suppressive. The immune system is engaged in a triadic relationship with the autonomic nervous system and endocrine system. The corticotropic and thyrotropic axes are most implicated. The less competent one aspect of the triad is that the greater the other branches will be in compensation. In allergic disorders, the adrenal cortex is incompetent in its response to aggression, producing more anabolic steroids related to cortisol, and creating a more permissive terrain related to an adaptive one. To compensate, the ANS, thyrotropic axis and immune system become more active, leading to hyperimmunity. Therefore, most simply, allergies are a hyperimmune response to an agent that has contacted the body. Allergies pose a particular challenge for the physician. The incidence of allergic disorders has increased considerably.1 In a 10-year period, food allergies in children increased fivefold. Skin allergies have increased 2.5-fold. The approach of preventative medicine and social work has been to reduce exposure to allergens. The assumption is that allergens are bad and must be reduced or eliminated. An allergen is like the color red. Red is neither intrinsically good nor bad. It simply is. Proteinaceous moieties simply are. They serve an intrinsic function for living systems. What makes them an allergen is not their existence but how the other reacts to it. This approach by reducing the allergen burden is wise because it reduces the further degradation of the terrain but does not offer a way to strengthen the buffering capacity nor address the ­elements of terrain. It mistakes

The Theory of Endobiogeny. https://doi.org/10.1016/B978-0-12-816964-3.00001-8 © 2019 Elsevier Inc. All rights reserved.

the aggressor for the cause of allergies, which according to the Theory of Endobiogeny is a hyperimmune terrain. The approach of biomedicine and pharmacology has been primarily to suppress the mechanisms of response to allergens and allergic symptoms. Over the last four decades, the number of oral and intravenous therapies of escalating potency and side effects has only increased, ever on the “hunt” for new approaches to suppression.2 Over this same time, the total failure to reverse or even diminish the incidence of allergic disease should serve as sufficient witness to the scientific bankruptcy of this approach except in the reversal of anaphylactic shock. According to the Theory of Endobiogeny, the precritical and critical terrain implicates mental, emotional, neurotransmitter, autonomic, endocrine, digestive, immune, and emunctory activity. The Endobiogenic approach reintegrates the allergen, allergic mechanism, allergic terrain, and external environment in order to personalize treatment to the individual.

Classification of allergic disorders Classically, allergic disorders are classified by the branch of the immune system that is most implicated in the allergic response. Recall that there are two types of immune response. The first is nonspecific or innate. The response is repetitive and general, and not specific to any particular type of allergen. The second type is specific or adaptive immunity (The Theory of Endobiogeny, Volume 2, Chapter 3). This response is highly choreographed and specific to particular allergens. There are also two forms of immune actors: cellular and humoral. Cellular elements are cells (Table 1.1). Humoral elements are protein-based products, typically released from cells, which travel through the blood (viz., humor). Allergic disorders are classified classically into four groups based on the elements of immunity involved (Table  1.2).3 This chapter will focus on type 1 allergies with a specific emphasis on eczema. Therefore, we will be discussing adaptive and humoral allergic disorders involving IgE.

1

2  The Theory of Endobiogeny

TABLE 1.1  Cellular and humoral elements of immunity Nonspecific: innate

Specific: adaptive

Cellular

Humoral

Cellular

Humoral

Neutrophils

Complement

T-lymphocytes

Immunoglobulins

B-lymphocytes

Cytokines

Natural killer Monocytes

Interleukins

Basophils Eosinophils NK lymphocytes NK, natural killer.

TABLE 1.2  Classification of immune disorders Disorder

Adaptive

Type 1 IgE mediated

Innate

Aspect

Example(s)

•

IgE from B-lymphocytes

Eczema, allergies, asthma (extrinsic), anaphylaxis, angioedema, urticaria, food and drug allergies

Type 2 IgG mediated

•

IgG from B-lymphocytes

Blood transfusion reactions, autoimmune hemolytic anemia

Type 3 Immune complex-mediated

•

Compliment-antibodyantigen complexes deposited in tissues and organs

Glomerulonephritis, rheumatoid arthritis, lupus

Type 4 Cell-mediated

•

T-lymphocytes

Infections: syphilis, TB, leprosy, viruses, parasites, contact dermatitis, autoimmune disease

•

Type 1 IgE mediated hypersensitivity: Summary of terrain The primary focus of the classical biomedical approach has been to focus exclusively on suppressing the mechanisms of allergy symptoms, histamine being the most well-known amongst them. The Endobiogenic approach establishes the proper place of histamine within the larger context of the global terrain and Endobiogenic equilibrium of each patient. 1. Cause: Hyperimmune precritical terrain 2. Agent: Allergen exposure 3. Response: Hyperimmune activity 4. Mechanism: Immune mediators (i.e., histamines, leukotrienes, etc.) 5. Effect: Allergic symptoms: pruritis, inflammation, heat, swelling, etc.

Cause: Precritical terrain: Hyperimmunity The precritical hyperimmunity terrain has three aspects: overfabrication of immune elements, spasmophilia, and permissive adrenal cortex activity. Overproduction (The Theory of Endobiogeny, Volume 2, Chapter  3) is initiated by excessive estrogens activity, due to its role in protein metabolism. The exocrine pancreas is solicited to increase the uptake of protein elements from the diet. The liver as a metabolic organic also contributes to the fabrication of immune elements (Fig. 1.1). Implicated in this fabrication is prominent parasympathetic tone and serum TSH. There is a latent hepatic insufficiency as an emunctory which plays a role in the critical terrain. The second aspect is the latent spasmophilia. There is elevated parasympathetic and alpha-sympathetic activity (The Theory of Endobiogeny, Volume 2, Chapter 11).

Allergic disorders Chapter | 1  3

Agent: Allergen exposure In most disorders, a single exposure to the agent or aggressor is sufficient to install the critical terrain. In the case of Type 1 allergies, mediated by immunoglobulin E (IgE), repeated exposure is required (Fig. 1.2).4

Response: Allergic terrain

FIG.  1.1  Endobiogenic terrain favoring overfabrication of immune elements. See text for details. (Images by PandaVector and EgudinKa/ Shutterstock.com © 2015 Systems Biology Research Group.)

The third aspect is the permissive adrenal cortex activity (The Theory of Endobiogeny, Volume 1, Chapter 6). The permissive activity of the adrenal cortex refers to the way in which its hormones create an environment favorable to actions of other hormones, physiologic and metabolic functions (Table 1.3). The more the adrenal cortex is dedicated to the production of adrenal androgens and estrogens, the greater its permissive function, and the lesser its adaptive capabilities. Based on the genetic inheritance, patients with an allergic terrain have a predominance of adrenal estrogens. The less efficient the gonads are in producing estrogens and androgens, the greater the appeal to the adrenal cortex. This tends to occur at the expense of metabolic activity dedicated to the production of glucocorticoids. These adrenal estrogens are not responsive to diminished feed-forward activity of FSH. Therefore, they serve as an unregulated source of estrogen for oversolicitation of proteins in the production of immune elements.

TABLE 1.3  Permissive activity of adrenal cortex Function Adrenal metabolic

Cellular nutrition

Comment Androgens

Favors production of adrenal androgens

Estrogens

Favors production of adrenal estrogens

Active membrane permeability

Favors the dynamic flux of nutrients into the cell for structural purposes relative to functional ones

Active intracellular osmolar gradient

Favors the dynamic flux of electrolytes and water into the cell for structural purposes relative to functional ones

Upon reexposure to an allergen, the organism, as noted above, engages in a nearly immediate response. The role of the neuroendocrine system is to manage this response. A response must be made, histamines must be expressed to allow immune cells (monocytes, neutrophils, etc.) to migrate from their hematogenous circuit of surveillance to the localized area of aggression. The problem is not that there is a response or that histamine is released. It is the quantity, quality, chronology and duration of the response that is responsible for the allergic disorder. The factors implicated, in order of importance, are Alpha, Corticotropic, Thyrotropic, Gonadotropic, and Somatotropic axes. Recall the general relationship of the catabolic axes to histamine and other mediators of inflammation (Table 1.4)

ANS Part of the spasmophilic nature of allergies is that the alphasympathetic activity is prolonged and the beta is delayed or insufficient. The intensity of the alpha has a number of direct effects: 1. Increased ACTH → increased histamine receptors 2. Increased TRH → increased histamine release 3. Increased histamine as an autacoid for Alpha Congestion of emunctories is another expression of the spasmophilia.

Corticotropic There is a hyperfunctioning ACTH (Fig. 1.3) for at least two reasons: hyperfunctioning Alpha, and insufficiency of the adrenal cortex response. The three results of this are: 1. Eosinophilia and basophilia, both of which play a role in the release of inflammatory mediators. It is compensatory for the insufficiency of cortisol response to the aggression and reflective of the intensity of the ACTH response.5, 6 Fundamentally, the role of the eosinophils are as an indirect method of adaptation and congestion when the adrenal cortical response is not sufficiently adapted to the needs of the organism. 2. T-lymphocyte maturation7, 8 (which adapts production of IgE) 3. Upregulation of histamine receptors on mast cells and other immune cells. The logic of this is that histamines stimulate ACTH.9 Histamines are in turn regulated by endorphins, which they directly stimulate and cortisol is relaunched by ACTH.10

4  The Theory of Endobiogeny

FIG.  1.2  Sensitization to allergens and manifestation of allergies. (A) Primary sensitization involves local macrophages (dendritic cell), which forms an epitope with a native T cell. Memory T-cells are formed and B cells activated to develop IgE receptors. (B) Shows that in the initial exposure, there is a rise in the number of IgE and T cells. Because IgE has not been released to circulating, symptoms are latent. On second exposure ((A) lower half), there is a proliferation of memory T-cells. Based on the balance of T regulatory cells to other lymphocytes, the response can be regulated or amplified ((B) middle and lower graphs). With subsequent exposure (C) in susceptible individuals, an immediate, then late phase reaction can develop. There is an IgE mediated response, with degranulation of mast cells and activation of basophils. Antigen presenting cells (APC’s) stimulate non-IgE dependent mechanisms of response including pro-inflammatory and immune activating interleukins and eosinophils. Various sites can be the scene of allergic manifestation (lower right corner). MHC, major histocompatibility complex; SIgA, secretory mucosal immunoglobulin A; T-reg, T-lymphocyte regulator cell; TCR, T-lymphocyte cell receptor. (Reproduced from Valenta R, Hochwallner H, Linhart B, Pahr S. Food allergies: the basics. Gastroenterology 2015;148(6):1120-1131 e1124. https://doi.org/10.1053/j. gastro.2015.02.006.)

TABLE 1.4  ANS-endocrine mediators of histamine activity Origin

Factor

↑ Demand

↑ Receptors

↑ Release

↓ Activity

Brain stem: ANS

αΣ

•

Pituitary: corticotropic

ACTH

Hypothalamus: thyrotropic

TRH

Peripheral: corticotropic

Cortisol

•

Variable: corticotropic

Endorphins

•

• •

Allergic disorders Chapter | 1  5

Thyrotropic TRH, stimulated by alpha (Fig. 1.3), augments the general rate of function of immune activity and impacts the mechanisms of allergies as follows: 1. Histamine release by immune cells (primed by ACTH) 2. TSH relaunching → T-lymphocyte release from thymus → IgE production 3. TRH mediated T4 → T3 conversion with heightened oxidative burst and inflammation

Gonadotropic Gonadotropic activity tends to be hyperfunctioning both at the central and peripheral levels within the follicular line of activity. FSH can be oversolicited from ACTH or TRH or both. The results of this hyper-FSH are:

1. Horizontal TSH relaunching → Lymphocyte excretion 2. Vertical estrogen relaunching → further hyperfabrication of immune elements 3. Congestion of mucosal lining → prolonged local inflammation and hyperpara response The further increase of estrogens has four effects: 1. Amplification of the hyperfabrication of additional immune productions 2. Thyroid relaunching11 3. Growth hormone (GH) relaunching12, 13 4. Extravasation of immune cells into tissues14

Somatotropic Once again both central and peripheral somatotropic hormones are implicated in allergic responses, especially when they evolve into a chronic state. The details of this will be

aS

TRH

ACTH

Histamine Re le

as

Cortisol

e

Histamine receptors

Ma

tura

tion

TSH

Interleukins Thymus gland

T3

Inflammation Eosinophil

Basophil

Extravasation

Oxidative burst

lgE

VL

VH

lgE

VL

CH1

VH

lgE

VL

CH1

Lympho T cell Lymphocyte T cell Lymphocyte T cell

VH

CH1

CL CH3 CH2

CH4 CH3 CH4 CH3

Lymphocyte

CH4

B cell

FIG. 1.3  Alpha stimulates ACTH and TRH. There is an insufficient cortisol response to ACTH. As ACTH continues its stimulation to readapt cortisol to the Endobiogenic requirements of the organism, it upregulates histamine receptors in anticipation of TRH’s actions. It mobilizes eosinophils and basophils to act in the time with insufficient cortisol. Finally, it stimulates the release of T-lymphocytes from the thymus. TRH stimulates the release of histamines, which prolong the time of alpha and play an important role in allergy symptoms. It also stimulates TSH, which in the long term stimulates the maturation of T-lymphocytes released by the thymus. TRH stimulates the conversion of T4 to T3, which increases the rate of oxidative burst, participating in the general inflammatory milieu. The release of interleukins, from T-cells, from Alpha, etc. creates an inflammatory environment that allows for the extravasation of T-cells. T-cells stimulate B cells that release IgE, which further stimulates basophils and other inflammatory mediators. (© 2015 Systems Biology Research Group.)

6  The Theory of Endobiogeny

discussed later. GH, insulin resistance, and hyperinsulinism are capital with respect to inflammation and restoration of tissue. Prolactin can play the following roles: 1. ACTH relaunching → increased histamine receptors and increased lymphocyte maturation 2. Insulin excretion, inflammation, and extravasation of immune cells15, 16 3. Sensibilization to estrogens

Emunctory Liver congestion as an emunctory: In the precritical terrain, liver is oversolicited as a metabolic organ and in a latent state of congestion as an emunctory.

Whenever possible, especially with children, determining the precise allergens is the easiest on the family dynamics and child’s compliance with a restrictive diet.

Nosology of type 1 allergic disorders by location Allergic disorders can be typed by their localization. This is a 19th-century nosologic system that persists and perpetuates the illusion that these disorders and their treatments are unrelated.

Airway 1. Allergic rhinitis 2. Asthma

Common allergens Any substance potentially can become an allergen. However, when you hear the sound of hoof beats, think of horses, not zebras. The more common allergens are listed below.

Gastrointestinal 1. Eosinophilic esophagitis 2. Food allergies

Airborne If it is not practical or when it is too costly to determine the precise environmental allergens, avoid what is commonly responsible for allergies. Avoidance implies efforts to meticulously clean not only the house of the patient but also sheets and stuffed animals, evaluating hidden and open leaks in bathrooms, basements, etc.

TABLE 1.5  BoF values of the general atopic terrain Axis

Index

Value/comment

Corticotropic

ACTH

↑

1. Dust mites 2. Pets (dander) 3. Pollen 4. Molds 5. Roaches

Adaptation

↑

Cortisol

↓/normal

Adrenal cortex

↑/normal

Cortisol/adrenal cortexa

1

FSH: E2 > 1

Pit. + thyroid

GH > ACTH

•

•

Buttocks

•

•

Back

•

•

Flexural folds

•

Flexor surfaces

•

Extensor surfaces

•

Trunk

•

Peri-articular

•

Distal extrem.

•

a

Beta: beta insufficiency without prejudice to quantitative value. Pit.: Pituitary. ACTH, adrenocorticotropin hormone; E2, estrogens; Extrem., extremity; FSH, follicle simulating hormone; GH, growth hormone.

TABLE 1.10  Logic of the topological evolution of eczema Age

Mobility

Location

Endocrine adaptative role

2–6 months

Stationary Sitting

Face and scalp

Alpha > Beta ↑ ACTH for adrenal cortex relaunching

6–12 months

Crawling

Extensor surfaces

FSH > ACTH by vertical stimulation as ACTH continues to attempt to relaunch the adrenal cortex

Trunk

FSH > estrogens

Flexor folds: antecubital, popliteal

Alpha + Para: to relaunch metabolism, relaunch catabolic activity for movement

Flexor surfaces

ACTH: cortico-thyrotropic harmonization for gross motor activity with ambulation

Peri-articular: wrists, ankles

General pituitary over solicitation with peripheral thyroid > adrenal cortex or estrogen response with hypermetabolism focused on the joints, which are active with increased gross motor movements

Distal extremities: hands, feet

GH > ACTH due to lifestyle and excessive eating, alpha relaunching for somato-corticotropic harmonization

≥1 year

Adults

Ambulatory

10  The Theory of Endobiogeny

Physical exam: Neuroendocrine topology of allergic reactions According to the Theory of Endobiogeny, because of the role of the endocrine system in morphology and tissue development, the relative predominance of various ANS and endocrine responses to the allergen will localize the allergic response with respect to the exterior of the organism. Topical allergic disorders, such as eczema and hives, offer a direct ability to determine the neuroendocrine influence on the specific localization of lesions (Table 1.9).

Phase 3: Oozing There is a hyper ANS activity with conflicting para and alpha during the attempt to regulate wound healing after phase 2. There is central hyperfunctioning of the somatotropic axis with GH > PL. This period favors the risk of superinfections.

Phase 4: Desquamation

The eczematous lesions have four possible phases of evolution of their pathophysiology beyond excess deposition of keratin (Table 1.11). The advancement depends on the evolution of the Endobiogenic response to eczema. The common ANS preponderance is a hyperalpha in response to hyperpara. The common emunctory congestion is ­hepatobiliary (primary), intestines (secondary), and skin (tertiary)

Eczema concludes its evolution, either by restitutio ad integrum or transition to chronicity with lichenification. If the insulin response is well-calibrated in quantity, quality, and chronology, the skin will heal. If GH > insulin, lichenification will result. In all cases of eczema, ACTH is the primary factor of terrain implicated in the critical terrain. Alpha sympathetic is second as a factor solicited to prolong and calibrate the activity of ACTH. Hyperpara follows the alpha response. With respect to emunctories, the hepatobiliary unit is the primary emunctory evolved, followed by the intestines and then the skin.

Phase 1: Pruritic erythema

Biology of functions of eczema

A hyperfunctioning alpha induces a histamine response and pruritis. The specific area is determined by the factors noted above. The pruritis will continue to be present during the evolution.

The general observations of the allergic terrain are the same as noted earlier. As we have characterized the evolution of the autonomic nervous system and somatotropic system in the four phases of eczema, the specific indices will once again vary, by phase and by age. Table 1.12 mentions specific changes in the somatotropic terrain most commonly associated with phase 1 eczema, the most common variety seen in general practice.

Evolution

Phase 2: Vesicular The vesicular lesions (vesicle or bullae) form under the influence of a hyper GH and hyper insulin environment. If thyroid activity is also hyperfunctioning, a cyst can form.

TABLE 1.11  Terrain of the phases of eczema

+, Proportionality or degree of hyper functioning; ++, very hyper functioning; 1°, primary; 2°, secondary; 3°, tertiary; GH, growth hormone.

Allergic disorders Chapter | 1  11

TABLE 1.12  BoF values in the somatotropic axis in phase 1 eczema Index

Value/comment

Pro-amyloid

↑

GH growth score

↑

Insulin

↓ for age

Somatostatin

↑/normal

Redox

↓

Fibrosis

↑/normal

o­ften short-term relief. The second is to use medicinal plants with antihistaminic and antiallergic properties, internally, or externally.

Antipruritic An antipruritic neutralizes expressed histamine and other immune mediators. It is the most downstream approach of what is discussed here. A poultice applied to the skin is quite efficient and effective as an antipruritic. Clay functions as both an absorbent and adsorbent. Sodium bicarbonate (baking soda) is an alkalizing agent that neutralizes histamines. Any cooling or astringent plant can also be used when preparing a poultice for the skin (cf. Viola tricolor below). ●

Treatment: Symptomatic The treatment of pruritis serves two purposes. First, it offers relief to the patient. Second, it reduces the risk of aggravation of the disorder such as superinfections and chronic evolution of the disease.

Pharmaceutical Antihistamines offer rapid relief from pruritis, especially when associated with insomnia. The acute use of antihistaminics should not be forgone, especially in children, those with an increased risk of superinfections or those who suffer from mental or emotional disturbance from their pruritis. The Endobiogenic approach is to use them at the lowest dose possible for the shortest period of time while the Endobiogenic terrain is being corrected. 1. Nonsedating: best choice when pruritis-induced insomnia is not an issue a. Cetirizine b. Loratadine 2. Sedating (least to most sedating) a. Chlorpheniramine b. Diphenhydramine c. Promethazine d. Hydroxyzine: Helpful short-term for insomnia secondary to pruritis, especially in patients with a comorbidity of anxiety 3. Broad acting agents with antihistaminic properties a. Cyproheptadine: reserve for short duration at low doses for patients with advanced psychological disturbances related to pruritis and/or insomnia or with comorbidities such as anxiety, abdominal migraines, etc. Risk of side effects is elevated.

Nonpharmaceutical There are two Endobiogenic approaches to symptomatic treatment. The first is antipruritic. This offers rapid but

●

●

Clay, 1 tbsp or Baking soda 1 tsp. or both Optional, Essential oils (1–2 drops total): ● Lavandula officinalis (Lavender) Antihistaminic ● Anthemis nobilis (Roman chamomile) Avoid if patient has ragweed (Ambrosia ssp.) allergy ● Matricaria recutita (German chamomile) Carrier fluid (choose 1), 1 tbsp ● Water ● Hydrolat: Rose (all ages) or peppermint (3 and older, for the intense feeling of heat) ● Chamomile tea (cooled)

Instructions 1. Mix dry ingredients 2. Add essential oil(s) if desired and mix well 3. Add carrier fluid and mix into a smooth paste 4. Apply to affected area. a. If the area is too sensitive to apply paste, apply the paste to cheesecloth and lightly apply to the affected area. In this case, add more fluid to soak the cloth.

Antihistaminics, antiallergics Antihistaminics prevent further expression of histamine by stabilizing mast cells (Table 1.13). They are midstream agents. Antiallergics function by various upstream neuroendocrine and some downstream neutralizing effects of mechanisms of allergies (Table 1.14). Some common medicinal plants have dual action (Table  1.15). The most efficient plants are Lavandula angustifolia, Agrimonia eupatoria, and Viola tricolor.18, 19

Etiologic treatment of eczema: Restoring adaptability to the global terrain Restoring adaptability to the global terrain has three general aspects: autonomic, endocrine, and drainage of inflammatory products. The general goals are summarized below, then matched to treatments in Table 1.16.18, 19

12  The Theory of Endobiogeny

TABLE 1.13  Antihistaminic medicinal plants Indication/ comment

Medicinal plant

Galenical

Arnica montana

BH, MT

Alpha > para and/ or low insulin resistance

Artemisia dracunculus

EO, BH

Mental spasmophilia: anxiety, depression, etc.

Hamamelis virginiana

BH, DE, MT

Constipation, pelvic congestion

Eucalyptus globulus

EO

Asthma comorbidity

Matricaria recutita

BH, EO, DE, MT

Anger exacerbates eczema, strong inflammatory component Safe on open wounds

BH, bulk herb; DE, dry extract; EO, essential oil; MT, mother tincture.

1. Autonomic: Relieve spasmophilia a. Para-Alpha: Reduce global hyperfunctioning b. Beta: Restore chronologic integration 2. Endocrine: Support Somato-Corticotropic integration a. First loop: i. Adrenal cortex response to adaptation demands

ii. Somatotropic installation of insulin resistance b. First-to-Second loop i. Somatotropic relaunching of second loop corticotropic activity for the second peak of cortisol > DHEA 3. Drainage: Hepatobiliary-Intestinal drainage a. Reestablish primary drainage mechanisms b. Relieve congestion of the skin as an emunctory

Etiologic treatment of the local terrain: Drainage and skin healing Drainage Drainage of the skin and regulation of local expressions of histamine activity are important intermediate steps in reducing symptoms and reversing the degradation of the terrain. They need to be used along with a treatment of the global factors of terrain discussed above. Both Burdock and Wild Pansy offer local and global drainage support, making them highly efficient and effective in all stages of eczema. NB: aggressive or rapid skin drainage can aggravate eczema if hepatobiliary-intestinal drainage has not been instituted at a prior time or simultaneously with regulated skin drainage. Arctium lappa (Burdock)18–20 Galenic: MT, DE, BH Summary: A polyvalent drainer and depurative ideal for immunodermatologic disorders.

TABLE 1.14  Antiallergic medicinal plants Medicinal plant

Galenical

Indication/comment

Arctium lappa

BH, MT

Polyvalent pancreatic-skin drainer, advanced inflammatory state

Borago officinalis

BH, MT

Regulation of edema and estrogenism

Cichorium intybus

BH, HL

Dysbiosis prominent in immune dysregulation

Citrus limon

EO

Congestion around wound

Cnicus benedictus

BH, MT

Difficulty initiating liver drainage, secondary fungal infection

Glycyrrhiza glabra

BH, MT

Asthma comorbidity Food allergy comorbidity Intestinal permeability

Ribes nigrum

GM

Adrenal insufficiency, tissue drainage required

Rosmarinus officinalis

BH, DE, EO, GM

Adrenal insufficiency, delayed wound healing

Rubus idaeus

GM

Asthma comorbidity and menstrual cycle dysregulation

Sambucus nigra

MT, leaf

Brain fog, viral implication

Taraxacum officinale

BH, DE, MT

Auto-toxicity, low insulin resistance, elevated CRH, strong hepatic implication

Urtica dioica

BH, DE, MT, Leaf

Skin drainage where hyperglycemia and elevated insulin resistance play an important role

BH, bulk herb; DE, dry extract; EO, essential oil; GM, gemmomacerate; HL, hydrolat; MT, mother tincture.

Allergic disorders Chapter | 1  13

TABLE 1.15  Dual antihistaminic, antiallergic plants Medicinal plant

Galenical

Indication/comment

Agrimonia eupatoria

BH, MT

Indirect antiallergic through drainage of pancreas

Fagus sylvatica

GM

Hypogammaglobulinemia

Fumaria officinalis

BH, HL

Strong implication of biliary congestion

Inula helenium

BH, MT

Asthma comorbidity Recurrent ENT infections Peripheral cortico-gonadotropic insufficiency

Lavandula angustifolia

BH, DE, EO, MT

Prominent spasmophilia, anxiety

Plantago major

BH, MT

Hepato-pancreatic implication Asthma comorbidity

Syzygium aromaticum

EO

Recidivistic infections; avoid in open wounds

Viola tricolor

BH, MT

Indirect antiallergic through drainage of pancreas hyperhistaminemia and multiemunctory congestion

BH, bulk herb; DE, dry extract; EO, essential oil; GM, gemmomacerate; MT, mother tincture.

TABLE 1.16  Summary of treatment of global terrain of eczema Category

Goal

Medicinal plant

Autonomic

↓ Para-alpha

Lavandula angustifolia (lavender) EO, BH, HL, MT Anthemis nobilis (Roman chamomile) EO, BH, HL, MT Matricaria recutita (German chamomile) EO, MS, BH, HL, MT

↑ Beta

Cinnamomum zeylanicum (cinnamon) EO, BH, HL Citrus paradisi (grapefruit) EO Crataegus oxyacantha (hawthorne): MT, GM, DE

↑ Cortisol

Ribes nigrum (cassis) GM, MT, Fruit Abies pectinata (balsam fir) GM Quercus pedunculata (oak) GM Thymus vulgaris (thyme) EO, BH Satureja ssp. (savory) EO, BH

↓ Aroma-tization

Achillea millefolium (yarrow) EO, BH, MT

Regulate GH-PL

GH low, cortisol low: Lamium album (white deadnettle) MT, BH GH elevated, cortisol low: Fragaria vesca (strawberry leaf) MT, BH

↓ Insulin resistance

Arctium lappa (burdock): MT, BH Agrimonia eupatoria (agrimony): MT, BH Juglans regia (walnut): MT, GM

Hepatobiliary

Arctium lappa (burdock): MT, BH Agrimonia eupatoria (agrimony): MT, BH

Intestinal

Viola tricolor (wild pansy): MT, BH Agrimonia eupatoria (agrimony): MT, BH Lamium album (white deadnettle) MT, BH

Corticotropic

Somatotropic

Drainage

BH, bulk herb; DE, dry extract; EO, essential oil; GM, gemmomacerate; HL, hydrolat; MT, mother tincture.

14  The Theory of Endobiogeny

Actions: Immune: immunomodulating (reduces TNFα, increases macrophage activity), antiallergic (leukotriene inhibitor), regulates abscess formation and regulation, helps eliminate pus. ID: antiinfectious (cutaneous and urinary): antibacterial (staphylococcus, streptococcus, gonococcus, and pneumococcus) antifungal: candida. Derm: cutaneous drainer. Onc: antitumoral. GI: choleretic, pancreatic stimulant (exocrine and endocrine) prebiotic (inulin), ­hepato-protectant, mild laxative through choleretic activity. Metabolic: antihyperglycemic, normalize blood sugar by increases hepatic storage of glycogen. Renal: diuretic (volumetric and azoturic). Use: All disorders requiring hepatopancreatic, renal, and/or cutaneous drainage, pulmonary disorders; DERM: wet, oozing eczema, psoriasis, cutaneous infections, cystitis, diabetics with cutaneous manifestations, and cradle cap. Method: Decoction of root: 2–3 g, minced, in 5 oz water: boil for 1 h, filter, and drink TID; Poultice: Infuse 20 g leaves in 8 oz water 15 min. Note: synergistic with hypoglycemants and diuretics can augment the activity of vagolytics such as Thyme. Viola tricolor (Wild pansy)18, 19, 21–25 Galenic: MT, BH Summary: The most broad-acting antiallergic, antiatopic plant. Actions: Immune: antiinflammatory (salicylates), skin, bronchopulmonary, genitourinary. Drainage: general depurative, Skin: #1 cutaneous drainer; hepatic drainer, intestines, Kidneys: volumetric diuretic. Dermatologic: keratolytic, cicatrisant. Infectious: antiinfectious. Pulm: antiinflammatory, expectorant. CV: veinotrope, anticoagulant, inhibits platelet aggregation. GI: mild laxative (mucilage). Use: inflammatory and infected dermatoses: eczema, psoriasis, urticaria, acne; varicose ulcers, venous insufficiency with pruritis of lower extremities; allergic asthma; Method: Tisane or Compress: Infuse 1 tsp. in 8 oz water 10 min, drink TID before meals or apply to affected area;

Wound healing: Oligoelements 1. Manganese (Mn) series: a. Manganese (Mn): i. Primary support for healing of the connective tissue (i.e., the dermis) ii. Clearing toxic material including microbial fragments b. Manganese-copper (Mn-Cu): When superinfections persist due to poor oxidation (evaluate oxidation and oxidoreduction indices in BoF) c. Manganese-copper-cobalt (Mn-Cu-Co): i. Chronic, degenerative eczema ii. Strong emotional disturbance or stress related to aggravation of disease

2. Sulfur (S): use for poor quality of skin repair. Cf. Asthma: Nutrition for a discussion 3. Zinc (Zn): use with recurrent skin superinfections

Alimentation Dietary interventions should start with the elimination of known or common food and environmental allergens, followed by a high fiber diet with bitter and sour foods to help drain the intestines and liver, respectively. Cruciferous vegetables (rich in sulfur—cf. Chapter  2) and foods rich in magnesium (cf. The Theory of Endobiogeny, Volume 2, Chapter 11) and those that support the liver (i.e., beets) are encouraged.

Conclusions Allergic disorders are hyperimmune disorders arising from a spasmophilia with overfabrication and overmobilization of immune elements relative to the downregulation of immune activity. This chapter addresses type 1 allergic disorders, which are IgE mediated with a particular emphasis on eczema. These disorders require an initial exposure to an allergen, which primes the system followed by a subsequent exposure, which initiates the hyperimmune response and inflammation. The general approach to treatment involves both reduction of exposure to known allergens and regulation of the terrain. The latter involves resolving ANS spasmophilia, supporting peripheral catabolic activity, reducing anabolic activity, and instituting appropriate drainage of the liver, gallbladder, intestines, and skin.

Case study #1: Chronic, recurrent worsening eczema in a child Chief complaint A 4-month-old infant was brought to the clinic with a complaint of itchy rash and constipation. The patient typically has 6–8 soft stools per day. Every 10–12 days, he will not stool for 2–3 days. The infant is exclusively breastfed and the mother is on a restrictive diet, avoiding dairy products and gluten-containing grains (Table 1.17).

Past medical history He was a product of natural spontaneous conception and delivered by assisted home birth with prolonged labor. The mother reported feeling traumatized emotionally by the difficulty of the labor. The infant has mild jaundice that resolved by the third day of life without phototherapy. The infant had a poor latch for breastfeeding and underwent frenectomy for sublingual ankyloglossia (Table 1.17).

Allergic disorders Chapter | 1  15

TABLE 1.17  Interpretation of history and examination Sign/symptom

ANS

Prolonged labor

↑ Alpha

Endocrine

Neonatal jaundice

Hepatobiliary insufficiency

Early feeding trouble

↑ Alpha (response)

Constipation

↑ Alpha > ↑ para

Eczema: general

↑ Alpha > beta

Eczema: pruritis

↑ Para ↑ Histamine

Physical examination It confirmed pruritic eczematous lesions on the cheeks with scratch marks in the area. The skin is intact with no signs of pus or infection (Table 1.17).

Treatment The patient was started on a topical treatment and given a decoction of Arctium lappa (Burdock). Topical solution, applied 4 times daily to cheeks: ● ● ●

● ●

●

Hepato-biliary-intestinal congestion Skin congestion ↑ ACTH > cortisol response

TABLE 1.18  Relationship of treatment to the signs, symptoms, and terrain Sign/symptom

ANS

Treatment

Constipation

↑ Alpha > ↑ para

Matricaria recutita

Eczema: general

↑ Alpha > beta

Matricaria recutita

Eczema: pruritis

↑ Para ↑ Histamine

Agrimonia eupatoria Arctium lappa Lavandula angustifolia (Topical) Baking soda

Baking soda 1 tbsp Lavandula officinalis (Lavender) EO 1 drop Eczema tisane (cf. below) 2 tbsp Internal: A tisane was made of the following:

●

Emunctory

Equal parts Arctium lappa (Burdock), Agrimonia eupatoria (Agrimony), and Matricaria recutita (German chamomile) ½ tsp. was steeped for 6 min in 200 mL of water, then cooled 4 times per day in between nursing ● The boy received 15 mL (1 tbsp) by a bottle with a nipple. The remainder was refrigerated for 48 h. Whatever was not consumed by that time was discarded and a fresh tisane made every second day.

Eczema resolved in 14 days. The patient continued the treatment for 3 months in total then discontinued it. The following table places the medicinal plants at the level of each symptom or sign (Table 1.18). The boy was presented again at 3-years for further treatment of chronic, intermittent eczema. From 4 months on he was maintained on a restrictive diet (Weston Price—cf. end of the chapter for details), fermented cod liver oil, exocrine pancreatic support, and Rosa canina (Dog rose) bud gemmotherapy DH1; despite this, eczema presented with greater severity with each recurrence. The patient was then started on a tincture of Avena sativa MT, Rosa canina GM D1, Ribes nigrum GM D1

Hepato-biliaryintestinal congestion Skin congestion

Matricaria recutita Agrimonia eupatoria Arctium lappa

at a dose of 1.5 mL twice per day. He was continued on exocrine pancreatic support, fermented cod liver oil, and the Weston Price diet. Eczema resolved within 6 months. The Avena sativa offered two key actions. The first was ­regulation of the gonado-thyrotropic relationship, critical for the precritical terrain. The second was exocrine pancreatic substitutive support, allowing for downregulation of the gonado-­thyrotropic solicitation of the organ. The Ribes nigrum offered a more general corticotropic support, general drainage, and correction of the allergic terrain.

Case study #2: Chronic, recurrent eczema with biology of functions The patient was presented at 10.5 years of age with a history of precocious puberty, moodiness with dark, brooding thoughts and irritability, and difficulty concentrating. All

16  The Theory of Endobiogeny

symptoms were worse when she consumed gluten and/or sweets. Past medical history was significant for eczema as a child. She had been asymptomatic for over 6 years. She was treated solely based on history and physical examination (Table 1.19). Within 6 months of treatment (Table 1.20) (including avoidance of aggravating foods), her temperament was bright and happy. Her concentration had improved and she was sleeping better and waking with more energy. On her 11th birthday, she had a BoF performed. The indexes of the corticotropic axis can be divided into structural and functional values (Table  1.21). The function values represent the global adaptive response to aggression. Here, we see the Adaptation index is elevated, indicating that in the adaptation response, ACTH is more predominant relative to FSH because the peripheral response is less efficient within the corticotropic axis in relationship to the gonadotropic (The Theory of Endobiogeny, Volume 1, Chapter 15). Cortisol activity is insufficient, as is the global adrenal cortex response,

with a Cortisol/Adrenal cortex ratio of 0.33. This indicates that the absolute output of both is low and that the relative ratio is also low, relatively favoring adrenal anabolic activity. The relationship imposes two outcomes. The first is a relative predominance of anabolism related to catabolism (Catabolism/ Anabolism index, low). The second is an extremely elevated expression of histamines. The elevated interleukin-1 index serves as a proxy for the general rate of function of the immune system. The index, 31 times above the upper limit of the normal range is indicative of hyperimmunity. The net allergic tendency was elevated (allergy index). Once the risk was adjusted for the role of the exocrine pancreas (cf. Table 1.24) one sees the true expressed allergic tendency (Allergy index adjusted). The structure values represent the structuro-functional activity of the organism that results in the formation of eczematous plaques. The relative predominance of anabolism in relationship to catabolism (catabolism/anabolism index, low) is once again repeated to evaluate the imposition of

TABLE 1.19  Physical exam findings and their correlation with the terrain Region

Finding

Terrain

Head, ears, nose, throat

Lips full

Pancreatic congestion

Lips dry with vertical lines

Dehydration, elevated alpha and angiotensin

Lips red

Mitochondrial insufficiency

Low hairline

Adrenal androgens

Cheeks red

Elevated beta bursting

Tongue: tip erythematous

Small bowel inflammation

Unremarkable: tonsils, sublingual veins Chest

Breasts: Tanner stage 3

Precocious puberty with increased estrogens, growth factors, insulin

Extremities

Hands warm and sweaty

Elevated beta, parasympathetic

Dark hair on lower legs

Adrenal androgens

Dermatographism: 2 s blanching, then prolonged and deep erythematous response Abdomen

Neurologic

Doughy, dense tissue

Hyperinsulinism

Liver: tender on palpation, superior-medial

Hepatic vascular congestion

Liver: tender on palpation, inferior-lateral

Hepatic metabolic congestion

Pancreas: tender above umbilicus

General pancreatic congestion

Pancreas: tender right of umbilicus

Exocrine pancreatic oversolicitation

Pancreas: tender left of umbilicus

Endocrine pancreatic oversolicitation

Colon: all points tender

Hypothalamic-pituitary oversolicitation

Glabella tap: brisk, upper and lower, no flutter

Elevated alpha and dopamine

Clonus, L > R, 3–4 beat

General peripheral neurologic incoherence from elevated TRH

Allergic disorders Chapter | 1  17

TABLE 1.20  Empirical treatment and its effects by axis and actions on the terrain Treatment

Ingredients

Axes

Actions

Atomidine

Trichloro-iodine

Thyrotropic

Improves efficiency of production and action of thyroid hormones

Vitamin D 1000 IU/ drops: 5 drops qAM

Vitamin D

Thyrotropic

Regulates duration of thyrotropic participation in adaptation, regulates immunity

Pituitary blend #1: 3 mL BID with meals

Rhodiola rosea

Adaptogenic

Regulates responsiveness of corticotropic axis in adaptation, regulates pituitary and immune function

Inula helenium

Pituitary

Regulates pituitary efficiency in stimulation of peripheral endocrine glands, antiallergic, antihistaminic

Ribes nigrum GM

Corticotropic Immunity

Supports peripheral corticotropic function, immunity, antiallergic

Quercus pedunculata GM

Corticotropic Pituitary

Supports peripheral corticotropic function, Endocrine redistributor

Melissa officinalis MT

Central nervous system thyrotropic digestion

Regulates thyrotropic, neurologic function and digestion

Vaccinium myrtillus MT

Somatotropic

Regulates peripheral insulin sensitivity, circulation

Arctium lappa MT

Drainage

Skin, hepatobiliary, pancreas, depurative, blood purifier, pancreatic stimulant, immune modifier, antiallergic

Digestion blend #1: 3 mL BID with meals

BID, twice per day; GM, gemmomacerate; MT, mother tincture; qAM, every morning.

TABLE 1.21  Indexes of the corticotropic axis at pretreatment

a Not an index but a ratio of two indexes. (F), function value; (S), structure value. High low values presented in red/blue respectively.

a metabolic program at the structuro-functional level. The ACTH index is evaluating the general organometabolic activity of the pituitary tropin on the adrenal cortex. By extension, it is evaluating the relative predominance of DHEA in relation to that of cortisol. By extension it is evaluating the role of ACTH in preparing the cell for metabolism through hydroelectric fluctuations that precede aldosterone and the implications of what aldosterone shall bring. Thus, in eczema, we evaluate the ACTH index in structure. The adaption-permissivity is presented in structure, again, related to the adaptive activity of the adrenal cortex in relation to its permissive in structuro-functional adaptation. It is ­quantitatively elevated, slightly favoring adaptation, but negative. The negative sign indicates that the actual achievement is not occurring as anticipated by the absolute value. The permissive actions of the adrenal cortex predominate, distorting the orderly process of anabolism, participating in the irregular, disorderly arrangement of the proteinaceous plaques in eczema. Finally, the rate of aromatization of adrenal androgens to adrenal estrogens is elevated, indicating there is a source of estrogens to drive hyperimmunity and plaque formation on the skin that is not regulated by FSH. The genito-thyroid index was quite low, typical in atopic disease, and indicative of a lymphocytic predominance. The gonado-thyrotropic index was quite elevated. It indicates that the solicitation of the thyrotropic axis by e­ strogens is

18  The Theory of Endobiogeny

r­esponsible for dysfunctional structuro-functional adaptation. Serum TSH was elevated. Serum TSH was quite elevated. Regardless of the free levels of T4 and T3 (not measured), the functional effects of peripheral thyroid hormones were in the upper limits of the normal. Thus, the patient was not effectively hypothyroid, but had a latent hypothyroid, as concluded by the low genito-thyroid and thyroid yield. The importance of the TSH is that it created profound imbalances within the somatotropic axis (Table 1.22). In the gonadotropic axis, we mention three indexes (Table  1.23). The FSH index is elevated, which indicates a congesting role of mucosal tissue. This is occurring because the organotissular estrogen yield is low. The conclusion is that relative to the intensity and duration of FSH activity, the ­organotissular activity of estrogens is insufficient. The tissular endocrinometabolic activity of estrogens is also insufficient (corrected estrogen index). It is now clear why the adrenal cortex has become the second gonad in producing estrogens. Finally, in the somatotropic axis, one notes two key groups of findings. The first group is factors related to overproduction and growth related to the adaptation response. These indexes are listed in their function values. First amongst them is the role of the pancreas, noted by the elevated somatotropic index (cf. The Theory of Endobiogeny, Volume 2, Chapter 8). It indicates that the exocrine pancreas is oversolicited and somatostatin has not been successful in ending this process (Table  1.24), nor has cortisol in suppressing it (Table  1.21), in this case.1 Insulin resistance

TABLE 1.22  Indexes of the thyrotropic axis at pretreatment

a Not an index. (F), function value. High low values presented in red/blue respectively.

TABLE 1.23  Indexes of the gonadotropic axis at pretreatment

(F), function value; (S), structure value. High low values presented in red/blue respectively.

TABLE 1.24  Indexes of the somatotropic axis at pretreatment

(F), function value; (S), structure value. High low values presented in red/blue respectively.

is also elevated, favoring hyperglycemia that exacerbates overgrowth of structures. The third is the growth hormone (GH) growth score, which is elevated, even adjusted for age. The second is cellular metabolism, whose values are presented in structure to evaluate their role in the production of the eczematous lesions. They are also elevated in function (not shown), which relate to the production of immune factors. First amongst them is the rate of metabolism. We reproduce the relative anabolic predominance (Catabolism/Anabolism index) noted in Table 1.21. The rate of metabolism is also elevated, concluding that the organism is in an absolutely hypermetabolic, hyperanabolic state with an anabolic predominance over catabolism. At the interface of global function and the cell is the insulin index. The low value, adjusted for age, indicates insufficient insulin sensitivity, which feeds into the profound oxidative insufficiency that is relative (redox) and absolute (oxidation index). The result is an important functional mitochondrial insufficiency often seen in atopic patients. Finally, the autophagy 2 index is elevated. Autophagy is the process of cellular destruction of biologically derived waste products. The index evaluates the relative risk of insufficient cellular autophagy in the face of oversolicited organotissular metabolism imposed by global metabolic demands. By extension it favors ­autotoxicity of the interstitial space, in this case, localized to the skin. By extension, it favors an interstitiallymphatic drainage regiment. One efficient prescription is Alnus glutinosa GM + Ribes nigrum GM (interstitial drainage) + Juniperus communis GM (hepatorenal drainage for autotoxicity) + Sorbus domestica GM (lympho-venous-hepatic drainage). Based on her birthday BoF and her adrenal androgen tissular phase of growth, she was started on the treatments listed in Table 1.25. The patient was requested to avoid high glycemic foods and gluten. She was encouraged to explore her artistic side

Allergic disorders Chapter | 1  19

TABLE 1.25  Rational treatment and its effects by axis and actions on the terrain Treatment

Ingredients

Axes

Actions

Atomidine

Trichloro-iodine

Thyrotropic

Improves efficiency of production and action of thyroid hormones

Oligoelements

Zinc-nickel-cobalt oligoelement

Pituitary-thyro-somatotropic

Pituitary regulation (zinc fingers: DNA transcription), insulin production, food sensitivity, methylcobalamin (B12) production, stress management

Pituitary blend #2: 3 mL BID with meals

Salvia sclarea MT

ANS-endocrine harmonization Cortico-gonado-thyrosomatotropic harmonization Dermatologic

Regulates hypothalamic TRH relaunching by alpha, supports adrenal cortex, estrogens, thyroid, digestion, pancreatic drainer, supports exocrine pancreatic excretions; cutaneous antiinflammatory and astringent

Avena sativa MT

Gonado-thyrotropic

Gonado-thyrotropic harmonization of estrogen responsiveness to FSH and thyroid responsiveness to estrogens, pancreatic function

Ribes nigrum GM

Corticotropic Immunity

Supports peripheral corticotropic function, immunity, antiallergic

Plantago major MT

Drainage

Hepato-biliary-pancreatic drainage, antiallergic, antihistaminic, immune regulator

BID, twice per day; GM, gemmotherapy; MT, mother tincture.

(aunt is a professional artist). She was compliant with the treatment for 9 months until summer time. She stopped the treatment before leaving for summer camp in Europe. While away at camp, she had a dysregulated sleep schedule and ate all her aggravating foods (high-glycemic and gluten-containing foods). She returned from camp with a resurgence of eczema that had not been present since her early childhood. The distribution of the eczema was the scalp, left ear, and left antecubital fossa (Table 1.26). In addition, she had 3 episodes of otitis media over the summer. Her fits of crying, dark mood, and irritability returned. She also complained of feeling fatigued. The patient had a number of significant improvements in her findings in her current BoF and comparison to the prior year’s BoF. Based on these changes, her treatment was revised to increase the quality of dermatologic and hepatobiliary drainage and antihistamine therapy (Table 1.27). TABLE 1.26  Topology of eczema and its correlates in the terrain Neuroendocrine hyperfunctioning Anatomy

Alpha + Para

Retro-auricular Flexural folds Distal extremities

ACTH

GH > ACTH

• • •

Her BoF was subsequently repeated 8 months after the second evaluation. The arc of evolution of the indexes is presented in Tables 1.28–1.31. Clinically, her eczema progressively improved and she began losing weight.

Discussion At 11 years of age, her precritical terrain for eczema was more severe than at 12 years. However, she did not manifest eczema at that time. The reason for this was that hepatobiliary and exocrine pancreatic function was sufficiently regulated that proteins were not overabsorbed, immune factors not overproduced and catabolic waste products insufficiently drained. The stress of going away to summer camp in another country and the consumption of a­ggravating foods brought out the ­necessary changes in her atopic terrain to manifest eczema, which had been latent for years. As the patient continued with her treatment over the following 8 months, she continued to have improvements in her eczema terrain and a reduction of the clinical expression of eczema. The duration of treatment and the lack of quick resolution is because of two reasons. First, the genetic ­nature of the disorder and the ease at which the phenotypic ­expression is maintained. This is due to the second reason: the patient was not compliant with the recommended dietary changes. Thus, there were constant solicitations on the exocrine pancreas, adaptative congestion of her liver and skin, and adaptative neuroendocrine changes. Despite this, the treatments were able to ameliorate the terrain. This witness the importance of a multifactorial approach to the treatment of eczema: terrain, alimentation, and lifestyle.

TABLE 1.27  Rational treatment and its effects by axis and actions on the terrain Treatment

Ingredients

Axes

Actions

Atomidine

Trichloro-iodine

Thyrotropic

Improves efficiency of production and action of thyroid hormones

Topical

1 tsp. coconut oil + lavender EO 1 drop to scalp BID

Dermatologic Corticotropic

Reduce inflammation, histamine expression

Drainage #1

Arctium lappa MT Raphanus niger MT Achillea millefolium MT

Drainage

Supports digestion, drainage

Pituitary blend #3: 3 mL BID with meals

Salvia sclarea MT

ANS-endocrine harmonization Cortico-gonado-thyrotrosomatotropic harmonization Dermatologic

Regulates hypothalamic TRH relaunching by alpha, supports adrenal cortex, estrogens, thyroid, digestion, pancreatic drainer, supports exocrine pancreatic excretions; cutaneous antiinflammatory and astringent

Viburnum lantana GM

Central nervous system Thyrotropic

Regulates TRH expression within the hypothalamus and its responsiveness to alpha relaunching

Arctium lappa MT

Drainage

Skin, hepatobiliary, pancreas, depurative, blood purifier, pancreatic stimulant, immune modifier, antiallergic

Plantago major MT

Drainage

Hepato-biliary-pancreatic drainage, antiallergic, antihistaminic, immune regulator

BID, twice per day; GM, gemmotherapy; MT, mother tincture.

TABLE 1.28  Evolution of corticotropic indexes

a Not an index but a ratio of two indexes. (F), function value; (S), structure value. High low values presented in red/blue respectively.

Allergic disorders Chapter | 1  21

TABLE 1.29  Evolution of thyrotropic indexes

a Not an index. (F), function value. High low values presented in red/blue respectively.

TABLE 1.30  Evolution of gonadotropic indexes

(F), function value; (S), structure value. High low values presented in red/blue respectively.

TABLE 1.31  Evolution of somatotropic indexes

(F), function value; (S), structure value. High low values presented in red/blue respectively.

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22  The Theory of Endobiogeny

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Ignacak A, Kasztelnik M, Sliwa T, Korbut RA, Rajda K, Guzik TJ. Prolactin—not only lactotrophin. A "new" view of the "old" hormone. J Physiol Pharmacol. 2012;63(5):435–443. Kagalwalla AF, Shah A, Li BU, et al. Identification of specific foods responsible for inflammation in children with eosinophilic esophagitis successfully treated with empiric elimination diet. J Pediatr Gastroenterol Nutr. 2011;53(2):145–149. Duraffourd  C, Lapraz  JC. Traité de Phytothérapie Clinique: Médecine et Endobiogénie. Paris: Masson; 2002. Lapraz  JC, Carillon  A, Charrié  J-C, et  al. Plantes Médicinales: Phytothérapie Clinique Intégrative et Médecine Endobiogénique. Paris, France: Lavoisier; 2017. Gao  Q, Yang  M, Zuo  Z. Overview of the anti-inflammatory effects, pharmacokinetic properties and clinical efficacies of arctigenin and arctiin from Arctium lappa L. Acta Pharmacol Sin. 2018;39(5):787–801. Toiu A, Muntean E, Oniga I, Vostinaru O, Tamas M. Pharmacognostic research on Viola tricolor L. (Violaceae). Rev Med Chir Soc Med Nat Iasi. 2009;113(1):264–267. Toiu A, Parvu AE, Oniga I, Tamas M. Evaluation of anti-­inflammatory activity of alcoholic extract from Viola tricolor. Rev Med Chir Soc Med Nat Iasi. 2007;111(2):525–529. Witkowska-Banaszczak  E, Bylka  W, Matlawska  I, Goslinska  O, Muszynski  Z. Antimicrobial activity of Viola tricolor herb. Fitoterapia. 2005;76(5):458–461. Klovekorn  W, Tepe  A, Danesch  U. A randomized, double-blind, vehicle-controlled, half-side comparison with a herbal ointment containing Mahonia aquifolium, Viola tricolor and Centella asiatica for the treatment of mild-to-moderate atopic dermatitis. Int J Clin Pharmacol Ther. 2007;45(11):583–591. Hellinger R, Koehbach J, Fedchuk H, et al. Immunosuppressive activity of an aqueous Viola tricolor herbal extract. J Ethnopharmacol. 2014;151(1):299–306.

Chapter 2

Asthma: An integrative physiologic approach Introduction Asthma is a global health problem that results in limitation of lifestyle choices for millions of people around the world. The standard biomedical approach reduces asthma-related mortality but not incidence, prevalence, or progression of the disease. The advantage of this approach is the ability to suppress symptoms and quickly relieve hypoxia. It can be lifesaving. However, it remains a reactive modality addressing downstream mechanisms rather than upstream causes of asthma. What is needed is a more comprehensive approach that addresses the upstream origins of asthma in its precritical state, treats the critical terrain and when necessary, manages symptoms that affect the quality of life or are lifethreatening. Endobiogeny offers such an approach because it takes a global systems integrative physiologic approach to the whole person who has asthma within a specific environmental context. According to the theory of Endobiogeny, asthma is a type of hyperimmune disorder. It is also a bronchial spasmophilia arising from an attempt to resolve a state of oxygen insufficiency relative to metabolic demands. It is a complex global systems disorder expressed locally in the airway. There is a multiplicity of contributing factors: genetic, epigenetic, phenotypic, geographic, lifestyle, and dietary. The key to treating and preventing asthma lies in a global ecologic approach to the person and their environment. To understand why the airways are targeted, one must understand the purpose of the pulmonary unit.

Pulmonary teleology The lung has four roles: oxygen ingress, carbon dioxide egress, acid–base balance, and defense against noxious agents. The first two roles of the lungs ensure efficient metabolism. Oxygen is required for oxidation of lipids and carbohydrates, the most efficient method of ATP production. The waste product of this oxidation is carbon dioxide gas. The lungs are the most efficient way to evacuate a gas. Because carbon dioxide plays a role in acid-base balance, the lungs along with the kidneys play a role in pH balance. The Theory of Endobiogeny. https://doi.org/10.1016/B978-0-12-816964-3.00002-X © 2019 Elsevier Inc. All rights reserved.

The airways are a potential point of entry for noxious agents including noncommensal organisms. The very act of respiration, which ensures the survival of the organism, threatens its very existence at every moment of our lives. Thus, a component of the pulmonary unit involves a local, sentinel immune system to guard against and sequester potentially noxious aggressors.

The pulmonary unit When discussing the function of the lungs, we evaluate it in the context of the thoraco-pulmonary system as a whole. This system ensures the regulation of the structural and functional activity of the lungs. The pulmonary unit (Fig. 2.1) consists of the airway and lungs. The airway commences with nose and proceeds past the larynx to include the trachea, bronchi, bronchioles, and alveoli. The alveoli are where gas exchange occurs. The lung consists of the parenchyma, pleural lining, and pleural fluid, which play a role in its elasticity and compliance.1 The thoracic component of the thoraco-pulmonary unit consists of osseous and muscular subunits of structure and function1 (Fig. 2.2). The thoracic cage is an osseous structure that plays a key role in basal and adaptive respiration. Its structures (viz., sternum, ribs, and spine) provide leverage during inspiration.1 Posture is implicit in this function. The musculature of the unit includes the diaphragm and accessory muscles (Fig.  2.2). These muscles assist in both anterior-posterior and cephalo-caudal movement of the lungs in inspiration and expiration, viz., pulmonary mechanics.2 Abdominal muscles also play a role. Finally, neural mediation is essential for activating the sequence of inspiration and expiration. It includes afferent and efferent inputs to regulate respiration based on physiologic requirements (Fig. 2.3). However, central nervous system factors can override these impulses, which introduces the role of emotions in respiration.1 Nervous system regulation is complex, including central, brain stem (vagus), sympathetic ganglia, and the peripheral nervous system for innervation of the various 23

24  The Theory of Endobiogeny

Pulmonary vein

Larynx Pulmonary artery Primary bronchi

Trachea

Secondary bronchi Tertiary bronchi Bronchioles

Alveolar duct Alveoli Cardiac notch

FIG.  2.1  Pulmonary unit. The pulmonary unit consists of the airway: trachea, bronchi, and bronchioles, the terminal alveoli and the lung parenchyma. (Image reproduced from NIH Public domain.)

Muscles of inspiration

Aclcessory Sternocleidomastoid (elevates stemum) Scalenes Anterior Middle Posterior (elevate and fix upper ribs)

Principal External intercostals (elevate ribs, increasing width of thoracic cavity)

Interchondrial part of internal intercostals (also elevates ribs) Diaphragm (domes descend, increasing vertical dimension of thoracic cavity: also elevates lower ribs)

muscles. Alpha-sympathetic input arises from the cervical and upper thoracic portions of the sympathetic ganglion. ANS innervation operates at three levels: larynx, bronchioles, and musculature. At the level of the larynx, it ensures the proper opening for the ingress of air, and closure of the larynx to prevent aspiration of food or particulate airborne matter, and also the ingress of air. The larynx helps stent the alveoli during exhalation prolonging the time of oxygen exchange. This is referred to as auto-PEEP (positive endexpiratory pressure) and clinically recognized as expiratory grunting. The ANS plays a key role in regulating the tonus of the bronchi and bronchioles: basal, constriction, and dilation. Pain, emotions, and sudden changes in temperature also affect autonomic function in several ways, as discussed

Muscles of expiration

Quiet breathing

Expiration results from passive recoil of lungs and rib cage

Active breathing Internal intercostals, except interchordial part

Abdominals (depress lower ribs, compress abdominal contents, pushing up diaphragm) Rectus abdominis

External oblique

Internal oblique Transversus abdominis

FIG. 2.2  Thoracic structures. The diaphragm is the primary muscle of respiration. The sternum plays an important role as a fulcrum during anterior expansion of the thorax. Accessory muscles play roles in superior expansion and can augment the volume and rate of both inspiration and expiration. (Reproduced from Alison McConnell A. Respiratory Muscle Training: Theory and Practice. 1st ed. Oxford: Elsevier; 2013.)

Asthma: An integrative physiologic approach Chapter | 2  25

Higher brain centers (cerebral cortex voluntary control over breathing)

+ –

+ –

Respiratory centers (medulla and pons)

Other receptors (e.g., pain) and emotional stimuli acting through the hypothalamus

Peripheral chemoreceptors O2¯, CO2, H+ Stretch receptors in lungs

+ Central chemoreceptors

–

+

CO2, H+

Irritant receptors –

Receptors in muscles and joints +

FIG.  2.3  Afferent input for regulation of respiration. (Reproduced from Alison McConnell A. Anatomy and physiology of the respiratory system. Respiratory Muscle Training. Churchill Livingstone; 2013 [chapter 1].)

in earlier chapters (viz., locus coeruleus, limbic area, TRH, etc.), which can play a role in the terrain in both types of asthmatics, allergic and nonallergic. There are two additional factors that are not strictly part of the structure or function of the pulmonary unit with respect to respiration but play an important role in the efficiency of the enterprise. The first is the structures of the oral cavity, nose, and sinuses (cf. The Theory of Endobiogeny, Volume 2, Chapter 9). This plays a role in conditioning air and exacerbating allergic asthma. The second is the immune system (cf. Chapter  1, and, The Theory of Endobiogeny, Volume 2, Chapter 9). The immune system guarantees the safety of the lungs. If the immune system were not present, our internal dialogue, to paraphrase Hamlet, would be: “To breathe or not to breathe—that is the question.” Of course, it is no question at all because respiration is essential for human life. The local pulmonary immune system consists of bronchialassociated lymphatic tissue (BALT), located in the subepithelial space of the airway. This is the second largest center of immune activity after the gut-associated lymphatic tissue (GALT). The lymphatic network of the ear, nose, and throat regulates regional immunity. The global immune system can be solicited when loco-regional immunity is insufficient to manage the aggression on the bronchial endothelium. Dysfunction of the other regional lymphatic tissue can create a global microbial burden that affects the ­regulation

of immunity and inflammation at the level of the lungs (cf. “Contributing factors to asthma,” below).

Asthma in children: Anatomical and neuroendocrine factors Children are particularly susceptible to upper and lower airway disorders. There are numerous anatomical factors listed below: 1. Relative macroglossia: partial blockage of the airway 2. Smaller airway relative to adults: greater increase in airway resistance during asthma 3. Cartilaginous thoracic cage: less leverage during dyspnea 4. Bronchioles susceptible to collapse during strained respiration worsening hypoxia 5. Higher basal respiratory rate with less capability of augmentation of rate to compensate for hypoxia There are also numerous neuroendocrine factors related to childhood that favor the onset of asthma in childhood: 1. Physiologic vagotonia until 4 years of age 2. Mental spasmophilia during the time of verbal, emotional, and intellectual development with hysteroid tendencies (cf. Volume 2, Chapter 11: Spasmophilia) 3. Increased TSH activity: favors mucous production 4. Immature immune system

26  The Theory of Endobiogeny

Pulmonary histology and the endocrine system The thoraco-pulmonary unit is comprised of all three germ layers (Table 2.1). Thus, the gonadotropic, thyrotropic, and ­somatotropic axes are implicated in the structural and structurofunctional activity of the unit. The corticotropic and thyrotropic axes are implicated in its functional adaptive activity. (cf. “Lung as emunctory,” below).

TABLE 2.1  Pulmonary histology Germ layer

Endocrine axis

Thoraco-pulmonary structure

Endoderm

Somatotropic

Alveoli

Mesoderm

Gonadotropic

Airway epithelium Lung parenchyma Pleural lining Bone Muscle

Ectoderm

Thyrotropic

Innervation Bone

Neutral

Psychosomatics of the lung Respiration is linked to the existential issues of life and death. Extrauterine life begins with inhalation and ends with exhalation. Various emotional states are associated with particular breathing patterns3 (Fig. 2.4).

Lungs as emunctory Introduction The lungs are emunctories linked to the thyrotropic axis in adaptation. The colon excretes solid waste, and the kidney excretes liquid waste. The lungs excrete gaseous waste, namely carbon dioxide. The primary source of carbon dioxide is the oxidation of glucose for ATP production, which is why it is linked to the thyrotropic axis in adaptation. There are three primary factors that increase carbon dioxide load: the rate of (1) metabolism, (2) glucose utilization, and (3) CO2 accumulation. The greater the absolute rate of general metabolism (elevated metabolic yield index) and the greater the relative predominance of anabolism (low catabolism/anabolism index), the greater the production of carbon dioxide will be. Examples include growth spurts in children, infections, hyperimmune response to an allergen, and changing of seasons. The greater the ­utilization of

Disgust

v o l u m e

Amusement (laughter)

Reaction time

v o l u m e

Sadness (crying)

Cold pressor

v o l u m e

FIG. 2.4  Emotional states and respiration. Various respiratory states alter the rate and volume of breathing. (Reproduced from Boiten FA. The effects of emotional behaviour on components of the respiratory cycle. Biol Psychol 1998;49(1–2):29-51. https://doi.org/10.1016/S0301-0511(98)00025-8.)

Asthma: An integrative physiologic approach Chapter | 2  27

glucose for ­oxidation, the greater the production of carbon dioxide will be. The greater the congestion of the lungs or cardiac insufficiency, the less the discharge of CO2 from the lungs and the greater its accumulation. This can be due to four ­reasons: (1) excess production, (2) insufficient ­compensatory renal metabolism of CO2, (3) insufficient compensatory skin or kidney emunctory function, and (4) a combination of the preceding (Table 2.2). TABLE 2.2  Causes of excess carbon dioxide load Cause

Reason

Example

Excess production

Rate of metabolism

Growth spurt Infection Allergic response

Rate of glucose oxidation

Excess intake: diet Excess uptake: exocrine pancreas Excess production: neoglucogenesis Excess mobilization: glycogenolysis

Excess accumulation

Excess production

Cf. above

Pulmonary congestion

Left cardiac insufficiency Emotional states, e.g., depression, grief

Renal metabolism

Diminished metabolism of CO2

Insufficient compensatory emunctory function

Skin Kidney

All four endocrine axes are implicated in pulmonary function as an emunctory. The gonadotropic axis initiates metabolism thus the need for oxidation of glucose for ATP production. The thyrotropic axis regulates oxygen uptake into cells, the somatotropic axis the amount of glucose or lipids entering the cells for oxidation. The corticotropic axis plays a role in adaptive metabolism.

Pancreato-pulmonary relationship The exocrine pancreas produces digestive enzymes that augment the rate of absorption of macromolecules from food (Fig.  2.5). The greater the intake of high-glycemic carbohydrates is the greater the presentation of glucose for oxidation.

Reno-pulmonary: Acid-base balance The kidney regulates chronic acid–base balance. In the proximal tubules, the interconversion of bicarbonate and carbon dioxide takes place: CO2 + H2O ⇄ H+ + HCO3− Upregulation of the rate of CO2 clearance by the kidneys is by genomic mechanisms, taking up to 24 h to occur. In contrast, the lungs can immediately excrete carbon dioxide by increasing expiratory volume or rate or both. Fig.  2.5 illustrates the net effects of the endocrine and exocrine pancreas and the kidneys on the lungs as an emunctory organ.

FIG. 2.5  Pancreas, kidney, and lungs. The exocrine pancreas increases the rate of uptake of fat and carbohydrates, which are oxidized to produce ATP. A by-product is CO2, which is exhaled by the lungs. The kidney regulates acid-base balance, related to protein metabolism to ammonia, CO2 and other factors. When the metabolic or organometabolic activity of the kidney is augmented, it may impair its emunctory function, putting further demand on the lungs. (Images by PandaVector and EgudinKa/Shutterstock.com © 2015 Systems Biology Research Group.)

28  The Theory of Endobiogeny

The necessity of asthma phenotypes Phenotypes have to be useful in some way, such as in managing the child or understanding the mechanisms of disease. It should be noted that phenotypes may vary over time and are not fixed and immutable. Andrew Bush,4 M.D., Department of Pediatric Respiratory Medicine, Royal Brompton Hospital.

Presence of atopy There are four approaches to phenotyping patients with asthma: atopic disease, clinical presentation, clinical response to treatment, and an Endobiogenic approach. The first approach is phenotyping by the presence of atopy. Experimental models in animals and objective measurements in patients (sputum and serum eosinophilia) make this a preferred approach for researchers. This approach has a number of shortcomings. It explicitly studies extrinsic (allergic) asthma. However extrinsic and intrinsic asthma have histopathology consistent with allergic asthma: T-lymphocytes and eosinophil infiltrates.5, 6 In clinical practice, this classification is not predictive of response to corticosteroid treatment in children with transient wheeze and atopy.4

Clinical presentation The second phenotyping approach is clinical. In young children, the frequency of wheeze is used. Episodic wheezing is associated with upper respiratory viral illnesses. Recurrent wheezes are associated with multiple environmental triggers. There are two advantages to this approach. First, it guides the duration and selection of treatment. In episodic, viral-induced asthma in children, short-term symptomatic use of a short-acting ­beta-agonists + high-dose inhaled steroids or leukotriene inhibitor is effective. In recurrent cases, chronic use of inhaled steroids is indicated and reduces the frequency of asthma exacerbations.4 There are two shortcomings to this approach. First, it was only phenotypes extrinsic forms of asthma. Second, it does not prevent the progression of disease in intermittent types4 because it is not addressing the global terrain.

Clinical response to treatment

Endobiogeny: Global systems neuroendocrine approach Asthma is described as a chronic immunologic disorder characterized by bronchial hyperreactivity, inflammation, and airway obstruction resulting in hypoxia and/or hypercapnia.7 This description is not incorrect, merely incomplete in three important ways. First, it only describes the downstream mechanism of airway dysfunction. Second, it fails to consider the global upstream precritical terrain. Third, it only describes extrinsic (allergic) asthma. There are two categories of asthma. Both have the same basic clinical result: dyspnea. However, the causes (precritical terrain), agents, responses (critical terrain), the order of importance of mechanisms and thus the treatment priorities differ. Thus, we must speak of two types of asthma: extrinsic and intrinsic. Because asthma is a spasmophilia of the lungs (in the critical terrain), the Endobiogenic phenotyping is according to the ANS function. We define asthma as a global neuroendocrine disorder primarily in vagotonic patients where relative demand for oxygen exceeds the capabilities of the organism to supply it. The general division is based on the agent that solicits an adaptative response. If it is allergic in nature, it is classified as extrinsic asthma. If it is not allergic in origin, it is classified as intrinsic asthma. In total there are five clinical phenotypes (Table 2.3). The definition of extrinsic asthma, specifically, can be defined as follows: Extrinsic (allergic) asthma is an excessive adaptation response primarily in vagotonic atopic patients to a moderate or weak allergen. The endocrine response is excessive in intensity, duration or both and greater in central response than peripheral response. It sets in place a prolonged, adaptative airway resistance. A global systems approach does not negate or exclusively rely on any of the other noted phenotyping systems. It embraces and integrates them into a highly specific and personalized approach to the treatment of asthma. The specific role of factors from eosinophilia to the environment, from exercise to age is determined by the assessment of the Endobiogenic terrain through history, physical examination, and biology of functions.

Extrinsic asthma The precritical terrain has three aspects: ANS, Endocrine, and Emunctory. The net effect is congestion of the airway due to global imbalances of terrain.

The third type is based on response to treatment. This forms the basis of the treatment recommendation of most national and international pulmonary societies. Its advantage is that Causes of extrinsic asthma: 1-ANS it offers clear algorithms of treatment escalation and de-­ escalation. It also considers the quality of life of patients. Type 1 extrinsic asthmatics are constitutionally vagotonic. Its disadvantage is that it is a reactive approach that does not There is no spasmophilia in the precritical terrain. Type 2 consider upstream managers of disease. extrinsic asthmatics are also constitutionally vagotonic.

Asthma: An integrative physiologic approach Chapter | 2  29

TABLE 2.3  Endobiogenic classification of asthma by precritical terrain Category

Type

Parasympathetic

Alpha sympathetic

Beta sympathetic

Extrinsic (allergic)

1

++ (vagotonic)

Normal

Normal

2

++ (vagotonic)

+

Insufficient

3

++ (reactionary)

++ (basal)

Normal

4

++ (vagotonic)

Normal

Normal

5

++ (vagotonic)

Normal

Insufficient

Present

Precritical spasmophilia

Intrinsic (nonallergic)

Precritical spasmophilia

Present

+, over-active; ++, hyper-functioning.

TABLE 2.4  Endobiogenic phenotypes of extrinsic asthma by precritical terrain Category

Type

Parasympathetic

Alpha sympathetic

Beta sympathetic

Extrinsic (allergic)

1

++ (vagotonic)

Normal

Normal

2

++ (vagotonic)

+

Insufficient

3

++ (reactionary)

++ (basal)

Normal

Present

+, over-active; ++, hyper-functioning.

They have a precritical spasmophilia due to elevated alpha. It is insufficiently elevated in relation to para, but sufficiently elevated to block or delay beta, hence the precritical spasmophilia. Type 3 extrinsic asthmatics have a baseline alpha which is quite elevated. Para is elevated in a reactionary and compensatory fashion. There is no spasmophilia in the precritical terrain (Table 2.4). Being vagotonic means they have genetic isoforms of the muscarinic parasympathetic receptors that have heightened affinity for acetylcholine, increased density in certain areas of the body, increased distribution, diminished threshold of response or any combination of the above. There is a physiologic vagotonia in nearly all children from 0 to 4 years of age that places children at risk for spasmophilia (The Theory of Endobiogeny, Volume 2, Chapter 11), and by extension extrinsic asthma that can be outgrown. However, vagotonic is that which has strong early signs of parasympathetic morphology and function and whose expression of vagotonia persists beyond 4 years of age. The summary of ANS activity on airway tonus is as follows: ● ● ●

d­ uration of oxygen exposure at the level of the alveoli. The rapid onset of beta (adrenaline) bronchodilates, then allows the organism to return to its basal tone (Fig. 2.6). Augmented parasympathetic activity congests the endothelial lining of the airway. This narrows the caliber of the bronchus and increases airway resistance. The teleology is to improve oxygenation. Inspiration is an active process using muscles and bones for leverage. Thus, the organism can compensate for a mild increase in airway resistance by increasing the work or rate or volume of inspiration. Expiration is normally passive. Normally during e­ xpiration, alveoli collapse. No oxygen exchange occurs. Mild increases in airway resistance prolong expiration, increasing

Parasympathetic: Basal tone and congestion of airway Alpha-sympathetic: Bronchoconstriction Beta-sympathetic: Bronchodilation

The ANS circuit constantly turns in a normal-­functioning terrain. Thus, the teleology of alpha-induced ­bronchoconstriction advances the goals of para because it augments briefly the

FIG.  2.6  Normal autonomic nervous system time-intensity graph. See text for details. Black arrow, cause and effect; gray arrow, sequential. (© 2015 Systems Biology Research Group.)

30  The Theory of Endobiogeny

TABLE 2.5  Three proofs of neuroendocrine origin of asthma Proof

Discussion

Comment

Constitutive role of autonomic nervous system

Para: persistent vagal tone Alpha: bronchoconstriction Beta agonists are the foundation of acute treatment

Even after treatment with beta agonist bronchodilators, asthmatics do not have normal FEV1

Endocrine implication

Corticosteroids are a secondary line of treatment in acute and subacute asthma

It witnesses the implication of peripheral corticotropic insufficiency

Inflammation

Mechanism, not cause; asthmatics have a genetic predilection to greater inflammation

Antiinflammatories do not alter the course of asthma or development of chronic lung disease

FEV1, forced expiratory volume, 1 s.

alveolar pressure, stenting them open. The net effect is an increase in the duration of oxygenation. Recall that types 2 and 3 extrinsic asthmatics have elevated alpha and/or insufficient beta. As long as the demand for oxygen does not increase rapidly or substantially, this also contributes to the airway resistance by broncho-­ constricting and not allowing for bronchodilation, respectively. The genetic origin of the role of the ANS in general and the implication of the neuroendocrine system can be demonstrated by three proofs (Table 2.5). The first proof is the constitutive role of the ANS in the asthma terrain. ANS dysfunction is the most upstream ­factor initiating numerous primary and secondary factors related to asthma (Fig. 2.7). ●

●

Elevated Parasympathetic ● Favors a slouching posture → Diminished inspiratory and expiratory volume ● Leads to congestion of bronchus → reduction in airway caliber → alveolar stenting ● Stimulates exocrine pancreas → Mucous production ● Stimulates endocrine pancreas → Insulin → Inflammation Elevated Alpha-Sympathetic ● Stimulates bronchoconstriction ● Augments histamine → Inflammation ● Relaunches TRH → Hyperimmune response

FIG.  2.7  Schematic representation of ANS effects on the airways in asthmatic patients. See text for details. (© 2016 Systems Biology Research Group.)

●

●

Elevated Para and Alpha with blocked or delayed Beta ● Spasmophilia → Airway hyperreactivity Insufficient Beta-Sympathetic → Insufficient bronchodilation

The cornerstone of rescue therapy involves manipulation of the ANS: beta-agonists (e.g., Albuterol, Salmeterol) and parasympatholytics (e.g., Atropine). There is a persistent hypervagal tone in asthmatics regardless of the degree of immune dysregulation, be it inflammation or hyperimmune response. The evidence of this comes from the fact that even when asthmatics are treated with antiinflammatory agents and bronchodilators, they continue to have force expiratory volumes at 1 s below that of nonasthmatic patients (Fig. 2.8). The second proof is the role of the endocrine system in etiology and/or exacerbation of numerous downstream factors related to immunity and inflammation. Global serum levels of endocrine factors may be normal but regardless

FIG.  2.8  Pulmonary mechanisms of normal subjects and asthmatics. Normal subjects have an optimal forced expiratory volume at 1 s (FEV1). Asthmatics during an asthma attack have the lowest FEV1. After bronchodilation, FEV1 improves but does not normalize. (Courtesy of the Global Initiative for Asthma.)

Asthma: An integrative physiologic approach Chapter | 2  31

there is a functional dysfunction of endocrine activity related to the etiology of asthma. The foundation of ambulatory and subacute management of asthma is endocrine in nature (inhaled, oral, and intravenous glucocorticoids, respectively). The third proof is that inflammation is not the cause of asthma. The use of antiinflammatory agents does not alter the progressive course of asthma.8 Our explanation of this is that inflammation is a mechanism in the presentation of asthma symptoms, not its cause.

Causes of extrinsic asthma #2: Hyperimmunity: Atopy Extrinsic asthma is equivalent to the term “allergic asthma.” Thus, all extrinsic asthmatics have a state of hyperimmunity that is consistent with the other atopic disorders (food, environmental and contact allergies, and, eczema), as discussed in Chapter 1. To summarize the pre-critical terrain of atopic patients: 1. Hyperestrogenism: fabrication of immune elements 2. Oversolicitation of the exocrine pancreas: increased uptake of proteins for immune elements 3. Oversolicitation of endocrine metabolic activity of the liver: production of proteins of the immune system

Causes of extrinsic asthma #3: Emunctories The greater the dysfunction of other modes of drainage and detoxification, the greater the solicitation of the lungs will be. In order of importance, the emunctories are listed below: 1. Exocrine pancreas mucous production 2. Liver congestion of detoxification and excretion 3. Skin secondary organ of respiration and gas exchange 4. Large intestines secondary drainage of hepatobiliary metabolized waste products (constipation)

Agents of the extrinsic asthma attack: Allergens Disruption in immune development Hygiene theory posits that the greater the disruption in immune function and the earlier its occurrence, the greater the risk of atopic disease will be. The disruption in immune regulation is related to an upset in the balance of Th1 to Th2 activity. Infections increase Th1 activity. The lower the exposure to infectious agents—the more “hygienic” the environment—the greater the increase in Th2 lymphocytes and the more hyperimmune the terrain’s response to aggressions become.9 The disruption in the development of the immune system can be broken down into three events and three major periods of immune development. Patients can experience insufficient exposure to diverse flora and/

or loss of endogenous flora. The three phases of immune development are prenatal, birth to 5 years, and 6 years to adulthood.

Epigenetics While there is clearly a genetic basis to the dysregulation of the terrain in asthmatics, and while the global incidence of asthma continues to rise, there are notable differences across regions. The greater the degree of economic development and the attendant rise in urban living and a Westernized diet, the greater the risk of asthma.

Summary of protective factors against extrinsic asthma 1. Geography ● Growing up in less industrialized countries ● Rural upbringing 2. Epigenetics ● Earlier exposure to other children (siblings and preschool)10 3. Diet 10, 11 ● Breastfeeding ● Early childhood exposure to full cream milk, fish, and whole wheat11 11 ● Early childhood exposure to fresh fruit 4. Environment ● Early exposure to cats, dogs, goose feathers (Ida down)11 ● Reduction of the burden of dust mites (cleaning house, removing carpets and plush toys, and hypoallergenic sheets)11

Summary of factors that exacerbate onset and severity of extrinsic asthma in a patient 1. Genetics ● Family history: earlier onset, more severe course, greater sensitivity to environmental aggressors12, 13 2. Epigenetic/Iatrogenic ● Premature birth: higher incidence, more severe asthma14 11 ● Prenatal maternal antibiotic use ● Early childhood exposure to antibiotics (1.5 times increased risk)11, 15 3. Diet ● Perinatal maternal consumption of refined grains, sugar, saturated fats, red meat11, 16 ● Childhood consumption of refined grains, sugar, saturated fats, red meat11, 17 ● Reduced consumption of fresh fruits, vegetables, omega-3 rich foods11, 16

32  The Theory of Endobiogeny

4. Geography ● Children of parents of a low-incidence country being raised in a high-incidence country (converges with host country incidence)17 ● Adopted children who are raised in a high incidence country before 2 years of age18, 19 5. Economic/Demographic ● Demographic and economic transitions toward affluence and urban living.16, 20–22 6. Environmental ● Volatiles ▪ ▪ ▪ ▪ ▪ ▪

Prenatal or postnatal exposure to secondhand tobacco smoke11 Smaller the size of particulate matter, the greater the concentration of particulate matter23 Earlier exposure to noxious airborne chemicals11 Specific gasses: sulfur dioxide, nitrogen dioxide, carbon monoxide, ozone24 Volatile household and industrial solvents are also associated11 Synthetic bedding11

Flora

●

▪

Pollen

Fauna

●

▪ ▪

Animal hair and dander Droppings of dust mites and cockroaches

Response: Induction of the critical terrain: ANS The early stages of compensation for oxygen requirement actually serve the organism given the dysregulated demand. Only with the progression of airway narrowing to a critical point of hypoxia or dyspnea do the adaptive mechanisms become adaptative. Regardless of the initial tone, in the face of an aggression the quantitative Para and Alpha increase with three results (Fig. 2.9): 1. Critical reduction in airway and increase in airflow resistance a. Bronchoconstriction from which the organism cannot compensate for oxygen regulation

b. Para: congestion c. Alpha: Histamines → inflammation → edema 2. Spasmophilia: airway reactivity 3. Infiltration of immune elements a. Hyper Alpha → Local hyperhistaminemia

Response: Induction of the critical terrain: Endocrine Because the critical terrain is solicited during an adaptation demand, the corticotropic and then thyrotropic axes are implicated. Their explicit actions in immunity and adaptation have been discussed elsewhere. Fig. 2.10 reviews the consequences of peripheral adrenal cortex insufficiency. In summary, we present a summary of their action with respect to pathophysiology and BoF indices (Table 2.6).

Response: Induction of the critical terrain: Mucous production Mucous is primarily composed of proteins. Thus, it has an inherent relationship to the exocrine pancreas and TSH in the uptake of proteins and the gonadotropic axis in the construction of mucous. Various aspects of the neuroendocrine system regulate the quantity and quality of mucous production. Thus, the quality of the critical response to aggression determines to what degree mucous is produced. Mucous production is variable in asthmatics. In general, extrinsic asthmatics have a less prominent expression of mucous relative to inflammation (Table 2.7). Bronchial mucous has three general purposes: physical defense against noxious and pathogenic agents, protectant of the epithelial surface when injured, and source of energy for the cells involved in reconstruction of the injured epithelium. In the pathophysiology of airway obstruction in asthmatics, mucous narrows the physical size of the lumen through obstruction. This is in contrast to the functional restriction by para.25 The general progression occurs over a 24-h period of time and can last as long as a week after an asthma attack has resolved: 0–5 h: IgE → inflammation → bronchial hyperreactivity 6–23  h: Histamine, leukotrienes, prostaglandins → edema 1–7 days: Mucous production → mucous plugs

FIG. 2.9  ANS response in the critical terrain of asthma. See text for details. (© 2016 Systems Biology Research Group.)

The predominance of mucous as a factor in the reduction of airway patency will vary based on the degree of solicitation of the exocrine pancreas (from alimentation or endocrine factors), estrogens, and TSH. Ultimately, it is a production of a hyperanabolic state, as opposed to the hypercatabolic state engaged in inflammation and hyperimmunity.

Asthma: An integrative physiologic approach Chapter | 2  33

FIG. 2.10  Peripheral adrenal cortex insufficiency in the allergic asthmatic terrain. Alpha sympathetic (αΣ) stimulates (red arrow) ACTH to calibrate precortisol corticotropic defense and mobilization. ACTH increases the number of histamine receptors, stimulates eosinophils and basophils, and, T-lymphocyte excretion from the thymus. Alpha stimulates TRH to calibrate thyrotropic activity. TRH stimulates the release of histamine from circulating cells. This compliments the actions of ACTH in upregulating the number of histamine receptors. Histamines, now released, can prolong alpha in a positive feedback loop. Alpha stimulates the release of pro-inflammatory interleukins. Together with histamine and increased histamine receptors, they create an inflammatory terrain that allows nutrients, humoral, and cellular factors to extravasate from hematogenous circulation into affected tissues. ACTH stimulates cortisol, but due to the insufficient response, there is insufficient inhibition of these processes. The net result favors a dysregulated hyperimmune state. (© 2015 Systems Biology Research Group.)

TABLE 2.6  Alpha-cortico-thyrotropic physiology and possible BoF correlations Physiology

Effect

BoF index

Value

↑ Alpha

Histamines Vasoconstriction

Leukocyte mobilization

↑or ↓

Alpha → TRH

Hyperimmunity Histamine release

Thyroid relaunching Thyroid relaunching corrected

↑

Thyroid > adrenal cortex

Hypermetabolism Inflammation

Metabolism rate Inflammation

↑

Response: Induction of the critical terrain: Bronchial secretions

treatment, be it pharmaceutical or nonpharmaceutical in nature.

In addition to the production of mucous, the general fluidity and viscosity of bronchial fluid are influenced by a number of factors. The quality of these excretions and their ease of expectoration are noted in Table  2.7. They provide a clue to the specific neuroendocrine terrain of the asthmatic patient and suggestions as to the most optimal

Response: Induction of the critical terrain: Emunctories The nature of the catabolic adaptative response in extrinsic asthmatics exacerbates the precritical emunctory c­ ongestion during an asthma crisis.

34  The Theory of Endobiogeny

TABLE 2.7  Neuroendocrine factors relating to mucous production Factor

Quantity

Quality

Para

↑

Fluid, less concentrated

Alpha

↑

Thickened

Beta

Excretion, secretion and expectoration

Pituitary

Depends

Thickened and stringy

TSH

↑

Thickened, stringy

Thyroid Pancreas, exocrine

Thickened and sticky, then fluid ↑

Thickened

1. Exocrine pancreas mucous production 2. Liver congestion of detoxification and excretion 3. Skin secondary organ of respiration and gas exchange 4. Large intestines secondary drainage of hepatobiliary metabolized waste products (constipation)

Mechanisms in extrinsic asthma Current thinking in reductionist medicine considers inflammation to be a key and emerging factor in the pathogenesis of asthma. Fig. 2.11 is a typical cartoon depicting the mechanistic cascade as the causative pathogenic factors: One may be surprised that our discussion to this point has been surprisingly light on the details of the inflammatory pathways, of the role of IgE, of interleukins, etc. There are two general reasons for this, both of which arise from clinical considerations. First, these highly detailed downstream events are the result of upstream factors that can be safely managed through the use of pharmaceutical agents and medicinal plants. Second, the use of specific downstream biologic agents has failed to change the course of asthma compared to placebo.26–28 For example, a 24-week trial of a subcutaneous TNFα blocker showed no change over placebo in FEV1 in severe persistent asthmatics.26 A newer generation agent, etanercept showed similar failures in moderate-to-severe asthmatics,28 as did a trial of an IL-4α blocker that inhibited IL-4 and IL-13 pathways.27 From an integrative physiologic perspective, the role of the above noted triad is not in dispute, nor is the need to manage it. However, because the mechanisms are managed by the upstream neuroendocrine response to the aggression, that is our level of assessment and treatment. When we consider the general mechanisms of asthma according to its relationship to specific neuroendocrine factors, we can develop a targeted approach to the treatment of the terrain that also treats the mechanisms of asthma over time (Table 2.8).

FIG.  2.11  Standard biomedical explanation of the pathogenesis of asthma. This schematic presents mechanisms of asthma symptom expression as causes of the disease. (Image reproduced with permission from Medscape Drugs & Diseases (https://emedicine.medscape. com/), Asthma, 2017, Available at: https://emedicine.medscape.com/ article/296301-overview.)

Long-term complications of asthma There are two major complications of poorly controlled asthma. The first is airway remodeling. The second is the progression of pulmonary dysfunction to chronic obstructive airway disease (COPD). Because the global terrain is dysregulated and overfunctioning, the repair response overproliferates constituents of the airway. The relative degree of proliferation of the various components (basement membrane, smooth muscles, epithelium, and the degree of hypersecretions) will vary based on the asthma phenotype based on the particular Endobiogenic terrain of the patient.29 On histological assessment, one notes the proliferation of the basement membrane of the bronchus (Fig.  2.12).29 In COPD, the local inflammatory milieu progresses to also affect the alveoli.

Contributing factors to asthma The following factors may contribute to either type of asthma, depending on the particular factor. The majority of studies have either focused on allergic asthma or not differentiated the types of asthmatics.

Genetics Asthma has a strong genetic basis, between 35% and 95% depending on the study.30 The World Health Organization estimates that asthma is due evenly to genetic and environmental factors.31 We interpret this to mean epigenetic and

Asthma: An integrative physiologic approach Chapter | 2  35

TABLE 2.8  General mechanisms of extrinsic asthma Category

Factor

Example

BoF, biomarkers

Bronchial hyperreactivity

Autonomic nervous system

Spasmophilia

Leukocyte mobilization index + Platelet mobilization index

Nonadrenergic, noncholinergic neuromediators

Bronchoconstrictors: substance P, neurokinin A, neurokinin B

Inflammation (local)

Mast cells

Bronchodilators

VIP

Histamine

Evoked histamine index Potential histamine index

Interleukins

Interleukin-1 index

Prostaglandins Cytokines T-lymphocytes

Airway obstruction

ACTH

Adaptation index ACTH index

TSH

Serum TSH

Eosinophils

Absolute and percent eosinophils Adaptation index

Basophils

Absolute and percent basophils Structure/function index

Mucous

cf. Table 2.7

Local airway substances

Substance P Neurokinin A Neurokinin B

VIP, vasoactive intestinal peptide.

e­ nvironmental factors that alter the phenotype of the individual across space and time. With respect to specific genetic loci, latent class analysis (LCA) of asthmatics has created statistical profiles of asthmatics based on age of onset, persistence of symptoms, and extrinsic vs intrinsic nature of asthma. These profiles have been associated with particular genes and single nucleotide polymorphisms (SNP’s).32–34 From the perspective of integrative physiology and global systems theory, these studies have not proven reliable in predicting disease prospectively as they reflect the genotype and not the phenotype. In fact, prospective studies of patients with SNP’s associated with asthma fail to predict the presence of the disease in cross-sectional population studies.35 Single genes and the LCA do not explain the complex upstream physiology that actually brings about asthma and the insufficiency of oxygen to the cells. Other studies have confirmed the highly heterogeneous association of genes with asthma, in line with the integrative physiologic view of the complexity and multifactorial elements of the terrain.36–39 In the future, certain subtypes of asthmatics

or risks of more severe exacerbations may be able to be characterized by genetic typing.40, 41 There may be ethnicity and race-specific variants in the asthma terrain that should also be considered.42 How this will produce specific therapies is not clear at this time. After millions of dollars spent on sophisticated genetic testing, family history remains the strongest predictor of asthma.43–46 Three factors have been found to be significant: (1) Family history of asthma (the more family members, the greater the risk), (2) Consanguinity of parents,47 and (3) Type O blood type, with greater risk in boys vs type O girls.48–51

Diet Digestion of food requires the constant activity of the parasympathetic nervous system. It stimulates the production of the various digestive juices and enzymes required for the proper digestion of food. Because parasympathetic tone is so implicated in all types of asthma, diet can play a role in the general elevation of parasympathetic tone as noted earlier.

36  The Theory of Endobiogeny

FIG.  2.12  From a histological assessment one easily sees a proliferation of the basement membrane (Bm). The epithelium (Ep) is noted on the right in the asthmatic patient to show signs of mucous hyperplasia and hypersecretion (in blue). The lumen has lost approximately 80% of its potency as a result. Stained pink, one notes hypertrophy of the smooth muscle (Sm) as well. Thus, there are elements of anatomical, structural, and functional impairments of airflow. (Reproduced from Holgate ST, Davies DE. Rethinking the pathogenesis of asthma. Immunity 2009;31(3):362–367 Holgate ST, et al. Asthma. Nat Rev Dis Primers 2015;1: Article number: 15025. https://doi.org/10.1038/n2015.25.)

GERD Gastroesophageal reflux disease (GERD) is commonly found amongst patients with Asthma52–55 and is often asymptomatic.54, 55 Gastric acid serves as an irritant of the airway and promotes inflammation of the bronchial epithelium, especially when patients are supine, such as during sleep.

Chronic low-grade infections Rhinitis and sinusitis are also commonly found amongst asthmatics, and they can be allergic in origin.56, 57 Chronic rhinitis and sinusitis can provoke airway reactivity contributing to the inflammatory milieu of the airways: inflammatory microbial products, migration of microbes into the airway, and exhaustion of buffering capacity. Periodontal disease is found more frequently in patients with asthma.58 It is not clear if it is the cause, effect or merely associated from common pathophysiology. In sum, factors that exacerbate asthma include transgenerational, intergenerational, environmental, diet, and lifestyle issues.

Epidemiology From an epidemiologic perspective, Asthma is a disease of affluence, but the greatest burden of morbidity and mortality is found in the developing world.31 In general,

atopic ­disorders have increased dramatically in the last 40– 50 years.59 The frequency of asthma is 300 million people worldwide and is anticipated to increase over time.30 The prevalence varies from 2% to 15% of the population, greater for affluent countries than emerging economies. Deaths from asthma are 1 in every 250 deaths globally, approximately 250,000 per year.30, 60 Patients of lower socioeconomic status have a greater disease burden.61 In our opinion, this is a combination of greater incidence of maternal smoking, the predominance of certain environmental burdens (tobacco, industrial toxins, dust mites, etc.) as well as less health education and access to healthcare. With respect to prevalence and mortality, one notes an inverse relationship. There are increasing trends in lifetime prevalence of asthma in developing countries, especially amongst children.62 In the United States, for example, the prevalence of asthma increased by nearly twofold in 15 years. In general, asthma is a disease of patients with compromised lung function: children and the elderly.63 Two-thirds of asthmatics develop a terrain with liminal symptoms before the age of 18 years. Before puberty, there is a 2:1 ratio of boys to girls.64 Half of all cases of pediatric asthma resolve by puberty. After puberty and throughout life, girls and women predominate in the incidence of asthma.64 The next most common time for diagnosis of asthma is in premenopausal adult women. According to the theory of Endobiogeny, the changes in terrain related to puberty and menopause may explain why an atopic terrain is more or less prominent at certain ages (cf. The Theory of Endobiogeny, Volume 1, Chapter 13). The younger age groups are more likely to have extrinsic asthma due to overactivity of central thyrotropic function and a general parasympathetic dominance in childhood. With the onset of puberty, there is greater sexual dimorphism in the role of estrogens. Because women have greater and more fluctuating estrogen activity, they are more subject to hyperimmunity and thus asthma as compared to men. They are also more subjected to structuro-functional spasmophilia, which plays a role in allergic asthma. Because of the crucial role of respiration in all physical activities, asthma can have immediate and chronic impacts on activities of daily living. There is a greater disease burden in developing countries despite a lower incidence of asthma.

Diagnosis of extrinsic asthma Endobiogenic approach to chief complaint: Symptoms Asthma may be diagnosed clinically in many cases. A history of dyspnea with wheeze or cough provoked by allergens, infections, food, cold, exercise, etc. is typically sufficient to diagnose the disorder.

Asthma: An integrative physiologic approach Chapter | 2  37

●

●

The symptoms of dyspnea are:

Endobiogenic physical examination

Inspiration ● Air hunger: a subjective feeling of not being able to sufficiently inspire to satisfy the need for oxygen. It can be associated with advanced states with anxiety and in status asthmaticus with a fear of auto-­ asphyxiation and death. ● Coughing (Cough variant asthma) Expiration ● Prolonged expiration ● Audible wheeze

Chest

Other questions to pursue: ● ● ● ● ● ● ●

Inciting factors Aggravating factors Ameliorating factors Age of onset Season of onset or recurrence Quality of home and work environment Quality of emotional environment

Observation ● Posture ● Spontaneous respiration ● Shape: Pectus excavatum Auscultation: Lungs The signs of asthma are related to airflow and pulmonary mechanics of the entire pulmonary unit, including accessory muscles, sternum, and ribs. NB: Auscultation should include the axillary region, superior and posterior aspects of the thoracic cage. ●

●

Airflow ● Inspiration: cough ● Expiration: wheeze ● Inspiration and expiration: diminished movement Pulmonary mechanics ● Inspiration ▪ ▪

Expiration: auto-PEEP (grunting) Inspiration and expiration: nostril flaring

Endobiogenic past medical history

● ●

ROS ●

●

●

● ● ● ●

Prenatal: maternal antibiotic use, smoking, atopy, stress, diet, dental work, etc. Birth: vaginal vs cesarean, premature vs term, pulmonary dysfunction or wheeze at birth Diet: duration of breastfeeding, formula use, and type, solid foods: age of onset and first foods, consumption of dairy products History of atopic disease GERD as an infant Rhinitis/sinusitis History of use of antibiotics in childhood

Family history ● ● ●

● ●

Palpation ● ● ●

Observation ● Head ● Tongue ▪ ▪

●

● ●

Tip: inflammation Color and coating

Orifice of canals of Wharton and Stensen Eyes ● Sclera ●

●

Atopic disease in parents or siblings Atopic disease in grandparents Country of origin of parents and grandparents and reasons for migration Location of domicile (rural/urban/suburban) Birth order, health of siblings

Caregiver employment (exposure to noxious agents at work) Local and regional air quality and proximity to heavy industries Tobacco or marijuana smoking in the house or car Age of earliest institutional environment (preschool, kindergarten, homeschooled, etc.)

Sternal notch Rib asymmetry Xiphoid process

HEENT

▪ ▪

Color Vascular pattern

Iris

●

▪

Exploded rosette

Infraorbital discoloration

●

▪ ▪

Environmental ●

Retraction of accessory muscles Altered body posture (leaning forward)

▪ ●

● ●

Black: Adrenal insufficiency Blue: Hepatic congestion Red: Sinus congestion

Ears ● Color and temperature of helix ● Tympanic membrane Nose: allergic salute Throat ● Tonsil pillars ● Tonsil size

38  The Theory of Endobiogeny

Auscultation ● Larynx: distinguish laryngeal disorders from lower respiratory tract disease Palpation ● Sinuses ● Submandibular lymph nodes

Abdominal Palpation ● Liver ● Gallbladder ● Pancreas, exocrine ● Pancreas, endocrine

Back Palpation ● Adrenals ● Dermatographia

Quantitative evaluations Certain evaluations may be pursued to either quantify the severity of asthma or to rule out other disorder. To quantify and monitor the longitudinal alteration of pulmonary function, spirometry with evaluation of forced expiratory volume at 1 s (FEV1) may be performed. The lower the FEV1, the more severely compromised the pulmonary mechanics are (Fig. 2.8). If the FEV1 is equivocal, or in cases such as GERD or exercise-induced asthma, a provocation test can be administered to provoke and measure bronchial reactivity. A number of other tests can be pursued, but they are neither necessary nor sufficient for a diagnosis of asthma. They merely characterize a particular aspect of the pathophysiology of asthma. For example, serum eosinophilia >4%, or sputum eosinophilia counts can be used to rule in asthma, but normal counts do not rule out asthma. As we have noted, from an integrative physiologic approach, eosinophils reflect the relative intensity of the ACTH solicitation of adrenal cortex function and the relative insufficiency of cortisol activity—but this is only one aspect of the global terrain of patients with asthma. Despite the fact that inflammation is associated with eosinophilic infiltration of the airway, use of antiinflammatory agents does affect eosinophilia or fractional exhaled nitric oxide in patients.65 Elevated serum IgE can be associated with extrinsic (allergic) asthma, but it neither confirms nor rules out asthma. Other evaluations are relevant to status asthmaticus (e.g., pulse oximetry and arterial blood gas).

Ruling out comorbidities GERD should be considered in three types of asthmatics: cough-variant,52, 53 refractory cases, and nocturnal asthma that occurs during sleep in patients without infectious or

allergic aggressions (i.e., intrinsic asthma). GERD is a common comorbidity, especially in adults.54, 55 Clinical severity of symptoms has been correlated to the severity of GERD.54 The more severe the asthma is the more likely that the GERD to be asymptomatic.54, 55 A majority of asthmatics show improvement in symptoms and reduced use of rescue medication when their GERD is properly managed.56 Chronic sinusitis and rhinitis can be evaluated by visualization, palpation, history, X-ray, CT, or MRI scans. Management of rhinitis and sinusitis can reduce the frequency of hospitalization in asthmatic patients.56, 57

Biology of functions When evaluating the biology of functions of a patient with a history of asthma, it’s important to remember that patients with a history of extrinsic asthma may be in a precritical terrain or in chronic, low-grade critical terrain. They may have other comorbidities including various atopic disorders. Thus, one may not find all the relevant indexes to be deranged according to the discussion below. However, what is presented is based on surveys of Endobiogenic patients with extrinsic asthma.

Children The critical findings on the BoF reflect disadapted corticoimmunologic activity that favors infections and allergies: adrenal cortex insufficiency, elevated histamines, and elevated IL-1. The exacerbating factors are somatotropic findings that are nearly always present in children with extrinsic asthma. The first group is the general factors of hypermetabolism (Metabolic activity) and over solicitation of the exocrine pancreas (Somatostatin index) that favor overfabrication of immune elements. The second group relates to cellular metabolism culminating in a functional mitochondriopathy (Pro-amyloid index). Frequently occurring factors occur over 80% in our study and are related to the adaptation capability of the organism. Commonly occurring factors occurred about 70%–75% of the time and relate to the maturation (adaptation index and ACTH index) and release (genito-thyroid) of lymphocytes, the role of eosinophilia in the patient (adaptation index) and thyroid function (genito-thyroid,66 thyroid index, thyroid yield, and thyroid relaunching) (Table 2.9). Many children diagnosed with asthma have other atopic disorders as comorbidity. The critical terrains of atopic disorders are slightly different. Thus, if two atopic disorders are co-expressed, the specific BoF findings proposed in Table 2.9 may not all be present.

Adults In adults, the role of the exocrine and endocrine pancreas by BoF evaluation is not as consistent a feature as it is in

Asthma: An integrative physiologic approach Chapter | 2  39

TABLE 2.9  BoF extrinsic asthma findings in children Frequency

Index

Value

Critical terrain

(S) Adrenal cortex

↓

(F) Evoked histamine

↑

(F) IL-1

↑

(F) Somatostatin

↑

(S, F) Metabolic activity

↑

(S) Insulin resistance

↑

(F) Redox

↓

(F) Pro-amyloid

↑

(F) Cortisol67

↓

(F) Adaptation permissivity of the adrenal cortex

↓ or negative

(S) ACTH

↑

Exacerbating factors

Frequently occurring

Commonly associated

↑

(F) Adaptation 66

(F) Genito-thyroid

↓

(F) Thyroid

↑

(F), Function value; (S), structure value.

children. However, findings may be different from physical examination or history. The role of the thymus is less pronounced. Finally, cortisol is less frequently diminished in adults than in children (Table 2.10).

Treatment of extrinsic asthma From a therapeutic standpoint, asthma is mostly managed with a combination of short- and long-acting ­bronchodilators

TABLE 2.10  BoF extrinsic asthma findings in adults Frequency

Index

Value

Critical terrain

(S) Adrenal cortex

↓

(F) Evoked histamine

↑

(F) IL-1

↑

(S, F) Metabolic activity

↑

(F) Redox

↓

Exacerbating factors

(F) Pro-amyloid Commonly occurring

67

↑

(F) Cortisol

↓

(F) Adaptation permissivity of the adrenal cortex

↓ or negative

(F) Adaptation

↑

(F), Function value; (S), structure value.

and inhaled corticosteroids that target the inflammatory and smooth muscle responses. Although effective in the majority of patients, this approach to management falls a long way short of being ideal, as reflected by low patient adherence to treatment, dependency on the use of inhaled drugs (sometimes for life), and the remaining unmet clinical need, especially from exacerbations, at the severe end of the disease spectrum (approximately 10%).The question that needs to be asked is whether this dependence on suppressive drugs is an end in itself or whether we should be aspiring to higher gains for asthma sufferers. Stephen T. Holgate,68 MD, FRCP, Medical Research Council Clinical Professor of Immunopharmacology at the Faculty of Medicine, Southampton, United Kingdom.

Considering that there are three subtypes of extrinsic asthma and a number of exacerbating factors, the need for a personalized approach to asthma treatment is self-­ evident from the perspective of Endobiogeny. The c­ lassical biomedical approach is focused exclusively on reacting to downstream mediators of airway disease rather than the upstream causes of asthma. The approach is helpful for acute management of hypoxia to be sure, but its limitations in long-term outpatient management belie the foundational soundness of this approach. Acute exacerbations of asthma should be managed according to the standard of care for the safe and effective amelioration of dyspnea and hypoxia. Patients with asthma should have a plan of care that instructs them on how to manage mild asthma attacks at home and when to contact their primary healthcare provider should they need additional ambulatory support. When using a beta-agonist rescue treatment space should always be used to ensure greater efficiency of delivery of medication. Goals should include both clinical signs of poor asthma management (i.e., the frequency of use of rescue therapies) as well as regular measurements of peak expiratory flow with target ranges for initiating home rescue therapy and for advancing to secondary and tertiary healthcare.

General considerations of the order of treatment Extrinsic asthma has more bronchoconstriction and inflammation than hypersecretions and mucous plugging. Histamine is elevated locally more than systemically. Outpatient management should be geared toward localized antiinflammatory and bronchodilating treatments, and systemic treatment of neuroendocrine mediators of local dysfunction. The general order of importance of treatment during acute exacerbation and beyond is: 1. Symptomatic and substitutive: pharmaceutical 2. Symptomatic: nonpharmaceutical

40  The Theory of Endobiogeny

3. Support acute adaptative response 4. Treat the terrain The potential rapidity of deterioration of asthma must be respected. The desire for “natural” treatments in refractory or poorly controlled asthma is not only inappropriate but may be fatal. The vast majority of deaths from asthma occur at home—suffocation occurs quickly before emergency services can transport the patient to the hospital.

Classification of pharmaceutical agents 1. Bronchodilators a. Beta-agonists (BA) i. Short Acting (SABA) 1. Albuterol 2. Levalbuterol 3. Pirbuterol ii. Long acting (LABA) 1. Salmeterol 2. Formoterol b. Anticholinergic i. Ipratropium ii. Atropine 2. Antiinflammatories a. Inhaled corticosteroids (ICS) i. Beclomethasone ii. Budesonide iii. Ciclesonide iv. Fluticasone v. Mometasone vi. Triamcinolone b. Leukotriene receptor antagonists (LTRA) i. Montelukast ii. Zafirlukast c. 5-lipoxygenase inhibitors i. Zileuton 3. Beta-agonist combination therapies a. + Antiinflammatory



i. Symbicort ii. Dulera iii. Advair b. + Anticholinergic i. Combivent ii. DuoNeb 4. Bronchodilator/antiinflammatory: methylxanthines a. Theophylline 5. Mast cell stabilizers a. Cromolyn 6. Emerging therapies a. TAS2R agonists (bitter taste receptors): present on tongue and bronchi, bronchodilate.69–71 Some thoracic societies recommend monitoring serum and sputum eosinophil counts.72 One advantage is p­ rediction of responsiveness to therapy.73 The lower the eosinophil count, the less likely inhaled steroids will be of benefit (suggesting a possible intrinsic case of asthma). Another is that it helps guide management to reduce disease burden and need for hospitalization more accurately than symptom ­evaluation.72 The current approach is to classify the severity of asthma according to the frequency of symptoms and peak flow performance (Table 2.11). Based on this, first line and alternative treatments can be assigned to each classification of severity (Table 2.12).

Symptomatic nonpharmaceutical therapy In order of importance, the order of symptomatic treatment is listed below. It can be used concurrently with pharmaceutical approaches (Table 2.13). 1. Antispasmodic 2. Decongestant 3. Antiinflammatory 4. Antiallergic 5. Antiinfectious 6. Mucolytic 7. Expectorant

TABLE 2.11  Clinical classification of severity of asthma Stage

Diurnal symptoms

Nocturnal symptoms

Peak flow performance

1: Intermittent

2/month

80% predicted with 20%–30% variability

3: Moderate persistent

Daily with daily use of beta-agonists

>1/week

61%–79% predicted

4: Severe

Permanent limitation of physical activity

Frequent

30% variability

PF, peak flow.

Asthma: An integrative physiologic approach Chapter | 2  41

asthma; the suggested usage here is as a general component of broncho-relaxation. Oral dosing is not expected to acutely relieve bronchospasm. 2. Se (Selenium) Discussed under nutrition 3. S (Sulfur): Helps protect the airways through the production of sulfurated proteins: glycosaminoglycans, chondroitin sulfate, dermatan sulfate, keratin sulfate, heparin (mast-cell derived), stimulates healing, and reduces inflammation79

TABLE 2.12  Classification of step-wise therapy based on clinical severity of asthma Severity

First-line

Alternate

1: Intermittent

None

2: Mild, persistent

ICS-LD

Theophylline-SR, or Cromolyn, or LTRA

3: Moderate persistent

ICS-MD + LABA

ICSMD + theophyllineSR or ICS-MD + LABA or ICS-MD + LTRA or ICS-HD

4: Severe persistent

ICS-HD + LABA and as needed: 1) Theophylline-SR

A diet rich in naturally occurring antioxidants in naturally occurring concentrations can also be of benefit (cf. below). Addressing dysbiosis may also prove to be of benefit (cf. Alimentation).

Additional antiinfectious support74, 75 1. Satureja montana EO 2. Cinnamomum zeylanicum EO 3. Cu-Au-Ag (Copper-Gold-Silver)

2) LTRA 3) Oral glucocorticoids

Efficient essential oils that can be nebulized directly into the lungs

-HD, high dose; ICS, inhaled corticosteroid; -LD, low-dose; LABA, longacting beta-agonist; LTRA, leukotriene receptor antagonist; -MD, mediumdose; SABA, short-acting beta-agonist; -SR, sustained release.

Some of these plants can also be used orally in other Galenical preparations.

Thanks to the polyvalent action of medicinal plants, a single plant can possess many of the above properties simultaneously.74, 75

1. Eucalyptus ssp. a. Galenic: EO, BH b. Summary: a diverse and well-tolerated EO for nebulized, inhaled, and oral use. Addresses pulmonary, immune, mucus and inflammatory issues directly, and indirectly through its actions on the pancreas. The Eucalyptus globulus EO and rectified products should be avoided in children under 2 years of age to avoid laryngospasm. c. Actions: ID: antiinfectious (ENT, pulmonary, urinary: antibacterial, antiviral, antifungal, antiparasitic: Plasmodium), Pulm: expectorant, mucolytic,

Additional antiinflammatory support: Oligoelements Regulation of immunity can be achieved in a number of ways. The most fundamental way is regulation of the neuroendocrine terrain as discussed prior. However, key oligoelements can assist in managing inflammation and healing. 1. Magnesium: Bronchodilation76–78: the effects have been studied for intravenous infusion for acute treatment of

TABLE 2.13  Symptomatic nonpharmaceutical treatments in order of importance of treatment Plant

Antispasmodic

Agrimonia eupatoria

•

Lavandula angustifolia

•

Plantago major

•

Thymus vulgaris

•

Decongestant

Antiinflammatory

Antiallergic

Antiinfectious

•

•

•

•

•

•

•

•

•

•

•, indirect

Viola tricolor

•, indirect

Arctium lappa

•, indirect

Eucalyptus ssp.

•

Mucolytic

Expectorant

•

•

• •

• •

•

•

•

•

42  The Theory of Endobiogeny

bronchodilator, antitussive, pulmonary drainer, and increases surfactant production (in  vitro); ENT: Nasal decongestant; Endo: Pancreas: hypoglycemant (E.O., through exocrine pancreatic activity), stimulates endocrine pancreatic activity; Reduces adiposity; Immune: febrifuge, antirheumatic, inhibits histamine release, inhibits inflammatory cytokines, and prostaglandin release from monocytes, antioxidant; GI: Augments hepatic microsomes; Neuro: Antalgic, mental spasmolytic; Note: Eucalyptus radiata for nebulized applications, esp. in children. d. Use: infectious disorders (pulmonary, urogenital— prostatitis, and parasites), infectious prophylaxis in diabetics; Pulmonary affections, infectious or metabolic: asthma, bronchitis, chronic cough, digestive disorders; diabetes, inflammatory disorders; rheumatisms; e. Methods: Leaf: Decoction 1 tsp. leaves in ¾ c. water 20 min; drink 3–4 times per day with meals; Gargle; decoction made with 1 tbsp leaves in ¾ c. water; EO: 3%– 10% topical; EO: Nebulize 1 drop/3 cc normal saline; 2. Thymus vulgaris ct. linalool a. Galenic: EO, BH, MT b. Summary: important for its activity in the corticoimmune axis with direct mucolytic properties. It is most indicated with adrenal insufficiency and when infections play a prominent role in inciting an asthma attack. c. Actions: Immune: antiinfectious (ENT, pulmonary, intestinal, pharyngeal, urinary, genital, and cutaneous), antifungal, antibacterial (gram +, gram −), antiviral, antiherpetic, anthelminthic, vermifuge; immune stimulant; antioxidant, antiinflammatory; febrifuge; Pulmonary: Mucolytic, expectorant; Digestive: neurotropic digestive carminative, eupeptic, choleretic, antigastric; ANS: Parasympatholytic (strong vagolytic); Endo: Adrenal: adrenal cortex stimulant, Gonad: Emmenagogue, binds to estrogen, progesterone receptors; Neuro: Analgesic Neuromuscular: Spasmolytic; Renal: volumetric diuretic d. Use: Dysmenorrhea, paralytic fear, spasmophilia, hypotension, infections, digestive disorders, rheumatic disorders e. Methods: EO: topical, internal (PO) Acute: 2 gtt TID; Nonacute: 0.5–2 drops/day; EO-rectal: 0.1%; Tisane (general use): ½ tsp./cup water, infuse 5 min; Neutropenia: 2 tsp. of Thymus vulgaris herb in 6 cups water. Boil 7 min, steep 7 min. Drink throughout the day.—p.42, Consultation Boucicault; Compress, Oral rinse: 1 tbsp/1 cup water; Bath: 1 cup in 4 L water; add to bath f. Contradictions: Pregnancy, HTN, Glaucoma, hyposecretory states

3. Lavandula angustifolia a. Summary: Broncho-spasmolytic, antiallergic, antiinflammatory, and antiinfectious. It stabilizes mast cells and is indicated when histamine activity is prominent and when emotional shocks play a role in asthma. It is well tolerated in all ages. 4. Abies balsamea (Balsam fir) a. Galenic: GM (bud), EO (needles) b. Summary: Beta-agonist, antiviral, excellent for use in acute extrinsic asthma attacks80 c. Actions: Osteo: osteoblastic (buds, stimulates osseous reconstruction); ID: antiinfectious (ENT, pulmonary); Pulm: antitussive, expectorant; Adrenal: adrenal cortex stimulant; ANS: sympathomimetic (beta > alpha). d. Use: i. Cortico-ID: Adrenal insufficiency with chronic infections (+ Betula verrucosa + Rosa canina esp. with fatigue), lymph node hypertrophy, asthma, esp. nebulized

Supporting the acute adaptive response Support for acute adaptation of the asthmatic response should be in the following order: 1. Reduce Para 2. Increase Beta 3. Peripheral Corticotropic support 4. Endocrine pancreas 5. Emunctories

Parasympathetic inhibition 1. Thymus vulgaris 2. Artemisia dracunculus81, 82

Beta support Do not nebulize the essential oils (EO) listed below. They can be added to tinctures, or in a base of vegetal oil and taken orally. They may not be tolerated late at night and may cause insomnia or tachycardia. Strong taste not well tolerated by smaller children and sensitive adults.74, 75 1. Ribes nigrum GM 2. Rosa canina GM 3. Cinnamomum zeylanicum (Cinnamon) 4. Satureja montana (Savory) a. Galenic: EO, BH b. Summary: It is most indicated for more advanced cases of asthenia and adrenal insufficiency when infections play a prominent role in inciting an asthma attack and in patient with strong spasmophilic tendencies or comorbidities, such as arthritis or intestinal candidiasis.

Asthma: An integrative physiologic approach Chapter | 2  43

c. Actions: Immune: Immunostimulant; ID: Antibacterial: gram +, gram −, antifungal, antiviral, antiparasitic, antiprotozoal; GI: eupeptic, carminative, astringent, rebalances intestinal flora; ANS: Sympathomimetic beta > alpha; Endo: Cortico: Adrenal cortex stimulant (general) improves permissive cortisol, Gonado: Increases serum androgens; Osteo: Antirheumatic; Neuro: Neuralgic; d. Use: Spasmodic Colitis, gastroenteritis, diarrhea, candidiasis, all infectious disorders, neurasthenia, depression (psychomotor retardation), asthma, rheumatic disorders, topical infections, e. Method: EO: PO: 0.5–5 drops/day, topical: mix with other EO’s, dilute and use in localized areas only; Hydrolat: PO 1–3 tsp. bid, as gargle, nebulized, compress; Tisane: 1–2 tsp. in ¾ c. water, infuse 10 min, 2–3 c/day; f. Contra: Pregnancy, nursing, hemorrhoids, hemorrhagic disorders, Crohn’s (esp. rectal EO), Relative: Adrenal overstimulation, hypertension, gastritis, hepatic failure.

Corticotropic axis: Peripheral Supporting global adrenal cortex and cortisol activity will reduce ACTH by vertical inhibition.74, 75 1. Ribes nigrum (Cassis) a. Galenic: GM b. Summary: The most versatile corticotropic regulator. It can be used in any disorder in which corticotropic, cortico-somatotropic or cortico-gonadotropic activity is implicated. c. Actions: Leaves: astringent, antihemorrhagic, antirheumatic, antiarthritic, antihypertensive, antiinflammatory, cicatrizing, glucocorticoid, antiallergic, venous and capillary vasoconstrictor, intestinal antiseptic, β-sympathomimetic. Gemmo: Adaptogen; Allergies: Best corrector of the allergic terrain; Endo: Cortico: adrenal cortex stimulant by regulating pituitary action, cortisol analogue that favors inhibition of ACTH by classical feedback; Immune: febrifuge, antiinfectious (ENT and pulmonary), Antiinflammatory (arteries, bronchus, mucocutaneous, digestive, urinary, and joints), antiexudative at the level of the tissues, Drainage: “A true drainer active at low doses” (P. Andrienne citing P. Henry) d. Use: Adaptogen; Allergies: environmental, sun, drug allergies, food allergies, and respiratory allergies; Inflammation: General and acute phase (+ Betula pubescens GM, Alnus glutinosa GM); ENT: parotitis, sinusitis, tonsillitis, laryngitis, croup, allergic rhinitis; Respiratory: Acute ­bronchitis in Adults:

(Ribes nigrum GM 60 mL, Populus nigra GM 60 mL + Satureja montana EO 0.5 mL, Cinnamomum zeylanicum EO 0.5 mL, Myrtillus communis EO 0.5 mL: 2 mL TID), Pediatric bronchitis: (Ribes nigrum GM 40 mL, Angelica archangelica MT 40 mL, Inula helenium MT 40 mL + Eucalyptus smithii EO 0.25 mL, Melaleuca quinquenervia EO 0.25 mL; DOSE: 1 mL TID) Bronchial-Allergic: + Sambucus MT); asthma, emphysema 2. Rosa canina (Dog rose) a. Galenic: GM b. Summary: A good sympathetico-corticotropic support in children and cases of asthenia, especially with comorbidities of ENT illnesses and/or food allergies. c. Actions: Endo: Cortico: adrenal cortex stimulant favoring production of adrenal androgens, ANS: βsympathomimetic, Drainage: drains tonsils and adenoids, ID: Antiinfectious (ENT) d. Use: Failure to thrive, Recurrent ENT disorders, Asthma, Allergies, Eczema, and Chronic sinusitis (+ Juglans regia + Hepar sulf 9c) 3. Quercus pedunculata (Oak) a. Galenic: GM b. Summary: An excellent polyendocrine product that redistributes the general endocrine activity allowing for a general regulation of the organism. c. Actions: Endo: Central: Pituitary: redistributes endocrine activity in a general way, Corticotropic: supports glucocorticoid production in the adrenals (gemma), supports adrenals without being stimulating, inhibits ACTH through similarity of action, ID: antiinfectious (dermatologic tropism and general support in part through its general regulatory activity on the adrenal cortex). d. Use: Any disorder of adrenal insufficiency such as asthma, immune dysfunction, allergies, sinusitis, etc., 4. Abies pectinata (Balsam fir) (cf. above) 5. Pinus sylvestris (Pine) a. Galenic: EO, GM, Hydrolat b. Summary: It is indicated for asthenic disorders, especially with cortico-immune insufficiency c. Actions: Endo: Cortico: adrenal cortex stimulant; ANS: Sympathicotonic; ID: antiinfectious (ENT, pulmonary++), Pulm: expectorant, sympathomimetic. d. Use: Chronic infections with adrenal insufficiencies (+ Fagus sylvatica GM, Rosa canina GM), Mental exhaustion with anxiety (+ Betula pubescens GM, Quercus pedunculata GM, and Tilia tomentosa GM) 6. Sequoia gigantea (Sequoia) a. Galenic: GM b. Summary: Use in cases of peripheral adrenal overstimulation where Cortisol: Adrenal cortex >5 with

44  The Theory of Endobiogeny

an absolute global adrenal cortex insufficiency and to restore bone after catabolic activity. c. Actions: Endo: Cortico: An adrenal cortex stimulant favoring adrenal androgens. It reduces cortisol and aldosterone by shifting adrenal metabolism toward Adrenal androgens. It inhibits ACTH by negative feedback. It promotes osseous reconstruction by assuring androgen availability and blocking estrogen receptors, therefore useful for assuring the foundation structure. It prevents estrogen insufficiency by invoking activity of growth factors and estrogen precursors. MS: relaxes muscles and ligaments d. Use: General: Revitalizer, general tonic, antisenescent, Adrenal fatigue (+Quercus pedunculata + Ribes nigrum), blocked immunity hyperalpha-corticotropic activity, osteoporosis, and muscular and ligamentous tension. 7. Glycyrrhiza glabra (Licorice) a. Galenic: BH, MT, DE b. Summary: Indicated for allergic and mucosal inflammatory conditions and as complimentary adrenal support. c. Actions: Endo: Cortico: Aldosterone-like (favors sodium retention), potentiates effects of corticosteroids, Gonado: Estrogenic, Allergy: antiallergic (respiratory), ID: antiinfectious (ENT, respiratory), Pulm: expectorant, Immune: antiinflammatory (digestive and respiratory), GI: digestive antispasmodic, antacid, antigastric d. Use: Asthmatiform bronchitis, asthma with a component of gastro-esophageal reflux or dysbiosis, asthma with food allergy comorbidity, etc.

Corticotropic axis: Peripheral: Essential oils Adding these essential oils to a tincture or in carrier oil along with microspheres is a very efficient method of addressing the role of the adrenal cortex in various disorders. They can also be diffused. Do not nebulize Satureja montana into the lungs. Avoid nebulizing Thymus vulgaris unless the chemotype has been determined as linalool variety.

order of importance, based on its role in pulmonary ­congestion and general detoxification: 1. Exocrine pancreas 2. Hepatobiliary 3. Skin 4. Intestines

Exocrine pancreas: Prescription medications Digestive enzymes, with meals.

Exocrine pancreas: Medicinal plants The following plants are selected for their dual role on the pancreas and the lungs. 1. Eucalyptus ssp. 2. Cinnamomum zeylanicum (Cinnamon bark), BH, EO83 3. Agrimonia eupatoria 4. Plantago major 5. Arctium lappa

Liver, skin, and intestines 1. Arctium lappa 2. Viola tricolor

An argument for the treatment of terrain Inflammation is noted to be an aggravating factor during acute, subacute and chronic reactive airway disease. Yet, the use of antiinflammatory agents does not halt the progress of the disease over time.8 Chronic use of beta-agonists exposes the patient to tachyphylaxis and is correlated with increased risk of asthma-related death84, 85 Finally, chronic use of the standard asthma treatments can result in various well-known morbidities noted above, such as growth stunting8 and bone fracture8, 86 and worsening of glycemic control in diabetics.87 Ultimately a treatment of the terrain must be instituted to truly address the issues of asthma. The three goals of treatment are as follows:

1. Thymus vulgaris (Thyme) 2. Satureja montana (Savory)

1. Modify the basal demand for oxygen and other nutrients a. Regulation of ACTH, TRH, and TSH 2. Adrenal cortex support (less intense than acute phase) 3. Emunctory drainage (less intense than acute but same order of importance)

Thyrotropic axis: Peripheral

Sample prescriptions for extrinsic asthma

1. Zingiber officinale 2. Avena sativa

5-year-old boy with extrinsic asthma and allergic rhinitis

Emunctory support

Support immunity and bronchial tone 1. Immunity: Cu-Ag-Au 1 mL sublingual in AM 2. Bronchial tone: Mg oligoelements, 1 mL sublingual BID AM and qHS

Emunctory support is part of the basic treatment plan for asthma. The emunctories should be drained in the f­ ollowing

Asthma: An integrative physiologic approach Chapter | 2  45

And add one of the following two based on cost and convenience. Option 1: Mother tincture + EO topical ANS, Corticotropic, Thyrotropic: Rhodiola rosea MT 15 mL, Ribes nigrum GM 30 mL, Avena sativa MT 15 mL: 2 mL four times per day for 5–7 days. Inflammation, Emunctories, Bronchospasm: Plantago major MT 50 mL, Viola tricolor MT 50 mL, Populus nigra GM 10 mL, DOSE: 2 mL four times per day for 14 days. Local pulmonary care Essential oils of ● ● ● ● ●

Thymus vulgaris 6 drops Lavandula angustifolia, 3 drop Eucalyptus globulus leaf, 3 drop Abies balsamea, 3 drop Olive oil, 15 mL Instructions

1. Mix essential oils and carrier oil in a glass dish 2. Warm between hands and apply with friction in a clockwise circular motion to anterior and posterior chest a. Prophylaxis: once per day b. Mild wheezing,  Pulmonary function test > 70% expected: 3 times per day c. During acute allergic asthma attack along with the standard of care treatment: 4 times per day 3. Apply residual mixture left on hands over cervical lymph nodes and sternal notch. Avoid the eyes. 4. Complete treatment by making a hollow fist and tapping across the upper chest (infraclavicular and sternal notch), then over lungs, right and left, and anterior and posterior

Ribes nigrum GM, 60 mL, Glycyrrhiza glabra root MT, 60 mL, Arctium lappa root MT 60 mL, Avena sativa leaf MT 60 mL + Eucalyptus smithii EO 3 mL, and Thymus vulgaris EO 2 mL; Dose: 2.5 mL twice per day before meals. #2: Nocturnal therapy: Angelica archangelica MT 60 mL, Matricaria recutita MT 60 mL + Lavandula angustifolia EO 3 mL; Dose: 4 mL 1 h before bed. #3: Bronchial epithelium: S oligoelements 1 mL sublingual BID AM and 1 h before bed. #4: Bronchial tone: Mg oligoelements, 1 mL sublingual BID AM and 1 h before bed. Table 2.14 presents a summary of the terrain and treatment of extrinsic asthma.

Environmental: Reduction of exogenous aggressors There are three general strategies with respect to exogenous aggressors: elimination of known aggressors—especially in TABLE 2.14  Summary of terrain and treatment of extrinsic asthma Factor

Extrinsic (allergic)

Cause

Vagotonia Hyperimmunity Exocrine pancreas Liver-gallbladder

Agent

Allergens

Response

Excessive adaptation to moderate or weak allergen Para-alpha Corticotropic Thyrotropic Thyro-somatotropic Exocrine pancreas Liver Skin Intestines

Mechanism

Bronchospasm Inflammation Airway obstruction

Effect

Hypoxia Hypercapnia Dyspnea Death

Symptomatic and root cause treatment priorities

Support Beta Support adrenal cortex Antispasmodic Decongestant Antiinflammatory Antiallergic and/or antiinfectious Mucolytic Fluidifiers and expectorants

Option 2: Decoction and tisane ● ● ● ● ●

Glycyrrhiza glabra root, 1 tbsp Eucalyptus globulus leaf, ½ tsp. Plantago major, ½ tsp. Avena sativa, ½ tsp. Thymus vulgaris or Lavandula angustifolia, ½ tsp. Instructions

1. Decoct Glycyrrhiza glabra root 1 tbsp in 4 cups of water for 15 min, remove from heat. 2. Add additional ingredients and let steep for 5–7 min. 3. Add honey to taste 4. Administer in 3–4 divided doses per day. #2: Local pulmonary care (cf. above).

12-year-old girl with extrinsic asthma and nocturnal exacerbation #1: ANS, Corticotropic, Thyrotropic, HepatobiliaryPancreatic drainage:

46  The Theory of Endobiogeny

the house, avoidance of known allergens, and moderation against that which cannot be completely avoided or eliminated. Elimination The house is the most important environment to focus on because it is the one that asthmatics—especially children—spend the most time. Unlike the work and regional environments, the patient will have the greatest relative control of the home environment. ● ● ● ● ● ● ● ●

Carpets Plush toys Dust Smoking of tobacco or marijuana around asthmatics Insect control Frequent washing of bedding Allergenic pets Mold Avoidance

● ●

Known allergens Nondomicile locations likely to have known aggressors Protection

● ●

●

Room ionizers HEPA (High-efficiency particulate absorber) filtration units Regular trips to areas dense in trees (unless pollen is an aggressor) and high elevations with cleaner air

Secondary treatments of asthma Alimentation Dietary interventions can reduce asthma burden at both pathophysiologic and clinical levels of evaluation. A Mediterranean diet, rich in fresh fruits and vegetables and omega-3 fatty acids from fish helps reduce the disease burden in asthmatics as measured by objective markers such as FEV116, 88–91 and may reduce progression to chronic obstructive lung disease.91, 92 Amongst fruit, apples are more protective than citrus but both are beneficial.88, 90 Diets rich in selenium and sulfur (buckwheat, onions, garlic, and cruciferous vegetables) may also be of benefit.93 Diets rich in magnesium (dark leafy green vegetables, nuts and seeds, fish, avocados, bananas, dark chocolate, and yogurt) are correlated with reduced disease burden.21, 22, 88, 91 Bitter foods and herbs may be of benefit in bronchodilation.69, 70, 79 Addressing dysbiosis may help address global dysfunction of the immune system. Results of animal trials are impressive94 however, metaanalysis of human trials are either equivocal or indicate benefit when probiotics are administered both pre- and postnatal for 2–5 years.95–97 Consumption of indigenous f­ ermented foods and drinks may be another option. Examples would include fermented drinks, such as kombucha, kvass, and foods, such as yogurt, natto,

kashk (fermented whey), sauerkraut, cornichon, etc. The summary of most beneficial foods by the correlative epidemiologic investigation is summarized in Table 2.15.

Vitamin and mineral supplementation According to the theory of Endobiogeny, foods are the most optimal source of vitamins and minerals for several reasons. A number of foods are efficient for the treatment of asthma due to synergistic association of vitamins and minerals in bioavailable chelates, and associated compounds that enhance absorption, distribution, and incorporation into cellular structure and cellular function (Table  2.15). However, quality sources of food may not always be available or affordable for patients. Compliance with a healthy diet can also be challenging. In other situations, supraphysiologic doses of vitamins or minerals may prove to be of benefit for a limited period of time in order to improve the buffering capacity of the organism. With respect to extrinsic (allergic) asthma, the alpha-tocopherol isoforms of Vitamin E can be of benefit.98 We recommend 25–100 mg per day of alpha-tocopherol vitamin E. Selenium is a trace mineral that regulates both immunity and cellular oxidation patterns. It acts as a cofactor in the formation of immune products as well as in the regulation of oxidation and inflammation. It has been shown to be of benefit in patients with asthma.93 100–200 μg/day is a conservative dosing schedule. We recommend the use of Selenium along with Sulfur as oligoelements in more advanced cases of asthma, dosed as 1 ampule or 2 mL twice per day before meals. In patients who have very reactive airways, especially with emotionally triggered asthma, and in patients in which the endocrine pancreas in more implicated, magnesium-rich foods and magnesium supplementation may be of benefit.76–78

Exercise therapy Exercise therapies such as yoga can improve ANS tone in asthmatics.99

Lifestyle Perhaps the most crucial barrier to more effective control of asthmatic symptoms and improved quality of life is the lack of compliance with treatment. The major barriers to compliance include. ● ● ●

●

Denial of disease Side effects of medications Improper understanding of the nature and triggers of asthma Insufficient communication between providers and patients regarding the ambulatory management of asthma.

Education about the disease may not be sufficient to change healthcare practices.100 Asthma action plans, based

Asthma: An integrative physiologic approach Chapter | 2  47

TABLE 2.15  Summary of most efficient foods for the treatment of asthma based on type of nutrient Food

Fruits

Apples

•

Avocados

•

Berries

•

Kiwi

Mg

Se

Vit. A, E

Class

S

•

•

Bananas Vegetables

Antioxidants and bioflavonoids

Pro-biotics

•

• •

Sprouts Dark leafy greens (best: spinach, collard greens, kale)

Vit B’s

• •

•

•

Endive

•

•

Tomato

•

•

Carrots

•

Gourds

•

Onions

•

•

Garlic

•

•

Grains

Buckwheat

•

Nuts and seeds

Flax, pumpkin, sunflower

•

Spices

Turmeric, ginger

Others

Brewer’s yeast

•

•

• •

•

Fermented drinks Fermented foods

•

•

•

•

• •

Cf. http://www.healwithfood.org/asthma/foods.php. Cf. Asthma recipes: http://www.healwithfood.org/asthma/recipes/maindishes.php.

on ­frequency of usage of rescue medication and/or peak flow values, as well as frequent monitoring with a medical home, appear to be the most efficient ways to improve asthma compliance.101, 102 A collaborative relationship is important in the face of what is deemed to be often a life-long and possibly progressive disease with chronic or permanent use of medication.103

Cause: Precritical terrain of intrinsic asthma: ANS

Intrinsic asthma

Cause: Precritical terrain of intrinsic asthma: Endocrine

Intrinsic asthma has a different terrain than extrinsic (allergic) asthma, even if it shares some elements of pathophysiology.

Both types (4 and 5) are intrinsic vagotonics. Type 4 asthmatics have a latent spasmophilia. Type 5 has an expressed spasmophilia in the precritical terrain (Table 2.16).

Definition

The two anabolic axes are oversolicited and overfunctioning in the precritical state but the organism is able to compensate for the oxygen demand:

Intrinsic asthma is a spasmophilic disorder of the airways in response to an oversolicitation of oxygen for metabolic demands of a nonallergic origin.

1. Gonadotropic (cf. Volume 2, Chapter 11: Spasmophilia and Structuro-functional for detailed discussion): a. Hyperestrogenism

48  The Theory of Endobiogeny

TABLE 2.16  Endobiogenic classification of asthma by precritical terrain Category

Type

Parasympathetic

Alpha sympathetic

Beta sympathetic

Intrinsic (nonallergic)

4

++ (vagotonic)

Normal

Normal

5

++ (vagotonic)

Normal

Insufficient

Precritical spasmophilia

•

i. BoF: various estrogen indices high b. Hypoluteal state i. BoF: Various androgenic indices low or lower than estrogen activity 2. Somatotropic: a. Insulin resistance > Insulin sensitivity with congestive tendencies i. BoF 1. Insulin index: low for age 2. Insulin resistance: high

Any factor that diminishes oxygen availability can also play a role. Examples include:

Cause: Precritical terrain of intrinsic asthma: Emunctory

The ANS and emunctory responses are similar, but the endocrine response is based in sequential overactivation of the four axes starting with the gonadotropic. ANS: First response

1. Exocrine pancreas: oversolicited a. BoF: Somatostatin index: normal or High 2. Lungs: congested 3. Hepatobiliary: congested

Agents of intrinsic asthma The onset of intrinsic asthma is typically due to a hyperanabolic response to the solicitation of the gonadotropic axis for structuro-functional activity (cf. Volume 2, Chapter 11: Spasmophilia: Structuro-functional). Examples include: 1. Childhood: 0–4 2. Grand phases a. Adolescence b. Menarche c. Gonadopause 3. Menstrual cycle 4. Genital recycling 5. Pregnancy It can also be due to nonallergic adaptation demands such as seasonal changes, cold, and exertion and adaptational spasmophilias (cf. The Theory of Endobiogeny, Volume 2, Chapter 11). 1. Emotional crisis 2. Cold 3. Exertion 4. Seasonal changes

1. Anemia 2. Dehydration 3. Tissue alkalosis 4. Neuromuscular diseases: thoracic cage, diaphragm, and accessory muscles.

Response: Critical terrain of intrinsic asthma

1. Hyper para 2. Hyper alpha 3. Beta a. Insufficient or b. Delayed Endocrine Second response (in order) 1. Gonadotropic: overfunctioning 2. Thyrotropic: overfunctioning (central > peripheral) 3. Somatotropic: overfunctioning a. Central: GH, PL per case b. Peripheral: always implicated 4. Corticotropic: insufficient peripheral function Emunctory and digestive organ 1. Exocrine pancreas: oversolicited a. BoF: Somatostatin index: normal or High 2. Lungs: congested 3. Hepatobiliary: congested

Mechanisms of intrinsic asthma The mechanisms of histopathology are the same as in extrinsic asthma. However, in intrinsic asthma, hypersecretions, and mucosal congestion play a greater role compared to bronchoconstriction and histamines for extrinsic asthmatics.

Asthma: An integrative physiologic approach Chapter | 2  49

Treatment of intrinsic asthma The basic approach to the asthma crisis is the same, but the symptomatic approach favors more pancreatic support and mucolytic and expectorant emphasis. Allergic and antiinfectious treatments generally do not play a role.

TABLE 2.17  Summary of principles of extrinsic and intrinsic asthma with differences highlighted in bold Factor

Extrinsic (allergic)

Intrinsic (nonallergic)

Cause

Vagotonia Hyperimmunity Exocrine pancreas Liver-gallbladder

Vagotonia Hyperanabolism Exocrine pancreas Liver-gallbladder

Agent

Allergens

Structuro-functional demand Functional demand

Response

Excessive adaptation to moderate or weak allergen Para-Alpha Corticotropic Thyrotropic Thyro-somatotropic Exocrine pancreas Liver Skin Intestines

Hyperanabolic response > oxygen presentation Para-Alpha Gonadotropic Thyrotropic Somatotropic Corticotropic Exocrine pancreas Hepato-biliary

Mechanism

Bronchospasm Inflammation Airway obstruction

Bronchospasm Airway obstruction Inflammation

Effect

Hypoxia Hypercapnia Dyspnea Death

Symptomatic Treatment priorities

Support Beta Support adrenal cortex Antispasmodic Decongestant Antiinflammatory Antiallergic and/or antiinfectious Mucolytic Fluidifiers and expectorants

Symptomatic treatment of intrinsic asthma 1. Symptomatic: pharmaceutical 2. Symptomatic: nonpharmaceutical importance) a. Antispasmodic b. Decongestant c. Mucolytic d. Fluidifying e. Antiinflammatory

(in

order

of

Supporting the acute adaptative response The initial treatment is the same as in extrinsic asthma: reduce para, increase beta, and support the adrenal cortex. The remainder is specific to the hyperanabolic terrain. 1. Reduce Para 2. Support Beta 3. Peripheral corticotropic support 4. Gonadotropic a. Reduce hyperestrogenism if required b. Support luteal activity as per terrain, that is, Asthma of following origins: i. Adolescent ii. Premenstrual progesterone insufficiency iii. Pregnancy iv. Postgonadopause 5. Thyrotropic a. Support peripheral thyroid activity to meet gonadotropic demand (cf. indications above for Gonadotropic)

Supporting the emunctories The approach is the same, in the same order of importance: 1. Exocrine pancreas 2. Hepatobiliary 3. Skin 4. Intestines 5. Chronic: Kidney response to chronic ACTH demand

Treatment of the terrain The general approach is similar in concept to extrinsic asthma, but the anabolic nature of the disorder requires a modification to the approach (Table 2.17):

Support Beta Support adrenal cortex Antispasmodic Decongestant Mucolytic Fluidifiers and expectorants Antiinflammatory

1. Modify the basal demand for oxygen and other nutrients a. Regulation of Gonado-thyrotropic activity when related to structuro-functional spasmophilia (cf. The Theory of Endobiogeny, Volume 2, Chapter 11) b. Regulation of Somatotropic response 2. Adrenal cortex support (less intense than acute treatment) 3. Emunctory drainage (less intense than acute but the same order of importance)

Additional considerations Functional: Emotional shock Plants are listed from most to least sedating: 1. Valeriana officinalis EO, MT

50  The Theory of Endobiogeny

2. Scutellaria lateriflora MT 3. Anthemis nobilis BH, EO 4. Lavandula angustifolia BH, EO, MT 5. Tilia tomentosa GM

Functional: Exertional: Adaptogens for exercise-induced asthma 1. Rhodiola rosea (Rhodiola) BH, DE, MT 2. Eleutherococcus senticosus BH, DE, MT 3. Ribes nigrum GM 4. Panax quinquefolius (Ginseng) BH, DE, MT

Sample prescriptions for intrinsic asthma 46-year-old premenopausal woman with exercise-induced asthma #1: Adaptation Rhodiola rosea MT 120 mL, Ribes nigrum GM 60 mL, Quercus pedunculata GM 60 mL, Lavandula angustifolia EO 2 mL, Thymus vulgaris EO ct. linalool 2 mL: 4 mL and AM, 2 mL afternoons for 6 months. #2: Digestion, Metabolic support Avena sativa MT 120 mL, Agrimonia eupatoria MT 120 mL, Artemisia dracunculus EO 4 mL: 3 mL before breakfast and dinner for 6 months.

New onset asthma in a 50-year-old postmenopausal woman with anxiety #1: Adaptation Rhodiola rosea MT 120 mL, Ribes nigrum GM 60 mL, Quercus pedunculata GM 60 mL, Lavandula angustifolia EO 2 mL, Thymus vulgaris EO ct. linalool 2 mL: 4 mL and AM, 2 mL afternoons for 9–12 months. #2: ANS, Anxiety, Gonadothyrotropic, Inflammation, Digestion, Metabolic Passiflora incarnata MT 60 mL, Salvia officinalis MT 60 mL, Achillea millefolium MT 60 mL, Menyanthes trifoliata MT 60 mL, and Artemisia dracunculus EO 4 mL: 3 mL before breakfast and dinner for 9–12 months.

Conclusions Asthma is a spasmophilic disorder related to the management of oxygen entry. According to the theory of Endobiogeny, there are two general types of asthma: extrinsic and intrinsic. Both types are rooted in various permutations of ANS dysfunction with the majority involving vagotonic individuals. Extrinsic asthmatics have a stronger hyperimmune, hyperhistaminic pathophysiology. Intrinsic asthmatics have more predominant role in anabolic f­ actors. The treatment approach to asthma must include both s­ymptomatic ­pharmaceutical

therapies to avoid morbidities of chronic asthma but also a treatment of the terrain. That latter treatment is multimodal including medicinal plants, alimentation, manual therapies, and lifestyle alteration.

References 1. McConnell A. Anatomy and physiology of the respiratory system. In: McConnell  A, ed. Respiratory Muscle Training: Theory and Practice. 2013. [chapter 1]. 2. Ratnovsky  A, Elad  D. Anatomical model of the human trunk for analysis of respiratory muscles mechanics. Respir Physiol Neurobiol. 2005;148(3):245–262. 3. Boiten FA. The effects of emotional behaviour on components of the respiratory cycle. Biol Psychol. 1998;49(1–2):29–51. 4. Bush A, Menzies-Gow A. Phenotypic differences between pediatric and adult asthma. Proc Am Thorac Soc. 2009;6(8):712–719. 5. Bentley AM, Menz G, Storz C, et al. Identification of T lymphocytes, macrophages, and activated eosinophils in the bronchial mucosa in intrinsic asthma. Relationship to symptoms and bronchial responsiveness. Am Rev Respir Dis. 1992;146(2):500–506. 6. Bentley AM, Durham SR, Kay AB. Comparison of the immunopathology of extrinsic, intrinsic and occupational asthma. J Investig Allergol Clin Immunol. 1994;4(5):222–232. 7. Murphy DM, O'Byrne PM. Recent advances in the pathophysiology of asthma. Chest. 2010;137(6):1417–1426. 8. Raissy HH, Kelly HW, Harkins M, Szefler SJ. Inhaled corticosteroids in lung diseases. Am J Respir Crit Care Med. 2013;187(8):798–803. 9. Dietert  RR. Maternal and childhood asthma: risk factors, interactions, and ramifications. Reprod Toxicol. 2011;32(2):198–204. 10. Midodzi WK, Rowe BH, Majaesic CM, Saunders LD, Senthilselvan A. Early life factors associated with incidence of physician-diagnosed asthma in preschool children: results from the Canadian early childhood development cohort study. J Asthma. 2010;47(1):7–13. 11. Dick S, Friend A, Dynes K, et al. A systematic review of associations between environmental exposures and development of asthma in children aged up to 9 years. BMJ Open. 2014;4(11):e006554. 12. Kuiper S, Muris JW, Dompeling E, et al. Interactive effect of family history and environmental factors on respiratory tract-related morbidity in infancy. J Allergy Clin Immunol. 2007;120(2):388–395. 13. McConnochie KM, Roghmann KJ. Parental smoking, presence of older siblings, and family history of asthma increase risk of bronchiolitis. Am J Dis Child. 1986;140(8):806–812. 14. Vogt H, Lindstrom K, Braback L, Hjern A. Preterm birth and inhaled corticosteroid use in 6- to 19-year-olds: a Swedish national cohort study. Pediatrics. 2011;127(6):1052–1059. 15. Murk W, Risnes KR, Bracken MB. Prenatal or early-life exposure to antibiotics and risk of childhood asthma: a systematic review. Pediatrics. 2011;127(6):1125–1138. 16. Saadeh D, Salameh P, Baldi I, Raherison C. Diet and allergic diseases among population aged 0 to 18 years: myth or reality? Nutrients. 2013;5(9):3399–3423. 17. Cabieses B, Uphoff E, Pinart M, Anto JM, Wright J. A systematic review on the development of asthma and allergic diseases in relation to international immigration: the leading role of the environment confirmed. PLoS One. 2014;9(8):e105347. 18. Hjern  A, Rasmussen  F, Hedlin  G. Age at adoption, ethnicity and atopic disorder: a study of internationally adopted young men in Sweden. Pediatr Allergy Immunol. 1999;10(2):101–106.

Asthma: An integrative physiologic approach Chapter | 2  51

19. Braback L, Vogt H, Hjern A. Migration and asthma medication in international adoptees and immigrant families in Sweden. Clin Exp Allergy. 2011;41(8):1108–1115. 20. Hijazi N, Abalkhail B, Seaton A. Asthma and respiratory symptoms in urban and rural Saudi Arabia. Eur Respir J. 1998;12(1):41–44. 21. Hijazi N, Abalkhail B, Seaton A. Diet and childhood asthma in a society in transition: a study in urban and rural Saudi Arabia. Thorax. 2000;55(9):775–779. 22. McKeever TM, Britton J. Diet and asthma. Am J Respir Crit Care Med. 2004;170(7):725–729. 23. Atkinson  RW, Kang  S, Anderson  HR, Mills  IC, Walton  HA. Epidemiological time series studies of PM2.5 and daily mortality and hospital admissions: a systematic review and meta-analysis. Thorax. 2014;69(7):660–665. 24. Jassal MS. Pediatric asthma and ambient pollutant levels in industrializing nations. Int Health. 2014;. 25. Erle  DJ, Sheppard  D. The cell biology of asthma. J Cell Biol. 2014;205(5):621–631. 26. Wenzel SE, Barnes PJ, Bleecker ER, et al. A randomized, doubleblind, placebo-controlled study of tumor necrosis factor-alpha blockade in severe persistent asthma. Am J Respir Crit Care Med. 2009;179(7):549–558. 27. Corren  J, Busse  W, Meltzer  EO, et  al. A randomized, controlled, phase 2 study of AMG 317, an IL-4Ralpha antagonist, in patients with asthma. Am J Respir Crit Care Med. 2010;181(8):788–796. 28. Holgate ST, Noonan M, Chanez P, et al. Efficacy and safety of etanercept in moderate-to-severe asthma: a randomised, controlled trial. Eur Respir J. 2011;37(6):1352–1359. 29. Wadsworth SJ, Dorscheid DR, Yang SJ. IL-13, asthma and glycosylation in airway epithelial repair. In: Chang C-F, ed. Carbohydrates— Comprehensive Studies on Glycobiology and Glycotechnology. London: IntechOpen; 2012. 30. Ober C, Yao TC. The genetics of asthma and allergic disease: a 21st century perspective. Immunol Rev. 2011;242(1):10–30. 31. WHO. Asthma Fact Sheet No.307. http://www.who.int/mediacentre/factsheets/fs307/en/, 2015. (Accessed 1 April 2015). 32. Siroux V, Gonzalez JR, Bouzigon E, et al. Genetic heterogeneity of asthma phenotypes identified by a clustering approach. Eur Respir J. 2014;43(2):439–452. 33. Hui  J, Oka  A, James  A, et  al. A genome-wide association scan for asthma in a general Australian population. Hum Genet. 2008;123(3):297–306. 34. Hancock  DB, Romieu  I, Shi  M, et  al. Genome-wide association study implicates chromosome 9q21.31 as a susceptibility locus for asthma in mexican children. PLoS Genet. 2009;5(8):e1000623. 35. Knight DA, Yang IA, Ko FW, Lim TK. Year in review 2011: asthma, chronic obstructive pulmonary disease and airway biology. Respirology. 2012;17(3):563–572. 36. Imboden M, Bouzigon E, Curjuric I, et al. Genome-wide association study of lung function decline in adults with and without asthma. J Allergy Clin Immunol. 2012;129(5):1218–1228. 37. Kabesch M. Novel asthma-associated genes from genome-wide association studies: what is their significance? Chest. 2010;137(4):909–915. 38. Zhang  G, Goldblatt  J, LeSouef  P. The era of genome-wide association studies: opportunities and challenges for asthma genetics. J Hum Genet. 2009;54(11):624–628. 39. Zhang  G, Goldblatt  J, Lesouef  P. Findings in genome-wide association studies on asthma lack generalisation. Clin Respir J. 2010;4(4):e8–e9.

40. Kim  JH, Cheong  HS, Park  JS, et  al. A genome-wide association study of total serum and mite-specific IgEs in asthma patients. PLoS One. 2013;8(8):e71958. 41. Xu M, Tantisira KG, Wu A, et al. Genome wide association study to predict severe asthma exacerbations in children using random forests classifiers. BMC Med Genet. 2011;12:90. 42. Torgerson  DG, Ampleford  EJ, Chiu  GY, et  al. Meta-analysis of ­genome-wide association studies of asthma in ethnically diverse north American populations. Nat Genet. 2011;43(9):887–892. 43. Kelso JM. The importance of family history in asthma during the first 27 years of life. Pediatrics. 2014;134(Suppl 3):S168. 44. Liu T, Valdez R, Yoon PW, Crocker D, Moonesinghe R, Khoury MJ. The association between family history of asthma and the prevalence of asthma among US adults: national health and nutrition examination survey, 1999–2004. Genet Med. 2009;11(5):323–328. 45. London  SJ, James Gauderman  W, Avol  E, Rappaport  EB, Peters  JM. Family history and the risk of early-onset persistent, early-onset transient, and late-onset asthma. Epidemiology. 2001;12(5):577–583. 46. Ly  NP, Celedon  JC. Family history, environmental exposures in early life, and childhood asthma. J Allergy Clin Immunol. 2007;120(2):271–272. 47. Bener  A, Ehlayel  MS, Bener  HZ, Hamid  Q. The impact of vitamin D deficiency on asthma, allergic rhinitis and wheezing in children: an emerging public health problem. J Fam Community Med. 2014;21(3):154–161. 48. Bottini N, Ronchetti F, Gloria-Bottini F. Cooperative effect of adenosine deaminase and ABO-secretor genetic complex on susceptibility to childhood asthma. Eur Respir J. 2002;20(6):1613–1615. 49. Chen YL, Chen JC, Lin TM, et al. ABO/secretor genetic complex is associated with the susceptibility of childhood asthma in Taiwan. Clin Exp Allergy. 2005;35(7):926–932. 50. De la Vega  AR, Gomez Cortes  J, Bacallao  GJ. Genetic polymorphism of ABO and Rh system in relation to bronchial asthma: preliminary report. Allergol Immunopathol. 1976;4(5):305–310. 51. Ronchetti  F, Villa  MP, Ronchetti  R, et  al. ABO/secretor genetic complex and susceptibility to asthma in childhood. Eur Respir J. 2001;17(6):1236–1238. 52. Sopo SM, Radzik D, Calvani M. Does treatment with proton pump inhibitors for gastroesophageal reflux disease (GERD) improve asthma symptoms in children with asthma and GERD? A systematic review. J Investig Allergol Clin Immunol. 2009;19(1):1–5. 53. Tomomasa T, Tabata M, Tokuyama K, Mitsuhashi M, Morikawa A. Gastroesophageal reflux is chronologically correlated with coughing but not with wheezing in children with bronchial asthma and gastroesophageal reflux symptoms. Pediatr Pulmonol. 1995;20(3):193–194. 54. Field  SK, Underwood  M, Brant  R, Cowie  RL. Prevalence of gastroesophageal reflux symptoms in asthma. Chest. 1996;109(2):316–322. 55. Harding  SM, Guzzo  MR, Richter  JE. The prevalence of gastroesophageal reflux in asthma patients without reflux symptoms. Am J Respir Crit Care Med. 2000;162(1):34–39. 56. Jain VV, Allison R, Beck SJ, et al. Impact of an integrated disease management program in reducing exacerbations in patients with severe asthma and COPD. Respir Med. 2014;108(12):1794–1800. 57. Oka A, Matsunaga K, Kamei T, et al. Ongoing allergic rhinitis impairs asthma control by enhancing the lower airway inflammation. J Allergy Clin Immunol Pract. 2014;2(2):172–178.

52  The Theory of Endobiogeny

58. Gomes-Filho  IS, Soledade-Marques  KR, Seixas da Cruz  S, et  al. Does periodontal infection have an effect on severe asthma in adults? J Periodontol. 2014;85(6):e179–e187. 59. Devereux G. The increase in the prevalence of asthma and allergy: food for thought. Nat Rev Immunol. 2006;6(11):869–874. 60. Bateman ED, Hurd SS, Barnes PJ, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J. 2008;31(1):143–178. 61. Zhang Y, McConnell R, Gilliland F, Berhane K. Ethnic differences in the effect of asthma on pulmonary function in children. Am J Respir Crit Care Med. 2011;183(5):596–603. 62. Pearce  N, Ait-Khaled  N, Beasley  R, et  al. Worldwide trends in the prevalence of asthma symptoms: phase III of the international study of asthma and allergies in childhood (ISAAC). Thorax. 2007;62(9):758–766. 63. Martin  AJ, Landau  LI, Phelan  PD. Lung function in young adults who had asthma in childhood. Am Rev Respir Dis. 1980;122(4):609–616. 64. CDC. 2012 National Health Interview Survey. http://www.cdc.gov/ asthma/nhis/2012/table1-1.htm#modalIdString_CDCTable_0; 2012. 65. Ishizuka T, Hisada T, Kamide Y, et al. The effects of concomitant GERD, dyspepsia, and rhinosinusitis on asthma symptoms and FeNO in asthmatic patients taking controller medications. J Asthma Allergy. 2014;7:131–139. 66. Hedayat K, Schuff BM, Lapraz JC, et al. Genito-thyroid index: a global systems approach to the neutrophil-to-lymphocyte ratio according to the theory of endobigoeny applied to ambulatory patients with chronic heart failure. J Cardiol Clin Res. 2017;5(1):1091–1097. 67. Hedayat K, Lapraz JC, Schuff BM, et al. A novel approach to modeling tissue-level activity of cortisol levels according to the theory of endobiogeny, applied to chronic heart failure. J Complex Health Sci. 2018;1(1):3–8. 68. Holgate  ST, Davies  DE. Rethinking the pathogenesis of asthma. Immunity. 2009;31(3):362–367. 69. Grassin-Delyle S, Abrial C, Fayad-Kobeissi S, et al. The expression and relaxant effect of bitter taste receptors in human bronchi. Respir Res. 2013;14:134. 70. Orsmark-Pietras  C, James  A, Konradsen  JR, et  al. Transcriptome analysis reveals upregulation of bitter taste receptors in severe asthmatics. Eur Respir J. 2013;42(1):65–78. 71. Clifford  RL, Knox  AJ. Future bronchodilator therapy: a bitter pill to swallow? Am J Physiol Lung Cell Mol Physiol. 2012;303(11):L953–L955. 72. Green  RH, Brightling  CE, McKenna  S, et  al. Asthma exacerbations and sputum eosinophil counts: a randomised controlled trial. Lancet. 2002;360(9347):1715–1721. 73. Bacci  E, Cianchetti  S, Bartoli  M, et  al. Low sputum eosinophils predict the lack of response to beclomethasone in symptomatic asthmatic patients. Chest. 2006;129(3):565–572. 74. Duraffourd  C, Lapraz  JC. Traité de Phytothérapie Clinique: Médecine et Endobiogénie. Paris: Masson; 2002. 75. Lapraz  JC, Carillon  A, Charrié  J-C, et  al. Plantes Médicinales: Phytothérapie Clinique Intégrative et Médecine Endobiogénique. Paris: Lavoisier; 2017. 76. Davalos Bichara  M, Goldman  RD. Magnesium for treatment of asthma in children. Can Fam Physician. 2009;55(9):887–889. 77. Scarfone  RJ, Loiselle  JM, Joffe  MD, et  al. A randomized trial of magnesium in the emergency department treatment of children with asthma. Ann Emerg Med. 2000;36(6):572–578.

78. Torres S, Sticco N, Bosch JJ, et al. Effectiveness of magnesium sulfate as initial treatment of acute severe asthma in children, conducted in a tertiary-level university hospital: a randomized, controlled trial. Arch Argent Pediatr. 2012;110(4):291–296. 79. Papakonstantinou  E, Karakiulakis  G. The 'sweet' and 'bitter' involvement of glycosaminoglycans in lung diseases: pharmacotherapeutic relevance. Br J Pharmacol. 2009;157(7):1111–1127. 80. Hedayat  KM. Essential oil diffusion for the treatment of persistent oxygen dependence in a three-year-old child with restrictive lung disease with respiratory syncytial virus pneumonia. Explore. 2008;4(4):264–266. 81. Dohi  S, Terasaki  M, Makino  M. Acetylcholinesterase inhibitory activity and chemical composition of commercial essential oils. J Agric Food Chem. 2009;57:4313–4318. 82. Kavvadias D, Abou-Mandour AA, Czygan FC, et al. Identification of benzodiazepines in Artemisia dracunculus and Solanum tuberosum rationalizing their endogenous formation in plant tissue. Biochem Biophys Res Commun. 2000;269(1):290–295. 83. Talpur  N, Echard  B, Ingram  C, Bagchi  D, Preuss  H. Effects of a novel formulation of essential oils on glucose-insulin metabolism in diabetic and hypertensive rats: a pilot study. Diabetes Obes Metab. 2005;7(2):193–199. 84. Sears MR. Adverse effects of beta-agonists. J Allergy Clin Immunol. 2002;110(6 suppl):S322–S328. 85. Nelson  HS. Is there a problem with inhaled long-acting betaadrenergic agonists? J Allergy Clin Immunol. 2006;117(1):3–16. quiz 17. 86. Vestergaard P, Rejnmark L, Mosekilde L. Fracture risk in patients with chronic lung diseases treated with bronchodilator drugs and inhaled and oral corticosteroids. Chest. 2007;132(5):1599–1607. 87. Slatore CG, Bryson CL, Au DH. The association of inhaled corticosteroid use with serum glucose concentration in a large cohort. Am J Med. 2009;122(5):472–478. 88. Butland BK, Fehily AM, Elwood PC. Diet, lung function, and lung function decline in a cohort of 2512 middle aged men. Thorax. 2000;55(2):102–108. 89. Garcia-Marcos  L, Castro-Rodriguez  JA, Weinmayr  G, Panagiotakos DB, Priftis KN, Nagel G. Influence of Mediterranean diet on asthma in children: a systematic review and meta-analysis. Pediatr Allergy Immunol. 2013;24(4):330–338. 90. Hyson  DA. A comprehensive review of apples and apple components and their relationship to human health. Adv Nutr. 2011;2(5):408–420. 91. McKeever  TM, Scrivener  S, Broadfield  E, Jones  Z, Britton  J, Lewis  SA. Prospective study of diet and decline in lung function in a general population. Am J Respir Crit Care Med. 2002;165(9):1299–1303. 92. Tanaka T. Flavonoids for allergic diseases: present evidence and future perspective. Curr Pharm Des. 2014;20(6):879–885. 93. Huang Z, Rose AH, Hoffmann PR. The role of selenium in inflammation and immunity: from molecular mechanisms to therapeutic opportunities. Antioxid Redox Signal. 2012;16(7):705–743. 94. Sagar  S, Morgan  ME, Chen  S, et  al. Bifidobacterium breve and Lactobacillus rhamnosus treatment is as effective as budesonide at reducing inflammation in a murine model for chronic asthma. Respir Res. 2014;15:46. 95. Ta V, Laubach S. Probiotic administration in early life, atopy, and asthma: a meta-analysis of clinical trials. Pediatrics. 2014;134(suppl 3):S141.

Asthma: An integrative physiologic approach Chapter | 2  53

96. Azad  MB, Coneys  JG, Kozyrskyj  AL, et  al. Probiotic supplementation during pregnancy or infancy for the prevention of asthma and wheeze: systematic review and meta-analysis. BMJ. 2013;347:f6471. 97. Elazab  N, Mendy  A, Gasana  J, Vieira  ER, Quizon  A, Forno  E. Probiotic administration in early life, atopy, and asthma: a metaanalysis of clinical trials. Pediatrics. 2013;132(3):e666–e676. 98. Abdala-Valencia  H, Berdnikovs  S, Cook-Mills  JM. Vitamin E isoforms as modulators of lung inflammation. Nutrients. 2013;5(11):4347–4363. 99. Cramer H, Lauche R, Dobos G. Characteristics of randomized controlled trials of yoga: a bibliometric analysis. BMC Complement Altern Med. 2014;14:328.

100.

101.

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Chapter 3

A clinical approach to the gonadotropic axis Introduction The gonadotropic axis is the foundation of life. It initiates metabolism, which initiates the formation, maintenance, and reparation of structure at all times. If there is no structure, there will be no need to adapt, to consume energy, or to procreate. Thus, the metabolic actions of this axis are its paramount ones. Procreation occurs less frequently and constitutes a secondary level of importance. There are three unique aspects of this axis (cf. The Theory of Endobiogeny, Volume 1, Chapters  7 and 10). First, it has two pituitary hormones (FSH, LH) regulated by a single hypothalamic hormone (GnRH). While all hormones are released in a pulsatile fashion, GnRH perhaps more than any other know hormone has a finely tuned alternation of amplitude, frequency, and peak sustain (Fig. 3.1).1, 2 Second, it has three principle peripheral hormones (estrogens, progesterone, gonadal androgens), regulated by two pituitary stimulins: FSH and LH. There are three classes of peripheral hormones excreted from stimulation of these two pituitary stimulins: estrogens, progestins, and gonadal androgens. With respect to organometabolic activity of the gonads, all are derived from cholesterol via pregnenolone, a progestin. Progestins are converted into androgens, and from androgens are derived estrogens. With respect to endocrinometabolic activity, the order is estrogens, then progesterone then androgens. Finally, it is the only axis whose primary peripheral hormones can be produced in a second gland (adrenal cortex). The adrenal cortex produces adrenal androgens (such as DHEA), estrogens and progesterone, all derived from cholesterol. In addition, DHEA can be aromatized within distal cells to gonadal hormones.3, 4

A brief review of actions of gonadotropic hormones FSH plays a complimentary role to that of estrogens. Inappropriate peripheral physiologic response or ­prolonged duration of solicitation implicates FSH in a number of disorders related to proteins and protein-rich structures. The Theory of Endobiogeny. https://doi.org/10.1016/B978-0-12-816964-3.00003-1 © 2019 Elsevier Inc. All rights reserved.

●

●

● ●

● ●

Upregulates the number of estrogen receptors in the periphery Upregulates absorption of proteins from ascending and proximal transverse colon Mucosal hypertrophy and congestion of tissues General regulation of proteins including formation of immunoglobulins, compliment, and other protein products of the immune system. Horizontal stimulation of TSH Fertility

Estrogens directly influence the activities implicated by FSH: ● ● ● ● ● ●

●

Mucosal surfaces Immunoglobulins Fertility Bone: Bone and cartilage growth Muscle: Muscle growth and texture Cardiovascular ● Vasodilatation ● Electrical discharge: estrogens lower the rate of depolarization, lowering the threshold of firing Sexual dimorphisms

LH plays key roles in ensuring the regulation and finalization of anabolism. Through its peripheral products it ensures a sufficient duration of estrogen activity in the first loop (i.e., progesterone) and androgen activity in the second loop. Androgens manage the completion of metabolism. Hence, the achievement of anabolism is directly under the influence of androgens, not estrogens. Like other steroidal hormones have genomic and nongenomic effects.5 The genomic of effects of androgens are5 as follows: 1. Cellular: Apoptosis 2. Muscles a. Skeletal muscle mass and density b. Smooth muscle proliferation 3. Bone: Epiphyseal lengthening 4. Cartilage: Cartilage closure 55

56  The Theory of Endobiogeny

FIG. 3.1  Pulsatility in the gonadotropic axis. The hypothalamic hormone, gonadotropin releasing hormone (GnRH) stimulates two pituitary hormones: follicle-stimulating hormone (FSH) and luteinizing hormone (LH). The manner in which the pituitary is able to distinguish which hormones are to be released is through the frequency of GnRH excretion, referred to as their pulsatility. When there is 1 pulse/h, it favors LH. When there is only 1 pulse in 3 hours, it favors FSH. In both cases, quantitatively, LH is excreted at a greater quantity. (Reproduced from Koeppen B, Stanton B. Berne and Levy Physiology, 6th ed. 2009. Copyright © 2010 by Mosby, an imprint of Elsevier, Inc. All rights reserved.)

5. Cardiovascular: Vasorelaxation 6. Immune a. Monocyte migration b. Foam cell production Nongenomic effects of androgens include6, 7: 1. Muscle: Smooth muscle relaxation 2. CNS a. Increased neuromuscular signal transmission by calcium regulation b. Neuroplasticity 3. Cell: Cellular proliferation and migration 4. Endocrinometabolic: Modulation of the transcriptional effects of classical androgen receptors There are three types of androgens: adrenal androgens (e.g., DHEA), gonadal testosterone, and gonadal dihydrotestosterone (DHT). They have varying degrees of receptor affinity and actions on tissues (Table 3.1). Progesterone promotes anabolism. It has a ­biphasic relationship with estrogens, promoting its activity at ­ low ­levels, inhibiting it at higher levels of progesterone ­expression. Its activity is summarized in Table 3.2.8, 9 Finally, gonadotropic hormones, most notably FSH, estrogens, and gonadal androgens play a role in comportment through their central receptors. Reactive FSH expression favors a general emotivity. Estrogen receptors are diffusely expressed in the central nervous system. A predominance of estrogens in relationship to androgens centrally favor the following tendencies: consideration of more options in

decision making, emotive quality of thinking, instinctual knowledge, contextualized recall of events, and reflective listening and speaking.10 In general, estrogen favors qualitative relationship-based analysis vs quantitative, hierarchical assessment. Androgens have similar central activity. A relative androgen predominance in relationship to that of estrogens in the brain influences favors the following behavior: sexual pursuit, initiation of erection, logical problem solving, aggression, diminished overt expressions of emotions, and motivation for reward.11 In general, androgens—testosterone in particular—favor quantitative, hierarchical assessment over qualitative relationship-based analysis. Some of these considerations can be observed (Table 3.4), others can be inferred from biology of function indexes.

Pathophysiology Broadly speaking, disorders related to gonadotropic dysfunction are disorders of generation, maintenance, or repair of tissues. The gonadotropic axis manages proteins, but solicits lipids and carbohydrates for energy for the anabolism of proteins. Thus, it calibrates the other axes in turn to its level of function. Gonado-thyrotropic coupling is for the regulation of lipids and carbohydrates for energy. Gonadosomatotropic coupling is for fashioning and anabolism, as well as carbohydrate mobilization. Mesodermal tissues are most closely linked to the gonadotropic axis for two reasons. First, they are the structures richest in proteins, such as serosal and mucosal surfaces, and tendons. Second, they are structures directly stimulated

A clinical approach to the gonadotropic axis Chapter | 3  57

TABLE 3.1  Summary of androgen activity by type of androgen Effect

DHEA

Testosterone

DHT

Androgen receptor affinity

1

10

30

Skin moisture Hair

Increases sebum Low hair line

Receding hair line

Muscle

Skeletal: mass, density, strength Smooth: relaxation, proliferation

Bone

Density, linear growth Epiphyseal closure

Genitals

Epididymis Vas deferens

Thrombosis

Increased clotting

Sexuality

Libido

Comportment Cognition

Prostate Glans penis

Erection Capacity to resist and persevere

Neuronal irritability

Neuronal stability Neuroplasticity

TABLE 3.2  Summary of progesterone activity Tissue

Function

Endocrine

Prevents suppression of endorphins by estrogens, allowing reduction in LH, FSH Inhibits expression of estrogen receptors Inhibits intracellular activity of estrogens Relaunches production of testosterone

Cellular

Growth factors Increased cell cycling

Bone

Regulation of bone mass: antagonism of cortisol receptors

Heart

Antiarrhythmic: faster repolarization: increased potassium current, reduced depolarizing calcium currents

Brain

Libido

Uterus, ovaries

Ovulation Implantation of fertilized egg Pregnancy

Mammary gland

Lobular alveolar development Suppression of lactation during pregnancy

by gonadotropic hormones, such as androgens regulation of the formation of red blood cells. Blood is a mesodermal ­tissue. While the gonadotropic axis has a privileged relationship with the mesoderm, it is implicated in the formation and growth of all tissues. From this observation, we can

observe four types of gonadotropic imbalances that result in tissular disorders: 1. Central gonadal oversolicitation > Peripheral gonadal response: a. Horizontal overstimulation of TSH, GH, PL: Cystitis, cysts, fibroids, and adenosis b. FSH > estrogens: Crohn’s disease and metrorrhagia c. LH > gonadal androgens: Acne and prostatic disorders 2. Hyperfunctioning of central and peripheral responses a. Follicular: PMS (estrogen predominance), ­menorrhagia, breast cancer, and uterine cancer b. Luteal: PMS (progesterone predominance), prostatic adenoma, and prostate cancer c. Follicular and luteal: Cardiovascular disease 3. Insufficient peripheral gonadal response: a. Estrogens: Metrorrhagia b. Progesterone: Infertility c. Gonadal androgens: Sarcopenia and impotence d. Global: Osteopenia and osteoporosis 4. Chronologic disorders a. Early activation of adult function: Precocious puberty b. Late activation of adult function: Delayed puberty c. Early deactivation of adult function: Premature menopause d. Incomplete deactivation of adult function: Climacteric symptoms due to hyperfunctioning of central factors Because the gonadotropic axis is also responsible for reproduction, perhaps more than any other axis, it has the greatest

58  The Theory of Endobiogeny

variety of signs on the exterior of the organism and the greatest degree of programmed change from childhood to adolescences to adulthood. We are oriented through subconscious assessments to evaluate the exterior features of other human beings, favoring symmetry as a sign of beauty.13 They are perceived in traditional cultures to, and, physiologically in fact do relate to fertility and strength, 14, 15 and are evanescent windows into the psychic experiences of joy, anger, aggression, etc.16 Thus, it should be no surprise that the envelope—the skin, hair, shape, and size of breasts, etc.—contains such a complex interaction of neuroendocrine factors and expresses through the face and body postures a range of emotional valences and mental states. Thus, from the evolutionary cultural perspective, we know our mates through the signs on their exterior.

Symptoms associated with the gonadotropic axis A number of symptoms are associated with the gonadotropic axis. Table 3.3 summarizes common historical information by region or system of the body.

Signs associated with the gonadotropic axis There are numerous signs that can be obtained by observation (Table 3.4), or, by examination of the skin (Table 3.5), hair (Table 3.6), head and neck (Table 3.7), breasts (Table 3.8), abdomen and genitals (Table  3.9), musculoskeletal system (Table 3.10) and adipose tissue (Table 3.11).

TABLE 3.3  Common gonadotropic symptoms Category

History

Endocrine

Activity

Dermis

Eczema

FSH

Excessive

Psoriasis

FSH

Excessive

Acne

LH

Excessive

Hot flashes

Androgens

Insufficient

Energy

Fatigability

Androgens

Deficient

Endocrine

Delayed puberty

FSH

Insufficient

Amenorrhea

FSH

Insufficient

Absence of secondary sexual characteristics

FSH

Insufficient

Delay in vertical growth

FSH

Insufficient

Difficulty with erection

FSH

Insufficient

Sterility

FSH

Insufficient

Signs of reduced estrogen

FSH

Insufficient

Eyes

Eyelashes fall out easily

Estrogen

Diminished

GI

Crohn’s disease

FSH

Hyperfunctioning

Disease of right colon

FSH

Oversoliciting

Libido, weak

FSH

Insufficient

PMS before ovulation, stops a few days before menstruation

Progesterone

Prominent, often excessive

PMS: breasts engorged

Progesterone

Prominent, often excessive

PMS: breasts painful

Estrogen

Prominent, often excessive

Breasts painful during menstruation

Progesterone

Excessive

Heavy menstrual flow

Estrogen

Excessive

Clotting, day 1 menstruation

Estrogen

Insufficient

Clotting D2,3 of menstruation

Progesterone

Prominent, often excessive

Genitourinary

A clinical approach to the gonadotropic axis Chapter | 3  59

TABLE 3.3  Common gonadotropic symptoms—cont’d Category

Puberty

History

Endocrine

Activity

Prolonged clotting at end of menstruation

Progesterone

Prominent, often excessive

Postmenstrual herpes outbreak

Progesterone

Insufficient with hypercompensatory aldosterone relaunching of LH

Menstrual irregularity

Androgens

Insufficient

Amenorrhea

Estrogen

Insufficient

Libido, weak

Estrogen

Insufficient

Libido, strong

Estrogen

Pronounced

Sexual desire

Progesterone

Strong

Sexual desire weak

Progesterone

Diminished

Reduced incidence of morning erection

Androgens

Insufficient

Weak ejaculation

Androgens

Deficient

Rapid onset with early end

Androgens

Prominent and excessive

TABLE 3.4  Gonadotropic signs determined by observations Part

Quality

Finding

Endocrine

Activity

Comment

Temperament

External state

Social tendency

Androgens

Prominent

Strength, confidence and leadership during crisis

Social tendency

Estrogen

Prominent

Socially sensitive, social harmonizer

Capacity to fight and resist

Androgens

Strong

Passivity, loss of professional efficacy

Androgens

Insufficient

Or: negative regardless of absolute value

Lack of self-esteem

Androgens

Diminished

Or: negative regardless of absolute value

Lack of motivation

Androgens

Diminished

Or: negative regardless of absolute value

Diminished interest in athletics

Androgens

Diminished

Or: negative regardless of absolute value

Emotionally sensitive

FSH

Reactive

Weak

Androgens

Diminished or blocked

Low pitched

Androgens

Prominent

Adrenal androgens in structure

High pitched

Estrogen

Predominant

In structure

Internal state

Voice

Tonality

Continued

60  The Theory of Endobiogeny

TABLE 3.4  Gonadotropic signs determined by observations—cont’d Part

Quality

Finding

Endocrine

Activity

Comment

Body

Build

Curvaceous

FSH

Predominant

In structure, women only

Shoulders wider than hips

Androgens

Predominant

In structure

Hips wider than shoulders

Estrogen

Predominant

In structure

Stocky, waist down

Androgens

Predominant

Adrenal androgens; in women, minimal curve of hips, congestion of legs

Right > left

FSH

Predominant

In structure

Left > right

LH

Predominant

In structure

Left ring-toindex finger ratio

>1

Androgens

Strong

Relates to fetal androgens; correlates with more “boy-like” behavior in girls: aggressive play in girls between 3 and 5 years of age12

Distal phalange, all fingers

Short and interrupted

Androgens

Strong

Laterality

TABLE 3.5  Gonadotropic signs on the skin Quality

Finding

Factor

Activity

Quality

Smooth

Estrogen

Good quality

Dry

Estrogen

Insufficient

Squamous (scaly)

Estrogen

Insufficient

Wrinkles

Present

Estrogen

Insufficient

Sebum

Oily

Estrogen

Predominant

Relative excess vs testosterone. Consider role of adaptative cortisol in decreasing tissular effects of estrogen

Lesions

Nasolabial

FSH

Oversolicited

With insufficient estrogen response

Sides of face

Androgens

Oversolicited

And poorly managed within the organism

Chin

Androgens

Oversolicited

And poorly managed within the organism

General tendency

Progesterone

Insufficient

General tendency

Androgens

Oversolicited

Buttocks, sides

Androgens

Oversolicited

Acne

Comment

Most likely deficient in postmenopausal women

A clinical approach to the gonadotropic axis Chapter | 3  61

TABLE 3.5  Gonadotropic signs on the skin–cont’d Quality

Finding

Factor

Activity

Comment

Color

Colored spots

FSH

Excessive

Elbows, knees

Elbow

Melanic spots

FSH

Excessive

May also be seen on knees

Knee

Melanic spots

FSH

Excessive

May also be seen on elbows

Striae

Horizontal orientation

Estrogen

Hyperfunctioning

Particularly found on trunk

Tissue

Infiltrated with water

Estrogen

Hyperfunctioning

Palm

Erythema

Estrogen

Excessive

Witnesses the tissular dominance of estrogens, also may imply liver congestion with retained estrogen metabolites

TABLE 3.6  Gonadotropic signs in hair Quality

Finding

Factor

General

Purpose

Gonado-corticotropic

Quantity

Hirsutism

Adrenal vs gonadal androgens

Strong

In women, in an absolute sense; appearance of hair depends on the androgens (adrenal vs gonadic). Adrenal: distal extremities distribution Gonadal: proximal extremities, midline chest and abdomen

Receding at temples

Gonadal androgens

Strong

Absolutely strong, and, gonadal > adrenal

Axillary abundance

Gonadal androgens

Strong

Pubic triangle

Enlarged

Androgens

Abundant

Estrogen

Good quality

Coarseness

Adrenal androgens

Prominent

Adrenal > gonadal androgens

Thinning

Androgens

Excessive

Relative to estrogens. Consider role of adaptative cortisol in decreasing tissular effects of estrogen

Dry, breakable

Estrogen

Insufficient

Location

Quality

Activity

Comment The purpose of hair is to manage temperature; It represents a delayed adaptation of structure, as opposed to the immediate adaptation to light of the eyebrows, which explains in part why a person can have hair and eyebrows of different pigmentation, thickness and density

Prominent

62  The Theory of Endobiogeny

TABLE 3.7  Gonadotropic signs of the head and neck Part

Quality

Finding

Factor

Activity

Comment

Eyelashes

Length

Long, fine

FSH

Predominant

In structure

Durability

Fall out easily

Estrogen

Diminished

Absolute drop or relatively insufficient

Coarseness

Coarse

Adrenal androgens

Predominant

Color

Darker

Adrenal androgens

Predominant

Color

Violaceous

FSH

Increased activity

Slightly violaceous

Estrogen

Hyperfunctioning

Short

Androgens

Predominant

Tonsils pillar

Neck

Length

Look for other signs of structural hyperandrogenism such as shorted distal phalange of fingers, dark hair, thick hair, etc.

TABLE 3.8  Gonadotropic signs with respect to breasts and areola Quality

Finding

Factor

Activity

Comment

Size

Small

FSH

Predominant

In structure due to efficient in structural estrogen solicitation

Voluminous, soft and supple

Estrogen

Prominent

Areola tend to be large and lightly colored

Left > right

LH

Predominant

TSH also involved in laterality

Right > left

FSH

Predominant

ACTH also involved in laterality

Density

Fibrocystic

Gonadal androgens

Predominant

Predominates over estrogens without prejudging the actual strength of estrogens

Tenderness

Tender

Estrogens

Excessive

Firm and often painful

Progesterone

Hyperfunctioning

Greatest in superior, exterior quadrants of breasts, left > right

Congestion

Diffuse with tension

Progesterone

Excessive

Congestion greatest in superior, exterior quadrants of breasts

Areola hirsutism

Hair growth, areola

Progesterone

Insufficient

Relative to gonadal androgens

Areola size

Large

Estrogen

Prominent

Tend to be lightly colored; breasts tend to be large, too

Areola coloration

Lightly pigmented

Estrogen

Prominent

Areola and breasts tend to be large too

Asymmetry

A clinical approach to the gonadotropic axis Chapter | 3  63

TABLE 3.9  Gonadotropic signs of the abdomen and genitals Part

Quality

Finding

Factor

Activity

Colon

Ascending, distal

Pain on palpation

FSH

Oversoliciting

Left distal colon

Pain on palpation

LH

Oversoliciting

Size

Small

FSH

Diminished and insufficient

Comment

Penis

TABLE 3.10  Gonadotropic signs with respect to muscles and ligaments Quality

Finding

Factor

Activity

Development

Underdeveloped

Para

Weak

Mass

Wasting

Androgens

Deficient and/or blocked

Increased

Androgens

Good quality

Muscle

Texture

Estrogens

Good quality

Ligament laxity

Lax

Androgens

Insufficient

Absolute or relative

Estrogens

Predominant

Absolute predominance

TABLE 3.11  Gonadotropic signs with respect to adiposity Part

Quality

Factor

Activity

Adiposity

Arm, proximal, right

FSH

Hyperfunctioning

Arm, proximal, left

LH

Hyperfunctioning

Knee, right

FSH

Hyperfunctioning

Knee, left

LH

Hyperfunctioning

Infra-umbilical

Estrogens

Excessive

Indexes of the BoF related to the gonadotropic axis There are two indexes in the biology of functions that model pituitary gonadotropic activity (Table 3.12). These indexes, follicle-stimulating hormone (FSH) and luteinizing hormone (LH), need to be understand in their Endobiogenic context. There are a number of factors that create a potential divergence between serum concentration of FSH and FSH activity. One example is genetic polymorphisms of the FSH β-subunit and the FSH receptor. A good clinical example is the difference between Southeast Asian and European

Correlate with elevated cortisol, weak TRH

women in morphology and internal function: hair and skin, breast size, standard range of serum FSH, gametogenesis, menstrual cycle regulation,17 etc. Another factor is the posttranslational glycosylation and electric charge when FSH binds to its receptors. This affects the endocrine, metabolic, and to some extent endocrinometabolic activity of FSH.2 From these observations, we conclude that serum measurement of FSH and LH may not be sufficiently clinically relevant in certain cases (cf. The Theory of Endobiogeny, Volume 1, Chapters 7 and 15). Another question asked in Endobiogeny is the yield of a hormone on its target organ. In other words, given the duration and intensity of stimulation, how efficiently did the target organ respond? When Dr. Duraffourd developed the FSH and LH indexes, it was to answer this question that he had in mind. When interpreting the ACTH, FSH, LH, and PL (Prolactin) indexes understand the following. The higher the value of the index, the lower the yield of the pituitary hormone is. The particular clinical action will depend on why the index is elevated (Table 3.13). There are a number of reasons. We present three for consideration. First, the target organ is not producing and excreting the intended hormone quickly enough to participate in a classical negative feedback circuit on its stimulating hormone. In this case, one can sustain central activity and/or support peripheral activity. Second, regardless of

64  The Theory of Endobiogeny

TABLE 3.12  Biology of functions indexes modeling central gonadotropic activity Relationship Index

Definition

Import

Direct

Inverse

Correlations

FSH

It evaluates the organometabolic activity of FSH

The index evaluates how efficiently the end organ is stimulated and how efficiently it responds in negative feedback

ACTH index

Tissular estrogens

Adaptation, LH index

LH

It evaluates the organometabolic activity of LH

The index evaluates how efficiently the end organ is stimulated and how efficiently it responds in negative feedback

ACTH index

the rate of excretion, negative feedback on its pituitarystimulating hormone is faulty or altered.18 For example, if the LH index is elevated, but peripheral androgen activity is also elevated, one needs to inhibit LH and possibly inhibit peripheral androgens. Third, regardless of the rate of excretion, negative feedback on another pituitary-­stimulating hormone is faulty or altered. This is most notably the case in regard to estrogen relaunching of LH to modify the level of progesterone or gonadal androgen a­ ctivity.19 Thus, estrogen indexes and LH index are elevated but there is an insufficiency of progesterone or gonadal androgens (Table  3.13). The lower the index, the greater the intensity of central pituitary action and the more quickly it is inhibited by peripheral factors. In terms of the FSH index, it is most closely linked to the quantitative organotissular estrogen index (Tables 3.13 and 3.14).

FSH index Progesterone Tissular androgens

Indexes modeling peripheral endocrine activity Peripheral gonadotropic function is even more complex than FSH and LH physiology (cf. The Theory of Endobiogeny, Volume 1, Chapters 7 and 15). Let us consider estrogen activity: it has endocrine, metabolic, and tissue functions, genomic and nongenomic. Estrogens can be produced in the ovaries, adrenals, or by peripheral conversions in various tissues.20, 21 The pattern of estrogen production varies based on hereditary factors, age and parturition status, and is affected by endocrine disrupters.20–23 There are multiple active forms of estrogens as well as varying degrees of activity of estrogen metabolites. There are two types of estrogen receptors (α, β), which have ­opposing activity with respect to cellular proliferation and various metabolic functions. There are genetic polymorphisms in p450 metabolism of estrogens. There are polymorphisms in receptor

TABLE 3.13  Some possible interpretations of elevated pituitary indexes Peripheral organ

BoF

Example

Treatment

Organometabolic yield low

↑ FSH

Insufficient organotissular estrogen activity relative to FSH stimulation

Sustain FSH: Inula helenium, Quercus pedunculata (indirect)

LH index elevated despite gonadal androgens activity elevated

Inhibit LH: Alchemilla vulgaris, Medicago sativa, Prunus africana

Insufficient calibration of peripheral luteal activity relative to that of estrogens

Inhibit LH: Alchemilla vulgaris, Medicago sativa, Prunus africana

↓ OTEYi ↓ Estrogen corrected Negative feedback faulty or altered

↑ LH ↑ Genital androgens ↑ Comparative genital androgens

Negative feedback on another pituitary hormone faulty or altered

↑ LH ↑ Genital androgens ↑ Comparative genital androgens

OTEYi, organotissular estrogen yield index.

Support estrogens: Angelica archangelica, Salvia officinalis, Salvia sclarea, etc.

Inhibit androgens: Fragaria vesca, Humulus lupulus, Menyanthes trifoliata

Inhibit FSH:Borago officinalis Inhibit estrogens:Vitex agnus castus Inhibit androgens:Fragaria vesca, Humulus lupulus, Menyanthes trifoliata

TABLE 3.14  Hormone classification based on metabolic action Activity

Description

Example

Endocrinometabolic

Hormonal regulation of cellular metabolism, based demands greater than that of the cell

FSH upregulation of estrogen receptors within the thyroid Estrogen regulation of cellular protein metabolism

Endocrinotissular

Hormonal regulation of tissular metabolism based on demands greater than the tissue

Programmatic increase in muscle tissue density by estrogens and androgens

Organometabolic

Hormonal regulation of organ metabolic activity as a whole based on demands greater than the cell

LH stimulation of the gonads to produce (secrete) progesterone by uptake and metabolism of cholesterol

Organotissular

Hormonal regulation of organ tissular activity based on demands greater than the cell

FSH and LH regulation of gonad size and activity form fetogenesis through gonadopause Endometrial growth during the menstrual cycle by estrogens and androgen

sensitivity and concentration, rate of aromatase activity, and nongenomic effects. In sum, all these factors create a true challenge in determining the qualitative metabolic effects of estrogens through measurement of serum levels of active hormones or urinary levels of metabolites.24–30 The biology of functions approaches these challenges by evaluating the functional effectiveness of peripheral gonadotropic hormones (Table 3.15) (cf. The Theory of Endobiogeny, Volume 1, Chapter 15). Recall that the theory of Endobiogeny characterizes hormones based on their effects on metabolism (cf. The Theory of

Endobiogeny, Volume 1, Chapter 4). There are seven levels of action, three basic, four combinatorial: (1) cellular, (2) tissular, (3) endocrine, (4) endocrinometabolic, (5) endocrinotissular, (6) organometabolic, and (7) organotissular. Here we review the actions (Table  3.14) relevant to the indexes presented in Table 3.15. Finally, when evaluating the effects of peripheral gonadotropic hormones, one must keep in mind that androgens and estrogens can be derived from the adrenal cortex. In addition, the adrenal androgen DHEA can be converted

TABLE 3.15  Biology of functions indexes modeling peripheral gonadotropic activity Relationship Index

Definition

Import

Direct

Inverse

Genital ratio

It measures the global tissular activity of androgens in relationship to that of estrogens

It evaluates it in acute adaptation

RBC

WBC

It evaluates it outside of adaptation syndromes

LMI

PMI

TSH

Osteocalcin

Genital ratio corrected (GRc)

Correlation

Estrogen index

It expresses the endocrinometabolic activity of estrogens

Nucleomembrane activity

Estrogen index corrected

It measures the tissular endocrinometabolic activity of estrogens

It evaluates the potential tissular growth within the modality of structural demands

Estrogen index

Organotissular estrogen yield (OTEYi)

It measures the global organotissular activity of estrogens relative to FSH stimulation

It evaluates the relative organotissular activity of estrogens in relation to the global activity of FSH. The higher the index, the greater the proliferation of estrogen receptors

WBC

FSH index

OTEYi

Genital androgen

It measures the tissular endocrinometabolic activity of androgens

It evaluates the potential tissular growth based on the endocrinometabolic activity of gonadal androgens in response to estrogens

Estrogen index corrected

Adaptation index

GRc

OTEYi Estrogen index

LMI, Leukocyte mobilization index; PMI, Platelet mobilization index; OTEYi, Organotissular estrogen yield; GRc, Genital ratio corrected.

66  The Theory of Endobiogeny

FIG. 3.2  Sites of estrogen production and corresponding indexes of the biology of functions. Gonadal androgens (top right) are produced in thecal cells from a progestane derivative. Estrogens (bottom right) can be produced through the intermediary androstenedione or by testosterone (red arrow). This activity is reflected in the rate of aromatized estrogens index (cf. Table 3.16). When estrogens are produced in the adrenal cortex (bottom left) from androstenedione, it is reflected in the aromatization index. When adrenal DHEA is converted by intracrinologic mechanisms to estrogens, it is reflected in the DHEA index. (© 2016 Systems Biology Research Group.)

TABLE 3.16  Estrogen production site and method Relationship Index

Definition

Import

Direct

Inverse

Correlations

DHEA

It evaluates the endocrinometabolic activity of DHEA

By extension it evaluates the level of its excretion and conversion to estrogens or androgens

Aromatization of estrogens

Progesterone index Gonadal androgens

Adrenal cortex permissiveness

Aromatization of estrogens

It measures the relative activity of the adrenal gland dedicated to aromatization

When it is elevated, evaluate the permissivity of the adrenal cortex and cortisol activity

Adrenal cortex permissivity

Rate of aromatized estrogens

It expresses the relative part of compensatory estrogens obtained through aromatization of gonadal androgens

Given a certain level of endocrinometabolic activity of estrogens, and given a certain level of estrogens produced by FSH stimulation, it evaluates the rate of estrogens produced by androgens produced by LH stimulation

Estrogen index

within cells and tissues to androgens or estrogens by a process called intracrinology (Fig. 3.2). There are a number of indexes in the biology of functions that model these dynamics (Table 3.16).

Conclusions The gonadotropic axis is related to the fundamental regulation of metabolism through protein management. However, it also affects comportment, general morphologic formation,

Genital ratio corrected, aromatized estrogens Aromatization of estrogens

and secondary sexual characteristics, linked to potentiality of fertility and reproduction. Because of this, there is a rich semiology of this axis. The axis is linked to numerous disorders related to protein management in general and to tissues derived from the mesoderm. Due to the complexity of regional variations in receptors, genetic polymorphisms, receptor subtypes, second messenger systems, etc. serum blood levels may not be accurate in determining the functional effects of hormones of this axis. The biology of functions offers a number of novel ways of evaluating not only the type of ­metabolic

A clinical approach to the gonadotropic axis Chapter | 3  67

activity of gonadotropic hormones, but the intensity and duration of action, origin of production, etc. A careful evaluation of the gonadotropic axis in symptoms, signs, and biology of functions offers a nuanced appreciation of central and peripheral levels of activity of this axis. But combining findings of the gonadotropic axis with that of the other axes through linking or coupling, the Endobiogenist is able to develop a sophisticated and complex assessment of the terrain in its various degrees of interrelatedness and integration.

References 1. Marshall  JC, Dalkin  AC, Haisenleder  DJ, Griffin  ML, Kelch  RP. GnRH pulses—the regulators of human reproduction. Trans Am Clin Climatol Assoc. 1993;104:31–46. 2. Nussey  S, Whitehead  S. Endocrinology: An Integrated Approach. Oxford: BIOS Scientific Publishers; 2001. 3. Labrie  F, Labrie  C. DHEA and intracrinology at menopause, a positive choice for evolution of the human species. Climacteric. 2013;16(2):205–213. 4. Labrie F, Luu-The V, Labrie C, Simard J. DHEA and its transformation into androgens and estrogens in peripheral target tissues: intracrinology. Front Neuroendocrinol. 2001;22(3):185–212. 5. Liu PY, Death AK, Handelsman DJ. Androgens and cardiovascular disease. Endocr Rev. 2003;24(3):313–340. 6. Heinlein  CA, Chang  C. The roles of androgen receptors and androgen-­binding proteins in nongenomic androgen actions. Mol Endocrinol. 2002;16(10):2181–2187. 7. Michels  G, Hoppe  UC. Rapid actions of androgens. Front Neuroendocrinol. 2008;29(2):182–198. 8. Kurokawa  J, Furukawa  T. Non-genomic action of sex steroid hormones and cardiac repolarization. Biol Pharm Bull. 2013;36(1):8–12. 9. Graham JD, Clarke CL. Physiological action of progesterone in target tissues. Endocr Rev. 1997;18(4):502–519. 10. Brizendine  L. The Female Brain. 1st ed. New York: Morgan Road Books; 2006. 11. Brizendine L. The Male Brain. New York: Broadway Books; 2010. 12. McIntyre MH. The use of digit ratios as markers for perinatal androgen action. Reprod Biol Endocrinol. 2006;4:10. 13. Tovee  MJ, Tasker  K, Benson  PJ. Is symmetry a visual cue to attractiveness in the human female body? Evol Hum Behav. 2000;21(3):191–200. 14. Lewis  MB. Fertility affects asymmetry detection not symmetry preference in assessments of 3D facial attractiveness. Cognition. 2017;166:130–138.

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Schacht R, Grote M. Partner choice decision making and the integration of multiple cues. Evol Hum Behav. 2015;36(6):456–466. 16. Wang Y, Zhang D, Zou F, et al. Gender differences in emotion experience perception under different facial muscle manipulations. Conscious Cogn. 2016;41:24–30. 17. Simoni  M, Casarini  L. Mechanisms in endocrinology: genetics of FSH action: a 2014-and-beyond view. Eur J Endocrinol. 2014;170(3):R91–107. 18. Nansel  DD, Trent  DF. Frequency modulation of pulsatile luteinizing hormone-releasing hormone stimulation can alter the effectiveness of direct androgen feedback on luteinizing hormone-releasing hormone-induced luteinizing hormone release. Endocrinology. 1979;104(2):532–535. 19. Barraclough CA, Haller EW. Positive and negative feedback effects of estrogen on pituitary LH synthesis and release in normal and androgen-­sterilized rats. Endocrinology. 1970;86(3):542–551. 20. Masood  DE, Roach  EC, Beauregard  KG, Khalil  RA. Impact of sex hormone metabolism on the vascular effects of menopausal hormone therapy in cardiovascular disease. Curr Drug Metab. 2010;11(8):693–714. 21. Hammond CB, Soules M. Clinical significance of estrogen metabolism and physiology. Contemp Ob/Gyn. 1978;11:41. 22. Gore AC. Neuroendocrine targets of endocrine disruptors. Hormones (Athens). 2010;9(1):16–27. 23. Dickerson  SM, Gore  AC. Estrogenic environmental endocrine-­ disrupting chemical effects on reproductive neuroendocrine function and dysfunction across the life cycle. Rev Endocr Metab Disord. 2007;8(2):143–159. 24. Matthews J, Gustafsson JA. Estrogen signaling: a subtle balance between ER alpha and ER beta. Mol Interv. 2003;3(5):281–292. 25. Zhao C, Dahlman-Wright K, Gustafsson JA. Estrogen receptor beta: an overview and update. Nucl Recept Signal. 2008;6:e003. 26. Hurvitz  SA, Pietras  RJ. Rational management of endocrine resistance in breast cancer: a comprehensive review of estrogen receptor biology, treatment options, and future directions. Cancer. 2008;113(9):2385–2397. 27. Zhu  BT, Conney  AH. Functional role of estrogen metabolism in target cells: review and perspectives. Carcinogenesis. 1998;19(1):1–27. 2 8. Pfeffer U, Fecarotta E, Vidali G. Coexpression of multiple estrogen receptor variant messenger RNAs in normal and neoplastic breast tissues and in MCF-7 cells. Cancer Res. 1995;55(10):2158–2165. 2 9. Nelson LR, Bulun SE. Estrogen production and action. J Am Acad Dermatol. 2001;45(3 suppl):S116–S124. 3 0. Feigelson  HS, McKean-Cowdin  R, Pike  MC, et  al. Cytochrome P450c17alpha gene (CYP17) polymorphism predicts use of hormone replacement therapy. Cancer Res. 1999;59(16):3908–3910.

Chapter 4

Regulation of the menstrual cycles Introduction The menstrual cycle is a unique phenomenon of physiology. It is exclusive to 51% of the population. It is a substantial energetic investment. It is an exquisite neuroendocrine orchestration of physiology not required for the growth, survival, or defense of the organism. It is repeated 400 times in the lifetime of a female, but the female generally cannot tolerate more than a 2.5% success rate. Success—fertility— requires a second party and results in the formation of a third party that is a tolerated cancer-like growth within the organism. This chapter discusses the evolution of female sexuality in its specific relationship to the menstrual cycle (Table  4.1). We consider three stages of female sexuality and reproduction capability: prefertility, fertility, and postfertility. We will not discuss the endocrine factors related to global maturation of the organism and its transition through each phase of life. The designation of a woman’s life by reproductive status is not to reflect a patrimonial, Western organization of female life through a one-dimensional lens. To the contrary, the female is the null state of biology. The adult fertile female physiology is the reference state for “normal” physiological function of the human being. The male is a necessary divergence from the female, but a divergence nonetheless. The survival of the species requires an understanding of fertility and reproductive status. Furthermore, the significant variation in endocrine activity across phases and within months (Fig.  4.1) is responsible in part for a number of commonly occurring disorders that are predominantly affecting woman. It is for this reason that we view the cycles of a woman’s life through this lens. The neuroendocrine activity of the female relative to its reproductive status has three implications with respect to their being: 1. Rhythmicity 2. Disorders arising from dysrhythmicity 3. Evolution of the personality

The Theory of Endobiogeny. https://doi.org/10.1016/B978-0-12-816964-3.00004-3 © 2019 Elsevier Inc. All rights reserved.

Rhythmicity is inherent to all organisms. However, women have nested spheres of rhythms to contend with: monthly within chronobiologic within developmental within cosmobiologic spheres of rhythmicity. The female organism must integrate the monthly variations of neuroendocrine cycle into the moment-by-moment demands of adaptation be it from physiologic or psychological demands. The same input of information, the same expression of neuroendocrine factors is expressed in a nonscalable fractal expression in space and time: ovaries, uterus, and global organism. Hopf fibration and circles of Villarceau graphically represent this type of dynamic. Adaptative changes in neuroendocrine and emunctory function throughout stage 2 alter the ability of the female organism to respond appropriately to the solicitation for the significant variation in function required throughout the menstrual cycle. Pregnancy, parturition, and postpartum functions (i.e., lactation) each define additional sets of rhythmic functions and relationships. Each month and through each progression from phase 1b to 3b, the female organism is faced with enormous endocrinometabolic and endocrinotissular demands that can lead to adaptative relationships and emunctory congestion. From this arise disorders particular to women: premenstrual dysphoria, breast, uterine, ovarian pathologies, and catamenial aggravation of chronic disorders. It also helps explain the prevalence of women in certain other types of disorders, such as gallstones, cholecystitis, cellulitis, and lymphatic congestion. The evolution of the female neuroendocrine activity related to fertility and reproduction can be represented as a bipyramid (Fig. 4.2). The apex of the top pyramid represents the premenarche state of potential fertility. There are four sides which represent four types of fertility history. The initial movement represents menarche. Each movement down one face represents a menstrual cycle. Each step is a new month. A women can continue down a vertical line, representing a regular and ideal cycle. Lateral moves, ­zigzags,

69

70  The Theory of Endobiogeny

TABLE 4.1  Fertility, phase, stage and ages of life Phase

Stage

Description

Age range

Prefertility

1a

Newborn, infancy, childhood, adrenarche

0–15

1b

Menarche

13–17

2a

Adolescence, adulthood

15–50

2b

Pregnancy

2c

Parturition

2d

Postpartum

2e

Premenopausal

46–56

3a

Menopause

Varies

Fertility

Postfertility

LH secretion patterns Day Night

Plasma gonadotropins

Childhood

Day Night

Puberty

Day Night

Day Night

Reproductive years

Menopause

LH

FSH

1st 2nd 3rd trimesters Fetal life

Birth

6 months

Infancy

Childhood

50 year

10–14 year Puberty

Reproductive years

Menopause

FIG. 4.1  Variability in FSH, LH throughout life in females. FSH and LH excretion patterns widely vary in circadian cycles as well as throughout the grand phases of life. During fetogenesis, FSH predominates because androgens are derived from the adrenal cortex. During reproductive years, it is the opposite. Note that both the total output and frequency of variation is key to fertility. (Reproduced from Barbara L. Hoffman et al. Williams Gynecology, 3rd ed., 2016. © McGraw-Hill Education.)

regressions, etc. represent adaptative changes in neuroendocrine function throughout life, such as postpartum, or after use of oral hormonal contraceptive medication, etc. The equator is premenopause. The descent is the tapering gonadic activity throughout menopause and gonadic recycling. The lower, or, inverted aspect of the pyramid represents a greater reliance on the adrenal cortex and adipose tissue for gonadal tissues. The inferior apex represents the last month before death.

A brief review of the role of the four axes in menses Central: Corticogonadotropic Central gonadotropic endocrine function refers to the activity of three hormones: hypothalamic gonadotropin releasing hormone (GnRH), and pituitary follicle stimulating hormone (FSH), and luteinizing hormone (LH). There are multiple methods of regulation of central gonadotropic

Regulation of the menstrual cycles Chapter | 4  71

r­ eduction of ACTH (by inhibition) activity plays a beta-like role that allows for the liberation of GnRH be it from CRH, low FSH/LH or other factors.

Central: Thyro-somatogonadotropic Thyro-somatotropic activity also regulates gonadotropic function. TRH directly relaunches GnRH to relaunch FSH activity. However, when TRH stimulates prolactin (PL), PL alters the pulsatile frequency of GnRH release to favor LH activity, diminishing FSH activity (Fig. 4.4). Recall that TRH and PL have an endocrine action on the corticotropic axis. This calibration of CRH and ACTH indirectly regulates the production and timing of excretion of GnRH, FSH, and LH. However, the action of TRH and PL on GnRH does not follow this pattern (Fig. 4.5). It is a more complex and complimentary series of actions that occur both centrally and peripherally (discussed later).

Central-peripheral gonadotropic FIG.  4.2  Bipyramid as a metaphor for the fertility lifecycle of women from menarche to death. See text for details. (Illustration by Tomruen from public domain.)

function. The classical, or, vertical relationship is that of GnRH stimulating FSH and LH. Low amplitude, high pulse excretion of GnRH releases FSH. Higher amplitude, slower pulse excretion releases LH. Implicit in this regulation is the role of inhibin A and B (discussed later) and activin, which inhibits and promotes FSH, respectively. There exists a coupling of corticogonadotropic function that calibrates the excretion and secretion of GnRH according to the relative achievement of the corticotropic axis (Fig.  4.3). There is direct stimulation of GnRH secretion (viz. production) by CRH. CRH plays a para-like role. Rising ACTH plays an alpha-like role in calibration and prolonging the time and amount of GnRH produced. A

FIG.  4.3  First loop central-central adjacent corticogonadotropic coupling. The downstream hormone FSH or LH is shown faded to indicate that it has not yet been excreted. (© 2015 Systems Biology Research Group.)

With respect to intrinsic functioning of the gonadotropic axis, both FSH and LH are responsive to peripheral activity (Fig. 4.6). FSH is relaunched by (1) diminishing estrogens (vertical), (2) rising progesterone (radial). LH activity is relaunched by (1) FSH (horizontal), (2) rising estrogens (radial), and (3) peak progesterone (vertical).

Central-peripheral corticogonadotropic In addition, there is a similar triadic relationship between the corticotropic and gonadotropic axes (Fig.  4.7). This regulates FSH and LH activity based on the degree of solicitation and achievements of ACTH and cortisol. It also regulates peripheral hormones. Recall that cortisol can diminish estrogens by increasing the binding of estrogens to sex hormone binding globulin (SHBG). Conversely, estrogens can diminish free cortisol by increasing its binding to cortisol binding globulin (CBG). These observations should be kept in mind when evaluating the progression of the menstrual cycle, especially during peak estrogen times (days 11–18, 21–23). In addition, recall that estrogens can diminish free

FIG. 4.4  Thyro-somatotropic regulation of central gonadotropic factors. The thyro-somatotropic axis of TRH-PL allows for subtle and dynamic management of the calibration of FSH and LH production. See text for details. (© 2015 Systems Biology Research Group.)

72  The Theory of Endobiogeny

FIG. 4.5  Multiaxial regulation of central gonadotropic factors. The thyro-somatotropic axis of TRH-PL in addition to regulating FSH and LH production directly (see Fig. 4.4), it also relaunches CRH during the turning of the endocrine loops from first to second. CRH and ACTH have the para-like, alpha-like, and beta-like action on GnRH, FSH and LH as previously described. Considering the direct stimulating actions of both TRH and PL, one can observe multiaxial regulation of FSH and LH production. The influence of TRH and PL serve to create a compensatory level of gonadic regulation of metabolism in the face of anticipated thyro-somatotropic anabolic fashioning. In the case of corticotropic axis, it is a calibration of anabolic response to the anticipated catabolic actions of the corticotropic axis. (© 2015 Systems Biology Research Group.)

progesterone by increasing its binding to CBG (not SHBG). This can affect peak progesterone days (16–25).

Central-peripheral thyro-somatogonadotropic

FIG.  4.6  Elaborated regulation of the gonadotropic axis. Red arrow, stimulation; blue arrow, inhibition. (© 2015 Systems Biology Research Group.)

Returning to the relationship of thyro-somatotropic activity on the gonadotropic axis, we find the relationship to be more nuanced and complex (Fig. 4.8). As noted earlier (Fig.  4.4), TRH relaunches FSH and PL relaunches LH. However, while altering central gonadotropic activity, both TRH and PL amplify estrogen’s endocrinometabolic activity regardless of the circulating levels of estrogens. TRH increases the sensitivity of estrogen binding to its receptors. PL augments the number of estrogen receptors. The sum of these relationships is shown in Fig. 4.8.

FIG. 4.7  ACTH stimulates cortisol. There is in the periphery a certain level of circulating estrogens. Estrogens can reduce free cortisol by stimulating its binding to CBG. Thus, at this first time, cortisol stimulates the binding of a certain portion of circulating free estrogens to SHBG. This allows a time for cortisol to liberate a material that estrogens will use at a later time. ACTH stimulates FSH in order to calibrate the intensity of FSH’s future action to the intensity of ACTH’s current vertical action. The rising levels of cortisol stimulated by ACTH allow for cortisol to calibrate and delay the release of FSH while cortisol engages in its action. Cortisol calibrates FSH to what it anticipates will be achieved in the periphery. In the second loop, the relationship and logic is the same. ACTH relaunches cortisol, which plays its alpha-like role on LH with respect to gonadal androgen production.

Regulation of the menstrual cycles Chapter | 4  73

Theca cells LH

Cholesterol

Pregnenolone

Delta 5

Androgens

Delta 4 Progesterone

FIG. 4.8  Nuanced approach to thyro-somatotropic regulation of central gonadotropic factors. The thyro-somatotropic axis of TRH-PL allows for subtle and dynamic management of the calibration of FSH and LH production. Despite the switch from FSH to LH and luteal hormones, both TRH and PL ensure estrogen efficacy and efficiency in various ways. See text for details. (© 2015 Systems Biology Research Group.)

FIG.  4.9  Theca cell production of pregnenolone, progesterone and gonadal androgens. (Reproduced from Andersen CY, Ezcurra D. Human steroidogenesis: implications for controlled ovarian stimulation with exogenous gonadotropins. Reprod Biol Endocrinol. 2014; 12:128. https:// doi.org/10.1186/1477-7827-12-128. © Andersen and Ezcurra; licensee BioMed Central 2014.)

Finally, it should be noted that the somatotropic axis also plays a direct role in the menstrual cycle. Insulin plays a general metabolic role. In addition to this, insulin-like growth factor-1 (IGF-1) and leptin play antagonistic roles. IGF-1 increases the quantitative production of estrogens while leptin antagonizes it.1 In summary, endocrine activity across all four axes, vertically, horizontally, and radially, all affect the quality of gonadotropic hormone activity. Thus, key hormones across the axes need to be considered when evaluating the progression of the menstrual cycle, not just gonadotropic hormones.

Granulosa cells: FSH, LH, estrogens, progesterone, androstenedione

Ovarian production of peripheral hormones The ovaries produce peripheral gonadic hormones in a particular way that is complex and unique. This method of endocrine production is relevant to the Endobiogenic notion that endocrine activity (i.e., receptor distribution, number and sensitivity, presence of cofactors, etc.) cannot be determined by serum levels of hormones (Chapter 3).

Theca cells: LH, progesterone, and androgens There are four units of function with respect to peripheral endocrine production: granulosa cells, theca interna cells, the follicle complex (ovum + granulosa + theca interna + theca externa), and the corpus luteum (granulosa + theca interna + theca externa).2 Theca cells (Fig. 4.9) produce pregnenolone from cholesterol. Pregnenolone can be converted to progesterone. In the ovaries, once converted, progesterone cannot be converted to androgens or estrogens. When pregnenolone is converted through a second pathway to androstenedione, two events can happen. Androstenedione can be converted to testosterone and the latter to dihydrotestosterone (DHT). Or, androstenedione can be transferred to granulosa cells where it is converted into estrogens.

The activity of granulosa cells depends on the phase of the menstrual cycle. The first phase is the follicular phase and can be divided into early, mid-, and late stages, culminating with ovulation. In the early follicular phase, granulosa cells express primarily FSH receptors. FSH promotes the production of an aromatase enzyme that converts the androstenedione produced in theca cells to estrogens (Fig. 4.10). In the late follicular phase, as the dominant follicle grows and estrogen production rises, estrogens within the granulosa cells of the follicle have an endocrinometabolic action that results in expression of LH receptors. This allows for a dramatic increase in the rate of production of progesterone, which regulates the production of estrogens. It does this by diminishing the rate of conversion of androstenedione to DHT. DHT production is irreversible and cannot be converted to estrogens. FSH stimulates the excretion of inhibin from granulosa cells, which diminishes the excretion of FSH. The continued rise in estrogen activity is related to the actions of LH + Progesterone, as well as that of TRH and PL noted earlier. Thus, in the late follicular phase the rise in progesterone comes more from granulosa cells, which have multiplied to a greater degree than theca cells (Fig. 4.11).

Corpus luteum: FSH, LH, estrogens, progesterone, androstenedione Once the ovum is released, the predominance of LH over FSH luteinizes the remaining granulosa and thecal cells to form the corpus luteum. The production of estrogens and progesterone continues under the influence of LH (or human choriogonadotropin hormone: hCG, if there is fertilization) (Fig. 4.12).

Ovarian stroma compartment

Intrafollicular compartment

Theca cells

Granulosa cells

LH

Cholesterol

FSH

Pregnenolone

Delta 5

Androgens

Aromatization

Estrogens

Delta 4 Progesterone

Early follicular phase (follicles 10–12 mm diameter) FIG. 4.11  Late follicular phase production of peripheral gonadal hormones. See text for details. (Reproduced from Andersen CY, Ezcurra D. Human steroidogenesis: implications for controlled ovarian stimulation with exogenous gonadotropins. Reprod Biol Endocrinol. 2014; 12:128. https://doi. org/10.1186/1477-7827-12-128. © Andersen and Ezcurra; licensee BioMed Central 2014.)

Luteal phase Corpus luteum Theca and granulosa luteal cells LH/hCG

FSH

Delta 5

Pregnenolone

Androgens

Estradiol

Cholesterol Delta 4

Pregnenolone

Progesterone

FIG. 4.12  Luteal phase hormone production in the corpus luteum. Luteinizing hormone and/or hCG (if there is fertilization) play the predominant role in production of progestanes, androgens, and estradiol. (Reproduced from Andersen CY, Ezcurra D. Human steroidogenesis: implications for controlled ovarian stimulation with exogenous gonadotropins. Reprod Biol Endocrinol. 2014; 12:128. https://doi.org/10.1186/1477-7827-12-128. © Andersen and Ezcurra; licensee BioMed Central 2014.)

Regulation of the menstrual cycles Chapter | 4  75

TABLE 4.2  Summary of location of peripheral gonadal hormone production within the gonads Cell

Androgens

Progesterone

Theca interna

•

•

Granulosa Corpus luteum

•

Estrogens

•

•

•

•

In summary, theca cells only produce luteal hormones: progesterone and androgens. Granulosa cells produce estrogens from theca-produced androgens as well as progesterone. Thus, they express FSH and LH receptors. After ovulation, the remainder of the follicle fuses to form the corpus luteum, a syncytium that produces all three types of hormones: androgens, progesterone, and estrogens (Table 4.2).

GnRH Luteal phase

Follicular phase

Luteal phase

LH FSH

Inhibin A Inhibin B

Introduction to the menstrual cycle The menstrual cycle is a multiendocrine process that selects and matures a follicle in the ovaries while preparing the uterus for a possible implantation of a fertilized egg. According to convention, the cycle is divided into two phases: follicular and luteal. The first day of the cycle is the first day of menstruation: the sloughing of the endometrial lining due to the absence of implantation of a fertilized egg. The follicular phase culminates with ovulation. The luteal phase starts the day after ovulation and ends with the first day of menses. The “ideal” cycle lasts the duration of a lunar month: 28 days, with a normal range of 25–30 days. In a 28-day cycle, each phase is 14 days long. Variability in the length of the menstrual cycle arises primarily from the efficiency of the follicular phase and its associated hormones.

A discussion on serum vs functional endocrine assessment Commonly, depiction of endocrine activity during the menstrual cycle exclusively features the average or ideal serum levels of gonadotropic hormones3, 4: GnRH, FSH, LH, Inhibin A, Inhibin B, Estradiol (E2), and Progesterone (Prog) (Fig. 4.13). According to an integrative physiologic perspective according to the theory of Endobiogeny, one must consider the functional activity of these hormones in the menstrual cycle, not strictly the quantitative output from the organs. What is more, there are other hormones that regulate, compliment, or antagonize the “primary” hormones involved in the menstrual cycle and hence fertility (Fig. 4.14).

E2 Prog

Endo Secretory

Menses Proliferative

Secretory

FIG. 4.13  Ideal serum levels of hormonal fluctuation during menstruation. (Reproduced from Hall JE. Neuroendocrine control of the menstrual cycle. In: Yen and Jaffe’s Reproductive Endocrinology, 8th ed. Elsevier; 2019 [chapter 7]. Copyright © 2019 Elsevier Inc.)

There are three reasons why this quantitative depiction is neither accurate nor instructive in clinical management of menstrual disorders: rhythmicity, variability, and qualitative activity.

Rhythmicity Implicit in the rhythmicity of endocrine function are the following factors: chronology, sequencing, integration, proportionality, and pulsatility. Pulsatility refers to the periodicity of excretion of a hormone. Implicit in this assessment is the amplitude of release (i.e., serum concentration), sustain (i.e., duration of the peak concentration), and half-life. For example, in Table  4.3, the variations in these factors with respect to LH are represented by their mean value. The total daily concentration of LH demonstrates little variation throughout the phases of the menstrual cycle. However, the variations in the other factors dramatically change the role of LH. The same observations hold true for all other hormones. The change in the quality of their periodicity changes the specific actions it has in specific tissues.

76  The Theory of Endobiogeny

FIG. 4.14  Summary of hormone activity of the menstrual cycle according to the theory of Endobiogeny. Details discussed throughout the text. (© 2016 Systems Biology Research Group.)

TABLE 4.3  Rhythmicity of central gonadotropic hormones throughout a menstrual cycle Phase

Periodicity (min)

Amplitude (mlU/mL/min)

Sustain (min)

LH half-life (min)

Total daily excretion (mlU/mL/24 h)

Early follicular

80

0.43

6.5

131

49

Late follicular

53

0.70

3.5

128

56

Midluteal

177

0.26

11.0

103

52

Modified from Table 2 in Reed BG, Carr, BR. The Normal Menstrual Cycle and the Control of Ovulation, Endotext, http://www.endotext.org/chapter/thenormal-menstrual-cycle-and-the-control-of-ovulation/?singlepage=true Accessed 2 April 2016.

Variability There are numerous reasons for variability in the quantitative excretion of hormones from glands: 1. Pulsatility: qualitative and quantitative variations 2. Chronology of polyendocrine action

3. Proportionality of polyendocrine action (i.e., antagonism, complementarity, etc.) 4. Multiple receptor isoforms distributed in different areas of the body 5. Genetic polymorphisms of receptor isoforms 6. Genetic polymorphisms in posttranslational mechanisms

Regulation of the menstrual cycles Chapter | 4  77

7. Environmental actors (xenoendocrine function, antiendocrine function, etc.) 8. Adaptative variations 9. Buffering capacity of the organism 10. Clearance rates of hormones

mones. Some indicative graphs are shown for luteinizing hormone (Fig.  4.15), as well as estradiol (Fig.  4.16) and progesterone (Fig. 4.17).

When we evaluate the range in quantitative endocrine output during the menstrual cycle, it becomes clear that the terrain of the individual patient is the only way to explain both normal and dysfunctional menses and fertility across a broad range of “normal” serum levels of gonadotropic hor-

According to the theory of Endobiogeny, endocrine activity is interrelated and integrated in its function. Neuroendocrine activity is calibrated through timing, antagonism, complementarity, receptor sensitivity modification, binding capacity, and many other factors. Thus, the qualitative, functional

Qualitative action

FIG. 4.15  Variations in quantitative LH output throughout the menstrual cycle. The dark blue line is the average serum value. The widest lines (yellow and orange) represent interwoman variability in serum levels. (Illustration by Mikael Häggström [Public domain], from Wikimedia Commons.)

FIG. 4.16  Variations in quantitative estradiol output throughout the menstrual cycle. The dark blue line is the average serum value. The widest lines (yellow and orange) represent interwoman variability in serum levels. (Illustration by Mikael Häggström [Public domain], from Wikimedia Commons.)

78  The Theory of Endobiogeny

FIG. 4.17  Variations in quantitative progesterone output throughout the menstrual cycle. The dark blue line is the average serum value. The widest lines (yellow and orange) represent interwoman variability in serum levels. (Illustration by Mikael Häggström [Public domain], from Wikimedia Commons.)

activity of multiple hormones and emunctories together can demonstrate the adaptive vs adaptative nature of the menstrual cycle.

Follicular phase The follicular phase is the first part of the menstrual cycle. The goal of the cycle is to select and mature a single follicle for ovulation. However, the process of follicle selection has two caveats. First, it begins at puberty. Second, it takes three regular menstrual cycles to mature a follicle (referred to as a Graafian follicle once ready to ovulate).

Development of follicles 1. Uterine life: Folliculogenesis 2. Birth: 400,000 primordial follicles 3. Childhood: Quiescence of primordial follicles 4. Puberty: Primordial follicles develop into early primary follicles with FSH relaunching 5. Fertility: Groups of primary follicles are developed. One dominates and progresses to maturity then ovulation. The remainders become atretic (Fig. 4.18) 6. Menopause: Quiescence It takes a minimum of 3 months of readaptation of the Endobiogenic terrain to determine its efficacy in reestablishing normal ovulation patterns. NB: Like the base melody of a Bach concerto, there is an underlying permissive endocrine function which is not explicitly discussed: cortisol, aldosterone, peripheral thyroid, growth hormone, IGF-1, insulin, etc. Their roles will be discussed under “pathophysiology.”

D1–4: Early follicular Endocrine and ovary: Time of FSH The first part of the follicular phase is the time of FSH. GnRH relaunches FSH around the 26th day of the prior cycle. FSH stimulates the recruitment of follicles developed in the prior menstrual cycles. As FSH starts to peak, there is a sharp rise in Inhibin B to slow down FSH activity while promoting estrogen relaunching (Fig. 4.19).

Endometrium and cervix The endometrium undergoes necrosis and sloughing of the accumulated lining form the prior cycle when there is no fertilization of an ovum. This process typically lasts for 4–5 days with a normal range of 3–8 days. Its variation is related to the quality of the estro-thyrotropic relationship in the luteal phase and early follicular phase (discussed later). Cervical mucus is thin and scanty (Fig. 4.19).

D5–10: Mid-follicular Endocrine and ovary: Time of estrogens and PL The selection of a dominant follicle drives a significant increase in Estrogen activity.4 Days 5–8: Rise in estrogen activity Granulosa cells primarily express FSH receptors. LH stimulates theca cells to produce androstenedione from cholesterol. Androstenedione is taken up by granulosa cells of the follicle to provide substrate for the increasing demand for estrogens. Rising estrogen levels diminish GnRH and FSH activity (Fig. 4.20).

Regulation of the menstrual cycles Chapter | 4  79

Antimüllerian hormone Inhibin B Primary follicle Primordial follicle

Stroma

Early antrum formation

m

Atretic follicle

Me

sov

ariu

Graafian follicle

Blood vessels Corpus albicans Estradiol Inhibin A

Germinal epithelium Mature corpus luteum Relaxin

Ovulation Androstenedione Testosterone

Early corpus luteum Progesterone Estradiol Inhibin A FIG. 4.18  General schematic representation of development of a follicle from uterine life to ovulation. See text for details. (From Strauss JF, Williams CJ. Ovarian Life Cycle. Yen and Jaffe’s Reproductive Endocrinology. 8th ed. [chapter 8] Copyright © 2019 Elsevier Inc.)

Early follicular phase summary 1

2

3

4

5

6

7

8

9

10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28

1

2

3

4

5

6

7

8

9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28

Endocrine GnRH

Ovulation

FSH E2

P2 LH

Follicle

Recruitment

Uterus

Necrosis

Cervix

Scant, thin

FIG. 4.19  Early follicular phase summary of endocrine activity according to the theory of Endobiogeny. Days 1–4, starting at the top down, witnesses a rise in gonadotropin releasing hormone (GnRH), which relaunches FSH activity. Estrogens (E2), progesterone (P2), and LH are all declining at this time as a response to the absence of implantation of a fertilized ovum at the end of the last period. Bottom left shows the status of development of the follicle, uterine lining (endometrium), and cervical mucus. (© 2016 Systems Biology Research Group.)

Days 8–10: Rise in PL, augmentation of estrogen Diminishing FSH affects the quantitative production of estrogens. However, estrogen activity continues to rise as evidenced by the further proliferation of the endometrium.

TRH relaunches PL, which increases the number of estrogen receptors. PL relaunches insulin to provide energy for the rapid growth of the dominant follicle and the endometrium (Fig. 4.20).

80  The Theory of Endobiogeny

Mid-follicular phase summary 1

2

3

4

5

6

7

8

9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28

Endocrine GnRH

No E2 recep E2 PL P2 LH

1

2

3

4

5

6

7

8

9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28

Follicle

Recruitment

Uterus

Necrosis

Proliferative phase

Scant, thin

πΣ + E2: copious, clear, elastic

Cervix

OVULATION

FSH

Selection

FIG. 4.20  Mid-follicular phase summary according to the theory of Endobiogeny. From top left, gonadotropin releasing hormone (GnRH) continues to rise, sustaining at first FSH which reaches its zenith by day 7. This results in a surge in estrogen (E2) activity, which suppresses further FSH activity. This rise in estrogen activity is both quantitative thanks to FSH, but also due to a peak of prolactin (PL, in gray), which augments the efficacy of estrogens. The continued rise in GnRH is for relaunching of LH in preparation for a surge in progesterone in the late follicular period to stimulate ovulation. Bottom left shows the status of development of the follicle, uterine lining (endometrium) and cervical mucus. E2, estrogens; No, number; P2, progesterone; Recep., receptors. (© 2016 Systems Biology Research Group.)

Endometrium The rise in estrogen activity and receptors allows for rapid growth of the endometrium.4 Cervical mucus, also under the influence of Estrogens and parasympathetic becomes increasingly abundant, clear, and elastic (Fig. 4.20).

D11–14: Late follicular Endocrine and ovary: Time of TRH, PL, and LH Day 11: Day of TRH: GnRH, FSH relaunching In order to sustain sufficient estrogen activity, TRH is relaunched. This in turn has four effects: 1. GnRH relaunching 2. FSH relaunching 3. Increased estrogen receptor sensitivity 4. PL relaunching Day 11: PL PL reaches its peak, upregulating estrogen receptors. This allows the organism to amplify the actions of ­existing estrogens while stimulating GnRH pulsatility to favor

the release of LH in preparation for ovulation in 3 days (Fig. 4.21). Day 12: FSH peak FSH peaks at this time based on the activity of day 11. This continues to sustain the rising estrogen activity and progressive proliferation of the endometrium. LH activity begins to rapidly increase. The FSH peak on days 12 and 14 increases a man’s desire for a woman. Women appear more attractive to men,5 behave more flirtatiously,6 wear shorter, and tighter clothing,7 and have a more appealing odor to men with whom they are already in a relationship if they have a natural menstrual cycle.7 Axillary pheromones from this stage can stimulate an LH surge in other women, or, if taken in the luteal phase, delay it8 (Fig.  4.22). Note that sperm can survive for 72 h from ejaculation, but the ovum can only survive for 24 h. Thus, the optimal time for coitus is on days 12–14, so that viable sperm is present at the time of ovulation. D12–13 LH double rebound ACTH slows down PL. However, the rise in PL has relaunched LH by changing GnRH pulsatility. The rising

Regulation of the menstrual cycles Chapter | 4  81

FIG. 4.21  The late follicular phase according to the theory of Endobiogeny. Left key to hormones, top to bottom: with assistance from TRH (red), GnRH reaches its peak by ovulation. With assistance from horizontal relaunching by ACTH, FSH reaches its peak around day 12. Estrogens (E2) reach their zenith at ovulation, around day 14, with assistance by TRH, GnRH, and FSH. In preparation for ovulation, once sees a dramatic rise in LH with a delayed response by progesterone (P2) by the end of the follicular phase. Bottom left shows the status of development of the follicle, uterine lining (endometrium), and cervical mucus. E2, estrogens; No, number; P2, progesterone; Recep., receptors. (© 2016 Systems Biology Research Group.)

LH prepares the organisms for ovulation. Granulosa cells express LH receptors, which has four effects: 1. Centralizes aromatization of cholesterol to androstenedione and then estrogens primarily within the granulosa cells 2. Prepares the granulosa cells to produce progesterone 3. Increased mitosis of the oocyte 4. Production of prostaglandins for ovulation

menstruation are determined largely by estrogen activity during the mid and late follicular phases. Cervical mucus has reached its peak fluidity and elasticity. Under a microscope a ferning pattern can be noted.

Day 14: Ovulation: LH  + progesterone + T4 +  prostaglandins LH reaches its peak for the follicular phase. The rise in prostaglandins from LH is thought to allow for a rupture in the mature Graafian follicle allowing for the oocyte to be released (Fig. 4.23). Rising progesterone along with a rise of T4 causes a quantum rise in basal body temperature around the time of ovulation.4

The follicular phase of the menstrual cycle has three stages (Fig. 4.24). The early stage is dominated by FSH and follicle recruitment. The mid-stage is characterized by FSHestrogen predominance for follicle selection and uterine proliferation. The late stage is an LH-Estrogen predominance assisted by TRH and PL, and regulated by ACTH. The culmination of the follicular phase is ovulation, which requires a combination of LH, prostaglandins (locally produced), progesterone, and T4 (heralded by peak body temperature).

Endometrium The endometrium has fully proliferated. The degree of proliferation and therefore the duration of bleeding at

Summary of follicular phase endocrine, follicle, and endometrial activity

●

Efficiency of FSH and estrogens within the ovary are the most indicative prospects of development of a viable ovum.

82  The Theory of Endobiogeny

7.0

Sexual attractiveness

7.0 6.5

6.5

6.0

6.0

5.5

5.5

5.0

5.0

4.5

4.5

4.0

4.0

3.5

3.5

3.0

3.0 2.5

2.5 0

Sexual attractiveness

(A)

2

4

6

8 10 12 14 16 18 20 22 24 26 28

(B) 7.0

7.0

6.5

6.5

6.0

6.0

5.5

5.5

5.0

5.0

4.5

4.5

4.0

4.0

3.5

3.5

3.0

3.0

2.5

2

4

6

8 10 12 14 16 18 20 22 24 26 28

0

2

4

6

8 10 12 14 16 18 20 22 24 26 28 Day of menstrual cycle

2.5 0

(C)

0

2

4

6

8 10 12 14 16 18 20 22 24 26 28 Day of menstrual cycle

(D)

FIG. 4.22  Sexual attractiveness of women using or not using oral hormonal contraception. The dotted line is the preference for a clean, unworn T-Shirt. The curved lines represent the mean preference rating of the scent of a woman’s t-shirt at various phases of the menstrual cycle. Men’s (A) preference for the scent of women peaked on days 12–13 if they were not on oral contraceptives. Women’s (C) preference for the scent of women’s t-shirts showed no statistically significant variation. Neither men nor women (B, D, respectively) found the scent of women’s t-shirt attractive if she was on oral contraceptives. (Reproduced from Kuukasjarvi S, Eriksson CJP, Koskela E, Mappes T, Nissinen K, Rantala MJ. Attractiveness of women’s body odors over the menstrual cycle: the role of oral contraceptives and receiver sex. Behav Ecol 2004; 15(4):579–584. https://doi.org/10.1093/beheco/arh050.) ●

●

Efficiency of estrogen activity on endometrial proliferation is the most important determination of the length of the menstrual cycle. LH-prostaglandin-progesterone-T4 surge is most indicative of ovulatory success

Luteal phase

FIG.  4.23  Endoscopic capture of spontaneous ovulation. (Reproduced from Lousse JC, Donnez J. Laparoscopic observation of spontaneous human ovulation. Fertil Steril. 2008;90(3):833-834. https://doi.org/10.1016/j. fertnstert.2007.12.049.)

The luteal phase is so named because of the luteinization of the granulosa cells. Once the ovum has been ovulated, the remaining complex of proliferated granulosa cells and theca cells form a new, temporary endocrine organ under the influence of the LH predominance. From a histological perspective, “luteinization” refers to the accumulation of the yellow carotenoid lutein. Functionally, luteinization is the transformation of the granulosa cells into an estroprogestive endocrine unit. That is to say, because progesterone is a luteal product of LH stimulation, there is a luteinization of the estrogen-producing granulosa cells. We can divide the luteal phase into three stages: early, mid-, and late. The early and mid-stages are spent in anticipation of ­implantation. If this does not occur, then the later stage

Regulation of the menstrual cycles Chapter | 4  83

FIG. 4.24  A summary of the follicular phase activity of gonadotropic hormones according to the theory of Endobiogeny. The intrinsic gonadotropic hormones are assisted by ACTH (horizontal stimulation of FSH, LH), as well as prolactin (PL: estrogen receptors) and TRH (GnRH relaunching, FSH relaunching, estrogen receptor sensitivity to estrogens). In summary, ovulation is a luteal feat which occurs within an environment prepared by follicular hormones in conjunction with corticotropic, thyrotropic, and somatotropic factors. Bottom left shows the status of development of the follicle, uterine lining (endometrium), and cervical mucus throughout the follicular phase. E2, estrogens; No, number; P2, progesterone; Recep., receptors. (© 2016 Systems Biology Research Group.)

proceeds with a dramatic reduction in the activity of all hormones related to the menstrual cycle.

a­ ctivity, which had declined with rising progesterone levels (Fig. 4.25).

D15–20: Early luteal

Endometrium and cervix

Endocrine and ovary

The endometrium enters a secretory phase with an augmentation of the number of glands and crypts. The cervical fluid becomes increasingly copious but thick and opaque witnessing the predominance of alpha over para in the luteal phase.

D15–20: Progesterone predominance, estrogen decline In addition to progesterone production from theca cells, the new luteal body now produces a significant amount of progesterone from the granulosa cells. Rising progesterone downregulates estrogen production but upregulates the number of estrogen receptors. GnRH, FSH, and LH levels diminish with rising progesterone and estrogens (Fig. 4.25). D18: GnRH relaunching: Alpha, CRH Alpha-sympathetic and CRH sustain GnRH relaunching to recalibrate global gonadotropic activity (Fig. 4.25). D19: Estrogen relaunching: PL After a peri-ovulatory nadir, rising PL activity opens up additional estrogen receptors, augmenting estrogen

D21–24: Mid-luteal Endocrine and ovary D21–24: Peak progesterone Implantation of a fertilized ovum should take place within approximately 10 days from ovulation. Progesterone is at its peak level of activity thanks the output of the corpus luteum. The sustained high-progesterone state further diminishes the sensibility and activity of estrogens (Fig. 4.26).

84  The Theory of Endobiogeny

FIG. 4.25  Early luteal activity according to the theory of Endobiogeny. Left key to hormones, bottom to top: LH reached its peak on day 14: ovulation (see Fig. 4.24) and now declines to its nadir. However, progesterone climbs to its zenith throughout this period. Estrogens (E2) decline due to the fall in GnRH and FSH activity. However, there is progressive rise in prolactin (gray line) which, at its peak, augments the efficacy of estrogens even in the face of falling quantitative values. GnRH is relaunched by alpha-sympathetic (αΣ) and CRH to prepare for a brief rise in LH in the mid-luteal phase in order to sustain progesterone. Bottom portion of image shows the status of development of the corpus luteum, uterine lining (endometrium), and cervical mucus. (© 2016 Systems Biology Research Group.)

D21: TRH, estrogen relaunching TRH is relaunched to sustain estrogen sensibility and further mature endometrial mucous in case there is fecundation. It also relaunches GnRH and FSH to help achieve the same goal (Fig. 4.26). D21: ACTH relaunching ACTH rises to limit PL and prevent excessive estrogen sensitivity. However, through horizontal stimulation it further relaunches FSH, indirectly calibrating the quality of the estrogen relaunching started on day 21.

what is referred to as the corpus albican. There is then a precipitous drop in progesterone activity. This causes an atrophy of the arteries nourishing the endometrium. Inhibin A (not depicted in the graphs) reaches its peak and prevents FSH and estrogen relaunching. In the face of the precipitous drop in estrogens and progesterone, the proliferated endometrium cannot maintain the metabolic activity required to sustain itself. Thus, within 3–4 days the endometrium undergoes ischemic necrosis and sloughs. Prostaglandins, released by the endometrium stimulate contraction, expelling the necrotic tissue (Fig. 4.27).

Endometrium and cervix Cf. above.

D25-menstruation: Late luteal Endocrine, ovary, endometrium In the absence of LH relaunching or human choriogonadotropin hormone (hCG), the corpus luteum degenerates into

Summary of luteal phase endocrinology The luteal phase creates a temporary endocrine organ: the corpus luteum, which is responsible for production of both estrogen and significant amounts of progesterone. In the early luteal stage, the luteal body is formed and progesterone reaches its peak levels. This diminishes the activity of other hormones. Alpha, CRH, and PL help relaunch GnRH

Regulation of the menstrual cycles Chapter | 4  85

FIG. 4.26  Mid-luteal phase summary according to the theory of Endobiogeny. Left key to hormones, from bottom up: LH peaks one last time to sustain the plateau of maximal progesterone (P2) during this crucial phase of support of a possibly implanted embryo. A peak of TRH is key to sustaining prolactin (PL) before its decline for the remainder of the cycle, as well as a final relaunching of estrogens and FSH. Bottom portion of image shows the status of development of the corpus luteum, uterine lining (endometrium), and cervical mucus. (© 2016 Systems Biology Research Group.)

and Estrogen activity. In the mid-luteal stage, the peak progesterone activity is sustained awaiting a successful implantation of a fertilized ovum. TRH is relaunched to further sustain GnRH, FSH, and estrogen in support of progesterone. In the late luteal stage, if there is no implantation, all hormone levels precipitously diminish (Fig. 4.28). ●

●

Estro-progestive activity is most determinant of implantation and pregnancy Efficiency of estro-progestive regulation and regulation of its regulators: TRH, PL, Alpha, ACTH is most implicated in minimizing symptoms of the late luteal stage (viz. premenstrual syndrome)

Conclusions The human female menstrual cycle constitutes a repetitive longitudinal variation in neuroendocrine activity. This significant fluctuation in hormonal and emunctory function is part of a strategy of preparing the female of childbearing

age on a monthly basis for the possibility of fertility with a mate. This activity, as metabolically demanding as it is, is a necessary requirement for propagation of the species. Its proper functioning not only ensures survival of the species, but diminishes the risk of disorders of menstruation and congestion of emunctories. The theory of Endobiogeny posits that given the significant variations of quantitative output of hormones during the menstrual cycle, and that this is not a valid way to determine what the model of optimal function is. Instead, the construct of optimal menstrual function must consider multiple nongonadotropic hormones and their functional and effective synergistic interaction with the key gonadotropic hormones. The menstrual cycle can be divided into two pages: follicular and luteal. The follicular is the time of absolute estrogen predominance and preparation of the endometrium for possible implantation of a fertilized follicle. The luteal phase is the time of absolute progesterone predominance to nurture any possible implantation. The sequencing of these two phases is key for optimal fertility and a symptom-free menstrual cycle.

FIG. 4.27  Late luteal phase according to the theory of Endobiogeny. The endocrine activity assumes that there has not been successful implantation of a fertilized egg. Left key, bottom to top: LH remains low until the late follicular phase. Progesterone (P2) activity precipitously diminish, as do estrogens (E2), and FSH. GnRH starts a gradual increase in activity to prepare the pituitary and ovaries for the next follicular phase. Bottom left key shows the status of involution of the corpus luteum, uterine lining (endometrium), and cervical mucus. (© 2016 Systems Biology Research Group.)

FIG. 4.28  Luteal phase summary according to the theory of Endobiogeny. The luteal phase is predominated by the luteal hormone progesterone (P2) and estrogens (E2), which are at their second highest peak of activity of the luteal phase. Where the follicular phase prepared the endometrium to receive a fertilized ovum, the luteal phase prepares the endometrium to nourish and nurture this fertilized ovum. Key to assisting gonadotropic hormones is a prolonged activity of prolactin for 2/3rds of the cycle, as well as TRH, CRH, ACTH, and alpha-sympathetic (αΣ). Bottom left shows the course of the corpus luteum, uterine lining (endometrium), and cervical mucus. (© 2016 Systems Biology Research Group.)

Regulation of the menstrual cycles Chapter | 4  87

References 1. Agarwal  SK, Vogel  K, Weitsman  SR, Magoffin  DA. Leptin antagonizes the insulin-like growth factor-I augmentation of steroidogenesis in granulosa and theca cells of the human ovary. J Clin Endocrinol Metab. 1999;84(3):1072–1076. 2. Andersen  CY, Ezcurra  D. Human steroidogenesis: implications for controlled ovarian stimulation with exogenous gonadotropins. Reprod Biol Endocrinol. 2014;12:128. 3. Hall JE. Neuroendocrine control of the menstrual cycle. In: Yen and Jaffe’s Reproductive Endocrinology. 8th ed.Elsevier; 2019 [chapter 7]. 4. Jones RE, Lopez KH. The menstrual cycle. In: Jones RE, Lopez KH, eds. Human Reproductive Biology. 3rd ed.Elsevier; 2006 [chapter 3].

5. Roberts SC, Havlicek J, Flegr J, et al. Female facial attractiveness increases during the fertile phase of the menstrual cycle. Proc Biol Sci. 2004;271(suppl 5):S270–S272. 6. Cantu SM, Simpson JA, Griskevicius V, Weisberg YJ, Durante KM, Beal DJ. Fertile and selectively flirty: women's behavior toward men changes across the ovulatory cycle. Psychol Sci. 2014;25(2):431–438. 7. Kuukasjarvi  S, Eriksson  CJP, Koskela  E, Mappes  T, Nissinen  K, Rantala MJ. Attractiveness of women’s body odors over the menstrual cycle: the role of oral contraceptives and receiver sex. Behav Ecol. 2004;15(4):579–584. 8. Stern K, McClintock MK. Regulation of ovulation by human pheromones. Nature. 1998;392(6672):177–179.

Chapter 5

Menstrual cycle disorders Introduction Disorders of the menstrual cycle can be nosologically categorized in multiple ways: symptoms, menstrual phase, or endocrine predominance/insufficiency. Each has advantages and disadvantages. Regardless of the classification system used, according to the theory of Endobiogeny, one must consider the global terrain of the organism. This includes endocrine function across all four axes, emunctories, glands, key organs, and the role of congestion. Disorders of the menstrual cycle are significant for two reasons. First, they affect a large portion of the population of girls and women, causing discomfort, pain, psychological affectations, and loss of productivity. Second, the adaptative compensations of disorders of menstruation can install acute, recurrent, or catamenial disorders such as premenstrual dysphoria and premenstrual migraines. Overtime, it can degrade the terrain through congestion of the pelvic basin, liver, gallbladder, and lymphatics. Finally, it can participate in various illnesses from uterine leiomyoma to breast cysts to breast cancer. The Endobiogenic approach to disorders of menstruation allows for treatment or amelioration of precritical and critical terrains of numerous disorders. Judicious treatment today may spare a woman tomorrow’s disorder.

General consideration of emunctories and glands

both endocrine products and waste products related to endometrial sloughing in the early follicular period. After metabolism in the liver, hormones must be excreted in a timely fashion, bound to bile salts. This is the primary route of estrogen elimination.1 Impairment in choleresis, cholagogy, or defecation can augment endocrine activity beyond the intended levels as managed by the global terrain,1 favoring premenstrual symptoms.2 In addition, hyperestrogenism impairs choleresis and increases the risk of gallstone formation.3

Exocrine pancreas Exocrine pancreatic function is implicated in two ways. The first is the apportionment of nutrients from the diet for the fabrication of hormones, prostaglandins, cervical mucous, and proliferation of the uterine lining. The second is its role in biliary motricity and chronology (cf. The Theory of Endobiogeny, Volume 2, Chapter 8).

Endocrine pancreas The endocrine pancreas plays its general role in glucose regulation for the rapid augmentation of metabolic activity related to growth of the uterus. Oversolicited endocrine function favors inflammation of the uterus and increased tendency toward cramping and bleeding, associated with diet2, 4 and addressed through dietary changes.5, 6

Liver

Intestines

The liver is implicated in all menstrual disorders (Table 5.1). Three categories of hepatic activity are most implicated (cf. The Theory of Endobiogeny, Volume 1, Chapter 7). Quantitative endocrine secretion and excretion can increase 30-fold above baseline levels throughout the menstrual cycle (Chapter  4). This creates repetitive, cyclical demands on the liver for metabolism of hormones. Otherwise, partial metabolites of hormones, with variable endocrinometabolic activity, will create a state of dysregulated hyperendocrinism.

As noted above, small intestinal function is key for transfer of nutrients to the portal vein and liver. The colon as an emunctory is important for the removal of waste products and to prevent reuptake of partially metabolized endocrine products.

Gallbladder The gallbladder refines, stores, and excretes bile made in the liver. Proper biliary function is required for the excretion of The Theory of Endobiogeny. https://doi.org/10.1016/B978-0-12-816964-3.00005-5 © 2019 Elsevier Inc. All rights reserved.

Pelvic circulation Numerous factors play a role in physiologic congestion of the pelvic circulation in order to support the growth of the follicle in the ovary and the growth of the endometrial lining. Overtime, chronic oversolicitation of these factors, such as alpha-sympathetic, or inefficiency of ovarian endocrine production favors an adaptative pelvic congestion 89

90  The Theory of Endobiogeny

TABLE 5.1  Hepatic function and its role in menstrual physiology Category

Event

Phase

Day(s)

Metabolic

Carrier proteins for hormones

Follicular, luteal

1–28

Conversion of T4 to T3

Follicular, luteal

5–25

Production of IGF-1

Follicular, luteal

5–25

Bile production

Follicular, luteal

1–28

Nutrition

Processing and distribution of increased nutrient demand

Follicular, luteal

5–25

Detoxification

Processing of endocrine metabolites for excretion

Follicular, luteal

1–28

Processing of necrotic and inflammatory material

Follicular

1–5

throughout the entire month, even in menopause. This observation explains why women have a higher frequency of neurovegetative dissociation with colder feet than hands. There are numerous commonly used plants with good tropism for pelvic drainage (Table 5.2). A few commonly used

TABLE 5.2  Medical plants with a primary tropism of pelvic drainage with additional tropisms related to menstrual physiology Plant

2° tropism

3° tropism

Achillea millefolium

Pelvic antiinflammatory, uterine antihemorrhagic

(−) Aldosterone

Endometrial antihemorrhagic

Genital antimicrobial

Uterine antiinflammatory and antimicrobial

Spasmolytic

Artemisia dracunculus

Genital antispasmodic and antimicrobial

Hypoglycemant

Cupressus sempervirens

Uterine antispasmodic

(+) Estrogenic

Lamium album

Antihemorrhagic

(+) GH, PL

Lavandula angustifolia

Spasmolytic

Hepatobiliary drainer

Matricaria recutita

Spasmolytic

Hepatosplanchnic drainer

Quercus pedunculata

Osteoblastic

Favors androgens, cortisol

Alchemilla vulgaris Anthemis nobilis

plants are listed below grouped by secondary tropism related to genitourinary conditions.

Hamamelis virginiana (Witch hazel) Parts used: leaf, stem, bark Galenic: MT, FE, DE, bulk herb Activity:7, 8 ●

●

● ● ●

● ●

Vascular: pelvic decongestant (venous stimulation), venotonic, vasoconstrictive, circulatory drainer, antiedematous, hemostasis Genitourinary: genitourinary antiinflammatory, antihemorrhagic, cicatrizant, and antiinfectious activity (antifungal > antiviral; bacteriostatic) Digestive: astringent, antidiarrheal Drainage: pelvic, splanchnic Mucocutaneous: antiinflammatory, cicatrizing, antihistaminic, analgesic, tissue regenerator ANS: alpha-mimetic (mild), antihistaminic Endo: corticotropic: mild stimulant through alpha-­ mimetic activity

Use: all pelvic pathologies: hemorrhagic cystitis, prostatitis, metrorrhagia, uterine and cervical cancer, prostate cancer; hemorrhoids, disorders associated with pelvic congestion: lower extremity edema, heavy legs, phlebitis, external hemorrhage; diarrhea, colitis; contusions, insect bites, small wounds, acne. Method: Leaf: ¼ tsp. in 5 oz. water; steep 10–15 min, drink 2–3 times per day; compress/bath: 1–2 tsp. leaves in 8 oz. water; steep 15 min.

Summary Each of the elements of the terrain has its own intrinsic function related to basal and adaptive metabolism outside the

Menstrual cycle disorders Chapter | 5  91

requirements of the menstrual cycle. These elements can be oversolicited, become congested or inefficient in their basal function. In this case, the organism expresses symptoms and exhibits signs outside specific days of the menstrual cycle. If the adaptive capabilities as related to the menstrual cycle are insufficient, then signs and symptoms will only be found during specific times of the menstrual cycle.

r­egulation by relaunching corticotropin-releasing hormone (CRH) and thus gonadotrophin-releasing hormone (GnRH) on day 18 (luteal phase). In adaptative states, it can be solicited to relaunch thryotropin-releasing hormone (TRH), prolactin (PL), or any level of the corticotropic axis (cf. below).

General consideration of neuroendocrine calibration of gonadotropic activity

Among the medicinal plants in Table 5.2, four are genital spasmolytics: (1) Anthemis nobilis (Roman chamomile), (2) Artemisia dracunculus (tarragon), (3) Lavandula an­ gustifolia (lavender), and (4) Matricaria recutita (German chamomile).

Parasympathetic During the follicular phase, para predominates. It participates in the growth of the follicle, increased production of estrogens, proliferation of the endometrium, and cervical mucous. It continues to play these roles in the luteal phase, but alpha predominates relative to para. Para may be oversolicited for three reasons. First is insufficiency of digestive and emunctory functions noted earlier. Second is inefficient production of gonadotropic hormones in the growing follicle. Third is in response to a reactive alpha elevated for other adaptive solicitations of the organism such as cold, change of seasons, emotional stress, etc.

Alpha-sympathetic Alpha predominates in the luteal phase. There are three roles of alpha. First, it installs a postcapillary adaptive congestion of digestive organs and emunctories. Second, it relaunches para and sustains the general elevation in metabolic demand that culminates around day 25 (if there is implantation). Third, it calibrates the central-peripheral harmony of endocrine

Genital spasmolytics

Beta-sympathetic Beta plays two roles. The first role is in general sequencing of autonomic function that must result in excretion or expulsion, be it hormones, bile, or the endometrial lining. Table  5.3 summarizes autonomic activity in the menstrual cycle.

Corticotropic Every level of corticotropic function is implicated in the progression of the menstrual cycle. Table 5.4 summarizes these activity and the days in which they are most prominent. Recall that the adrenal cortex is a source of adrenal androgens. Androstenedione is normally produced by the theca cells and aromatized in the granulosa cells of the ovary. In cases where the ovarian response to luteinizing hormone (LH) is insufficient, the adrenal cortex can be solicited to shift its metabolism away from cortisol and a­ daptative

TABLE 5.3  Summary of autonomic activity in the menstrual cycle ANS

Adaptive

Phase

Day

Adaptative

Para

Digestive juices

Follicular Luteal

5–25

Hyperpara state Alpha oversolicitation

Cervical mucous production

Follicular

5–14

Follicle growth

Follicular

5–13

Congestion

Follicular Luteal

5–25

Endocrine relaunching

Luteal

18

Excretion of hormones

Follicular Luteal

1–28

Emunctory function Endometrial growth

Alpha

Para relaunching

Beta

Excretion of digestive juices Bowel motricity

Congestion Alpha ≫ Para Oversolicitation of Para Insufficient or delayed Beta: spasmophilia

92  The Theory of Endobiogeny

TABLE 5.4  Summary of corticotropic activity Hormone

Adaptive

Phase

Day

Adaptative

CRH

GnRH relaunching

Luteal

18

ACTH

Limits prolactin

Follicular, luteal

11, 21

Corticotropic relaunching: • Allergies • Hypercortisolemia

Relaunches FSH

• Autoimmune flare-up • Catamenial depression • Catamenial migraines Cortisol

Permissive function

General

1–28

Hyperestrogenism (cf. thyrotropic chart) Hypoestrogenism (cf. thyrotropic chart)

Uterine development

General

1–28

Intracrinology to estrogens or androgens

Follicular, luteal

5–25

Irritability Acne (jaw line)

Cell nutrition

General

1–28

Cell nutrition Regulates estrogens DHEA

Aldosterone

Edema

a­ctivity to adrenal androgens. The luteal insufficiency can be due to an oversolicitation of follicle-­ stimulating hormone (FSH), estrogens, or insufficient prolactin activity. It can also be due to theca metabolic imbalance where progesterone is produced in favor of androstenedione. The adrenal cortex excretes estrogens and to a lesser degree progesterone. From menstrual days 10–25, an insufficiency of estrogens can also solicit a similar response from the adrenals to aromatize adrenal androgens directly to estrogens at the expense of other endocrine products. Finally, dehydroepiandrosterone (DHEA) itself can be aromatized by intracrinologic means.

Immunity

Thyrotropic

Metrorrhagia: Estrogen insufficiency

The role of TRH is discussed in Chapter  4. Thyroidstimulating hormone (TSH) plays two key roles in the menstrual cycle: endocrine and endocrinotissular (Table  5.5). Peripheral thyroid hormones play a general role of calibrating metabolic energy. T4 along with the rise in progesterone around ovulation contributes to the rise in body temperature. Gonado-thyrotropic coupling is a key relationship in the progression of the menstrual cycle, mating, and fertility.

Introduction

Somatotropic Every level of somatotropic function is implicated in the progression of the menstrual cycle. The general activity of nutrient uptake, distribution, and storage applies throughout the cycle. The specific roles of PL and insulin-like growth factor 1 (IGF1) are discussed in Chapter 4. Recall that PL can be stimulated by TRH, alpha, and dopamine. It is inhibited by somatostatin.

Prostaglandins and other immune products play two key roles in the menstrual cycle. On day 14, they assist in rupturing the follicle to allow for ovulation to occur. Administering antiinflammatory medications during ovulation can reduce the frequency of successful ovulation.9, 10 Prostaglandins assist in the necrosis and removal of endometrial tissue in the early follicular phase.11 During cases of menorrhagia, metrorrhagia, or menometrorrhagia regulating prostaglandin activity can result in symptomatic relief.

Metrorrhagia is abnormal uterine bleeding. When the term is used by itself, it refers to uterine bleeding (“spotting”) that occurs in the late follicular or luteal phases of menstruation. It is due to insufficient estrogens12 to sustain the proliferating endometrium. The following graph recapitulates the rise of estrogens and its relationship to other endocrine factors across both phases (Fig. 5.1). We can generally divide metrorrhagia into the timing of its occurrence: follicular or luteal. There are three causes of estrogen insufficiency: reduced availability of peripheral estrogens, insufficient stimulation of FSH, and inhibition of FSH (Fig.  5.2). The general schematic is summarized below. One will note that all the follicular factors can also be present during the luteal phase. In addition, because of progesterone predominance during luteal

Menstrual cycle disorders Chapter | 5  93

TABLE 5.5  Summary of thyrotropic activity Endo

Adaptive

Phase

Day

TRH

Thyroid relaunching

General

Hypothyroidism Hyperthyroidism

Estrogen sensitization

General

Estrogen-predominance premenstrual syndrome Metrorrhagia Multiple days of blood clots

Endocrine relaunching: GnRH, FSH, PL

Follicular Luteal

11 21

Adaptative

Central hyperthyroidism: • Hyperfollicular state • Hyperestrogenism • Hyperprolactinism o Cysts: ovarian, breast • Intense dreams • Sugar cravings • Explosive emotional outbursts

TSH

Thyroid relaunching

General

Growth factor

Follicular Luteal

Hypothyroidism, peripheral Hyperthyroidism, peripheral 5–25

High serum TSH + hyperestrogenism: menorrhagia Low serum TSH + hyperinsulinism + gonadal androgens > estrogens: • Oligomenorrhea • Insufficient endometrial development • Insufficient cervical mucous development • Uterine fibroids

T4

T3

Endocrine relaunching: GH → IGF-1

Follicular Luteal

5–25

Low serum TSH + low GH growth score + low intracellular growth factors: poor follicular maturation

Ovulation

Follicular

14

Catabolism to nourish anabolism

General

Hyper-T4: heat intolerance Hypothyroidism, peripheral Hyperthyroidism, peripheral

Cellular energy production

General

Hyper-T3: cold sensitivity Hypothyroidism: polymenorrhea with menometrorrhagia Hyperthyroidism: oligomenorrhea with scant flow

days 15–25, ­peripheral luteal dominance is a factor unique to the luteal phase.

Follicular metrorrhagia Fig.  5.3 presents an overview of the follicular causes of metrorrhagia. NB: in the discussion on biology of functions findings, actual results will vary depending on the time of the menstrual cycle that labs are drawn, and the presence or the absence of other disorders. The specific level of es­ trogen insufficiency depends on hologenetic considerations (genotype, phenotype, phase of life, epigenetics, and com­ mensal flora). When multiple indexes are listed modeling various aspects of activity, such as estrogens, only one of the ­indexes needs to be abnormal. The others may be normal.

Type 1-reduced availability: Sympathetico-corticotropic Strong cortisol activity stimulates sex hormone-binding globulin (SHBG) to bind free estrogen, reducing available estrogens. This can arise from excessive alpha, CRH, adrenocorticotropic hormone (ACTH), or excessive cortisol activity. The latter can be due to elevated alpha or beta-­ melanocyte-stimulating hormone (β-MSH), which augments the stimulatory activity of ACTH.

Treatment Treatment favors the regulation of sympathetico-corticotropic activity rather than the augmentation of estrogen activity.

94  The Theory of Endobiogeny

Metrorrhagia 1

2

3

4

5

6

7

9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28

8

TRH

No implantation TRH

Endocrine αΣ, CRH

GnRH

No E2 recep E2 sensitivity TRH T4 FSH

ACTH No E2 recep

E2

ACTH PL

P2 LH

1

2

3

4

5

6

7

8

9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28

Follicle

Recruitment

Uterus

Necrosis

Proliferative phase

Cervix

Scant, thin

πΣ + E2: copious, clear, elastic

Selection

Dominance

Corpus luteum

Luteinization

Corpus albican

Secretory phase αΣ > πΣ + P2 >E2: copious, thick, opaque

FIG. 5.1  Optimal endocrine activity throughout the menstrual cycle according to the theory of endobiogeny. Estrogens (E2) start to rise from day 6 or 7, due to rising FSH, which stimulates quantitative production. Prolactin (PL, in gray) in the mid-follicular phase, and TRH in the later follicular phase, improve estrogen sensitivity and efficacy. Estrogens reach their peak during ovulation, around days 14–15, then decline once progesterone (P2) becomes the dominant peripheral gonadotropic hormone. A second peak of estrogens is observed in the mid-luteal phase thanks again to both TRH and PL. Any time from the mid-follicular to late luteal phases (days 7–24 in an ideal cycle) in which there is a sudden drop in estrogens, metrorrhagia will occur. (© 2016 Systems Biology Research Group.)

SHBG binds E2

Hyper cortisol

Reduced availability

Metrorrhagia

Blocks ACTH prevents horizontal FSH relaunching

Delays FSH Delays GnRH FSH

LH

Early GnRH switch

Slows down FSH

Cf. follicular

Hyper cortisol Insufficient stimulation

Follicular

Luteal

Hyper ACTH

Luteal predominance

Hyper progesterone

Reduced estrogens

Hyper PL

Dopamine

Inhibition

FIG. 5.2  Metrorrhagia schematic by menstrual phase and endocrine origin. (© 2016 Systems Biology Research Group.)

Type 1A: ↑ Alpha In this case, the general hyperfunctioning is due to elevated alpha-sympathetic activity. Reducing alpha with alphasympatholytics can improve the general functioning of the corticotropic axis:

●

●

●

Passiflora incarnata (passionflower): with comorbid insomnia, anxiety, or nervous asthenia Lavandula angustifolia (lavender): with comorbid insomnia, anxiety, or nervous asthenia or inflammation Matricaria recutita (German chamomile): when anger or hepatic congestion is more implicated

Menstrual cycle disorders Chapter | 5  95

FIG. 5.3  Overview of the follicular causes of metrorrhagia. There are three general categories for insufficient estrogens resulting in metrorrhagia: (1) reduced availability, (2) insufficient stimulation, and (3) inhibition. Reduced availability can occur due to three reasons (1, 2a, 2b) related to corticotropic action on the gonadotropic axis. Insufficient stimulation can be due to insufficient central gonadotropic regulation that is endogenous or from early switch of GnRH pulsatility to favor LH and luteal hormones (2c). Inhibition is related to dopamine action on FSH (3). See text for details. (© 2016 Systems Biology Research Group.) ●

Leonurus cardiaca (motherwort) BH, MT: with comorbid tachycardia, anxiety, or elevated cortisol

Treatment prescription: Metrorrhagia 1A A 39-year-old dental hygienist experiences spotting on days 11–13 of her cycle most months. She also complains of insomnia and tachycardia on days 10–14. ● Sympatholytic-Corticotropic: Passiflora incarnata MT 60 mL, Leonurus cardiaca MT 60 mL + Lavandula angustifolia EO 2 mL: 4 mL AM and before bed on menstrual days 10–14, and 3 mL twice per day the remainder of the cycle.

Type 1B: ↑ ACTH + ↑ cortisol + ↓ adrenal cortex In type 1b, the hyperfunctioning of the corticotropic axis lies within the axis itself, such as an altered threshold for response of cortisol to stimulation (Fig. 5.3). Global adrenal function is diminished, particularly the anabolic adrenal steroids, which could have been a source of estrogens. Table  5.6 lists anticipated biology of function (BoF) findings. The treatment approach is to support the adrenal cortex and/or inhibit ACTH. Examples include: ● ●

●

Ribes nigrum (cassis bud) GM: best general support Fragaria vesca (strawberry leaf) MT, BH: when associated with hyperfunctioning central thyro-somatotropic activity such as cysts, adenofibromas, etc. Matricaria recutita (German chamomile) BH, EO, MT: when alpha or ACTH are particularly prominent

Treatment prescription: Metrorrhagia 1B A 22-year-old history major states that since she entered college at 18 years, she experiences light bleeding on days 12–14. She is fatigued for most of the first half of her cycle, then feels fine for the second half. She has left ovarian cysts and occasionally her left side hurts around days 14–15. ● Cortisol regulator/Anabolic adrenal cortex support: Passiflora incarnata MT 60 mL, Ribes nigrum GM 160 mL, Fragaria vesca MT 40 mL + Lavandula angus­ tifolia EO 3 mL: 4 mL AM and afternoons on days 1–16 of the menstrual cycle

Type 1C: ↑ ACTH + ↑ cortisol + ↑ adrenal cortex In this subtype, global adrenal function is either normal but not sufficiently matched to cortisol activity, or, it is quantitatively elevated (Fig. 5.3 and Table 5.7). The goal of treatment is slightly modified in this context to also specifically shift adrenal cortex metabolism away from cortisol with the use of Sequoia gigantea (sequoia) bud glycerin macerate and Quercus pedunculata (oak) bud glycerin macerate as a general endocrine redistributor.

Treatment prescription: Metrorrhagia 1C A 42-year-old former accountant currently homeschools her 3 children, all under the age of 10 years. From 1 year after the birth of her third child, she started experiencing bleeding within 2 days of the end of menstruation, which lasts 4 days. It can be light or heavy. It can occur intermittently or on consecutive days and last anywhere between 1 and 8 days. Some months she has no problems at all. She feels it may be

96  The Theory of Endobiogeny

TABLE 5.6  Anticipated corticotropic BoF findings in Type 1B metrorrhagia Index

Values

Example

Normal range

ACTH

↓ or normal

0.001

0.71–3

Cortisol

↑ or normal with cortisol/ adrenal cortex >4

10

3–7

↓

2

Adrenal cortex

TABLE 5.8  Anticipated BoF findings in Type 2A metrorrhagia

TABLE 5.7  Anticipated corticotropic BoF findings in Type 1C metrorrhagia Values

Example

Normal range

ACTH

↓ or normal

0.001

0.71–3

Cortisol

↑ or normal with cortisol/ adrenal cortex >4

18

3–7

Adrenal cortex

↑ or normal

4

2.7–3.3

related to her stress levels and is definitely worse when she sleeps 4

Adrenal cortex

Varies

FSH

↓ or normal

Estrogen index

↓ or normal

Estrogen index corrected

↓ or normal

Organotissular estrogen yield

↓ or normal

Gonadotropic

2.7–3.3

Index

Axis

The treatment strategy requires three levels of approach: central, peripheral, and emunctory. Inhibition of ACTH (and alpha when implicated) will allow for proper sequencing of FSH. The type of peripheral adrenal support will depend on whether the adrenal cortex is elevated, normal, or low (Tables 5.6 and 5.7). Peripheral estrogen and hepatic function must be supported (cf. The Theory of Endobiogeny, Volume 2, Chapter 7). The following plants are polyvalent plants with estrogenic activity. The first three also have hepatic tropism. ● ●

●

●

Salvia officinalis (Dalmatian sage): best general support Salvia sclarea (Clary sage): use with low adrenal cortex activity and peripheral thyroid insufficiency; use with caution with elevated adrenal cortex activity Avena sativa (Milky oat) BH, MT: use with peripheral thyroid insufficiency or any condition that requires exocrine pancreatic support Angelica archangelica (Angelica): use with psychological or neuromuscular spasmophilia

Avena sativa (Milky oat)7, 8 Part used: Fruit, arial parts, seeds Galenic: MT, FE, DE, bulk herb, microsphere Activity: ●

●

Endo: (1) thyroid: thyroid stimulant (T4, T3), reduces TSH by feedback regulation, (2) gondotropic: follicular: gonadotropic, stimulates ovaries, allowing estrogen to be produced and FSH counter regulated by classical feedback, regulates the thyroid activity to the needs of estrogen, luteal: mild LH stimulant, thus mild augmentation of genital androgens; Metabolic: hypoglycemant, hypolipemiant through excretion (produces bile acids and reduction of Hmg-CoA reductase)

Menstrual cycle disorders Chapter | 5  97

●

● ●

GI: regulates endocrine pancreatic activity through its improvement of carbohydrate metabolism through its improvement of thyroid activity Lymph: lymphatic drainage ANS/Neuro: neuro-regulatory: enlivening in AM, soporific at night through its reduction of alpha-sympathetic activity required to stimulate the thyroid

Use Addresses trifecta of gonado-thyro-somatotropic activity; use in hypothyroidism during pregnancy, menstrual disorders, postmenopausal hypothyroidism, osteoporosis due to low estrogen, hypothyroid metabolic disorders—use to reduce dose of thyroid medications, autoimmune thyroiditis (Grave’s disease), thyroid nodules in euthyroid patients, postoperative state after thyroid lobectomy for nodules; consider in patients in a low genito-thyroid index if thyroid metabolic index and and/or thyroid yield are also low, obesity (hypothyroid). Method: Tisane (neuro): 1 tbsp leaves in ¼ L water, 10 min; drink throughout day; decoction of grain: 20 g/L water: boil 15–20 mint (laxative, diuretic). Contraindications: Hyperthyroid Grave’s disease, other hyperthyroid states; hyperestrogenic states, hyperinsulin states. Salvia officinalis (Dalmatian Sage) is a polyvalent plant that works across all four axes (Fig. 5.4).7, 8 In addition to being estrogenic, it regulates peripheral thyroid gland activity and stimulates the adrenal cortex. It also supports hepatic function,13–16 endocrine function, and is an astringent to the mucosa, which can improve nutrient absorption. It is also antimicrobial and can help regulate enteric flora. Clary sage has a stronger estrogenic activity than Dalmatian Sage. Clary sage is contraindicated in patients with reproductive tract cancers and relatively contraindicated in survivors of these cancers.

Treatment prescription: Metrorrhagia 2A A 31-year-old preschool teacher has light spotting on days 8–11 of her menstrual cycle. Her hair lacks luster on those days. For the first 2 weeks of her cycle, she experiences postprandial fatigue in the evening but difficulty falling asleep at night if she takes a short nap after dinner. On days 8–11 her lower eyelids appear slightly puffy.

●

●

●

Sympathetico-Cortico-Gonadotropic adaptation: Passi­ flora incarnata MT 60 mL, Ribes nigrum GM 80 mL, Salvia officinalis MT 100 mL + Lavandula ­angustifolia EO 3 mL: 3 mL before breakfast and dinner on days 1–15 of the menstrual cycle Gonado-Hepato-Pelvic Drainage: Avena sativa MT 60 mL, Agrimonia eupatoria MT 120 mL, Hamamelis virginiana MT 60 mL + Angelica archangelica root EO 1 mL, Artemisia dracunculus EO 2 mL: 3 mL before breakfast and dinner on days 1–15 of the menstrual cycle

Type 2B: Insufficient stimulation: Blocked ACTH horizontal stimulation In certain terrains, the cortisol response to ACTH is very quick. Often times, the ACTH relaunching of cortisol activity is brutal or intense (such as in epilepsy) and this evokes a quick cortisol response. Regardless of the absolute level of cortisol activity, the rate of response inhibits ACTH before it has time to stimulate the release of FSH by horizontal stimulation (Fig.  5.3). Anticipated BoF findings are listed in Table 5.9. Often times, cortisol activity appears low on the biology of functions. Thus, type 2B is an exception with respect to corticotropic activity and relative or absolute estrogen insufficiency.

FIG. 5.4  Polyvalent action of Salvia officinalis. See text for details. (© 2016 Systems Biology Research Group.)

98  The Theory of Endobiogeny

TABLE 5.9  Anticipated BoF findings in Type 2B metrorrhagia

TABLE 5.10  Anticipated BoF findings in Type 2C metrorrhagia

Axis

Index

Values

Axis

Index

Values

Corticotropic

ACTH

↑ or normal

Gonadotropic

LH

Cortisol

↓ or normal with cortisol/adrenal cortex progesterone or gonadal androgens, antiallergic. Actions (aerial parts): Neurologic: anxiolytic. Endo: cortico: aldosterone antagonist (inhibits aldosterone production—used with elevated aldosterone index). ­gonado: antigonadotropic (inhibits FSH > LH). Immune: antiallergic, antioxidant, febrifuge. Mucotaneous: astringent, antiinflammatory, antiulcerous, antiseptic, ­cicatrisant. Renal: volumetric diuretic.

Menstrual cycle disorders Chapter | 5  103

TABLE 5.14  PMS syndromes by estro-progestive predominance and upstream factors and downstream consequences Level

Endo

Symptoms

Ovaries

P2 > E2

Breast engorgement, L > R and diffuse Luteal predominance • Android, asymmetry: L > R • Acne after adolescence • Breast or uterine fibroids • Menstrual clots: few but prolonged • Breast engorgement resolves with initial menstrual flow

E2 > P2

Breast tenderness Abdominal cramping

↑ αΣ + ↑ cortisol

Recurrent infections Herpes reactivation

↑ αΣ > ↑ πΣ

Insomnia

↑ αΣ + ↑ CRH, ACTH, cortisol + ↓ adrenal cortex + hepatic congestion

Catamenial migraines

↑ αΣ + ↑ CRH, ACTH, cortisol + ↓ adrenal cortex + ↓ central serotonin

Catamenial exogenous depression

↑ αΣ + ↑ ACTH, cortisol, adrenal cortex + ↓ central serotonin

Aggravation of endogenous depression

↑ TRH

Vivid dreams Emotional outbursts

↑ FSH

Emotional sensitivity

Mixed

Hyperfunctioning: para, alpha, FSH, TSH, GH, PL, pancreas, estrogens

Growth of ovarian cysts Growth of breast cysts

Downstream

↑ Adrenal androgens with insufficient aromatization

Irritability Aggressiveness

↑ Gonado androgens > estrogens, hyperinsulinism

Growth of uterine fibroids

↑ Aldosterone

Abdominal bloating Rapid weight gain

Upstream

TABLE 5.15  Progesterone predominance, treatment actions, and options Predominance

Progesterone

Estrogens

Action

Medicinal plant

Relative

↓

↓

↑ P2 ↑ E2

Achillea millefolium Salvia officinalis, Salvia sclarea

←→

↓

↑ E2

Salvia officinalis, Salvia sclarea

↑

↓

↓ LH ↑ E2

Lithospermum officinale, Medicago sativa Salvia officinalis, Salvia sclarea

↑

←→

↓ LH

Lithospermum officinale, Medicago sativa, GLA oils

↑

↑

↓ LH, FSH ↓ E2

Lithospermum officinale, Medicago sativa, GLA oils Vitex agnus castus, Fragaria vesca

Absolute

←→, normal; E2, estrogens; GLA, gamma linoleic acid; P2, progesterone.

104  The Theory of Endobiogeny

Method: Tincture: limit to 1.25 mL TID; tisane: no >5 g/1 cup water, 15 min steep. Use: GU: hypergonadal states with fluid retention: mastopathy, cellulitis, hyperplastic obesity (high alpha, histamine, estrogen), dysmenorrhea, PMS (+ oil), premenopause. Allergies: congestive allergic disease. Contraindications: Pregnancy and nursing. Note: Epilepsy: can interact with antiepileptics possibly increasing seizure risk. Hepatotoxicity: prolonged use of an infusion, or acute high-dose use of an infusion can increase the risk of toxicity from pyrrolizidine alkaloids.

Vitex agnus castus (Chaste tree)7, 8 Parts used: berry, flowering tops Galenic: MT, FE, MS, bulk herb Summary: diminishes peripheral and central gonadotropic activity but favors catabolic thyroid activity to support peripheral gonadotropic factors. Actions: Neuro: sedative, dopamine agonist (inhibiting prolactin)17, 18. ANS: α-sympatholytic. Endo: central: inhibits the general relaunching of hypothalamic and pituitary hormones17, 18, gonado: follicular: inhibits FSH (risk relaunching ACTH by blocking FSH), inhibits estrogen uptake at peripheral receptors (ERα ERβ17, 18), luteal: diminishes serum testosterone (favors progesterone through altering LH activity18–37); thyro: increases T4/T3 ratio; somato: low doses: relaunches prolactin; higher doses: reduces prolactin by stimulation of D2 dopaminergic receptors, reduces prolactin sensitivity to TRH stimulation18, 38. GU: uterine antispasmodic, regulator of menstrual cycle. Derm: antiseptic, vulnary. ONC: antitumoral. Homeopathic: 1x: central oxytocic (may relaunch prolactin); 3x: peripheral oxytocic, antivasopressin. Use: PMS (especially when symptoms last into the luteal phase), mastodynia, fibromas, polycystic ovary syndrome (PCOS), polycystic ovaries, endometrial hyperplasia, menorrhagia, insomnia (especially in hyperluteal women with elevated alpha) (¼ tsp. FE Vitex +1 ¼ tsp. Lotus corniculatus qHS); uteritis (Vitex agnus castus, Alchemilla vulgaris, Achillea millefo­ lium, Achillea millefolium macerate oil (30 mL each) + essential oils of Cinnamomum zeylanicum 2 mL, Syzygium aromaticum 2 mL, Lavandula angustifolia 2 mL: vaginal infusion OR pelvic friction rub), acne, breast cancer; improve lactation (low dose: 1 capsule/day); frigidity and low libido (3x-30c). Contraindications (standard and high dose): pregnancy, nursing, conditions in which relaunching of ACTH is undesirable. Caution: potentiates dopaminergics (i.e., levodopa, bromocriptine), works contrary to effects of antidopaminergics (i.e., domperidon, buspirone).

Fragaria vesca (Strawberry)7, 8 Parts used: fruit, leaf, root (hard to find)

Galenic forms: MT, FE, MS, bulk herb, raw fruit Summary: supports adrenal cortex, slows down aromatization of gonadal androgens to estrogens, diminishes pituitary overactivity. Actions (leaf and root): Endo: corticotropic: stimulates glucocorticoid production, by its inhibition ACTH and adrenal androgens; gonadotropic: inhibits transformation of androgens to estradiol; thyrotropic: inhibits TSH; somatotropic: inhibits prolactin, GH, growth factors. Derm/ mucosal: astringent, wound healer, antalgic. Immune: antioxidant, antiinflammatory. Cancer: antiproliferative (cf. endo). Neuro: antalgic,39 antimyalgic, antineuralgic. Renal: volumetric diuretic. Use: GYN: fibroids (uterine and breast), metrorrhagia, PMS. Derm: acne, eczema, psoriasis, cheloids. Pain: chronic pain. Adrenal: low cortisol:adrenal cortex ratio and low TSH. Method ●

●

General: tisane: 1 tsp. leaf ±1 tsp. Matricaria recutita flowering tops; steep 15 min in 1 cup water: drink TID o PO: GI disorders + ¼ tsp. colloidal silver in the tisane o Gargle: ENT disorders o Poultice: dermatologic disorders CV: 500 g fruit/day; infusion 1 tsp./150 mL infused 5–10 min

Contraindications: constipation, hypercortisol states, chronic use during growth phases in children with normal or insufficient growth.

A brief discussion on gamma linoleic acid Essential fatty acids (EFAs) are a source of phospholipids. Phospholipids contribute to several aspects of structure and function of the organism. Structurally, it contributes to membrane integrity and fluidity. Functionally, it provides the substrates for the production of prostaglandins and leukotrienes. Prostaglandins can be inflammatory (2-series) or antiinflammatory (1-, 3-series). Based on the location of chemical bonds, EFAs can be classified as omega-3, 6, or 9. The omega-6 series is generally pro-inflammatory. Refined grains (i.e., white bread) and red meat from animals raised on corn and soy contain the omega-6 oils that produce pro-­ inflammatory prostaglandins. One type of omega-6’s, γ-linoleic acid (GLA) produces antiinflammatory prostaglandins (Fig. 5.7) that cannot be converted to pro-­inflammatory products. Oils are the primary source of GLAs. The richest source is borage (Borago officinalis) seed. Cassis seed (Ribes nigrum) is the second richest source. These oils are typically taken in encapsulated form internally. Hemp oil and spirulina can be consumed orally as well. To a lesser degree, oats and barley also contain GLAs. According to an Endobiogenic reflection, a generally proinflammatory terrain is favored by several Endobiogenic f­ actors

Menstrual cycle disorders Chapter | 5  105

FIG. 5.7  An Endobiogenic consideration of prostaglandin pathways. Prostaglandin-1 series (left) are antiinflammatory. Consumption of foods or supplements rich in omega-6 GLA favors production of these prostaglandins. The same is true of omega-6 fatty acids such as EPA. Prostaglandin series 1 and 3 inhibit series 2 pro-inflammatory prostaglandins (blue arrows). Luteinizing hormone (LH) stimulates (red arrow) production of inflammatory prostaglandins. (Reproduced from Belch JJF, Hill A. Evening primrose oil and borage oil in rheumatologic conditions. Am J Clin Nutr. 2000;71(1);352s-356s. doi:https://doi.org/10.1093/ajcn/71.1.352s.)

related to the solicitation of the immune system, primarily from the thyrotropic axis. Secondary roles are played by the corticotropic axis and insulin activity. However, with respect to late luteal (i.e., breast engorgement) and early follicular phase (i.e., menorrhagia) symptoms, LH specifically solicits the production of the pro-inflammatory 2-series prostaglandins (PGG2) locally. This is to allow for necrosis of the endometrial lining when there is no implantation of a fertilized ovum.11 During congestive states, especially with luteal oversolicitation, the PGG2s are overproduced. This leads to various inflammatory, edematous, and congestive phenomenon associated with PMS and menorrhagia. The clinical efficacy of GLA oils is mixed. From the Endobiogenic perspective, we find three reasons for this. First, patients are not stratified according to their terrain. Some patients may have a generally pro-inflammatory terrain due to alpha-cortico-­thyrotropic dysregulation. This is reflected in the pro-inflammatory, and inflammation and comparative inflammation indexes. Or, it may be due to somatotropic desynchronization. One typically notes low serum TSH, elevated cortisol index, low insulin resistance, and often elevated insulin index. In this first case, GLA will be helpful, but not in the second. The inflammation is arising from other factors. Second, GLA is used as a sole therapy, not in conjunction with an endo-

biogenic treatment of the terrain, such as regulation of LH and pelvic drainage. Finally, the doses are often insufficient given its role as a sole therapeutic agent. Borage oil is the most efficient source of GLA and can be used throughout the luteal phase, especially in the mid to late stages. The recommended dose when used in conjunc­ tion with luteal management is 400 mg once per day in the evenings with meals.

Borago officinalis (Borage oil)7, 8 Parts used: seed Galenic: Oil Actions: Oil: rich in omega 6 (GLA) and omega 9 (linoleic and oleic acids). Cell: antiinflammatory, reduces proinflammatory prostaglandins, stabilizes cell membranes, enhances membrane fluidity. CV: platelet antiaggregant. Use: Internal: PMS, menorrhagia, eczema, hypercoagulable states due to platelet aggregation. External: vaginal dryness.

A brief consideration of vitamin E Vitamin E is a lipid-soluble vitamin. There are two general forms with various subgroups: tocopherols and tocotrienols.

106  The Theory of Endobiogeny

TABLE 5.16  Sources and servings of vitamin E Source

Per 100 g serving (mg)

Wheat germ oil

150

Almond oil

95

Canola oil

44

Sunflower oil

41

Hazelnuts

20

Almonds

15

Olive oil

14

Each subgroup has unique properties. In general, the vitamin E class is an antioxidant and free radical scavenger. It regulates oxidation of the lipid membrane. Thus, cells are more stable and less subject to necrosis or damage from free radicals in the presence of vitamin E. It also has platelet antiaggregant properties, is antifibrotic, regulates cholesterol and thus has a general antidegenerative role in the organism. Excessive amounts of vitamin E impair normal immune surveillance of cancerous growth and promote certain types of cancer. Thus, vitamin E is best used in moderate amounts as a compliment to a treatment of the global terrain of the patient. The richest sources of dietary vitamin E are listed in Table 5.16.

Case study A 27-year-old woman presents with complaint of PMS symptoms. She has a normal 29-day cycle with 4 days of moderate bleeding that tapers progressively each day. She notes on days 26–29 breast tenderness with severe abdominal cramping. She feels fatigued and slightly depressed. She is easily irritated. She yells at her husband then cries afterward for yelling at him. She has to wear loose-fitting clothing, as she gains about 3 kg in water weight. On the day before her menstruation, she develops nasolabial acne. Her breast tenderness resolves on day 3 of bleeding. She has estrogen predominant PMS as noted by her symptoms. She has an adrenal insufficiency (depression, fatigue) with an appeal that yields more DHEA (irritability) than cortisol. She maintains a hyperfolliculinic state (emotionality) with insufficiency of androgens and possibly progesterone (nasolabial acne). The following is a symptomatic treatment that can be initiated for short-term relief: ●

●

Mg oligo AM and before dinner o Optional based on severity of irritability: lithium oligo twice per day Borage oil 400 mg nightly day 18 to day 7 of the following cycle

●

Topical massage: wheat germ oil 5 mL, sesame oil 10 mL, Lavandula angustifolia EO 5 mL, Achillea mille­ folium EO 5 mL, Matricaria recutita EO 5 mL: massage to breasts and lower abdomen nightly day 20 to day 4 of the following cycle And the following for treatment of the terrain.

●

●

Central gonado-thyrotropic: Borago officinalis MT 60 mL, Alchemilla vulgaris MT 60  mL, Lithospermum officinale MT 60 mL, Leonurus cardiaca MT 60 mL + Lavandula angustifolia EO 4 mL: 3 mL BID day 20 to day 4 Peripheral cortico-gonado-drainage: Fragaria vesca MT 60 mL, Vitex agnus castus MT 60 mL, Betula pu­ bescens GM 60 mL, Hamamelis virginiana MT 60 mL: 3 mL BID day 20 to day 4

Disorders of menstruation Menstruation refers to the necrosis and expulsion of the proliferated endometrium after a failure of implantation of a viable, fertilized ovum. It is, according to the medical convention, the start of the subsequent menstrual cycle. Thus, disorders of menstruation are disorders that occur in the early- and mid-follicular phase. However, menstrual disorders are the result of two factors. The first is the quality of the estrogen activity on endometrial proliferation in midto-late-follicular phase. The second is the estro-progestive relationship in the mid-to-late luteal phase. Thus, it can be an extension of PMS symptoms.

Extension of PMS estro-progestive symptoms into menstruation Table 5.17 recapitulates the estro-progestive relationship in both late luteal (viz. PMS) and early follicular phases (viz. menstruation). The approach to treatment will be similar to the regulation of central and peripheral gonadotropic factors discussed previously. However, the timing varies. If the symptoms are expressed in both the luteal phase as PMS and during menstruation, then treatment can begin after ovulation and continue until the resolution of menstruation. Remember that treatment should continue for at least 3 months in order to assess the re-equilibration of neuroendocrine activity.

Menorrhagia, menometrorrhagia The best approach to treatment of menorrhagia is to use regulating treatments throughout the menstrual cycle for 3 months or longer. The treatment goals are listed below: ●

● ●

Primary: regulate estrogens through central/peripheral management Secondary: regulate uterine inflammation Tertiary: decongest the pelvis, drain the liver

Menstrual cycle disorders Chapter | 5  107

TABLE 5.17  Assessment and treatment of early follicular symptoms Endocrine relationship

Symptom

Late luteal: PMS

Early follicular: Menstruation

P2 > E2

Breast engorgement

L > R Diffuse

Resolves day 1

Clots

Few, large, prolonged • D1 onwards: ↑ LH > P2, ↓ E2 • D2-end: P2 > E2

E2 > P2

↑ E2, absolute

Breast tenderness

Present

Persists until bleeding tapers

Abdominal cramping

Present

varies

Clots

Multiple, small, multiple days • D2–3: ↑ E2, FSH > LH

Duration of bleeding

Menorrhagia (Heavy) and/or Menometrorrhagia: prolonged and heavy (>5 days) and/or Irregular (i.e., flow does not taper)

Case study For the last 7 years, a 31-year-old woman has a menstrual cycle of normal length (30 days). In the last 6 days of her cycle, she experiences tender breasts, abdominal cramping, and a feeling that her uterus will fall out through her vagina. Her menstruation lasts 6 days. The first 3 days are so heavy that she has to miss work because she feels fatigued and light headed. Day 1 she changes her menstrual pads every 3–4 h. She passes many small clots on days 2 and 3. This woman has an estrogen predominant PMS with menorrhagia despite a normal cycle length. Therefore, she has appropriate timing of estrogen response to FSH, TRH, etc. This is noted by the normal length of her menstrual cycle. However, the estrogen response is excessive in the follicular phase. This is noted by the observation of heavy bleeding. The PMS symptoms that start 6 days before menstruation are indicative of an estrogen surge in the luteal phase. Her progesterone is likely of a normal amount but insufficient to her estrogens. This is noted by the absence of any signs of hyperprogesteronism during PMS or menstruation (i.e., large clots). Because of the severity of her uterine congestion, special consideration should be given to this.

General approach to treatment of estrogen predominant PMS with menorrhagia and a normal menstrual cycle length ● ●

Borage oil: 400 mg with dinner daily × 3 months Vaginal suppository: Achillea millefolium EO 4%, Anthemis nobilis EO 2%, Matricaria recutita EO 1%, Lavandula angustifolia EO 2%: days 21–29 of the menstrual cycle inserted nightly with a panty liner to prevent leakage

●

●

Gonadotropic: Lithospermum officinale MT 60 mL, Borago officinalis MT 60 mL, Vitex agnus castus MT 80 mL, Achillea millefolium MT 40 mL + Lavandula angustifolia EO 4 mL: 4 mL BID daily × 3 months Drainage and decongestion: Lamium album MT 60 mL, Hamamelis virginiana MT 60 mL, Malva sylves­ tris MT 60 mL, Agrimonia eupatoria MT 60 mL: 4 mL BID daily × 3 months

Oligomenorrhea: Catabolism exceeds anabolism Oligomenorrhea is defined as a menstrual cycle lasting over 35  days. According to the theory of Endobiogeny, it is a follicular phase incompetence of the development of the endometrial lining. The incompetence is from catabolic predominance, be it absolute or relative in nature. In this, one finds insufficient proliferation of the uterine lining. The follicular phase prolongs until a certain level of endometrial proliferation has been accomplished. As a result, the entire duration of the menstrual cycle gets prolonged.

Precritical terrain The precritical terrain varies. Globally, it typically involves hyperfunctioning central nervous system activity with subsequent disruption in neuroendocrine regulation of metabolic efficiency. Regionally, there is emunctory and vascular congestion. This can impair the quality of (anabolic) nutritional efficiency. The order of importance of regional factors of the precritical terrain is (1) hepatobiliary: insufficiency of exocrine activity for protein production; insufficient metabolic activity for excretion of inflammatory proteins, (2) pelvic congestion: impairing adaptability of endometrial nutrition, (3) uterine congestion

108  The Theory of Endobiogeny

and/or tissular acidity, implicating possible veno-lymphatic stasis, and (4) intestines: intestinal inflammation with risk of permeability.

Agent The agent that installs the critical state of catabolism > anabolism is an augmented level of central nervous ­system-autonomic functioning with adaptive focus on the thyrotropic axis in the follicular phase. Examples include emotional stress, physiologic stressors (e.g., seasonal changes, chronobiologic evolution, and intense exercise), and iatrogenic and lifestyle choices.

Critical terrain In the critical terrain of oligomenorrhea, there is insufficient anabolic activity to nourish the endometrium and sustain it during its period of (rapid) development. This insufficiency of anabolism, and predominance of catabolism, may be relative or absolute (cf. biology of functions discussion). Thus, both the origins of reduced anabolism and catabolic predominance must be investigated. One or both may be present. Reduced anabolism relates to impaired phasic pulsatility of central trophins in the follicular phase (cf. Chapter 4: Regulation of the menstrual cycles and The Theory of Endobiogeny, Volume 1, Chapter  7: Gonadotropic axis). Dopamine has a generally inhibitory role on most central hormones. In situations in which dopamine inhibits FSH greater than it inhibits LH, there may be an impairment in the quality of estrogen activity in an absolute, quantitative sense, or relatively so in relationship to androgens. Or, prolactin may stimulate GnRH pulsatility to favor LH too early and at the expense of FSH in the follicular phase. In either case, dopamine or prolactin, there is an insufficiency of estrogens phase (cf. The Theory of Endobiogeny, Volume 1, Chapter 9: Somatotropic axis). Increased catabolism has three general subcategories: (1) insufficient neurocalmative factors, (2) excessive CNSstimulating factors, and (3) excessive alpha-sympathetic tone. The first is insufficient neurocalmative factors to regulate CNS-sympathetic activity. Examples include insufficient diurnal GABA (γ-aminobutyric acid), endorphins, or enkephalins. Insufficient nocturnal serotonin can impair n­ ighttime inhibition of the corticotropic axis, specifically cortisol, which can favor an absolute catabolic predominance. The second subcategory is excessive stimulating factors of CNS-sympathetic reactivity. In this case, there may be excessive diurnal serotonin, which augments awareness of environmental information and hyperfunctioning of the central nervous system and by extension, sympathetic activity. This, in turn, can lead to cortico-thyrotropic relaunching favoring catabolism. There may be elevated dopamine activity, which stimulates TRH, again relaunching the

t­hyrotropic axis and favoring a catabolic predominance. This is related to the chain of serotonin-dopamine-TRH-­ histamine-serotonin (cf. The Theory of Endobiogeny, Volume 1, Chapter  3: Autonomic nervous system and Chapter  8: Thyrotropic axis and Volume 2, Chapter  10: Thyrotropic axis: Signs, symptoms, and BoF indexes). The third subcategory is excessive alpha-sympathetic tone, which may arise from various causes. Here, three possible consequences are relative: (1) corticotropic overstimulation, (2) thyrotropic overstimulation, or (3) mixed cortico-thyrotropic yoking. In the first scenario, when cortisol activity is greater than that of the anabolic adrenal steroids, anabolism may be blocked or delayed. In the second scenario, any level of thyrotropic activity may be overstimulated. TRH relaunching by alpha can overstimulate the entire thyrotropic axis, resulting in an absolutely hypercatabolic state. Direct TSH stimulation by alpha (low serum TSH) favors somatotropic desynchronization, inflammation, hyperinsulinism, and/or low insulin resistance (cf. The Theory of Endobiogeny, Volume 1, Chapter 8: Thyrotropic axis, discussion on Thyroid-stimulating hormone (TSH)). The third scenario favors a mixed picture. In the critical terrain, the implication of regional factors varies from that of the precritical terrain. They are (1) local uterine congestion, (2) regional pelvic congestion, and (3) lymphatic congestion. The importance of tissular acidity within the endometrium should not be discounted. This may be due to impaired drainage, local dysbiosis, or both. Finally, one may observe endometrial accumulation of intracellular or extracellular toxins (cf. biology of functions).

Mechanisms Catabolic predominance implies anabolic insufficiency, and thus there is impairment in the ability to proliferate the uterine lining. As a consequence, the follicular phase of the menstrual cycle is prolonged to achieve a relatively sufficient endometrial growth prior to ovulation.

Result The result is a menstrual cycle lasting over 35 days. Thus, rather than 14 days for each phase, follicular and luteal, the follicular phase is extended to 21 days or longer.

Biology of functions findings Two caveats must be noted in order to properly utilize the BoF in evaluating oligomenorrhea (and other disorders). In evaluating metabolic activity, the indexes of the BoF indexes model anticipation of global achievement. It cannot be specific to a particular organ or unit of function. In the proliferation of the uterine lining during the follicular phase, the activity of catabolism in structure (S) is relevant. This refers to the recycling of preexisting material to “­nourish anabolism.”

Menstrual cycle disorders Chapter | 5  109

The anabolism of the endometrium is an adaptive response of the uterus to global solicitation. It is not for intrinsic endometrial structural integrity. Thus, we evaluate the anabolism value in function (F). There are four indexes and a ratio of two indexes that are evaluated in oligomenorrhea (Table 5.18). The first is the ca­ tabolism/anabolism index. It evaluates the relative predominance of catabolism in relationship to that of anabolism. In oligomenorrhea whatever the absolute value of the index, its value in function is greater than its value in structure. The second and third indexes are the catabolism index and anabolism index. They evaluate the absolute global anticipated level of catabolic and anabolic achievement, respectively. They may be low, normal, or elevated. The ratio to evaluate is the value of the catabolism index in structure (S) to that of the anabolism index in function (F). The normal ratio is 1.6:2. In oligomenorrhea, it is greater than 2. The third index is the metabolic yield index. It evaluates the final global rate of metabolic achievement. This index may also be absolutely low, normal, or absolutely elevated. What is significative is that the function value is less than that of its structure value. In order for the biology of functions to be significative, it should be drawn after menstruation but before ovulation. If the menstrual cycles have some regularity to them, this should be easy to calculate. For example, assume the cycle lasts 36 days. The luteal phases is approximately 14 days in duration. This leaves 36 − 14 = 22 days for the follicular phase (vs the “optimal” 14 days). If there are 4 days of menstrual bleeding, there are 22 − 4 = 18 follicular days of development of the endometrium. To err on the side of caution, wait at least 5 additional days to ensure that the neuroendocrine terrain of endometrial growth is well established. Thus, blood samples can be drawn during days 10–22. Table  5.18 shows some possible combinations of indexes that favor oligomenorrhea. In both cases, there are two commonalities. The first is that the catabolism/anabolism index is greater in function than structure. The ­second

TABLE 5.18  Case studies in biology of functions indexes related to oligomenorrhea

is that the relative predominance of the absolute rate of catabolism-to-anabolism is greater than 2. What is left to determine is whether the absolute rates of catabolism, anabolism, and metabolic yield are low, normal, or elevated. In case 1, the absolute rates of catabolism, anabolism, and metabolic yield are all low. In case 2, the absolute rate of catabolism (catabolism index) is elevated and the absolute rate of anabolism (anabolism index) is absolutely low. With respect to metabolic yield, it is absolutely high in structure and higher in structure than its function (which is normal). There are a number of factors that may contribute to the state of metabolism, but they are not sine non qua with respect to diagnosis by biology of functions, but are ­helpful to evaluate. In the thyrotropic axis, one may find a low ­serum TSH with elevated thyroid yield. In the corticotropic axis, one may find an elevated cortisol index, or, adrenal cortex greater in function than in structure. In the somatotropic axis, signs of somatotropic desynchronization may be present, such as elevated insulin index and/or low insulin resistance, and, low growth hormone growth score. At the metabolic level, the following indexes may be elevated: ischemia, nucleocytopathogenicity, the various autophagy indexes, redox, and harmful free radicals.

Treatment The three general emphasis of treatment are three: (1) ­ restore proper metabolic relationships, (2) address ­precritical ­elements of regional dysfunction, (3) address critical terrain elements of congestion. We recommend starting with polyvalent symptomatic treatments with utero-­pelvic tropism (Table  5.19). In treatment of the terrain, the specific n­ euroendocrine strategy depends on the origin of the metabolic imbalance. In cases of catabolic predominance, diminish neurocortico-thyrotropic elements that favor catabolism. In cases of anabolic insufficiency, ensure proper folliculo-estrogenic competency and/or proper somatotropic synchronization (Table 5.20). Vagino-cervical douches may be indicated to regulate dysbiosis and regional acidity, for which, of the plants listed below, the most efficient are Matricaria recutita and Hamamelis virginiana.

Exemplary prescriptions

AH G EO N R M EIO L

Based on an Endobiogenic approach to oligomenorrhea, a number of prescriptions can be derived. For example, in the case of oligomenorrhea rooted in central hyperfunctioning (CNS and ANS) with high cortisol and somatotropic desynchronization, one may use the following: ●

(F), Function value; (S), Structure value.

Neuroendocrine: 4 mL twice a day for 3–6 months Passiflora incarnata MT 60 mL, Lithospermum of­ ficinale MT 60 mL, Leonurus cardiaca MT 60 mL, Poterium sanguisorba MT 60 mL, Artemisia dracuncu­ lus EO 4 mL

110  The Theory of Endobiogeny

TABLE 5.19  Polyvalent utero-pelvic plants with symptomatic and critical terrain actions Indication

Medicinal plant

General pelvic actions

Hamamelis virginiana

For catabolic excess or predominance

For anabolic insufficiency

Emmenagogue

Utero-pelvic

Neuroendocrine

Pelvic drainer, decongestant, antiinflammatory, anti-infectious

Crocus sativa

• (indirect)

Rhodiola rosea

•

Leonurus cardiaca

•

Favors ovarian-uterine function as an integrated block

Estrogen regulator, oxytocic, adaptogenic, improves MSH, serotonin, endorphins, GABA activity Adaptogen, serotonergic, dopaminergic, cholinergic,

Central nervous system sedative

Estrogenic (mild), (–) TRH, Reduces cortisol fixation

Malva sylvestris

Pelvic decongestant, antiinflammatory

Blocks insulin

Matricaria recutita

Antiinflammatory, pelvic decongestant

Sympatholytic, parasympatholytic

Anthemis nobilis

Uterine antiinflammatory, antimicrobial, renal drainer

Sympatholytic, parasympatholytic

Thymus vulgaris

•

Spasmolytic

Improves estrogen binding

Artemisia dracunculus

•

Utero-pelvic drainer

Estrogenic

Foeniculum vulgare

•

Uterine antispasmodic

Estrogenic, oxytocic

Salvia sclarea

•

Pelvic drainer

Estrogenic, (−) PL

Achillea millefolium

Antiinflammatory, pelvic decongestant

Progesteronic

Angelica archangelica

Uterolytic, uterine antiinflammatory

Estrogenic, CNS sedative

Cupressus sempervirens

Pelvic drainer, uterine antispasmodic, lymphatic decongestant, antiinfectious

Estrogenic

Melaleuca leucadendron

Uterotonic antispasmodic, pelvic decongestant

Estrogenic, oxytocic, sympatholytic, parasympatholytic

Key: (−), inhibits; CNS, central nervous system; GABA, γ-aminobutyric acid; MSH, melanocyte-stimulating hormone; PL, prolactin; TRH, thyrotropin-releasing hormone.

●

● ●

●

TSH-Drainage: 4 mL twice a day for 3–6 months Zea mays GM 80 mL, Malva sylvestris MT 80 mL, Carduus marianus MT 80 mL, Cupressus sempervirens EO 4 mL Oligoelement: Inositol 400–500 mg twice per day Vaginal dysbiosis douche: Matricaria recutita BH 1 tsp, Hamamelis virginiana BH 1 tsp, 1 tsp Illite clay: steep 15 min in 200 mg water. Cool, shake well, aliquot into a douche bottle, and apply in the evenings before bed for 3–4 weeks Alkaline diet favoring fermented foods, and tisane of Anthemis nobilis 4 cups per day

Polymenorrhea: Thyrotropic insufficiency Polymenorrhea is defined as a menstrual cycle that is shorter than 21 days. In our opinion, any cycle less than 25 days should be addressed Endobiogenically, as it is degraded the

buffering capacity and installs chronic congestive states. The shortening of the menstrual cycle occurs due to a peripheral thyroid insufficiency that truncates luteal maintenance of the endometrium.

Precritical terrain The precritical terrain varies based on the cause of peripheral thyroid insufficiency. It is not uncommon to find and oversolicited central nervous system with hyperfunctioning that is irregularly irregular in intensity. Accompanying this are periodic surges of cortico-thyrotropic activity followed by periodic reductions in activity. In the precritical phase, the reductions in activity are brief (milliseconds to minutes).

Agent The instigator of polymenorrhea is a critical level of CNSANS activity that is sufficiently intense and/or prolonged in

Menstrual cycle disorders Chapter | 5  111

TABLE 5.20  Medicinal plants addressing endocrine aspects of the critical terrain of oligomenorrhea Endocrine

Medicinal plant

Comments

Corticotropic

Passiflora incarnata

All cases of absolutely elevated cortisol due to adrenal overstimulation

Sequoia gigantea GM

When cortisol elevated and cortisol/adrenal cortex > 4

Lithospermum officinale

Use when hyperfunctioning of FSH, LH, and TSH implicated

Medicago sativa

Inhibits LH, estrogenic, antiandrogenic; use if history of acne on jawline or chin, or aggressive irritability

Alchemilla vulgaris

Inhibits LH but progesteronic; use when LH inhibition is required while supporting progesteronic activity for ovulation and the luteal phase activity

(−) TRH

Leonurus cardiaca Fabiana imbricata

Can indirectly reduce PL activity if it is primarily dependent on TRH vs fopamine

(−) TSH, serum

Zea mays GM

Hepatorenal drainer

Lithospermum officinale

Use when hyperfunctioning LH also implicated

Lycopus europaeus

Use with absolute hyperthyroidism

Melissa officinalis

Thyrotropic adaptogen, alpha-sympatholytic and spasmolytic Use with variable thyroid symptoms (hyper- and hypofunctioning)

Avena sativa

Harmonizes the estro-thyrotropic relationship Supports exocrine pancreatic function by substitutive properties Use in patients at risk of Hashimoto’s thyroiditis, or weaning thyroid replacement therapy

GH

Lamium album

Relaunches growth hormone to re-establish somatotropic synchronization and quality of anabolism (use when GH growth score index is low)

PL

Poterium sanguisorba

Reduces dopamine relaunching. Use favored in women with insomnia described as “tired but wired” when trying to initiate sleep

Fragaria vesca

Broader inhibition of pituitary than Poterium sanguisorba; supports adrenal cortex function; use in woman with a history of ovarian cysts, fibrocystic breast disease, polyps, and other disorders of hypertrophy or hyperplasia

LH

Thyroid

Key: GH, growth hormone; PL, prolactin; TRH, thyrotropin-releasing hormone.

activity resulting in dysfunctional thyrotropic activity lasting 24 h or longer.

Critical terrain The critical terrain is an insufficiency of thyroid tissular activity during the luteal phase of menstruation lasting 24 h or longer. For example, a hyperfunctioning appeal by TRH to prolactin inadvertently stimulates peripheral thyroid activity (cf. Chapter 4: Regulation of menstrual cycle), but is followed by a drop in thyroid activity during a “recovery phase” that lasts longer than 24 h. This can be due to a pause in TRH, TSH, peripheral thyroid gland output, or various cellular mechanisms of diminishment of the function of thyroid hormones. Thus, the interruption is in maintaining luteal endometrial integrity. This is in distinction to oligomenorrhea, where the insufficiency is in sustaining follicular endometrial proliferation.

Mechanisms The mechanism is insufficient tissular maintenance of the endometrium. This is primarily due to insufficient ­oxidative metabolism to maintain the metabolic demands of the

p­roliferated endometrium. Secondarily, it can be related to insufficient perfusion and distribution of nutrition to the endometrium.

Result Polymenorrhea: Menstrual bleeding that occurs less than every 21  days. If estrogen tissular activity is low in the follicular phase, the menstrual bleeding will be light. If it is increased, the bleeding will be heavier and/or of longer duration. Thus, assuming a 14-day follicular phase, if the cycle is 18 days long, then there is 4 days of luteal activity before thyroid tissular activity is disrupted.

Biology of functions If the patient’s polymenorrhea has a regular pattern, e.g., every 18 days, labs for the biology of functions must be drawn 24–48 h before menstruation. There are three groups of indexes to be evaluated: (1) thyrotropic, (2) gonadotropic, and (3) metabolic (Table 5.21). Where there are both structure and function values, structure values are the point of focus, as it is a question of structural maintenance. As noted under oligomenorrhea, indexes of metabolism are global in nature and not

112  The Theory of Endobiogeny

TABLE 5.21  Terrain of polymenorrhea by biology of function (BoF) indexes Axis

Index

Value

Interpretation

Gonadotropic

Somatotropic estrogen yield (S) (2.1–206)

↓, low normal (2.1

The thyroid is not sufficiently efficient in responding to demand for and distributing the material required for tissular maintenance or growth

Somatotropic

Catabolism (S)

↓

There is an absolute catabolic insufficiency to nourish anabolism and sustain metabolic activity

Anabolism (S)

↓

There is an absolute anabolic insufficiency.

Metabolic yield (S)

↓

There is an absolute hypometabolic state

a

This is a ratio of two existing indexes. For both indexes, there are only function values.

specific to a particular organ, tissue, or compartment. Thus, there may be some discrepancy in the biology of functions results in certain cases, through the general pathophysiology of the critical terrain is value within the uterine compartment. In the thyrotropic axis, there are two indexes to evaluate, both of which only have function values. The first is thy­ roid yield no. 2, which expresses the relative part of t­ issular activity of the thyroid in relation to central stimulation by TRH or TSH. By extension, it helps to evaluate the relative threshold of participation of the thyroid in cellular distribution of energy. This index answers the question, given the level of effective activity of thyroid hormones in tissu­ lar production of ATP, how responsive was this activity to central stimulation? The second index is the comparative thyroid yield, which expresses the relative part of tissular thyroid activity in relation to its total metabolic activity. By extension, it contributes to the evaluation of the relative threshold of solicitation of activity of orientation of the thyrotropic axis for cellular distribution. The ratio of these two indexes should be 1.6–2. When the ratio is greater than 2.1, it indicates that the thyroid is sufficiently responsive to neither central stimulation nor peripheral demand by tissues and cells for the distribution of energy for structural activity. In the gonadotropic axis, the structure value of the ­somatotropic estrogen yield should be noted. It evaluates the relative part of estrogens in their quantitative output for organo-tissular growth in relation to that of the efficiency of global FSH activity. In other words, it answers the question, relatively speaking, how efficient are estrogens in the growth of tissues within an organ given a certain level of FSH stimulation and preparation of the organ for estrogen activity? It may be absolutely or relatively low. The normal range is 2.1–206. A structure value estrogens

PMS: breast tenderness

Estrogens > progesterone

PMS: irritability

DHEA

PMS: acne

● ● ●

● ●

D (day) 1–4: uterus feels heavy, lower pelvic pressure D1: large clots D2–4: heaviest bleeding -7D-menstruation: irritability, moodiness, cramping -6D-menstruation: breast tenderness -5D-D3 (of next cycle): increased acne, occasionally cystic

The review of systems contributed additional information about her terrain. ● ● ●

●

Hepatobiliary

•

Review of systems

●

Hepatobiliary Colon, skin

•

Premenstrual ●

•

Chronobiologic: sensitive to the full moon Alpha-spasmophilia: bruxism Alpha-TRH: anxiety: low grade, general Thyrotropic: TRH: dreams: vivid, intense, color, with conversation, up to 5 per night Corticotropic: adrenal androgens: body odor: intensified during first pregnancy adrenal androgens

Hepatobiliary

●

●

Cortico-somatotropic: fatigue/fibromyalgia: easily fatigued and irritable by 4 p.m.; second wind at 9 p.m.; difficult to nap during day Gonadotropic: LH, androgens: acne: face and buttocks

Past history Trauma There were a number of significant traumatic events occurring at key times of chronobiology unfolding of thyrotropic and gonadotropic activity (Table 5.25). The patient’s parents divorced when she was 5 years old. At 12 years of age, she discovered the reason for her parent’s divorce was the father’s embracing of his homosexuality. The patient was shocked as this was discordant with how she wished to see her father. Even though the family is secular Ashkenazi Jewish, this was considered to be a social stigma. The ­patient had conflict with her mother, whom she described as controlling throughout her adolescence. At 16 years of age, she ran away from home for a short period of time.

TABLE 5.25  Traumatic events by chronobiologic endocrine function Chronobiologic axis Event

Gonadotropic

5 years: parents divorced

Thyrotropic Thyroid tissular

12 years: patient discovered reason for divorce was father’s homosexuality—patient shocked (central thyrotropic implication), considered it to be a social stigma

Gonadic, metabolic

Central TRH reactivity

16: Ran away from home due to conflict with mother (central thyrotropic implication)

Gonadic, endocrine

Central TRH reactivity

Menstrual cycle disorders Chapter | 5  115

Medical history The patient was born term by induced vaginal birth. She was characterized as being an easy baby, good feeder, and good sleeper. She had normal development. Table 5.26 summarizes key medical events with indication of the implication of various endocrine axes.

Intestines From 3 to 12 years, she suffered from recurrent constipation.

At 27, iatrogenic amenorrhea was induced for 6  months with high-dose hormone therapy (patient could not recall the specific protocol). Upon resuming menstruation, it was described as light bleeding. She had PMS symptoms of painful cramping and irritability. As noted above, her m ­ enstrual symptoms changed postpartum. She has two live births at 33 and 36. She nursed each of her two children for 2.5 years each time.

Infectious disease/immunologic

Thyroid

From 5 to 12 years of age, she was treated 2 or more times per year for allergic asthma, chronic bronchitis, pneumonia, tonsillitis, and allergies to cats. She developed postantibiotic lactose intolerance. The patient had enlarged, retrograde tonsils partially obstructing the eustachian tubes which were removed at 12.

Around the time of her first live pregnancy, in her 30s, she was noted to have elevated thyroid peroxidase antibodies (TPO) at 1010 (normal 0–34 IU/mL). Antithyroglobulin antibodies (TGA) were within normal limits.

Dermatologic

The patient had two episodes of renal calculi, 5 years to the day apart. The first was at 36, 15 weeks pregnant. The second was at 41. She was treated by empiric endobiogenic treatment both times.

From 14 years of age, she started to experience cystic acne.

Gynecologic At 16 years of age, she experienced a ruptured ovarian cyst and noted fibrocystic breast changes. At 17 years of age, for these gynecologic issues, she was started on oral contraceptive therapy, which continued until 27 years of age. She was diagnosed with endometriosis at 19 years of age. She was treated twice surgically (cf. below).

Renal

Surgical history 12: Tonsillectomy: retrograde tonsils 19: Endometriosis cauterization 27: Endometriosis cauterization

TABLE 5.26  Past medical history by endocrine axis and emunctory dysfunction Axis Event

Corticotropic

5–12: recurrent allergic asthma, allergies, bronchitis

•

Gonadotropic

Somatotropic

Emunctory Exocrine pancreas Hepatobiliary Colon, lung

14-present: cystic acne

•

16: ruptured ovarian cyst, fibrocystic breasts

•

17–27: oral contraceptive therapy

•

19: endometriosis, treated twice with surgical interventions at 19, 27

•

27: iatrogenic amenorrhea × 6 months

•

30’s: elevated thyroid peroxidase antibodies (1010, normal 0–34 IU/mL), normal antithyroglobulin antibodies

Thyrotropic

•

•

Hepatobiliary Colon, skin

•

Hepatobiliary Hepatobiliary

•

Hepatobiliary

•

Liver ± exocrine pancreas

116  The Theory of Endobiogeny

Psychological 20s: Depression—psychomotor variety, during an abusive relationship with a man. Comment: It reflects an impaired adaptability at the level of the adrenal cortex with insufficiency of global output, along with a spasmophilia and insufficient central serotonin. Note how this is different from the atopic terrain in which there is elevated adrenal cortex activity and insufficient cortisol output.

Social The patient is married to a real estate developer from South Africa. The husband travels for long periods of time overseas for his work. The patient has a daughter and son from their marriage and has helped raise a stepson from 5 years of age. She enjoys dancing and yoga. Since the birth of her second child for 4 years, her time devoted to dancing significantly diminished.

She was a social worker by training. At 36 years of age, the patient started a website and annual conference promoting natural childbirth and positive child-bearing. It was started in part to compensate for her feeling of lack of support and positive experiences in her own childhood. At 41.5 years of age, she sold her controlling interest in the company. She has experienced years of financial distress—the project was successful and life changing for thousands of people, but not profitable. She also experienced emotional and mental stress from balancing her work with family life. At 38 years, she started a communal living project that involved purchasing land and building sustainable, environmentally respectful housing, and creating a community of like-minded people. While she found this fulfilling, it was also stressful. This mainly affected her menstruation and sleep cycles. At 41, she started a course to become a certified nutritionist.

Physical examination The relevant findings are summarized in Tables 5.27–5.30.

TABLE 5.27  Physical examination of the head, eyes, ear, nose, and throat Endocrine axis Finding

ANS

Acne: cystic, jawline, chin Sclera: injected

Corticotropic

Gonadotropic

DHEA

Testosterone

Thyrotropic

Somatotropic

Emunctory Hepatobiliary Colon, skin

Alpha

Sclera: blue tinge

Kidney

Orifice, canal of Stensen dilated

Exocrine pancreas

Saliva copious

Para

Sublingual veins: dark blue, congested

Alpha

Liver

TABLE 5.28  Physical examination of the breasts Endocrine axis Finding

Corticotropic

Gonadotropic

Breasts: left > right

LH > FSH

Breasts: moderate size, soft

Estrogens

Breasts: scattered fibrocystic masses

Androgens

Breasts: areola dark brown

ACTH

Breasts: nipples: wide, long, no discharge

Androgens

Thyrotropic

Somatotropic

TSH

Prolactin

Prolactin

Menstrual cycle disorders Chapter | 5  117

TABLE 5.29  Physical examination of the abdomen Endocrine axis Finding

ANS

Liver: lower > upper

Alpha

Corticotropic

Gonadotropic

Thyrotropic

Somatotropic

Emunctory Liver: metabolic > circulatory congestion

Murphy’s point

Gall bladder

Superior to umbilicus

Pancreas, general

Left, peri-umbilical area

Dysbiosis

Colon tender: ileocecal

ACTH, structure

Colon tender: ascending colon

FSH

Colon tender: distal transverse

LH

Colon tender: descending (all areas)

Growth hormone Prolactin

Colon tender: rectosigmoid

ACTH, function

TABLE 5.30  Physical examination of other parts of the body Endocrine axis Finding

ANS

Corticotropic

Gonadotropic

Buttocks, lateral: papular acne with white heads

Androgens

Muscle: thigh to calf ratio 2.3:1, good architecture

Relative: DHEA > gonadal androgens

Thyrotropic

Somatotropic

Emunctory, other

TSH appeal > T4 response

Superior, medial tibial surface tender L/R Medial-inferior to tibial tuberosity, left: tender

Pelvis

Medial-inferior to tibial tuberosity, right: tender

Gallbladder

Hands warm, feet cold, both moist

Alpha, Para

Pelvis

118  The Theory of Endobiogeny

Biology of functions-pretreatment

Treatment

Amongst the pretreatment evaluation of her terrain, key indexes of the biology of functions are selected for presentation and discussion relating to the corticotropic (Table 5.31), gonadotropic (Table  5.32), thyrotropic (Table  5.33), and ­somatotropic axes (Table 5.34). All values in structure except where only function values calculated.

The patient wished to be a partner in the formation of the treatment plan. We encouraged this because she had been seen over many years and was studying holistic nutrition (Table 5.35).

TABLE 5.31  Pretreatment corticotropic indexes

High low values presented in red/blue respectively.

TABLE 5.32  Pretreatment gonadotropic indexes

High low values presented in red/blue respectively.

TABLE 5.33  Pretreatment thyrotropic indexes and immunity

High low values presented in red/blue respectively.

TABLE 5.34  Pretreatment somatotropic indexes

High low values presented in red/blue respectively.

TABLE 5.35  Treatment and actions on the terrain Endocrine axis Product

Ingredient

Menstrual tincture 3 mL twice per day

Lithospermum off. MT-MS

ANS

Corticotropic

Vitex agnus castus MT-MS

ADHS adrenal

(−) TSH

Soma

Misc. Diuretic

(−) TRH, TSH (−) LH (−) αΣ

(−) FSH, E, T

+T4/T3

(−) PL Inflammation Circulation

Achillea millefolium FE-MS

(−) Aldo

+P

Eupeptic Lv-GB Pelvis Hemostatic

Borago officinalis FE-MS

(−) Aldo

(−) FSH > LH

Diuretic

Ananas sativa FE-MS

Exo Panc.

Lemon FE-MS

Eupeptic Antiinflam.

Vitamins and minerals

Cell function +βΣ +

Cornus off. DE Schisandra chinensis DE

Adapt.

+ +

Ginkgo biloba DE

Iodine

(−) FSH, LH

Redwine polyphenols

Gotu kola

Tranquility 2 caps twice per day

Corticotropic

Leonurus cardiaca MT-MS Medicago sativa MT-MS

Endophytal 12: 1 capsule twice per day

Corticotropic

Passiflora incarnata DE

GABA (−) αΣ

Griffonia simplicifolia DE

+ Sero TSH

Borage oil

Inflammation

Probiotics

Dysbiosis

Adapt, adaptogen; Antiinflam, antiinflammatory; BID, twice per day; DE, dry extract 4:1; E, estrogens; Exo-Panc, exocrine pancreas; FE-MS, fluid extract derived microsphere; GB, gallbladder; LV-GB, liver-gallbladder; MT-MS, mother tincture derived microsphere; P, progesterone; T, gonadal androgens; Misc., miscellaneous

120  The Theory of Endobiogeny

Diet

Review of systems

Bone broth, healthy fats, lean proteins, whole grains (soaked and sprouted).

Sleep: less sensitive to light and noise, less intense dreams, sleeps from 10 p.m. to 5 a.m. without waking. She also expressed reduced sensitivity to the moon.

Lifestyle Patient was encouraged to dance more and find other avenues for personal time and time with her husband.

Follow-up The patient presented 1 year later, after her 43rd birthday. Her menstruation cycle became regular: 26 days. Her menstruation shortened to 3 days with lighter bleeding and no clots. During PMS, there was reduced breast tenderness, improved mood stability, and less heaviness of the uterus. Acne was less severe and no longer cystic.

TABLE 5.36  Pretreatment corticotropic indexes

High low values presented in red/blue respectively.

TABLE 5.37  Pretreatment gonadotropic indexes

High low values presented in red/blue respectively.

Social/lifestyle The patient spent more time traveling with her husband. Her children were moved to a Waldorf (Rudolf Steiner philosophy) School closer to home. The patient was dancing 5 days per week and felt more embodied and at ease in her body.

Biology of functions-posttreatment The corticotropic, gonadotropic, and thyrotropic axes showed the greatest improvements, which was consistent with the improvement in symptoms (Tables 5.36–5.39).

Menstrual cycle disorders Chapter | 5  121

TABLE 5.38  Pretreatment thyrotropic indexes and immunity

High low values presented in red/blue respectively.

TABLE 5.39  Pretreatment somatotropic indexes

High low values presented in red/blue respectively.

Conclusion Disorders of the menstrual cycle can occur in either follicular or luteal phases. They can be due to dysendocrinism related to the regulation of that particular phase, or, a consequence of dysendocrinism of states preceding it. Regulation of gonadotropic hormones requires coordinated activity by central and peripheral hormones of the other three axes. Regulation of menstrual cycle disorders must address endocrine, autonomic, emunctory, and congestive elements of the terrain. Because of the nature of the menstrual cycle, most therapies will need to be applied for a minimum of 3 months before evaluating their efficacy in addressing the imbalances of the terrain.

References 1.

Sandberg AA, Slaunwhite Jr WR. Studies on phenolic steroids in human subjects. II. The metabolic fate and hepato-biliary-enteric circulation of C14-estrone and C14-estradiol in women. J Clin Invest. 1957;36(8):1266–1278. 2. Cheng  SH, Shih  CC, Yang  YK, Chen  KT, Chang  YH, Yang  YC. Factors associated with premenstrual syndrome—a survey of new female university students. Kaohsiung J Med Sci. 2013;29(2):100–105. 3. Friedman GD, Kannel WB, Dawber TR. The epidemiology of gallbladder disease: observations in the Framingham study. J Chronic Dis. 1966;19(3):273–292. 4. Wurtman  JJ, Brzezinski  A, Wurtman  RJ, Laferrere  B. Effect of nutrient intake on premenstrual depression. Am J Obstet Gynecol. 1989;161(5):1228–1234. 5. Frackiewicz  EJ, Shiovitz  TM. Evaluation and management of premenstrual syndrome and premenstrual dysphoric disorder. J Am Pharm Assoc (Wash). 2001;41(3):437–447.

6. Pearlstein T, Rivera-Tovar A, Frank E, Thoft J, Jacobs E, Mieczkowski T. Nonmedical management of late luteal phase dysphoric disorder: a preliminary report. J Psychother Pract Res. 1992;1(1):49–55. 7. Duraffourd  C, Lapraz  JC. Traité De Phytothérapie Clinique: Médecine Et Endobiogénie. Paris: Masson; 2002. 8. Lapraz  JC, Carillon  A, Charrié  J-C, et  al. Plantes Médicinales: Phytothérapie Clinique Intégrative Et Médecine Endobiogénique. Paris: Lavoisier; 2017. 9. Skomsvoll JF, Rodevand E, Koksvik HS, et al. Reversible infertility from nonsteroidal anti-inflammatory drugs. Tidsskr Nor Laegeforen. 2005;125(11):1476–1478. 10. Stone  S, Khamashta  MA, Nelson-Piercy  C. Nonsteroidal anti-­ inflammatory drugs and reversible female infertility: is there a link? Drug Saf. 2002;25(8):545–551. 11. Jones RE, Lopez KH. The menstrual cycle. In: Jones RE, Lopez KH, eds. Human Reproductive Biology. 3rd ed. Elsevier; 2006 [chapter 3]. 12. Bickers W. Ethinyl estradiol in the treatment of metrorrhagia. Am J Obstet Gynecol. 1946;51:100–103. 13. Estevez  M, Ventanas  S, Ramirez  R, Cava  R. Analysis of volatiles in porcine liver pates with added sage and rosemary essential oils by using SPME-GC-MS. J Agric Food Chem. 2004;52(16):5168–5174. 14. Lima  CF, Andrade  PB, Seabra  RM, Fernandes-Ferreira  M, PereiraWilson  C. The drinking of a Salvia officinalis infusion improves liver antioxidant status in mice and rats. J Ethnopharmacol. 2005;97(2):383–389. 15. Lima CF, Carvalho F, Fernandes E, et al. Evaluation of toxic/protective effects of the essential oil of Salvia officinalis on freshly isolated rat hepatocytes. Toxicol In Vitro. 2004;18(4):457–465. 16. Lima  CF, Valentao  PC, Andrade  PB, Seabra  RM, FernandesFerreira  M, Pereira-Wilson  C. Water and methanolic extracts of Salvia officinalis protect HepG2 cells from t-BHP induced oxidative damage. Chem Biol Interact. 2007;167(2):107–115.

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Carmichael A. Can Vitex agnus castus be used for the treatment of mastalgia? What is the current evidence? Evid Based Complement Alternat Med. 2007;5:247–250. 18. Wuttke W, Jarry H, Christoffel B, Spengler B, Seidlova-Wuttke D. Chaste tree (Vitex agnus-castus)-pharmacology and clinical indications. Phytomedicine. 2003;10:348–357. 19. Dante G, Facchinetti F. Herbal treatments for alleviating premenstrual symptoms: a systematic review. J Psychosom Obstet Gynaecol. 2010;32(1):42–51. 20. Mazaro-Costa  R, Andersen  ML, Hachul  H, Tufik  S. Medicinal plants as alternative treatments for female sexual dysfunction: utopian vision or possible treatment in climacteric women? J Sex Med. 2010;7(11):3695–3714. 21. Freeman EW. Therapeutic management of premenstrual syndrome. Expert Opin Pharmacother. 2010;11(17):2879–2889. 22. van Die MD, Bone KM, Burger HG, Reece JE, Teede HJ. Effects of a combination of Hypericum perforatum and Vitex agnus-­castus on PMSlike symptoms in late-perimenopausal women: findings from a subpopulation analysis. J Altern Complement Med. 2009;15(9):1045–1048. 2 3. van Die MD, Burger HG, Teede HJ, Bone KM. Vitex agnus-castus (chaste-tree/berry) in the treatment of menopause-related complaints. J Altern Complement Med. 2009;15(8):853–862. 2 4. Doll  M. The premenstrual syndrome: effectiveness of Vitex agnus castus. Med Monatsschr Pharm. 2009;32(5):186–191. 2 5. He Z, Chen R, Zhou Y, et al. Treatment for premenstrual syndrome with Vitex agnus castus: a prospective, randomized, multi-center placebo controlled study in China. Maturitas. 2009;63(1):99–103. 2 6. Imai  M, Kikuchi  H, Denda  T, Ohyama  K, Hirobe  C, Toyoda  H. Cytotoxic effects of flavonoids against a human colon cancer derived cell line, COLO 201: a potential natural anti-cancer substance. Cancer Lett. 2009;276(1):74–80. 2 7. Daniele  C, Thompson Coon  J, Pittler  MH, Ernst  E. Vitex agnus castus: a systematic review of adverse events. Drug Saf. 2005;28(4):319–332. 2 8. Halaska M, Beles P, Gorkow C, Sieder C. Treatment of cyclical mastalgia with a solution containing a Vitex agnus castus ­extract: results of a placebo-controlled double-blind study. Breast. 1999;8(4):175–181.

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Chopin Lucks  B. Vitex agnus castus essential oil and menopausal balance: a research update [Complementary therapies in nursing and midwifery 8 (2003) 148-154]. Complement Ther Nurs Midwifery. 2003;9(3):157–160. Atmaca M, Kumru S, Tezcan E. Fluoxetine versus Vitex agnus castus extract in the treatment of premenstrual dysphoric disorder. Hum Psychopharmacol. 2003;18(3):191–195. Xu  H, Fabricant  DS, Piersen  CE, et  al. A preliminary RAPD-PCR analysis of Cimicifuga species and other botanicals used for ­women’s health. Phytomedicine. 2002;9(8):757–762. Gorkow C, Wuttke W, Marz RW. Effectiveness of Vitex agnus-castus preparations. Wien Med Wochenschr. 2002;152(15–16):364–372. Schellenberg R. Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study. BMJ. 2001;322(7279):134–137. Berger D, Schaffner W, Schrader E, Meier B, Brattstrom A. Efficacy of Vitex agnus castus L. extract Ze 440 in patients with pre-menstrual syndrome (PMS). Arch Gynecol Obstet. 2000;264(3):150–153. Bergmann  J, Luft  B, Boehmann  S, Runnebaum  B, Gerhard  I. The efficacy of the complex medication Phyto-Hypophyson L in female, hormone-related sterility. A randomized, placebo-controlled clinical double-blind study. Forsch Komplementarmed Klass Naturheilkd. 2000;7(4):190–199. Loch EG, Selle H, Boblitz N. Treatment of premenstrual syndrome with a phytopharmaceutical formulation containing Vitex agnus castus. J Womens Health Gend Based Med. 2000;9(3):315–320. Halaska  M, Raus  K, Beles  P, Martan  A, Paithner  KG. Treatment of cyclical mastodynia using an extract of Vitex agnus castus: results of a double-blind comparison with a placebo. Ceska Gynekol. 1998;63(5):388–392. Milewicz A, Gejdel E, Sworen H, et al. Vitex agnus castus extract in the treatment of luteal phase defects due to latent hyperprolactinemia. Results of a randomized placebo-controlled double-blind study. Arzneimittelforschung. 1993;43(7):752–756. Kanodia L, Swarnamoni D. A comparative study of analgesic property of whole plant and fruit extracts of Fragaria vesca in experimental animal models. Bangladesh J Pharmacol. 2008;4:35–38.

Chapter 6

A clinical approach to somatotropic axis Introduction The somatotropic axis is the second of two anabolic axes. It is the great fashioner of structure. It lengthens, widens, expands, and ultimately helps replicate the number of structural units. In function, it is the great furnisher of regular, steady energy for acute and chronic needs, both during and outside adaptation. It stands at the crossroad of endocrine function. It is the end of the first, turns it to the second loop, and then completes the second loop. In summary, the somatotropic axis plays a key role in the sequencing of catabolic and anabolic activity, first loop preparation, and second loop completion. The somatotropic axis has four unique features related to all these activities. First, prolactin (PL), a pituitary somatotropic hormone, has a thyrotropic hypothalamic hormone that stimulates it (TRH). It is the only hormone whose axial hypothalamic counterpart (somatostatin) inhibits it. In all other cases, hypothalamic hormones stimulate pituitary counterparts. Second, the somatotropic axis has three hypothalamic and two pituitary hormones, paired as such: GHRH (growth hormone-releasing hormone) stimulates GH (growth hormone), TRH (thyrotropin releasing hormone) stimulates PL (prolactin), somatostatin inhibits prolactin. Recall that the other anabolic axis, gonadotropic, has two pituitary but one hypothalamic hormone. In peripheral gonadotropic activity, progesterone serves as the competitive agonist-antagonist factor in regulating estrogens and androgens in both timing and duration of activity. In the somatotropic axis, PL stimulates insulin from the endocrine pancreas. Third, instead of a peripheral hormone antagonizing insulin, it is an intracellular effect stimulated by GH, namely insulin resistance, which maintains the competitive agonist-antagonist actions. Finally, rather than having two or three peripheral hormones, the somatotropic axis has the greatest number of peripheral hormones ranging from cellular growth factors (i.e., insulin, insulin like growth hormone, etc.) to regulators of digestion and nutrient extraction (i.e., vasoactive intestinal peptide, cholecystokinin, etc.). The Theory of Endobiogeny. https://doi.org/10.1016/B978-0-12-816964-3.00006-7 © 2019 Elsevier Inc. All rights reserved.

A brief review of somatotropic endocrine function The somatotropic axis manages nutrients, cell structure, cell energy, storage of energetic material, and progression of endocrine loops. ●

● ● ●

●

Nutrients: Extraction and processing: exogenous and endogenous sources, availability, distribution, timing of entry of nutrients Architecture: Growth factors Energy: Glucose and lipids for ATP production Storage: Carbohydrates as glycogen, lipids as adipocytes Loops: Starter energy before first loop, passage from first to second loop, completion of second loop

Somatostatin has central and peripheral actions. Its general function is as an inhibitor of anabolic hormones that ultimately is pro-anabolic. The true managers of peripheral somatotropic activity are the pituitary hormones: growth hormone (GH) and prolactin (PL). They have agonistantagonist function that is competitive and additive in nature. The chronologic relationship of GH and Prolactin is key to the regulation of both somatotropic function and endocrine progression throughout the two loops. GH activity is summarized in Table 6.1, Prolactin in Table 6.2. The peripheral hormones adapt the organism in its basal, immediate, and chronic demands. Insulin-like growth factor manages growth, adhesion, and expansion of cells. It serves as a barometer of nutritional integrity and somatotropic synchronization (Table 6.3). Glucagon participates in basal and adaptation states: it provides substrates for structural and functional energy (glucose, free fatty acids). It is a catabolic hormone in an anabolic axis, produced in Islet cells of the endocrine pancreas. It constantly functions to regulate glycemia, and the availability of both glucose and free fatty acids for cellular oxidation and ATP production (Table 6.4). Glucagon has an agonist-antagonist, competitive-additive relationship with insulin, similar to the relationship between growth hormone and prolactin. 123

124  The theory of endobiogeny

TABLE 6.1  Summary of growth hormone action by location and endobiogenic mechanism Location

Mechanism

Action

Comment

Central

Endocrinometabolic

Dreams

GHRH initiates, TRH affects vivacity of dreams

Peripheral

Endocrine (liver)

IGF production

IGF’s responsible for most effects attributed to GH on bone, muscle and cartilage

Endocrinometabolic (nonvital organs)

Insulin resistance

Ensures timing and productivity of GH as a distributor of nutrients by delaying time of glucose entry into cell

Endocrinometabolic (liver)

Glucose: gluconeogenesis, blocks hepatic uptake of glucose

Favors circulating glucose for second loop entry and completion of anabolism

Nutrient distribution

Lipids: lipolysis

Augments free fatty acids for nonglucose ATP production in first loop

Amino acids: uptake into cells

Prepares cells to produce enzymes, DNA when the cell enters a construction phase

Electrolytes: calcium, phosphorous, sodium

Calibrates quantitative entry from effects of catabolic cortico- and thyrotropic activity

Endocrinotissular

General plan of growth and shaping of all organs

Vertical growth of muscle, bone, cartilage, special tropism for liver and endocrine pancreatic integrity

Metabolic

Restoration, reparation of cellular elements

All classes and structures: glycolipids, proteoglycans, cell membrane, DNA integrity, etc.

GHRH, growth hormone releasing hormone; IGF, insulin like growth factors; TRH, thyrotropic releasing factor.

TABLE 6.2  Actions of prolactin by location Location

Action

Comment

Hypothalamus

CRH relaunching

Relaunches ACTH, re-adapts cortisol

Pancreas, endocrine

Insulin excretion

Helps close anabolic loop

General

Wide of structure

Suppresses apoptosis, increases proliferation of cells; when activity estrogens + progesterone, favors proliferation of cancer cells in breast, ovaries, uterus

Immunity: auto-defender of life

Inflammation, extravasation

Favors pus production

Vasculature: auto-sustainer of life

Angioneogenesis

Favors metastasis of tumors, especially breast and prostate

Mammary glands: allosustainer of life

Lactation: production and flow

Oxytocin stimulates let-down

TABLE 6.3  Actions and effects of insulin-like growth factor Action

Effect

Comment

Endocrinometabolic

Inhibits apoptosis Promotes oxidation

Oxidation favors increased ATP production, free radical production

Endocrinotissular

Lengthening of tissues and organs

Most targeted: bone, cartilage, muscle

Nutritional integrity

IGF-1 expression commensurate to mineral intake

Most beneficial: zinc, selenium, and magnesium

Longevity

Inversely correlated to IGF-1

Reduce caloric intake by 15%

Pathophysiology

Insufficient IGF-1

Failure to thrive in children

Excess IGF-1

Atherosclerosis, uterine fibroids, and tumors

A clinical approach to somatotropic axis Chapter | 6  125

TABLE 6.4  Actions of glucagon in management of glucose and lipids Metabolite

Action

Comment

Glucose

Basal glycemia: glycogenolysis, gluconeogenesis

Constant regulation of glycemia in moderate adjustments

Starter energya to initiate adaptation

Evaluate relative to adrenaline (rapid, large adjustments of glycemia): children: adrenaline > glucagon, adults: glucagon > adrenaline

Lipolysis

Beta-oxidation for ATP production

Lipids a

A starter engine is a noncombustion engine that starts the combustion engine so that it can run the car per the demands of the driver.

Insulin: Endocrine pancreas Insulin is the restorative hormone, counteracting catabolic actions of both loops, growth-promoting hormone par excellence. It is involved in the utilization, preservation, and storage of nutrients but has unique functions in the brain (Table 6.5).

Integrating the somatotropic axis First loop 1. Central: a. GHRH stimulates GH b. GH: i. Increases circulating free fatty acids ii. Increases uptake of minerals, amino acids iii. Stimulates hepatic IGF-1 excretion iv. Stimulates Prolactin (turn the loop, prepare for insulin) v. Installs insulin resistance (prevent early closing of anabolism by insulin) vi. Inhibits GHRH by classical feedback c. PL: Turns the loop

2. Peripheral: IGF-1 a. Initiates growth b. Prepares cell for insulin c. Inhibits GH by classical feedback Second loop 1. Central a. TRH i. Stimulates PL ii. Stimulates Insulin b. PL i. Inhibits GH, releases insulin resistance from insulin receptors ii. Stimulates Insulin 2. Peripheral a. Insulin i. Conserves carbohydrates, proteins and lipids ii. Provides substrates for ATP production iii. Stimulates growth of cell, finalizes all that was prepared preceding it iv. Closes the door of anabolism

TABLE 6.5  Conservative effects of insulin Substance/location

Utilization

Preservation

Storage

Carbohydrates

Glucose entry into cells

Inhibits glycogenolysis

Glycogenesis

Lipids

Free fatty acid entry into cells

Blocks lipolysis

Lipogenesis

Proteins

Blocks proteolysis

Blocks gluconeogenesis (from amino acids)

–

Electrolytes

Potassium entry into cells

Diminishes renal sodium excretion

–

Cell

–

Reduces autophagy of organelles

–

Cardiovascular

Vasodilator: improves microvascular flow for nutrient distribution

–

–

Brain

–

Synaptic plasticity

Memory: formation, consolidation, recall

126  The theory of endobiogeny

3. Central/Peripheral a. Somatostatin i. Inhibits all somatotropic hormones and central thyrotropic hormones that relaunch the somatotropic axis: 1. GHRH 2. PL 3. IGF-1 4. Insulin 5. TSH

Pathophysiology As with the gonadotropic axis, the somatotropic is most implicated in the structural formation and maintenance of the endoderm. This includes structures such as the liver, pancreas, and lungs. However, pathophysiologic conditions related to dysfunction of the somatotropic axis are not limited to this embryonic lineage, which refers to structural formation. It touches all tissues and all functions because of its role in structural activity and adaptation. Thus, imbalances related to the axis can be broadly divided into disorders structural integrity, structural adaptation, and function. The gonadotropic and somatotropic axis are typically implicated in structural disorders. In functional disorders, the two catabolic axes are implicated: corticotropic and thyrotropic. The somatotropic axis is also implicated in adaptation because of the role of glucagon which is why it is also implicated in disorders of adaptation, structuro-functional, and global (Table 6.6).

Symptoms related to the somatotropic axis Because the axis plays a role in so many fundamental aspects of structure, function, adaptation, and personality,

there are numerous symptoms reported by the patient or elicited by the physician that relate to this axis (Table 6.7).

Signs related to the somatotropic axis Signs related to the axis are more numerous than symptoms. The somatotropic axis plays a key role in formation of structure and function. One can observe temperament (Table 6.8) related to the axis. On examination, one can look for signs related to the skin (Table 6.9), head (Table 6.10), mouth (Table  6.11), chest and breasts (Table  6.12), abdomen (Table 6.13), back and skeletal system (6.14).

Biology of function indexes related to the somatotropic axis The greatest number of hormones and varieties of actions related to metabolism are within the somatotropic axis. It is no surprise then that the indexes of this axis are the most numerous of those of the four endocrine axes. The indexes are drawn from numerous biomarkers and indexes. Chief among them are osteocalcin1–5 and alkaline phosphatase bone isoenzymes,6–8 both biomarkers derived from bone. The bone serves as an indicator of global metabolism and these biomarkers are related to global intracellular function (The Theory of Endobiogeny, Volume 1, Chapter 15).7–9 In turn, they are both related to growth hormone activity.7 In addition to these two biomarkers, TSH, a pro-anabolic factor that happens to stimulate the thyroid gland, is also key. The higher the serum TSH, the more anabolic activity of the somatotropic axis tends to be at the level of global management (Tables 6.15–6.17). The inverse will be true for intracellular functions such as oxidation of glucose and mitochondrial function. There is a dialectic between ­osteocalcin

TABLE 6.6  Pathophysiology related to the somatotropic axis Category

Subcategory

Example

Structural adaptation

Adenosis

Polyps

Cysts

Breast, ovary, kidney, brain, pancreas, ganglion, etc.

Fibroids

Leiomyoma of uterus

Hyperplasia

Cancer, obesity

Hypertrophy

Cancer, obesity, tonsil hypertrophy

Lipomas

Lipomas

Cicatrization

Keloids, delayed wound healing

Cellular metabolism

Diabetes, hypoglycemia

Neurologic metabolism

Multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, sphingolipidosis

Inflammation

General fragilization of terrain

Functional adaptation

A clinical approach to somatotropic axis Chapter | 6  127

TABLE 6.7  Symptoms related to the somatotropic axis by region Category

Finding

Factor

State

Dermatologic

Purulent acne

Prolactin

Hyperfunctioning

Eczema

Pancreas

Oversolicited

ENT

Recurrent sinusitis, tonsil infections

Pancreas

Oversolicited

Breast

Breast milk, abundant postpartum

Prolactin

Strong

Perimenstrual lactation

Prolactin

Excessive

Increased appetite

Insulin

Predominant

Dislike of fruit

Insulin

Excessive

With low insulin resistance

Hypoglycemia

Insulin

Hyperfunctioning

with low insulin resistance; may present as hyperglycemia on fasting measurement with normal HgA1c

Bloating

Pancreas

Congested

Chronic gastritis

Pancreas

Congested

Anal fissures

Pancreas

Congested

Hemorrhoids

Pancreas

Congested

Menstrual cycle, irregular

Prolactin

Insufficient

Libido, strong during luteal phase

Prolactin

Strong

Menstrual cycle blocked

Prolactin

Excessive or hyperfunctioning

Amenorrhea

Prolactin

Excessive or hyperfunctioning

General feeling of coldness

Prolactin

Excessive and predominant

General fatigue

Prolactin

Insufficient

In corticotropic relaunching

Weight gain

Prolactin

Insufficient or excessive

In corticotropic relaunching

Diabetes

Insulin

Diminished function

Typically, hypersecreted; function is diminished in glucose delivery but hyperfunctioning in lipid management

Weight gain

Insulin

Diminished function

Typically, hypersecreted; function is diminished in glucose delivery but hyperfunctioning in lipid management

Bone

Osteoporosis

Prolactin

Excessive

Favoring inflammation and osteoclasty

Oncology

Angioneogenesis and cancer growth

Prolactin

Hyperfunctioning

Rheumatology

Autoimmunity: polyarthritis

Prolactin

Hyperfunctioning

Gastrointestinal

Genitourinary

Metabolic

Comment

Correlate with strong FSH and TSH with latent hypothyroidism

In conjunction with TRH and general central hyperthyroidism and typically prolonged relaunching of corticotropic axis and cortisol

TABLE 6.8  Signs of temperament related to the somatotropic axis Quality

Finding

Factor

Activity

Comment

External

Social tendency

Growth hormone

Prominent

Desire to gather people for their mutual benefit

External

Fear

Prolactin

Excessive

Correlate with strong central alpha

Internal

Poor adaptation to stress

Prolactin

Hyperfunctioning

Evaluate for signs of weak cortisol, weak ACTH

Internal

Maternal feeling

Prolactin

Prominent

Evaluate for signs of strong estrogen, strong oxytocin (erect nipple)

Internal

Lack of maternal feeling

Prolactin

Ineffectual

Evaluate for signs of weak cortisol, weak ACTH

TABLE 6.9  Dermatologic signs related to the somatotropic axis Quality

Finding

Factor

Activity

Comment

Subcutaneous tissue

Infiltrated, dense, woody

Prolactin

Prominent

Correlate with thyroid function and lymphatic congestion

Acne

Pus

Prolactin

Hyperfunctioning

Freckles

Present

Prolactin

Prominent

An oversolicitation of weak or below-average adrenals, with peripheral blockage of MSH

Furuncle

Present

Prolactin

Excessive

A deep folliculitis

Keratosis

Present

GH

Hyperfunctioning

With hyperandrogenism that relaunches FSH, excess estrogen + latent hypothyroidism: elevated TSH + peripheral thyroid insufficiency

Scar

Pruritic

GH

Hyperfunctioning

Skin color

Pale, milky

Prolactin

Prominent and hyperfunctioning

Nail thickness

Thick and strong

GH

Predominant

Nail deformity

Pitting

GH

Overfunctioning

Can also be sign poor hepatic absorption of nutrients (correlate with scalloped tongue)

TABLE 6.10  Signs of the head related to the somatotropic axis Quality

Finding

Factor

Activity

Hair

Ability to grow long

GH

Strong

Brow

Prominent

GH

Prominent

Postpubertal GH expression; when it is stimulated by TRH, the number of GH receptors is increased

Eyelashes

Thick, overlapping

GH

Prominent

Arises from an appeal of FSH to GH; in children and women, because they have fewer adrenal androgens, the effects of GH are more pronounced, hence the thicker eyelashes

Thinly spaced

GH

Not prominent

Insufficient stimulation of intracellular growth factors by FSH

Polyp

GH

Hyperfunctioning

Implies elevated insulin activity

Length of osseous portion

Insulin

Prominent

Correlate with strong thyroid and/or strong cortisol activity; increased metabolic activity demands a longer period of respiration, which requires a larger antechamber for the nose

Length of cartilaginous portion

GH

Prominent

Reflects delayed end of growth; correlate to strong cortisol, weak somatostatin, weak thyroid activity, elevated insulin resistance and other factors

Bulbous

GH

Excessive

GH adapted to parasympathetic insufficiency in the face of strong cortisol

Nose

Comment

A clinical approach to somatotropic axis Chapter | 6  129

TABLE 6.11  Signs of the mouth related to the somatotropic axis Part

Quality

Finding

Factor

Activity

Comment

Lips

Size

Full, thick

Pancreas

Congested

Implies elevated para

Mucosa, oral

Ulceration

Aphthous ulcer

GH

Hyperfunctioning

Teeth

Spacing

Widely spaced

GH

Strong

Tongue

Fissures

Fissures

GH

Hyperfunctioning

Tongue

Size

Large, thick, with dental impression

Growth hormone

Excessive

Growth hormone compensation in the tissular nutrition activity to compensate for hypothyroidism; GH congests the splanchnic circulation to augment nutrient absorption, which leads to glossal edema

Uvula

Shape

Bifid

Somatotropic

Excessive

Growth factors > antigrowth, resulting in a TSH relaunching of the thyroid (hyperthyroid state), resulting in strong ACTH/ LH to maintain strong TSH stimulation of the thyroid

Tonsils

Size

Hypertrophy

Pancreas

Congested

Congestion, pancreas

Tonsils

Color

Erythema

Pancreas

Congested

Congestion, pancreas

Tonsils

Coating

Coating, white

Colon

Congested

Congestion, colon

Postpubertal GH expression

TABLE 6.12  Signs of the chest and breast related to the somatotropic axis Part

Quality

Finding

Factor

Activity

Comment

Sternum

Orientation

Convex

GH

Hyperfunctioning

Correlate with PTH

Breast

General

Underdeveloped

Prolactin

Diminished in structure

Size

Voluminous and dense

Prolactin

Prominent

Erection

Erect

Prolactin

Hyperfunctioning

Size

Large

Prolactin

Prominent

Duct

Expression

Prolactin

Excessive

Nipple

Often voluminous; cause is prolactin, consequence is elevated insulin/ weak insulin resistance and strong estrogen and androgens

May also be hyperfunctioning

TABLE 6.13  Signs of the abdomen related to the somatotropic axis Part

Quality

Finding

Factor

Activity

Comment

General

Proximal

Adiposity, doughy

Insulin

Excessive and typically reactive and hyperfunctioning

Correlate with elevated cortisol and altered insulin resistance

Pancreas

Mid-point between umbilicus and xyphoid

Pain on palpation

Pancreas

Congestion

Congestion, pancreas

Pancreas

Medial-right from umbilicus

Pain on palpation

Pancreas

Exocrine congestion

Congestion, pancreas, exocrine

Pancreas

Medial-left from umbilicus

Pain on palpation

Pancreas

Endocrine overtaxed

Congestion, pancreas, endocrine

Colon

Descending, distal

Pain on palpation

GH

Oversoliciting

TABLE 6.14  Signs of the back, extremities, and bones related to the somatotropic axis Part

Quality

Finding

Factor

Activity

Comment

Scapula, right

Inferior-medial, T6-7

Pain on palpation

Liver

Congested

Congestion, liver

Scapula, left

Inferior-medial, T7-T8

Pain on palpation

TSH, PL

Oversoliciting

Congestion, colon, transverse and descending

T7-T10

Paraspinal

Pain on palpation

Endocrine pancreas

Congested

Chronic congestion

Hand

Dorsum

Edematous

Prolactin

Hyperfunctioning

Knee, right

Thickness

Thick knee

FSH-TSH-GH

Overfunctioning

Foot

Shape

Hallux valgus (bunion)

GH

Excessive

Foot

Dorsum

Edematous

Prolactin

Hyperfunctioning

Foot

Arch

Flat

Prolactin

Predominant, likely excessive

Bone

Width

Wide

Prolactin

Prominent

Bone

Length

Long

GH

Prominent

Postpubertal

TABLE 6.15  Indexes assessing central somatotropic activity Relationship Index

Definition

Import

Direct

Inverse

Correlations

GH growth score

It calculates the level that results from the endocrinometabolic activity of growth hormone. By extension, it evaluates the role played by the somatotropic axis in the general adaptation syndrome and in the summoning and distribution of structural and functional energy

High: increased utilization of nutrients, risk of adenoidal growths Low: risk of somatotropic desynchronization due to a hyperalpha and/or central hyperthyroid activity

Growth score

Growth score corrected

Antigrowth index Adenosis index

Prolactin

It expresses the level of prolactin activity. It witnesses the level of solicitation of the general adaptation syndrome of Endobiogeny and its systematized modules

High: prolactin is active in turning the first loop in order to relaunch cortisol Low: prolactin is either diminished by central somatostatin and/or not required due to the quality of cortisol activity

Somatostatin

Growth hormone index

High: serum TSH, cortisol index Low: dopamine activity, cortisol index

A clinical approach to somatotropic axis Chapter | 6  131

TABLE 6.16  Indexes assessing peripheral somatotropic activity Relationship Index

Definition

Import

Direct

Inverse

Somatostatin

It expresses the level of activity of somatostatin; indirectly it witnesses the relative level of activity of the exocrine pancreas

High: exocrine pancreas oversolicited and contributing to disorders of excess nutrients and hypertrophic growth Low: insufficient exocrine pancreas activity, somatostatin allows for prolonged endocrine activity and hyperplastic growth

Antigrowth index

Cortisol

Insulin

It measures the level of functional endocrinometabolic activity of the insulin

High: hyperinsulinism, risk of somatotropic desynchronization Low: hyperinsulinism due to insufficient membrane sensitivity

Catabolism/ anabolism Cortisol

Insulin resistance

It measures the level of inhibition of insulin at membrane level, independently of the temporary inhibition linked to adaptation syndrome

Low: organism may be compromised in distribution of glucose to vital organs High: favors prolonged first loop activity, risk of nourishment of vital organs at expense of other organs and tissues

Growth index corrected

It expresses the intracellular activity of growth factors

It evaluates the role of IGF-1 and other growth factors

Alkaline phosphatase bone isoenzyme

Correlations

Insulin resistance Redox Harmful free radicals Insulin Cortisol

Redox Harmful free radicals

Osteocalcin

Antigrowth, demyelization, membrane expansion

TABLE 6.17  Indexes assessing general metabolic effects of somatotropic hormones Relationship Index

Definition

Import

Direct

Inverse

Correlations

Catabolism

It measures the level of catabolic activity of the organism

Catabolism nourishes anabolism

Thyroid index

Adrenal cortex index

Genitothyroid Catabolismanabolism

Anabolism

It measures the level of anabolic activity of the organism

Anabolism ensures the restoration of the organism

Catabolism

Catabolismanabolism

Metabolic yield

It measures the overall metabolism rate of the organism

It expresses the general degree of efficacy of the organisms be it in its level of production or repartitioning

Catabolism, anabolism

Ischemia, membrane fracture

Ischemia

It measures the level of tissular congestion relative to the cell metabolic activity

Demyelination index corrected

It expresses the relative level of adaptability of the energeticometabolic response of insulin in its chronologic rapport to that of the endocrine activity of growth hormone

Adenosis

It measures the degree of relative activity of endocrine factors propitious for hyperplasia

Bone remodeling

Metabolic yield

Splanchnic congestion

High: desynchronization of somatotropic activity with insulin preceding growth factors

Insulin index

Growth index corrected

Amylosis Somatostatin

High: it captures all the events that solicit an organ to augment its yield, its rate of production and its volume. It favors a terrain for all adenoidal growths

Osteocalcin

Ischemia index, TRH/ TSH index

132  The theory of endobiogeny

and TSH reflected in the indexes, as they vary inversely with each other.6, 10, 11 The lower the osteocalcin, the greater intracellular metabolism tends to be for a given serum TSH. The prolactin index is currently the only strictly central somatotropic index in the biology of functions (Table 6.15). Dr. Duraffourd created it to evaluate how prolactin plays a role in solicitation of the adaptation syndrome and its role in turning the first loop and by extension how effectively somatostatin is able to downregulate prolactin at the end of the second loop. The GH (growth hormone) growth score does not evaluate the endocrine function of GH with regard to production of insulinlike growth factor 1 (IGF-1) in the liver. It evaluates the role of GH in the timing and distribution of nutrients, which is an endocrinometabolic activity. The index is low in disorders of somatotropic desynchronization such as Crohn’s disease, multiple sclerosis, chronic fatigue syndrome, and fibromyalgia. It is elevated in disorders of hypertrophy and hyperplasia such as adenoidal growth such as of the breast or prostate and in diabetes mellitus type two. It is normally several fold elevated during normal pediatric growth. The somatostatin index (Table 6.16 and The Theory of Endobiogeny, Volume 2, Chapter 8) is evaluating peripheral somatostatin activity and by extension central activity is inferred. There are a number of indexes that evaluate the function of strictly peripheral somatotropic activity related to distribution of nutrients. The activity of glucagon from alpha-islet cells of the endocrine pancreas is discussed under the discussion of indexes related to the autonomic nervous system, because of its role in adaptation (The Theory of Endobiogeny, Volume 2, Chapter  1). We discuss here four key indexes. The first is somatostatin, excreted from delta-islet cells of the endocrine pancreas and other areas of the gastrointestinal tract. Strictly speaking, the index evaluates peripheral somatostatin activity and its role in ending growth.12–15 This occurs in two ways: installing an antigrowth milieu, and inhibiting excretion of digestive enzymes. Thus, the index evaluates the actions of somatostatin on the exocrine pancreas. Cortisol inhibits excretion of digestive enzymes but also inhibits somatostain.16–19 The index effectively evaluates the relative role of somatostatin vs cortisol and the competency of the exocrine pancreas. Somatostatin ends exocrine pancreas activity because it is prolonged or excessive. Cortisol inhibits it, diminishing the exocrine pancreas’ ability to play its proper role in nutrient extraction and all that that implies. The evaluation of beta-islet cell endocrine pancreas activity is through the insulin index (Table 6.16). The insulin resistance index, technically speaking, is an evaluation of the intracellular, inner membrane response to insulin activity on the outer portion of the membrane. It is included here to complete the arc of activity within the pancreas. Finally, there are indexes evaluating the role of growth and antigrowth factors. Here we discuss the growth index corrected. It corrects the evaluation of growth hormone’s metabolic

effects on cellular function to account for the role of other intracellular growth factors. There are numerous indexes evaluating a general metabolic activity regulated by the somatotropic axis. The catabolism/anabolism index is discussed with the indexes of the corticotropic axis (The Theory of Endobiogeny, Volume 2, Chapter 2). That index is evaluating the relative predominance of catabolism in relationship to that of anabolism. In the somatotropic axis we have the quantitative estimation of catabolism and anabolism individually (Table 6.17). The catabolism index is formed by the ratio of thyroid metabolic activity in relationship to that of global adrenal cortex activity. Peripheral thyroid hormone activity favors catabolism, especially T4. Adrenal cortex activity, particularly the anabolic hormones, if excessive, will try to initiate anabolism before catabolism is completed. This diminishes catabolic achievement. Since catabolism feeds anabolism according to the theory of Endobiogeny, it will diminish anabolic achievement as well (The Theory of Endobiogeny, Volume 1, Chapter  6). The anabolism index contains the catabolism index in its numerator. The greater the rate of catabolism, the greater the rate of material presented for anabolism will be. The metabolic yield is simply the sum effects of both catabolism and anabolism. The demyelination index evaluates the risk of loss of the myelin sheath due to somatotropic desynchronization. This index is particularly helpful evaluating symptoms of neuropathy and chronic pain. The adenosis index evaluates the risk of adenoidal growth, which is a type of hyperplastic growth. Hyperplasia is a growth in the number of cells. It reflects a thyro-somatotropic relationship based in a latent or expressed hypothyroidism in the face of augmented somatotropic growth activity. Cells and tissues have an intrinsic metabolism that is regulated by assessment of intrinsic needs. Because they are situated in a global environment, the endocrine system adapts the intrinsic function to the needs of regional or global metabolism. Of all the axes, the somatotropic influenced by TSH is the most influential. The indexes discussed in Table  6.17 a general indication of the direction and magnitude of growth. There are consequences to this that refer to the method in which the cell obtains nutrients and electrolytes, and the degree to which they are oxidized or utilized in some other fashion. The indexes in Table 6.18 discuss these activities. Active cell permeability refers to the transport of substances into the cell through pores and channels in an active manner, meaning with the use of ATP to drive movement against its gradient. Passive permeability refers to the diffusion of substances or their movement down a concentration gradient. It is proportional to the membrane fluidity of the cell membrane20 and typically refers to the movement of small, nonpolar molecules.21 This distinction is significant because only the first method can be regulated. The second cannot. In states of hypertrophy or hyperplasia, one

A clinical approach to somatotropic axis Chapter | 6  133

TABLE 6.18  Indexes assessing cellular metabolic activity as regulated by somatotropic hormones Relationship Index

Definition

Import

Direct

Inverse

Correlations

Active cell permeability

It measures the degree of dynamic activity of cross-membrane permeability

High: favors first loop nutrition via membranebound channels

TSH

Insulin

Somatostatin

Passive cell permeability

It measures the degree of strictly osmotic cross-membrane permeability

Low: favors insufficient membrane fluidity

Necrosis; adaptation permissivity

No denominator

Redox

it measures the global oxidoreduction activity of the organism

Low: favors impaired response to microbial infections

Insulin index

Somatostatin index

Noxious free radicals

it measures the global rate of circulating free radicals

Pro-amyloid index

It measures the level of intra-cell hypometabolism. By extension, it evaluates the degree of cellular respiratory insufficiency and the degree of nutritional insufficiency

High: favors mitochondrial insufficiency

wishes to regulate the rate and magnitude of nutrient entry. Disorders such as diabetes will have elevated active permeability and diminished passive permeability. In this case, the use of a higher protein, lower carbohydrate diet, will prove more beneficial in our experience. In disorders such as chronic fatigue syndrome and neuropathy, the inverse is found: too much passive diffusion and insufficient active diffusion. The cell membrane is too fluid. Anecdotally, we have observed that a whole grain, high fiber diet with fish or vegetarian proteins is more corrective of this situation. Redox is the sum of reduction and oxidation of glucose and lipids for ATP production. It is the consequence of the quality of insulin activity, somatostatin, and membrane permeability. Excessive redox favors inflammation and free radicals, both beneficial and harmful.22 Insufficient redox can play a role in compromised immunity, or, the reliance on ketones and other substances for energy. It increases the risk of mitochondrial insufficiency, reflected in the proamyloid index. The mitochondrion plays a key role in cell health and nucleus regulation.23

Conclusions The somatotropic axis has many levels of function. It is a fashioner of structure in its material crystallization. It is a regulator of structural activity of the cell related to its intrinsic maintenance of its material structure. The axis regulates the structuro-functional adaptation of cellular activity and its participation in functional adaptation. The axis plays a role in

Oxidoreduction index

DNA fracture

Insulin resistance

Reduction index

the entire ecology of metabolism in its general sense of the rate of function and the particular sense of nutrient apportionment, distribution and timing of entry and utilization. There are many aspects of somatotropic function that can be determined by history, examination, and biology of functions. The axis plays a role in disorders ranging from cancer to chronic fatigue, from diabetes to multiple sclerosis. A proper assessment of somatotropic function allows from a regulation of disorders of structure, adaptation, and metabolism.

References 1. Hwang YC, Jeong IK, Ahn KJ, Chung HY. The uncarboxylated form of osteocalcin is associated with improved glucose tolerance and enhanced beta-cell function in middle-aged male subjects. Diabetes Metab Res Rev. 2009;25(8):768–772. 2. Lee NK, Sowa H, Hinoi E, et al. Endocrine regulation of energy metabolism by the skeleton. Cell. 2007;130(3):456–469. 3. Im JA, Yu BP, Jeon JY, Kim SH. Relationship between osteocalcin and glucose metabolism in postmenopausal women. Clin Chim Acta. 2008;396(1–2):66–69. 4. Kim  YS, Paik  IY, Rhie  YJ, Suh  SH. Integrative physiology: defined novel metabolic roles of osteocalcin. J Korean Med Sci. 2010;25(7):985–991. 5. Kindblom JM, Ohlsson C, Ljunggren O, et al. Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men. J Bone Miner Res. 2009;24(5):785–791. 6. Baqi L, Payer J, Killinger Z, et al. The level of TSH appeared favourable in maintaining bone mineral density in postmenopausal women. Endocr Regul. 2010;44(1):9–15.

134  The theory of endobiogeny

7. Magnusson P, Degerblad M, Saaf M, Larsson L, Thoren M. Different responses of bone alkaline phosphatase isoforms during recombinant insulin-like growth factor-I (IGF-I) and during growth hormone therapy in adults with growth hormone deficiency. J Bone Miner Res. 1997;12(2):210–220. 8. Stepan J, Havranek T, Formankova J, Skrha J, Skrha F, Pacovsky V. Bone isoenzyme of serum alkaline phosphatase in diabetes mellitus. Clin Chim Acta. 1980;105(1):75–81. 9. Lapraz  JC, Hedayat  KM, Pauly  P. Endobiogeny: a global approach to systems biology (part  2 of 2). Glob Adv Health Med. 2013;2(2):32–44. 10. Baqi L, Payer J, Killinger Z, et al. Thyrotropin versus thyroid hormone in regulating bone density and turnover in premenopausal women. Endocr Regul. 2010;44(2):57–63. 11. Guo CY, Weetman AP, Eastell R. Longitudinal changes of bone mineral density and bone turnover in postmenopausal women on thyroxine. Clin Endocrinol (Oxf). 1997;46(3):301–307. 12. Celinski SA, Fisher WE, Amaya F, et al. Somatostatin receptor gene transfer inhibits established pancreatic cancer xenografts. J Surg Res. 2003;115(1):41–47. 13. Danila  DC, Haidar  JN, Zhang  X, Katznelson  L, Culler  MD, Klibanski A. Somatostatin receptor-specific analogs: effects on cell proliferation and growth hormone secretion in human somatotroph tumors. J Clin Endocrinol Metab. 2001;86(7):2976–2981. 14. Frohman LA, Downs TR, Chomczynski P. Regulation of growth hormone secretion. Front Neuroendocrinol. 1992;13(4):344–405.

15.

16. 17.

18. 19. 20. 21.

22. 23.

Frohman  LA, Downs  TR, Kelijman  M, Clarke  IJ, Thomas  G. Somatostatin secretion and action in the regulation of growth hormone secretion. Metabolism. 1990;39(9 suppl 2):43–45. Hofland  LJ. Somatostatin and somatostatin receptors in Cushing’s disease. Mol Cell Endocrinol. 2008;286(1–2):199–205. Pedroncelli AM. Medical treatment of Cushing's disease: somatostatin analogues and pasireotide. Neuroendocrinology. 2010;92(suppl 1): 120–124. Schonbrunn A. Glucocorticoids down-regulate somatostatin receptors on pituitary cells in culture. Endocrinology. 1982;110(4):1147–1154. van der Hoek J, Lamberts SW, Hofland LJ. The role of somatostatin analogs in Cushing's disease. Pituitary. 2004;7(4):257–264. Freedman JC. [chapter 3]. Cell membranes. In: Sperelakis N, ed. Cell Physiology Source Book. 4th ed.Elsevier; 2012. Sperelakis N, Freedman JC. [chapter 8]. Diffusion and permeability. In: Sperelakis N, ed. Cell Physiology Source Book. 4th ed.Elsevier; 2012. Droge W. Free radicals in the physiological control of cell function. Physiol Rev. 2002;82(1):47–95. Kotiadis VN, Duchen MR, Osellame LD. Mitochondrial quality control and communications with the nucleus are important in maintaining mitochondrial function and cell health. Biochim Biophys Acta. 2014;1840(4):1254–1265.

Chapter 7

Disorders of the prostate: Lower urinary tract obstruction and prostatitis Introduction

Anatomy

The prostate serves as a refinement of the masculine impetus within the male of the species. Its function reflects the quality of this venture. It is a refinement of the masculine impetus because it has developed through evolutionary forces to offer a highly calibrated expression of male masculinity for the purposes of management, cohesion, and reproduction. This is opposed to female masculinity, which is more nuanced and tends to be more gathered and enfolded into the feminine aspects of femininity. The prostate is a glandular organ unique to men and therefore, presents the opportunity of dysfunction unique to them. It has no analog in the female. The prostate is the meeting place of sperm and urine. It is the meeting place of the sacred and the profane, the future, and the past. It is the management of all these aspects of the dynamic in its dialectic that leads the man to completion or to stagnation. Derived from the Greek word meaning “to stand (-statis) before (pro-),” the prostate possesses a function of guarding, protecting and of witnessing in a proactive manner. The prostate sits at the crossroads of creation and consumption, guarding the propriety of patrimony in its most literal sense. It protects the vital fluids during their period of quiescent maturation. It completes the elements that introduce the enflourishing of the masculine polarity of consciousness: directionality, force, movement, and procreation into the feminine polarity of centeredness, stillness, reception, and nurture. The intrinsic function of the prostate is constantly subjected to local, regional, and global activity of the organism. It is subjected to local anatomical integrity through its proximity to the urinary bladder and rectum. This exposes it to a risk of infection. It is subjected to regional neuroendocrine and metabolic demands through its relationship to the testicles and seminal vesicles for maturation of sperm. The sum of these observations place a man at risk to lower urinary tract obstruction (LUTO) and prostatitis. Understanding the anatomical and physiologic particularities of this male organ clarifies the specific risk factors related to disorders of the prostate.

The prostate is a walnut-shaped, walnut-sized exocrine gland (Fig. 7.1). It weighs, on average, 15–20 g by the end of adolescence. It is situated inferiorly to the urinary bladder, directly touching it. The urethra passes through the transition zone of the prostate (Figs. 7.1 and 7.2). The prostate sits

The Theory of Endobiogeny. https://doi.org/10.1016/B978-0-12-816964-3.00007-9 © 2019 Elsevier Inc. All rights reserved.

Ureter

Vas deferens

Seminal vesicle Opening of ejaculatory duct Opening of prostatic ducts

Verumontanum Utricle Prostate

Membranous urethra Urogenital diaphragm

Cowper’s gland

Corpus cavernosum Opening of Cowper’s duct Bulbous urethra Corpus spongiosum Glands of Littré Fossa navicularis Penile urethra Corpus cavernosum

FIG. 7.1  Anatomy of male urogenital structures. The prostate sits at the crossroads of excretion of urine and semen, and nourishment of s­emen. (Reproduced from Kim B, Kawashima A, LeRoy AJ. Imaging of the male urethra. Semin Ultrasound CT MR 2007;28(4):258-273. https://doi. org/10.1053/j.sult.2007.05.003.)

135

136  The Theory of Endobiogeny

Posterior

a

a

b e

e

c

c

f b d

Anterior

d

Ejaculatory duct FIG. 7.2  Prostate zonal anatomy. Central zone (a), anterior fibromuscular stroma (b), transition zone (c), peripheral zone (d), periurethral gland (e), and anterior horn of the peripheral zone (f). (Reproduced from De Marzo, et al. Inflammation in prostate carcinogenesis. Nat Rev Cancer 2007;7:256–269. https://doi.org/10.1038/nrc2090.)

atop the urogenital diaphragm. It is anterior and inferior to the seminal vesicles, which are bilateral organs. Fluid from the seminal vesicles enters the prostate through its rear portion, the central zone. It is itself posterior and superior to the testicles and penis.1

Histology The prostate has four zones that are engaged in various activities (Table 7.1).2 The zones have numerous canals that transport material into the prostatic portion of the urethra. When the distal portion of the urethra is diminished in caliber, from hypertrophy of the apex of the gland or sphincter dysfunction, it can create a secondary passive congestion of the base of the gland, further worsening dysuria. Because the prostate develops from two types of embryologic layers, it is subjected to dysfunction from

two endocrine axes. The somatotropic axis is involved in structural issues. The gonadotropic axis is implicated in structurofunctional disorders due to the role of gonadal androgens. The gonadotropic axis initiates dysfunction of the somatotropicregulated, endodermal-derived tissue. It also can also stimulate evolution of an adenoma to a fibroadenoma from influence on the mesodermal-derived, gonadotropic-regulated anterior band of the prostate. The relationship of the four zones of the prostate to the urethra and the seminal vesicles is demonstrated in Fig. 7.2. The seminal vesicles sit posterior to the urinary bladder.

Physiology The primary teleology of the prostate is to assure successful contribution of male gametes for procreation. It accomplishes this through five physiologic roles:

TABLE 7.1  Zones of the prostate, pathology, embryology, and endocrine influence Embryology

Endocrine

Zone

Location

Volume

Pathology

Endoderm

Somatotropic

Transition

Circumferential: proximal urethra

5%

Adenomas (100%) Cancer (20%) Chronic prostatitis

Central

Posterior: ejaculatory ducts

20%

Cancer (2%)

Peripheral

Circumferential: distal, posterior urethra

70%

Cancer (78%) Chronic prostatitis

Anterior

Anterior: fibromuscular band

5%

N/A

Mesoderm

Gonadotropic

Disorders of the prostate: Lower urinary tract obstruction and prostatitis Chapter | 7  137

1. Conduit for testicular sperm 2. Conduit for seminar vesicular energetic material for sperm 3. Conditioning of nutrients for sperm 4. Formation of semen for sperm 5. Conduit for semen and sperm to be ejaculated for insemination

Semen and sperm The motility aspect of sperm is hypothesized to be a type of symbiosis, not unlike mitochondria.3 It is an airborne amphibious delivery vehicle for male gametes to fuse with female gametes for the propagation of the species. Semen is the gelatinous, plasmatic support system for this vehicle. Sperm and semen are bound to the functioning of two unique prostatic enzymes which are in turn linked to pancreatic function and gonado-thyro-somatotropic management. Semen is a complex liquid that is composed sequentially by four different glands, of which the prostate is but one (Table 7.2). Semen contains sperm and various nourishing and protective factors for sperm. The role of the prostate is to support and nourish sperm. Support is accomplished thanks to the enzyme prostatic acid phosphatase (PAP), described as early as 1936.4 PAP is an enzyme that works in an acidic environment to liberate phosphate from nutrients.5 Phosphate is key to cell membrane integrity (phospholipid bilayer), DNA, adenosine triphosphate (ATP), and other aspects of cell structure and function. PAP is expressed primarily in the prostate, although there is an evidence of its activity at low levels in other organs, including the cervix

TABLE 7.2  Composition of semen with contribution by each implicated gland Gland

Contribution (%)

Description

Testes

2–5

Spermatozoa

Seminal vesicles

65–75

Amino acids, citrate, enzymes, fructose, prostaglandins proteins, vitamin C

Prostate

25–30

Prostatic acid phosphatase, citric acid, fibrinolysin, prostate specific antigen, proteolytic enzymes, zinc

Bulbourethral glands

90%). Serum concentrations of T2 are 14-fold greater than that of DHT. However, that is somewhat misleading, because the majority of DHT is derived from tissular T2 conversion, in particular the prostate,17 by an irreversible conversion by 5-alpha reductase18 (Fig. 7.3). That is to say, DHT cannot be converted back into T2, which could then be converted into estrogens which could have regulated the activity of DHT. The prostate is uniquely sensitive to DHT because it is particularly rich in the 5-alpha reductase enzyme.

138  The Theory of Endobiogeny

Lumen

ERβ

Apoptosis

Testosterone

Luminal epithelium

Estradiol

AR Serum testosterone

DHT

Testosterone Basal epithelium

5αR1

DHT

5αR2

Local

Apoptosis

ERβ

Estradiol Basement membrane Stroma

Aromatase Estradiol Testosterone

ERα

Cell proliferation

Local

FIG.  7.3  Reduction of testosterone to dihydrotestosterone. ERα mainly in stroma, mediates cell proliferation; ERβ mainly in epithelium, results in apoptosis. Aromatase: predominantly stroma, regulates androgens; basal epithelium: DHT conversion; luminal epithelium: action of T2, DHT. 5αR, 5αreductase; AR, androgen receptor; DHT, dihydrotestosterone; ER, estrogen receptor; T2, testosterone. (Reproduced from Ho CK, Habib FK. Estrogen and androgen signaling in the pathogenesis of BPH. Nat Rev Urol. 2011;8(1):29-41. https://doi.org/10.1038/nrurol.2010.207.)

DHT stimulates genetic transcription of enzymes related to cell growth. There is primary production of DHT in the testicles, skin, and liver. However, the majority of prostatic DHT is produced by intracrinologic conversion of T2.18 In addition to the two gonadal androgens, there are adrenal androgens (exemplified by dehydroepiandrosterone (DHEA)). DHEA can also be converted to T2 and then converted irreversibly to DHT. Thus, there are two sources for DHT intracrine production. Each type of androgen plays different roles in structure and function (Table 7.3).17, 19

Somatotropic As noted earlier, the endodermal origin of most of the prostate gland links it to somatotropic function in its basic structural formation and structuro-functional adaptations. A proper regulation of growth hormone (GH) and prolactin (PL) ensures the appropriate calibration of quantity, quality, and chronology of insulin resistance and insulin activity from the endocrine pancreas.

Thyrotropic-exocrine pancreas Thyroid-stimulating hormone (TSH) links what is initiated by androgens and completed by insulin. TSH’s thyrotropic role is calibration of T4. Its thyro-somatotropic role is stimulation of the exocrine pancreas to support the nutritive

metabolic activity related to semen production and nourishment of sperm. Latent hypothyroidism favors adenomatous hypertrophy of the prostate. Peripheral thyroid hyperfunctioning with low serum TSH favors inflammatory, edematous swelling of the gland.

Autonomic nervous system The pelvic basin is richly innervated with parasympathetic and alpha-sympathetic fibers arising from the sacral nerves. The autonomic nervous system (ANS) plays a key role in the sequencing of the muscular activity of the bladder, sphincters, pelvic floor, and prostatic muscles. These muscles are crucial to maintain continence and assure proper urination, defecation, and ejaculation. Parasympathetic predominates in the structuro-functional exocrine activity of the prostate gland. Alpha and beta-sympathetic help calibrate the quality of secretions and their excretion into the respective ducts.

Summary The prostate is derived from endodermal tissue rich in the capability to produce DHT. Its structural integrity and structurofunctional activity is closely linked to the somatotropic ­response to general metabolic demand from androgens. The mesodermal-derived anterior band—the guard that guards

Disorders of the prostate: Lower urinary tract obstruction and prostatitis Chapter | 7  139

TABLE 7.3  Summary of androgen activity by type of androgen Effect

DHEA

Testosterone

DHT

Androgen receptor affinity

1

10

30

Skin moisture Hair

Increases sebum Low hair line

Receding hair line

Muscle

Skeletal: mass, density, strength Smooth: relaxation, proliferation

Bone

Density, linear growth Epiphyseal closure

Genitals

Epididymis Vas deferens

Thrombosis

Increased clotting

Sexuality

Libido

Comportment Cognition

Prostate Glans penis

Erection Capacity to resist and persevere

Neuronal irritability

Neuronal stability Neuroplasticity

DHEA, dehydroepiandrosterone; DHT, dihydrotestosterone.

the guardian—subjects to the prostate to restrictive edema and aggravation of urinary tract obstruction. The prostate is an exocrine gland whose function is related to the quality of exocrine pancreatic activity and by extension diet and TSH. The exocrine pancreas participates in the quantity of exogenous nutrients presented to the prostate. This relationship can be indirectly reflected in the level of PAP. The endocrine pancreas participates in the nourishment and utilization of these nutrients by the prostate. This relationship can be indirectly reflected in the level of PSA.

Lower urinary tract obstruction Because the urethra passes through the prostate, enlargement of the prostate will compress the urethra, resulting in outlet obstruction (see Fig. 7.1).20 A question of terminology must be addressed prior to discussing these disorders. The academic literature refers to bladder outlet obstruction (BOO). In our opinion, BOO is too narrow a term. The bladder outlet is not the only portion of the urethra’s passage that may be obstructed. The prostatic portion of the bladder can also be compressed or obstructed. We propose the term LUTO as more inclusive of sphincter resistance and mechanical compression or kinking. The US literature largely speaks of benign prostatic hypertrophy (BPH). In a sense, BPH is sufficiently broad. However, here some consider hypertrophy as synonymous with enlargement of the gland. We wish to make the distinction between enlargement and hypertrophy. Hypertrophy we reserve for the classical pathological observation of adenomatous growth—a benign cancerous growth—cell by

cell, of one or more zones of the prostate. Enlargement is a general term that indicates that the size of the total organ, tissue layer by tissue later is larger than its prepathologic volume. This can be due to inflammation, edema, hyperplasia, or other causes. Thus, we propose the term benign prostatic enlargement (BPE). There are two causes of LUTO that we will discuss in this chapter. The first is adenomatous growth of the prostate. The second is inflammation and edema of the prostate. In both cases, there is excessive DHT and inflammatory or edematous factors. However, in adenomas, the gonadosomatotropic actions favoring hyperplasia are the primary source of volumetric enlargement of the prostate. In the second case, the cortico-thyrotropic and thyro-somatotropic impact on inflammation and edema is initiatory and play the prominent role in prostate enlargement. These observations have important consequences on treatment. The end result in either case is lower urinary tract symptoms (LUTS). With both origins of BPE, one finds autonomic dysfunction which is the spasmophilic dialectic (cf. The Theory of Endobiogeny, Volume 2, Chapter  11) of a hyperfunctioning alpha-sympathetic and parasympathetic on the urinary bladder and implicated sphincters. In adenomas, parasympathetic usually initiates. In the edematous type, para is compensatory. The role of the ANS needs to be addressed here, as it becomes an important and nuanced part of treatment strategies. Hyperfunctioning para and alpha can cause disproportionally aggravated dysuria symptoms in LUTO. They affect the tonicity of the detrusor muscle and the sphincters related to continence. That is to say, a man with

140  The Theory of Endobiogeny

TABLE 7.4  Lower urinary tract stages and symptoms Stage

Dysuria

Bladder function

Comment

1

Delayed onset Urgency Frequency Incomplete voiding

Intact

Outlet partially obstructed from hypertrophy in the prostate portion of urinary bladder or due to ANS hyperfunctioning or both Pelvic heaviness Symptoms aggravated by pelvic congestion

2

Stage 1 and: Reduced strength of stream Dribbling

Hyperexcitable

Bladder distended to produce enough force to overcome outlet obstruction

3

Stage 2 and: Passive urination

Hypoexcitable

Damaged reflex arcs

a mild degree of prostate enlargement may have symptoms consistent with stages 2 or 3 LUTO (Table 7.4) because of the disproportionate role of the ANS. Urinary symptoms that are highly variable, worse during the day at work than at night, or aggravated by emotional states, are more likely to be related to ANS tone. These patients tend to have a faster response to sympatholytic treatment but plateau at some point. One must treat the terrain. In addition, further improvements in urination will occur with dietary changes, counseling therapies, biofeedback, or other approaches that allow for at-will modification of autonomic tone. LUTS occur in stages,20 outlet obstruction (stage 1), urinary retention (stage 2), and advanced bladder distention (stage 3) (Table 7.4). Stage 1 is characterized by frequency, dysuria, and urgency. Urination occurs more frequently than historically typical for the patient. The greater the hypertrophy of the prostate, the more frequent the urination due to incomplete voiding. It is more frequent in the second half of the night and aggravated by all factors that increase pelvic congestion, from sympathetic tone to stress to constipation. Dysuria refers to any alteration in the onset, flow strength, or completion of micturition. In stage 1, the dysuria is a delay in onset of the urinary stream. Urgency is the third symptom. It is a feeling that one must urinate in a short period of time to avoid incontinence. A feeling of pelvic heaviness may accompany urgency. Stage 2 results in urinary retention. There is incomplete voiding. Dysuria advances to include reduced strength of the urinary stream. With further hypertrophy, there is postvoid dribbling of urine. The structuro-functional activity of the bladder alters. Due to hypertrophy of the detrusor muscle, the bladder becomes hyperexcitable. The functional bladder capacity decreases and feelings of urgency intensify. In stage 3, the bladder becomes distended, losing tone as the detrusor muscle is damaged from chronic distention. The patient needs to resort at times to passive urination through manual compression of the bladder. This is accompanied by a passive augmentation of urinary volume (in order to stimulate reflex arcs to stimulation contraction of the detrusor), leading to urinary incontinence.

Adenoma of the prostate Precritical terrain Adenoma of the prostate is a benign tumorous growth. It occurs in the transition zone of the prostate, which circumferentially encompasses the proximal urethra. The precritical terrain in all adenomas is as follows: ●

● ●

●

ANS: hyperfunction πΣ > hyperfunction αΣ in metabolism and/or congestion TSH: elevated activity Somatotropic: hyperfunctioning GH > hyperfunctioning PL ● Insulin: implicated in its hyperfunction as a reaction to the above Exocrine pancreas: oversolicited

Past critical terrain In all cases of BPE, the past medical history offers a rich tapestry of the way in which androgens have participated throughout structural and structuro-functional demands. Adrenal androgens can be evaluated for their role in transitioning through the grand phases of life. Examples include thick, dark hair at birth and onset of adrenarche, and how the man experienced emancipation between 28 and 32 years (cf. The Theory of Endobiogeny, Volume 1, Chapter 13). Gonadal androgens can be evaluated in the history of neonatal, adolescent and adult acne, and its location. The more examples of adaptation noted, the greater the ability to determine if the response is stereotypic and genetic, or modified by epigenetic factors or adaptative compensations in other systems. Because DHT production is extremely low and prostate physiology is limited, there will be few examples of hypergonadal androgenism in childhood. In the case of a prostate adenoma, a childhood history of other adenomas is relevant. In our experience, approximately 66% of men who develop a prostatic adenoma had a history of other types of adenomatous growths during

Disorders of the prostate: Lower urinary tract obstruction and prostatitis Chapter | 7  141

c­ hildhood and earlier adulthood. Typical examples include a history of recurrent tonsillitis, adenoidectomy, tonsillectomy, or appendectomy. Severe acne in adolescence may also be associated with an increased tendency to localize adenoidal growth in the prostate in later life as well as prostate cancer.21, 22

Initiator of the critical terrain: Diminished gonadal androgens In the face of an adenomatous precritical terrain, when a man experiences an alteration in gonadal androgen production, he is at risk of developing an adenoma of the prostate.

Case study in prevention A 48-year-old man presented for evaluation. He was concerned about developing an enlarged prostate like his father and uncles. At presentation, he had no urinary dysfunction. Past medical history was significant for adenomatous growth and adaptative androgen compensation in adolescence and emancipation phase. He had chronically enlarged tonsils (adenoma) with recurrent otitis media and tonsillitis. He had tonsillectomy and adenoidectomy at 5 years of age. From 14 to 18  years, he had moderately severe acne (Chapter 8) with scarring around the jaw line (gonadal androgen insufficiency with hyper luteinizing hormone (LH) and adrenal androgen overcompensation). At 28 (emancipation phase), he had a recurrent of acne of his jaw line. A few months later, he ended a serious engagement before the wedding. He realized he had a deep fear of abandonment and could not get married. His acne spread to his chin, more on the left side than the right. At this time, he also noted thinning of the hair on the sides of his head, indicative of DHT. His exam demonstrated pelvic congestion (feet colder than hands, tender pelvic congestion point on left leg). Exam was also significant for exocrine pancreas oversolicitation (tender exocrine pancreas point and enlarged opening of Stensen’s canal). His labs were unremarkable with a TSH of 2.7. His biology of functions showed an increase in the rate of adrenal androgen production (rate of gonadal androgens index) and elevation of androgen tissular activity (comparative genital androgeny index). This index expresses the level of metabolic activity of tissue targets of gonadal androgens and by extension their functional level of activity within the structure of the organism (Chapter 3). Adenoma index was normal. Based on the total assessment, it was determined that he was in a state of gonadal recycling with hypercompensation of androgens, similar to earlier periods of his life. However, all the elements of an adenoma terrain were not present (normal TSH, normal adenoma index). The strategy of care was to focus on regulation of gonadal androgens and pelvic congestion. A simple tisane of Urtica dioica root (gonadal androgens) and Hamamelis virginiana (pelvic drainage) was instituted, to be taken in the evenings 1 h before bed. To avoid overtaxing the exocrine pancreas, he was asked to avoid all nonaged cheeses and soft, creamy cheeses such as brie and camembert. He was asked to limit aged cheeses to two servings per week. All deli meats were stopped and only 2 servings of grass-fed beef per week.

Critical terrain The critical terrain involves an overabundance of DHT. As summarized in Fig. 7.5, there are four causes. The first three are in reaction to a decline in androgens, absolute or relative in nature. They are: intrinsic LH over-compensation based on intrinsic gonadotropic vertical loops (1a), adrenal androgen over-compensation with intracrinologic conversion of DHEA to DHT (1b), or, LH over-stimulation by factors outside gonadotropic vertical functioning. (1c). The fourth is compensatory luteal entrainment to a given level of somatotropic activity (1d).

Factor 1a: Primary LH reactivity In this situation, there is an intrinsic overreaction of the LH-androgen axis. There is a decline in peripheral androgen activity with an overcorrection by LH. In our experience, this most often occurs during a period of genital recycling (cf. The Theory of Endobiogeny, Volume 1, Chapter  13), or gonadopause, which is not demarcated by a specific and unifocal event in men. Until the late 60s, serum LH (Fig.  7.4) and testosterone do not substantially decline. However, from the late 40s, there is a steady rise in sex hormone-binding globulin (SHBG) with commensurate decline in free testosterone. Free testosterone represents the available testosterone for use. The primary LH (over) response is to this decline of free testosterone.23 Diminished androgen production can be endogenous to the gonads. There can be genetic, epigenetic, nutritional, or environmental factors that impair production. Nutritional factors can include zinc deficiency.9 Environmental factors may relate to xenoestrogens or persistent environmental pollutants.24 More typically, it occurs due to diminished availability of gonadal androgens form increased SHBG. Hypercortisolemia and/or hyperestrogenism will be the most likely reasons for this (cf. The Theory of Endobiogeny, Volume 1, Chapter 10).25 SHBG binds androgens far more than estrogens, keeping androgens in reserve, allowing only about 2%–4% in circulation (Table 7.5).26 These alterations can arise during seasonal adaptations (cf. The Theory of Endobiogeny, Volume 1, Chapter  12 and Volume 2, Chapter  11), attempts to adapt DHEA for gonadotropic recycling or peripheral depression.

142  The Theory of Endobiogeny

Free testosterone (pmol/L)

Testosterone (nmol/L) 22

400

20

350

18

300

16

250

9

4

–7

75

9

–7

70

4

–6

4 55

9

4 –4

45

40

–7

75

–7

70

–6

65

–6

60

–5

55

–5

50

–4

–4

Age (year)

–5

0

50

20

0

9

30

4

4

6

9

40

4

8

9

50

4

10

9

60

4

12

45

SHBG (nmol/L)

70

LH (U/L)

–4

14

65

0

9

0

–6

200

60

12

–5

14

40

BMI < 25 kg/m2 BM 25–29 kg/m2 BM ≥ 30 kg/m2

Age (year)

FIG. 7.4  Androgen activity overtime in men. In the graph, the relationship of total and free testosterone, LH and sex hormone binding globulin (SHBG) are demonstrated in men categorized by body mass index range (green: normal, blue: over-weight, and red: obese). The problem men face is not the quantitative production capability of testosterone per se (upper left), which declines only by 10% between 40 and 80 years of age. The problem is the rise in SHBG, by 50%–80% over this same time period (bottom right). Thus one notes a 25%–30% decline in free testosterone (upper right) which is progressive over three decades (50–80 years). Finally, LH response, as measured by serum levels, to this decline is delayed by 20–25 years. It is only in the 70's that one notes doubling of LH in compensation. (Reproduced from Wu FCW, Tajar A, Pye SR, et al. Hypothalamic-pituitary-testicular axis disruptions in older men are differentially linked to age and modifiable risk factors: the European Male Aging Study. J Clin Endocrinol Metab. 2008;93:2737.)

FIG. 7.5  Development of the prostate adenoma terrain. The first step is hyperandrogenism. This can occur for four reasons. 1a: LH overcorrection. In the face of declining gonadal androgen activity LH overcompensates. 1b: Adrenal androgen overcorrection. DHEA is converted by an intracrine process locally in the prostate to testosterone and then DHT. This process is outside the LH-gonadal androgen feedback loop. 1c: LH is overstimulated from various adjacent central factors regardless of current androgen activity. This is accompanied by increases exocrine prostate activity. 1d: Compensatory LH overfunctioning to match elevated thyro-somatotropic activity. This is accompanied by increased endocrine prostate activity. 2: Horizontal TSH relaunching by overfunctioning LH. This results in 3: exocrine pancreatic activity, especially uptake of proteins from the diet. According to the theory of Endobiogeny, a rise in prostatic acid phosphatase (PAP) is reflective of the role of the exocrine pancreas. 4: Endocrine pancreas is adapted to the exocrine pancreatic function to deliver nutrients taken up from the diet. There is a rise in prostate-specific antigen (PSA) which is reflective of insulin activity on the prostate. See text for additional details. (© 2018 Systems Biology Research Group.)

Disorders of the prostate: Lower urinary tract obstruction and prostatitis Chapter | 7  143

TABLE 7.5  SHBG activity and hormone concentration Steroid Progesterone a

Testosterone b

Estradiol

Total conc. (nmol/L)

SHBG-bound (%)

Other proteins (%)

% unbound

FC (nmol/L)

0.6

0.6

97

2.4

0.014

20

55

43

2.0

0.4

0.1

30

68

2.0

0.002

FC, free concentration; SHBG, sex hormone binding globulin; Conc., concentration. a

Values for adult men.

b

Values for adult females.

Modified from Nussey S, Whitehead S. Endocrinology: An Integrated Approach. Oxford: BIOS Scientific Publishers; 2001.

Factor 1b: Adrenal androgen overcompensation In this second response to insufficient gonadal androgens, the more efficient response comes from adrenal androgens. DHEA sulfate (DHEAS) can be converted into adrenal androgens through a process called intracrinology.27, 28 Once DHEAS has entered a cell, it is converted back into DHEA then further converted into various androgens according to the requirements of the particular cell and tissue. The hormones produced within the cell act only within that cell, then are excreted in an inactivated form. Thus, DHEA helps achieve a regionally specific modification of gonadotropic activity, reducing the risk of systemic exposure to increased levels of androgens and estrogens.27–29 However, it cannot be regulated by LH, nor does it inhibit LH in turn, which is searching for a gonadal androgen feedback. This type of dynamic is similar to that seen in acne (Chapter 8), which is no surprise given the association between the two conditions.21, 22

Factor 1c: Primary LH overstimulation The third type of gonadotropic dysfunction is central gonadotropic. There is an oversolicitation of LH from other factors not related to the quality of gonadal androgen activity at the time of overstimulation of LH (cf. The Theory of Endobiogeny, Volume 1, Chapter 10). 1. Corticotropic a. CRH overstimulation by alpha, prolactin, or other factors i. GnRH → LH ii. ACTH → LH b. ACTH horizontal stimulation of LH i. Direct stimulation in the milieu of hyperaldosteronism ii. Indirect: ACTH → FSH → LH 2. Gonadotropic a. FSH relaunching of LH i. From GnRH → FSH → LH (adaptative) ii. From ACTH → FSH → LH (adaptative) iii. For estrogen calibration (adaptive or adaptative)

b. Estrogens: hyperestrogenism with LH relaunching to calibrate androgen activity (cf. FSH) 3. Somatotropic a. Prolactin relaunching switches GnRH from FSH to LH stimulation: i. TRH → PL → GnRH → LH ii. Dopamine → PL → GnRH → LH iii. Alpha → PL → GnRH → LH iv. Factors related to relaunching of CRH by PL (cf. above) One origin of corticotropic stimulation of LH is peripheral depression. Central relaunching of PL can be due to TRH, dopamine, or central alpha. This can be due to various causes such as a chronobiologic seasonal change with adaptative installation of hyperprolactinism. Or, it could be after a very stressful event, such as the death of a spouse, loss of a job, etc. The hyperandrogenism results in oversolicitation of proteins. This results in congestion of the prostate in its exocrine function of producing semen and maintaining the structural integrity of the gland proper. The congestion augments the amount of nutrients and duration of time available for cells to take them up. Initially, the congestion is solicited by para. Alpha is solicited overtime for postcapillary congestion to augment para’s passive congestion. If and when alpha predominates regionally, there will be LUTS.

Factor 1d: Compensatory LH overfunctioning This is the fourth of the four initiators of hyperandrogenism. In this case, there is a preexisting hyperactivity of thyrotropic and somatotropic axes, which favors the structuration and growth of tissues. LH readapts itself—entrains itself— to a compensatory level of function by adapting gonadal androgens for utilization of proteins for tissue growth. A contributing factor is again congestion of the prostate. This time it is to support the endocrine function of the prostate in production of DHT. The same relationship of para and alpha respond to these demands and can result in local prostate congestion or regional pelvic congestion.

144  The Theory of Endobiogeny

Factor 2: Thyrotropic: TSH Regardless of the origin of hyperfunctioning LH, there will be a compensatory horizontal relaunching of TSH by LH. TSH can play two roles in the size of the prostate. If serum TSH is low, it favors somatotropic desynchronization—especially if cortisol activity is also elevated. This results in elevated insulin activity and/or low insulin resistance, inflammation, and edema. When serum TSH is elevated, especially if there is latent or frank hypothyroidism, TSH serves as a pro-anabolic growth factor in tissues.

Factor 4: Somatotropic: Endocrine pancreas and PSA The endocrine pancreas, namely insulin, increases in a compensatory fashion based on the relative level of activity of the exocrine pancreas. PSA reflects the relative role of insulin in the growth of the prostate. Fig. 7.5 summarizes the development of the terrain.

Consequence: Prostatic adenoma

Factor 3: Somatotropic: Exocrine pancreas and PAP

Adenoma evolution

TSH solicits the exocrine pancreas to support its role as a growth factor. PAP reflects the contribution of the exocrine pancreas to the growth of the prostate. In treatment, a pancreas sparing diet will be key, especially avoiding ­nonfermented dairy, soft cheeses and animal proteins, especially red meat and deli meats in particular.

Prostate adenoma growths within the transition zone, which is of endodermal origin (somatotropic regulation). As the adenomatous terrain persists, the growth can involve the fibrous layers of the anterior zone (Fig.  7.6) Thus, the adenoma can evolve into a fibroadenomas, similar to what is seen in breast growths. Or, with further

Prostate zones

a

a

b e

e

c

c b d a Central zone

d

b Fibromuscular zone c Transitional zone d Peripheral zone

Ejaculatory duct

e Periurethral gland region Prostate zone Peripheral

Transition

Central

Focal atrophy Acute inflammation Chronic inflammation Benign prostatic hyperplasia High-grade PIN Carcinoma High prevalence Medium-high prevalence

Low prevalence None Nature reviews Cancer

FIG. 7.6  Adenoma and adenocarcinoma by prostate zone. Adenomas (listed as benign prostatic hypertrophy) mostly occur in the transitional zone (c). Significant urinary dysfunction can occur with a relatively small growth. Adenocarcinoma mainly occurs in the peripheral (d) and transition zones (c). (Reproduced from De Marzo, et al. Inflammation in prostate carcinogenesis. Nat Rev Cancer 2007;7:256–269. https://doi.org/10.1038/nrc2090.)

Disorders of the prostate: Lower urinary tract obstruction and prostatitis Chapter | 7  145

a­ugmentation of gonadotropic activity, it can involve the muscular bands of the prostate and develop into an adenomyoma. Finally, it can become a fibroadenomyoma.

Medial

Lateral

Adenoma devolution: Cancer The majority of prostate cancers occurs in the posterior zone and are asymptomatic (Fig.  7.6). However, up to 1/5th of all prostate cancers develop in the transition zone. They can develop as a devolution of prostatic hypertrophy. A sudden rise in cortisol suppresses somatostatin and the immunoprotective role of histamines. This can herald the transition of the adenoma from a benign to a pathologic tumor.

Cortisol

Painful “crow’s foot” - left: pelvic congestion - right: gall bladder

Clinical evaluation The clinical evaluation of LUTO and prostatic adenoma has three levels of assessment: (1) local: prostate, (2) regional: pelvic, and (3) global: neuroendocrine terrain. Because the digital rectal exam is invasive and uncomfortable, the evaluation is best done in the reverse order.

Physical examination 1. Global terrain a. Hyperalpha: dry mouth, cold hands or feet, etc. b. Hyperpara: abundant saliva, dilated open of Stensen’s canal, moist hands or feet, etc. c. Gonadotropic i. LH: structural vs functional hyperlutealism 1. Structural: left-sided structures larger than right-sided structures ii. Structural androgenism (functional will be determined by biology of functions) 1. Hair a. Color, coarseness, distribution (midline, proximal vs distal aspects of extremities) b. Muscle: quantity, quality, thigh-to-calm ratio d. Thyrotropic i. TRH: glabellar tap: prolonged flutter after tap, brisk deep tendon reflex, clonus ii. TSH, T4: TSH/T4 point tender inferior and medial to the tibial tuberosity (Fig. 7.7). e. Somatotropic i. GH: fissures on tongue, cracks on heels, skin tags, moles, bulbous nose, etc. ii. PL: pustular acne iii. Insulinism: doughy mid-abdominal adiposity 2. Regional a. Pancreas: dilated opening of canal of Stensen, tender pancreas points: general, exocrine, endocrine (Fig. 7.8)

TSH  T4 ¯ (left > right as LH more easily distributed than FSH)

FIG.  7.7  Significance of points on the distal extremity. The point is found two fingers below the inferior aspect of the tibial tuberosity and on the medial aspect of the tibia. It extends a distance of the distal thumb. On the right, tenderness represents gallbladder congestion, or postcholecystectomy, gallbladder oversolicitation. On the left, tenderness reflects pelvic congestion. The past the distal edge is a bilateral finding of latent hypothyroidism representing an appeal of TSH to the thyroid for production of T4. (With permission from Duraffourd and Lapraz, © 2002.)

b. Colon: tender points: mid-ascending and proximal transverse (FSH), distal transverse and proximal descending (LH), hepatic flexure (TRH/TSH), splenic flexure (TSH), mid-descending (GH), distal descending (PL) (Fig. 7.9) c. Pelvic congestion: left leg, tender inferior and medial to tibial tuberosity (Fig. 7.7) 3. Prostate exam: digital rectal exam: size, symmetry, nodularity, and texture

Imaging of the urogenital system Uroflowmetry remains the gold standard. However, doppler ultrasound, penile cuff test, and other studies offer good true positive values and should be considered when invasive urodynamic studies are not practical or readily repeated.30

Blood tests To perform a biology of functions, there are a number of levels of evaluation that one may perform.

146  The Theory of Endobiogeny

Liver congestion: secretory

Liver congestion: circulatory

Splanchnic congestion hepato-pancreatic blockage

Zone of distress Murphy’s point: Congestion: sphincter of Oddi

Hepatic congestion, extra-hepatic: sphincter of Oddi, splanchnic congestion, duodenal plexus

Endocrine pancreas overtaxed General pancreatic congestion Exocrine pancreatic congestion

FIG. 7.8  Reflection points related pancreas solicitation, exocrine, and endocrine. Tenderness on moderately deep palpation is indicative of oversolicitation of the pancreas without prejudging the ultimate competency of the pancreas or reason for solicitation. (Used with permission from Duraffourd and Lapraz, © 2002.)

glucose, blood urea nitrogen, and creatinine with estimated glomerular filtration rate), TSH, and osteocalcin 2. Role of central vs peripheral dysplastic factors: cancer embryonic antigen, CA 19-9 (TRH on pancreas, thyro-somatotropic by extension), CA 15-3 (thyroid), and CA 125 (FSH) 3. Additional thyroid studies: free T4, free T3 to be evaluated against each other and TSH 4. PSA ((ng/ml), total and % free): make sure patient has not engaged in vigorous exercise (especially equestrian and bike riding) or sex within 24 h of blood test. 5. PAP (ng/ml) 6. Prostate nutrition: PAP/PSA total ratio (normal 0.7–1.3) Addition studies can be performed based on the work up and the differential diagnosis. For example, if one suspects a urinary tract infection as the provoker of acute urinary retention, a urinalysis and urine culture should be performed.20 FIG.  7.9  Cartography of endocrine solicitation of nutrient absorption from the colon. The various points of the colon are linked to central endocrine factors and their appeal for nutrients related to the functioning of the hormones they stimulate. (Modified by Systems Biology Research Group and used with permission from Duraffourd and Lapraz, © 2002.)

1. Standard panel: complete blood count (CBC) with differential and platelets, creatine kinase total, lactate dehydrogenase total, alkaline phosphatase total and isoenzymes, complete metabolic panel (to include sodium, potassium, chloride, calcium total serum, total protein,

Biology of functions The biology of functions needs to be approached with a working hypothesis of the origin of the prostate adenoma. For example, if one suspects a type 1a primary reactivity of LH with overcompensation of androgens, one finds indexes of elevated androgens but an LH index (normal 0.3–4) that is normal or only slightly low (e.g., 0.01–0.29). This suggests that the pituitary does not receive sufficient feedback from androgens to downregulate androgen production

Disorders of the prostate: Lower urinary tract obstruction and prostatitis Chapter | 7  147

TABLE 7.6  Indexes modeling coupled endocrine relationships in prostate adenoma Index

Value b

Comment

Follicular implicationa

High

It expresses the relative part of the gonadotropic axis as a whole in the pathogenicity of the organism

Thyrotropic implicationa

Highb

It expresses the relative part of the thyrotropic axis as a whole in the pathogenicity of the organism

Hypothalamometabolic implicationa

Highb

It expresses the relative metabolic responsibility of the thyro-somatotropic axis (TRH-PL) in the pathogenicity of the organism

Global upstream 2a

Highb

It expresses the relative compensatory activity of the thyro-somatotropic axis in relationship with that of the thyro-metabolic fraction of the thyrotropic axis in its implication. In other words, how TRH-PLinsulin response to the metabolic demands imposed by peripheral thyroid hormone activity

Global upstream 3a

Highb

It expresses the relative compensatory part of the thyro-somatotropic axis in relationship that the follicular fraction of the gonadotropic axis. By extension it contributes to the evaluation of the relative part of the level of central metabolic activity in comparison to that of the centripetal axial endocrine activity. In other words, how TRH-PL-insulin responds to the demands for energy imposed by FSH

a

  Has only function value.

b

  At least two of these indexes will be elevated, varies by terrain.

TABLE 7.7  Gonadotropic indexes in prostate adenoma Index

Value

Comment

LH

Varies

Adenoma 1a: 1a: normal to slightly low Adenoma 1b: very low

Rate of global androgens

High

Indicates global androgen activity from all origins in all forms of hormonal effects

Rate of adrenal androgens

High or normal

Indicates global adrenal androgen activity, which can be aromatized to T2 then DHT

Rate of gonadal androgens

High or normal

Indicates global gonadal androgen activity

Genital androgens

High

General endocrinometabolic tissular activity of gonadal androgens on tissues for structural purposes

Comparative genital androgeny

High

The specific endocrinometabolic tissular activity of gonadal androgens on androgen-rich tissue, such as the prostate, for structural purposes

Musculotropic index

Varies

High: favors a risk of hypertrophy of the fibromuscular anterior zone

(Chapter 3). In type 1b LH overstimulation, one would expect the LH index to be very low (e.g., Zea mays or Cornus sanguinea or Lithospermum officinale or Lycopus europaeus + Poterium sanguisorba or Mercurialis annua or Fragaria vesca Fabiana imbricata or Leonurus cardiaca dose > Lithospermum officinale or Lycopus europaeus

TABLE 7.15  Treatment options based on thyrotropic index values for prostate adenoma Index

Value

Comment

Thyroid

↓

Ascophyllum nodosum, selenium, L-tyrosine, Avena sativa, Salvia officinalis, Salvia sclarea, Prunus amygdalus GM (bud > rootlet)

Thyroid yield

↓

Even if thyroid index normal, Ascophyllum nodosum, selenium, L-tyrosine, Avena sativa, Salvia officinalis, Salvia sclarea, Prunus amygdalus GM (bud > rootlet)

Global TRH of adaptation

↑

Fabiana imbricata or Leonurus cardiaca

TRH/TSH

↓

Ascophyllum nodosum

activity is low, a plant like Salvia officinalis or Salvia sclarea is efficient. They support adrenal cortex, estrogens and thyroid activity, as well as various digestive and emunctory support. Supporting estrogens risks relaunching LH. Thus, one must use medicinal plants that also block LH. The second goal is to inhibit LH activity. One can do this indirectly by improving cortisol (noted above), directly inhibiting it (e.g., Medicago sativa) or with progesteronic plants (e.g., Achillea millefolium, Alchemilla vulgaris). Progesterone competes

152  The Theory of Endobiogeny

TABLE 7.16  Treatment options based on somatotropic index values for prostate adenoma

TABLE 7.17  Corticotropic and immunity indexes in prostate adenoma

Index

Value

Comment

Index

Value

Comment

Pelvic congestion

↓

Hamamelis virginiana, Urtica dioica root, Alchemilla vulgaris, Achillea millefolium, Lavandula angustifolia, etc.

Cortisol

↓

Salvia officinalis, Salvia sclarea, Prunus africana, Ribes nigrum Eleutherococcus senticosus

Metabolic yield

↑

Address thyroid and adrenal imbalance

Aldosterone

↑

Borago officinalis

↑

Adenosis

↑

Address gonado-thyrosomatotropic imbalances

Evoked histamine

Hamamelis virginiana, Artemisia dracunculus, Matricaria recutita, Lavandula angustifolia

Growth index or Growth index corrected

↑

If thyroid index is low: Prunus amygdalus GM (bud > rootlet), if androgens elevated: Urtica dioica root, if adenoma terrain still active: Fragaria vesca in all cases: low glycemic diet

Platelet mobilization

↓

Menyanthes trifoliata, Cinnamomum zeylanicum, Sadenosyl methionine (SAMe)

Inflammation

↑

Necrosis

↓

Improve thyroid activity, especially TSH if thyroid yield is low

Menyanthes trifoliata, Curcumin longa, Cinnamomum zeylanicum, Lavandula angustifolia

Somatostatin

↑

Low glycemic diet, Juglans regia, Agrimonia eupatoria, Plantago major, Avena sativa

Insulin index

↓

Juglans regia, magnesium, improve TSH activity

Insulin resistance

↑

Juglans regia, magnesium, improve TSH activity

Redox

↓

Improve thyroid and insulin sensitivity, exercise, hyperbaric oxygen therapy

Pancreatic index

↑

Dual pancreatropes: Juglans regia, Vinca minor, general pancreatic drainage: Rubus fruticosus GM

GH growth score

↑

Fragaria vesca

Expansivity index

↑

Address factors related to adenosis

with testosterone for the 5-alpha-reductase e­nzyme, thus indirectly reducing the rate of production of DHT from T2. Directly inhibitors of 5-alpha-reductase can also be used (listed under DHT in table below). The third method is to support testosterone production (e.g., Eleutherococcus senticosus) while inhibiting DHT conversion with 5-alpha-­ reductase inhibitors (e.g., Urtica dioica).

Medicago sativa (Alfalfa) Essence: helps restore the peripheral gonadal balance when androgens > estrogens due to central factors Parts used: whole herb

Galenic: MT, FE, MS, bulk herb Actions: Endo: gonado: anti-LH, antiandrogenic, estrogenic.39 Vasc: rich in silica, improves elasticity of vascular wall. Metab: hypolipemiant (intestinal absorption modification, enzymatic substitution activity).39 Heme: contains vitamin K, uterine antihemorrhagic. Use: All hyperluteal states: progesterone-predominant PMS, prostatic adenoma, prostatitis, Cardiovascular disorders: atherosclerosis, arteritis, hyperlipidemia. Notes: Can increases photosensitivity

Eleutherococcus senticosus (Eleuthero) Essence: An adaptogen favoring cortico-androgenic competency while supporting estrogen’s role in first loop physiology. NB: Eleuthro’s androgenic activity is essentially adaptogenic. In cases of hypogonadal androgenism, it offers androgenic-like activity. In cases of hyperadrenal or hypergonadal androgenism, it provides information to LH about endogenous androgenic activity, allowing LH to be downregulated, similar to the way in which Ribes nigrum inhibits ACTH in high-cortisol states. Parts used: leaf, root Galenic: MT, FE, MS, bulk herb Actions: General: adaptogen40, 41. Endo: gonado: estrogenic, testicular androgen stimulant, cortico: glucocorticoid stimulant,42 somato: antihyperglycemant (improves passive glucose diffusion, improves postprandial insulin sensitivity). Immune: immunomodulatory,23 immunostimulant, antiinflammatory, antioxidant. ID: poly-antimicrobial23: bacteria, viruses. Heme: leukocytogenic,23 thrombocytogenic. GU:

Disorders of the prostate: Lower urinary tract obstruction and prostatitis Chapter | 7  153

uterine ­anti-inflammatory. GI: hepatoprotectant23. Metab: hypolipemant (binds low-density lipoprotein (LDL)).23 ONC: antitumoral.23 DIUR: chloretic.41 Use: All states of debilitation: Compromised buffering capacity; intolerance to stress; chronic fatigue; pre, during, postchemotherapy; chronic and acute infectious states. All states of corticotropic disadaptation: Endogenous depression; insomnia; corticotropic circadian dysrhythmia. Gonadal disorders root in peripheral gonadal insufficiency and central overcompensation: Menorrhagia, certain types; metrorrhagia, certain types; acne; prostatic adenoma and hypertrophy. Preparation: Root: 2 tbsp decocted for 12–15 min in 1 L water. Strain, drink throughout the day. Start for 3 weeks before change of seasons. Note: can interfere with antihypertensive medications.

Urtica dioica (Nettle) root Essence: a depurative that regulates peripheral gonadal androgen metabolism and associated factors Parts used: root Galenic: MT, FE, MS, bulk herb Actions: Endo: gonado: blocks growth factors at level of prostate, prevents binding of testosterone and DHT to SHBG, inhibits aromatase activity (reduces conversion of testosterone to estrogen), inhibits 5-α-reductase (reduces conversion testosterone to DHT).43 GU: pelvic decongestant. Immune: antiproliferatives;44–48 antiinflammatory, antirheumatic (inhibits formation of inflammatory agents), stimulates T-cells. Renal: diuretic (volumetric, chloruretic, uricosuric). Detox: purifier, astringent. CV: antihypertensive (mild: inotrope negative, increases nitric oxide release).49, 50 Use: prostatic hypertrophy, prostate cancer, androgenic alopecia, hypertension, congestive heart failure, rheumatic congestions Method: BH: 3–5 tbsp dry root in 4c water; decoct 3 min and steep 10 min, drink in 3 even doses/day

­activity should be addressed as indicated. Fragaria vesca is the most efficient plant for this, especially if there is insufficient adrenal cortex activity as well. The role of prolactin varies in prostate disease. It is generally reactive but can be an inducing element if it is responsible for shifting GnRH pulsatility favor LH. Its reactive element is more in its thyro-somatotropic role of TRH-PL-insulin, often in response to thyroid metabolic activity or exocrine pancreatic oversolicitation.

Exocrine pancreas, ANS, decongestion Cf. discussion on symptomatic management.

Diet Pancreas-sparing diet. Cf. symptomatic treatment above.

Lifestyle Table 7.18 summarizes factors to avoid that injure the prostate or worsen pathophysiology, and those to encourage that have help relieve the role of congestion.

Surgical intervention When urinary outflow is significantly compromised, various interventions are available. When it involves hematuria, recurrent urinary tract infections with or without renal involvement, intervention is warranted. These include transurethral prostatectomy (TURP). Urinary ­incontinence and retrograde ejaculation are adverse outcomes from this

TABLE 7.18  Lifestyle guidance for BPE Category

Principle

Example

Avoid

Inflammation

Tobacco products

Prostate irritation or injury

Horseback, bicycle riding Constipation

Prostate overactivity

Excessive sexual activity

Diminishes perineal flow

Prolonged sitting

Frequent standing

For every 55 min of sitting, walk for 5 min

Exercise

Aerobic exercise: walking, running, elliptical

Prostate emptying

Moderate sexual activity

Thyrotropic regulation Thyrotropic regulation involves improving the efficiency of the peripheral thyroid’s response to TSH. Thus, improving thyroid yield is the goal here. This can be accomplished with plants like Avena sativa, or oligoelements alone or in combination that improve the rate of production of thyroid hormones: iodine, selenium, and copper being the most important. Because zinc is important to keep PSA inactive, Zn-Cu can be an efficient oligoelement to use.

Somatotropic regulation Somatotropic regulation involves inhibition of central and peripheral hyperfunctioning. Central GH and prolactin

Encourage

154  The Theory of Endobiogeny

approach. Various minimally invasive procedures have been developed to diminish prostate size using lasers, microwaves, high-pressure directed water flow, and other methods.51

driven and very focused on their professional life, critical, demanding, or with perfectionist tendencies.

Edematous BPE

The aggressor is some type of adaptation demand expressed through cortico-thyrotropic yoking. There are three general categories. The first is chronobiologic. The second is a substantial and sudden conflict or stressor. The third is a slow, progressive conflict, or stressor that reaches a critical point of fragilization.

A second nosologic classification of BPE is one in which edema is the prominent features of prostate enlargement and the consequent LUTO. Hyperandrogenism is always present, but the peripheral estro-somatotropic features are not, so there is no adenoma. The hyperandrogenism precedes onset of pathologic prostate enlargement. In the majority of cases, there is an adaptation demand expressed through corticothyrotropic yoking (cf. The Theory of Endobiogeny, Volume 1, Chapter 10). This is the state in which alpha-sympathetic stimulates both the corticotropic and thyrotropic axes. The man who has an adaptative response—one that does not return to the prior state of function—will express this inflammatory terrain at the level of the prostate. The inflammatory terrain is expressed, in general, in the most metabolically active tissues be it from injury and repair (e.g., a joint), or, because a hyperfunctioning metabolism. The latter is the case during the adaptative response, expressing itself at the level of the prostate. There are the three reasons for edema. The first is hyperfunctioning cortico-thyrotropic, the second hyperfunctioning thyro-somatotropic, and the third induced inflammation. The third is due to a weak corticotropic response with elevated histamines and aldosterone. Some combination of these three may be present in the terrain.

Aggressor

Critical terrain The critical terrain is one in which edema of the androgenized prostate occurs. Immune factors are implicated, be it from a neuroendocrine installation of adaptative inflammation, interleukins driving a hyperimmune state, or histamines. A combination of these three may also be present.

Hyperimmune terrain The first type of terrain is a hyperimmune terrain similar to that of the allergic terrain (Chapter 1). This is rooted in a hyperfunctioning alpha, ACTH, TRH favoring increased histamine activity and sensitivity and diminished cortisol, and/or global adrenal cortex function to regulate histamine activity (Table 7.19). Edema comes about thanks to extravasation of fluid from capillaries due to histamine’s role in vascular endothelial integrity.52

Hyperinflammatory terrain Precritical terrain The precritical terrain is one of hyperandrogenism with pelvic congestion and pancreatic oversolicitation. Any of the causes 1a–1d discussed in prostate adenoma may be the cause of this state. Often there is a precritical spasmophilia. Regardless, the ANS is oversolicited and hyperfunctioning. As in our prior discussion, it is important to determine two things. The first is the temperament of the patient based on an investigation of their infancy, and qualities of their personality. There is a slight majority of patients in this category are vagotonic with a hyperfunctioning parasympathetic tone at time of presentation. For example, the patient may be described as having been a quiet and easy baby, or a shy or clingy toddler, etc. Alpha-sympathetic tone is also hyperfunctioning. It is in part compensatory to the vagal tone, especially at the level of the pelvis to prevent urinary incontinence. At the time of presentation, regardless of the vagotonia, there is globally elevated alpha-sympathetic tone. One may find cold hands and feet, dry stringy saliva, ischemic hard palate, etc. (cf., The Theory of Endobiogeny, Volume 2, Chapter 1). Those who have a primary elevation of alpha with compensatory para are often described and

A hyperinflammatory terrain is one in which there is central and peripheral hyperfunctioning of alpha, the corticotropic, and thyrotropic axes. The Endobiogenic notion of this inflammation is one rooted in a functional adaptability of the organism due to endogenous demands (Table 7.20). It is sufficient for either cortisol or thyroid to be elevated in

TABLE 7.19  ANS-endocrine mediators of histamine activity Factor

Effect on histamines

↑ Central alpha

↑ Demand

↑ Peripheral alpha

↑ Local use as autacoid

↑ ACTH

↑ Receptors

↑ TRH

↑ Release

↓ Cortisol

Insufficient downregulation

↑ Interleukins

Increased release of products from immune cells, including histamines

Disorders of the prostate: Lower urinary tract obstruction and prostatitis Chapter | 7  155

TABLE 7.20  ANS-endocrine mediators of inflammation Factor

Effect on inflammation

↑ Central alpha

↑ Cortico-thyrotropic solicitation

↑ ACTH

↑ Cortisol relaunching

↑ Cortisol

Suppression of somatostatin → somatotropic desynchronization Catabolism of tissues

↑ TRH

↑ TSH stimulation

↓ TSH serum

Somatotropic desynchronization

↑ Thyroid peripheral

Increased rate of catabolism and glucose oxidation

↑ Insulin

Increased entry of glucose for oxidation with free radical production

↑ Insulin resistance

As above

↑ Free radicals

Cf. insulin

↑ Necrosis

Consequence of inflammation, favors edema

the inflammatory terrain, or both may be elevated. Edema comes about due to injury of cells from radicals and/or cell necrosis, resulting in leakage of cytoplasm. Edema can come about due to elevated aldosterone activity in either hyperhistaminemia or an inflammatory terrain. Finally, a man may have a combination of both these terrains (Table 7.21).

TABLE 7.21  ANS-endocrine mediators of mixed type hyperhistaminic-inflammatory terrain

Evaluation The evaluation will be similar to that of adenoma (cf., above). However, the focus on physical exam should also include symptoms and signs of elevated TRH, ACTH, alpha, and histamines (Table 7.22).

BoF In assessing the terrain of edematous BPE, the same axes of function are evaluated, but with emphasis on a different group of indexes related to inflammation and edema (Tables 7.23–7.27).

Pharmacologic treatment Cf. Prostate adenoma.

Symptomatic treatment Symptomatic treatment of BPE due to edema is downstream treatments. They address the consequences of the disequilibrated terrain. The specific selection depends on the presence of histamine, inflammation, aldosteroneinduced edema along with pelvic congestion, ANS, and spasmolysis (Table  7.28). A full discussion of these plants is in Chapter 1, Allergies, Tables 1.13–1.15. Here, we present those that are the most efficient in prostate disease because they also address autonomic dysfunction and/or emunctory drainage, in particular pancreatic and pelvic.

Prescription for inflammatory BPE with LUTO Arnica montana MT 40 mL, Matricaria recutita MT 40 mL, Hamamelis virginiana MT 40 mL, Lavandula angustifolia EO 1.5 mL, Melaleuca leucadendron EO 1.5 mL, Dose: 4 mL 3–4 times per day until symptoms resolve.

Factor

Effect on inflammation

↑ Central alpha

↑ Cortico-thyrotropic solicitation

↑ ACTH

↑ Histamine receptors

↓ Cortisol

↓ Histamine regulation

↑ TRH

↑ Histamine release ↑ TSH stimulation

↓ TSH serum

Somatotropic desynchronization

↑ Thyroid peripheral

Increased rate of catabolism and glucose oxidation

↑ Insulin

Increased entry of glucose for oxidation with free radical production

Treatment of the endobiogenic terrain

↓ Insulin resistance

As above

↑ Free radicals

Cf. insulin

↑ Necrosis

Consequence of inflammation, favors edema

The treatment of the Endobiogenic terrain has two aspects. The first is the regulation of upstream factors and luteal dysfunction (cf. Tables 7.10 and 7.11). The second is adaptative yoking: sympathetic, corticotropic and thyrotropic, and the thyro-somatotropic consequences (Tables 7.29–7.31).

Prescription for allergic-terrain BPE with LUTO Eleutherococcus senticosus MT 40  mL, Agrimonia eupatoria MT 40 mL, Hamamelis virginiana MT 40 mL, Lavandula angustifolia EO 2 mL, Dose: 4 mL 3–4 times per day until symptoms resolve.

156  The Theory of Endobiogeny

TABLE 7.22  Symptoms and signs particular to edematous prostate enlargement Neuroendocrine

Symptoms

Signs

↑ Alpha

Dry mouth Oral herpes or canker sores when stressed Hypertension

Stringy saliva Injected sclera Dilated pupils Cold extremities Rapid lid movement on glabellar tap

↑ Histamine

Allergies, dermatitis, pruritis, angioedema Gastric acidity Hypervigilance

Dermatographia Rapid, prolonged or intense erythema of skin with rolling palpation

↑ ACTH activity

Social, outgoing, determined, or forceful

Bushy eyebrows

↑ Cortisol

Insomnia Early waking with vigorous exercise in morning Oral herpes or canker sores when stressed

Fat deposits on zygomatic arch Striae Cortisol point, distal lateral femur tender

↑ TRH

Vivid dreams Imaginative, tangential thinker, creative problem solver

Flutter on glabellar tap Very brisk deep tendon reflexes Clonus

↑ Insulin, ↓ Insulin resistance

Intense sugar cravings Susceptibility to hypoglycemia

Edematous, enlarged neck flap Skin tags Mid-gut doughy adiposity

Comments

These signs may be absent on the exterior and only present in the middle or interior structures and confirmed by biology of functions

The symptoms are central and the signs mentioned are functional, may not be present but BoF may confirm TRH’s metabolic role

TABLE 7.23  Indexes modeling coupled endocrine relationships in edematous BPE Index

Value

Comment

Gonadotropic implication

↑

It expresses the relative part of the gonadotropic axis as a whole in the pathogenicity of the organism

Thyrotropic implication

↑

It expresses the relative part of the thyrotropic axis as a whole in the pathogenicity of the organism

Hypothalamometabolic implication

↑

It expresses the relative metabolic responsibility of the thyro-somatotropic axis (TRH-PL) in the pathogenicity of the organism

Global upstream 2

↑

It expresses the relative compensatory activity of the thyro-somatotropic axis in relationship with that of the thyro-metabolic fraction of the thyrotropic axis in its implication. In other words, how TRH-PL-insulin response to the metabolic demands imposed by peripheral thyroid hormone activity

Global upstream 3

↑

It expresses the relative compensatory part of the thyro-somatotropic axis in relationship that the follicular fraction of the gonadotropic axis. By extension it contributes to the evaluation of the relative part of the level of central metabolic activity in comparison to that of the centripetal axial endocrine activity. In other words, how TRH-PL-insulin responds to the demands for energy imposed by FSH

Disorders of the prostate: Lower urinary tract obstruction and prostatitis Chapter | 7  157

TABLE 7.24  Gonadotropic indexes in edematous BPE Index

Value

Comment

LH

Low

Rate of global androgens

↑

Indicates global androgen activity from all origins in all forms of hormonal effects

Rate of Adrenal androgens

↑ or normal

Indicates global adrenal androgen activity, which can be aromatized to T2 then DHT

Rate of gonadal androgens

↑ or normal

Indicates global gonadal androgen activity

Genital androgens

↑

General endocrinometabolic tissular activity of gonadal androgens on tissues for structural purposes

Comparative genital androgeny

↑

The specific endocrinometabolic tissular activity of gonadal androgens on androgenrich tissue, such as the prostate, for structural purposes

TABLE 7.25  Thyrotropic index in edematous BPE Index

Value

Comment

Thyroid

Varies

When high, can participate in necrotic inflammation

Thyroid yield

Varies

When high, favors necrotic inflammation and somatotropic desynchronization with elevated free radicals

Global TRH of adaptation

↑ or normal

It expresses the relative metabolic activity of TRH in relationship to its endocrine function. The higher the index, the greater the TRH activity outside of stimulation of TSH

TRH/TSH

↑ or normal

High favors TRH, endocrine pancreas

Thyroid relaunching corrected

Varies

High, favors a stronger emotional component in relaunching TRH and releasing histamines

TABLE 7.26  Somatotropic indexes in edematous BPE Index

Value

Comment

Pelvic congestion

Low

Indicates pathologic congestion

Growth index or Growth index corrected

↑

Or both may be elevated

Necrosis

Varies

High: inflammatory type Normal/low: tends to occur with histaminic edema

Somatostatin

Varies

Favors a low index

Insulin

Varies

High: inflammation type Normal/low: normal/low: tends to occur with histaminic edema

Insulin resistance

Varies

Low: inflammatory type Normal/high: tends to occur with histaminic edema

Redox

Varies

High, favors more harmful free radical activity with cell fracture and inflammation

Pancreatic index

Varies

High: exocrine pancreas plays a greater role than that of the endocrine Low: endocrine pancreas plays a greater role than that of the exocrine

GH growth score

Varies

Low: inflammatory type Normal/high: tends to occur with histaminic edema

Expansivity index

Varies

It expresses the potential level of cellular growth in its structural metabolic adaptation function. In other words, how likely cells are to growth not from a programmatic need for expansion, but in response to an adaptation demand

158  The Theory of Endobiogeny

TABLE 7.27  Corticotropic and immunity indexes in edematous BPE Index

Value

Comment

Cortisol

Varies

High: inflammatory type and/or somatotropic desynchronization due to somatostatin inhibition and resulting harmful free radicals Normal or low: histamine-induced edema

Aldosterone

Varies

Often high; if low, comparative aldosterone index will typically be elevated

Evoked histamine

Varies

Tends to be low, especially with elevated cortisol and/or adrenal cortex activity

Platelet mobilization index

↓

Favors spasmophilia; leukocyte mobilization index may also be low, favors a more important role for splanchnic decongestion

Inflammation index

↑

It expresses the effective level of inflammatory activity of the organism of endogenous origin in its functional actuality. By extension it witnesses the threshold and gradient of inflammatory reactivity of the subject

Interleukin 1

Varies

High: favors more edema from hyperimmunity

TABLE 7.28  Symptomatic treatment of edematous BPE Medicinal plant

Antihist.

Antialler.

Agrimonia eupatoria

•

•

Arnica montana

•

•

↓ Alpha, beta

Delays insulin

Artemisia dracunculus

•

•

↓ Alpha and para

Estrogenic

Borago officinalis

•

Eucalyptus globulus

•

Lavandula angustifolia

•

Antiinflam.

•

Plantago major

•

Endocrine

↓ Para (indirect)

• •

•

•

•

Emunctory Drainage: hepatopancreatic (exocrine, endocrine), portal

(−) FSH > LH, (−) aldosterone

•

Melaleuca leucadendron Matricaria recutita

ANS

Kidney: diuretic Exocrine pancreas

↓ Alpha, beta, para

Drainage: pelvis

Antispasmodic, ↓ alpha and para

Estrogenic (mild)

Drainage: pelvis

↓ Alpha and para

(−) ACTH

Drainage: pelvic, splanchnic, hepatic

•

(−), inhibits; Aller., allergic; ANS, autonomic nervous system; Hist., histaminic; Inflam., inflammatory.

Drainage: hepatopancreatic (exocrine, endocrine)

Disorders of the prostate: Lower urinary tract obstruction and prostatitis Chapter | 7  159

TABLE 7.29  Treatment options based on thyrotropic index values for prostate adenoma Index

Value

Comment

TSH, serum

↓

Lycopus europaeus, Lithospermum officinale; if necrosis elevated: Zea mays GM or Cornus sanguinea GM

Thyroid

↑

Lycopus europaeus, Lithospermum officinale

Thyroid yield

↑

Lycopus europaeus, Lithospermum officinale; if serum TSH low and/or necrosis elevated: Zea mays GM or Cornus sanguinea GM

Global TRH of adaptation

↑

Fabiana imbricata or Leonurus cardiaca

TRH/TSH

↑

Fabiana imbricata or Leonurus cardiaca

TABLE 7.30  Treatment options based on somatotropic index values for prostate adenoma Index

Value

Comment

Pelvic congestion

↓

Hamamelis virginiana, Alchemilla vulgaris, Achillea millefolium, Lavandula angustifolia, and cf. Table 7.25

Growth index or Growth index corrected

↑

If androgens elevated: Urtica dioica root

Necrosis

↑

Zea mays GM or Cornus sanguinea GM

Insulin index

↑

Arnica montana; if free radicals elevated: Malva sylvestris

Insulin resistance

↓

Arnica montana; if free radicals elevated: Malva sylvestris + slow down TSH and/or cortisol

Redox

↑

Lavandula angustifolia, glutathione, alpha-lipoic acid

Pancreatic index

↑ or ↓

Dual pancreatropes: Juglans regia, Vinca minor, general pancreatic drainage: Rubus fruticosus GM

GH growth score

↓

Lamium album, inhibit alpha

TABLE 7.31  Corticotropic and immunity indexes in prostate adenoma Index

Value

Comment

Cortisol

↑

Sequoia gigantea if cortisol-to-adrenal gland ratio > 4, Passiflora incarnata, Lithium oligo if TSH low, Leonurus cardiaca, Eleutherococcus senticosus

Aldosterone

↑

Borago officinalis

Evoked histamine

↑

Hamamelis virginiana, Artemisia dracunculus, Matricaria recutita, Lavandula angustifolia

Platelet mobilization

↓

Menyanthes trifoliata, Cinnamomum zeylanicum, S-adenosyl methionine (SAMe)

Inflammation

↑

Menyanthes trifoliata, Curcumin longa, Cinnamomum zeylanicum, Lavandula angustifolia, and cf. Table 7.25

160  The Theory of Endobiogeny

Prescription for treatment of the inflammatory terrain of BPE with LUTO Lithium oligo: 1 ampule AM and afternoons. Somato-drainage: Malva sylvestris MT 40  mL, Menyanthes trifoliata MT 40 mL, Hamamelis virginiana MT 40 mL, Eucalyptus radiata EO 2 mL, Melaleuca leucadendron MT 1 mL, Dose: 4 mL 3 times per day. Neuroendocrine: Passiflora incarnata MT 30  mL, Ribes nigrum GM 30 mL, Menyanthes trifoliata MT 30 mL, Alchemilla vulgaris MT 30 mL, Lavandula angustifolia EO 2 mL, Dose: 4 mL 3 times per day.

Prescription for treatment of the allergic-terrain of BPE with LUTO Allergy-drainage: Agrimonia eupatoria MT 40 mL, Viola tricolor MT 40 mL, Hamamelis virginiana MT 40 mL, Eucalyptus radiata EO 2 mL, Melaleuca leucadendron MT 1 mL, Dose: 4 mL 3 times per day. Neuroendocrine: Passiflora incarnata MT 30  mL, Eleutherococcu senticosus MT 30 mL, Menyanthes trifoliata MT 30 mL, Urtica dioica root and leaf MT 30 mL, Lavandula angustifolia EO 2 mL, Dose: 4 mL 3 times per day.

Conclusions BPE is a condition that arises in the face of a hyperandrogenism. When it occurs in an adenomatous terrain, the enlargement of the prostate is due to a benign hyperplasia of the prostatic tissue. When it occurs due to inflammatory, histaminic/allergic, or hyperaldosteronism, it is related to edema of within the cell or in the tissular space. In either case, the enlargement of the prostate results in LUTO. The importance of the Endobiogenic nosologic classification is that it allows for a more precise selection of therapeutic based on the pathophysiology involved.

is not sufficient in many cases as a sole therapy. Men are subject to recurrent, relapsing episodes if the terrain is not addressed.

Pathophysiology According to the theory of endobiogeny, the ANS and endocrine precritical terrain of prostatitis is similar to what has been discussed in BPE. Particular to prostatitis are factors that favor the following series of events: congestion → stasis → inflammation → translocation or ascension of microorganisms → infection. According to the theory of endobiogeny, metabolic factors of structure, structuro-functional, and functional activity are capital. Anatomical factors can also play a role (Tables 7.32 and 7.33). What makes chronic prostatitis challenging to treat is that the elements of the terrain that favor it create a relative isolation of the gland from systemic circulation.

TABLE 7.32  Metabolic structuro-functional and functional elements of terrain favoring prostatitis Element

Factor

Consequence

Nutritional congestion: pelvis, prostate

↑ πΣ

Hyperemia → distention of tissues, compression: lymphatics, venous outflow

Vascular congestion: pelvis, prostate

↑ αΣ

Delayed egress of blood → edema, compression: lymphatics, venous outflow

Mucosal congestion: urinary bladder, urethra, descending colon

↑ FSH, ↑ αΣ

Stasis, favors bacterial overgrowth

Inflammation

↑ Thyrotropic ↑ Insulin ↑ Cortisol

Capillary/lymphatic leak → translocation of microbial agents

Prostatitis Introduction Prostatitis is an infection and/or inflammation of the prostate gland. It can be acute or chronic in nature. Prostatitis primarily affects the transition and peripheral zones (Table 7.1, Fig. 7.6). Chronic prostatitis can be challenging to treat due to the prominence of pelvic congestion in the precritical and critical terrains. Most cases are chronic and asymptomatic. Only a fraction of men will be properly referred, diagnosed, and treated. Most men die with and not because of p­ rostatitis. The majority of recognized cases of chronic p­ rostatitis involve chronic pelvic pain.53 Thus, treatment of acute prostatitis should be prompt and aggressive to avoid evolution to chronic prostatitis. Both acute and chronic prostatitis will require treatment of the terrain, especially in chronic cases. Chronic oral antibiotic therapy

TABLE 7.33  Anatomic structural and functional elements of terrain favoring prostatitis Category

Example

Structuro-functional

Urinary bladder voiding dysfunction Bladder neck obstruction Ejaculatory duct obstruction Pelvic side wall tension

Immune compromise

HIV, iatrogenic (radiation therapy, chemotherapy, postsurgical)

Disorders of the prostate: Lower urinary tract obstruction and prostatitis Chapter | 7  161

Microbial agents Bacteria cause the majority of cases of prostatitis. The majority of bacterial infections are caused by Gram-negative bacteria.53, 54 They can be transmitted by sexual activity, or translocation for the colon or urinary bladder of the man himself. The presence of viruses such as cytomegalovirus (CMV), fungi, or rare organisms should raise suspicion for immunocompromised status, such as HIV, or autoimmune disorders such as Wegener’s granulomatosis53 1. Escherichia coli 2. Enterococcus ssp. 3. Pseudomonas ssp. 4. Chlamydia trachomatis 5. Ureaplasma ssp. 6. Trichomonas vaginalis

Presenting symptoms: Acute prostatitis Men with acute prostatitis can present with typical infectious symptoms that are systemic or local in nature. They can also present with symptoms related to immunologic complexes lodging in joints or muscles. The symptoms can be similar to those associated with urinary tract infections. 1. Loco-regional a. Perineal pain b. Prostatic pain c. Dysuria d. LUTO 2. Regional a. Low back pain b. Low abdominal pain 3. Systemic, infectious a. Fever b. Chills c. Malaise 4. Systemic, immune a. Arthralgias b. Myalgias

Presenting symptoms: Chronic prostatitis Chronic prostatitis can be more complex to diagnose. There are three courses: asymptomatic, intermittent, and painpredominant. In the latter two, the symptoms are generally local or regional in nature. 1. Asymptomatic: incidental diagnosis or on autopsy 2. Intermittent symptoms a. Dysuria b. LUTO c. Urinary tract infections 3. Pelvic pain predominance

a. Pelvic pain: any area for a duration of 3 or more months out of 6 months i. Urethral ii. Testicular iii. Scrotal iv. Rectal v. Perineal vi. Suprapubic vii. Coccygeal b. Negative urine cultures c. LUTO d. Ejaculatory pain e. Erectile dysfunction

Physical examination Acutely, the prostate may feel hot and boggy on digital rectal palpation. In chronic cases, it may be asymptomatic, or nodular and tender to palpation. Localized pain may be present in the pelvic pain predominant type.

Evaluation Acutely, history and exam are the most pertinent, along with a urinalysis and urine culture. In chronic cases, a work up similar to BPE may be instituted.53

Treatment of prostatitis: Role of antibiotics There are four classes of antibiotics that can be helpful in treating prostatitis53, 55, 56: 1. Fluoroquinolones: ciprofloxacin 2. Third-generation cephalosporins: ceftriaxone 3. Tetracyclines: doxycycline 4. Folate synthesis inhibitors: trimethoprim/sulfamethoxazole From an Endobiogenic perspective, the indications for use of antibiotics are three: 1. Severity of acute infection 2. Chronic terrain not sufficiently responsive to medicinal plant therapy 3. Immunocompromised status For acute cases, antibiotic use is generally recommended for 2–4 weeks.53, 55 For chronic cases, it is recommended for 4–6 weeks. In any case, if antibiotics are used, it is best to use them with an Endobiogenic treatment that is symptomatic as well as well oriented to treating the terrain. Antibiotics in conjunction with alpha-blockade is superior to antibiotics alone in alleviating symptoms and reducing frequency of recurrence.57 In more severe cases of urinary dysfunction, there can be a role for combination therapy for the first 2  weeks of treatment in conjunction with an Endobiogenic approach.

162  The Theory of Endobiogeny

Treatment of prostatitis: Endobiogenic approach

TABLE 7.34  Polyvalent essential oils in the treatment of prostatitis

There are three principles to local therapy, regional therapy, and systemic therapy.

Local therapy: Rectal Rectal administration of therapies is a highly efficient treatment approach. It allows for diffusion of a high concentration of therapeutic elements, avoiding first-pass hepatic metabolism and dilution through global circulation and distribution. Consider the following: Oral The prostate receives less than 1% of total blood flow, but let us assume it is 1%. You make a tincture with 5 mL (4000 mg) essential oil per 250 mL. At a dose of 5 mL, the patient receives 80 mg EO. Assume the liver metabolizes 50% of the EO. This leaves 40 mg. Of the 40 mg remaining, 1% is distributed to the prostate, or 0.4 mg from a starting concentration of 80 mg. Rectal Now consider a rectal infusion in which 0.75 mL (600 mg) of essential oil are mixed with 1 tbsp (15 mL) of carrier oil. This is a 10% concentration. Let us assume that 15% diffuses through the rectosigmoid colon to the prostate. The patient receives 90 mg of EO vs 0.4 mg from oral dosing. There are two common methods of rectal administration of therapies. The first is as an infusion of a small ­volume of liquid, as in the example above. The second is as a suppository. Essential oils can be mixed with a lipid-based carrier (oil, shea butter, etc.). Concentrated extracts, such as fluid extracts can also be used. Depending on the terrain of the patient, the severity of infection and the essential oils used, the concentration can vary from 5% to 20%. Table 7.34 lists essential oils with good antimicrobial and genital tropisms. Values in percentage are listed for the individual essential oil.

Formula for rectal suppository for prostatitis

Apply twice per day for 6 weeks, then nightly for 20 weeks

Range (%)

Other benefits

Lavandula angustifolia

1–20

Pelvic decongestant, sympatholytic, antalgic

Melaleuca leucadendron

1–10

Pelvic decongestant, genital antimicrobial tropism, antispasmodic

Thymus vulgaris, ct. linalool

1–5

Gram negative, parasympatholytic

Achillea millefolium

1–10

Pelvic decongestant, competes for 5-alpha reductase activity, antiinflammatory, cicatrizing

Juniperus communis

1–4

Urinary antiseptic, diuretic

Syzygium aromaticum

0.5–2

Antispasmodic, analgesic, broad spectrum antimicrobial with antifungal action

Prescription for acute prostatitis Month 1 ● ●

● ●

Mg oligo 1 dose BID Cu-Ag-Au 1 dose QID × 1 week, then TID × 1 week, then BID × 2 weeks Rectal suppository 1 BID Pelvic drainage, antimicrobial: Ribes nigrum GM 60 mL, Achillea millefolium MT 60 mL, Matricaria recutita MT 60 mL, Hamamelis virginiana MT 60 mL + Melaleuca leucadendron EO 3 mL, Lavender EO 2 mL: 4 mL BID Month 2–3

● ●

In a base of shea butter: Melaleuca leucadendron EO 5% Lavandula angustifolia EO 5% Achillea millefolium EO 3% Syzygium aromaticum EO 0.5%

Essential oil

●

Rectal suppository 1 nightly Pelvic drainage, antimicrobial: Ribes nigrum GM 60 mL, Achillea millefolium MT 60 mL, Matricaria recutita MT 60 mL, Hamamelis virginiana MT 60 mL + Melaleuca leucadendron EO 3 mL, Lavandula angustifolia EO 2 mL: 4 mL BID Terrain:Lithospermum officinale MT 60 mL, Medicago sativa MT 60 mL, Salvia sclarea MT 60 mL, Achillea millefolium MT 60 mL: 4 mL BID

Oral treatments for prostatitis

Conclusions

Oral treatments are similar to what was discussed for prostatic adenoma, focusing more on pelvic drainage and support of the immune system.

Chronic prostatitis is an often-silent affliction in men. The indication for treatment is treatment of symptomatic disease or treatment of asymptomatic disease in

Disorders of the prostate: Lower urinary tract obstruction and prostatitis Chapter | 7  163

i­mmunocompromised men. The treatment approach may involve antibiotics, especially for the first episode of acute infection. However, recurrent disease may occur, in which case, an Endobiogenic treatment that is symptomatic, antiinfectious, and addresses elements of the critical terrain may prove helpful.

18. 19.

20.

21.

References 1. Kim B, Kawashima A, AJ LR. Imaging of the male urethra. Semin Ultrasound CT MR. 2007;28(4):258–273. 2. Abdelsayed  GA, Danial  T, Kaswick  JA, Finley  DS. Tumors of the anterior prostate: implications for diagnosis and treatment. Urology. 2015;85(6):1224–1228. 3. Dolan MF, Melnitsky H, Margulis L, Kolnicki R. Motility proteins and the origin of the nucleus. Anat Rec. 2002;268(3):290–301. 4. Gutman E, Sproul E, Gutman A. Significance of increased phosphatase activity at the site of osteoplastic metastases secondary to carcinoma of the prostate gland. Am J Cancer. 1936;28:485–495. 5. Muniyan S, Chaturvedi NK, Dwyer JG, Lagrange CA, Chaney WG, Lin MF. Human prostatic acid phosphatase: structure, function and regulation. Int J Mol Sci. 2013;14(5):10438–10464. 6. Henttu  P, Vihko  P. Growth factor regulation of gene expression in the human prostatic carcinoma cell line LNCaP. Cancer Res. 1993;53(5):1051–1058. 7. Rao  AR, Motiwala  HG, Karim  OM. The discovery of prostate-­ specific antigen. BJU Int. 2008;101(1):5–10. 8. Heinlein  CA, Chang  C. The roles of androgen receptors and ­androgen-binding proteins in nongenomic androgen actions. Mol Endocrinol. 2002;16(10):2181–2187. 9. Prasad AS. Zinc deficiency in human subjects. Prog Clin Biol Res. 1983;129:1–33. 10. Dutkiewicz S. Zinc and magnesium serum levels in patients with benign prostatic hyperplasia (BPH) before and after prazosin therapy. Mater Med Pol. 1995;27(1):15–17. 11. Chadha  KC, Nair  BB, Chakravarthi  S, et  al. Enzymatic activity of free-prostate-specific antigen (f-PSA) is not required for some of its physiological activities. Prostate. 2011;71(15):1680–1690. 12. Darago  A, Sapota  A, Matych  J, Nasiadek  M, SkrzypinskaGawrysiak  M, Kilanowicz  A. The correlation between zinc and ­insulin-like growth factor 1 (IGF-1), its binding protein (IGFBP-3) and prostate-specific antigen (PSA) in prostate cancer. Clin Chem Lab Med. 2011;49(10):1699–1705. 13. Djavan B, Bursa B, Seitz C, et al. Insulin-like growth factor 1 (IGF1), IGF-1 density, and IGF-1/PSA ratio for prostate cancer detection. Urology. 1999;54(4):603–606. 14. Lehrer S, Diamond EJ, Stagger S, Stone NN, Stock RG. Serum insulin level, disease stage, prostate specific antigen (PSA) and Gleason score in prostate cancer. Br J Cancer. 2002;87(7):726–728. 15. Pollak  M, Beamer  W, Zhang  JC. Insulin-like growth factors and prostate cancer. Cancer Metastasis Rev. 1998;17(4):383–390. 16. Nadler RB, Humphrey PA, Smith DS, Catalona WJ, Ratliff TL. Effect of inflammation and benign prostatic hyperplasia on elevated serum prostate specific antigen levels. J Urol. 1995;154(2 Pt 1):407–413. 17. Jones RE, Lopez KH. The male reproductive system. In: Jones RE, Lopez  KH, eds. Human Reproductive Biology. 3rd ed.Amsterdam; Boston: Elsevier Academic Press; 2006. xviii, 604 p. [chapter 4].

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Ho CK, Habib FK. Estrogen and androgen signaling in the pathogenesis of BPH. Nat Rev Urol. 2011;8(1):29–41. Jones  RE, Lopez  KH. Sexual differentiation. In: Jones  RE, Lopez  KH, eds. Human Reproductive Biology. 3rd ed.Amsterdam; Boston: Elsevier Academic Press; 2006. xviii, 604 p. [chapter 5]. Alawamlh OAH, Goueli R, Lee RK. Lower Urinary Tract Symptoms, Benign Prostatic Hyperplasia, and Urinary Retention. Med Clin North Am. 2018;102(2):301–311. Ugge H, Udumyan R, Carlsson J, et al. Acne in late adolescence and risk of prostate cancer. Int J Cancer. 2018;142(8):1580–1585. Sutcliffe S, Giovannucci E, Isaacs WB, Willett WC, Platz EA. Acne and risk of prostate cancer. Int J Cancer. 2007;121(12):2688–2692. Snyder PJ. Male reproductive aging. In: Yen and Jaffe’s Reproductive Endocrinology. 8th ed.Elsevier; 2019 [chapter 15]. Toft G. Persistent organochlorine pollutants and human reproductive health. Dan Med J. 2014;61(11):B4967. Lewis  JG, Mopert  B, Shand  BI, et  al. Plasma variation of ­corticosteroid-binding globulin and sex hormone-binding globulin. Horm Metab Res. 2006;38(4):241–245. Nussey  S, Whitehead  S. Endocrinology: An Integrated Approach. Oxford: BIOS Scientific Publishers; 2001. Labrie  F, Labrie  C. DHEA and intracrinology at menopause, a positive choice for evolution of the human species. Climacteric. 2013;16(2):205–213. Labrie F, Luu-The V, Labrie C, Simard J. DHEA and its transformation into androgens and estrogens in peripheral target tissues: intracrinology. Front Neuroendocrinol. 2001;22(3):185–212. Samaras N, Samaras D, Frangos E, Forster A, Philippe J. A review of age-related dehydroepiandrosterone decline and its association with well-known geriatric syndromes: is treatment beneficial? Rejuvenation Res. 2013;16(4):285–294. Malde S, Nambiar AK, Umbach R, et al. Systematic review of the performance of noninvasive tests in diagnosing bladder outlet obstruction in men with lower urinary tract symptoms. Eur Urol. 2017;71(3):391–402. Hieble  JP. Therapeutic strategies for benign prostatic hypertrophy. Drug Discov Today. 2004;1(2):243–248. Emberton  M, Cornel  EB, Bassi  PF, Fourcade  RO, Gomez  JM, Castro  R. Benign prostatic hyperplasia as a progressive disease: a guide to the risk factors and options for medical management. Int J Clin Pract. 2008;62(7):1076–1086. Andersen  JT, Nickel  JC, Marshall  VR, Schulman  CC, Boyle  P. Finasteride significantly reduces acute urinary retention and need for surgery in patients with symptomatic benign prostatic hyperplasia. Urology. 1997;49(6):839–845. McConnell JD, Bruskewitz R, Walsh P, et al. The effect of finasteride on the risk of acute urinary retention and the need for surgical treatment among men with benign prostatic hyperplasia. Finasteride Long-Term Efficacy and Safety Study Group. N Engl J Med. 1998;338(9):557–563. Dong  Y, Hao  L, Shi  Z, Wang  G, Zhang  Z, Han  C. Efficacy and safety of tadalafil monotherapy for lower urinary tract symptoms secondary to benign prostatic hyperplasia: a meta-analysis. Urol Int. 2013;91(1):10–18. Kuduk-Jaworska  J, Szpunar  J, Gasiorowski  K, Brokos  B. Immunomodulating polysaccharide fractions of Menyanthes trifoliata L. Z Naturforsch C. 2004;59(7-8):485–493. Huang C, Tunon H, Bohlin L. Anti-inflammatory compounds isolated from Menyanthes trifoliata L. Yao Xue Xue Bao. 1995;30(8):621–626.

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Lindholm P, Gullbo J, Claeson P, et al. Selective cytotoxicity evaluation in anticancer drug screening of fractionated plant extracts. J Biomol Screen. 2002;7(4):333–340. Bora KS, Sharma A. Phytochemical and pharmacological potential of Medicago sativa: a review. Pharm Biol. 2010;49(2):211–220. Chen TS, Liou SY, Chang YL. Antioxidant evaluation of three adaptogen extracts. Am J Chin Med. 2008;36(6):1209–1217. Davydov  M, Krikorian  AD. Eleutherococcus senticosus (Rupr. & Maxim.) Maxim. (Araliaceae) as an adaptogen: a closer look. J Ethnopharmacol. 2000;72(3):345–393. Pearce  PT, Zois  I, Wynne  KN, Funder  JW. Panax ginseng and Eleuthrococcus senticosus extracts—in  vitro studies on binding to steroid receptors. Endocrinol Jpn. 1982;29(5):567–573. Nahata A, Dixit VK. Ameliorative effects of stinging nettle (Urtica dioica) on testosterone-induced prostatic hyperplasia in rats. Andrologia. 2011;44(suppl 1):396–409. Durak  I, Biri  H, Devrim  E, Sozen  S, Avci  A. Aqueous extract of Urtica dioica makes significant inhibition on adenosine deaminase activity in prostate tissue from patients with prostate cancer. Cancer Biol Ther. 2004;3(9):855–857. Kayser K, Bubenzer J, Kayser G, et al. Expression of lectin, interleukin-2 and histopathologic blood group binding sites in prostate cancer and its correlation with integrated optical density and syntactic structure analysis. Anal Quant Cytol Histol. 1995;17(2):135–142. Konrad L, Muller HH, Lenz C, Laubinger H, Aumuller G, Lichius JJ. Antiproliferative effect on human prostate cancer cells by a stinging nettle root (Urtica dioica) extract. Planta Med. 2000;66(1):44–47. Lichius JJ, Lenz C, Lindemann P, Muller HH, Aumuller G, Konrad L. Antiproliferative effect of a polysaccharide fraction of a 20% metha-

nolic extract of stinging nettle roots upon epithelial cells of the human prostate (LNCaP). Pharmazie. 1999;54(10):768–771. 48. Sokeland J. Combined sabal and urtica extract compared with finasteride in men with benign prostatic hyperplasia: analysis of prostate volume and therapeutic outcome. BJU Int. 2000;86(4):439–442. 49. Legssyer  A, Ziyyat  A, Mekhfi  H, et  al. Cardiovascular effects of Urtica dioica L. in isolated rat heart and aorta. Phytother Res. 2002;16(6):503–507. 50. Testai L, Chericoni S, Calderone V, et al. Cardiovascular effects of Urtica dioica L. (Urticaceae) roots extracts: in vitro and in vivo pharmacological studies. J Ethnopharmacol. 2002;81(1):105–109. 51. Chung ASJ, Woo HH. Update on minimally invasive surgery and benign prostatic hyperplasia. Asian J Urol. 2018;5(1):22–27. 52. Parsons  ME, Ganellin  CR. Histamine and its receptors. Br J Pharmacol. 2006;147(suppl 1):S127–S135. 53. Khan  FU, Ihsan  AU, Khan  HU, et  al. Comprehensive overview of prostatitis. Biomed Pharmacother. 2017;94:1064–1076. 54. Kim  SH, Ha  US, Yoon  BI, et  al. Microbiological and clinical characteristics in acute bacterial prostatitis according to lower urinary tract manipulation procedure. J Infect Chemother. 2014;20(1):38–42. 5 5. Fowler Jr. JE. Antimicrobial therapy for bacterial and nonbacterial prostatitis. Urology. 2002;60(6 suppl):24–26. discussion 26. 5 6. Perletti G, Marras E, Wagenlehner FM, Magri V. Antimicrobial therapy for chronic bacterial prostatitis. Cochrane Database Syst Rev. 2013;(8):CD009071. 5 7. Barbalias  GA, Nikiforidis  G, Liatsikos  EN. Alpha-blockers for the treatment of chronic prostatitis in combination with antibiotics. J Urol. 1998;159(3):883–887.

Chapter 8

Acne: Disorder of luteal androgen management Introduction Acne is the most common skin disorder, affecting 80% of the population at least once in their life, with 20% having severe acne.1 While acne is a superficial disorder, it is not a superficial concern. The acne terrain of adolescences is associated with a later onset of menarche due to hyperandrogenism.2 The acne terrain is one that may return during genital recycling: 38–42, then 48–52, etc.3 In these periods of life, the patient may be at increased risk of disorders such as cystic breasts, polycystic ovaries, and uterine fibroids in women.3–6 And in men, there is a risk of prostatic adenoma. All these disorders share the commonality of dysregulated androgenism.7 The reproductive organs and skin are among the compartments with greatest androgen activity.8–10 According to the theory of endobiogeny, acne is an expression of a luteal imbalance on the envelope of the organism rooted in gonadal androgen insufficiency. In other words, there is a relative or absolute insufficiency of gonadal androgens (i.e., testosterone or dihydrotestosterone (DHT)) relative to the intensity or duration of demand by luteinizing hormone (LH). When it occurs in a particular precritical terrain, acne occurs. What has been taught to be the “cause” of acne: genetic factors,11 bacterial overgrowth, sebum production, etc.12 are downstream mechanisms of the upstream imbalance of the precritical and critical terrains. Thus, the goal of treatment is not to serve as Venus’s handmaiden in the vanity fair of life and make acne lesions “go away.” Rather, the Endobiogenist considers acne as a global disorder expressed locally on the skin that requires equilibration based on past imbalances and future risk of disorders.

Acne definitions The term acne refers to a dermatologic condition that involves comedones, papules, pustules, and/or cystic lesions. A hair follicle is a pilosebaceous exocrine gland. Thus, it has a channel that allows for its exocrine product (sebum) to be excreted onto the skin. The Theory of Endobiogeny. https://doi.org/10.1016/B978-0-12-816964-3.00008-0 © 2019 Elsevier Inc. All rights reserved.

A comedo (plural: comedone) is a clogged hair follicle (Fig. 8.1). An open comedone is referred to as a black head, in which the hair follicle is partially clogged. The sebum is oxidized and turns black. A closed comedone is a white head. It is a completely obstructed follicle. A papule is a closed, erythematous, and inflammatory nodule. A pustule is a closed lesion containing pus. A pustulopapule: erythematous, inflammatory pustular lesion. Finally, a cystic nodule is a cystic lesion that is firm and painful to touch.13

Acne severity Acne severity can be divided into three grades: mild, moderate, and severe. Mild acne involves comedones with minimal papulopustules. Moderate acne involves comedones and a moderate number of inflammatory papules with pustules. Severe acne involves the presence of nodulocystic lesions: comedones, inflammatory lesions, large nodules, and/or scarring.13

Acne classification Acne classification is again divided into three grades: vulgaris, fulminans, and conglobate. Acne vulgaris is noninflammatory, open or closed comedones with inflammatory papules, pustules, and/or nodules. It affects areas with the densest population of sebaceous follicles (e.g., face, upper chest, back). Local symptoms include pain and tenderness. Acne fulminans is acne vulgaris with fever. Acne conglobate is severe acne with multiple comedones, and tends to heal with disfiguring scars.13

Review: Skin physiology The skin is the envelope of the organism. It consists of three layers from outer to inner layers: epidermis, dermis, and hypodermis. The epidermis is of ectodermal origin and is therefore most influenced by the thyrotropic axis. The inner two layers, the dermis and hypodermis, are of mesodermal origin, and are most influenced by the gonadotropic axis 165

166  The Theory of Endobiogeny

stool. The skin is solicited as a second rank emunctory to excrete the waste products. The result of oversolicitation of the exocrine pancreas is increased uptake of nutrients, especially proteins (Fig. 8.3). During the critical response, this oversupply of nutrients will be focused on the skin, supporting a hypermetabolism of the skin. NB: The emunctory congestion of the skin (precritical terrain) arises before the hypermetabolism (critical terrain).

Provoking event: Peripheral luteal insufficiency

FIG.  8.1  Normal skin pore, white heads, and blackheads. See text for details. (Reproduced from Medical gallery of Blausen Medical 2014. WikiJ Med 2014;1(2). https://doi.org/10.15347/wjm/2014.010).

(Table 8.1 and Fig. 8.2). According to the theory of endobiogeny, the skin is the first brain, a metamembrane, or envelope of the organism. It is rich neuroendocrine receptors as well as local production of these factors.14, 15 Thus, the skin is a semiautonomous organ that is submitted to global and regional functioning of the terrain.

Pathophysiology According to the theory of endobiogeny, acne is a disorder in which the skin is oversolicited as a metabolic organ and congested as an emunctory.

Precritical terrain: Emunctories The precritical terrain is a hypervagotonic state, often in vagotonic patients. There is simultaneous congestion of the following emunctories as a result: (1) liver, (2) exocrine pancreas,16 and (3) colon.17, 18 The result of congestion of the liver and colon is a reduction of toxin excretion in the

According to the theory of Endobiogeny, the provoking event in most cases of acne is an insufficiency of peripheral luteal hormones: gonadal androgens or progesterone. In the case of neonatal acne, it may be for three reasons: (1) luteal insufficiency, (2) iatrogenic from maternal progesterone therapy, and (3) excessive postnatal DHEA production before the onset of degonadicization of the adrenal cortex (cf. below).

Critical terrain: Endocrine The critical terrain of acne is one that results in excessive androgens at the level of the skin.19 While androgens are clearly associated with acne from the perspective of the standard biomedical approach, quantitative serum excess has not been consistently found.2, 6 As we have discussed in The Theory of Endobiogeny, Volume 1, Chapters  6–9, serum blood levels of hormones cannot be a reliable due to polymorphisms in receptor density, subtypes, nuclear response elements, intracrinologic conversion, etc.19–31 The location of acne on the face, other signs, symptoms and personality traits related to luteal excess (premenstrual breast enlargement, enjoyment of aerobic sports, competitive spirit, etc.), and the biology of functions (cf. case study) may prove more beneficial in evaluating the functional level of expressed luteal activity in the patient. There are three possible responses to the initial insufficiency or deficiency of peripheral luteal hormones:

TABLE 8.1  Epidemiology of acne Class

Acne type

Frequency

Prevalence

Pathophysiology according to theory of endobiogeny

Structurofunctional

Adolescent

70%–80%

M > F

Gonadal androgen insufficiency

Adult genital recycling

5%–10%

F > M

Alteration in central-peripheral gonadal dynamic

Adaptive

Neonatal

5%–10%

M > F

Maternal hyper-LH: endogenous or exogenous (i.e., progesterone therapy)

Adult adaptive

Varies

Varies

Varies. Inductors include luteal phase of menstrual cycle, changing of seasons, weather changes, emotional stressors

Acne: Disorder of luteal androgen management Chapter | 8  167

FIG.  8.2  Layers of the skin with embryologic and endocrine relationships. See text for details. (Modified and reproduced from Medical gallery of Blausen Medical 2014. WikiJ Med 2014;1(2). https://doi.org/10.15347/wjm/2014.010).

FIG. 8.3  Precritical terrain of acne according to the theory of Endobiogeny. See text for details. (© 2015 Systems Biology Research Group.)

(1) overcorrection of the perceived level of gonadal androgen activity, (2) adrenal androgen compensation, and (3) a combination of the two. In the first case, LH may be hyperfunctioning in its response (Chapter 7). A perceived insufficiency is a relative insufficiency. This

means that there is sufficient peripheral luteal output, but it does not match the level, intensity or duration of LH demand. This can be due to upstream vertical stimulation of GnRH, such as a hyperfunctioning prolactin.32 Or, it can be due to radial TRH stimulation. A third reason

168  The Theory of Endobiogeny

would be horizontal central stimulation of ACTH to FSH then LH.33 It can also be due to peripheral radial estrogen relaunching of LH by estrogens, according to the theory of Endobiogeny. In the second case, there is an appeal made to the adrenal cortex for increased production of adrenal androgens, such as DHEA. Once DHEA is excreted, it can be converted to gonadal androgens within tissues that signal their requirement for it.7, 34, 35 The anabolic adrenal androgen activity is greater than permissive cortisol activity, resulting in impaired antiinflammatory action from cortisol (Fig. 8.4).33 In either case: prolonged or excessive LH demand proliferates androgen receptors, making the organism more sensitive to the effects of androgens. In this terrain, the demand for luteal hormones is partially met by the adrenal cortex in the form of adrenal androgens: DHEA and androstenedione. These androgens do not inhibit LH, but can be converted within cells to testosterone and/or DHT. Thus, LH continues to rise. The consequence of this dysregulated androgenism is an augmentation of the rate of sebum secretion (within the gland). This is a necessary but not sufficient step for the development of acne. The evidence for this terrain is found in the epidemiology of acne.2, 3, 13, 36 There are two types of acne: transient and persistent. Persistent, recurring acne reflects a dysregulation

of the structuro-functional role of progesterone and/or gonadal androgens. This is the acne that occurs in adolescents or adults. In the biology of functions, one should evaluate the structural values of the indexes. Transient acne is acne of adaptation, thus they are functional in nature. They reflect the challenge that the organism faces in adapting peripheral luteal products during these states (Table  8.1).13, 37, 38 For example, neonates on average have the same density of sebum on their skin at birth as late adolescents and adults. The levels start to decline and reach their nadir around 6 months of age until the onset of puberty.37 The origin of the adrenal androgens is presumed to be intracrinologic conversion of DHEA within the skin of infants, as DHEA levels are elevated at birth and then decline.19 This is referred to in the theory of Endobiogeny as postnatal degonadicization of the adrenal cortex early in life (cf. The Theory of Endobiogeny, Volume 1, Chapter 13). Of course, not all infants have acne despite these elevated levels of sebum. The precritical terrain must be already installed for acne to occur. The sex distribution of nonneonatal acne also supports the Endobiogenic theory as well. In adolescence, the incidence of acne occurs more frequently in males than females.39 In males, acne arises primarily due to an insufficiency of gonadal androgens: testosterone and/or DHT. Due to sexual dimorphism of physiology, three aspects of male physiology favor acne arising for gonadal androgen insufficiency: (1) greater demand for gonadal androgens in men than women, (2) greater capacity for adrenal androgen production, and (3) less estrogens than women. Conversely, in adulthood, acne in women occurs in a ratio of 2.5:1 vs men.3, 39 In women, acne arises primarily from a relative or absolute insufficiency of progesterone, such as occurrence of premenstrual and catamenial acne,38 or it may be a more chronic structuro-functional disorder.

Exacerbating factors: Neuroendocrine Gonadotropic

FIG. 8.4  Critical terrain of acne according to the theory of Endobiogeny. An insufficiency of luteal products (center) requires an adjustment of their activity. One way is intense solicitation by LH (solid black arrows). Regardless of response, there is a proliferation of androgen receptors (bottom right). If there is insufficient feedback (center, broken blue arrow), there will be a quantitative excess of gonadal androgens. An alternate pathway of response to insufficient luteal products is an appeal to DHEA (center left, broken orange arrow). DHEA has direct action on androgen receptors (solid black arrow) or can be aromatized in the periphery to gonadal androgens (dot and dash black arrow). DHEA does not offer feedback on LH nor is it inhibited by luteal products, hence the risk of dysregulated androgens once again. See text for details. (© 2015 Systems Biology Research Group.)

The hyper LH solicits a relaunching of FSH to meet the level of solicitation of LH. In the acne terrain, we observe two relationships and several downstream events. The first is that there is a hyperfunctioning FSH that far exceeds the level of response of estrogens. This results in excess sebum excretion and a congestion of tissue, in this case the skin. However, estrogen activity is not deficient. It is typically elevated, but insufficient relative to the FSH demands. This favors a hypermetabolic state that favors anabolism. The second is that androgen activity regardless of origin (adrenal or gonadal) exceeds the level of estrogen activity.33 Thus, while there is a hyperanabolic state, protein management is not well organized. It is this aspect of the terrain that is shared with uterine fibroids, according to the theory of Endobiogeny. Finally, there is an inability to regulate androgens. The androgens solicit the skin to produce sebum in

Acne: Disorder of luteal androgen management Chapter | 8  169

excess of local requirements.10, 40 This excess source of fat is fuel for beta-oxidation for ATP production and structural material for bacteria. The overgrowth of bacteria is related to the mechanism of acne.40, 41

Corticotropic As noted earlier, the adrenal cortex is solicited to produce adrenal androgens.2, 6, 10, 33 This demand shifts metabolism of pregnenolone from cortisol to adrenal androgens, which are then aromatized in the periphery to androgens (or estrogens) by intracrinologic mechanisms within specific tissues and cells according to their individual demands (Fig.  8.5). This method is not subject to central

­regulation.34 The insufficiency of cortisol relative to adrenal androgens compromises the ability of the organism to regulate inflammation at the level of the skin, which is solicited from somatotropic dysfunction.33 The insufficiency may be relative, such as when one sees in the biology of functions elevated cortisol activity (cortisol index), which is adaptive in nature, not permissive (adaptation permissivity index), and favors an inflammatory terrain (pro-­ inflammatory index).

Thyrotropic Comedones involve the clogging of follicular pore by keratinocytes (proteinaceous substances) as well as sebum (fatty

FIG.  8.5  Metabolism of adrenal cortex steroids. All adrenal cortex steroids are derived from cholesterol, which is converted to pregnenolone. Pregnenolone, based on the activation of certain enzymes, can either follow the pathway that leads to corticosteroids, mineralocorticoids, adrenal androgens, or adrenal estrogens. In the acne terrain, there is relatively less 21-hydroxylase activity in relationship to that of 17α-hydroxylase and 3-βdehydrogenase. In the case of the latter enzymes, adrenal androgens are favored over cortisol. (Modified and reproduced from Diagram of the pathways of human steroidogenesis. WikiJ Med 2014;1(1). https://doi.org/10.15347/wjm/2014.005. via Wikimedia Commons.)

170  The Theory of Endobiogeny

substances). The rate of turnover of keratinocytes in the epidermis requires a hypermetabolic state rooted in a dysregulation of the thyrotropic axis, which covers this layer of the skin. The hyperfunctioning LH relaunches TSH by horizontal stimulation to readapt T4 activity for the regulation of androgens through testosterone-binding globulin. Thus, we find hyper TSH activity favoring: (1) cell membrane expansion, (2) increased estrogen sensitivity, and (3) exocrine pancreas solicitation. There is also T4 insufficiency, which results in reduced binding of androgens to sex hormonebinding globulin (SHBG).42

Somatotropic The entire somatotropic axis is oversolicited in the acne terrain. The skin of patients with acne show elevated ­insulin-like growth factor-1 (IGF-1) expression (the result of growth hormone stimulation) and insulin resistance.40 IGF-1 upregulates mTOR to promote intracellular anabolism, especially in the face of elevated amounts of branch chain amino acids.43 They also regulate lipid metabolism.41 Serum prolactin levels are sometimes noted to be elevated.44 From the perspective of Endobiogeny, the presence of pus in acne is itself indicative of a certain level of prolactin activity. The various mechanisms of somatotropic disturbance are presented in Table 8.2.

ANS In the face of a hyperparasympathetic state, there is a reactive alpha sympathetic that plays a role in local and global phenomenon. Locally, it can install local vasomotor

TABLE 8.2  Summary of somatotropic factors related to acne Antecedent

Result

Consequence

Radial • Insufficient cortisol

↑ GH

Insulin resistance Hyperinsulinism • GH > insulin: lipid metabolism: sebum

• Estrogen relaunching

Hypertrophic growth of pilosebaceous unit

Horizontal: hyper TSH Hyper αΣ Hyper TRH

↑ PL

Hyper πΣ Hyper TSH → exocrine pancreas Insulin resistance Prolactin

↑ Insulin

Hyperinsulinism Pustular acne PL ≫ GH: cystic acne Disadapted growth of pilosebaceous unit Disadapted growth of commensal organisms Inflammation Papular acne

c­ onstriction. Metabolically, it can cause sebum to become too thick and thus inspissated. Globally, it can contribute elevated prolactin and hyperinsulinism and all that that implies (Table  8.3). Periodic surges in beta excrete sebum. Emotional lability and emotional dysregulation with autonomic surges is associated with acne.45 The beta surge can initiate the clogging of the pores and the outbreak of acne.

Summary of the acne terrain In summary, patients who develop acne have: 1. Precritical terrain ● Hyper parasympathetic ● Congested emunctories ▪ ▪ ▪

Liver Colon Exocrine pancreas

Oversolicitation of skin as emunctory 2. Critical terrain ● Insufficiency progesterone and/or gonadal androgens ● Overreactive LH ● ↑ Adrenal androgens with Cortisol insufficiency ● Hypermetabolic state 3. Results ● ↑ Sebum secretion and excretion ● Hyperkeratosis ● Congestion of hair follicle ● Overgrowth of commensal skin bacteria ● → Acne ●

Factors that aggravate the terrain and increase prevalence of acne A number of factors have been correlated with acne. The first is intestinal and skin dysbiosis. The reasons for this are complex, likely related to dysregulation of the global and local immune response. The second is diet. Societies that have very low consumption rates of high glycemic carbohydrates and higher consumption rates of fermented foods have a low incidence of acne. Additionally, when they are settled into urban areas and consume a standard Western diet, acne prevalence increases.40

Mechanisms of acne formation There are four mechanisms of acne, erroneously referred to as causes in classical dermatology. The first is hyperproliferation of keratin in the epidermis. This second is excessive excretion of sebum from the sebaceous gland in the dermis. The third is a dysregulation of the ecology of the commensal bacteria Propionibacterium acnes, and fourth: inflammation.12 Table 8.3 reviews the physiology and pathophysiology of these factors. The quality of sebum is fundamentally

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TABLE 8.3  Layers of skin, metabolism, physiology and pathophysiology Layer

Endocrine

Element

Physiology

Pathophysiology

Epidermis

Thyrotropic

Keratin (proteins)

Local adaptation response

Hyperkeratosis: excessive keratin → excessive catabolic adaptation

Dermis

Gonadotropic

Sebum (lipids): excreted from holocrine gland

Hydrophobic barrier, thermoregulation, antimicrosis, regulates inflammation (vitamin E)

Rich in fatty acids, hypersebum state provides material for growth of bacteria

Commensal flora

Prevents growth of noncommensal flora

Overgrowth of noncommensal flora fed on proteins (keratin) and fat (sebum), immune response stimulates pus formation

Inflammation

Allows immune system to response to dysbiosis

Prolonged inflammation results in symptoms associated with acne: redness, pain

Epidermis, dermis All

Corticothyrotropic

different in patients with acne vs those who do not have acne.40 In the former, there is a greater amount of oleic acid. Oleic acid serves as a substrate for P. acnes, aids in its adherence, and contributes to the production of biofilm, which allows noncommensal bacteria.46 Both androgens and IGF-1, as well as diet, contribute to this phenomenon.

Physical examination The physical examination of the acne patient should be thorough. While acne is most prominent on the face, it may also occur on the chest, back, and buttocks (Table 8.4). It

TABLE 8.4  Neuroendocrine determinates of acne localization Axis

Hormone

Location

Corticotropic

ACTH

Forehead

DHEA

Jaw Buttocks, lateral

Gonadal androgens

Chin

Gonadal androgens + hyper-Para

Chest

Gonadal androgens + intestinal congestion

Buttocks, midline

FSH

Nasolabial

Somatotropic

General

Upper arms

Gonadosomatotropic

General

Shoulders Upper back

Gonadotropic

should be determined, or confirmed from a more adequate history, if the acne is structuro-functional or functional in nature. The architecture of the skeletal muscles, cut of the jaw, quality, and color of hair and skin should be all evaluated. The presence of any signs from the other axes should also be evaluated. Finally, the state of the implicated emunctories should be evaluated: liver, pancreas, colon, and skin. The signs have been discussed in The Theory of Endobiogeny, Volumes 2, 7, and 8). The localization of acne depends on the relative oversolicitation of pituitary and peripheral hormones (Table 8.4). For example, if there is hyperfunctioning ACTH, to stimulate adrenal androgens or cortisol, acne will appear on the forehead. If there is a hyper FSH, to readapt estrogens or for horizontal stimulation of LH, the acne will appear around the nostrils or above the lateral aspects of the upper lip. One way to determine if gonadal androgens are insufficient or absolutely deficient is the localization of acne to the chin. This indicates that gonadal androgen are absolutely in excess, but relatively insufficient in relationship to the level of LH stimulation. All this guides the Endobiogenist in the assessment of the terrain and the choice of personalized treatment beyond regulation of androgens and drainage of the skin. For example, in Fig.  8.6 the adult women has severe papulopustular acne on the forehead (ACTH), nasolabial area (FSH), jawline (DHEA), and chin (gonadal androgens).

Blood evaluation Serum hormone testing for androgens, LH, etc. is not recommended. They pose challenges given the large cyclic variations, be they mensal and general circadian fluctuations in men and women.10 The biology of functions is not necessary for simple cases of acne, but can be instructive in general. It can be quite helpful in complex cases, especially refractory ones, or where there are a number of comorbidities such

172  The Theory of Endobiogeny

FIG. 8.6  Adult female with severe acne involving ACTH, FSH, DHEA, and gonadal androgens all in excess. (Reproduced from Williams HC, et al. Acne vulgaris. Lancet 2012;379(9813):361-372. https://doi.org/10.1016/ S0140-6736(11)60321-8.)

as ovarian cysts, premenstrual conditions, prostate enlargement, depression, etc. Indexes related to luteal function were extensively discussed in Chapter 7. In the full case study at the end of this chapter, the cluster of indexes related to the general noncystic acne terrain is demonstrated.

Procedures A standard approach to the treatment of acne vulgaris includes procedures and pharmaceutical treatments.12,13 Three examples of procedures are (1) manual extraction of comedones, (2) intralesional steroid injections, and (3) superficial peels, such as glycolic or salicylic acid.47

Treatment: Pharmaceutical The American Academy of Dermatology, based on analysis of the quality of studies and strength of conclusions, recommends stepped-up treatment protocol based on the severity of acne.48 The recommendations are derived from a mix of good and limited quality studies, and good and limited strength of patient-based evidence. However, the context of the studies, like most standard medical studies, is based on considering the mechanisms of disease to be its cause, using single chemical entities, and determining success based on suppression of symptoms. Thus, these treatments, while evidenced-based, remain substitutive, suppressive, or reactionary in nature.13 Pharmaceutical treatments can be divided into various categories. The first is topical, oral, and injectable, generally

speaking, applied to mild, moderate, and severe acne, respectively. The second is type of action. There are comedolytics, antidesquamatory, antiinflammatory, and antimicrobial. Many pharmaceutical products have some combination of these actions (Table 8.5).13, 48 In addition, systemically acting endocrine products are also used. Retinoids include tretinoin, tazarotene, and adapalene. Topical antibiotics include dapsone, clindamycin, and erythromycin. Resistance by P. acnes is an increasing concern.48 Various oral antibiotics are used in severe acne, including tetracyclines, azithromycin, and others. The risk of systemic dysbiosis exists, such as vaginal candidiasis.13, 48 There are three types of hormonal therapy used for acne: (1) glucocorticoids, (2) oral contraceptives, and (3) androgen inhibitors. Glucocorticoids can be used topically, or orally in more extreme cases of acne. Oral contraceptives have three effects understood to be helpful in acne. The first is their estrogenic activity, which can counterbalance androgens and stimulate SHBG’s binding of androgens. The second is an upregulation of the production of SHBG by the liver. The third is their central effects on gonadotropins.13 Spironolactone is a diuretic that has peripheral gonadotropic actions. It inhibits both androgen production and competitively binds to androgen receptors. In addition, it is antiinflammatory. However, there are risks of dysmenorrhea, gynecomastia, and dizziness, which, according to dermatologists, can be treated with oral contraceptives.49

Treatment: Topical and symptomatic Because the final expression of the acne terrain is on the envelope, topical treatments are efficient for both symptomatic and locoregional regulation of the mechanisms of acne, namely sebum production and keratin formation.

Clay Green clay has a number of desirable properties related to acne.50 It is antimicrobial and an adsorbent that helps draw out and absorb excessive sebum.51, 52 Clay can be drying to the skin, especially if left on too long and when made with water (cf. below).

Lactic acid: Yoghurt Yoghurt contains lactic acid, which hydrates and exfoliates skin,50 and reduces the number of lesions in acne.53 Lactic acid breaks down keratin, and is neocollagenic, cicatrizing, and antiinflammatory as well.47 According to studies, lactic acid is most effective for comedones, papulopustular lesions, and lightening scars.47 This latter effect may only occur when a concentrated extract is used, as opposed to using yoghurt. Traditional, thin yoghurt (not Greek-style, not yoghurt thickened with carrageenan or pectin) can be used in place of water when making a clay mask as it keeps it well hydrated for longer than water does.

TABLE 8.5  Summary of pharmaceutical treatments and their effects on mechanisms and terrain of acne Product

Comedolytic

Antidesquamation

Retinoids

Antiinflamatory

• •

•

Cortisol-like

Estrogenic

Antiandrogenic

• •

Antibiotics

•

Glucocorticoids

•

Contraceptives Spirinolactone

Antimicrobial

• • •

•

•

Acne: Disorder of luteal androgen management Chapter | 8  173

Benzoyl peroxide

Keratolytic

174  The Theory of Endobiogeny

Tisanes and decoctions

Hygiene

In addition to, or in place of yoghurt, clay can be prepared with a tisane or decoction adapted to the local or global terrain of acne. The following medicinal plants are depurative and antimicrobial54–56:

The face should be washed 1–2 times per day, not more to avoid irritation or drying. Examples include pine tar and facial scrubs with natural abrasives and exfoliants (e.g., baking soda, rice brain, oatmeal, raspberry seeds, almonds, etc.)50 Exfoliants can be added to a simple clay mask made with water and used as a facial scrub instead of a mask, or, as both.

1. Arctium lappa (Burdock): best general treatment a. Decoct 1 tsp. roots in 100 mL water for 15 min. 2. Viola tricolor (Wild pansy): for stronger inflammatory component a. Steep 1 tsp. in 100 mL water for 8 min 3. Borago officinalis (Borage): when hyper-FSH and ­hyper-LH are more predominant, esp. nasolabial acne a. Steep 1 tsp. flowering tops in 100 mL water for 8 min

A recipe for a facial scrub ● ● ●

Essential oils Essential oils can be added to the clay-yoghurt mixture for symptomatic treatment of bacterial overgrowth, drainage as well as the restoration of proper peripheral gonadal balance. Be sure to avoid essential oils rich in phenolics and ketones, which can be irritating to the skin. Avoid essential oils that are photosensitizing. 1. Antimicrobial54–57 a. Lavandula angustifolia b. Matricaria recutita c. Pelargonium graveolens d. Melaleuca alternifolia 2. Estrogenic54, 56 a. Salvia sclarea b. Salvia officinalis c. Angelica archangelica seed d. Cupressus sempervirens 3. Progesteronic54, 56 a. Achillea millefolium

A recipe for a face mask ●

Add the following in a small glass bowl or cup and mix well ● 1 tbsp green clay ● 1 drop Salvia sclarea EO ● 1 drop Lavandula angustifolia EO ▪ Optional: 1 drop Matricaria recutita EO

● ●

● ● ●

●

Add 1 tbsp plain, full fat yoghurt and mix well Add Arctium lappa decoction to dilute mixture to desired thickness Use 3–4 times per week after a facial wash. Rinse thoroughly when done Start at 5 min and increase duration up to 20 min or as tolerated Keep moist if necessary by misting tepid, distilled water on the face mask

● ● ● ● ●

1 tbsp clay 1 drop Salvia officinalis EO 1 tsp. finely ground almond meal ● Cystic acne: add ¼ tsp. baking soda 1 tbsp spearmint (Mentha spicata) tea Mix into a consistent, slightly thin paste. Wash face with warm water Massage scrub on face and let sit 2–3 min Rinse, pat dry.

Treatment: Oral Enteral therapy will include a prominent drainage activity, which is the precritical terrain of acne. The specific endocrine treatment depends on a number of clinical factors (Table 8.6). A symptomatic, systemic approach to acne addresses elements of the mechanisms of disease. For example, mTOR suppression involved in hyperanabolism of lipids can be accomplished with resveratrol or Vitamin D.40 Probiotics can also be used to address aspects of the enteric dysbiosis contributing to global inflammatory imbalance.58 Antibiotics can be used in more severe cases and have a synergistic effect with probiotics.58 The more typical Endobiogenic approach is to the acute treatment of acne is that of drainage, along with antiinflammatory and antiinfectious plants (Table 8.7).54, 56, 59–62 Many plants will possess all these activities, as well as neuroendocrine ones, making them highly efficient. Treatments that address the fundamental upstream neuroendocrine elements of the critical and precritical terrain are listed in Table 8.8. The most efficient plants are in bold, meaning that they work across multiple neuroendocrine and/or emunctory actions.54, 56

Treatment: Oligoelements Various oligoelements can be helpful in support of the acne terrain, listed in the following: 1. Stress: Mg 2. Liver: sulfur. Raphanus niger is a good source of sulfurated compounds63 3. Skin-colon: Mn-Cu-Co

Acne: Disorder of luteal androgen management Chapter | 8  175

TABLE 8.6  Treatment notes based on various considerations and ages of patients with acne Category

Subcategory

Caution

Chronobiologic

Infants

Avoid topical or enteral products that are irritating to the infant’s gentle skin; if acne is severe, use rectal infusions

Adolescents

Avoid excessive or sustained androgenic therapy to prevent early closure of epiphyseal growth plates

Pregnancy

Avoid strong estrogenic therapies except in weeks 0–35 of gestation Favor topical treatments

Adult males

Determine if the gonadal androgen insufficiency is absolute or relative

Adult females

Determine if luteal insufficiency is exclusively progesteronic or also androgenic

Cancer Cancer survivors

Avoid strong estrogenic therapy except in topical form; with history of certain dermal cancers, favor corticotropic regulation over estrogen therapy

Sex

Past medical history

TABLE 8.7  Oral treatments for drainage and mechanisms of acne Drainage Liver

Colon

Inflammation

Dermal infection

•

•

•

•

Dermal depurative, keratolytic, cicatrizant

•

•

Laxative

Immunoregulatory

•

↓ Pus, antihyperglycemant

Agrimonia eupatoria

•

•

•

•

Juglans regia

•

•

•

(Intestinal dysbiosis)

Antihyperglycemant

Fragaria vesca

•

•

•

Broad endocrine (cf. below)

Malva sylvestris

Laxative

Salvia sclarea

•

Plant

Skin

Viola tricolor

•

Arctium lappa

•

Dual pancreatrope

4. Skin-estrogen production: Zn-Cu for estrogen insufficiency and prominent role of infection 5. Skin-exocrine pancreas: Zn-Ni-Co 6. Skin-endocrine pancreas: Se + Mg

Treatment: Diet and lifestyle The diet should be pancreas-sparing, avoiding unfermented dairy, red meat, and unrefined grains given the role of the exocrine pancreas in the pathophysiology of acne.64, 65 Chocolate avoidance may help, due to the presence of both dairy and sugar.36 Lifestyle modification and techniques of emotional regulation may be helpful.45

Other

↓ Para

Antihypoglycemant •

•

Cicatrizing, broad neuro-endocrine (cf. below)

A brief case study in adolescent acne A 14-year-old girl presents with a 6-month history of papular acne. It started around the time of a growth spurt. It is distributed across the forehead and around the nostrils. It worsens in the last 4 days of her menstrual cycle, when she also develops a few scattered acne lesions on her jawline. She complains of water retention and abdominal cramps that are mild. In her past medical history, breast development started at 10.5 years, menarche at 12.7 years. This girl has had normal installation of gonadotropic activity during puberty. During her growth spurt, she developed a luteal insufficiency in which gonadal androgens were produced in favor of progesterone. This is evidenced by the

176  The Theory of Endobiogeny

TABLE 8.8  Treatment of the precritical and critical terrain of acne Axis

Factor

Action

Therapy

ANS

Para

↓

Alpha

↓

Lavandula angustifolia Salvia sclarea

Cortisol

↓

Ribes nigrum Eleutherococcus senticosus Salvia sclarea Fragaria vesca

DHEA

↓

Fragaria vesca

FSH

↓

Borago officinalis Lithospermum officinale Salvia sclarea

LH

↓

Lithospermum officinale Alchemilla vulgaris Medicago sativa

Estrogens

↓

Salvia sclarea

Progesterone

Adapt as indicated

Alchemilla vulgaris Achillea millefolium

Androgens

↓ Androgen receptors

Humulus lupulus

Regulate

Eleutherococcus senticosus

TSH

↓

Lithospermum officinale Cystic acne: Zea mais GM

Thyroid

Regulate

Avena sativa Salvia sclarea: stimulates

GH

↓

Fragaria vesca

Prolactin

↓

Fragaria vesca

Insulin

↓

Cf. dual pancreatrope, below Cystic acne: Malva sylvestris

Corticotropic

Gonadotropic

Thyrotropic

Somatotropic

fact that she continues to grow. Also, she has an estrogenpredominant PMS rooted in progesterone insufficiency. The nasolabial acne indicates that her FSH is hyperfunctioning in order to regulate estrogens. Thus, a regulator of FSHestrogen activity should be considered. The acne on the forehead indicates that there is a hyper ACTH to relaunch the adrenal cortex which is contributing DHEA especially in the last days of her menstrual cycle, when she develops acne on her jaw line.

General treatment ● ● ● ●

Pancreas sparing diet Mn-Co-Cu 1 unit BID Clay face mask 4 times per week Cortico-Gonadotropic tincture: Ribes nigrum GM 75 mL, Salvia sclarea MT 40 mL, Alchemilla vulgaris MT 85 mL, Fragaria vesca MT 40 mL + Lavender EO 3 mL: 3 mL BID

●

Drainage tincture: Arctium lappa MT 120  mL, Raphanus niger MT 60 mL, Hamamelis virginiana MT 60 mL: 3 mL BID

A full case study in acne A 19-year-old male presents with a 4-year history of acne. He is seeking a natural treatment. His acne started at 15. Around this time he also became interested in weight lifting, playing American football, and wrestling. At first, his acne was papulopustular. It first appeared on the forehead, then also around the nasolabial region. This resolved by 16 but he developed more cystic acne. It appeared along the jaw line, chin, and submandibular area. At 17 he developed acne in the medial gluteal region as well as where he expressed it at 16. Aggravating factors include constipation, a high carbohydrate diet, and stress. Comment: The location of the acne at various ages was indicative of how he moved through puberty. The onset of

Acne: Disorder of luteal androgen management Chapter | 8  177

acne was at 15 years, the time of gonadic tissular activity. The chronobiologic unfolding was focusing on the growth of tissue mass, such as muscle. LH activity was increased to open up more androgen receptors and increase the rate of androgen production. The onset of acne at this age suggests that the patient had difficulty in establish the proper LH-Gonadal androgen responsiveness. The intensity of his weight lifting and physical activity may have further oversolicited LH demand. The papulopustular nature reflected his general terrain and the role of prolactin in pus formation. However, the acne at first was on the forehead. This witnesses that initial adaptation response to augment gonadal androgen activity was through ACTH solicitation of adrenal androgens. Adrenal androgens could then be converted to gonadal androgens. It may have also represented horizontal stimulation of LH by ACTH. The nasolabial acne represents FSH solicitation. This may also have been the result of ACTH horizontal stimulation. At 16 years, the time of gonadic endocrine activity, he developed cystic acne. The development of cystic acne indicates hypersolicitation of the pituitary. FSH, LH TSH, growth hormone and prolactin activity exceeded in degree of intensity, chronology, quality, and quantity of response those of the peripheral hormones. Because the skin was the most congested and metabolically active organ, the cysts localized there. The evolution of his acne around the jaw is a reflection that in fact he had more than competent DHEA— it was excessive. The appearance on the chin indicated an absolute excess of gonadal androgens as well. It suggests, in conclusion, that the rate of production was insufficient and/ or that the timing of response to LH was, or both. At 17, still the time of gonadic endocrine function, he developed gluteal acne. This witnessed a further congestion of the colon.

Past medical history ● ● ● ●

●

●

Term vaginal birth, induced Breast fed 4 months 9 months: Eczema, resolved by 12 months 2: Reactive airway disease, required as needed Albuterol for 1 year. 4–17: Recurrent viral upper respiratory infections in the winter: rhinopharyngitis, laryngitis, and bronchitis. He became ill sooner than other children and took longer to recover. 7–19: Recurrent constipation lasting for 7–14  days with a bowel movement every 3–4 days. They would occur around periods of mental stress, such as before examinations.

He was never treated with antibiotics. Furthermore, the history is not strongly suggestive of a dysbiosis from iatrogenic or insufficient maternal-child interaction (i.e., cesarean section birth, absence of breast feeding).

The history is significant for atopic disease: eczema and reactive airway disease. This terrain (Chapters 1 and 2) implicates two things relative to the acne terrain. The first is the implication of the exocrine pancreas. The second is immune dysregulation. The constipation indicates a tendency to express alpha > para during times of high adaptation demand. In the case of the acne terrain, its congestion the colon, retoxification, and solicitation of the skin as an emunctory organ.

Diet As a child his diet consisted of typical American foods rich in refined wheat flour bread, cheese, and meats. However, he also ate rice and yoghurt as well as fruit. As an adolescent, he drank 2 L of fluorinated tap water per day. Between 15 and 18 years of age, his diet consisted of a high calorie diet (3000 cal per day) to maintain a lean yet muscular body mass for American football, wrestling, and bodybuilding. He ate a high volume of carbohydrates (400 g/day). This consisted of refined wheat flour breads and fruit: 3–4 green apples per day, 2–3 bananas per day. He enjoyed smoked salmon and sardines as well as chicken breast. However, the majority of his proteins were derived from beef sausage, deli meats, and ground beef. In total he consumed about 60–70 g of protein per day. He also ate a high amount of peanut butter daily, cheese, and milk. He ate few vegetables. He attempted to change his diet a few times but could never maintain a low carbohydrate diet for more than a few days before feeling very hungry. Comment: The elevated consumption of carbohydrates (bread and lactose from the milk) oversolicited both exocrine and endocrine pancreas. The development of the cystic acne favored a greater implication of the endocrine pancreas. The carbohydrates congested the lungs and then the skin as a tertiary emunctory. The high consumption of fats in the peanut butter and dairy favored diminished choleresis, which in turn favored toxin excess, shunted to the skin for metabolism. The high consumption of proteins, especially the inflammatory red meats favored an inflammatory terrain and reduced omega 3:6 ratio. The patient had been using a clay as a facemask 2–3 days per week for over 1 year at the time of the evaluation. It helped reduce the inflammation and pain of the cystic lesions but did not resolve the acne. He was offered but was never compliant with encapsulated supplements or tinctures in the past.

Physical examination Physical examination findings and their significance are in Table 8.9.

178  The Theory of Endobiogeny

TABLE 8.9  Physical exam findings and their significance Location

Finding

Significance

HEENT

Cystic acne: jaw line, chin, submandibular, painful to palpation

LH > androgens, androgens > estrogens, both gonadal and adrenal androgen activity increased on face

Opening of canal of Stensen dilated, L > R

Exocrine pancreatic insufficiency: carbohydrates

Sublingual veins dark blue and tortuous

Hepatic congestion

Eyelashes long, dark and curled

FSH with appeal to TSH to calibrate thyroid to estrogen activity

Liver tender, inferior-lateral portion only

Metabolic liver insufficiency

Midpoint between umbilicus and right costal margin at nipple line

Gallbladder congestion

Pancreas reflection point tender, right < left of umbilicus

Endocrine pancreas relatively more implicated than exocrine pancreas

Colon tender: ileocecal junction, ascending colon, transverse colon, recto-sigmoid area

(In order): ACTH-structural adaptation, FSH, LH, ACTH-functional adaptation

Good muscular texture and architecture

The quality of gonadal androgen activity is calibrated at the level of muscle

Calves least developed musculature despite engaging in leg exercises

Tissular effects of adrenal androgens (calves) is focused on the envelope (the skin) more than within the interior

Abdomen

Extremities

HEENT: Head, eyes, ears, nose and throat.

Acne at time of presentation The acne at time of presentation was on the neck, jawline, chin, and nasolabial region with cystic lesions and black heads (Fig. 8.7).

Biology of functions There are a number of ways to evaluate the indexes of the biology of functions. One way is a sequential axial format

related to the order of the general adaptation syndrome of Endobiogeny and the endocrine loops. To be demonstrative with respect to acne, we will group the indexes according to a radial arrangement based on the critical terrain. This approach is helpful in acne because androgen activity is expressed in two axes (gonadotropic and corticotropic) by two glands (adrenal cortex and gonads), with multiple hormones (DHEA, testosterone, DHT, etc.). After assessing the general state of androgens within the terrain, our analysis turns

FIG. 8.7  Pretreatment acne in an adolescent male. Note the presence of acne on the jawline, neck, and nasolabial regions. (© 2014 Kamyar M. Hedayat.)

Acne: Disorder of luteal androgen management Chapter | 8  179

to an evaluation of estrogens and their ability to regulate androgens. This is followed by a thyro-somatotropic evaluation of metabolism.

Androgens At times, for the beginning student of Endobiogeny, the number of nuanced indexes that seem to be evaluating very similar activity seems overwhelming, if not redundant. Disorders such as acne and prostatic enlargement are good examples in which this level of nuanced evaluation of physiology helps elucidate the precise level of dysfunction (Table 8.10). When we approach the indexes describing androgen activity, we seek to determine in the acne terrain, what the origin of the hyperandrogenism is (Fig.  8.4 and accompanying text). In this case, the source of the hyperandrogenism is the gonads, as noted in the elevated genital androgens index. This index evaluates the general tissular endocrinometabolic activity of gonadal androgens. By extension, it evaluates their potential for specific activity within the structural components of the body. In other words, it evaluates how androgens, through their endocrine activity stimulate a metabolic response for the production of specific structural elements of the cells: enzymes, organelles, sebum, etc. The value is about 10-fold above normal. How are androgens affecting the metabolism of androgen-rich organs, such as the skin? This is answered in the comparative genital androgeny. It is about 10-fold above normal as well. Therefore, we can conclude that genital androgens are excessive and hold the potential to stimulate excessive structural metabolic activity within cells. What is stimulating these gonadal androgens? The answer is LH. The LH index is low, indicating that it is overstimulating gonadal androgen activity and is being inhibited by it. What about estrogens relaunching LH to calibrate androgen activity? This is not occurring in this young man, as noted by the low value of the rate of total androgens index. What is the role of DHEA? The DHEA index is very low, indicating that DHEA activity is not dedicated to conversion to gonadal hormones peripherally.

TABLE 8.10  Indexes related to androgens Index

Value

Range

LH

0.01

0.86–6

Rate of gonadal androgens

0.97

0.05–0.09

Comparative genital androgeny

3.13

0.1–0.3

Rate of global androgens

0.14

0.2–0.25

DHEA

0.03

5–9

High low values presented in red/blue respectively.

Estrogens Estrogens at higher levels are antiandrogenic, as they stimulate SHBG to bind androgens.42, 66 The ability to oppose gonadal androgens can help regulate their activity. At every level of function, the patient had insufficient estrogen activity (Table 8.11). The Estrogen index corrected evaluates for estrogens what the genital androgens index does for androgens.

Thyrotropic axis There are a number of aspects of the thyrotropic axis that are of interest. The first is its relationship to the epidermis (Fig.  8.2, Table  8.4), which is a source of keratin, in excess in acne. The second is the general role of peripheral thyroid activity in tissular metabolic activity, such as the production of keratin (Table  8.12). This is represented in the relative thyroid efficiency index, which was elevated. TABLE 8.11  Estrogen activity Index

Value

Range

General quantitative estrogens

728

809–1438

Quantitaitve level of estrogen production is low

Estrogen index

0.16

0.2–0.4

The endocrinometabolic activity of estrogens is low

0.18

0.2–0.5

The tissular endocrinometabolic activity of estrogens is low

Fraction of metabolic estrogens*

12.9

18–107

The specific metabolic activity of estrogens is low

Genital ratio corrected

0.87

0.7–0.85

The relative level of gonadal androgen to estrogen activity is high outside of adaptation, favoring androgens in tissular activity

Estrogen index corrected

Interpretation

*In the prior version of the Endobiogenic Medical Assistant (EMA), the Estrogen index was called the metabolic estrogens index. Fraction of metabolic estrogens is a completely different index. High low values presented in red/blue respectively.

TABLE 8.12  Thyrotropic indexes

High low values presented in red/blue respectively.

180  The Theory of Endobiogeny

It expresses the relative part of tissular metabolic activity of the thyroid in relationship to that of its metabolic activity, properly said. In other words, what is the relative role of the thyroid in stimulating tissue production of metabolic products—such as keratin, sebum, etc., relative to its role in driving oxidative metabolism for ATP production and general cellular energy? The thyroid index evaluates this latter function. It is low, which is not surprising given that fact that this young man is very active in aerobic activity (American football, wrestling, etc.) as well as weight lifting. According to the theory of Endobiogeny, sporty people have a low thyroid metabolic activity to prevent muscle wasting given the level of exertional strain of their skeletal muscle. This refers not to the quantitative level of thyroxine or triiodothyronine output from the thyroid gland, but the cellular sensitivity to this hormones are reflected in the ratio of lactate dehydrogenase (LDH) to creatine phosphokinase (CPK), which is the formula for the thyroid index (cf. The Theory of Endobiogeny, Volume 1, Chapter  15). One notes that both his LDH and CPK are absolutely elevated, witnessing the level of muscle turnover. However, the ratio (thyroid index) is quite low. At the time of the blood draw, a cystic terrain was not present. That would have involved a low serum TSH (his was high-normal). In addition, there would be a high insulin index, low insulin resistance, and low GH growth score (Table  8.13). In his case, it was quite the opposite. Acne does not progress in a linear manner of development and regression. It occurs in waves followed by periods of stability, then regression. It is reasonable to conclude that at the time of the blood draw, the patient was in a pause-phase in acne development (see Table 8.13), but retained elements of the critical terrain (Tables 8.10–8.12).

Somatotropic axis In the somatotropic axis we wish to evaluate two aspects of the terrain: (1) metabolic activity and (2) nutritional demands of the cells. The former relates to acne ­production,

TABLE 8.13  Somatotropic indexes

High low values presented in red/blue respectively.

the latter to selecting a nutritional program. With respect to metabolic activity (Table  8.13) we are interested in evaluating the general and specific aspects of growth hormone, IGF-1, insulin, and insulin resistance. According to Melnick (cf. critical terrain), acne can be considered as a metabolic syndrome of the skin follicle.40 We anticipate seeing a hypermetabolic, hyperanabolic terrain when the patient is the phase of developing new papules and papulopustular lesions. That would be reflected in an elevated rate of metabolism index and low catabolism/anabolism index. The fact that this was not present again confirms that the patient was in a pause phase of development of acne lesions at the time of the blood draw. We noted the role of IGF-1 in sebum production, which would be reflected in an elevated corrected growth index. Again, it was not elevated at this time. However, the other aspects of a metabolic syndrome somatotropic dysfunction were present: elevated GH growth score (value corrected for patient’s age), insulin, and insulin resistance indexes. The GH growth score evaluates the general role of growth hormone is the delivery of excessive nutrients that was present. Finally, the somatostatin index was quite elevated, confirming the role of exocrine pancreas in liberating excess nutrients for systemic absorption (Chapter 6, and The Theory of Endobiogeny, Volume 2, Chapter 8).

Cellular nutrition and alimentary advice The biology of functions can assist in determining the optimal diet for the patient. This is accomplished by evaluated key indexes related to cell membrane activity (Table 8.14). The cell membrane is made of phospholipids with cholesterol periodically inserted. Active permeability refers to the entry of electrolytes and nutrients through channels, which allows them to be concentrated against a gradient according to the demands of the cell. Passive permeability refers to the movement of small lipophilic molecules down their concentration gradient directly through the membrane, which cannot be regulated by the cell. The greater the fluidity of the

TABLE 8.14  Indexes related to cell membrane activity Index

High

Low

Insulin resistance

Low glycemic diet

Small frequent meals with whole grains and healthy fats

Active cell permeability

Purine proteins

Vegetarian or pescatarian (favor white fish) protein

Passive cell permeability

Foods rich in beta-glucans and fiber

Vegetarian fats: walnuts, flax seeds, sprouted seeds

Acne: Disorder of luteal androgen management Chapter | 8  181

TABLE 8.15  Indexes related to cell membrane activity in the patient Index

Value

Range

Insulin resistance

142

1.25–2.5

Active cell permeability

451

6–9

Passive cell permeability

0.02

4–9

Tincture The patient was started on a single tincture at low dose (Table  8.16). It consists of Fragaria vesca MT 80 mL, Medicago sativa MT 80 mL, Humulus lupulus MT 80 mL, Agrimonia eupatoria MT 60 mL, Viola tricolor MT 120 mL, and Menyanthes trifoliata MT 60 mL, dose: 2 mL twice per day.

High low values presented in red/blue respectively.

Results membrane due to heat and/or cholesterol, the greater the passive cell permeability. Excessive passive permeability allows certain small molecules to enter down their concentration gradient regardless of the requirements of the cell, placing it at risk of excess nutrient entry. The patient noted that his acne is worsened by situational stress and diet. Based on the value of his indexes (Table 8.15) he was recommended a low-glycemic diet with purine proteins and healthy fats.

Treatment Diet 1. 2 L water/day 2. Purine proteins, nuts, seeds, raw, and lightly cooked vegetables 3. Stop all refined carbohydrates, nonfermented dairy, deli meats

The patient’s acne cleared up significantly within 2 weeks (Fig. 8.8). The complexion improved in all areas. The right cystic lesions nearly resolved. The number of cystic lesions and the relative degree of inflammation were reduced on the left. Nearly all the blackheads resolved.

Conclusions According to the theory of Endobiogeny, acne is an endocrine disorder of luteal hormone excess at the level of the skin, resulting in excess sebum production, narrowing or plugging of hair follicles, and dysbiotic growth of commensal and noncommensal flora. Acne can be structurofunctional or functional. Structuro-functional refers to how the organism adapts to specific structural needs, such as the neonatal period, adolescences, and genital recycling in adulthood. Functional acne is in response to adaptation demands, such as stress or disruptions in chronobiologic rhythms. The acne terrain represents dysfunction in all four

TABLE 8.16  Actions of the tincture on the acne terrain Plant (MT)

Corticotropic

Gonadotropic

Somatotropic

Emunctory

Other

Fragaria vesca leaf

↑ Cortisol ↓ DHEA

(−) Androgens → estrogens

(−) GH

Digestive and dermal astringent, wound healer

Antiinflammatory

Humulus lupulus

↓ Androgen receptors Estrogenic

Neurotropic antispasmodic Antiinflammatory (COX-2)

Agrimonia eupatoria

GI astringent, ↑ biliary secretions, pancreatic drainer, dual pancreatrope

Antiinflammatory

Viola tricolor

Drainage: skin, liver, intestines

Depurative, antiinflammatory, antiinfectious, keratolytic, cicatrisant

Eupeptic

βSympathomimetic parasympatholytic Antiinflammatory

Menyanthes trifoliata

Estrogenic, antiandro-genic

GH, growth hormone; GI, gastrointestinal; MT, mother tincture.

182  The Theory of Endobiogeny

FIG. 8.8  Two weeks postendobiogenic treatment for acne. See text for details. (© 2014 Kamyar M. Hedayat.)

endocrine axes and emunctories related to lipid-protein metabolism and detoxification. Acne, while superficial, may reflect systemic imbalances or risks of future disorders and should be investigated and treated systemically. A symptomatic suppression of topical mechanisms of disease may offer short-term results, but do not address the underlying imbalances found in the acne terrain.

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Chapter 9

Motricity of the bowel Introduction This chapter reviews the motricity of the digestive tract (DT), offering simple approaches to addressing minor disturbances of this system. We use the term “digestive tract” rather than “gastrointestinal tract” (GI) because sum of all units of active related to digestion involve more than stomach and intestines, it also includes mouth (salivary glands and mastication), esophagus, liver, gallbladder and exocrine pancreas. Rate and sequencing of motricity is key to good digestive and immune function, and each unit of function of the DT plays a role. The sequencing of the movement of food, and excretion of nutrients is key to proper breakdown and absorption of nutrients. The rate of motricity must be optimal in order to favor absorption but avoid putrification and dysbiosis. The DT is integrated at all times to regional and systemic demands from the neuroendocrine system, central nervous system, and other factors and thus its function is seldom intrinsic and never dissociated from the global requirements for nutrition. As with other physiologic conditions, excess and insufficient activity may present with the same type of disorder, viz., malnutrition, but for different reasons. Other conditions are distinct, such as the rate of removal of stool and its quality, viz., diarrhea vs constipation (Chapter 10). The most basic internal function is digestion and extraction of nutrients. The purpose of this is twofold. The first is presentation of basic macromolecules for energy production through oxidation. The second is the storage of nutrients to be utilized during periods of scarcity and adaptation demand. Thus, the DT contributes to the material integrity and buffering capacity of the organism. The DT is open at both ends receiving nutrients and extruding waste. Thus, it is exposed to the constant threat. It is no surprise, therefore, that it contains the single largest portion of the immune system. This openness poses particular risks for certain types of disorders. Some, like dysbiosis, have already been discussed (The Theory of Endobiogeny, Volume 2, Chapter 6). Others, such as inflammatory bowel disorders, will be discussed in Chapter 11. We prefer the term DT to gastrointestinal tract (GIT). GIT refers only to the portion from the stomach to

rectum. DT encompasses mouth to anus and implies the activity of the annexal organs (Fig. 9.1).

Overview of function The DT (Fig. 9.1) provides the means for the body to process food in order to ensure cellular nutrition: (1) degradation of macromolecules: proteins, polysaccharides into small molecules, (2) hydrochloric acid secreted by the stomach, and (3) bile secreted by the liver, various digestive enzymes released by other exocrine glands (secretion). The DT in the adult is more than 7 m long, the majority of that being comprised of the jejunoileal portions of the small intestines.1 The DT extends from the mouth to the anus. It contains several segments with different functions. In general, the segments function to physically and enzymatically break down nutrients, move them through the bowel, and defend the organism. The digestive system is associated with accessory glands and organs: salivary glands, liver, gallbladder, and exocrine pancreas. They have three major roles: 1. Salivary glands, gall bladder, exocrine pancreas: Digestion, the majority of digestive juices are produced by them 2. Liver, gall bladder, exocrine pancreas: Regulation of pH to appropriate levels for various parts of the DT 3. Liver: Nutrient processing, storage, and distribution after digestion Absorption allows for the passage of nutrients from the intestinal epithelium into the blood or lymph. The average adult consumes per day approximately 800 g of food and 1200 mL of water per day. The accessory and intestinal glands secrete 7000 mL of fluid per day and excrete 100 mL of water in feces. There is a crucial role played by the endocrine system with respect to the quantity and concentration of nutrients from which nothing can escape.

Evolutionary requirement for digestive tract Absorption mechanisms in the DT arose out of the evolutionary development of complexity. Once multicellular

1. Glycosides are compounds bound to a sugar moiety. An example of a toxic glycoside is amygdalin, found in bitter almonds. When hydrolyzed, it releases cyanide gas. There are beneficial glycosides, such as the laxative compounds found in Aloe and Senna. The Theory of Endobiogeny. https://doi.org/10.1016/B978-0-12-816964-3.00009-2 © 2019 Elsevier Inc. All rights reserved.

185

186  The Theory of Endobiogeny

is the following. First, it is in part based on genetic capabilities of enzymatic efficiency and quality of parasympathetic (viz., vagotonia vs nonvagotonia) and sympathetic activity, local somatotropic endocrine activity as well as global endocrine function (i.e., the effects of cortisol and TSH on exocrine pancreatic function). Second, the organism modifies the digestive capabilities at the level of stomach and small intestines and resorptive activity within the colon according to its actual Endobiogenic terrain. Consider two vagotonic patients. One has allergies, the other asthma. There is a genetic predisposition in the first to respond to the oversolicitation demand for proteins. In the second case, since asthma is also a hyperimmune state, the same overabsorption of proteins exist, but there is also an overabsorption of glucose that congests the lungs that was not present in the first, allergic patient, assuming they have a similar diet. The purpose of the DT in providing materials at the cellular level justifies every aspect of the structural and functional activity of the DT: its length, duration of transit, the specific purpose of each of its constituent parts, their functional organization, the order of their sequence, and their connections. The selection of nutrients is primarily programmed and not limited to the simple extraction of substances used by the body. It responds to the real needs, occasional and basic of each cell, tissue, organ, system, function, and of the digestive system and of each of its functions, including its functional specificity at successive levels.

Management of energy exchange FIG.  9.1  Digestive tract and annexal organs. The notion of the digestive tract is more comprehensive than gastrointestinal tract, as it includes the important role of mastication, of taste, saliva, etc. as well as the annexal glands (liver, gallbladder, and exocrine pancreas), as well as the anus. (Reproduced from Mariana Ruiz LadyofHats [Public domain], via Wikimedia Commons.)

organisms grew beyond a certain number of cells or tissues, passive diffusion of micromolecules was no longer sufficient. A more sophisticated system of hydrolysis and absorption was required. The advantage was that a much broader range of nutrient sources of higher complexity and organization could be used, thanks to the process of digestion, absorption, and assimilation.

Purpose of digestion The purpose of digestion is to extract and selectively regulate the nutrients necessary for the functioning of the body. This can be for basal metabolic and structural requirements. It can be for acute, occasional, or basic demands. It can be for adaptive demands or adaptability. What is key to ­appreciate with respect to the selective nature of digestion

The DT is the main system that manages the energy exchange with the outside environment. It controls and continuously provides the material to ensure cellular nutrition in constant dynamic adaptation to the requirements of the structure and of the functional status by constantly taking into account the specific and general needs of the organism. It is the system responsible for the provision of nutrients at the cellular level, which explains the priority of basic over urgent needs based on the location. The closer to the extremities (mouth, anus), the more urgent needs will predominate compared to basic ones. The reverse is true when closer to the center of the DT (ileum). This observation offers some insights into the origin of disorders from aphthous ulcers to ileocecal Crohn’s disease. The sequence of the specific distribution of endocrine, metabolic, and catalytic elements is distributed along the DT with a particular sequential functional nature of the autonomic nervous system. Digestive motility plays a very important role in the digestive process, and sequencing of its function is key. It ensures mixing, release, and absorption. It manages contact time within various segments. It ensures the proper evacuation of waste resulting from food processing. ANS inevitability plays a key role in this movement.

Motricity of the bowel Chapter | 9  187

Distribution of the microbiota The particular distribution of the microbial flora is based on adaptative needs of the organism during specific ages and stages of life, seasons, diet, etc.2–5 The microbiota plays key roles in nutrient reclamation and production. This fact itself has been key to the evolution of the size and activity of the human brain.3 The microbiota’s activity is continuous outside of food absorption and outside of exogenous absorption because it plays a capital role in immunity. Also, as symbiotes, they have their own a priori program of development and existence. They do not exist merely to serve us or be served by us.

Other important functions of the digestive tract Defensive nature of the digestive tract The DT is the interface between the outside and inner worlds. The DT contains the largest portion of lymph nodes and immune cells in the gut-associated lymphatic tract (GALT). There is a crucial role played by the symbiotes of the intestines in immunity discussed in The Theory of Endobiogeny, Volume 2, Chapter 5.6

Management of the organism The DT with its accessory glands is an integrated system and not a simple transport channel open toward the outside. Together with its accessory glands, the digestive system is a complete system. It is under the control of the Endobiogenic management and its cyclical loop operation. From the moment the food is ingested, all the mechanisms of the digestion are simultaneously triggered: the cascade of digestive and annexal activities, their coordination of interaction, harmonization, and prioritization between the different levels of activity. The ANS and local digestive hormones, in a permanent relationship with the global organism, coordinate all this activity. From this derives the need to consider all the connections between the systems and the functions in order to understand the origin and the onset of the disease. Its role in a broader sense involves processing undigested foods into assimilable forms, processing endogenous substances, and maintaining a close relationship with the circulatory and respiratory system, which plays a role in the distribution of nutrients to the cells. Recall that while the purpose of digestion is to produce energy, it requires a considerable amount of energy to digest and distribute nutrients. Once nutrients are distributed into cells, energy (ATP) cannot be produced with any great efficiency without oxygen (cf. Chapter 2). What ultimately is the purpose of the cardiovascular system? It is to distribute nutrients obtained from digestion of food, oxygen to oxidize it, and extract the

potential for energy for cellular activity, and to return waste from cellular activity back to the DT for expulsion (as well as to the kidneys).

The walls of the digestive tract Structure and purpose The mucosal folds of the DT contain a large number of convolutions with the presence of villi (brush border), which increase 600-fold the absorptive surface of the small intestine to 300 m2 (Fig. 9.2). The benefits of this are an increased absorptive capacity.7 Because the intestines are continuously being exposed to external and internal substances, they are themselves an organ of increased metabolic activity with an increased cellular turnover rate. Each day, 17 billion epithelial cells are replaced and the entire epithelium of the small intestine is renewed every 5 days. The installation of disorders, such as ulcerative colitis from an inability to sufficiently renew epithelial cells witnesses the Endobiogenic observation that the DT is inexorably imbricate with global neuroendocrine activity.

Factors affecting the turnover of intestinal epithelium There are a number of factors affecting the turnover of the intestinal epithelium (Table  9.1). During waking hours, ­ingestion of food creates a significant demand for t­urnover

Villus Crypt

Lumen

Brush border membrane Tight junction Intestinal epithelial cell (enterocytes, BBM cells) Lamina propria FIG. 9.2  Brush border of the intestines. See text for details. (Reproduced from Pdeitiker [Public domain], Wikimedia Commons.)

188  The Theory of Endobiogeny

TABLE 9.1  Factors affecting turnover of intestinal epithelium

TABLE 9.2  Factors affected anabolism of the intestinal epithelium

Repair

Example

Significance

Factor

↑ Anabolism

↑↑ Demand for repair

Alimentation

The passage of food increases the exposure of intestinal epithelium to exogenous and endogenous aggressors

ANS

Para sympathetic

Endocrine, central

Growth hormone

Somatostatin

Endocrine, peripheral

Gastrin Epidermal growth factor

Somatostatin Secretin

Vitamins

Folic acid Glutamine Vitamin A Vitamin D

↓ Need for repair

Fasting

↑↑ Rate of repair

Night; Intestinal flora; Lactation

Reduces the proliferative activity of the intestines In hypercatabolic states, can reduce the rate of intestinal damage, favoring wound healing and reconstruction Increase rate of mitosis for healing and reconstruction Witnesses the importance of rhythmic living Witnesses importance of fasting for at least 3 h before sleep

↓ Anabolism

diarrhea (Chapter 10), promoting these factors favors resolution of illness. Conversely, other somatotropic hormones diminish anabolism of the DT epithelium, which is favorable in a situation such as DT cancers.

Muscle fibers responsible for motility of the intestinal epithelium. In other words, while the consumption of food is necessary for life and nourishment, including for the intrinsic nourishment of the DT, it is also damaging to the epithelium. In contrast, fasting reduces the proliferative activity of the intestines.8 This can be used to the advantage in acute states of injury to the intestines, such as in infectious diarrhea (Chapter  10) or inflammatory bowel disease (Chapter  11). Nighttime, during sleep with the aid of the intestinal flora, participates in the repair of the intestinal epithelium.6, 9 Melatonin and oxytocin are also important factors.10, 11 It indicates how the essential integrity of the intestinal barrier is linked to intrinsic and extrinsic chronobiologic and cosmobiologic factors (cf. The Theory of Endobiogeny, Volume 1, Chapters 5, 6, 11).12, 13

Factors affecting anabolism of the mucosal lining Proper regulation of anabolism of the mucosal lining is capital for the DT because it is constantly at risk of exposure to particular toxins, pathogenic organisms and chemical moieties of foods (i.e., glycosides and phenolic moieties).1 Table 9.2 lists the local and global neuroendocrine factors that regulate the anabolism of the mucosal lining (i.e., epithelium) of the DT. At the neuroendocrine level, it is parasympathetic and somatotropic hormones, systemic and locally produced that favor anabolism.14, 15 In addition, there are key vitamins and the amino acid glutamine.16–20 In situations of chronic denudation, such as chronic ­postinfectious

The most proximal and distal aspects of the DT contain striated muscle under voluntary control. These include the pharynx, proximal esophagus, and the external anal sphincter. The remainder of the tract contains involuntary smooth fiber muscles in two layers: (1) internal circular and (2) external longitudinal.

Histological aspects of the digestive tract Mucosal layer Epithelium consisting of projections called villi (singular, villus), consisting of a single layer of cells. Each villus has thousands of microvilli: tiny projections referred to as the brush border.1, 7 Within each villus are three essential elements: lymphatic vessels, a capillary network and venous drainage (Fig. 9.3). Each plays a direct or indirect role in the quality and quantity of nutrient absorption. Within the core of the villus are lacteals, a type of lymphatic duct involved in nutrition. Bile emulsifies fats and lipase enzymes from the exocrine pancreas break down fats into fatty acids, which are then absorbed by the villi. The fatty acids are modified and combined within chylomicrons transport units. Lipids avoid first pass metabolism by the liver.7 They are taken directly into the lymphatic system. Via the thoracic duct, they enter into the right atrium. From general circulation, chylomicrons will enter the liver from the hepatic artery and be metabolized. The capillary network within the villi regulates the absorption of all other nutrients into the liver via the portal

Motricity of the bowel Chapter | 9  189

FIG. 9.3  Microstructure of the villi. The villi contain thousands of microvilli on their surfaces. Within, they contain a network of capillaries, veins, and lymphatic channels. See text for details. (Image by user Tefi/Shutterstock.com.)

vein.21 After being processed by the liver, nutrients enter general circulation via the hepatic vein and the inferior venous cava. Venous drainage of the intestinal villi, such as the large intestine, pancreas, and parts of the stomach, is not done directly into the vena cava, but first passes through the liver (portal vein).21 It then flows into a second capillary network before leaving the liver and returning to the heart. Within the mucosa are glands with exocrine and endocrine activity. Exocrine activity includes the excretion of acids, enzymes, water, electrolytes, and mucous into the lumen of the small intestine. Endocrine function includes the release of local hormones into circulation to regulate the quality and chronology of digestive activities. Finally, a thin muscular layer exists around the

mucosa that allows for proper mixing and movement of chyme from the stomach.1, 7 The layer immediately outside the mucosal layer is the submucosa (Fig. 9.4). It consists of a neural network called Meissner’s plexus as well as blood and lymph vessels. The external muscular layer contains two layers. The internal layer consists of circular fibers that constrict the intestinal tract. The external layer consists of longitudinal muscle fibers that constrict the DT. Between these two layers is Auerbach’s plexus, a network of nerves that coordinates their contractions and relaxation. The serosal layer consists of connective tissue connecting the intestines to the abdominal wall, fixing the DT to the abdominal cavity.7, 22

FIG. 9.4  The muscular outer structures of the intestines and local innervation. See text for details. (Reproduced from Goran tek-en [CC BY-SA 3.0] via Wikimedia Commons.)

190  The Theory of Endobiogeny

Nervous organization of the digestive tract The nervous system installed in its wall controls sensory, motor, and secretory functions of the DT: the enteric nervous system. This local system is in close relationship with the autonomic nervous system, and there is ongoing information flowing between them.1

Enteric nervous system In the evolutionary imperative perhaps no other function so encompasses the importance of circadian rhythmicity than the intestinal tract. Diurnal rhythmicity is key to the proper mixing, propulsion, digestion, extraction, and expulsion of alimentation and its detritus. Thus the local enteric networks and their integration into regional and global ANS imperatives is capital for intestinal health and that of the global organism. It is no surprise that melatonin, the global regulator of the circadian rhythms is 4000-fold more concentrated in the intestinal tract than in the pineal gland.5 There are two neural networks: the myenteric plexus of Auerbach and the submucosal plexus of Meissner.1 Their neurons serve two general roles: motor or sensory. Motor functions include excitation or inhibition of smooth muscles activity. Secretomotor and vasodilator activity are related to glandular activity and arteriolar tonus.7 Sensory activity is both mechanical and chemoreceptive. There are interneuronal modulators, ascending and descending, and finally, regulators of peristaltic rhythm by the cells of Cajal.1 The interstitial cells of Cajal (ICC) are the fundamental intrinsic pacemakers of the intestinal tract.23 Each section has its own particular rhythm of contracts per minute: stomach: 3, duodenum: 12, ileum: 9, and colon: 3. The connection between enteric and global rhythmicity is expressed through the actions of melatonin on the rhythmic integration of the ICC.24 In other words, melatonin acts as a metronome for the ICC. Enteric neurons establish synapses with other neurons of one or/and the other plexus, or ending on smooth muscle

or glands, and form a complex circuit of relations and local or remote projections. For example, stimuli in the upper part of the small intestine can influence the activity of smooth muscle and glands in the stomach, as well as in the lower part of the DT. The enteric nervous system is sufficiently autonomous to act alone in a highly coordinated manner but is connected to the central nervous system through the autonomic nervous system. The ANS innervation contains cholinergic and adrenergic factors that release other neurotransmitters of which several are small peptides. ATP and nitric oxide play major roles in the nervous system as enteric neurotransmitters and as neuromodulators. The intercellular junction (nexus) allows the propagation of the wave of depolarization thus ensuring the coherent motility of the DT.7

Autonomic nervous system and the enteric nervous system Overview The ANS plays a crucial role in the regulation of the DT function (Fig.  9.5). Digestion is one of the primary domains of influence of the parasympathetic nervous system. Thus, we find that Para plays the agonistic role, and alpha the antagonistic role. Innervation by the ANS involves two serial neurons acting on a target organ: pre- and postganglionic fibers. Preganglionic fibers originate in the CNS. For Para, this is the medulla oblongata. For Alpha, it is the locus ceruleus. All autonomic preganglionic fibers use acetylcholine as a neurotransmitter. Postganglionic fibers are divergent (Fig.  9.5).7 The discharge of the preganglionic motor neurons (sympathetic and parasympathetic) of the medulla oblongata and of the spinal cord is controlled by peripheral afferents and central (encephalic) afferent input. It is the central afferent fibers that are involved in the cephalic phase of salivary, gastric and pancreatic secretions, gastrointestinal motility, and regulation of splanchnic circulation.25

FIG. 9.5  Summary of para- vs alpha-sympathetic activity. Para is within the preganglionic activity of para and alpha because both use acetylcholine as their neurotransmitter. In postganglionic fibers, para uses Ach but has different receptors (muscarinic). Alpha uses different neurotransmitters and receptors. αΣ, alpha-sympathetic; βΣ, beta-sympathetic; πΣ, para-sympathetic; Ach, acetyl choline; Mu, muscarinic receptor; NE, norepinephrine; Nic, nicotinic receptor. (© 2018 Systems Biology Research Group.)

Motricity of the bowel Chapter | 9  191

Parasympathetic (to Auerbach’s plexus) Both central and peripheral branches of the parasympathetic nervous system innervate the DT and associated glands (Table  9.3). The majority of the DT is innervated by the vagus nerve. Thus, the fundamental motricity and production of digestive juices arise from central regulation.1, 7 The Vagal parasympathetic segment also contains an inhibitory pathway that is nonadrenergic and noncholinergic. They are mediated by various vasopeptides, chief amongst them vasoactive intestinal peptide and nitric oxide.26 This pathway is particularly functional at the level of the lower sphincter of the esophagus and of the proximal stomach.27

TABLE 9.4  Sympathetic innervation of the digestion tract and its actions Phase

Origin

Action

Preganglionic

Splanchnic nerve Hypogastric nerve

Transmission of action potential

Postganglionic

Superior and inferior mesentery plexi

Digestive tract • Mouth • Esophagus • Stomach • Small intestines • Ascending colon

Sympathetic

• Transverse colon

The sympathetic innervation of the intestinal tract arises from the sympathetic ganglion chain (Table 9.4).7

Hepato-pancreatic vessels Hypogastric plexus

Elements of regulation of ANS and treatment The nature of substances regulating the ANS has consequences on the effects of prescribed treatments. Recall that parasympathetic is always within alpha-sympathetic. Acetylcholine, the Para neurotransmitter is the de facto presynaptic neurotransmitter for Alpha. Afferent fibers are involved in sensory transmission from the wall of DT. Efferent fibers are involved in motility. Thus, we find that a substance (or medicinal plant) can simultaneously have vagolytic and alpha sympatholytic activity. This implicates that

TABLE 9.3  Parasympathetic innervation of the digestion tract and its actions Branch

Origin

Exit

Action

Vagus (cranial nerve X)

Central: medulla oblongata

Central, “wanders” throughout body

Digestive tract • Mouth • Esophagus

Digestive tract: • Descending colon • Rectum

the plant is primarily working at the level of the presynaptic acetylcholine activity. Conversely, when a plant is described as having opposite effects on the ANS it implicates that it has an activity that is both pre- and postsynaptic. Table 9.5 gives examples of medicinal plants with action on the ANS related to digestion and demonstrates at what level of synaptic function it is working. Salvia sclarea (Clary sage) is a modulator of the ANS. It has alpha-and parasympatholytic activity but does not forcibly inhibit the role of alpha in regulating, for example, corticotropic function. Thus, one of the levels of its action is presynaptic, at the level of acetylcholine (Ach) and not a blockage of excretion of noradrenaline (NA) at postsynaptic level. Conversely, Fumaria officinalis (Fumitory) and Mentha piperita (Peppermint) are slightly vagomimetic but also alpha-sympatholytic. Thus, in the presynaptic chain, it increases Ach activity at the level

• Stomach • Small intestines • Ascending colon • Transverse colon Hepato-pancreatic vessels Sacral nerves (pelvic branch)

Spinal cord: T12-L1

S2-S4

Digestive tract: • Descending colon • Rectum

TABLE 9.5  Pre- and postsynaptic effects of various medicinal plants Presynaptic (Ach)

Medicinal plant

Para

Alpha

Salvia sclarea

↓

↓

Fumaria officinalis Mentha piperita

↑

↑

Postsynaptic (NA) Alpha

↓

192  The Theory of Endobiogeny

of digestion. However, it inhibits the release of noradrenaline at the terminal junction, which is how it can have these two opposing effects.28, 29 The observations of action of certain medicinal plants according to the theory of Endobiogeny may at times be in opposition to experimental, in  vitro and in  vivo data. The reason for this is that in the global system, in clinical practice, we find that the eupeptic or trophic actions of medicinal plants allow digestion to be more efficient, and in this way, they indirectly reduce the need for an adaptative parasympathetic function. In this way, they are vagomimetic at the metabolic level, but vagolytic with respect to the actual level of activity of the vagus nerve within the DT. The ANS participates in the integrated and simultaneous regulation of the following activities: (1) information, (2) sequencing: movement and evacuation, (3) congestion, and (4) permanent regulation of (a) glandular response thresholds, (b) quality of the secretions, (c) intensity of motility and glandular responses, (d) activating buffer systems, (e) installation of the phenomena of congestion (major role), (f) changes the impregnation time of secretions by establishing stagnation zones, and (g) contributions to the inflammatory phenomena. The ANS allows the passage from one digestive level to another by adjusting the sphincter tonus at various levels through the discharge of adrenalin:(1) Upper Esophageal sphincter, (2) Lower Esophageal sphincter, (3) Pylorus, (4) Sphincter of Oddi, (5) Bauhin’s (Ileocecal) valve, and (6) Anal sphincter.30 The primary role of the parasympathetic (tonus and secretions) and secondary beta-sympathetic (expulsion) are very closely involved in regulating the functioning of digestive glands (liver, pancreas), thus playing a major role in the endocrine and metabolic regulation of the body. When treating disorders of motricity, the most effective therapeutic results arise from restoring the normal qualitative and chronologic relationship of the ANS. Cf. The esophageal tone for an example of treating esophageal reflux.

Autonomic control of the gastrointestinal tract The start of digestion is not when the food arrives in the intestines or even the stomach. The flow of digestive juices, from the oral cavity to the duodenum begins with the first thought, sight, or smell of food.31 Peak flow of saliva is reached within 15 min of the first placement of food within the oral cavity, hydrochloric acid peaks by 30 min, and pancreatic enzyme by 38 min.31 The advantage of this process is that it allows the downstream segments of the DT to be prepared to immediately start processing food. Further downstream, it will stimulate the movement of stool further down the colon. As the purpose of the digestion is essentially global cellular nutrition, one sees the logic of the relationship of the autonomic nervous system to this function. Parasympathetic

holds the vital position.31–33 It determines the quantity of secretions discharged into DT.34, 35 Alpha-sympathetic complements the role of para in two ways. At the cellular level, it calibrates the quality of secretions.31 At the muscular level, it calibrates the time in which the bolus is mixed with the secretions by creating more or less extended stasis and retention zones for processing and assimilation.7 Finally, beta-sympathetic changes level of function through contraction and expulsion.36 The nature of secretions changes at various digestive levels; beta initiates the dynamic bowel contraction to allow the passage between the mouth and esophagus, then the stomach, the duodenum/small intestine and finally the rectum for evacuation of waste. This simple physiological observation helps to understand how malfunction of the two branches of the ANS generate all types of congestive and inflammatory phenomena at the DT level, directly connected to their hyperfunctioning. The accessory glands of the digestive system (liver-gallbladder and exocrine pancreas) can be considered as major hubs that help the endocrine and metabolic processes in the DT, thus involving the entire body. The roles of the ANS in digestion are summarized in Table 9.6. A bad management of autonomic balance will have as a secondary result sleep disorders through the intervention

TABLE 9.6  Summary of autonomic nervous system activity within the digestive tract Alphasympathetic

Betasympathetic

Basic level of secretory metabolic function

Prolongs action of parasympathetic

Increase of sphincter tonus generates beta sympathetic response

Regulates the activity of the mucous membranes

Calibrates and limits secretory activity based on local needs

Autolysis of beta induces the relaxation of sphincters, allows the excretion of the content and its movement and evacuation level by level

Increases congestion

Increases the tonus of the sphincter and digestive motility

Followed by a release of para which starts a new cycle

Boosts exchanges between the membranes

Promotes the increase of the processing time of the nutrient in the sector concerned by increasing their tonus

Parasympathetic

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TABLE 9.6  Summary of autonomic nervous system activity within the digestive tract–cont’d Parasympathetic

Alphasympathetic

Improves the assimilation of nutrients

Prepares the evacuation of the production obtained

Strong influence on anabolic activity

Determines the action of beta and the pathway toward the exterior

Betasympathetic

Starts each loop circuit, increases the digestive motility and the tonus of sphincters Induces the secondary alpha sympathetic response which will allow the dynamic evacuation in a third phase

of the circulating hypnogens, the consequence of which is poor digestion (postprandial fatigue, indigestion, etc.).37 In case of digestive solicitation outside of normal mealtimes, there will be solicitation of the para/alpha coupling, which boosts the digestive activity to allow recovery of energy, adapted qualitatively and quantitatively to this solicitation. From this, secondary consequences follow.

Neurotransmitter, autonomic, and hormonal interaction on digestion There are permanent connections between food and cellular nutrition, essential at all levels for ensuring:(1) maintenance of the body’s structure and (2) its functionality, both basic and adaptive. It is clear that the endocrine manager is fully involved in this management, and that there are inseparable connections between the autonomic nervous and endocrine systems. The similarity of the elements that are involved in the regulation of digestion as well as that of the brain function (digestion of emotional and mental phenomenon) may be understood because of this purpose. There are peptides distributed throughout the DT of which several are involved in the regulation of the central nervous system.2, 11, 24, 34, 38–47 Table 9.7 is not exhaustive, merely demonstrative that hormones normally thought of as enteric have central roles and vice versa. Glutamate, leptin, and

TABLE 9.7  Central and peripheral roles of various hormones Hormone

Peripheral

Central

Gastrin

HCl production Gastric motility

Mediates stress response Formation, expression of fearbased memories

CCK

Satiety

Anxiogenic

VIP

Inhibits gastrin Inhibits digestion

Circadian rhythm, SCN

Melatonin

Exocrine pancreatic enzyme production Intestinal motility

Circadian regulation Corticothyrotropic calibration

Serotonin

Glucose absorption Para autacoid

Mood and learning Awareness regulation to circadian rhythm

GABA

Inhibits glucagon

Regulation of neuronal excitability

Somatostatin

Inhibits digestive hormones

Inhibits central hormones

CCK, cholecystokinin; HCl, hydrochloric acid; VIP, vasoactive intestinal peptide; SCN, suprachiasmatic nucleus.

many others can be added to this list.26, 31, 35 This demonstrates the enfolded nature of digestion, consciousness and being. It establishes the integration of the DT (periphery) with the entire body. It confirms the regulation of the DT by the brain, which participates in the normal functioning of digestive cycles from the moment food enters the mouth. But it also establishes the regulation of the brain by the DT, bringing us again to our observation that the various scales of the organization of the organism are constantly integrated and interrelated across scale, space, and time. The characteristic of these substances is that they follow one another according to a specific order along the DT. They act in a manner that is specific, and limited in time and space. They transmit information related to a specific metabolic function. Locally, they use paracrine type signals of endocrine cells (somatostatin, autacoids, etc.) by local diffusion. Remotely, as a buffer system, they reduce the effects of central control over the actors providing the metabolic response. They also avoid shocks to which the body may be submitted according to its operating mode and its needs and adaptive responses. Finally, there is an inverse effect at the cerebral level. The classical axial hormones are not normally associated with the digestive process; however, they each have

194  The Theory of Endobiogeny

particular effects on the process as they are the primary respondents in the adaptation response.48–50 Digestion of exogenous nutrients at some point is contrary to the acute survival demands of the organism, thus the endocrine system, in general, must determine the precise role of digestion. In basal metabolism, because the endocrine system manages metabolism, it creates the demand for particular nutrients in quantity, quality, and distribution according to particular tissular demands. The particular roles of cortisol, estrogens, progesterone, TSH, TRH, etc. are discussed elsewhere. All enteric hormones are somatotropic hormones, and thus they constitute the bulk of the discussion of this chapter.

Stages of digestion There are four stages of digestion. The first is the oral-­ gastro-duodenal phase. It is the phase of psychological awareness of food, preparation, and execution of the physical and chemical processing of food for transformation and assimilation, resulting in a digestible nutrient. The second is the absorption of food. This is the jejunoileal phase within the small intestines. It is the time of physiological absorption to meet the basic needs. The third is the rectosigmoid phase, within the colon. It is the time of reabsorption and reuse of nutrients for adaptation demands (Chapter 11). The final phase is the anorectal phase, which is the elimination of unabsorbable parts of food, the sloughing of DT epithelium, and the waste products of the intestinal microbiome and the global system.

Endocrine relationship The various endocrine axes affect the segments of the DT in particular ways. The corticotropic axis impacts both adaptive and basic nutritional requirements based on the role of aldosterone, which influences water and electrolyte absorption. The gonadotropic axis impacts global structural and basal nutritional requirements related to proteins. The thyrotropic axis maintains a relationship with lymphoid system, including the spleen. The axis also affects cholesterol metabolism and hence gallbladder function. It also regulates muscle turnover, again, impacting protein hydrolysis and absorption. The somatotropic axis regulates the general energy requirements and distribution of nutrients. It has the greatest number of locally produced hormones in the DT which affect all aspects of digestion and absorption.

Cephalic-oral phase The cephalic phase is the commencement of the digestive process. It involves food association, visualization or olfaction; hence memory, mood, emotions, associations, and hedonics all play a part, with a key role played by the ­vagus

nerve, both centrally and peripherally.31, 51 Then comes sight of the food, providing qualitative visual information. Next comes gustation or taste, which is important for proper functioning of the gastric phase of digestion and emptying.31, 52–54 The presence of chemoreceptors in the mouth provides qualitative gustatory information. This is key to allow for the immediate liberation of nutrients, such as glucose prior to replenishment from the diet, and a calibration of the types and quantity of digestive juices required for the food being masticated. Mastication stimulates receptors in the brain. The efferent pathways include parasympathetic (primarily vagus nerve) and sympathetic fibers. The fibers activate neurons in the gastrointestinal nervous plexus, which, in their turn, influence secretion and contractile functions.

Mastication Innervation for mastication comes from somatic nerves of skeletal muscles of mouth and jaw. There are three primary roles for mastication: (1) release of inhibition of reflexes that hold jaws closed by activation of mechanoreceptors, (2) rhythmicity of chewing, and (3) calibration of the rate of digestion or absorption of food through the small intestines.55 The goals of mastication are four. The first is the breaking large pieces of food into smaller particles. The second is grinding food to increase surface area broken for exposure to salivary enzymes. The third is easy and safety of swallowing. The fourth is oral predigestion of carbohydrates and lipids prior to entry into the stomach. This aids the normal progression of subsequent digestive phases and influences energy balance.55 By our estimate, most people chew 5–10 times, whereas many foods require anywhere from 10 to 100 mastications for optimal absorption of nutrients.55 The optimal amount of mastication from our perspective is 20–40, assuming proper preparation of food. This includes soaking grains and legumes, certain cooking techniques, marinating meats in acidic compounds, etc.

Saliva The oral phase cannot be accomplished without the intervention of the salivary impregnation of food, which moistens and lubricates it, and improves taste (Fig. 9.6).31, 55, 56 The daily volume of salivary secretions is approximately 500 mL in adults, the majority being released within the first 15–30 min of each meal.31, 56 There are three pairs of salivary glands. The parotid glands open behind the second upper molars through the papilla of Stensen’s duct. The submandibular gland’s saliva is carried through Wharton’s duct beneath the lower jaw. Finally, the sublingual glands have no duct. They drain directly under the tongue. The composition of their secretions explains their important role in the digestion.19, 40, 41 The first is ­moistening and

Motricity of the bowel Chapter | 9  195

FIG. 9.6  Salivary glands. There are three, paired salivary glands: parotids, submandibular and sublingual. See text for details. (Reproduced from Ellis H. Anatomy of the salivary glands. Surgery (Oxford) 2012;30(11):569-572. Copyright © 2012 Elsevier Ltd. All rights reserved.)

lubrication. It is primarily composed of water and electrolytes. The secondary composition is salivary mucins. They improve the viscosity of saliva and lubricate food for easier swallowing. Saliva also solubilizes and dilutes food, improving the hedonics of taste and calibrating parasympathetic function and other enteric endocrine hormones.19 The second role is as antimicrobial protection. This occurs due to the presence of lysozymes and immunoglobulins: systemic: IgG, IgM, IgA, and local, secretory IgA. The third role is the initiation of digestion of carbohydrates with salivary amylase, and lipids with salivary lipase. Their activity is comparable to that of pancreatic enzymes with an optimum pH of 6.5–7. There is also partial digestion of polysaccharides in the mouth. The fourth role is the information conveyed to the pancreas. The innervation of the salivary glands is a mixture of local and central input. The majority of parasympathetic innervation is nonvagal, from the salivary nuclei of the brainstem.31 Sympathetic innervation originates in the ganglions of cervical regions 2–6 and affects the submandibular and sublingual glands. The quantity and quality of the salivary secretions play an important role in predigestion of food. In case of a secretory insufficiency or excess, quantitative or qualitative at their level, for whatever reason, there will be downstream consequences at the level of organs and systems that will compensate for this anomaly upstream.

ANS and regulation of the salivary secretion The effects of the ANS on saliva are different depending on the nature of autonomic induction (Table  9.8). Parasympathetic increases the abundance and richness of saliva. Hyperfunctioning para increases the risk of parotitis

TABLE 9.8  Role of parasympathetic and alphasympathetic on saliva production Factor

Para

Alpha

Quantity

↑

↓

Quality

Fluid, aqueous

Viscous

Composition

↑ Proteins ↑ Enzymes

↓ Proteins ↑ Mucous

Role

Immediate liberates glucose for adaptive needs

Calibration of saliva to adaptive needs of organism

Distribution

Parotids +++ Submandibular Sublingual

Absent Submandibular Sublingual

Pathology

Parotitis Cancer Aspiration pneumonia

Lithiasis

196  The Theory of Endobiogeny

and parotid cancer according to the theory of Endobiogeny. It also increases the risk of aspiration pneumonia, particularly in children with congenital disorders. Alpha-sympathetic calibrates what para initiates in order to regulate the excessive activity of the salivary glands. A temporary excess of alpha may be adaptive, indicating redistributing water and electrolytes to more essential areas. Prolonged expression of alpha is adaptative and favors parotid stone formation. What is key is the balance of para and alpha.

Functional pairing: ANS-salivary glands Parotid-pancreas-parasympathetic The parotid gland acts as exocrine pancreas analogue in that parotid amylase breaks down carbohydrates in the mouth. Naturally from this arises a functional association between the two glands. What links them together is parasympathetic regulation of their general rate of production of digestive enzymes. In cases of chronic pancreatic exocrine insufficiency, there is a parasympathetic stimulation at the upstream and downstream levels (Table 9.9). Downstream, para stimulates exocrine pancreatic metabolic function to

restore its production of enzymes. If chronic, it often results in pancreatic congestion (cf. The Theory of Endobiogeny, Volume 2, Chapter 8). Upstream, at the level of the parotids, para stimulates a compensatory salivary hyperfunctioning to increase amylase activity. Clinical signs are an increase in the volume of the parotid indicating vagal reaction in response to the insufficiency of pancreatic exocrine secretions, hypertrophy and/or inflammation around the opening of the canal of Stensen. Treatment favors medicinal plants with substitutive amylase activity, such as Plantago major, Carica papaya (leaf), Avena sativa, and Secale cereale rootlet gemmotherapy.28, 29 The particular selection will depend on other aspects of the terrain that is deranged. In cases of excessive exocrine function of the pancreas, one still finds a hyperfunctioning parasympathetic tone (Table 9.10). However, its purpose downstream is to maintain the stimulation of exocrine pancreatic activity based on the adaptative demands of the organism. Upstream, the hyper para is for induction of salivary hyperfunction, increasing amylase activity at the buccal level to aid in the digestive process and reduce partially the demands on the pancreas. The clinical signs are identical to those in the example of pancreatic insufficiency. However, the approach

TABLE 9.9  Para-parotid-pancreas activity due to pancreatic enzyme insufficiency Downstream

Upstream

Treatment

Comorbidities

Para stimulates exocrine pancreatic metabolic function to restore its production of enzymes Clinical: tender pancreatic head reflection point

Para stimulates a compensatory salivary hyperfunctioning to increase amylase activity Clinical: − palpable increase volume of parotid gland

Plantago major

Hives, allergies intestinal, pulmonary conditions

Carica papaya

Celiac, inflammatory bowel disease

− hypertrophy and/or inflammation around opening of canal of Stensen

Avena sativa

Thyroid dysfunction Atopic disease Recurrent ear, nose, throat infections

Secale cereale

Elevated liver enzymes

TABLE 9.10  Para-parotid-pancreas activity due to excess pancreatic enzyme output Upstream

Downstream

Treatment

Comorbidities

Hyperpara: to promote increased salivary output to assist pancreas Clinical: – palpable increase volume of parotid gland

Hyperpara to maintain exocrine pancreatic output according to systemic demand Clinical – tender pancreatic head reflection point

Rubus fruticosus

Recurrent ENT, inflammatory or exudative disorders, diabetes,57 gastritis, sinusitis, colitis, acne, abscesses, furoncles, weeping eczema

Vaccinium myrtillus

Diabetes, eye disease, intestinal ulcers, chronic, recurrent intestinal and urinary tract infections

– hypertrophy and/or inflammation around opening of canal of Stensen

– tender general pancreatic reflection point

Motricity of the bowel Chapter | 9  197

to treatment is different. In this case, one should improve cortisol activity to slow down exocrine pancreatic function and restore an appropriate relationship of somatostatin on the pancreas if cortisol is found to be low on Biology of Functions. The pancreas should also be drained, with plants such as Rubus fruticosus (leaf or bud) or Vaccinium myrtillus leaf, not the fruit.28, 29

Submandibular glands-liver-alpha sympathetic In a similar fashion, there is a relationship between the submandibular glands, the liver, and alpha-sympathetic related to the adaptation response (Table 9.11). In cases of insufficient hepatic secretion, downstream alpha augments to increase congestion to improve dwell time and support activity of the liver. Upstream, there is excessive stimulation of secretory activity of submandibular and submental glands. The clinical sign is the increased volume of submandibular salivary glands. The general approach to treatment is to drain the liver and reduce the global functioning of alpha and para. The most efficient plants in our therapeutic canon are Agrimonia eupatoria, Alchemilla vulgaris, Crataegus oxyacantha, and Salvia sclarea, each having both the actions described and additional properties according to the associated comorbidities (Table 9.11). In cases of excessive hepatic secretion, downstream alpha-sympathetic activity augments to increases congestion of the liver and support its hyperfunctioning. Upstream, alpha overstimulates the secretory activity of submandibular and submental glands. The clinical signs and approach to treatment are identical.

Sequence of the various functions during the oral phase There is initialization of vagal secretory stimulation at the level of the mouth. This local change of ANS function ­informs immediately the entire body that the mechanisms

of digestion are active, which activates changes at both the secretory and motor levels. The secretory changes occur in the (1) Stomach (hydrochloric acid, gastrin14), (2) Pancreas (insulin, enzyme secretion), and (3) Gallbladder (bile). The motor activity includes immediate closure of the lower sphincter of the esophagus, and an increase of motility of the DT and basal tone of the sphincters. Thanks to specific (involuntary) motor mechanisms and the secretion of lubricating mucus, the esophagus—a simple tube—allows the passage of the food from the mouth (the only voluntary motility) downstream where the food will be processed.58 Reflexes triggered by pressure receptors in the walls of the pharynx coordinate swallowing. Oropharyngeal passage involves motor innervation at three levels. First is parasympathetic, by the vagus nerve. The second is sympathetic, from the cervical dorsal root and ganglion relay points. The third is receptors in the oropharyngeal cavity. The pharyngeal phase commences when the bolus arrives in the pharynx. The soft palate rises and lodges against the posterior pharyngeal wall, thus preventing food from entering the nasal cavity. When the tongue pushes the food in the pharynx, the bolus flips the cartilaginous epiglottis, which closes the glottis. The esophageal phase follows. The proximal one-third of the esophagus contains voluntary skeletal muscle. The remainder contains involuntary smooth muscle.58 The same requirements for ANS sequencing are in play with the esophageal passage of food. Proper timing and duration of Beta play a key role in preventing obstructing and choking. Achalasia is the impaired passage of food during the esophageal phase. It can be treated easily with essential oils, which nearly instantaneously reestablish the proper role of adrenaline in the sequencing of muscle contraction. For acute treatment, Piper nigrum (Black pepper) essential oil is the most efficient.59 For systemic or chronic regulation of beta-sympathetic tone, we recommend Cinnamomum zeylanicum (Cinnamon) essential oil or a decoction of the bark.60, 61

TABLE 9.11  Alpha-liver-submandibular glands in adaptation Downstream

Upstream

Treatment

Comorbidities

Hyperalpha to congest liver Clinical: tender liver, superiormedial costal margin

Hyperalpha stimulation of submandibular, submental glands Clinical: – palpable increase volume of submandibular gland

Agrimonia eupatoria

Best general support; allergies Intestinal, pulmonary conditions, dual pancreatrope

Alchemilla vulgaris

Pelvic congestion, luteal phase disorders, acne

– hypertrophy and/or inflammation around opening of canal of Wharton

Crataegus oxyacantha

Heat with digestion, anxiety, tachycardia

Salvia sclarea

Fatigue, adrenal insufficiency, hypothyroidism with hypogonadism

198  The Theory of Endobiogeny

Treatment of achalasia Acute: Piper nigrum essential oil ● ●

General population: Inhale for 3–5 min before eating Neurologically impaired, children, elderly: ● Place 1–3 drops on bib or clothing for passive inhalation throughout the meal

Chronic, Systemic: Cinnamomum zeylanicum Leaf essential oil, oral: ●

1 drop in 1 tsp. vegetable glycerin, 15 min before meals and consume per orum

Bark decoction, oral: ● ● ● ●

Esophageal veins are a junction between the portal venous system that absorbs nutrients from the small intestine and the superior vena cava. In case of portal vein hypertension or obstruction, splanchnic venous return is carried out in part by the esophagus toward the superior vena cava. This can result in esophageal varices.63 Draining the portal vein and ensuring good splanchnic drainage is important in these cases. The two most efficient plants for Portal and Splanchnic drainages are Carduus marianus and Matricaria recutita.28, 29 They should be used in conjunction with a vasculotonic plant, such as Corylus avellana gemmotherapy, or vasculoprotective plants, such as Cichorium intybus, Vaccinium myrtillus.9, 29 The specific selection will depend on the patient’s comorbidities (Table 9.12).

Esophageal varices formulas

Crush 15 cm bark Decoct in 250 mL water for 20–30 min Strained Consumed 15 min before meals

The passage of food requires a negative pressure gradient but is aided by the positive pressure gradient between the oral cavity and the chest. The oral cavity, pharynx, and proximal esophagus require a pressure gradient of 10 mmHg, which is equal to atmospheric pressure. However, the distal esophagus requires a higher pressure gradient, typically >12 mmHg, which aids in preventing reflux from the stomach.62 These differences in pressure should have the tendency to force the passage of air (downward) and of the stomach contents (upward) in the esophagus. This does not occur, because the contraction of the sphincter muscles closes the two extremities of the esophagus. There is an importance of sequencing and synergy of reflex phenomena in the swallowing process. As the skeletal and smooth muscles are involved in this reflex, the swallowing center must direct the efferent activity: toward the skeletal muscles (by somatic nerves) and toward the smooth muscle (vegetative nerves: parasympathetic fibers).58

(cf. The Theory of Endobiogeny, Volume 4 for a more complete discussion about esophageal varices and additional medicinal plant prescriptions) A 63-year-old alcoholic man with esophageal varices with recurrent bleeds, mild hepatic cirrhosis, and type 2, ­noninsulin-dependent diabetes can be treated with: Matricaria recutita MT 80 mL, Carduus marianus MT 80 mL, Vaccinium myrtillus 80 mL: 4 mL before lunch and dinner and 8 mL before bed during the acute phase of recovery, then 2.5 mL before lunch and dinner, and 5 mL before bed. A 57-year-old woman with esophageal varices, anticipatory anxiety, insomnia, and palmar erythema can be treated as follows: Carduus marianus MT 120 mL, Matricaria recutita MT 40 mL, Corylus avellana GM 80 mL: 4 mL before lunch and dinner and 8 mL before bed during the acute phase of recovery, then 2.5 mL before lunch and dinner, and 5 mL before bed.

TABLE 9.12  Treatment of esophageal varices using medicinal plants Plant

Drainage

Vascular

Autonomic

Other

Carduus marianus

Portal, splanchnic, hepatobiliary

Circulatory tonic

Alpha-sympathomimetic (mild, on microcirculation)

Hypoglycemant

Matricaria recutita

Hepatic, splanchnic

Hypotensive

Sympatholytic, vagolytic

Eupeptic, antiulcerative (gastric)

Cichorium intybus

Portal

Vasculoprotective, hypotensive

Parasympathomimetic

Eupeptic, exocrine pancreatic stimulant

Vaccinium myrtillus

Intestines, pancreas

Vasculoprotective, capillary tonic

Corylus avellana

Lungs, heart, neurologic

Vasculotonic

Hypoglycemant, antigastritic Alpha-sympatholytic (indirect by action on locus ceruleus)

Eupeptic, antiulcerative (gastric), hepatic anticirrhotic

Motricity of the bowel Chapter | 9  199

Esophageal peristalsis Two sphincters play a crucial role in the passage of food: the upper esophageal sphincter (UES) and lower esophageal sphincter (LES). The esophageal phase of swallowing starts at the passing of the pharyngeal contractile wave through the UES, the skeletal muscle around the esophagus just below the pharynx, which prevents the entry of air into the DT. The tonus of the UES is ensured by the basal parasympathetic tone.58 Patients who suffer from Aerophagia have excessive parasympathetic activity, which lowers the resting tone of the UES, allowing more air to enter into the esophagus. During swallowing, a pharyngeal contractile wave propagation by the parasympathetic increases UES tonus. Alpha further increases and tonifies the UES tone. Beta leads to its opening. After the passage of the bolus the UES sphincter closes. The glottis opens and breathing resumes. Progression of food down the esophagus is possible, thanks to the striated muscles for the upper portion and the smooth muscle of the distal portion (parasympathetic plays a very important role). The bolus is pushed by peristaltic esophageal waves. It takes 9 s for a bolus of food to reach the stomach. Gravity plays no role. At the very least, we recommend that patients chew the subsequent bit of food for 10 s (or longer) after swallowing the prior bolus. The opening of the LES, which remains relaxed during the swallowing phase allows for penetration of the bolus into the stomach. Closure of the LES blocks the passage between the esophagus and the stomach, thus preventing reflux of stomach contents (Fig. 9.7).58, 64 It provides a barrier

between the stomach and the esophagus. This is facilitated by the fact that the last portion of the esophagus is located under the diaphragm (subject to the same abdominal pressures as the stomach).58 If a large piece of food does not reach the stomach during the first peristaltic wave, the distension of the esophagus by that piece activates receptors that trigger reflexes resulting in repeated waves of peristaltic activity (secondary peristalsis). From top to bottom, the lower part of the esophagus consists of three structures. The first is the epiphrenic ampulla. The second is the vestibule; which is the tapered end of the lower esophagus. This is where the LES is located, between the thorax and abdomen. The third is the cardia: the junction between the mucosa of the esophagus and that of the stomach. This junction is subject to numerous anatomic variations some of which promote the risk of gastroesophageal reflux.58 Normally it forms a z-line. If this line becomes circular, it shows an upward slide of the esophagus that may cause a hiatal hernia. During inspiration, the diaphragm tightens the digestive lumen preventing the reflux of the stomach into the thorax. There is a high-pressure zone: 15–55 cm of water (intraesophageal −5 cm and intragastric +8 cm). Therefore, the proper functioning of LES depends closely on the local anatomical conformation (need for a sufficient length of the intraabdominal esophagus, 3–5 cm) and on autonomic regulators. The esophagus penetrates obliquely into the stomach (angle of His), making a sort of valve, doubled by the muscular ring that constitutes the diaphragm (=external sphincter). The junction between the esophagus, the stomach, and the diaphragm is ensured by a ligament system (phrenogastric and phrenoesophageal ligament).

Local autonomous regulation of the lower esophageal sphincter (LES)

FIG. 9.7  The lower esophageal sphincter prevents reflux of bolus in the stomach back into the esophagus. See text for details. (Reproduced from Fuchs KH, et al. Shackelford’s Surgery of the Alimentary Tract, 2 vol. Set (8th ed.). Copyright © 2019 Elsevier Inc. All rights reserved.)

There is a need for a permanent and balanced parasympathetic tonus to avoid the reflux at the time of the meal but not excessive in order to avoid the risk of stagnation of the food in the esophagus. The arrival of a bolus in the end portion of the esophagus will distend the epiphrenic ampulla, which then generates the alpha-sympathetic reaction rather than beta-sympathetic discharge, allowing the opening of LES sphincter during its lysis. There are other factors from the downstream areas that are also involved, chemical or hormonal in nature: Gastrin, secretin result in increased vagal tonus. Gastro-esophageal reflux disorder (GERD) can arise due to insufficient LES tone, or excessive tone on the pyloric sphincter of the distal stomach.58 According to an Endobiogenic nosology, GERD type 1 is a hyperfunctioning of parasympathetic tone on the LES. During contraction of the stomach, with normal intragastric pressure, there is a retrograde movement of chyme and acid. The treatment is to use parasympatholytic plants with

200  The Theory of Endobiogeny

TABLE 9.13  Treatment of GERD, type 1, using parasympatholytic, eupeptic medicinal plants Plant

ANS

Other properties

Indications

Thymus vulgaris

Parasympatholytic

Adrenal cortex stimulant Emmenagogue

Ocimum basilicum

Sympatholytic, parasympatholytic

Adrenal cortex stimulant FSH/LH stimulant, estrogenic

GERD + depression, fatigue, insomnia GERD + amenorrhea, infertility, etc.

Carum carvi

Muscular spasmolytic, parasympatholytic

Reduces adrenal androgens, cholagogue, carminative, estrogenic, uterolytic

GERD + irritability, acne on jawline

Menyanthes trifoliata

Beta-mimetic

Antiinflammatory, antiandrogenic, estrogenic

GERD + inflammation, acne, prostatic hypertrophy, uterine leiomyoma, etc.

DIET

Reduce volume of food per meal, avoid acidic, fatty or fried foods, or red meat

e­upeptic activity (Table  9.13). The volume of food consumed should be reduced. In addition, the diet should be modified to avoid acidic, fatty or fried foods or red meat.14 Cf. Regulation of the stomach. GERD type 2 is a spasmophilic hyperfunctioning of alpha- and parasympathetic activity, where alpha is greater than para. The delay in beta occurs at the level of the pyloric sphincter. During contraction of the stomach, there is elevated intragastric pressure to overcome the resistance at the level of the pylorus. This results in retrograde movement of chyme and acid into the esophagus. The treatment involves the use of Para- and Alpha-sympatholytic plants in conjunction with beta-mimetics (Table  9.14). The volume of food consumed should be reduced. Nonacidic beverages should be consumed 30 min before or 1 h after the meal has

been completed. The patient should feel unstressed when eating. The diet should be modified to avoid acidic, fatty or fried foods.14 Cf. Regulation of the stomach. For example, in a patient with GERD type 2, depression and insomnia, one can use (in addition to dietary changes): ●

Salvia sclarea MT 60 mL, Menyanthes trifoliata MT 60 mL, Lavandula angustifolia EO 2 mL: 3 mL before meals

For a patient with GERD type 2, intestinal candida and anal itching, one can use (in addition to dietary changes): ●

Juglans regia MT 120 mL, Lavandula angustifolia EO 1 mL, Cinnamomum zeylanicum EO 1.5 mL 3 mL before meals

TABLE 9.14  Treatment of GERD, type 2, using medicinal plants that regulate the ANS Plant

ANS

Other properties

Indications

Salvia sclarea

Parasympatholytic Alphasympatholytic

Supports adrenal cortex and thyroid, estrogenic, eupeptic, pancreatic drainer

GERD + nervous asthenia, fatigue, amenorrhea, hypothyroidism, etc.

Lavandula angustifolia

Parasympatholytic Alphasympatholytic

Reduces adrenal cortex activity, hepatobiliary drainer, antiallergic, antispasmodic

GERD + insomnia, chronic fatigue, allergies, migraines, etc.

Cinnamomum zeylanicum

Beta-mimetic

Eupeptic, regulates intestinal flora, antimicrobial with tropism for digestive tract

GERD + intestinal candidiasis or intestinal parasites, dysbiosis with bloating and gas, asthma

Menyanthes trifoliata

Beta-mimetic

Antiinflammatory, antiandrogenic, estrogenic, beta-sympathomimetic

GERD + inflammation, acne, prostatic hypertrophy, uterine leiomyoma, etc.

Diet

Reduce volume of food per meal, drink 30 min before, or, 1 h after meal, feel unstressed when eating, avoid acidic, fatty or fried foods

Motricity of the bowel Chapter | 9  201

Regulation of the stomach

Gastric volume

Gastric phase

The empty volume is approximately 50 mL in adults. It can expand 30-fold to 1500 mL at the end of a meal. The receptive relaxation is done through para, coordinated by the swallowing center in the brainstem. Peristalsis occurs every 3 min. The cells are located in the layer of smooth longitudinal muscle. Alternating depolarization/repolarization discharges are the fundamental electrical rhythm of the stomach. The endocrine system (primarily local), as well as neurotransmitters, respond to the quantity of gastric contents emptied in the duodenum at each contraction.

The gastric phase of digestion is triggered by the modification of the gastric motility, which is controlled by various factors.14 Stimulatory events are of two kinds. The first is a general distention of the stomach, which stimulates local reflexes and the vagus nerve. The second is specific aspects of food, viz., amino acids and rising pH. This triggers G cells to releases gastrin (Table  9.15). Gastrin stimulates hydrochloric acid in the stomach and zymogens in the pancreas, in anticipation of the intestinal phase of digestion. The inhibitions of the gastric phase are three. The first two are intrinsic to the stomach. The first is falling pH, which inhibits gastrin release. The second is negative emotional valences that stimulate sympathetic tone to dominate parasympathetic tone and slow down the general motricity of the stomach. The third is feedback from the intestines. When there is duodenal distension, or excessive fatty acids, hypertonicity of chyme or noxious substances, there is inhibition of gastric phase stimulants. Local reflexes, the vagus nerve, and the pyloric sphincter are inhibited to prevent further release of chyme into the small intestine. Thus, it is clear from an Endobiogenic perspective that a common cause of prolonged dwelling of food in the stomach and/or GERD is biliary or exocrine pancreatic insufficiency, as well as spasmophilia with alpha-sympathetic predominance over para and beta.

Gastric anatomy and function Antrum The lower portion of the stomach, the antrum, has a layer of smooth muscle much thicker than the upper part. The glands of this region produce little acid, but they contain endocrine cells that secrete the hormone gastrin.65

Fundus: Parietal cells and hydrochloric acid The epithelial layer lining the stomach invaginates into the mucosa, thus forming many tubular glands in the thin walls of the upper portions of the stomach, body, and fundus. Cells at the orifices of these glands produce mucus. The Parietal cells produce approximately 1.5 L of hydrochloric

TABLE 9.15  Summary of gastric hormones Hormone

Function

Location

Stimulated by

Inhibited by

Gastrin

Gastric acid production Pepsinogen secretion Increase gastric mucus Increase gastric motility Pyloric sphincter constriction Reduced gastric emptying

G cells (stomach and duodenum)

Diet: alcohol, amino acids, caffeine Vagus nerve Antral distention Duodenal distension

Gastric acidity Somatostatin Secretin Glucagon

Somatostatin

Inhibits gastrin secretion Reduces gastric motility Reduces gastric emptying

Gastric D cells

Gastric acidity

Vagal stimulation

Motilin

Increases gastric motility Increases gastric emptying Associated with the interdigestive migratory motor complex (MMC)

Entero-chromaffin-like cells in proximal small intestine

CCK

Reduces gastric acid secretion Reduces gastric emptying Gallbladder contraction

Duodenal and jejunal I cells

Increased fat in duodenal chyme

Secretin

Reduces gastric acid secretion Reduces gastric emptying Increases pancreatic secretions

Duodenal and jejunal S cells

Increases acidity in duodenal chyme

Modified from Jolliffe DM. Practical gastric physiology. Contin Educ Anesth Crit Care Pain 2009;9(6):173-177.

202  The Theory of Endobiogeny

acid (HCl) per day,65 which can increase twofold under the influence of histamine.66 The greatest rate is during meals. The concentration of protons in the lumen of the stomach = 150 mM = or 3 × 106 their concentration in the blood. ATPase pump pumps hydrogen ions in and potassium ions out of the stomach lumen to maintain a high degree of acidity. As the hydrogen ions are secreted into the lumen, the bicarbonate ions are secreted by the opposite side of the cell into the blood, thus lowering the acidity of the venous blood coming from the stomach. HCl plays three main roles in the body. It modifies the ionization of polar molecules and degrades proteins in the food. It has no action on lipids. It destroys most bacteria associated with food or colonizing the nose, throat, and mouth. Finally, via excretion of intrinsic factor, it helps protect alimentary vitamin B12 from degradation in the stomach, allowing it to be absorbed in the small intestines.65

Principal cells: Pepsin and protein digestion Principal cells excrete enzymes that aid in the digestion of proteins.65 Pepsinogen is a preenzyme converted to pepsin by an autocatalytic, positive-feedback process that occurs in a low acidity environment (created by HCl). Pepsin is inactivated in the alkaline environment of the small intestine. Bicarbonate from the exocrine pancreas neutralizes stomach acid and deactivates it.65

Pepsinogen-HCl functional pairing The enzymes in the small intestine can compensate for the absence of pepsin and ensure complete digestion of proteins. Thus, a different type of cell secretes each of the three main exocrine substances: mucus, acid, and pepsinogen. The neural pathways and duodenal hormones that are involved in this regulatory process act directly on the parietal cells or indirectly, influencing the secretion of gastrin, which in turn influences directly the secretion of acid by the parietal cells. Thus, the chyme obtained contains molecular fragments of macromolecules: proteins, polysaccharides, and lipid droplets that cannot cross the epithelium of the gastric wall. There is little absorption of organic nutrients in the stomach because the food is partially dissolved and digested. There is thus a need for an antiacid mucus.65

Dynamics of gastric regulation The mandatory sequencing of the digestive dynamics involves phenomena that are upstream and downstream of the stomach. Parasympathetic nerves of the stomach trigger the secretion of acid when seeing the food or sensing it in the mouth. Before the food arrives in the stomach the following occurs: (1) increased concentration of protons, (2) reduced buffering agents against protons to favor acidity, and (3) inhibition of gastrin if acidity is too elevated. The

following foods trigger secretion of gastric acid regardless of the gastric pH when they have reached the stomach: (1) Proteins, (2) Calcium, and (3) Coffee (including decaffeinated). Avoidance of these foods or delay until the end of the meal is advantageous in patients suffering from hyperacidity and/or reflux. The gastric phase begins, once the food has reached the stomach. During this time there is: (1) increased arrival of proteins, (2) increased concentration of peptides, (3) decreased concentration of protons, (4) increased release of gastrin, and (5) increased secretion of hydrochloric acid. These responses to peptides and to low acidity explain why the amount of acid secreted increases after a protein-rich meal. Thus, the buffering of the acid, secretion of gastrin, and the quantity of secreted acid increase proportionally with the protein content of a meal. When the stomach phase is completed, the bolus reaches the duodenum. The rise in duodenal acidity form chyme stimulates a reflex that inhibits the secretion of acid in the stomach. Several paracrine agents may affect acid secretion, chiefly histamine and prostaglandins. All told, the numerous hormones produced within the stomach stimulate or inhibit the gastric phase of digestion (Table  9.15). They demonstrate how digestion is determined both by the quality and timing of food entry, but also by systemic physiological and psychological considerations as well.14

Histamine and acidity Histamine released by the gastric mucosa may cause a considerable increase in acid secretion by the parietal cells.65 Acid solutions reduce digestive enzyme activity and bile salts in the small intestine. This reflex helps reduce the secretion of acid by the stomach each time the chyme enters the small intestine. Otherwise, gastric secretions would be so acidic that the liquids rich in bicarbonate ions simultaneously secreted in the small intestine by the liver and the pancreas could not neutralize them. Prolonged consumption of acid-reactive foods (red meat and refined carbohydrates) can affect long-term pancreatic enzymatic activity, increasing the risk of disorders such as amyloid diseases (viz., Alzheimer’s disease and diabetes type 2) and stroke. Pancreatic enzymes are constantly excreted outside of meals, especially during sleep to remove accumulated protein and proteoglycans species such as fibrinous clots, amyloid proteins, etc. This witnesses the value of a diet rich in alkaline-reactive foods and overnight fasting of 13–14 h between dinner and breakfast.8 Late dinners or evening snacking reorients pancreatic enzymes stored for nocturnal cleansing toward diurnal digestive activity. Reflex inhibition of the secretion of gastric acid is affected by seven factors: (1) Volume and composition of the meal, (2) distension of the walls, (3) high acidity of the

Motricity of the bowel Chapter | 9  203

chyme in the duodenum, (4) hypertonic solutions, (5) solutions containing amino acids, fatty acids or monosaccharides, (6) enterogastrones: family of duodenal hormones that inhibit propulsive activity of stomach in releasing chyme (Secretin, Cholecystokinin, and Gastric inhibitory peptide), and (7) long and short nervous reflexes.14 This is in order to adjust the secretory activity of the stomach and the digestion and absorption capacity of the small intestine. There is a brief and mild physiological reflux in healthy persons during the postprandial period. There is also a persistent GERD (gastroesophageal reflux) in infants up to the age of 3 months, because of the immaturity of the LES. There are generally no major consequences outside the postprandial and postural regurgitation frequent at this age.

The small intestine: Functional considerations

Villus

The digestion of food continues in the small intestine where food digestion phenomena are completed. Substances not digested upstream are digested then absorbed. This includes water and electrolytes, as well as nutrients. The absorptive capacity in the duodenum and the rest of the intestine implies that the luminal structure is adapted to this function according to the requirements and the specific adaptive purpose of different intestinal segments. The intestinal loop is approximately 5–7 m long, with two-fifth proximal, and three-fifth distal. With the villi and microvilli, the absorptive area can be as great as is approximately 300 m2 (3200 ft2—about the size of a large home).1 Other structures include the valves, which are transverse folds of mucosa

and the intestinal villi. There are the crypts of Lieberkühn, which are folds of mucosa between the villi (Fig. 9.8). The crypts and villi regulate the timing of gastric and intestinal digestion and absorption. What is more, they have an exocrine pancreatic-like activity. They also contain stem cells due to the rapid turnover of the intestinal epithelium, given its exposure to chemical moieties, noncommensal microbes and wide swings in pH.67 There is also the mucosal chorion, a type of connective tissue which is the axis of the villi. They have intense vascular activity, a very developed vascular system, with a rich lymphatic network. Protection of mucosa is ensured by the mucous secretions produced by Brunner’s glands located in the connective-vascular submucosa of the first segment of duodenum D1.1 This mucous is alkaline mucus acting as an antiacid buffer. Epidermal growth factor is also secreted to constantly repair the mucous damaged by the acidity of chyme. The cell types present in the mucosa are suitable for absorption to enable the structuring of the body (Table  9.16). There are different distribution according to the portion of the digestive tube. All cell types are present in the duodenum. In the ileum, only D, EG, and EC cells are present. For defense, the lamina propria cells contain a series of mononuclear cells. The arrival in the duodenum of gastric acid chyme with high osmolality will induce two joint phenomena: inhibition of gastric activity and installation of the digestive assimilation phase. Inhibition of the gastric activity to curb the nutrient intake in order to allow enough time for the activation of the duodenal segments and enable them to exercise their functions. It is augmented by four factors: (1) lipids (strong association), (2) acidity, (3) hypertonic solutions, and (4)

Differentiated cells Absorptive Enterocyte

TABLE 9.16  Small intestinal cell types and activity

Secretory

Cell type

Goblet Enteroendocrine Tuft Paneth

Crypt

FIG.  9.8  Structure and function of the intestinal villi. The villi and the crypts between them contain absorptive, secretory, progenitor, and stem cells. These cells have various roles related to the timing and progression of digestion and absorption of nutrients. See text and Table 9.16 for details. (Reproduced from Carulli AJ, Samuelson LC, Schnell S. Unraveling intestinal stem cell behavior with models of crypt dynamics. Integr Biol 2014;6(3):243257. DOI: https://doi.org/10.1039/C3IB40163D [CC BY 3.0].)

Activity

Enterocytes

Digestive enzymes

Apical membrane

Digestive enzymes

Crypts

Progenitor cells Transit-amplifying (TA) Stem cells +4 stem cell (QSC) Crypt base columnar Cell (CBCC/ASC)

Example

Endocrine cells

Goblet cells

Mucous, alkaline

Paneth cells

Digestive enzymes Bactericidal lysozymes

S cells

Secretin

I cells

Cholecystokinin

D cells

Somatostatin VIP

G cells

Duodenal gastrin

EG cells

Enteroglucagon

EC cells

Enterochromaffin cells

204  The Theory of Endobiogeny

distension. It results in four events: reduction of (1) gastric evacuation, (2) entry of chyme into the duodenum, (3) entry of large molecules, and (4) secretion of acid and pepsin. Large meals with irregularity in the evacuation of chyme results in three events: (1) rapid digestion of proteins and polysaccharides by the enzymes of the small intestine, (2) Introduction of a hypertonic solution in the small intestine, and (3) risk of vomiting or dumping syndrome. The installation of the digestive assimilation phase occurs through induction of biliary and pancreatic secretions. Both phenomena involve neuroendocrine mechanisms. The ANS is involved in local reflexes accented by distention of the stomach (parasympathetic). The primarily endocrine involvement is local from the somatotropic axis. Gastric gastrin stimulates the secretion of pancreatic enzymes. Duodenal secretin also stimulates the exocrine pancreas. Recall that it is diminished by gastrin and stimulated by acidity, proteins, and fatty acids. Cholecystokinin slows down gastric evacuation and also stimulates exocrine pancreatic secretions. Finally, the exocrine pancreas itself excretes bicarbonate to buffer the acidity of gastric chyme.1, 14

Activity of the small intestine Parasympathetic fibers arise from the brain stem. Sympathetic innervation arises from the dorsal marrow segments 6–12. These segments play a role in fast contractions and propulsion of chyme. Neuronal and hormonal regulation ensures a constant and even flow into the small intestine through the control of gastric emptying, moving into the duodenum and then into the small intestine. The intestines handle approximately 2000 mL of liquid each day. Most of it

is from endogenous digestive juices: saliva, gastro-duodenal, hepatobiliary, and exocrine pancreatic. Of course, it also absorbs the water content of foods and ingested liquids. One swallows up to 500 mL of air during a meal. Burping (eructation) is the escape of this air before it leaves the stomach. Once it passes into the intestines, it expresses itself as gurgling (borborygmus) until it reaches the rectum. Then it expresses itself as flatus. These conditions can be treated with medicinal plants according to the theory of Endobiogeny (Table 9.17).28, 29

Motility During a meal, there are alternating contractions and stationary rhythmic relaxation of intestinal segments, without visible movement toward the large intestine. Segmentation allows for mixing of the chyme, pushed upwardly and downwardly toward the intestine. Unlike the gastric rhythm that is normally unified, the intestinal rhythm varies throughout the intestine, each successive region having a frequency slightly slower than the upstream region: Duodenum: 12/min, Terminal ileum: 9/min.30

Concept of migration motility complex Meals augment the peristaltic waves in the lower part of the stomach. They travel short distances (about 60 cm) along the small intestine before the propulsive force fades, after which they migrate slowly taking 2 h to reach the large intestine.1, 30, 31 This is a repetitive process that functions in a repetitive loop that ends with a subsequent meal, which restarts the segmented activity again. Small intestinal

TABLE 9.17  Treatment of eructation, borborygmus, and flatus Location of air

Clinical

Medicinal plants

Best galenic form

Route

Gastrum

Eructation

Achillea millefolium

Tisane, oral

Tisane: oral

Rosmarinus officinalis

EO, inhalation

EO: inhalation

Mentha piperita

EO, tisane

Lavandula angustifolia

EO

Tisane: oral EO: topical

Origanum vulgare

EO, tisane

Thymus vulgaris

EO, tisane

Achillea millefolium

Tisane

Carum carvi

EO

Mentha piperita

EO, tisane

Rosmarinus officinalis

EO

Intestines

Rectum

Borborygmus

Flatus

Tisane: oral, rectal EO: inhalation, rectal

Notes: EO inhalation: 2–3 min, Tisane: 3–5 min steep, ½ tsp. per 200 mL water, may use less if feeling distended; avoid Mentha piperita with known gastric reflux, Topical: should be diluted; works within 5–10 min with friction rub or heat, Rectal: Dilute; Do Not Use Mentha piperita in rectal application >1% dilution.

Motricity of the bowel Chapter | 9  205

­ igration which takes longer than 2 h favors stagnation and m microbial overgrowth due to delayed digestion of residual material.

Role of motilin Motilin is a gastrointestinal hormone that stimulates motility. It directly stimulates motility complexes within the DT, particularly the duodenum and jejunum. Indirectly, it stimulates the release of acetylcholine.1, 30, 31 Reflexes occurring at different points along the DT can alter the contractile activity in the various parts of the small intestine. We mention four: (1) gastroileal reflex, (2) gastric evacuation, (3) increases of segmentation in the ileum, and (4) intestinointestinal reflex. This last reflex can completely shut down motility in cases of significant distension of the large intestine, including from constipation, lesions of the intestinal wall, or presence of bacterial infections.1, 30, 31 The duodenum is the part of the DT in which the hepatobiliary and exocrine pancreatic secretions meet. The common bile duct and the pancreatic duct merge together at the ampulla of the hepatopancreatic sphincter, also known as the sphincter of Oddi. Both ducts and the ampulla are encircled by circular and longitudinal muscle bunds that allow for “milking” or contraction of the ducts. A separate bundle of muscles forms the sphincter. Both bile and zymogens and bicarbonate are excreted into the duodenum. Malfunction of this sphincter—particularly in spasmophilic terrains (cf. The Theory of Endobiogeny, Volume 2, Chapter  11)—can lead to upstream dysfunction of the respective glands, and downstream impairment of digestion and commensal populations. According to the theory of Endobiogeny, Murphy’s point is a reflection point for spasming of the sphincter of Oddi. Murphy’s point is the middle of an imaginary line drawn from the umbilicus perpendicular to the right costal margin.

Intervention of exocrine pancreatic secretions The exocrine secretory activity of the pancreas, diminished outside of digestive period, is necessary for the digestion of carbohydrates, lipids, and proteins. The nutrients found in the small intestine trigger through hormonal reflexes secretions that participate in their own digestion. The pancreatic secretions are rich in electrolytes, particularly bicarbonates. They are also rich in enzymes: (1) glycolytic enzymes: alpha amylase, (2) lipolytic enzyme: lipase and phospholipases, and (3) proteolytic enzymes: endopeptidases (trypsin or chymotrypsin and elastase) and exopeptidases.68 Most of the proteolytic enzymes are secreted in inactive forms (zymogens), which are activated by other enzymes in the duodenum, for example, conversion of trypsinogen to trypsin via enterokinase.

In contemporary medicine, the role of digestive enzymes is generally limited to patients with frank signs of enzymatic deficiency, in extremis, such as pancreatitis, cystic fibrosis, and pancreatic cancer.69 The theory of Endobiogeny identifies certain signs and symptoms with a relative insufficiency of pancreatic enzymes (cf. The Theory of Endobiogeny, Volume 2, Chapter  8). Empirically, we have found that digestive enzymes are beneficial for relative insufficiency as well as frank deficiency of exocrine pancreatic excretions. In addition to the use of enzymes, a number of medicinal plants have substitutive, enzyme-like activity (Table 9.18).22, 28, 29, 70, 71 When various medicinal plants are combined in various combinations a broad spectrum of digestive support can be offered to patients related to the role of the pancreas in various types of disorders. By simply combining two or three of these medicinal plants, a number of disorders and their emunctory elements of terrain can be addressed quite efficiently. Table 9.19 demonstrates the combination of Plantago major with one other plant to indicate the types of disorders that can be treated. In other words, given a patient with signs or symptoms of exocrine pancreatic insufficiency, the particular combination any of plants can be more precisely selected by considering the global terrain and the disorders that the patient suffers from. Similarly, a combination of Avena sativa + Medicago sativa can be used to treat signs and symptoms of exocrine pancreatic insufficiency in patients who also have one or more of the following conditions: acne, ear, nose, and throat infections (adults) and estro-androgenic imbalances, such as PMS, prostate conditions, cysts (ovarian or otherwise), etc.

Exocrine pancreatic secretion The exocrine pancreas has classically been understood to be stimulated by the vagus nerve and enterohormones already discussed.25 Exocrine pancreatic secretions are released throughout various phases of the digestive process. The cephalic phase (thought, association, sight, smell, or taste of food)31 stimulates approximately 15%, gastric distention 15%, and intestinal phase the remaining 70%.25, 68 In the stomach secretin increases the secretion of bicarbonate from the pancreas in anticipation of the acidic chyme to come. In the duodenum, cholecystokinin increases enzyme secretion from the exocrine pancreas for digestion of fats and amino acids. The quality of exocrine pancreatic function is influenced by the initial tastes of food as they stimulate a certain level and quality of pancreatic excretion as well as the glycemic response and origin of fats (animal vs vegetable, fried vs added after cooking).72, 73 In our experience, the following practices as the initial actions of degustation optimize the participation of exocrine pancreatic function: (1) eating sour or bitter foods (i.e., pickled foods, lemons, vinegar in water), (2) avoiding high glycemic foods, and (3) chewing slowly and pacing the meal.

206  The Theory of Endobiogeny

TABLE 9.18  Medicinal plants with pancreatic enzymatic activity Plant

Amylase

Disaccharidases

Plantago major

•

•

Avena sativa

•

•

Gonado-thyrotropic regulator, lymphatic drainer, antiatherosclerotic

Secale cereal

•

•

Hepato-regenerator

Ficus carica

•

•

•

Digestive epitheliogenic, antigastritic, neurologic antispasmodic, calms hypothalamic-reticular activating system pathways

Carica papaya leaf

•

•

•

Eupeptic, antigastritic, hypolipemiant

Ananassa sativa leaf

•

•

•

Antiinflammatory, eupeptic, reduced coagulability of blood, rich in manganese and sulfur

•

•

Antihemorrhagic, hypolipemiant, estrogenic, antiLH, antiandrogenic

Medicago sativa

•

Proteases

Lipase

Other properties Drainage: ENT, liver, kidney; hepato-protectant, pulmonary antispasmodic and mucolytic, hypolipemant, antiinfectious, antiallergic

TABLE 9.19  Broad spectrum enzymatic substitution and treatment of the complex terrain imbalances Combination

Possible disorders treated

Plantago major + Hordeolum vulgare

Allergies, all gastric and hepatic disorders, bronchopulmonary disorders, hypercholesterolemia

Plantago major + Medicago sativa

Allergies, all gastric and hepatic disorders, bronchopulmonary disorders, acne, prostate enlargement, uterine fibroids

Plantago major + Ficus carica

Allergies, all gastric and hepatic disorders, bronchopulmonary disorders, spasmophilia, anxiety, insomnia

Plantago major + Carica papaya

Allergies, all liver disorders, colitis, pancreatitis

Plantago major + Ananassa sativa

Allergies, all liver disorders, colitis, pancreatitis, thrombophlebitis

Liver-gallbladder: Bile Bile is essential in digestion of lipids. It is secreted continuously by hepatocytes. It is stored and concentrated between meals by the gallbladder.30 Adrenaline stimulates secretion via vesicular contraction. In between meals, residual bile in the common bile duct returns to the gallbladder by retrograde flow. Bile is induced by neural action during the preparatory phase. The sight and smell of food during the cephalic food stimulates it.31 Once food has been

s­wallowed, antral-pyloric distension stimulates it. Once food has entered the duodenum, CCK and fatty substances in the chyme stimulates its excretion.1, 30

Role of mucous Intestinal mucous and mucins are produced by enteric goblet cells. They play an immunologic role in trapping potential pathogens.74 They also play an important role in the release of energy for host bacteria from its rich proteoglycan composition.74, 75 The inner lining of mucus serves as a barrier against the invasion of flora into the epithelium or systemically. The outer layer serves as a medium for commensal flora to anchor themselves as well as an energy source. Mucous in stool represents an oversolicitation of the protective nature of mucous against invasive flora. The use of the plants listed in Tables 9.18 and 9.19 can regulate intestinal flora.28, 29

The small intestine: A privileged place of enzymatic absorption of nutrients Role of hydrolytic enzymes produced by the cells of the intestinal lining and the pancreas complete degradation of molecules into more basic forms: polysaccharides to monosaccharides, proteins to amino acids, and lipids to fatty acids. Nonenzymatic absorption is under the control of the endocrine manager. It occurs by active absorption in the case of vitamins and minerals, and passive diffusion in the case of water. Local digestion reduces the molecular size of the food based on the contributions of three units: gallbladder, exocrine pancreas, and the epithelium of the intestines. Pancreatic enzymes and bile salts are responsible for the majority of digestion. Recall that the enterocytes of the small intestine contain digestive enzymes as well.

Motricity of the bowel Chapter | 9  207

Absorption of carbohydrates (rapid energy) The absorption of carbohydrates (intense and brief energy) holds a privileged connection with the somatotropic axis. Recall that the somatotropic axis contains both the hyperglycemant hormone glucagon and the hypoglycemant hormone insulin. More upstream, prolactin stimulates insulin and growth hormone (GH) installs insulin resistance.76 Traditionally, humans have had a daily intake of 250–800 g of carbohydrates. Approximately two-thirds are consumed as polysaccharide starches. One-third are consumed as disaccharides, such as sucrose (table sugar = fructose + glucose), lactose (milk sugar = galactose + glucose), and maltose (various sources = two glucose molecules). Digestion of lactose from dairy products occurs in three places: Amylase from saliva and the exocrine pancreas, and by oligosaccharidases from the enterocytes of the small intestine. Monosaccharides, such as glucose and fructose are directly absorbed without any further digestion.1

Oligosaccharidases and pediatric growth Oligosaccharidases are a family of enzymes that break down starches of intermediate complexity. Lactases are the second type of oligosaccharidase enzyme. They specifically hydrolyze lactose into galactose and glucose. Lactase activity is most elevated at birth when infants are consuming large quantities of human breast milk. Lactase activity diminishes with age. Dairy products, hence the activity of lactase, favors the activity of GH, and insulin-like growth factors (IGF) activity.77 The general programming of c­ hildhood is

a somatotropic program designed to augment the exterior architecture of the organism through GH and IGF’s (cf., The Theory of Endobiogeny, Volume 1, Chapter 13). As children age and insulin activity increases, the programming shifts to the interior architecture of the cell, thanks in part to the initiative of estrogens. Thus, we find in the biology of functions that the GH growth score, which evaluates the role of GH in energy distribution, is 6- to 60-fold above normal adult ranges until the end of adolescence (Fig. 9.9). The second type of pancreatic enzyme is α-glucosidase, which breaks down starches into glucose. Like many other pancreatic enzymes, it has low activity at birth that increases with age.78 Increasing activity of α-glucosidase leads to a more pronounced glycemic response by increasing the amount of monosaccharides absorbed into the bloodstream increasing insulin resistance. This may be problematic for long-term health as is the consumption of free sugar found in sweetened beverages and fruit juices. This has been associated with increased risk of type 2 diabetes.79 According to the theory of Endobiogeny, this higher insulin resistance is physiologic in children because it is ultimately pro-growth. The insulin response will be commensurately large in its time. Thus, we observe in the biology of functions that the insulin resistance index in children is approximately twofold that of adults (data not shown). We also observe that the degree of insulin sensitivity, while it varies throughout childhood is approximately ½ that of adults (Fig.  9.10). The insulin index evaluates the level of membrane sensitivity to insulin. As insulin resistance rises, generally speaking, insulin sensitivity declines. However, the lower the insulin index, the greater the ultimate effect of insulin will be as a pro-growth factor.

FIG. 9.9  GH growth score index. The index is several fold elevated compared to adults, witnessing the Endobiogenic notion of childhood being a growthhormone programming with fashioning of the exterior. NB: Scale is logarithmic; Norms: Children: 9000–12,000, Adults: 200–1500. (Unpublished data, used with permission from Duraffourd, Lapraz and Harms-Ringdahl, Uppsala University; 2008.)

208  The Theory of Endobiogeny

FIG. 9.10  Insulin index. The insulin index evaluates the effective membrane sensitivity of cells to insulin. According to the theory of Endobiogeny and as observed in this graph, the mean efficacy of insulin activity is diminished throughout childhood (0.5–1.5) and approaches the normal adult level during the later period of adolescence (1.5–5). (Unpublished data, used with permission from Duraffourd, Lapraz and Harms-Ringdahl, Uppsala University; 2008.)

Proteins (median energy) Proteins offer a median, bridging energy. They have a privileged connection with the gonadotropic axis, which initiates protein metabolism for cellular and tissular activity.80, 81 Two-thirds of protein is derived from exogenous origin, one-third is from endogenous recycling. Most of this comes not from turnover of muscle but recycling of digestive enzymes and mucous secreted into the DT, as well as desquamated intestinal cells thanks to their high rate of turnover. Daily intake is typically 40–50 g/day, typically of vegetarian origin. In affluent countries, it can be up to 125 g/day, increasingly of animal origin. Recall that carbohydrate digestion begins with saliva in the mouth. In contrast, protein digestion begins with hydrochloric acid and pepsin in the stomach. The majority of proteins are sufficiently hydrolyzed for absorption in the small intestine. Again we find that they can be derived from the pancreas (trypsin, chymotrypsin, and carboxypeptidase), intestinal epithelium (aminopeptidase) or enterocytes. Most proteins are absorbed by active transport in the proximal small intestine. Small quantities of intact proteins can cross the intestinal epithelium into the interstitial fluid. The ability to absorb intact proteins is much greater in infants than in adults. This allows the infant to absorb maternal antibodies secreted into the breast milk until their endogenous immunity improves, but also increases the risk of food allergies. Recall that adaptive reabsorption of

proteins occurs in the ascending and transverse colon, according to Dr. Duraffourd’s hypothesis (Chapter 11 and The Theory of Endobiogeny, Volume 2, Chapter 5).

Lipids (intense and sustainable energy) The absorption of lipids has a privileged connection with the thyrotropic axis, which stimulates lipolysis and uses lipids as fuel for beta-oxidation.82 Daily intake varies widely from 25 to 160 g/day. Most lipids are formed into chylomicrons (triacylglycerols, phosphoglycerides, cholesterol, and fat-soluble vitamins) and enter into the lymphatic lacteals and then into hematogenous circulation without first-pass hepatic metabolism. The process requires emulsification of the lipids, which occurs thanks to bile and pancreatic lipase. Emulsification is required for long-chain fatty acids. In contrast, medium chain triglycerides (viz., coconut and olive oils) are absorbed into lacteals without emulsification and offer a source of nourishment to those with biliary-pancreatic insufficiency or those requiring rest of oversolicited gallbladder and pancreas (Table 9.20).83 The same is true of short-chain fatty acids, though these are derivatives of dietary fiber and are produced in the colon by fermentation (or by consumption of fermented drinks such as Kombucha),84 which play important roles in regulating inflammation and cancer risk.85 Butyric acid can be easily consumed from common dairy products (Table 9.21).

Motricity of the bowel Chapter | 9  209

TABLE 9.20  Fatty acids, sources of consumption and locations of absorption Fatty acid

Example

Source

Absorption

Short chain

Acetic acid Butyric acid Propionic acid

Resistant starches: whole grains, beans, lentils Pectin: apples, apricots, blackberries, carrots Fructooligosaccharides, inulin: Jerusalem artichoke, onions, leeks, wheat, rye, asparagus

Large intestine (production and absorption)

Butyric acid

Kombucha Cheese and butter (cf. Table 9.21)

Small intestines

Propionic acid

Swiss cheese

Small intestines

Coconut oil Olive oil

Small intestines

Medium chain

Fat-soluble vitamins are four: A, D, E, and K. and they are dissolved in micelles. Therefore proper biliary function is important for absorption of these vitamins.1 Water-soluble vitamins: are absorbed by diffusion or by transport. Vitamin B12 binds to the protein intrinsic factor in the stomach, which protects it from hydrolysis until it reaches the distal ileum, where it is absorbed.11

chelates are more bioavailable than oxalate and phytate chelates. The regulation of its intestinal absorption is hormonal via vitamin D and parathyroid hormone.86 Other minerals absorbed in the small intestines include K, Mg, Ca, Zn, and Iodine.1 The body loses 1–2 mg of iron per day just from the desquamation of epithelial cells, which must be replaced from the diet. Only 10% of ingested iron is absorbed into the bloodstream daily.87 For example, if a person consumes 20 mg of iron, approximately 2 mg is absorbed. The majority (75%) is deposited in marrow for erythropoiesis for hemoglobin. Approximately 15% is stored in the liver and heart thanks to ferritin for later use. The remainder (10%) is used for various other processes, such as mitochondrial cytochrome complexes for ATP production.87 The source of iron is important, as they have different rates and methods of absorption. Heme-bound iron, as is found in mammalian flesh, is absorbed via a heme transporter. Nonheme bound iron, such as that consumed from animal liver or heart, or vegetarian sources, such as lentils or spinach, must be reduced from Fe3+ to Fe2+ by duodenal cytochrome B. In the Fe2+ state, it can be absorbed via a DMT1 transporter. Once absorbed, iron may be stored in mucosal ferritin for use by the intestinal epithelium, or transported across the basal membrane via a ferroportin, bound to transferrin for hematogenous transport and distribution.87

Absorption of water and the minerals

Colon

Out of 9000 mL of liquid ingested and secreted, 1500 mL (17%) reaches the large intestine to affect the consistency of stool. The majority is absorbed in the small intestines.7 Sodium is absorbed by an active process by a Na/K ATPases pump.1 Calcium can be absorbed only in ionized form. Gastric acidity augments calcium absorption by freeing it from the protein complex. Calcium supplements are less efficiently absorbed outside of meals or with concomitant use of antacids. Bioavailability of synthetic calcium depends on the chelate to which it is bound. Glycinate and chloride

Comparative anatomy

TABLE 9.21  High butyric acid dairy products Dairy product

Butyric acid (mg)/100 g

Butter

2000

Emmentaler Swiss

1133

Gouda (favor aged >3 years)

975

Edam

810

Camembert

780

Cream

750

Cottage cheese

150

Yogurt

100

Absorption of vitamins

The colon is 6 cm in diameter and 120 cm long (vs 5000– 7000 cm for the small intestines). Approximately 1500 mL of chyme enters the colon each day and it absorbs all but 100 mL of that.88 It begins at the ileocecal valve with the annexed appendix. We can divide the colon into five anatomical segments: (1) ascending, (2) transverse, (3) descending, (4) sigmoid, and (5) rectum, ending at the anus. The colonic mucosa is different from that of the small intestines in four

210  The Theory of Endobiogeny

key ways. It has a smaller epithelial surface, is flat and devoid of villi, lacks convolutions, and its glandular crypts are deeper than in the small intestine. We find four cell types: (1) enterocytes, (2) goblet cells, (3) endocrine cells, and (4) secretory cells. Compared to the small intestine, the colon lacks Paneth cells and digestive enzymes. The chyme enters the colon through the ileocecal sphincter, which is normally closed. After a meal there is an augmentation of the ileocecal reflex which stimulates contractions of the terminal ileum resulting in relaxation of the sphincter muscle, allowing chyme to enter the large bowel. This increases distension of the colon, which stimulates a reflex contraction of the sphincter preventing the feces to return into the small intestine.88 The right and left colon are in origin and function as separate entities fused together.88 The right colon is of midgut origin, the left is of the hindgut. Classically, the right colon is seen as a place of mixing and the left a conduit for defecation. This is true. However, from the Endobiogenic perspective, both halves of the colon are integrated into a much large role in adaptation response and endocrine calibration of nutrient and electrolyte reclamation (Chapter 11).

Innervation As everywhere in the DT, innervation involves two systems: extrinsic and intrinsic. The right colon receives innervation from the vagus nerve and the superior mesenteric ganglion. The left colon derives its parasympathetic innervation from sacral segments 2–4 and sympathetic innervation from the inferior mesenteric plexus. Intrinsic sympathetic fibers are within the thickness of the lumen.88 The left colon is more densely innervated by these fibers, corresponding to the need for greater motility for expulsion of feces.

Motility of the colon It uses the same mechanisms as the rest of the DT but with slower contractions of the circular smooth muscle: 2–3 per hour.30 Propulsion of the contents of the colon takes 18–24 h. There are two types of contractions: segmental and mass. Segmental contractions are more frequent, are involved in mixing of colonic content, and lack propulsive effect.89 They cause a retrograde movement of ascending colon feces toward the cecum to facilitate reabsorption of nutrients by increasing contact time (recall relationship to ACTH of structure). Pressure on the left colon prevents too quick a progression and incontinence. Mass contractions occur after meals (gastrocolic reflex), are strong and move the content of feces toward the rectum. They occur about 3 times per day in adults.30 Because of the elevated parasympathetic tone of infancy, most infants have a prominent gastrocolic reflex. They typically stool within 20 min of consumption of breast milk, formula or a meal.

Unlike the peristaltic wave, during which the smooth muscle is relaxed after the passage of the contraction wave, the smooth muscle of the colon remains contracted for a certain period after mass movement. Colonic motility also depends on the volume of residual food in the colon, the nature of the diet, and the quality of motor function of the anus. Food higher in insoluble fiber increases transit times. Recall that the anus contains involuntary smooth muscle (internal anal sphincter) and voluntary skeletal muscle (external anal sphincter).89 The voluntary nature of the external anal sphincter is implicated in power struggles between caregivers and young children. Voluntary withholding can be a cause of the delay of evacuation of stool.

Main absorption processes in the colon The colon should be considered as more than a simple transit route for excretion of waste. It also represents a secondary opportunity for nutrient reclamation in adaptive and adaptative states. The colon plays an important role in the reabsorption phenomena for finalizing the structuring of the body and recovering matter in adaptation situations requiring the additional intake of specific nutrients. The colonic phase, which lasts for days, is much longer than the small intestine digestive phase that lasts only a few hours. It allows the adjustment of the nutritional response to the needs of digestion itself, the adaptive response of the global organism and the functional specificity of the various segments of the colon. There are endocrine receptors in the epithelium of the colon which helps regulate this process (Chapter 11). The colon completes the processing of protein and carbohydrates. The majority of carbohydrates are absorbed into the small intestines. Certain polysaccharide (cellulose, fibers, and pectin) need to be metabolized by anaerobic glycolysis by enteric bacteria.85 This produces 400–700 mL of various gas per day as well as water and organic acids. The gaseous components are reabsorbed and eliminated by the lungs and can generate gas and flatulence. The other residues eliminated by defecation. Proteins not sufficiently digested and absorbed in the small intestines are putrefied by saprophytic commensals of the colon. This results in the production of amines, such as histamine, tyramine, and ammonia, which can be absorbed into the bloodstream and alter cognition and behavior. Certain vitamins are synthesized by local bacteria in the colon (cf. The Theory of Endobiogeny, Volume 2, Chapter 5).

Stool Approximately 150 g of feces are expelled per day in a healthy adult. 100 g is water, 50 g solids. The solid material includes bacteria, undigested polysaccharides (fibers), keratin, fatty and muscular residues, bile pigments, ­cholesterol,

Motricity of the bowel Chapter | 9  211

electrolytes (especially potassium), and epithelial iron. Approximately 50% of alimentation is expelled within 2 days, 90% in 5 days. The rectum is normally empty and is filled as a result of sigmoid contraction. Continence is ensured by the segmental contractions of the left colon delaying the passage into the sigmoid, which by expanding creates a sort of storage tank. The action of levator ani muscles creates an angle with the sigmoid junction and allows the voluntary control of opening or closing of the external striated muscle portion of the anal sphincter. The internal smooth muscle of this sphincter is not controlled by this mechanism: rectalsphincter reflex.88 Sudden distension of the walls of the rectal ampulla (mechanic receptors) results in contraction of the rectum. This leads to relaxation of the internal anal sphincter, stimulating contraction of the external anal sphincter. This, in turn, leads to increased peristaltic activity in the sigmoid colon, then relaxing the external anal sphincter. Mechanisms involved include deep inspiration, closure of the glottis and contraction of the abdominal and thoracic muscles.

Conclusions The DT runs from the mouth to the anus. More than a simple tube, it is a site of dynamic neuroendocrine and immunologic activity dedicated to safeguarding the organism in the act of consumption of food and extrusion of waste. It is an element of the buffering capacity of the organism. Its role in digestion and absorption of nutrients contributes to the buffering role of other cellular, tissue, and organ processes in the organism. The DT is closely integrated into the functioning key emunctories, such as the liver and gallbladder and is itself a key emunctory (colon). Support of the structural and functional integrity of the DT is key to the proper functioning of the organism.

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Chapter 10

Disorders of intestinal transit Disorders of rapid transit: Diarrhea

Overview of causes of diarrhea

Introduction

Diarrhea occurs when the net secretion of water and osmotic forces exceeds the net absorptive capacity of the bowel and the interstitial osmotic forces. The causes of diarrhea can be categorized in multiple manners: infectious vs noninfectious, disorders of absorption vs disorders of secretion, disorders of immunity, endocrine, or autonomic pathologies. From the practical clinical aspect, categorizing diarrheal disorders in the following way allows for the clearest approach to treatment:

The intestines play a key role in digestion and absorption of nutrients. Along with this comes a perfunctory requirement for defense against nonself-biological organisms and chemical entities in alimentation that may be perceived as such. Diarrheal disorders represent a compromise in one or both of these primary roles of the digestive tract. These disorders are addressed for two reasons. First, they affect the quality of life and daily activities. More importantly, they affect absorption of nutrients, growth, and regeneration of tissue. In the long term, they can be a source of degradation of the buffering capacity. These disorders offer a glimpse into local, locoregional, regional, and global aspects of the functioning of the organism with respect to both autoregulation and in the face of external and internal aggressions.

Definition Diarrhea is defined by both frequency and consistency of stool. The frequency is 3 or more stools per day of a watery consistency. In children, severe diarrhea, which may require hospitalization and intravenous hydration, is defined by the number of stools per day relative to the age (Table 10.1). Cardiac output in children is more dependent on heart rate than stroke volume, making children more susceptible to dehydration late in the course of their illness. Guarding against dehydration is more crucial in children than in adults.

1. Disorders of secretion 2. Disorders of absorption 3. Disorders of transit

Secretory diarrhea Introduction Disorders of secretion reflect hypersecretory states. Infectious agents that invade the endothelial lining of the intestines typically cause these disorders.

Acute diarrhea The release of enterotoxins by pathogenic organisms alters the rate of membrane-bound ion channels. As the rate of ion excretion into the lumen of the intestine increases, the rate of water movement increases, resulting in a flow of water and electrolytes, namely potassium and bicarbonate, that exceeds the intestine’s absorptive capacity1 (Fig. 10.1).

Chronic diarrhea TABLE 10.1  Severe diarrhea in children Age

Stool frequency

All

≥5 in 5 h or less

0–11 months

>9 stools per 24 h

12–24 months

>14 stools per 24 h

2–18 years

>19 stools per 24 h

The Theory of Endobiogeny. https://doi.org/10.1016/B978-0-12-816964-3.00010-9 © 2019 Elsevier Inc. All rights reserved.

The transition to a chronic infectious or postinfectious diarrheal state is favored by two factors: the release of cytotoxins and a dysregulated immune response by the host (cf. The Theory of Endobiogeny, Volume 2, Chapters 3–6). Cytotoxins secreted by the pathogenic organisms attract immune cells that release prostaglandins, platelet activating factor, and other factors that can create a chronic hypersecretory state.2 Both acute and chronic hypersecretory disorders can become disorders of absorption if the adaptative response 215

216  The Theory of Endobiogeny

Healthy tissue

Bacterial-induced diarrhea Increased Gl motility

Movement of Gl contraction

< 85% H2O

> 85% H2O

Extracellular pathogens

Intracellular pathogens

Ion channel

Tight junctions

AQP3

Shigella

Aquaporins Ion channels H2O AQP2

H2O H2O Aquaporins

Salmonella

Nucleus

H2O TRENDS in Microbiology

FIG.  10.1  Healthy intestinal tissue (left) maintains integrity through tight junctions. Water is exchanged across enterocytes through aquaporins. In bacterial-induced diarrhea (right), these elements are compromised. This results in entry of noncommensal organisms and loss of water into the enteric lumen, resulting in diarrhea. (Used with permission from Guttman JA, Finlay BB. Subcellular alterations that lead to diarrhea during bacterial pathogenesis. Trends Microbiol 2008;16(11):535-542. doi:10.1016/j.tim.2008.08.004.)

accelerates the destruction of, or impairs the regeneration of villi in the small intestines or columnar epithelial cells in the colon.

Pathophysiology of secretory diarrhea Anatomic From the perspective of Endobiogeny, the following can be considered: 1. Nose: hyposmia and anosmia impair the ability to detect odors associated with infected foods. Patients with anosmia have a higher incidence of food poisoning3 2. Stomach: suppression of hydrochloric acid increases risk of acute bacterial enteritis4, 5 3. Splanchnic congestion: favors a congestion of the viscera, which provides a terrain favorable to infections

Neuroendocrine factors The specific elements of the disadapted terrain are presented in Table  10.2. The specific combinations for each individual’s terrain may vary.

Clinical presentation History There is an increased volume of stool often with a foul odor. Fasting does not diminish the volume of stool output.

Seasonality The seasonality of the diarrhea at the time of onset often gives a clue to the most likely microbial origin. Viral infections can occur all year. Bacterial infections are more likely in the summer.

Disorders of intestinal transit Chapter | 10  217

TABLE 10.2  Neuroendocrine factors of infectious diarrhea Location

Factor

Activity

Effect

ANS

Para

↑

Metabolic intestinal mucosal congestion, stasis

Alpha

↑

Immunity: delayed or blocked

Histamine, autocoid

↑

Inflammatory congestion Loss of epithelial tight junction Easier translocation of pathogenic organisms

Beta

↑

Hyperglycemia: favors rapid growth of pathogenic organisms and inflammation

Cortisol

↑

Suppresses thymic immune function Hyperinsulinism Inflammation Blocked anabolism

Cortisol

↓

Insufficient mobilization of immune system

Aldosterone

↑

Endocrino-nutritional congestion of bowel mucosa Lympho-venous stasis

Gonadotropic

FSH

↑

Mucosal congestion

Thyrotropic

TRH

↑

Hyperbeta response (cf. above), insulin-linked inflammation

TSH

↑

Congestion, stasis of mucoid tissue (cf. FSH)

Thyroid

↑

Pro-inflammatory

Thyroid

↓

Impaired immunity: reduced oxidative burst, hydrogen peroxide for phagocytosis

Insulin

↑

Inflammation, or low insulin resistance may be present

Corticotropic

Somatotropic

Quality of stool ●

●

●

Nonbloody, no mucous: small intestine origin of disease Bloody, with or without mucous: large intestine origin of disease Green: rapid transit (cf. rapid transit diarrhea (RTD))

Systemic complaints Lack of fever does not rule out the presence of an infectious agent. Some organisms more typically cause fever than others: Campylobacter, Adenovirus, Rotavirus, and Cryptosporidium.

Duration of diarrhea Diarrhea lasting >14 days has an increased likelihood to occur due to a parasite, although bacteria or viruses may also be responsible for chronic infectious in some cases.

to use a target pharmaceutical antimicrobial therapy (Table 10.3).2, 6 Calprotectin is a marker of intestinal inflammation and is elevated proportional to clinical severity of infection (bacterial > viral infections).7, 8 Cultures have a low sensitivity but may be indicated in chronic diarrhea to rule out a parasitic infection.

Treatment of secretory diarrhea: General considerations Maintaining adequate hydration is capital. Therapeutic interventions should be chosen that exhibit antiinfectious properties, symptomatic relief, bowel tropism, and elements of the terrain. During the acute phase of illness, symptomatic treatment is often sufficient to restore the terrain of the patient to the prior state of function.

Hydration: Avoid ●

Laboratory evaluation Stool testing is generally not necessary or helpful except in cases of epidemics, chronic disease, or the need

● ● ● ●

Hyperosmotic beverages such as fruit juices Acidic beverages High-fructose fruits or honey High-fiber foods Greasy, fried, or fatty foods

218  The Theory of Endobiogeny

TABLE 10.3  Summary of secretory diarrhea characteristics by history and stool testing Stool characteristics

Small bowel

Large bowel

Appearance

Watery

Mucoid and/or bloody

Volume

Large

Small

Frequency

Increased

Highly increased

Blood

Possibly positive but never gross blood

Commonly grossly bloody

pH

Possibly 5.5

Anion gap

Normal ( duck ● Red meat: lamb > goat > beef Raw: sprouts: alfalfa, broccoli, radish, etc.

TABLE 10.5  Symptoms related to malabsorption diarrhea Stool

Nutrient intolerance

Watery

Carbohydrates

●

Abdominal Bloody

Lipids Proteins Giardia

Steatorrhea

Distention

Pain

●

±

●

●●

●

●

Nausea

Vomiting

●

● ● ●

Perianal excoriation

● ●

Disorders of intestinal transit Chapter | 10  223

Neuroendocrine

TABLE 10.6  A list of low fructose foods Fruits

Vegetables

Others

Pineapples

Asparagus

Eggs

Berries

Leafy green vegetables

Chicken, duck, turkey

Lemon and lime

Celery

Sardines, herring, anchovies

Rhubarb

Mushrooms

Bison: pasture raised, grass fed

Potatoes Root vegetables: parsnips, turnips, beets

Medicinal plants Astringents See “hypersecretory diarrhea.” Emunctory support Ensure good hepatobiliary-pancreatic support and select plants with cicatrizing properties16–18 (Table 10.8).

Summary of plants with exocrine pancreatic tropism by enzymatic activity When a specific type of food is identified as causing the secretory diarrhea, in addition to minimizing or avoiding that food for 6–12 weeks, medicinal plants with specific substitutive activity can be selected. Table 10.9 summarizes the specific substitutive activity of common medicinal plants with exocrine pancreatic tropism.16, 17

Regeneration of epithelial surface ● ●

Ficus carica GM Remineralization ● Argillite clay ● Equisetum arvense ● Urtica dioica root

ANS: reduce global autonomic activity, favoring plants that are spasmolytic and/or with an intestinal tropism. In addition to those noted above: ● ●

Matricaria recutita Artemisia dracunculus

Case study: Postviral gastroenteritis malabsorption The patient is a 23-year-old graduate student. He suffered from a mild case of viral gastroenteritis with nausea, vomiting, and diarrhea that lasted for 4 days. As he started to eat his normal diet again, he started experiencing diarrhea again. However, this time, it was bloody as well as watery. He experienced abdominal distention that worsened throughout the day. He started on an elimination diet and found that avoiding brown rice and fruit and animal proteins completely resolved the issue. However, he stated that he ate “like a cave man” and did not wish to avoid animal proteins. The patient was diagnosed with postviral denudation of the intestinal villi and insufficiency of amylase, disaccharidases, and protease enzymes. He was started on the following: 1. Diet a. Juice of 1 lemon diluted half strength before meals b. Fish: sardines, herring, and anchovies c. Fowl: broiled or grilled d. Berries and sprouted pumpkin seeds e. Low fructose vegetables f. Avoidance: everything else 2. Tincture: Raphanus niger MT 60 mL, Alchemilla vulgaris MT 50 mL, Copper oligo 10 mL, Dose: 2 mL twice per day before lunch and dinner 3. Tisane: Plantago major 100 g, Avena sativa 100 g: 1 tsp. steeped 6–8 min in 1 cup water, twice daily before meals 4. Clay 1 tsp. in chamomile tea (1 tsp. flowering tops steeped 12–15 min in 1 cup water and used to hydrate clay) at bed time

TABLE 10.7  Short- and medium chain fatty acids appropriate for malnutrition Fatty acid

Example

Source

Absorption

Short chain

Acetic acid Butyric acid Proprionic acid

Pectin: blackberries, carrots Fructo-oligosaccharides, inulin: Jerusalem artichoke, onions, leeks, asparagus

Large intestine (production and absorption)

Butyric acid

Kombucha Parmigiano Reggiano cheese, aged 24 months or longer

Small intestines

Coconut oil Olive oil

Small intestines

Medium chain

224  The Theory of Endobiogeny

TABLE 10.8  Medicinal plants with emunctory and astringent properties Plant

Hepato-biliary

Exocrine pancreatic

Intestines

Other

Arctium lappa

Choleretic Hepato-protectant

Dual pancreatrope

Reduces inflammation by immuno-modulation

Cutaneous drainer

Alchemilla vulgaris

Choleretic

Astringent

Antiinflammatory Cicatrizing Hemostatic

Agrimonia eupatoria

Stimulates hepatobiliary secretions

Dual pancreatrope

Astringent

Portal decongestant Cicatrizing

Fumaria officinalis

Choleretic Hepatic drainer

Drainer

Drainer

Spasmolytic: Sphincter of Oddi

Juglans regia

Stimulates hepatic macrophages

Dual pancreatrope

Astringent

Antiseptic Cicatrizing

Plantago major

Induces hepatic enzymes

Carbohydrates

Astringent Antiinflammatory

Antiinfectious Hepato-renal drainer

Salvia sclarea

Choleretic

Stimulates flow of secretions

Astringent

Para-alpha sympatholytic Muscular antispasmodic Cicatrizing

Proteases

Lipase

TABLE 10.9  Substitutive pancreatic actions of medicinal plants Plant

Amylase

Disaccharidases

Plantain (Plantago major)

●

●

Milky oat (Avena sativa)

●

●

Rye bud (Secale cereale)

●

●

Fig bud (Ficus carica)

●

●

●

Papaya leaf (Carica papaya)

●

●

●

Pineapple (Ananassa sativa)

●

●

●

●

●

Alfalfa (Medicago sativa)

●

The patient started introducing bison and apples after 8 weeks with only mild distention and slightly loose stools. After 12 weeks, he tolerated all foods again. After 16 weeks, he discontinued all treatments.

Rapid transit diarrhea Introduction RTD is a functional disorder of hyperfunctioning of the motricity of the enteric system.

Pathophysiology Neurologic Most typically those affected by RTD are vagotonic with hyperfunctioning para ≫ hyperfunctioning alpha. External or internal aggressors relaunch alpha, with a sufficiently strong beta response that the cycle of para-alpha-beta remains entrained until there is a sufficient reduction of alpha-sympathetic tone. The most common type of aggression is an anticipatory anxiety related to performance (examinations, public speaking, artistic performance, etc.).

Disorders of intestinal transit Chapter | 10  225

Iatrogenic Laxatives, magnesium products, including antacids, opiate withdrawal.

●

Autonomic nervous system ANS: reduce global ANS, favor plants that are spasmolytic and/or with an intestinal tropism16, 17

● ● ●

Introduction Constipation is one of the most common digestive complaints. It is defined as23, 24.

Treatment

●

Constipation: Disorders of delayed or dysfunctional transit

●

Matricaria recutita Angelica archangelica Artemisia dracunculus Origanum majorana

Alpha-sympatholytics with digestive tropism16, 17 ● ● ●

Melissa officinalis Salvia sclarea

Hard stools are not a sine quo non of constipation, as a patient may have normally formed stools that are difficult to pass due to obstruction or neuromuscular defects. The etiology of constipation is not always the colon or even the pelvic floor, but may be due to dietary, lifestyle, or psycho-emotional issues that impact the locoregional function of the colon and the demands that are placed on it during adaptive and adaptative states, or as a matter of adaptability. Constipation should be placed within the context of local, locoregional, regional, and systemic dynamics of the Endobiogenic terrain of each patient.

General alpha-sympatholytics16, 17 ●

●

≥3 months duration ≥2 of the following symptoms: ● Delayed transit: ≤2 bowel movements per week ● Altered consistency: stools that are: ▪ Hard and dry and/or ▪ Painful to pass ● Increased effort: straining to evacuate stool ● Blocked passage: sensation of anorectal obstruction ● Lack of completion: sensation of incomplete defecation ● Self-intervention: manual stimulation of defecation Insufficient criteria for irritable bowel syndrome

Inhalation during stress: ● Cananga odorata EO ● Citrus aurantium amara EO Oral ● Ilex aquifolium GM ● Leonurus cardiaca MT, FE, BH

Pathophysiology Lifestyle Encourage active ways of managing anxiety: breathe work, meditation, mindfulness, etc.

Broadly speaking, constipation can be divided into two general categories: primary and secondary. Primary causes are colonic in nature. Secondary causes are extra-colonic (Fig. 10.2).

Constipation

Primary: Colonic

Secondary: Extra-colonic Structure and function

Metabolic

Behavioral Latrogenic

Transit

Obstructive

Structural Functional

Normal

Slow

Structuro-functional

Connective tissue Food sensitivities

FIG. 10.2  Nosologic categorization of constipation according to the colonic vs extracolonic origin of pathophysiology. See text for details. (© 2015 Systems Biology Research Group.)

226  The Theory of Endobiogeny

Primary causes are divided into two subtypes: disorders of transit and obstructive disorders. Disorders of transit are further divided into disorders of normal and slow transit. Secondary causes are numerous and include regional and systemic physiologic disorders and behavioral factors that affect colon motility. There is considerable overlap between causes. For example, some secondary disorders result in normal transit constipation (NTC), others in slow transit constipation (STC). It is important not to be too categorical when evaluating the causes of constipation.

Normal transit constipation NTC is the most common type of constipation. The patient has 3 or more stools per week, but the stool is difficult or painful to pass. There is no sensation of colorectal fullness, nor is there a feeling of abdominal fullness.23

Etiology Etiology of NTC is variable and may involve one or more of the following factors.

Diet ● ●

●

Insufficient intake of fiber Insufficient intake of water for the endobiogenic equilibrium of the patient Disorders of fluid management (cf. Endocrinometabolic below)

Enteric ecology ●

Dysbiosis

Emunctory Insufficiency of bile excretion due to: ●

●

Autonomic nervous system ● Parasympathetic insufficiency: diminished rate of bile production ● Alpha-sympathetic excess: permits tonic closure of sphincter of Oddi ● Beta: blocked or insufficient for excretion of bile Gonadotropic ● Estrogen excess: diminishes biliary secretion ● Progesterone excess: favors biliary stasis

Physical examination Stool is not palpable in the distal colon. Evaluates for locoregional and global signs of ANS dysfunction. Palpate gallbladder points on abdomen, legs, and feet; evaluate hepatopancreatic blockage.

Treatment: General considerations Constipation is a phenomenon more than it is a disease. The causes are many and thus the best approach will vary based on the etiology. The most common causes of constipation are due to imbalances in the ecology of the intestine, dietary, and lifestyle factors. Thus, the first approach should address these imbalances.

Symptomatic Glycerin suppositories It is suitable for occasional use, up to 3 times per week for all ages. It creates an osmotic diuresis and acts as a lubricant for the passage of stool.

Stimulant laxatives Stimulant laxatives offer short-term relief from constipation, but can cause bloating, gas, and spasmophilia.

Endobiogenic treatment of terrain Water The consumption of water does not in and of itself guarantee improved consistency of stool, although dehydration can favor reduced water content in stool in order to conserve total body water. The movement of water is based on its osmolality and pH. In order of preference12, 13: 1. Alkaline spring waters 2. Artesian well water 3. Distilled water: not recommended; if only safe water available, enhance mineral content: a. Schussler cell salts b. Argillite clay

Diet Because dietary factors are the most common causes for constipation, they are the most efficient and safest longterm approach to treatment.

History

Soluble fiber

Perform a detailed evaluation of the frequency of defecation, ease of passage, and quality of stool. Evaluate for symptoms of dysfunctional ANS activity, excessive estroprogestive state (e.g., strong premenstrual syndrome (PMS) symptoms in women), or iatrogenic causes such as oral estro-progestive contraceptive pills.

A diet rich in fiber is the best way to assure adequate colonic motility.25 There are two types of fiber: soluble and insoluble. Soluble fibers dissolve in water, are fermented in the colon and can serve as prebiotics. They may slow the movement of food through the colon. Soluble fiber foods can be used effectively for NTC disorders. Soluble fibers

Disorders of intestinal transit Chapter | 10  227

are typically found in the pulp, and insoluble fibers in the skin of foods.26 The skin of every fruit and vegetable should be eaten whenever possible, including the skin of gourds such as acorn squash. Patients with a history of a low-fiber diet are advised to start at 5–10 g/day and increase to a goal of 30–40 g/day. Patients should drink 6 glasses of water per day, and add 1 additional glass (250 mL) per 10 g fiber after the first 10 g/day.

TABLE 10.10  High fiber foods by category of food—cont’d Legumes

Lentilsa a

Black beans

a

Pinto beans

a

Kidney beans

Vegetables

13

Navy beans

1 cup

11

a

1 cup

6

1 cup

16

1 cup

9

1 cup

7

1 cup

6

Broccoli

1 cup

4

Spinach, cookeda

1 cup

4

Pistachiosa

4 oz

12

Hazlenutsa

4 oz

9

Pumpkin seedsa

4 oz

4

Almondsa

4 oz

2.5

Grapefruita

1

14

1 med

12

1 cup

8

1

5

1

5

1

4

1

4

1

4

2

4

4

3

Split peas

a

Kale

a

Yam

a

Fruits

a

Avocado

a

Raspberries a

Pear

a

Apple

a

Banana

a

TABLE 10.10  High fiber foods by category of food Category Grains

Food

Serving

Bran cereal

1 cup

Barley

1 cup

Bulgur

1 cup

Freekeh

Blueberry a

Orange

Fiber (gm)

a

Figs, dry

20

a

Dates

14

15

1 cup

a

Honey is a natural demulcent. Being rich in fructose and water,27 it can also serve as a mild osmotic diuretic (combine with sesame or olive oil) and consume in between meals for best effect.

1 cup

a

Grean peas

Honey

15

13

a

Nuts

1 cup

1 cup

Chick peas

Fructose is a monosaccharide that is absorbed both by passive diffusion and via a glucose symporter. Fructose is the sweetest of all monosaccharides, but has a low glycemic impact, thus it is safe to use with type two diabetics subtypes a and c (according to the theory of Endobiogeny, discussed elsewhere). When the concentration of fructose is sufficiently elevated, it overwhelms the absorptive mechanisms and becomes an osmotic diuretic in the colon. Thus, while most fruits, gram per gram are not as high in fiber as vegetables, the combination of high water content, soluble fiber (pulp), insoluble fiber (skin), and fructose content makes them an excellent method for improving both transit time and stool consistency (Tables 10.10 and 10.11).23, 26

15

a

Lima beans

Fruit

1 cup

a

Gluten-free.

8

Bold, high in protein.

1 cup

7

3 tsp.

7

Quinoaa

1 cup

6.5

Whole wheat spaghetti

1 cup

6

1 cup

4.5

Groats (Kasha)

1 cup

4.5

Ezekiel bread

2 slices

4

Fermented foods offer a natural source of bioavailable commensal organisms, reflecting the external ecologic terrain as well as the internal terrain of the organism. Thus, fermented foods are best chosen that are produced locally with soilbased organisms. Some examples of fermented foods by region of the world:

1 cup

4

●

1 cup

4

1 cup

3.5

Flax seeds

a

Buckwheata a

a

Oats, raw a

Corn

a

Brown rice

Fermented foods

Asia: ● Food: tempeh, miso, soy sauce, tamari, natto, kimchi (cabbage) ● Drinks: Pu-erh tea, kombucha (fermented tea beverage)

228  The Theory of Endobiogeny

TABLE 10.11  Best fruits for constipation by season of growth Spring

Summer

Autumn

Winter

All year juices

Grapes

Strawberries

Apples

Grapefruit

Prune

Watermelon

Figs

White grape

Watermelon juice

Pomegranate

Apple

Pears Quince

● ● ● ● ●

●

Caucuses: kefir, yoghurt India: idli, dosas Africa: injera (bread made from teff) Americas: sourdough bread, buttermilk Middle East: Torshi (pickled, fermented vegetables), dugh (fermented yogurt drink), kashk (fermented whey made from dugh), shubat (fermented camel milk) Europe: Jamón ibérico (Iberian ham), pepperoni, salami, sauerkraut, prosciutto, crème fraîche, skyr (Icelandic whey-yogurt), kvass (fermented rye beverage), Cidre poiré, cornichons

●

●

Dose: ● 0–11 months: ¼ tsp. ● 12–23 months: ½ tsp. ● 2–4 years: 1 tsp. ● 5–7 years: ½ tbsp ● 8 years and older: 1 tbsp Frequency: 1–2 times per day followed by 250 mL of spring water if it does not interfere with sleep and urinary habits ● AM before breakfast ● Before bed

Summary of dietary approach for NTC Probiotics Probiotic organisms can be administered in powder or tablet form when a more aggressive correction of the gut flora is required. Both bacterial (i.e., Lactobacillus ssp. and Bifidus ssp.) and fungus (i.e., Saccharomyces boulardii) can be used.28–31 They can reduce the frequency of glycerin suppository use.32

1. Extra-virgin olive oil: 1 tbsp in AM followed by a glass of water with lemon juice 2. Water: 6–10 glasses per day 3. Soluble fibers: 30–40 g/day 4. Fermented foods: 2 servings/day

Lifestyle ●

Cleansing diets Cleansing diets, performed around the changing of the seasons with seasonal fruits and vegetables can be helpful for maintenance of health and bowel regularity: ● ● ●

Grape cure Apple-sardine diet Fruit-vegetable-brown rice diet

●

Movement: regular exercise, yoga, and other meditative movement practices can aid in the stimulation of normal colonic motricity34, 35 Sleep: restorative sleep, starting from 11 p.m. and continuing through 5 or 6 a.m. can improve the efficiency of hepatobiliary and colonic activity, respectively

Medicinal plants

Oils

The choice of medicinal plants depends on the etiology of constipation. Some general guidelines for the most common types are presented.

Oils can aid in the passage of stool in two ways: choleresis and as a lubricant.33

Restoration of gut ecology

● ●

Choleretic: olive oil Lubricating: ● Olive: best general oil ● Sesame: children full of energy and anxious adults ● Borage oil: obese individuals ● Flax oil: obese individuals, asthmatics, inflammatory disorders

Essential oils are efficient for this purpose:16, 17 ●

● ● ●

Artemisia dracunculus (tarragon) EO, MS: use in cases of spasmodic colon Syzygium aromaticum (clove) EO Mentha piperita (peppermint) EO Satureja montana (savory) EO: with an infective component, or for blocked or delayed beta

Disorders of intestinal transit Chapter | 10  229

Emunctories Use plants that favor hepatobiliary drainage, cholagogues and choleretics.16, 17 In estrogenic females and obese patients, avoid using aggressive choleretics at first ● ● ● ● ● ●

Carduus marianus (milk thistle) Cynara scolymus (artichoke) leaf Mentha piperita (peppermint) Raphanus niger (black radish) Rosmarinus officinalis (rosemary) Taraxacum dens leonis (dandelion)

hot dogs. This has been her general diet. She started eating salad at a salad bar but it did not help with her constipation. When she was asked to describe her salad she said, “Iceberg lettuce, croutons, bacon bits, and blue cheese dressing.” The patient was asked to do the following in an incremental fashion since she was not used to eating a high-fiber diet with plenty of water: ●

Demulcents Demulcents are mucoprotective agents that relieve pain and inflammation of the mucous membranes.16, 17 ● ● ● ● ● ●

Althea officinalis (marshmallow) Glycyrrhiza officinalis (licorice) root Trigonella foenum graecum (fenugreek) seed Plantago ovata (psyllium) seed: also mucilaginous Honey + sesame oil Glycerin: helpful for children for a short period of time

● ●

Laxatives Favored for dry stools in patients who often are overweight, and/or consume excessive amounts of animal proteins and fatty animal-based foods16, 17; exam: red tongue with yellow coating ● ● ●

Taraxacum officinale (dandelion) root Berberis vulgaris (barberry) root Cascara sagrada (cascara) bark

Treating anal fissures ● ●

● ● ● ●

Peanut oil 1 mL Clay: 1 pinch ● Optional: baking soda: 1 pinch if experiencing burning Lavender EO 1 drop Mix well Rinse anus with warm water, lightly pat dry Apply mixture to anus AM, afternoons (after defecation) and before bed

● ●

Week 1: ● Fruit-vegetable-brown rice diet × 6 days ● Olive oil and 6 glasses of water per day ▪ AM: 1 tbsp olive oil +1 glass water 15 min before meal ▪ 2 glasses water between breakfast and dinner Week 2: flax bread, 2 squares per day (10 g fiber) Week 3: ● 1 cup puréed sweet potatoes 2–3 per week (6 g fiber) ● 1 cup hummus 2–3 times per week (6 g fiber) ● Buckwheat, 1 cup once 2–3 times week (4 g fiber) ● Continue with 2 pieces of flax bread (10 g fiber per square) ● Smoothie for breakfast (17 g fiber): ▪ Protein powder, 1 scoop ▪ ½ Avocado (6 g fiber) ▪ ½ cup frozen raspberries (4 g fiber) ▪ 1 cup kale (7 g fiber) ▪ Dilute with unsweetened vanilla almond milk to taste Week 4: 1 serving of fermented food 4 times per week Week 6: movement ● Standing up every 55 min and walking around for 5 min ● 20 min of brisk walking 4 times per week with a friend

By week 3, she started having 1 stool per day but it was still painful. By week 12, she was passing 2 stools per day that were no longer painful.

Slow transit constipation Introduction STC is defined as passing hyperpara

Mouth

Saliva stringy ± dilated opening of canal of Stenson

Abdominal tenderness

Gallbladder point (sphincter of Oddi)

ACTH: ileocecal, rectosigmoid colon FSH: ascending, proximal transverse colon LH: distal transverse, proximal descending colon TSH: splenic flexure colon TRH: hepatic flexure colon GH: mid-descending colon PL: distal descending colon

Neurologic

Glabellar tap: rapid lower eye lid response

Glabellar tap: TRH: flutter pre- or posttap DTR: TRH: brisk response

Extremities

Tender pelvic congestion point

Physical exam One may note abdominal bloating and palpable stool in the distal colon. Evaluate for signs of elevated autonomic function (cf. The Theory of Endobiogeny, Volume 1, Chapter 1) and neurologic function rooted in thyrotropic dysfunction resulting in spasmophilia (cf. The Theory of Endobiogeny, Volume 1, Chapter  11). Findings related to colon oversolicitation by central endocrine factors may or may not be present. When they are, they help determine a more comprehensive approach to treatment of the global terrain (Table 10.12).

Hands cool ± moist Feet colder than hands ± moist

Treatment Dietary approach for STC: Insoluble fiber Insoluble fiber does not dissolve in water and is metabolically inert. It acts as a bulking agent, drawing in water and stimulating the colon through a mild irritant effect. It is best used with STC. The skins of fruits and vegetables contain insoluble fiber. In summary, patients should be encouraged to consume plenty of water, insoluble fiber, fermented foods, and oils.26

Psychological and lifestyle Because of the predominance in autonomic and adaptative physiology, regulation of this tone is important. Therapies can be divided into three groups: psychological, psychophysiological, and psycho-mechanical. In the first group is cognitive behavioral therapy (CBT).36 CBT helps shift the framework of perception that installs an adaptative physiology. In the second group is biofeedback37, breath work, and other techniques that modify heart rate variability as a marker of autonomic tone.36 They reduce global alpha-sympathetic tone, improving the normal autonomic cycling and hence colon motricity, offering a feeling of empowerment for the

Endocrine

patient with respect to emotional state and bowel function. In the third group are exercises with breath work, such as yoga and Tai chi.34, 35 Certain yoga asanas (poses) and movements can assist through compression-relaxation on intestinal muscular tension and regulation of ANS tone through breath work with respect to colon motricity and spasmophilia.

Enteric ecology Cf. Normal transit constipation.

Emunctory Cf. Normal transit constipation.

Correcting the autonomic terrain Parasympathomimetics16, 17 ● Syzygium aromaticum (clove) ● Fumaria officinalis (fumitory)

Disorders of intestinal transit Chapter | 10  231

● ●

Mentha piperita (peppermint) Rosmarinus officinalis (rosemary)

Alpha-sympatholytics16, 17 ● ● ●

Origanum majorana (marjoram) Citrus aurantium (neroli, petitgrain) Melissa officinalis (lemon balm)

Para- and alpha-sympatholytics with intestinal tropism16, 17 ●

Matricaria recutita (German chamomile)

Antihistaminics with intestinal tropism16, 17 ● ● ●

Agrimonia eupatoria (agrimony) Fumaria officinalis (fumitory) Plantago major (plantain)

Beta-mimetics16, 17 ● ●

Cinnamomum zeylanicum (cinnamon) Satureja montana (savory)

Mineral ●

●

Hypercalcemia ● Remove or diminish iatrogenic sources of calcium: antacids, supplements, etc. Hypokalemia ● K oligoelement 2 droppers BID AM and qHS ● Potassium-rich foods

Enemas An enema is a water-based hyperosmotic treatment that is forcefully entered into the distal colon, stimulating a bowel movement. Coffee grounds offer the advantage of also stimulating peritoneal “dialysis” with removal of toxins. Enemas are more helpful for STC, with dilated colon and mild to moderate obstructive disorders. They can result in electrolyte depletion and dehydration with excessive use.

Case study #1: STC in a 5-year-old girl A mother brings her 5-year-old in for complaint of constipation and said that she was “sick of the dog and pony show” it took to get the child to stool. She had one older and one younger child who both were perfect at going to the bathroom, she pointed out in front of the child. The child stools 3 times every 2 weeks. The stool is so large, it clogs the toilet at least twice per month. The mother states that she is an avid juice and water drinker (4 cups per day) and likes to eat carrots and apples. She often complains of tummy pain

that diminishes her appetite. She has a history of recurrent otitis media treated 4 times with antibiotics. She has chronic nasal congestion with clear discharge. It takes about 45 min for the little girl to wind down and sleep at night. On physical examination, she appears slightly thin, pale, and gangly. She has reddish-purple infraorbital discoloration. Her palate is ischemic and pale. Her tonsils are congested, 2+ with crypts. The opening of the canals of Stensen are dilated, right > left. Superficial veins are apparent on her eyelids and chest. She is not compliant with a full abdominal exam but stool is palpated in the descending colon. One may conclude that her constipation is slow transit due to elevated alpha ≫ para. This terrain also explains her recurrent otitis and physical exam findings. One may also conclude that there is an element of stool withholding that has to do with a power struggle between the mother and the daughter. The patient was treated with the following: 1. Inulin powder: ½ tsp. in each cup of apple juice 2. Hepatobiliary-pancreato-ENT: Agrimonia eupatoria 40 g, Avena sativa 40 g, peppermint 40 g: ½ tsp. of mixture steeped 4–6 min in 120 mL water, drink three times per day before meals 3. ANS-sleep: Tilia tomentosa GM 50 mL, Rosmarinus officinalis GM 10 mL, 2 droppers before bed By 4 weeks, stool frequency improved to 4 times in 2 weeks. By 12 weeks, it improved to every other day (7 times per 2 weeks) but was still large and hard. The patient had less defiance tendencies toward her mother, but it persisted to some degree nevertheless. In addition, stool frequency did not improve beyond this even after 3 additional months of treatment. At 6 months of treatment, the mother agreed to go to behavioral counseling with her daughter for dyadic relationship management. After 6 weeks of counseling that included a reward system and body awareness skills, the girl felt comfortable to stool daily without further prompting. The treatment of inulin, tisane, and tincture were continued for another 6 months, then discontinued without any further need for treatment.

Case study #2: STC in a 39-year-old man A 39-year-old man presents on September 18 with a 4-week history of constipation. He states that he has been regular most of his life. For the last month, he stools every 3–4 days. He has a feeling of fullness, complains of feeling toxic and tired and experiences pain but then relief once he does pass the stool. He admits to having inserted his finger in his rectum to stimulate the passage of stool on two occasions. When you look at his chart, you note that his birthday is on October 27 and that he will turn 40 years old. He states that he was an easy child, a good sleeper, and eater. He ­describes his parents as loving with no childhood trauma he can recall.

232  The Theory of Endobiogeny

On physical examination, one notes dark circles under his eyes, which he says is also new for the last 3 weeks. His saliva is stringy and thick and not abundant. When you comment on this, he notes that his saliva has always been abundant, fluid, and easy to swallow. His liver is slightly full but not enlarged. It’s tender on palpation in the ­superior-medial portion and the gallbladder point is tender. The rest of his examination is unremarkable. The context of this new-onset constipation is the chronobiologic unfolding of genital recycling that occurs sometime between 38 and 42 years of age. In this case, it is occurring on the cusp of his 40th birthday. The unfolding begins approximately 2.5–3 months before one’s birthday. The second nested chronobiologic context is seasonal adaptation. The autumn adaptation begins in preautumn, around August 18, which is the day of onset of the constipation. It is also 2.5 months before his 40th birthday. Within the milieu of two nested chronobiologic demands the patient had an insufficient adrenal cortex adaptation to recalibrate both the seasonal cortisol demand as well as the genital recycling demand for adrenal androgens. Thus, the dark circles under the eyes. A hyperalpha response was solicited to support adrenal cortex response. Thus, one notes in the thickening saliva, full liver with superior-medial tenderness (vascular congestion) and constipation. There is also an insufficiency of choleresis, which is contributing to the constipation. Recall that bile has a mild laxative effect. A symptomatic approach to treatment will be to use osmotic diuretics and choleretics. A treatment of the terrain will start with adrenal cortex support with a special consideration for adrenal androgens. Alpha-sympatholytics will also need to be employed because they have installed themselves within the bowel motricity in a manner that needs to be disengaged from the organism. Hepatobiliary drainage will complement the treatment. 1. Lemon juice treatment TID × 1 week before meals: adrenal cortex support (vitamin C), sustains transition from alpha to beta, stimulates hepatic flow, cholagogy, and choleresis, general hepatobiliary drainage a. ⅓ cup organic, fresh squeezed lemon juice (2 medium sized) b. ⅛ cup water for dilution c. Cayenne pepper, 6 dashes d. Sea salt, 1 pinch e. Betula pubescens GM D1: 6–10 drops 2. ANS-adrenal cortex tincture: 4 mL BID before meals through January 18 to sustain the full adaptation of adrenal cortex function. a. Sequoia gigantea GM 80 mL b. Quercus pedunculata GM 80 mL c. Ilex acquafolium GM 40 mL

d. Passiflora incarnata MT 40 mL e. Lavender EO 4 mL f. Cinnamon leaf EO 2 mL 3. Hepatobiliary tincture: 3 mL before lunch and before dinner until March 30 to support genital recycling and prespring catabolic discharge. a. Raphanus niger MT 80 mL b. Taraxacum officinale MT 80 mL c. Carduus marianus MT 80 mL Thanks to the lemon juice treatment the patient started defecating daily within 24 h of treatment. By the 5th day, the stool was slightly loose and the patient was defecating 3–4 times per day. However, the patient saw this as a detoxification response and felt energized and focused. The patient continued the treatment until the dates instructed. By early December, the dark circles resolved. By early March, he noted his saliva was more abundant again.

Secondary causes of constipation Structural Obstructive disorders of the distal colon can result in delayed evacuation of stool. Examples include pelvic basin neoplasms, volvulus, and uterovaginal prolapse.

Structuro-functional Structuro-functional disorders are disorders of the functionality of intestinal motility and contraction due to tissular and organic structural insufficiencies. Megacolon, chronic laxative use, Hirschsprung’s disease, and ultrashort-segment Hirschsprung’s disease are three examples. The latter may take over a decade to diagnosis and will present as constipation refractory to standard-of-care treatments. If typical therapies fail to resolve constipation over a 1–2 year period of time, referral to a gastroenterologist with colonoscopy and biopsy may be indicated.

Functional Pelvic floor dysfunction may occur as a result of injury to the sacral nerves and certain plexi involved in coordinating defecation. This may occur from stretch injuries from repeated pregnancies, spinal cord lesions, outlet obstruction, strokes with diminished blood flow to the respective nerves, and familial dysautonomia syndrome.

History Patient will complain of prolonged or excessive straining, incomplete evacuation of stool. Or they will report the use of intravaginal pressure and/or digital evacuation of stool.

Disorders of intestinal transit Chapter | 10  233

Treatment

Pathophysiology

Manual therapies, such as visceral manipulation and acupuncture can be helpful.38, 39

The stool accumulates in size and becomes progressively dry. When the stool finally passes, it is hard and painful, often resulting in anal tears. A vicious cycle then begins in which stool is withheld because of the pain associated with the prior experience (cf. adults, below).

Metabolic Diabetes mellitus. Poorly managed diabetes can result in an autonomic neuropathy due to glycalation-related damage.40, 41

Treatment Support the restoration of myelination and nutrition of the nerve. Improve glycemia and reduce oxidative damage. 1. Alpha-lipoic acid: 2000 mg per orum TID × 4 weeks, then 1000 mg PO BID × 5 months 2. Liposomal curcumin 5 mL BID × 6 months 3. Neuro-Lymphatic tincture: 3–4 mL BID × 6 months a. Vaccinium myrtillus MT 200 mL b. Vinca minor MT 160 mL c. Melilotus officinalis MT 120 mL d. Cypress EO 6 mL e. Marjoram EO 4 mL

Connective tissue and immune disorders Various connective tissue disorders may result in fibrosis of segments of the intestines: scleroderma, amyloidosis, multiple sclerosis, etc.

Treatment The treatment needs to be specified to the specific type of disorder. The tincture below is a general approach to both fibrosis and sclerosis with drainage of connective tissue and the ground matrix. 1. Fibro-sclerosis tincture: 3–4 mL twice per day a. Alnus glutinosa GM 60 mL b. Ribes nigrum GM 20 mL c. Ilex aquifolium GM 60 mL d. Betula pubescens GM 60 mL e. Viscum album GM 40 mL

History The history is notable for one or more of the following: 1. “Man-sized” stools 2. Repeated clogging of toilet with plumbing-related expenses 3. Passing of odiferous flatus for several days that can “clear a room” before finally passing a stool 4. A series of small, soft stool of poor consistency or smearing of stool on underwear due to involuntary passage before passing the large, hard stool. This represents the passage of fresh, normally formed stool around the partial blockage of the large, hardened stool. 5. Bright red blood on wiping (due to anal fissure)

Treatment 1. Laxatives: foods or supplements 2. Dyadic behavioral counseling: parent-child interactions42 3. Body-sensing and awareness skills for the child to avoid withholding43 4. Acupuncture44

Behavioral: Adults Withholding of stool in adults can arise from childhood issues as noted above. If the onset is in adulthood, look for rectosigmoid and anal pathologies. When this area is already inflamed or injured, the passage of stool aggravates the condition. Thus, a withholding pattern begins that creates a cycle of pain and further withholding. Examples of such pathologies are inflammatory bowel disease with incomplete healing of ulceration, abscesses, anal fissures, and thrombosed hemorrhoids.

History Bright red blood is reported on wiping, but not in the toilet.

Behavioral: Children

Treatment

There are only two things that a toddler can control in their lives: what goes in their mouths and what comes out of their anus. Children may diminish consumption of fluids, and withhold stool for two general reasons: (1) due to a desire to not discontinue engagement in an enjoyable activity, or (2) as an expression of autonomy against the will of the mother.

Specific to the etiology. Behavioral counseling45 and biofeedback training may be required.43

Food sensitivities Food sensitivities, mediated by IgA or IgG phenomenon, may present with constipation (normal or delayed transit).

234  The Theory of Endobiogeny

In the case of nursing infants, the mother’s dietary intake should be taken along with the infant’s when considering an elimination diet.

Iatrogenic A number of commonly prescribed medications can affect bowel motricity.

Psychiatric 1. Antidepressants (tricyclics, MAO inhibitors) 2. Psychotropic medications

Autonomic 1. Sympathomimetic drugs 2. Anticholinergics 3. Opioids

Metalotherapy 1. Iron 2. Bismuth

Hydroelectrolyte 1. Antacids (aluminum and calcium compounds) 2. Calcium channel blockers

Immunologic 1. Nonsteroidal antiinflammatory drugs (NSAIDs)

Functional 1. Cholestyramine 2. Stimulant laxatives, chronic use

Conclusions Disorders of intestinal transit fall into two general categories: rapid transit (diarrhea) and normal/slow transit (constipation). The etiologies are varied from infectious to autonomic to systemic disorders. For each type of transit disorder, there are particular signs and symptoms associated with it. This allows the Endobiogenist to personalize therapy with the most targeted dietary, lifestyle, and medicinal plant therapies.

References 1. 2.

Guttman JA, Finlay BB. Subcellular alterations that lead to diarrhea during bacterial pathogenesis. Trends Microbiol. 2008;16(11):535–542. Schiller LR, Pardi DS, Spiller R, et al. Gastro 2013 APDW/WCOG Shanghai working party report: chronic diarrhea: definition, classification, diagnosis. J Gastroenterol Hepatol. 2014;29(1):6–25.

3. Santos DV, Reiter ER, DiNardo LJ, Costanzo RM. Hazardous events associated with impaired olfactory function. Arch Otolaryngol Head Neck Surg. 2004;130(3):317–319. 4. Canani  RB, Cirillo  P, Roggero  P, et  al. Therapy with gastric acidity inhibitors increases the risk of acute gastroenteritis and community-acquired pneumonia in children. Pediatrics. 2006;117(5):e817–e820. 5. Leonard  J, Marshall  JK, Moayyedi  P. Systematic review of the risk of enteric infection in patients taking acid suppression. Am J Gastroenterol. 2007;102(9):2047–2056 [quiz 2057]. 6. Sell  J, Dolan  B. Common gastrointestinal infections. Prim Care. 2018;45(3):519–532. 7. Duman  M, Gencpinar  P, Bicmen  M, et  al. Fecal calprotectin: can be used to distinguish between bacterial and viral gastroenteritis in children? Am J Emerg Med. 2015;33(10):1436–1439. 8. Shastri YM, Bergis D, Povse N, et al. Prospective multicenter study evaluating fecal calprotectin in adult acute bacterial diarrhea. Am J Med. 2008;121(12):1099–1106. 9. Guandalini S, Pensabene L, Zikri MA, et al. Lactobacillus GG administered in oral rehydration solution to children with acute diarrhea: a multicenter European trial. J Pediatr Gastroenterol Nutr. 2000;30(1):54–60. 10. Guandalini S. Probiotics for prevention and treatment of diarrhea. J Clin Gastroenterol. 2011;45(suppl):S149–S153. 11. Colin-Gonazlez  AL, Santamaria  A. Garlic, gastrointestinal protection and oxidative stress. In: Gracia-Sancho  J, Salvado  J, eds. Gastrointestinal Tissue: Oxidative Stress and Dietary Antioxidants. Elsevier; 2017 [chapter 20]. 12. Charrié J-C, Clairemont de Tonnerre M-L. Se Soigner Toute L’année au Naturel. France: Prat Editions; 2017. 13. Charrié  J-C, Souffland-Groussard  M, Bartczak  S, Paslin  D, Lapraz  JC. Les clés de L’alimentation Anti-cancer et Maladies Inflammatoires, Infectieures, Auto-immune. France: Terre Vivante Editions; 2017. 14. Morrison KD, Underwood JC, Metge DW, Eberl DD, Williams LB. Mineralogical variables that control the antibacterial effectiveness of a natural clay deposit. Environ Geochem Health. 2014;36(4):613–631. 15. Williams LB, Metge DW, Eberl DD, et al. What makes a natural clay antibacterial? Environ Sci Technol. 2011;45(8):3768–3773. 16. Duraffourd  C, Lapraz  JC. Traité de Phytothérapie Clinique: Médecine et Endobiogénie. Paris: Masson; 2002. 17. Lapraz  JC, Carillon  A, Charrié  J-C, et  al. Plantes Médicinales: Phytothérapie Clinique Intégrative et Médecine Endobiogénique; 2017. 18. Sen  S, Chakraborty  R. Herbs, gastrointestinal protection and oxidative stress. In: Gracia-Sancho  J, Salvado  J, eds. Gastrointestinal Tissue: Oxidative Stress and Dietary Antioxidants. Elsevier; 2017 [chapter 19]. 19. Guarino A, Guandalini S, Lo Vecchio A. Probiotics for prevention and treatment of diarrhea. J Clin Gastroenterol. 2015;49(suppl 1):S37–S45. 20. Sangiovanni E, Fumagalli M, Dell’Agli M. Berries: gastrointestinal protection against and oxidative stress and inflammation. In: GraciaSancho  J, Salvado  J, eds. Gastrointestinal Tissue: Oxidative Stress and Dietary Antioxidants. Elsevier; 2017 [chapter 18]. 21. Deleted in review. 22. Bach AC, Babayan VK. Medium-chain triglycerides: an update. Am J Clin Nutr. 1982;36(5):950–962. 23. Lacy BE, Mearin F, Chang L, et al. Bowel disorders. Gastroenterology. 2016;150(6):1393–1407.

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Simren M, Palsson OS, Whitehead WE. Update on Rome IV criteria for colorectal disorders: implications for clinical practice. Curr Gastroenterol Rep. 2017;19(4):15. Yang J, Wang HP, Zhou L, Xu CF. Effect of dietary fiber on constipation: a meta analysis. World J Gastroenterol. 2012;18(48):7378–7383. Dreher  ML. Whole fruits and fruit fiber emerging health effects. Nutrients. 2018;10(12). Pasupuleti VR, Sammugam L, Ramesh N, Gan SH. Honey, propolis, and royal jelly: a comprehensive review of their biological actions and health benefits. Oxid Med Cell Longev. 2017;2017:1259510. Russo  M, Giugliano  FP, Quitadamo  P, Mancusi  V, Miele  E, Staiano A. Efficacy of a mixture of probiotic agents as complementary therapy for chronic functional constipation in childhood. Ital J Pediatr. 2017;43(1):24. Mirghafourvand  M, Homayouni Rad  A, Mohammad Alizadeh Charandabi S, Fardiazar Z, Shokri K. The effect of probiotic yogurt on constipation in pregnant women: a randomized controlled clinical trial. Iran Red Crescent Med J. 2016;18(11):e39870. Mezzasalma  V, Manfrini  E, Ferri  E, et  al. A randomized, double-blind, placebo-controlled trial: the efficacy of multispe­ cies probiotic supplementation in alleviating symptoms of irritable bowel syndrome associated with constipation. Biomed Res Int. 2016;2016:4740907. Choi JS, Kim JW, Kim KY, Lee JK, Sohn JH, Ku SK. Synergistic effect of fermented rice extracts on the probiotic and laxative properties of yoghurt in rats with loperamide-induced constipation. Evid Based Complement Alternat Med. 2014;2014:878503. Jin L, Deng L, Wu W, Wang Z, Shao W, Liu J. Systematic review and meta-analysis of the effect of probiotic supplementation on functional constipation in children. Medicine (Baltimore). 2018;97(39):e12174. Ramos CI, Andrade de Lima AF, Grilli DG, Cuppari L. The shortterm effects of olive oil and flaxseed oil for the treatment of constipation in hemodialysis patients. J Ren Nutr. 2015;25(1):50–56. Evans S, Lung KC, Seidman LC, Sternlieb B, Zeltzer LK, Tsao JC. Iyengar yoga for adolescents and young adults with irritable bowel syndrome. J Pediatr Gastroenterol Nutr. 2014;59(2):244–253.

35.

Zhou C, Zhao E, Li Y, Jia Y, Li F. Exercise therapy of patients with irritable bowel syndrome: a systematic review of randomized controlled trials. Neurogastroenterol Motil. 2018;e13461. 36. Jang  A, Hwang  SK, Padhye  NS, Meininger  JC. Effects of cognitive behavior therapy on heart rate variability in young females with constipation-predominant irritable bowel syndrome: a parallel-group trial. J Neurogastroenterol Motil. 2017;23(3):435–445. 37. Turnbull GK, Ritvo PG. Anal sphincter biofeedback relaxation treatment for women with intractable constipation symptoms. Dis Colon Rectum. 1992;35(6):530–536. 38. Xiong F, Wang Y, Li SQ, Tian M, Zheng CH, Huang GY. Clinical study of electro-acupuncture treatment with different intensities for functional constipation patients. J Huazhong Univ Sci Technol Med sci. 2014;34(5):775–781. 39. Zhang  T, Chon  TY, Liu  B, et  al. Efficacy of acupuncture for chronic constipation: a systematic review. Am J Chin Med. 2013;41(4):717–742. 40. Haines  ST. Treating constipation in the patient with diabetes. Diabetes Educ. 1995;21(3):223–232. 41. Ihana-Sugiyama N, Nagata N, Yamamoto-Honda R, et al. Constipation, hard stools, fecal urgency, and incomplete evacuation, but not diarrhea is associated with diabetes and its related factors. World J Gastroenterol. 2016;22(11):3252–3260. 4 2. Tabbers MM, DiLorenzo C, Berger MY, et al. Evaluation and treatment of functional constipation in infants and children: evidencebased recommendations from ESPGHAN and NASPGHAN. J Pediatr Gastroenterol Nutr. 2014;58(2):258–274. 4 3. Ahadi  T, Madjlesi  F, Mahjoubi  B, et  al. The effect of biofeedback therapy on dyssynergic constipation in patients with or without irritable bowel syndrome. J Res Med Sci. 2014;19(10):950–955. 4 4. Broide  E, Pintov  S, Portnoy  S, Barg  J, Klinowski  E, Scapa  E. Effectiveness of acupuncture for treatment of childhood constipation. Dig Dis Sci. 2001;46(6):1270–1275. 4 5. Chattat R, Bazzocchi G, Balloni M, et al. Illness behavior, affective disturbance and intestinal transit time in idiopathic constipation. J Psychosom Res. 1997;42(1):95–100.

Chapter 11

Inflammatory bowel diseases Introduction: Adaptive role of the intestines based on an endobiogenic reflection This chapter discusses an Endobiogenic approach to two common inflammatory bowel diseases (IBDs): Crohn’s disease (CD) and ulcerative colitis (UC) also referred to as recto-hemorrhagic colitis. IBDs are disorders expressed in genetically susceptible individuals,1, 2 when the intestines are unable to adapt to local or systemic adaptation. Because the disorder remains latent across generations, across space, and time, one must look beyond genetic mechanisms to include epigenetic factors and adaptability in order to understand the Endobiogenic cause of disease.2, 3 One must place the intestines within the context of their intrinsic function and role in regional and global adaptation. Current thinking in the scientific literature views IBD as a disorder of dismicrobialism in those with a genetic susceptibility.1, 2, 4 The genetic foundation is undeniable. However, we find shortcomings in this approach that have led us to a very different approach to understanding IBD. For example, the risk of developing CD is 50% amongst monozygotic twins and less than 10% for dizygotic twins, indicating that there is even more than a genetic predisposition at play.1, 2 However, there are more than 160 genetic loci that have been correlated with IBD.2 Even if causation was to be shown, as opposed to association, it would still indicate a multifactorial origin to the expression of IBD, requiring a more nuanced approach to diagnosis and treatment, which is our position, as this chapter will detail. Contemporary models of disease focus on the interaction between the microbiota and the intestines as if they exist within a vacuum. The exact relationship of the changes in the microbiota has not been established.5 It is not clear if it is causative, associated, or the result of other local or systemic imbalances. Even when diet and lifestyle issues are considered, such as smoking, they are seen through a narrow lens of downstream physiology viz. oxidation, inflammation, and transcription mechanisms.2–4 IBD is a disease of the intestines, on this we agree. However, the intestinal tract is completely integrated into the global functioning of the terrain and submitted to neuroendocrine regulation. It The Theory of Endobiogeny. https://doi.org/10.1016/B978-0-12-816964-3.00011-0 © 2019 Elsevier Inc. All rights reserved.

primarily functions to serve the vital organs and tissues of the organism. Its intrinsic metabolic activity of the intestines is disproportionately small given its mass and weight compared to that of the remainder of the body, especially the brain, heart, and kidneys.6 The approach of Endobiogeny is to contextualize this disease of the intestinal tract to genetic, epigenetic, neuroendocrine, dietary, lifestyle and geographic factors, as well as chronobiologic cycles of genetic programming. The small and large intestines are the conduit and apparatus by whish the entire metaorganism of host + commensal flora obtain nutrients for nourishment (cf. The Theory of Endobiogeny, Volume 2, Chapters  5 and 6). However, as tissue, they have their own intrinsic metabolic requirements. Being subjected to constant threat from external agents and aggressions from fluctuations in pH, chemical moieties, etc., the intestinal epithelium has a high rate of turnover. This makes them susceptible to changes in the balance of metabolic demand to nourishment of the nourishing apparatus. Their primary role is to regulate the absorption of nutrients, discharge of potentially toxic waste, and regulation of fluid according to the global needs of the organism. At all times, the local and global needs must be balanced to avoid a state of nutritional excess or deficiency at either level. The role of the commensal flora must also be considered.1, 4 They aid in digestion for their own benefit, the benefit of their local intestinal host, and the global metaorganism of host + flora. They have their own terrain within the metaterrain, and their own response within the metaresponse of the global organism to aggressions. Thus, the regulation of the regulating capabilities of the intestines is capital and is linked to global neuroendocrine demands. Throughout the intestines are areas rich in receptors for central endocrine hormones that ensure the precise regulation of nutrients and electrolytes related to the production or activity of the endocrine glands that they stimulate. Small intestines: They express the quotidian responsibility of absorption of nutrients according to the exogenous presentation of nutrients and the endogenous demands of the organism.7 Ileocecal zone: It is a transition zone between the evagination from villi in the small intestines and the ­invagination 237

238  The Theory of Endobiogeny

of the colon composed of columnar epithelial cells.7 This zone is a key point in structural adaptation with r­espect to the management of electrolytes, water, and nutrients (Table 11.1). Large intestines: The role of intestines is to absorb water and residual nutrients from stool.8 The colon is rich in endocrine receptors.9–12 Dr Duraffourd, originator of the theory of Endobiogeny, hypothesized that each segment of the colon is rich in central endocrine receptors based on the nutrient requirements of the end organ that it stimulates (Table 11.1). In other words, the central hormone directly stimulates nutrient absorption from the segment rich in its receptors. Or, it upregulates the receptors of its peripheral hormone in that particular segment of the colon, which then alters nutrient reclamation.12 The global manager finely tunes reclamation of key elements of adaptation and buffering capacity ­during ­periods

of oversolicitation and hyperfunctioning (Fig. 11.1). For example, adrenocorticotropic hormone (ACTH) solicits the adrenal cortex for aldosterone excretion during adaptation states. Aldosterone retains water and minerals to improve perfusion pressure within general circulation.12 There is an increase in the reuptake of fluid and electrolytes from the rectosigmoid segment of the distal colon in adaptation states.12 The teleology, we posit, is a second source of electrolytes and fluids during a surge in aldosterone’s actions in a manner independent of its renal actions and intake of fluids or minerals from the diet. According to the theory of Endobiogeny, the distribution of IBD within the intestinal tract, from mouth to anus, is a result of their auto-pathogenic axis and by extension the critical Endobiogenic terrain expressed in the face of an ­aggression. Evaluating the basic function of each segment of the intestinal tract, the colon in particular, allows

TABLE 11.1  Endo-enteric relationships by location, receptor, hormone, and, metabolites Location

Microbiotic metabolism

Metabolites reclaimed

Central receptor

Peripheral hormone

Ileocecal junction

Fermentation: polysaccharides, cellulose, pectins, oligosaccharides carbohydrates → shortchain fatty acids (SCFA), iodine scavenging

Water Electrolytes

ACTH: structural adaptation

Adrenal cortex: aldosterone

Ascending right colon

As above + Muscle fibers, mucous, desquamated cells Lipid hydrolysis

Proteins

FSH

Gonads: estrogens

Hepatic flexure

Bile acids: enterohepatic recycling

Lipids

TRH/TSH

Pancreas: insulin, glucagon Gallbladder

Right transverse colon

Deamination of proteins SCFA Phenols, indoles Lipid fermentation

Proteins

FSH

Gonads: estrogens

Left transverse colon

Lipid fermentation: desaturated fatty acids, sterols

Proteins

LH

Gonads: androgens

Iron, proteins

TSH

Spleno-humoral immunity

Lipids Trace metals

GH Prolactin

Pancreas: insulin; relaunching of second loop of adaptation and augmentation of ACTH

Water Electrolytes

ACTH: functional adaptation

Adrenal cortex: aldosterone

Splenic flexure Descending colon

Recto-sigmoid

Flora putrification Final reduction of nondigested, nonmetabolized material pH neutral

Inflammatory bowel diseases Chapter | 11  239

g­ astrointestinal tract from oral mucosa to the anus in contract to UC, which affects only the colon.13, 14 The broad distribution of disease reflects the extent of hypersolicitation of all endocrine axes at the level of pituitary disadaptation (cf. below for a discussion of central endocrine receptors and enteric physiology).

Epidemiology and risk factors Geographic Northern sections of Europe and North America have the greatest incidence.15 In cooler areas of the world, there is a greater demand for adaptability during the change of seasons due to the cold. Because of the role of alpha-­ sympathetic in relaunching seasonal adaptation, it can also relaunch the critical terrain in late or recidivistic CD patients. ● ● ● ●

FIG.  11.1  The Endobiogenic cartography of global-enteric relationships. Central hormones adapt the rate of functioning of reclamation of elements of nutrition and buffering capacity according to the relative level of demand they have placed on their end organs. See Table 11.1 and text for details. (Modified with permission from Duraffourd and Lapraz, unpublished © 2015 Systems Biology Research Group.)

us to link it to endocrine activity and arrive at a rational understanding of localized inflammation, skip lesions and long-segment affliction in patients with IBD.

Crohn’s disease Introduction CD is a chronic, recurrent inflammatory bowel disorder.1, 13 According to the theory of Endobiogeny, the chronicity of the disease implies that there is a structural factor of initiation (SFI) that is unable to resolve a particular physiologic demand of the organism. An SFI is a factor of dysfunction is a genetically derived, disadapted response the organism’s demand for structural maintenance (cf. The Theory of Endobiogeny, Volume 1, Chapter 13). When the organism has difficulty maintaining or adapting some basic elements of cellular or tissular structure, a series of compensatory responses are installed, which creates the precritical terrain. In the face of an aggressor, the critical terrain is expressed and the symptoms of disease become manifest. The recurrent nature of the disorder implies that there is a disadaptation that occurs in the face of an aggression. Thus, CD is a structuro-functional disorder at the level of the intestinal tract—a difficulty maintaining the integrity of the intestines in the face of an intense adaptation demand. CD is an ulcerative disease that affects all layers of the mucosa. It may affect any part of the mucosal lining of the

Northern Europe: 16 per 100,000 North America: 12 per 100,000 people Southern Europe: 8 per 100,000 All other areas: 5 per 100,000

Industrialization, affluence, and diet Industrialized nations have a greater incidence, but this may be because countries of Northern Europe and North American have been industrialized for longer periods of time than other areas of the world, which brings with it an increased consumption of refined and preserved foods. Also, a large percentage of North America claims descent from Northern Europe. As less industrialized countries become more industrialized, the incidence of CD increases.15 Sex Pediatric ● In childhood onset, boys outnumber girls in diagnosis of new-onset CD. We find that this witnesses the role of the hyperandrogenic terrain that solicits a strong folliclestimulating hormone (FSH) response readapt the level of estrogen production Adult ● In adult onset CD, women outnumber men; women are particularly susceptible in our experience with first incidence in gonadopause in the late 30s or early 40s. This witnesses in our opinion, the greater role of FSH in adult females than in adult males in general, and witnesses the hyperfolliculinic response to a drop in estrogens during gonadopause.

Pathophysiology of CD Precritical terrain FSH has two key functions relevant to CD. First, FSH has a preparatory action on the cells.16–18 There are multiple,

240  The Theory of Endobiogeny

complex actions working at the level of the membrane, nucleus, and other areas of the cell related to transcription and translational modification.16 FSH through its second messengers stimulates growth factors, preparation of cholesterol for conversion into estrogens, upregulation of aromatase enzyme, etc. In general, FSH is known to have extra-gonadal sits of action.18 According to the theory of Endobiogeny, tissue, especially mucosa, become congested during this time in order to augment the amount and duration of exposure of tissue to nutrients. The second action of FSH is its classical vertical stimulation of estrogens. The SFI in CD is an insufficiency of estrogen activity relative to the intestinal requirement for initiation of protein metabolism. The response from FSH is intense due to the threshold of response from the pituitary. Due to an inability of the organism to readapt primary gonadal estrogen production to this level of FSH activity, the FSH response becomes excessive and prolonged (Fig. 11.2). There is an absolute hyper-FSH state and an absolute hyperestrogenism, with FSH >> estrogens. This imbalance in FSHestrogen relationship solicits a parasympathetic response

resulting in a spasmophilia with impaired adaptation arising from exocrine pancreas and parathyroid insufficiency. In our experience, CD patients are vagotonic by nature (Fig. 11.3). The vagus nerve solicits the exocrine pancreas to readapt the level of proteolytic enzyme expression in order to meet the appeal to proteins that FSH makes. The exocrine pancreas, similar to the gonad, is not able to sufficiently response to this appeal. This installs a hypervagal state in the chronic attempt to stimulate the exocrine pancreas. The sympathetic response to the hypervagal state is strong and greater than that of para (red heavy arrow, Fig. 11.3). At the level of metabolism, there is a hypermetabolic state with catabolic predominance thanks to the strong alpha response. In effect, the hypermetabolism brings about a chronic demand for proteins not met due to proteolytic enzyme insufficiency. The catabolic predominance further fragilizes tissue integrity, already congested. The hyperfunctioning sympathetic activity makes an appeal to the parathyroid gland, which becomes exhausted and incompetent in its ability to mobilize calcium for cellular or global adaptation (shown in gray, Fig. 11.3).

FSH

LH

Cortisol

Estrogens

Androgens

Delays anabolis

Protein intake

Protein utilization

Chromosome Nucleus

Impaired adaptation Catabolism > anabolism Proteolytic enzymes Insufficient to demand

Precritical

Disproportional action

Ribosomes Mitochrondnon Golgi apparatus

Delayed action

Endoplastic reticulum

FIG. 11.2  Structural factor of initiation (SFI) in Crohn’s disease. The SFI is a hyperfunctioning FSH, depicted by the heavy black arrow. The precritical terrain (lower left) is one of impaired adaptation in which catabolism exceeds anabolism and there is insufficient proteolytic enzymes to restore tissues (cf. Fig. 11.3 and text). This is the first step in compromising the quality of tissue. The second influence is the generally elevated cortisol activity (upper left) which delays anabolism, further impairing the general regulation of the cell cycle. Estrogen activity is hyperfunctioning, but not relative to the FSH demand. The demand created by estrogens for proteins is not sufficiently adapted (gray box). Estrogens, as is typical, relaunch LH and androgens, which initiate an intense protein utilization (red box) that exceeds the quality of estrogens in protein utilization. This is the final event that impairs the quality of mucosal tissue, resulting in a fragilization of the mucosa. (© 2015 Systems Biology Research Group.)

Inflammatory bowel diseases Chapter | 11  241

FIG.  11.3  Precritical terrain of Crohn’s disease. In addition to the structural factor of initiation (SFI), the precritical terrain fragilizes adaptability and the quality of the intestinal mucosa, in an attempt to compensate for the SFI hyper demand for proteins. In vagotonic patients, there is a hyperfunctioning parasympathetic tone to adapt exocrine pancreatic function (black arrow) to produce more proteolytic enzymes. The insufficiency of the response (gray arrow) makes a reactive appeal (broken green arrow) back to para, resulting in a further rise in vagal tone. There is a reactive alpha-sympathetic surge in response to this (heavy red arrow), which favors catabolism (Cata) over anabolism (Ana). Alpha-sympathetic stimulates the parathyroid glands (black arrow) to adapt the level of calcium activity to assist in the adaptation demand it has installed. The parathyroid hormone response is insufficient, thus, so is calcium response (gray arrow). This results in a reactive appeal (broken green arrow) to the sympathetic nervous system with a further reactive response in an (ultimately unsuccessful) attempt to re-relaunch the parathyroid glands (broken red arrow). In sum, there is a catabolic predominance both due to alpha and insufficient proteolytic enzymes to repair injured intestinal mucosa. In addition, the patient is not prepared to face an aggression due to impaired precritical adaptability at the level of the parathyroid gland. (© 2015 Systems Biology Research Group.)

Returning to the endocrine system, the hypersympathetic state overstimulates the adrenal cortex with a net effect of delaying metabolism (cf. The Theory of Endobiogeny, Volume 1, Chapter 6). There is a strong appeal to luteinizing hormone (LH) primarily from horizontal FSH stimulation and secondarily from radial estrogen stimulation. The androgen activity is relatively strong and greater than estrogens (Fig.  11.2). The net effect of this dysendocrinism is poor quality of protein assemblage be it enzymes, cytoskeleton, or tissular architecture reflected in the dysplastic architecture.19 According to the theory of Endobiogeny, we conclude that CD is a disorder of dysadaptability of protein management in the face of an aggression. Initiating factor of the critical terrain of CD In the face of an aggression, real or perceived, the autonomic nervous system is the initiating factor in Crohn’s colitis. It is the perception of stress that itself is a risk factor installation of the critical terrain.20 The aggression may be from diet or infections or psychic traumas.21, 22 For example, patients with IBD have an internalizing psychological tendency compared to nonaffected siblings, and the severity of internalization of feelings has been correlated to

s­everity of symptoms.22 Using arbitrary units of function, if the ­sympathetic-parasympathetic ratio is 3:1.8 (1.66) in the precritical state, it is 8:3 (2.66) in the critical terrain. The sympathetic response includes both alpha and beta. It is the brutality of the sympathetic response to an aggression, be it from the interior or the exterior that installs the intensity of the endocrine response resulting in ulceration of the mucosa.

Critical terrain of CD The critical terrain of CD involves sequential involvement of each axis: corticotropic, gonadotropic, thyrotropic then somatotropic. In the discussion the four axes involved, somatotropic, we review the concept of a special triadic endocrine relationship called a trépied (Fig.  11.4, and Theory of Endobiogeny, Volume 1, Chapter  9). There is a dysfunctional trépied in the CD patients which is key to understanding the degree of inflammation, ulceration and delayed wound healing (Fig.  11.5). Upon conclusion of the discussion of the critical endocrine terrain, the pre- and critical terrains are schematically summarized in Fig. 11.6.

242  The Theory of Endobiogeny

Third axis of solicitation: thyrotropic

FIG.  11.4  Trépied of alpha-sympathetic, prolactin (PL) and growth hormone (GH). Alpha stimulates GH and PL. GH stimulates PL, but PL inhibits GH. This is the trépied relationship. In terms of adaptation, in a first time, alpha initiates adaptation, in a second time, alpha stimulates GH to calibrate nutrient entry (first loop). In a third time, both alpha and GH relaunch PL to progress adaptation (from first to second loop). At a fourth time, once rising PL activity has inhibited GH, alpha’s final peak of PL helps complete adaptation (end of the second loop). (© 2018 Systems Biology Research Group.)

FIG.  11.5  The alpha-prolactin (PL)-growth hormone (GH) trépied in inflammatory bowel disease (IBD). The normal trépied is described in the text and Fig.  11.4. In IBD, the trépied is dysfunctional. Alpha is hyperfuncitoning, leading to a hyperadaptation. It also drives an intense PL that inhibits GH before GH can have its time in calibrating nutrients. Thus there is prolonged adaptation, hyperinsulinism, inflammation, delayed wound healing (in part due to insufficient nutrient accumulation), and ulceration of mucosa. (© 2018 Systems Biology Research Group.)

First axis of solicitation: corticotropic 1. Central: ACTH hyperfunctioning. At the level of the intestines, ACTH receptors are stimulated in the ileocecal junction to augment the absorption of water and electrolytes for structural adaptation, thus the predilection of inflammation of the terminal ileum 2. Peripheral: cortisol and adrenal cortex hyperfunctioning, cortisol > global adrenal activity → hypercatabolic state a. Net imbalance: ACTH > cortisol > adrenal cortex Second axis of solicitation: gonadotropic 1. Central: FSH hyperfunctioning intensified a. Mucosal hypertrophy of colon → increased anabolic demand for proteins 2. Peripheral: gonadal hyperfunctioning, estrogens ≫ androgen → impaired completion of protein anabolism → mucosal ulcerations a. Net imbalance: FSH ≫ estrogens > androgens

1. Central a. Thryotropin-releasing hormone (TRH) hyperfunctioning: i. TRH → gallbladder → excess bile excretion → autodigestion of the small intestines ii. TRH → PL → pancreas → insulin → mistiming of GH-insulin relationship → inflammation b. TSH hyperfunctioning i. FSH → TSH → congestion of mucosal tissues ii. TSH → insufficient T4, parathyroid hormone → insufficient calcium for adaptation 2. Peripheral a. Peripheral thyroid → hyperfunctioning → hypercatabolic, use of fat for energy, insufficient lipid management for cellular reconstruction b. Net imbalance: generally hyperfunctioning axis Fourth axis of solicitation: somatotropic Alpha has a classic trépied relationship with prolactin (PL) and growth hormone (GH) (Fig.  11.4). When this trépied functions normally, in a first time, alpha initiates adaptation. As the first loop of the general adaptation advances, in a second time, alpha stimulates GH to start the process of calibrating nutrients except glucose. This is the role of PL at the end of the second loop. In a third time, alpha also stimulates PL to advance adaptation by turning the first loop to the second. The GH response is initially greater than the PL response. As PL levels rise, be it from alpha, GH, or TRH, in time it inhibits GH in order to end the time nutrient apportionment, thus beginning the time of insulin and glucose to generate adenosine triphosphate (ATP) to fuel metabolism. And with this, in the fourth time, PL (along with somatostatin) ends adaptation. In IBD, the genetic heritage favors both a hyperfunctioning alpha and a hyperfunctioning and early responding PL during adaptation states (Fig. 11.5). Thus, when alpha stimulates GH and PL, the PL response is far greater than GH, and precedes it in time. GH is inhibited too quickly and PL remains in a hyperfunctioning state. This impairs somatotropic synchronization of glucose entry and energy production, resulting in free radical production, inflammation, ulceration, and delayed wound healing. The key to treating this imbalance is to inhibit alpha and relaunch GH. It may seem paradoxical that a medicinal plant such as Lamium album is efficient in IBD, as it stimulates GH and PL from the anterior pituitary. By relaunching GH with Lamium album, one restores the competency of GH in relationship to PL. This gives information to alpha to downregulate its stimulation of the somatotrophs in the pituitary. This is similar to the role of Eleutherococcus senticosus in prostate enlargement (Chapter 7) and acne (Chapter 8) with respect to androgens and LH.

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FIG. 11.6  Summary of precritical and critical terrain and pathophysiology of Crohn’s disease according to the theory of Endobiogeny. The precritical terrain (lower left) fragilizes the intestinal mucosa, meaning that it easily is susceptible to injury during adaptation states (cf. Figs. 11.2 and 11.3). In the critical terrain (upper and middle image), a hyperfunctioning alpha relaunches the entire axial sequence of endocrine activity: ACTH and cortisol, FSH and estrogens, LH and androgens, TRH-TSH-thyroid. Most crucial to the ulceration in a Crohn’s colitis is the disruption of the alpha-PL-GH trépied (Fig. 11.5). The end result in mucosal edema, inflammation, fissures, and ulceration. (© 2015 Systems Biology Research Group.)

1. Central a. PL hyperfunctioning → i. Hyperinsulinism ii. ACTH → relaunching of second loop adaptation, functional adaptation demands, and involvement of rectosigmoid colon iii. Abscess (favored) b. GH delay 2. Peripheral a. Hyperinsulinism proceeding GH with low insulin resistance → i. Elevated free radicals → inflammation → necrosis ii. Delayed wound healing iii. Fistula formation Emunctory congestion The exocrine pancreas continues to be congested. The liver becomes congested at the metabolic level and possibly for circulatory reasons due to the quantity of endocrine metabolites and inflammatory proteins that need to be metabolized as a result of the critical terrain. Tissue pathology With respect to history, the colon in CD shows chronic intestinal inflammation. There is activation of TH1 cells promoting interleukin-2, tissues necrosis factor alpha, ­ ­arachidonic acid, proteases, platelet activating factor, and

free radicals. The net effect is mucosal ulceration forming crypts in the mucosal endothelium, muscularis layers, and affecting the mesentery and lymph nodes. One can find abscesses with a neutrophilia within the crypts and ­mucosa.1, 13

Anatomical distribution of CD CD is characterized classically has having “skip” lesions: areas of affected and unaffected areas of ulceration (Fig.  11.7). From the Endobiogenic perspective, it witnesses the role of the various central hormone receptors on the colon and their particular role in the patient’s Endobiogenic terrain (cf. Fig.  11.1). For example, in Fig.  11.7, A (top) represents an ACTH predominance in the critical terrain for maintenance of structure. B (middle) and C (bottom) represent ACTH in structure, LH, TRH, and GH.

Pediatric In children, the onset of CD is 12–15 years,5, 21, 23 in the gonadic metabolic and tissular phases of chronobiologic unfolding (cf. The Theory of Endobiogeny, Volume 1, Chapter 13). This is a time of intense demand for estrogens for structural growth. The areas of frequency of ­presentation are presented below with comments with respect to the Endobiogenic significance of these findings.

244  The Theory of Endobiogeny

● ●

Small intestine alone: 30% Mouth, esophagus, stomach: rare but possible: 20%

Clinical presentation CD presenting in childhood tends to be more severe and progresses more rapidly.5 Symptoms are presented below by system.

Gastrointestinal Abdominal pain ● Right lower quadrant or periumbilical, often relieved with defecation ● Lower left quadrant pain may be more prevalent if there is a greater affectation of rectosigmoid colon Bowel habits ●

● ●

Diarrhea, intermittent, typically not bloody, or mucopurulent unless rectosigmoid colon involved Urgency to defecate Foul stool (rectal involvement with abscess)

Fistula-related presentations ● Recurrent urinary tract infections ● Feculent vaginal discharge ● Feculent soiling of skin ● Retroperitoneal abscess FIG. 11.7  Skip lesions in Crohn’s disease. (A) Isolated lesion (red) at the distal ileum, (B) skip lesions (red), affecting, with endobiogenic significance in parentheses: ileum, ileocecal junction (ACTH), ascending colon (FSH), hepatic flexure (TRH/TSH), mid-transverse colon (LH), mid to distal descending colon (GH), and (C) skip lesions (red) exclusively affecting the colon, whose Endobiogenic significance is noted in (B). (Reproduced from Samir, vectorized by Fvasconcellos [CC-BY-SA-3.0] via Wikimedia Commons.)

●

●

●

Terminal ileum: 50%–70% ● It witnesses the role of structural disadaptation by ACTH, possibly installed during adrenarche from 11 to 12 years of age Colon (typically ascending colon): 50%–60% ● It witnesses the role of FSH as a SFI and oversolicitation during Crohn’s colitis Gastric and duodenum: 30%–40%

Systemic ● Anorexia ● Weight loss ● Growth delay (in children may precede diagnosis of disease by 1 year or more)

Review of systems ●

●

●

Keen on sports, which improves the discharge of alpha, reducing the violent explosion of beta Vivid dreams, witnessing the inflammatory, fragilizing role of TRH in its stimulation of the endocrine pancreas Diet: tends to be rich in animal proteins, refined carbohydrates, animal fats, processed fats, which present daily insult and injury to the intestinal epithelium

Adult In adults, expression of CD is more evenly distributed, reflecting the settling of the organism into its adult Endobiogenic ­endocrine equilibrium.24 ● ●

Ileocecum: 30% Colon (rectosigmoid most prominent): 20%

Physical examination Morphology ● ●

Pale skin, darker hair in fair-skinned patients Feminine face with a masculine body (all ethnic origins)

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Pertinent findings Head, ears, eyes, nose, and throat (HEENT) ● Dilated veins on eyelids, nasal bridge, forehead ● Dark eyebrows, possibly bushy ● Long eyelashes ● Enlarged parotid and submandibular glands ● Dilated canal of Stensen ● Sublingual veins dilated, dark blue Abdominal ● Hepatic congestion, portal congestion ● Small intestine/dysbiosis: often tender ● Colon tender on palpation: all areas Extremities ● Right leg, tender on palpation at inferior and medial to tibial tuberosity, indicative of gallbladder congestion

Laboratory studies Fecal calprotectin and serum C-reactive protein (CRP) can serve as helpful markers of remission of the critical terrain.25, 26 Studies suggest that they may be superior to remission determined by clinical symptoms.27 This mirrors our experience with the biology of functions (Tables 11.2–11.5). Patients can be symptomatically in remission but still have numerous elements of the critical terrain, which keep the patient fragilized and susceptible to flare-up. In addition, labs for the biology of functions (including vitamin D) are recommended to follow the evolution of the terrain based on the integrative physiologic principles.

Biology of functions Once a patient has been diagnosed with CD, there are essentially three terrains one can view. The first is the critical terrain proper during an active flare-up (Tables 11.3–11.6). The second is a patient in remission with elements of the

critical terrain present, but not sufficiently elevated to bring about active disease. We refer to this as the suppressed critical terrain. We hypothesize that based on the genetically inherited terrain, there are various phenotypic subtypes of CD. For example, in some patients who are clinically asymptomatic in a suppressed critical terrain may have elevated brain stem activation, or inflammation, a hyperoxidative state, etc. Finally, there is the true correction of the critical terrain to a precritical state, typically with some Endobiogenic treatment. In the critical terrain, most of the elements will be deranged (high or low). In the suppressed critical terrain, the patient is asymptomatic and some of the elements of the critical terrain will remain deranged but less so than in the critical terrain. In the precritical terrain, the patient is asymptomatic and has derangements consistent with the precritical terrain. Some aspects, such as the exocrine pancreas, need to be assessed by physical exam. Table 11.2 summarizes the criteria we propose for number of deranged indexes per axis. There is overlap between the number of deranged indexes across the three categories. For example, the criteria for thyrotropic axis and immunity are 7–9 deranged indexes. For the same group, the suppressed critical terrain is 4–7. The reason for this that even there are not a substantial reduction in the number of positive signs in one axis, there will be in the two or more of the other axes. The one that continues to be the most deranged is likely to be the autopathogenic axis of the patient (cf. The Theory of Endobiogeny, Volume 1, Chapter 13). The first group of indexes is grouped together as “neurocorticotropic” because of the implication of sympathetic activation of the corticotropic axis (Table 11.3). In order to discuss terrain, we introduce new indexes not previously discussed. The immediate adaptation score #2 witnesses the global peripheral catabolic neuroendocrine activity during immediate adaptation: alpha, beta, and the adrenal cortex. It witnesses alpha-sympathetic engagement of the entire adrenal unit: medulla (adrenaline) and cortex (cortisol). There is also the adaptation entrainment score adjusted index. It witnesses, in the face of the relative degree of entrainment of sequential axial function starting with corticotropic axis the

TABLE 11.2  Criteria of indexes deranged per stage of terrain of Crohn’s disease Axis

Critical

Suppressed critical

Precritical

Neuro-corticotropic

>5/11

3–5/11

3/7

2–4/7

6/9

4–7/9

6/9

4–7/9

3/5

2–3/5

1–2/5

Total indexes deranged

28–41

15–28

bud Fragaria vesca Salvia sclarea

Adrenal support with hepato-splanchnic drainage44, 45 ●

Quercus pedunculata

Gonadotropic Reduce central overactivity44, 45 ● ● ●

Angelica archangelica Lithospermum officinale Borago officinalis

Support peripheral tissular estrogen activity44, 45 ● ● ●

Avena sativa Angelica archangelica Salvia sclarea

Central: GH Relaunch GH to restore the chronologic relationship with insulin44, 45 ●

Lamium album Peripheral: Insulin Delay effects of insulin on cell membrane44, 45

● ●

Arnica montana Malva sylvestris

Lamium album (White deadnettle) Parts used: leaf, flower44, 45 Galenic: MT, FE, MS, bulk herb Summary: supports hypophyso-pancreatic axis, use in children with failure to thrive, in adults with wasting or ulcerative disorders, in chronic fatigue states with brain fog Actions: GU: uterine vasoconstrictor, antimetrorrhagic, antihemmoragic by vasoconstriction, pelvic decongestant by venous stimulation. Endo: somatotropic: supports hypophysopancreatic axis, prolactogenic, increases GH and growth factors. Neuro: relaunches dopamine. GI: antidiarrheal, astringent. ID: urinary antiinfectious. Derm: vulnery, stimulates fibroblasts. HEME: antianemic. Pulm: expectorant, bronchial fluidifier. CV: venoconstrictive, venotonic, antiinflammatory. Use: GU: uterine bleeding, cystitis, vaginitis, leukorrhea, pelvic congestion, prostatitis. GI: colitis. Vascular: hemorrhoids, phlebitis, varicose veins. Metabolic: failure to thrive in children, chronic fatigue. Neurologic: brain fog. HEME: hemorrhagic anemia. Pulm: bronchitis, emphysema. Method: Tisane: 2 tsp./cup; infuse 8 min; Douche: of tisane for vaginal infections

Thyrotropic Reduce central hyperthyroidism44, 45 ● ● ●

Lithospermum officinale Lycopus europaeus Leonurus cardiaca

Modulate peripheral thyroid terrain according to the Endobiogenic state of the patient and support PTH ● ●

Calcium (ascorbate, glycinate, malate) Vitamin D (10,000 IU in AM × 4 days, then 5000–6000 IU in AM × 3 days, then reassess)

Arnica montana (Arnica) Parts used: flower44, 45 Galenic: MT, MS, bulk herb Summary: helpful in allergic/anxiety states with tachycardia, insomnia, etc. and in all disorders of inflammation rooted in a hyperinsulinism with somatotropic desynchronization. Actions: Oil infusion ● Neuro: antalgic, antimyalgic, antineuralgic, antispasmodic, spasmolytic Actions: Other galenic forms ●

Somatotropic Central: PL Inhibit PL activity, favoring plants with tropism for the intestines44, 45 ● ●

Fragaria vesca Poterium sanguisorba

● ●

Endo: ● Somatotropic: hyperglycemant (reduces the insulin activity at the level of cell) ● Posterior pituitary: oxytocic Immune: reduces histamine release from platelets CV: bathmotrope negative, strongly chronotrope negative, dromotrope negative, inotrope positive, facilitates coronary circulation, coronary vasodilator

TABLE 11.9  Overview of treatment of terrain of Crohn’s disease by polyvalent action of key medicinal plants Medicinal plant

Corticogonado

Gonado-thyro

Thyro-somato

Poterium sanguisorba Fragaria vesca

•

Salvia sclarea

•

Somato-cortico

Somato-gonado

Thyro-cortico

Other

• indirect

• indirect

Astringent, antihemorrhagic Antiseptic

•

•

Astringent, antihemorrhagic Antimicrobial Hepatobiliary-pancreatic support Astringent Antimicrobial

Avena sativa

•

Exocrine pancreas

Lithospermum officinale

•

• indirect

Lycopus europaeus

•

• indirect

Leonurus cardiaca

•

•a

Cortico-gonado, corticotropic-gonadotropic; Gonado-thyro, gonadotropic-thyrotropic; Thyro-somato, thyrotropic-somatotropic; Somato-gonado, somatotropic-gonadotropic. a

Reduces fixation of cortisol.

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•

254  The Theory of Endobiogeny

●

● ●

HEME: anticoagulant, antiecchymotic, eutrophic, hemostatic ANS: sympatholytic GI: hepatoprotective49

Use: hyperthyroid conditions with low insulin resistance, anxiety with insomnia, diurnal chronic fatigue and recurrent hypoglycemia, allergic diseases, cardiovascular disease, chronic fatigue, any disorder of inflammation rooted in a hyperinsulinism with somatotropic desynchronization. Cautions: cardiotoxic and hallucinogenic at high doses, can diminish the activity of antihypotensive and anticoagulant medications. Avoid during pregnancy and nursing

Malva sylvestris (Mallow) 44, 45

Parts used: flower Galenic: MT, MS, bulk herb Summary: all disorders of inflammation rooted in a hyperinsulinism with somatotropic desynchronization, especially recurrent infections and genitourinary disorders. Actions: Immune: antiinflammatory: digestive and pulmonary tropisms. CV: decongestant: tropisms: ear, nose, throat, pelvic, urinary. ID: antiinfectious: tropisms: ear, nose, throat, lungs. GI: emollient, antigastritic, laxative, anticolitic. Endo: somatotropic: hyperglycemiant (reduces effects of insulin on cell; increases insulin resistance). Use: Any disorders of inflammation rooted in a hyperinsulinism with somatotropic desynchronization, especially where inflammation has led to passive congestion with impaired drainage, GI: UC, small intestinal dysbiosis, ID: recurrent or prolonged bronchitis—especially dry, GU: pelvic congestion states: PMS, menorrhagia, menometrorrhagia, prostatitis, prostatic adenomas where inflammation plays a more prominent role.

Arnica vs mallow Arnica and mallow are interchangeable with respect to their actions on insulin activity. However, they are not equivalent. Arnica’s spheres of influence are primarily CNS and heart, especially in a person with a personality trait of anxiety. Malva’s spheres of influence are chest, abdomen, and pelvis, especially where inflammation of the mucosa is implicated in the disorder.

● ●

Intestines: support cicatrization of mucosal tissue and tonification of mucosa44, 45 ● ● ● ● ●

Medicinal plants ●

● ● ●

● ●

Alchemilla vulgaris Carduus marianus Agrimonia eupatoria Plantago major Pancreas: support exocrine function44, 45

●

Avena sativa

Maintain central inhibition of endocrine activity, especially FSH and TSH Hepato-pancreatic drainage Re-equilibrate enteric flora Pediatric Crohn: ensure good mineralization of bones and adequate vertical growth and weight gain 31 ● Vitamin D 2000–5000 IU per day in combination with calcium and magnesium and trace boron, vanadium, and phosphorous. ● Bone mineralization tincture: Sequoia gigantea GM 60 mL, Abies pectinata GM 60 mL, Rubus fruticosus GM 60 mL, Betula alba GM 60 mL: 3–4 mL twice per day ● Bone mineralization dry extract: Equisetum arvense 1 capsule twice per day

Sample treatment ● ●

●

●

●

Fragaria vesca Lamium album Plantago major Poterium sanguisorba Green Illite clay

Treatment: Management of the terrain

Drainage Liver: ensure good hepatic drainage44, 45 ●

Plantago major Digestive enzymes

Vitamin D 5000 IU in AM with calcium and magnesium Illite clay 1 tbsp in evenings before bed—soak all day in a tisane of Anthemis nobilis tisane: 1 heaping teaspoon of flowering tops steeped 15–20 min in 200 mL water. Strain and add to clay, mix well, let sit all day. Mix again in evening before bed and consume. ANS-cortico-somato-intestine: Matricaria recutita MT 60 mL, Poterium sanguisorba MT 40 mL, Fragaria vesca MT 60 mL, Malva sylvestris MT 80 mL, Lavandula angustifolia EO 4 mL, Dose: 3 mL TID before meals Gonado-thyrotropic-pancreas: Lycopus europaeus MT, Borago officinalis MT, Angelica archangelica MT, Agrimonia eupatoria MT, Eucalyptus globulus EO 2.5 mL, Cupressus sempervirens EO 1.5 mL, Dose: 3 mL TID before meals

Diet ● ● ●

Pancreas sparing diet Vegetarian or pescatarian diet in general Fermented foods

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Lifestyle ● ●

Regular aerobic exercise, de-stressing techniques Pediatric Crohn’s: be sure to address psychosocial issues related to body image, altered lifestyle, and compliance with treatment regimen

Case study in Crohn’s flare-up and treatment We present the case of a 14-year-old boy with CD who underwent a major flare-up in part due to noncompliance. We follow his recovery from critical to suppressed critical to remission terrain. He was diagnosed at 11.4 years. His CD was under management by a pediatric gastroenterologist, who started him on adalimumab. The family had a long tradition of use of medicinal plants and was referred to our practice for management. The primary gastroenterologist was open to collaboration with us. In addition to adalimumab, he was started on a decoction, tisane, clay, and vitamin D. The family stopped adalimumab after 9 months—1 year before flare-up and did not inform the gastroenterologist. They stopped the Endobiogenic treatments 6 months before flare-up and had not informed us of this. He had been scheduled for biology of functions blood drawn for routine Endobiogenic follow-up. The symptoms of CD flareup started hours after blood drawn, resulting in hospitalization. After stabilization, he was discharged home on adalimumab once again. His Endobiogenic treatment was as follows: ●

Adaptation decoction of Eleutherococcus senticosus root 1 tbsp decocted in 4 cups of water for 15 min. This decoction was used to steep 2 tbsp of the following t­isane for 8–10 min

TABLE 11.10  Neuro-corticotropic terrains of Crohn’s disease

High low values presented in red/blue respectively.

●

● ●

Cortico-gonado-enteric tisane of Lamium album, Poterium sanguisorba, Fragaria vesca, and Inula helenium equal parts Vitamin D 10,000 IU in the morning Calcium-magnesium supplement

Tables 11.10–11.14 demonstrate the recovery of his terrain over a 12-month period of time from critical to remission terrain. The neuro-corticotropic activity (Table 11.10), most susceptible to acute changes, also showed the clearest return to remission by 8 months and more so by 1 year after his flare-up. The gonadotropic axis (Table 11.11) is perhaps the most complex to interpret for two reasons. First, it contains the SFI, which is the hyper-FSH response. Second, this boy was in puberty and at an age where this axis is the most implicated in the development of secondary sexual characteristics and increases tissue mass in general. In general, the patient experienced a favorable correction of central and peripheral gonadotropic activity by 8 months postflare-up. This was probably part of the process of recovery toward restitutio ad integrum. However, 1 year on, the terrain showed the precritical imbalance of slightly elevated FSH activity due to insufficient estrogen activity and an appeal to LH which is also elevated. In the biology of functions, the FSH to LH indexes should have a ratio of approximately 2:1. One notes that while both are elevated in the critical terrain. FSH is 10-fold more elevated than LH, supporting the notion of the SFI being FSH and a graver increase in its activity in the critical terrain drives a number of key aspects of the pathophysiology.

256  The Theory of Endobiogeny

TABLE 11.11  Gonadotropic terrains of Crohn’s disease

High low values presented in red/blue respectively.

TABLE 11.12  Thyrotropic terrains of Crohn’s disease

High low values presented in red/blue respectively.

The thyrotropic axis and immune function (Table 11.12), is yoked along with the corticotropic axis to alpha-­sympathetic activity. While not deterministically linked, they are interrelated and integrated. We note a similar and clear improvement in thyrotropic function and immunity by 1-year postflare-up. The somatotropic axis (Table  11.13), while showing improvement overtime, has indexes with the greatest degree of derangement away from the normal values. This is not surprising since CD is a structuro-functional disorder. As with the gonadotropic axis, since this adolescent was in puberty, there were fluctuations in GH growth score activity. First, we note it to be elevated as a compensatory response to the injury to the colon. Then, 1 year after the flare-up, it is low again, representing a fundamental elevation of PL and alpha delaying GH timing.

The psychological profile of CD is not well understood. We are not aware of specific, validated psychotherapeutic interventions. We did offer advice to the family and supported a more communicative style between the patient and his father. The mother and patient already had a very open style of communication. While the two indexes we have discussed were less severe 1 year on than they were during the flare-up, they were worse than they were at 8 months postflare-up (Table 11.14). In effect, we concluded that at the psychological level, the patient came out of a remission into a suppressed critical phase. Fortunately, since the physiologic terrain was sufficiently improved, we did not consider the patient to be at risk of a further flare-up as long as he stayed on his treatments.

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TABLE 11.13  Somatotropic terrains of Crohn’s disease

High low values presented in red/blue respectively.

TABLE 11.14  Psychological indexes related to Crohn’s disease

High low values presented in red/blue respectively.

Ulcerative colitis Introduction UC is a chronic, recurrent inflammatory bowel disorder of the left distal descending and rectosigmoid colon.2, 14 It is an ulcerative disease that affects the superficial mucosal layer of the distal colon. In contrast, CD affects all layers of the bowel. According to the theory of Endobiogeny, UC is a functional disorder of adaptation at the level of the distal colon, where CD is a structuro-functional disorder of intestinal integrity. With regard to UC, we make three observations: 1. Chronicity implicates a SFI unable to resolve a physiologic demand 2. Recurrence implicates disadaptation each time the organism faces an aggression 3. Localization to the distal colon indicates a functional disadaptation of cortico-somatotropic activity (ACTH in adaptation, GH for tissue repair) It can be concluded that from the perspective of Endobiogeny, CD and UC are not on a “spectrum” of IBD with respect to the fundamental elements of precritical terrain, SFI and hence the fullness of the genetic and epigenetic

heritage. They do share phenotypic expression of inflammation and mucosal ulceration and hence symptomatic pharmacologic treatment will have commonalities. If one wishes to treat beyond suppression of symptoms, if one wishes to prevent the onset of disease in those at risk or truly bring the patient into remission, the distinction in the terrain must be noted, respected, and addressed in the long-term treatment.

Epidemiology and risk factors Genetic Family history is associated with higher risk of disease.1, 2

Immunity The immune system is dysregulated with autoimmune tendency. One finds dysbiosis with hyperimmune response to noncommensal organisms, with an increase in anaerobic sulfate-reducing bacteria (oxidize hydrogen [H2] and reduce sulfates [SO 4 2− ] from decaying organic material). This increases the general inflammatory terrain of the intestines.50 According to the theory of Endobiogeny, ­dysbiosis is not causative but predilecting and itself a downstream event of immune dysregulation and the precritical terrain.

258  The Theory of Endobiogeny

Diet Consumption of dairy products is associated with UC exacerbation. Again, this needs to be seen in the light of the genetic inheritance and dysbiosis.3

Nutritional Vitamin A regulates T-helper cell differentiation. Patients with UC have lower levels of vitamins A than controls.51, 52 Supplementation may improve the state of immune dysregulation and clinical symptoms such as blood in stool.51

Psychological UC is a disorder of adaptability and adaptation. The perception of stress more than any “objective” evaluation of stress is key in the risk of flare-ups.38, 39, 53 UC patients suffer from a higher incidence than the general population of anxiety and depression. Depression, according to the theory of Endobiogeny, is also a disorder of dysadaptability. Both disorders share commonalities. In the precritical terrain, both are vagotonics with dysfunction of the exocrine ­pancreas (Fig.  11.8). In the critical terrain is exaggerated alpha-­ ­ sympathetic response and overfunctioning corticotropic axis (Fig.  11.9). Psychological and ­psychosocial stressors are associated with UC e­ xacerbation. According to a systematic review of trials to date, psychotherapy is

helpful in improving subjective assessment of mood, and psychopharmacology therapy improves both mood and symptoms of UC.54

Comorbidities Adults and children with IBD have a higher incidence than age-matched controls of autoimmune and other inflammatory conditions.55–57 Incidence risk is twofold, commensurate to severity of disease and inversely related to use of salicylates in therapy.57 Most commonly occurring are uveitis and sclerosing cholangitis. Other manifestations include ankylosing spondylitis, spondyloarthropathies, pyoderma gangrenosum, pleuritis, erythema nodosum, and multiple sclerosis. Chronic UC is associated with a 2.4-fold increased risk in colon cancer.58

Epidemiology Similar to CD with respect to age, sex, geographic clime, and industrialization. UC tends to occur more commonly than CD, up to 3 times more often.15

Pathophysiology Precritical terrain UC occurs in vagotonic individuals (Fig. 11.8). The SFI is a general insufficiency of exocrine pancreatic enzymes. This

FIG. 11.8  Precritical terrain of ulcerative colitis. In vagotonic patients, there is an oversolicitation of the exocrine pancreas for general augmentation of digestive enzymes (black arrow). The response is insufficient (gray arrow), which solicits a reactive appeal (broken green arrow) which puts the patient in a hyperfunctioning parasympathetic state. This solicits a rise in alpha-sympathetic (black arrow) to match its tone. Alpha (αΣ) makes an appeal to beta-sympathetic (βΣ) which is delayed or blocked (gray broken arrow). This has two consequences: (1) blocked adaptation, (2) spasmophilia. Alpha also stimulates ACTH, and ACTH’s stimulation of the adrenal cortex is insufficient as well (broken gray arrow). This, along with a level of peripheral thyroid activity not sufficiently adaptated to alpha-sympathetic tone results in a total sympathetico-cortico-thyrotropic incompetence to adapt to future aggressions. The rising alpha tone that attempts to (unsuccessfully) readapt beta and adrenal cortex activity leads to a further reactive rise in parasympathetic tone (broken green arrow). (© 2015 Systems Biology Research Group.)

Inflammatory bowel diseases Chapter | 11  259

FIG. 11.9  Critical terrain of ulcerative colitis. It can be understood in three parts. The first is autonomic. Hyperfunctioning alpha (top center) stimulates a hyperfunctioning beta (adrenaline, top left), which favors hyperglycemia and inflammation. The second is the relaunching of the catabolic axes (center), again, by alpha. Central functioning exceeds peripheral gland response (gray, small print). The third is a disruption of the alpha-prolactin (PL)-growth hormone (GH) trépied (top right), discussed in Fig. 11.5. This participates in ulceration of distal colon mucosa. (© 2015 Systems Biology Research Group.)

entrains a hypervagal state which in turn solicits a reactive hypersympathetic response. This installs a spasmophilia, resulting in blocked adaptation. The adaptation dysfunction is rooted in dysfunctional yoking of alpha to the corticothyrotropic response. There is a hyper-ACTH response with insufficient adrenal cortex response. In the thyrotropic axis, peripheral thyroid activity is weak. In summary, the precritical terrain is a blocked neuroendocrine adaptation response with exocrine pancreatic insufficiency.

Aggressor and critical terrain: Ulcerative, hemorrhagic colitis

TABLE 11.15  ANS changes in the precritical and critical terrains of ulcerative colitis ANS

Precritial

Critical terrain

πΣ

++

++

αΣ

++

++++

βΣ

Blocked (spasmophilia)

+++

αΣ, alpha-sympathetic; βΣ, beta sympathetic; πΣ, parasympathetic. + Refers to the intensity of hyperfunctioning, the more pluses, the greater the hyperfunctioning.

Sympathetic In the face of some type of aggressors: a perceived stressor, an exaggerated response to a true aggressor,38, 39, 53 change of seasons, infection, diet, etc., the sympathetic nervous system is the initiating factor of a hemorrhagic UC. Ultimately, it is all three branches of the autonomic nervous system that are entrained into a hyperresponse in the face of an aggression. Table 11.15 summarizes the difference in the ANS between the precritical and critical terrains. Similar to CD, global sympathetic tone is elevated and far exceeds the parasympathetic response.

Endocrine response The endocrine response is detailed below and summarized in Fig. 11.9.

Corticotropic: First axis of solicitation 1. Central: ACTH in hyperfunctioning in adaptation: a. ACTH ≫ glucocorticoids, with adaptive cortisol blocking anabolism

b. Hypermetabolism of rectosigmoid colon to augment absorption of water and electrolytes for adaptation 2. Peripheral: insufficient adrenal cortex a. Cortisol > global adrenal cortex (relative): blocked anabolism in the face of mucosa proliferates → ­ulceration → hemorrhage

Thyrotropic: Second axis of solicitation 1. Central a. TRH hyperfunctioning: relaunches PL b. TSH hyperfunctioning: Expansion of cell membranes beyond anabolic capacity due to cortisol’s blockage of anabolism 2. Peripheral a. Peripheral thyroid insufficiency: absolute or relative to central functioning → insufficient lipid incorporation into growing and repairing cells → hemorrhage, blocked wound healing

260  The Theory of Endobiogeny

Somatotropic: Third axis of solicitation

Physical examination

The dysfunction of the alpha-PL-GH trépied is similar to that discussed in CD.

Abdominal exam similar to Crohn’s with respect to colon, liver, and pancreas; greater likelihood of pain on palpation of the distal colon from the splenic flexure distal to the rectosigmoid region

1. Central a. PL hyperfunctioning → i. Hyperinsulinism → inflammation of mucosa ii. ACTH relaunching → prolonged hypermetabolism of distal colon iii. Abscess formation favored iv. GH delay → impaired wound healing b. GH delay i. Insufficient insulin resistance → desynchronized nutrient entry in relationship to insulin → impaired cicatrization → ulceration, hemorrhage 2. Peripheral a. Hyperinsulinism proceeding GH with low insulin resistance → i. Elevated free radicals → inflammation → necrosis ii. Delayed wound healing iii. Fistula formation

Tissue pathology On biopsy of the distal colon, one notes a hyperimmune pattern with chronic inflammation. Cytotoxic T cells infiltrate the epithelium of colon. There are B-lymphocytes and increased IgG and IgE. Antibodies to the colon, smooth muscle, and cytoskeleton have been documented. Abscesses, granulomatous tissue, and pseudo-polyps may be present.59

Anatomical distribution of UC The most common areas of expression of UC are the anal verge, rectum, and rectosigmoid segments. Less common is pancolitis and least common is ileocecal involvement.60

Clinical presentation Similar to the colorectal symptoms associated with CD.

Laboratory studies: Critical terrain It is identical to that of CD with respect to CRP, fecal calprotectin, stool lactoferrin, and biology of function labs. Fecal calprotectin is the most sensitive and specific test in IBD in general of those listed, but is more targeted for UC than CD.25

Biology of functions: Critical terrain A similar consideration will be made in evaluating UC using the biology of functions as with CD. We start with a series of criteria to determine the critical vs suppressed critical vs precritical terrain (Table 11.16). It is important to note that as a functional disorder of adaptation, it is the adaptation indexes that will be the area of focus. And, most typically, it is the adaptation indexes that will be more deranged than those of structure. The first group of indexes is grouped together as “neuro-­ corticotropic” because of the implication of sympathetic activation of the corticotropic axis (Table 11.17). In order to discuss terrain, we introduce new indexes not previously discussed in other chapters or with respect to CD. The immediate adaptation index witnesses the relative role of the peripheral adrenal gland in the immediate adaptation syndrome. It will be elevated in both critical terrains. The CRH index evaluates the central activity of CRH. The greater the index, the greater the intensity of solicitation of the corticotropic axis is, and by extension, the less effective cortisol and aldosterone are in their negative feedback capacity. Treatment favors alpha-sympatholytics and central oxytocics such as Arnica montana or Taraxacum officinale to downregulate the amplifying role of vasopressin in ACTH relaunching and by extension vasopressin inhibitors (e.g., Taraxacum officinale).44, 45 Thus, one must also

TABLE 11.16  Criteria of indexes deranged per stage of terrain of ulcerative colitis Axis

Critical

Suppressed critical

Precritical

Neuro-corticotropic

>6/11

3–6/11

LH) Immune: antiallergic, antioxidant, febrifuge; Mucotaneous: astringent, antiinflammatory, antiulcerous, antiseptic, cicatrisant; Renal: volumetric diuretic.

Method: Tincture: limit to 1.25 mL TID; Tisane: no more than 5 g/1 cup water, 15 min steep. Use: ●

●

GU: hypergonadal states with fluid retention: mastopathy, cellulitis, hyperplastic obesity (high alpha, histamine, estrogen), dysmenorrhea, PMS (+ oil), premenopause; Allergies: congestive allergic disease. Contra: Pregnancy and nursing

●

●

Epilepsy: can interact with antiepileptics possibly increasing seizure risk; Hepatotoxicity: prolonged use of an infusion, or acute high dose use of an infusion can increase the risk of toxicity from pyrrolizidine alkaloids.

Borago officinalis (Borage oil) Essence: a regulator of disturbed immunity rooted in proinflammatory prostaglandins Parts used: seed Galenic: oil Actions: Oil: Rich in Omega 6 (GLA) and Omega 9 (Linoleic and oleic acids) ●

●

●

Cell: antiinflammatory, reduces pro-inflammatory prostaglandins, stabilizes cell membranes, enhances membrane fluidity CV: platelet antiaggregant Use: Internal: PMS, menorrhagia, eczema, hypercoagulable states due to platelet aggregation; External: vaginal dryness

Carduus marianus (Milk thistle) Essence: #1 hepato-protective and hepato-regenerative plant, especially with porto-splanchnic congestion Part: aerial parts, fruit, seed Galenic: MT, DE, BH Actions: ●

● ●

●

● ● ●

GI: hepato-protector, hepatic detoxificant (phases 1 and 2), hepatic antifibrotic, antiinflammatory, hepato-biliary drainer, portal decongestant, splanchnic decongestant, choleretic, mild cholagogue, hepatoregenerator (leaves), antidiarrheal; Immune: antiviral (esp. hepatitis C), antiinflammatory; Metab: hypoglycemant, hypocholesterolemant, reduces hepatic iron load, galactogen; CV: strong chronotrope positive, strong inotrope positive (seeds), circulatory tonic (arteriotrope, venotrope, lymphotrope), mild alpha-sympathomimetic, antiedematous; ONC: antitumoral, antiproliferative; Heme: hemostatic; ANS: mild alpha-sympathomimetic. Use:

●

Hepatic: hepatitis: viral, drug induced, acute and chronic; Cirrhosis, sclerosing cholangitis, cholecystitis, digestive disorders;

276   Appendix A

●

● ●

● ● ●

GI (general): portal congestion, splanchnic congestion, gastric ulcer from retrograde biliary flow, esophageal dysplasia from GERD; Cardiac: right-sided cardiac insufficiency, HTN; Vascular: venous and arterial insufficiency, phlebitis, hemorrhoids; Oncologic: adjuvant to chemotherapy; Heme: hemochromatosis; Metabolic: diabetes, hypercholesterolemia with a strong role from hepatic congestion and insufficiency, obesity.

Cichorium intybus (Chicory) Essence: optimal plant for metabolic syndrome with or without allergies, and by implication dysbiosis Parts used: root, leaf Galenic forms: MT, DE, BH, H NB: Root and leaf are rich in minerals, but only the root is rich in Inulin. Actions1, 2: ●

Method: Tisane (aerial): ½ tsp./250 mL water, infuse 10 min; 2–3 cups/day. Precautions: may cause mild GI upset, allergies associated with asteraceae family; May interfere with medications that use CYP450 enzymes for metabolism at high doses. ●

Carica papaya (Papaya, papayer) Essence: a targeted play for gastro-pancreatic dysfunction and metabolic implications Parts used: fruit Galenic: MT, DE Action: GI: eupeptic, antigastritic, pancreatin-like enzymes, hypolipemiant by enzymatic substitution. Use: GI: gastric ulcers, dyspepsia, all inflammatory conditions rooted in exocrine pancreatic dysfunction, metabolic disorders rooted in hyperlipidemia

●

●

● ● ● ● ●

Use: ●

Carum carvi (Caraway) Essence: a digestive and estro-androgenic regulator at central and peripheral levels Parts used: seed Galenic: EO, BH Action: ● ● ● ●

GI: carminative, digestive stimulant, antiflatulent; Neuro: antispasmodic (GI, Mental), antalgic; ANS: parasympatholytic; Endo: Cortico: reduces adrenal androgens (indirect by GnRH-FSH stimulation), Gonado: stimulates GnRHFSH, estrogenic, emengogue.

Use: GI: Flatulence, dyspepsia, irritable bowel syndrome, Neuro: spasmophilia GI and mental, ANS: all hypervagal states implicating digestion or function of the genito-urinary structures; Endo: all disorders rooted in hyperandrogenism and/or estrogen insufficiency: Acne, metrorrhagia, progesterone-predominant PMS symptoms, infertility, ­ amenorrhea, oligomenorrhea, prostatic adenoma, etc.

GI: aperitive, eupeptic, gastric protector, hepatic protector, portal decongestant, choleretic, pancreatic stimulant (exocrine), mild laxative (through fermentation of inulin in the root by intestinal flora), balances enteric flora (favors Bifidobacter and Lactobacillus ssp. due to FOS content of inulin), improves absorption of calcium and magnesium; Metab: hypoglycemant (indirect by sensitization of cell to insulin), hypocholesterolemant, hypotriglycerolemant; Immune: antiallergic (including anaphylaxis), antiinflammatory, antioxidant, immunomodulator (through support of enteric flora); CV: antiarrhythmic, bathmotrope negative, chronotrope negative, dromotrope negative, inotrope negative, hypotensive, vasculoprotective, Renal: diuretic (volumetric, azoturic), ANS: parasympathomimetic (mild); ONC: antitumoral; MS: analgesic, antiarthritic; Derm: depurative.

●

GI/CV: hepato-renal drainage in patients with: HTN, cardiac rhythm disturbances, hyperlipidemia or arterial disease; As a digestive aid in patients with hepatic cirrhosis and portal hypertension, disorders of enteric flora (dysbiosis), constipation due to insufficient digestive secretions, prediabetics, thin people who have trouble gaining weight, pruritis requiring hepato-renal drainage, low vagal tone with pancreatic insufficiency; Derm: skin disorders with hepato-biliary congestion.

Method: Tisane (leaf): 10–15 g/1 L water, infuse 15 min; Decoction (Root): 2.5 g/250 mL water, 15 min decoction; drink 2–3 times per day after meals. Precautions: (Relative): Hypotension, bradycardia.

Cinnamomum zeylanicum (Cinnamon, cannelle) Essence: a promoter of fullness of energetico-metabolic activity through adrenal gland relaunching, adaptability and improved digestion; a resolver of spasmophilic and infectious conditions rooted in asthenia.

Appendix A   277

Parts used: bark (C. cassia), leaf and branch (C. verum) Galenic: EO, H, FE, BH Action: ●

● ●

● ●

●

● ● ●

GI: eupeptic, carminative, choleretic, astringent, musculotropic antispasmodic (digestive and uterine), prebiotic, equilibrates gut flora, intestinal drainer; Immune: antiinflammatory, antipyretic; ID: immunostimulant, antiinfectious: gram +, gram −, antifungal, antiparasitic, dermatophytosis; tropism: ENT, pulmonary, intestinal, genital, urinary, skin; ANS: sympathomimetic17 (beta ⋙ alpha); Endo: Cortico: adrenal cortex stimulant,17 favoring glucocorticoids; Somato: pancreatropic-exocrine, reduces insulin resistance (aqueous18 and EO19–22); CV: inotrope +, chronotrope +, mild hypotensive due to peripheral vasodilation, fluidifies blood (rhealogic); Neuro: analgesic; Metabolic: hypolipemant: cholesterol, triglycerides; Heme: antihemorrhagic.

Use: Neuro: asthenia, spasmophilia rooted in adrenal gland insufficiency, GI: achalasia, eosinophilic esophagitis, bloating, flatus, dysbiosis, GERD rooted in pyloric spasmophilia, steatorrhea, ID: bacterial, fungal and parasitic infections (+ Juglans regia): GI: gastroenteritis, inflammatory bowel disease aggravations, etc., GU: cystitis, vaginitis, prostatitis; Pulm: bronchitis, pneumonia; ENT: otitis media, pharyngitis, sinusitis, rhinitis, etc.; Derm: mycoses, Endo: disorders of adrenal cortex insufficiency: fatigue with secondary excitation in the evenings, asthma, allergies, etc.; CV: bradycardia, hypotension; Metab: metabolic syndrome, hyperglycemia, diabetes mellitus type 2a and 2c, Immune: inflammatory conditions. Method: EO: 0.5–5 drops per day in divided doses; MT: 0.25–1.5 mL tid; Bark: (1) Decoction: 1 tsp. broken bark/ ¾ c. water; boil 3 min, steep 10 min, (2) Infusion: 1 tsp., steep 15–20 min, drink 2–3 cups per day; Suppository: 5%–10% w/w; Vaginal douche: 1.5 tbsp decocted in 1 L water. Contra: pregnancy (teratogenic), children < 6 years; GI ulcers, hepatic insufficiency (consumes GSH). Note: do not use essential oil on broken skin, in a bath, rectally or vaginally; do not add thyme and cinnamon EO in the same mixture—causes precipitation.

Citrus limon (Lemon, citron) Essence: promotes movement and flow through rheologic regulation and regulates buffering capacity Parts used: fruit Galenic: EO, GM, FE, FP Actions: ANS: sympathomimetic for tonifying microvasculature; CV/Heme: vitamin P (bioflavanoids)-like a­ctivity,

anticoagulant, antiecchymotic, antihemorrhagic, capillary antithrombotic, leukopoietic; Metab: alkalizer, Immune: febrifuge, antiallergic, antiinflammatory, GI: eupeptic, antigastritic, antacid by neutralizing hydrochloric acid, carminative, ID: antiinfectious (ENT, pulmonary), MS: antirheumatic, Renal: diuretic (volumetric, azoturic, choleretic, uricosuric). Use: CV/Heme: all states of vascular congestion, bruising, thrombosis, etc., edema, cellulitis, leukopenia, Metab: acidosis, hyperoxidative states rooted in excessive insulin activity/insufficient insulin resistance with elevated harmful free radicals, ID: infectious conditions rooted in congestion and stasis due to capillary compression from edema, especially recidivistic or chronic infections: Pulm: bronchitis, pneumonia; ENT: otitis media, pharyngitis, sinusitis, rhinitis, etc.; use as secondary EO. Method: Cellulitis, superficial circulation: Essential oil: Topical: antiviral; bacteriostatic); Digestive: astringent, antidiarrheal ANS: Alpha-mimetic (mild), antihistaminic; Endo: Corticotropic: mild stimulant through alphamimetic activity.

Use: Genito-Pelvic: all pelvic pathologies: hemorrhagic cystitis, prostatitis, metrorrhagia, uterine and cervical cancer, prostate cancer; hemorrhoids, disorders associated with pelvic congestion: lower extremity edema, heavy legs,

phlebitis, external hemorrhage; diarrhea, colitis; Derm: contusions, insect bites, small wounds, acne; ONC: complimentary treatment for all genito-pelvic tumors: prostate, ovarian, uterine, peritoneal, colon, anal, etc. Method: Leaf: ¼ tsp. in 5 oz water; steep 10–15 min, drink 2–3 times per day; compress/bath: 1–2 tsp. leaves in 8 oz water; steep 15 min.

Humulus lupulus (Hops) Essence: a superb regulator of neuro-luteal and inflammatory disorders Parts used: flower Galenic: MT, DE, FE, BH Actions: Neuro: neurotropic antispasmodic, sedative,27 ANS: sympatholytic; Endo: Androgens: reduces adrenal androgen production, antiandrogenic,28, 29 reduces peripheral androgen receptors, Estrogens: estrogenic,30, 31 Immune: COX-2 inhibitor,32 GI: eupeptic. Use: Neuro: anxiety, panic attacks, insomnia, fugue states, psychosis with aggressive behavior, Endo: all disorders rooted in androgenic excess of gonadal or adrenal origin: atopic disease, acne, atherosclerosis, prostate enlargement, alopecia, uterine fibroids, fibrocystic breasts, Immune: Inflammatory conditions, esp. atherosclerosis, rheumatic joint disease, etc., GI: dyspepsia. Note: may antagonize antidepressants, interfere with hormonal medications.

Ilex aquifolium (Holly) Essence: a particular neuro-pulmonary spasmolytic well suited to children, and women with fibrocystic breasts Parts used: shoots Galenic: GM Actions: ANS: alphasympatholytic; Neuro: spasmolytic: neurologic, bronchial; antiepileptogenic; Renal: renal failure (tubular > glomeruli) GYN: antifibrotic to breasts Use: Neuro: neuro-pulmonary spasmophilia: asthma, seizures, cephalgia, migraine; petit mal seizures (+ Tilia tomentosa GM + Cannabinols + magnesium, potassium); Renal: renal insufficiency (+ Fagus sylvatica GM + Anthemis nobilis EO); GYN: fibrocystic breasts (+ Betula pendula GM).

Inula helenium (Elecampane) Essence: a deep acting remedy for pituitary regulation and pulmonary pathologies Part used: root

Appendix A   283

Galenic: MT, FE, BH, P Actions: ●

●

● ●

●

●

Endo: Central: anterior pituitary stimulant (FSH, TSH GH > ACTH, anti-PL), Cortico: Adrenal cortex stimulant; Gonadotropic: LHRH stimulant favoring FSH and LH, but ultimately estrogens; Somato: Antiprolactogenic; Allergies: antiallergic (pharyngeal and pulmonary), sudorific; GI: aperitif; ID: antiinfectious (genital, ENT, pulmonary, urinary), antiviral, antibacterial, antifungal; Pulm: “a marked pulmonary tropism,” expectorant, mucillagenous demulcent; Renal: diuretic (volumetric, azoturic, chloruric).

Use: Endo: all disorders rooted in anterior pituitary insufficiency: failure to thrive, senescence, infertility, amenorrhea, etc.; Immune: allergies, ID: General: Lyme disease, ENT: otitis media, rhinitis, sinusitis, pharyngitis, laryngitis, tracheitis; Pulm: bronchitis (wet), bronchiolitis, pneumonia (viral, bacterial), Urinary: nephritis, cystitis, urinary tract infections; Genital: bacterial vaginitis, vaginal candidiasis, prostatitis; Pulm: chronic irritant cough. Caution: avoid in active tumors, pregnant and lactating women except under close supervision.

Juglans regia (Black walnut) Essence: #1 metabolo-pancreatic regulator, GI astringent and antiinfectious Parts: bark, hull, leaf, bud Galenic: MS, MT, GM, DE, BH Activity All forms: ●

●

●

●

●

GI: digestive astringent, antigastritic, stimulates hepatic macrophages and plasmocytes, antidiarrheal, pancreatic drainer, dual pancreatrope, exocrine and endocrine pancreatic stimulating; “Juglans acts on the functionality of the pancreas and contributes to the assurance of a good regulation at once exocrine and endocrine, whose role is capital in the genesis and continuation of urticaria and pruritic dermatologic disorders”1; ID: antiseptic, antibacterial (staphylococcus, proteus), antimycotic, antiinfectious (ENT, pulmonary); Metabolic: dual Antidiabetic,33 hypoglycemiant, hypolipemiant; CV: antiatherosclerotic, arteriotrope, arterial protector, veinotonic; Derm: antiinflammatory, cicatrising, antiseptic.

GM: balances GI flora, chronic parasites and Lyme disease Use: ●

●

● ●

● ●

●

Method: BH: acne, furuncle, eczema, psoriasis, impetigo, diabetic skin ulceration (+ Clay); Prep: Decoction (Metabolic): ½ tbsp/4 c water, 5 min decoction; drink in 3 divided doses or apply to dermatomycosies; Infusion (GI): 1 tbsp in 4 c water, steep 15 min, drink throughout day.

Lamium album (White deadnettle) Essence: supports hypophyso-pancreatic axis, use in children with failure to thrive, in adults with wasting or ulcerative disorders, in chronic fatigue states with brain fog Parts used: leaf, flower Galenic: MT, FE, MS, bulk herb Actions: ●

●

● ● ● ● ● ● ●

GU: uterine vasoconstrictor, antimetrorrhagia. antihaemorrhagic by vasoconstriction, pelvic decongestant by venous stimulation; Endo: Somatotropic: supports hypophyso-pancreatic axis, prolactogenic, increases growth hormone and growth factors; Neuro: relaunches dopamine; GI: antidiarrheal, astringent; ID: urinary antiinfectious; Derm: vulnery, stimulates fibroblasts; Heme: antianemic; Pulm: expectorant, bronchial fluidifier; CV: venoconstrictive, venotonic, antiinflammatory. Use:

●

● ●

1. Projet Vitadil urticaire Londres 2.doc.

Drainage: all disorders arising from exocrine or endocrine pancreatic oversolicitation; GI: delayed gastric emptying, gastroesophageal reflux due to pancreatic insufficiency, intestinal permeability (“leaky gut”), ulcerative colitis, Crohn’s disease, etc.; Metab: diabetes, prediabetic states, hypercholesterolemia; ID: ENT infections and chronic congestion, dysbiosis, Parasites: (+ Ficus carica GM + Cornus sanguinea GM + Thymus vulgaris EO, Artemisia absinthium EO); CV: atherosclerosis, arteritis, venous insufficiency; Derm/Allergies: skin disorders: urticaria (+ Plantago major + vitamin E + zinc), angioedema, dermatitis, eczema, psoriasis, acne, furuncle, impetigo, skin ulceration, etc.; Pulm: chronic pulmonary disorders: chronic obstructive pulmonary disease, sarcoidosis, etc.

GU: uterine bleeding, cystitis, vaginitis, leukorrhea, pelvic congestion, prostatitis; GI: colitis; Vascular: hemorrhoids, phlebitis, varicose veins;

284   Appendix A

● ● ● ●

Metabolic: failure to thrive in children, chronic fatigue; Neurologic: brain fog; Heme: hemorrhagic anemia; Pulm: bronchitis, emphysema.

Method: Tisane: 2 tsp./cup; infuse 8 min; Douche: of tisane for vaginal infections.

Lavandula angustifolia (Lavender) Essence: #1 polyvalent sympatholytic: all spasmophilias, infections, pelvic disorders Part: flowering top Galenic: MS, EO, MT, BH Activity: ● ● ●

● ● ● ● ● ● ●

● ●

ANS: α-sympatholytic >> β-sympatholytic > vagolytic; Endo: Cortico: reduces adrenal cortex activity; Neuro: central nervous system sedative, GABAergic, can accentuate the effects of central nervous system sedatives, urinary antispasmodic, antimyalgic, antineuralgic; Immune: antiallergic; Pulm: respiratory antiinflammatory, expectorant; GI: choleretic, hepatobiliary and renal drainer; GU: pelvic decongestant (venous activity), uterotonic; CV: arterial dilatator, venotonic, hypotensive; Heme: anticoagulant (vitamin K antagonist); ID: antibacterial (streptococcus, staphylococcus), antiinfectious (biliary, cutaneous, genital, urinary, intestinal ENT and pulmonary), antiparasitic scabicide), antiinflammatory, antioxidant; Derm: antibacterial, scabicidal, cicatrizing; Renal: volumetric diuretic.

●

Method: MT: 1–3 mL BID-TID, EO: 2–3 drops BIDTID, Tisane: 1.5 g (2 tsp.) steeped 3–5 min, BID-TID, Bath: 15 min infusion of tisane or 5–10 drops EO mixed with salt, EO topical: 3%–10%; dilution, friction rub, EO neat: on upper lip, in antihelical fold.

Leonurus cardiaca (Motherwort) Essence: #1 plant of TRH disorders related to anxiety and thyro-cardiac manifestations Parts used: whole plant Galenic forms: BH, MT, DE Actions1, 2: ●

●

●

●

●

● ● ●

●

●

●

●

●

●

● ●

Neuro-ANS: all hyperalpha states, primary or reactive: spasmophilia, insomnia, migraines, insomnia; Neuro-Immune: immune suppression, hyperimmunity, autoimmunity; Psych: anxiety, panic attacks, depression (peripheral > central); Drainage: pelvic, bronchial, venous congestive states: hemorrhoids, varicose veins, all pelvic and genital disorders, etc.; Infections: esp. aggravated by spasms or congestion: sinusitis, otitis media, bronchitis, influenza, cystitis, ­ vaginitis, prostatitis, dysbiosis; Derm (pruritic, erythematous): eczema, psoriasis, acne, scabies; CV: tachycardia, arrhythmias, stroke risk, hypertension, Reynaud’s disease; Pulm: asthma, bronchitis, pneumonia; GU: uterine spasms, dysmenorrhea, menorrhagia, infertility, vaginismus, sexual frigidity;

Endo: Thyroid: TRH antagonist, TSH antagonist, Cortico: inhibits cortisol, reduces fixation of cortisol to its receptors; Gonado: slightly estrogenic, emmenagogue, uterotonic—improves uterine contractions; Neuro: central nervous system sedative (lowers alpha, TRH),34 neurotropic antispasmodic; ANS: α-sympatholytic, beta-blocker (by regulating adrenal cortex activity), mild parasympatholytic; CV: cardiosedative, antiarrhythmic, hypotensive, bradycardic, hypotensive, inotrope positive, chronotrope negative, bathmotrope negative; MS: reduces muscular hyperexcitability (slightly vagolytic); Pulm: expectorant; Renal: diuretic; Cancer: antineoplastic (lymphoma, breast, colon, prostate). Use:

Use: ●

GI: ulcers, gastritis, colitis, constipation, gastro-­ esophageal reflux (pyloric spasmophilia).

● ● ●

CV: hypertension, anxiety-induced dysrhythmias; Endo: Thyro: Grave’s induced tachycardia; Neuro: all neurologic conditions rooted in hyperfunctioning of TRH especially if exacerbated with elevated cortisol: neurosis, psychiatric disorders (esp. with excessive, bizarre or uncontrollable thoughts), poor sleep due to intense dreams, brain fog with central hyperthyroidism (+ Sambucus nigra MT, Arnica montana MT, Ribes nigrum GM).

Contra: hypotension, bradycardia, pregnancy, esp. first trimester, lactation (may reduce production of milk through inhibition of prolactin). Note: reinforces effects of beta blockers, CNS sedatives and antiepileptics.

Lithospermum officinale (Stoneseed) Essence: primary central gonado-thyrotropic regulator for all conditions implicating FSH, LH, and TSH

Appendix A   285

Parts used: whole plant Galenic: MT, DE, BH, FE, P Actions: ●

●

●

● ●

Endo: Gonado: antigonadotrope: FSH and LH antagonist35 (thus relaunching ACTH); Thyro: TSH antagonist, T4-like activity, inhibitor of deiodization, reducing conversion of T4 to T3.36 “The knees that call for the use of Lithospermum are those in which you see imbricated signs of FSH, LH and TSH (tender medial aspects with overgrowth of skin).” p.60, Consultation Boucicaut, Christian Duraffourd (unpublished); GU: urinary and prostatic antiinflammatory, antilithiac, antioxidant; Metab: antigout, hypouricemant, dissolves gall stones and kideny stones; Renal: Volumetric diuretic, uricosuric; Derm/ID: antiseptic.

Use: Endo: Gonado: all disorders of hyper-FSH: fibromas, psoriasis, Crohn’s disease, etc. Hyperestrogenisms of central origin: PMS, cystic mastopathy, hot flashes, spasmophilic states in hyperfolliculinic women with hyperthyroidism, all disorders of hyper-LH: acne, fibroids, fibrocystic breasts, prostate enlargement, prostate cancer; Thyro: Grave’s disease, thyroid nodules, posthemi-thyroidectomy; GonadoThyro: autoimmune conditions with elevated FSH and hyperfunctioning thyroid, ONC: various cancers dependant on elevated FSH (CA 125), LH and TSH/Thyroid activity (CA 15-3), especially breast, ovarian, uterine, colon, and prostate; Metab: Gout, kidney stones, gall stones esp. in hyperfolliculinic women; CV: Tachycardia. Method: tisane: 30–45 g/1 L water; drink 2–3 cups per day. Contra: pregnancy, nursing, anterior pituitary insufficiency. Precautions: in high doses: may cause atrophy of sexual organs, hypothyroidism.

Lycopus europaeus (Gipsywort) Essence: primary central gonado-thyrotropic regulator for all conditions implicating FSH, LH, TSH and TRH where peripheral thyroid activity is also indicated Parts used: plant Galenic: MT Actions: Endo: Gonado: Anti-FSH, anti-LH, Thyro: central thyroid antagonist (TSH>TRH),35 inhibits the transformation of T4 to T3, diminishes the peripheral effects of thyroid hormones.37 Use: Endo: Gonado: all disorders of hyper-FSH: fibromas, psoriasis, Crohn’s disease, etc. Hyperestrogenisms

of central origin: PMS, cystic mastopathy, hot flashes, spasmophilic states in hyperfolliculinic women with hyperthyroidism, All disorders of hyper-LH: acne, fibroids, fibrocystic breasts, prostate enlargement, prostate cancer Thyro: Grave’s disease, thyroid nodules, posthemi-­ thyroidectomy, Gonado-Thyro: autoimmune conditions with elevated FSH and hyperfunctioning thyroid, ONC: various cancers dependant on elevated FSH (CA 125), LH, TSH/Thyroid activity (CA 15-3) or TRH action on pancreas (CA 19-9), especially cancers of breast, ovarian, uterine, colon, prostate and pancreas, especially when at risk of rapid growth or metastasis. Contra: pregnancy, nursing, anterior pituitary insufficiency.

Malva sylvestris (Mallow) Essence: an ideal plant to address disorders of inflammation rooted in a hyperinsulinism with somatotropic desynchronization, especially recurrent infections and genitourinary disorders Parts used: flower Galenic: MT, MS, bulk herb Actions: ●

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Immune: antiinflammatory: digestive and pulmonary tropisms; Drainage: decongestant: ear, nose, throat, pelvic, urinary; ID: antiinfectious: tropisms: ear, nose, throat, lungs; GI: emolient, antigastritic, laxative, anticolitic; Endo: Somatotropic: hyperglycemiant (reduces effects of insulin on cell; increases insulin resistance).

Use: Endo: Somato: any disorders of inflammation rooted in a hyperinsulinism with somatotropic desynchronization, especially where inflammation has lead to passive congestion with impaired drainage: hypoglycemia, chronic fatigue syndrome, fibromyalgia, posttraumatic stress disorder, inflammatory bowel disease flare up (Crohn’s disease, Ulcerative colitis), multiple sclerosis flare up, depression (peripheral), anxiety related to hypoglycemia; etc.; GI: Colitis (inflammatory and infectious), small intestinal dysbiosis, ID: recurrent, recidivist, and/ or prolonged otitis media, sinusitis, rhinitis (+ Ribes nigrum GM + Plantago major MT) bronchitis—esp. dry (+ Inula helenium MT + Ribes nigrum GM + Plantago major MT + Glycyrrhiza glabra MT); GU: pelvic congestion states (+ Hamamelis virginiana + Lavandula angustifolia EO): PMS, menorrhagia, menometrorrhagia, prostatitis, prostatic adenomas where inflammation plays a more prominent role. Note: Cf. Arnica montana for a differentiation from Malva sylvestris.

286   Appendix A

Matricaria recutita (German chamomile) Essence: #1 nonsedating plant for treatment of anger and its physiologic consequences, excellent antiinflammatory and antimicrobial Part used: flower and leaf Galenic: EO, MT Actions1, 2: ●

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●

GI: increases secretions: salivary, gastric, biliary; choleretic, aperitif, eupeptic, antigastralgic, antigastritic, antiulcerous, antacid, musculotropic digestive antispasmodic; Immune: antiinflammatory (uterine, digestive), febrifuge, sudorific, antihistaminic; ID: antibacterial (EO: gram +; Tisane: gram +, gram −), antifungal, antiparasitic; Derm/Mucosal: cicatrisant of digestive mucosa; ANS: sympatholytic, vagolytic; Endo: ● Cortico: reduces ACTH; Neuro: antalgic, sedative, neurotropic antispasmodic (arteries); Osteo-Articular (EO, topical): antiinflammatory, antalgic, muscle relaxant; CV: hypotensive; Drainage: decongestant: hepatic, splanchnic, pelvic; Heme: leukocytogenic (increases leukocytes), mitostatic, chemoprotective, anticoagulant (platelet antiaggregant): can potentiate the effect of anticoagulants; Cancer: antimitotic, antiproliferative.

instill 5 mL of mixture over 5 min per rectum; repeat 4 times per day until resolution of colitis.

Medicago sativa (Alfalfa) Essence: helps restore the peripheral gonadal balance when androgens > estrogens due to central factors Parts used: whole herb Galenic: MT, FE, MS, bulk herb Actions ● ● ●

●

Use: All hyperluteal states: progesterone-predominant PMS, prostatic adenoma, prostatitis, Cardiovascular disorders: atherosclerosis, arteritis, hyperlipidemia. Notes: can increases photosensitivity.

Melaleuca leucadendron (Cajeput) Essence: a genito-infectious plant with neuro-pulmonary harmonization; use where latent or active spasmophilia plays a role in recurrent genito-urinary, intestinal or respiratory infections Parts used: leaves Galenic: EO Actions: ●

Use: ●

● ●

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●

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ID: All noninfectious pathologies requiring a general inhibition of secretory and congestive phenomena; Wound: cicatrization; ANS: inhibition of alpha-sympathetic and parasympathetic activity; GI: indigestion, gastric ulcer, duodenal ulcer, ulcerative colitis, Crohn’s ileitis, GI infections, inflammation, spasmodic colitis; Neuro/Psych: anger, nervous conditions, insomnia, depression (overstimulated), abdominal migraines, neuralgia; Allergies: allergies, allergic asthma, infected eczema; GU: herpetic vaginitis. menstrual spasms; Metab: cachexia, loss of appetite.

Method: Tisane (GI, infections, gargle, compress): 2–3 tsp. in ¾ c. water; infuse 5–10 min, 3–4 cups per day; Gastric ulcer: Tisane: 1 tsp. leaf + 1 tsp. Fragaria vesca, steep 15 min in 1 cup water + ¼ tsp. colloidal silver; drink TID for 1–2 weeks; Colitis: Hamamelis virginiana MT + essential oils of Matricaria recutita, Boswellia carterii and Lavandula officinalis, in a base of Olive oil and PEG-20:

Endo: Gonado: anti-LH, antiandrogenic, estrogenic38; Vasc: rich in silica, improves elasticity of vascular wall; Metab: hypolipemiant (intestinal absorption modification, enzymatic substitution activity)38; Heme: contains vitamin K, uterine antihemorrhagic.

● ● ● ●

●

●

ID/Immune: antibacterial, antiviral; antiinfectious to genito-urinary, intestinal and respiratory tracts; immunostimulant; Pulm: expectorant, mucolytic; Drainage: pelvic decongestant by venous stimulation; ANS: sympatholytic, parasympatholytic; Neuro: antineuralgic (external), antispasmodic: muscular and neurologic; Endo: Cortico: oxytocic, peripheral; Gonadotropic: estrogenic (mild, with chronic use); GU: uterotonic.

Use: ID: GU: vaginitis, cystitis, prostatitis, ENT: sinusitis, Pulm: bronchitis; Rheum: osteo-articular pain, rheumatic pain; GU: all disorders of pelvic congestion: hemorrhoids, dysmenorrhea, varicose veins, prostate enlargement etc., labor, uterine spasms, lactation (let down); Neuro: spasmophilias, esp. rooted in an adaptative response to infections: migraines, asthma, muscle spasms, etc. Method: General topical: 3%–10% (3–10 drops/5-mL carrier oil); Focal friction rub: 20%–50% (1–5 mL/5-mL carrier oil); Bath: 2%–5% (2–5 drops per 5-mL carrier oil + MgSO4 salts + 1 tbsp NaHCO3); Contra: pregnancy (except during labor).

Appendix A   287

Melilotus officinalis (Yellow sweet clover) Essence: a superb regulator of lympatico-vascular flow and its neuro-cardiopulmonary determinants Parts used: flower Galenic: MT, H, FE, DE, BH, SWFP Actions:

Melissa officinalis (Melissa, lemon balm)

Essence: #1 neuro-thyroid adaptogen in Hashimoto’s thyroiditis and spasmophilics Parts: stem with leaves Galenic: MS, BH, DE, EO Actions: GI: eupeptic, digestive, antinausea, antispasmodic, an● Lymph: lymphatic antithrombotic, stimulates lymtigastralgic, choleretic, hepatoprotective; CNS: anxiolytic phatic pump and increases lymphatic tone; (GABA-ergic, prolongs GABA activity), neurocalmative, ● Vascular: capillaries and veins: improves cognitive enhancer (muscarinic and nicotinic receptors), microcirculation; enhances attention and memory; CV: antiarrhythmic, bath● ANS: central nervous system sedative, α-sympatholytic, motrope negative, vascular antispasmodic; Metabolic: hyantispasmodic (digestive, pulmonary, uterine); pocholesterolemant; Immune: antiviral (aqueous extract), ● Heme: improves blood rheology, antiaggregant of bacteriostatic, fungistatic, antiparasitic (Leishmania), anplatelets, reduces coagulation but does not prolong tioxidant, antiinflammatory, antineoplastic (minor effect); bleeding time, anticoagulant (vitamin K antagonist): ANS: alpha-sympatholytic; ENDO: General: adaptocontains coumarins which can reinforce the effect of genic (nervous system, thyroid36), Cortico: antioxytocic, anticoagulants; Gonado: inhibits FSH, LH (lithospermic acid), Thyro: ● Cardiac: bathmotrope negative; inhibits TSH. ● Pulm: antispasmodic, expectorant; Use: ● Muco-Cutaneous: eutrophic, improves tissue regenNeuro: all spasmophilias of a structural or functional eration and wound healing due to improvement in nature: GI: gastroesophageal reflux (pyloric spasm), dysmicrocirculation; pepsia, colic; CV: arrhythmias, arterial hypertension; ● Opthalmic: antiinflammatory; Neuro: dyskinesia (+ Nicotiana tabacum MT + Salvia of● Renal: diuretic (mild). ficinalis MT or EO); insomnia, nervousness; GI: gastric Use: ulcers, duodenal ulcers, dysbiosis, nausea, Endo: dysadaptLymph: Lymphatic congestion (+ Sorbus domestica ability, easy fatigability, recurrent infections—esp. viral, GM), cellulitis (+ Citrus limon EO + Mentha spicata EO etc. Thyro: central hyperthyroidism; GYN: uterine spasms + Zingiber officinale EO), recurrent infectious disorders of third trimester, morning sickness, pelvic spasms. Method: Tisane: 3 g leaves/1 cup water, steep 10 min for (+ Avena sativa MT + Cupressus sempervirens EO), Vasc: CV: disorders of blood stagnation (hypertension, conges- digestive issues and drink after meals, steep 15 min for nertive heart failure), atherosclerosis (+ Agrimonia eupatoria vous system/insomnia and drink before bed; Compress: 50 g MT + Juglans regia MT), phlebitis, claudication, varicose leaves/L of water; infuse 15 min, use in bath or as a comveins (+ Achillea millefolium MT + Ruscus aculeatus + press; EO, internal: 1–2 drops 1–3 times per day diluted and Castanea sativa GM ), variceal ulcers, GU: hemorrhoids encapsulated, EO, topical: 5%–30% diluted in carrier oil, (+ Hamamelis virginiana MT + Achillea millefolium apply 2–3 times per day to affected area; Hydrolat: 1–3 tsp. MT or Alchemilla vulgaris MT), Neuro: dementia, age-­ in water, 1–3 times per day. associated memory, diabetic neuropathy, anxiety, spasmoContra: central hypothyroidism; severe bradycardia. philic disorders: asthma, insomnia, migraines, IBS, Opth: inflammatory occular disorders: conjunctivitis, blepharitis, Mentha piperita (Peppermint) iritis, corneal abrasion; Pulm: wet, spasmodic bronchitis (+ Ribes nigrum GM + Populus nigra GM + Cupressus sem- Essence: excellent digestive tonic, antiinfectious and antalgic for superficial neuromuscular and dermatologic pervirens EO). Method: infusion: 1 tsp. dried flower steeped in 5 oz disorders Parts used: leaf and flower water; drink 2–3 times per day; Compress, enema, eye bath Galenic forms: EO, BH (dilute with distilled water), lotions and ointments: Decoct Actions: 1 tsp. in 5 oz water for 3 min: Use: ulcerations, contusions, GI: antiflatulent, digestive, eupeptic, cholagogue, cholehemorrhoids. Contraindications: use of anticoagulants; relative: retic, exocrine pancreatic stimulant (lipase, amylase), antin39 Concurrent use of pharmacologic sedatives, or in asthmat- ausea, balances enteric flora ; Neuro: antalgic, analgesic; ics, with chronic use; Toxicity: GI disturbance, vomiting Neuro: antispasmodic (biliary, intestinal, bronchial); Pulm: pulmonary antispasmodic, expectorant, antiinfectious; with high doses. ID: antiinfectious (antibacterial, antiviral) tropism: ENT, Note: discontinue 3 days prior to elective surgery.

288   Appendix A

pulmonary; ANS: mild: sympatholytic, parasympathomimetic; Endo: Gonado: mild antigonadotrope. Use: GI: bloating, flatulence, borborygmus, dysbiosis, irritable bowel, colitis, Neuro: spasmophilias: biliary spasm, constipation, migraines, cephalgia—esp. triggered by cervical muscular tension (direct application of EO); ID: dysbiosis, pharyngitis, bronchitis, sinusitis, otitis, asthma, insect bites; Allergies: pruritis. Method: EO: Analgesic: 0.1%–1% (2–20 drops/5 mL carrier), Nasal or buccal application: 0.25%–1% (5–20 drops/5 mL carrier): Antalgic: 1%–5%(1–5 mL/5 mL carrier); Hydrolat: PO: 1–3 tsp. bid; Diffusion, compress or tisane: 1 tsp. dry leaves in ¾ c. water, 10 min infusion (keep covered), before meals. Note: menthones in high dose can be neurotoxic; Can cause glottic closure in high doses, esp. infants; Irritating to the skin in infants and small children; can be irritating to the eyes if applied close to the eyes above a dilute concentration; Avoid in gastro-esophageal reflux originating in weak gastro-esophageal sphincter and/or hiatal hernia.

Menyanthes trifoliata (Bogbean) Essence: an excellent regulator of disadaptation through restoration of ANS sequencing, estro-androgenic balance and regulation of inflammation Parts used: leaf Galenic forms: MT, BH, FE Actions: ANS: β-sympathomimetic activity, parasympatholytic; GI: aperitif, eupeptic; Endo: Gonado: estrogenic, antiandrogenic (very strong); Immune: immunomodulatory (water fraction; contains selenium),40 antiinflammatory41; ONC: antitumorous.42 Use: Neuro: use in all states of spasmophilia rooted in a blocked beta: asthma, migraines, emotional lability, depression, etc., use in all states in which spasmophilia results in intense and brief bursts of beta: Anger outbursts, posttraumatic stress disorder with irritability and anger, short tantrums in children who intimidate their care givers; Immune: all inflammatory disorders, especially with a spasmophilic terrain; Endo: Gonado: all disorders rooted in gonadal androgen excess with insufficient estrogens: acne, enlarged prostate, uterine fibroids, postmenopausal hyperandrogenism, hirsutism, acne, etc., estrogenic insufficiency where androgen activity needs to be regulated: amenorrhea, oligomenorrhea, infertility, vaginal dryness, etc.; ONC: prostate cancer.

Passiflora incarnata (Passionflower) Essence: #1 sympatho-corticotropic regulator with anxiety and disorders of elevated cortisol

Part used: flower Galenic forms: MT, BH, DE Actions: Neuro: musculotropic and neurotropic antispasmodic (digestive and cardiovascular), sympatholytic, sedative43–49 without somnolence or reduction of vigilance, improves sleep latency and quality, GABA-ergic, antiepileptic; ANS: alpha-sympatholytic; CV: hypotensor, (−) chronotrope, (−) dromotrope, improves peripheral circulation, circulatory drainer; Pulm: oxygenator, pulmonary antispasmodic. Use: ANS: all hyperalpha states; Neuro: epilepsy, migraines, anxiety, insomnia, posttraumatic stress disorder, spasmolytic states that affect mind-gut activity: nervous diarrhea, colic, abdominal migraines, cephalgic migraines; Psych: hysteria, anguish, depression (peripheral), Endo: Cortico: all disorders rooted in hyperalpha with elevated cortisol: depression (peripheral), posttraumatic stress disorder, chronic fatigue syndrome, fibromyalgia, migraines, etc.; CV: supraventicular tachycardia (SVT), hypertension, Pulm: pulmonary hypoxia (+Vinca minor MT + Crocus sativa MT). Method: Tisane: 2 g (1 tsp.)/150 mL water, steep 10– 15 min, drink 2–3 times per day. Precautions: excessive doses can cause headaches and altered vision; can augment the effect of hypnotics.

Pinus sylvestris (Pine) Essence: a revitalizer is asthenic patients with cortico-immuno-insufficiency Parts used: bud (GM), needles (EO, hydrolat) Galenic: EO, GM, hydrolat Action: Osteo: antiarthritic (buds), improves articular cartilage formation, antiosteoporotic, Rheum: antiarthrosic; Endo: Cortico: adrenal cortex stimulant; ANS: sympathicotonic; ID: antiinfectious with viral tropism (ENT, pulmonary), Pulm: expectorant, antiseptic. CV: drains spinal column; Psych: revitalizer and regenerator during states of mental fatigue. Use: Osteo: ankylosing spondylitis (+ High dose Vitamin D), osteoarthritis (large and small joints), Regenerates cartilage, bone and tendons and ligaments (+Rosa canina or Ribes nigrum GM + Ampelopsis weitchii MG), Osteoporosis (+Rosa canina GM + Sequoia gigantea GM, Betula ssp. GM, Rubus fruticosus GM), Rickets (+Rosa canina GM + Abies balsamea GM, Rubus fruticosus GM), Rheum: Chronic rheumatism (+ Fraxinus excelsior GM + Rosa canina GM + Harpagophytum procumbens MT); ID: Chronic infections with immunoglobulin deficiency (+Fagus sylvatica GM), Prolonged subacute, chronic or recidivistic infections, in general + Rhodiola rosea MT and/or Eleutherococcus

Appendix A   289

senticosus MT, specific tropisms: Pulm (+ Glycyrrhiza glabra MT): wet bronchitis with inspissated mucous, ENT (+ Plantago major): otitis externa > otitis media, sinusitis, rhinitis, tonsillitis, pharyngitis, laryngitis; Endo: adrenal insufficiencies (+ Fagus sylvatica GM, Rosa canina GM): adrenal fatigue pattern, recurrent infections, insomnia (certain types), Neuro: mental exhaustion with anxiety (+ Tilia tomentosa GM + Ficus carica GM + Quercus pedunculata GM + Betula pubescens GM), Senescence: premature aging (+ Vaccinium vitis idaea GM) Method: Essential oil: Inhaled or Nebulized: Ear, nose, throat, lower respiratory infections 1 drop/3 mL 0.9%–3% normal saline or albuterol according to indication, Topical: Chest, joints: 1%–15% adults (1–15 mL/5 mL carrier oil), Bath: 2%–5% (2–5 drops/5 mL carrier), Internal 1–3 mL/250 mL tincture; Hydrolat: 1–4 tbsp 3–4 times per day for acute infections, 1–4 tbsp 2–3 times per day for chronic asthenia.

Plantago major (Plantain) Essence: #1 polyvalent drainer for disorders of ear, nose, throat, upper and lower airways, and GI Part used: leaf Galenic forms: MS, MT, DE, BH Actions: ● ● ●

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Pulm: antitussive, mucolytic, expectorant, antispasmodic; ENT: ENT drainer and antiinfectious; Immune: immunostimulant: interferon, lymphocytes), digestive antiinflammatory, antiallergic (antihistaminic, reduces leukotrienes): “by reducing excess histamine, plantain participates in the diminution of pathologic urticarial manifestations as well as all cutaneous disorders of a dermatologic nature”1; GI: antigastritic, antacid, astringent, digestive antispasmotic antiulcer: gastric and duodenal; Hepato-Renal: hepatorenal drainer, hepato-protector; Pancreas: hypoglycemant by its invertase and other diastase activity; CV: venotonic, venoconstrictor, mild antihypertensive; Heme: hematopoietic—bone marrow and spleen, antihemorrhagic; Metabolic: hypolipemiant by hepatorenal drainage and enzymatic activity; ID: antiinfectious (ENT, pulmonary: staph, beta-­ hemolytic strep, antiviral: herpes, adenovirus, antiparasitic: helminths); Renal: diuretic (volumetric, uricosuric, azoturic); Neuro: antispasmodic; Cancer: antitumoral; Drainage: GI: Hepatic: enzyme inducer, Intestinal: astringent, Pancreatic: increased activity of digestive enzymes; Respiratory: expectorant; Urinary: volumetric diuretic, uricosuric.

Use: ●

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● ● ●

● ●

General: all disorders rooted in hepato-pancreatic dysfunction of a digestive or infectious nature, particularly ear, nose, throat, bronchus and lungs and inflammatory conditions rooted in hepatobiliary dysfunction; Drainage: liver, kidney, exocrine pancreas ear, nose and throat, airways; GI: gastritis, hyperacidity, nausea, vomiting, diarrhea, liver disease; ID: tonsillitis, otitis, cystitis; Pulm: bronchitis, asthma, chronic cough; Allergies/Immune: asthma, allergic reactions, psoriasis, hives, urticaria (+ Juglans regia + Zn, Vitamin E); Metab: hypercholesterolemia, edema, gout; Wound: wound healing in eczema, psoriasis, conjunctivitis, ulceration of skin, contusions, anal fissures, hemorrhoids, venous congestion, insect bites.

Method: Tisane: 2–3 tsp./1 c water, steeped 5 min, 3–4 ×/day; Compress for eye disorders: infuse 2 tbsp in ¾ cup water for 15 min. Contra: none.

Populus nigra (Black poplar) Essence: a supreme aid in treatment of spasmodic neurocardio-vascular conditions and inflammation of airways. Use as a companion to primary treatments, especially Ribes nigrum and Alnus glutinosa Parts used: buds Galenic: GM Actions: Neuro: antalgic; CV: arterial antispasmodic; Increases collateral artery formation; Immune: antiinflammatory with particular tropism for airway: trachea, bronchus, bronchioles and to some degree alveoli; Renal: diuretic, uricosuric. Use: Rheum: Acute rheumatic disease: gout, arthritis (+ Ribes nigrum GM + Fraxinus excelsior GM + Fagus sylvatica GM + Pinus sylvestris EO), etc., Vasc: claudication (+ Ruscus aculeatus GM + Citrus limon EO), Neuro: Neurodegenerative diseases: autism, Alzheimer, poststroke (+ Ficus carica GM); Pulm: Tracheitis (+ Ribes nigrum GM + Plantago major MT + Alnus glutinosa GM for 4–6  weeks), bronchitis (+ Ribes nigrum GM), add Alnus glutinosa if requires treatment 4 weeks or longer with persistent symptoms.

Poterium sanguisorba (Salad burnet) Essence: #1 somato-metabolic regulator, with far-reaching implications in human health Parts used: root, leaf and flower

290   Appendix A

Galenic: MT, FE, BH Actions: Endo: Somato: inhibits GH and PL (stronger antagonist than Fragaria vesca); GI: antiinflammatory (colon),50 digestive astringent and cicatrizant, antigastritic, antidiarrheal, digestive antihemorrhagic,51 ANS: sympatholytic; ONC: Antitumoral (metabolic and inhibiting angioneogenesis); CV: antioxidant, antiinflammatory; Immune: antiseptic; Derm: antihemorrhagic, cicatrizant; Renal: diuretic. Use: Endo: Somato: all conditions that require inhibition of both GH and PL, and, all conditions that involve hyperfunctioning of growth factors: GI: Diarrheal or hemorrhagic GI conditions: Crohn’s disease (esp. distal colon affectation) and Ulcerative colitis flare-up, diarrhea, gastritis, gastric or duodenal ulcers; ONC: any solid tumor at risk or actively metastasizing, skin cancers, malignant mastopathies, Neuro: neuro-degenerative disorders: multiple sclerosis, Alzheimer’s disease, congenital neuromyopathies, chronic fatigue syndrome, fibromyalgia, insomnia rooted in elevated cortisol and somatotropic desynchronization Psych: dysadaptability in prolactigenic individuals (milky-white skin, easily startled, easily sick, numerous psychic affections, sensitive to external emotional and environmental influences); CV: atheroma (atherosclerosis), risk of thromboembolism, Rheum: arthroses, Osteo: calcification of the spine, Derm: psoriasis, squamous eczema, Metab: breast adenomas, diabetes mellitus type 2b, prediabetes. Method: Decoction: 5 min, 25–30 g of root/500 mL water, 1–3 times/day. Contra: pregnancy, nursing, failure to thrive in children.

Quercus pedunculata (Oak) Essence: an excellent polyendocrine product that redistributes the general endocrine activity allowing for a general regulation of the organism Parts used: bud Galenic: GM (with respect to actions listed below, other Galenic forms available) Actions: Endo: General: Quercus pedunculata (aka robur) is a plant of both structuro-structural and structuro-functional activity of the organism. It has a polyendocrine function at the level of the pituitary that along with its corticotropic tropism allows for a general regulation of the organism, assuring growth, regulation, defense and fertility. It possesses a synergy more on the endocrino-metabolic function at the pituitary level than endocrino-endocrine, allowing for both intra-pituitary regulation and centrifugal regulation. It is a general regulator that reestablishes the general equilibrium and equanimity of the organisms in its structural and structuro-functional activities; Corticotropic: supports glucocorticoid production in the adrenals, supports adrenals

without being stimulating, inhibits ACTH through similarity of action (as cortisol); Gonado: stimulant of gonadal endocrino-tissular activity favoring androgens but not at the expense of estrogens; ID: antiinfectious (dermatologic tropism and general support in part through its general regulatory activity on the adrenal cortex); Immune: febrifuge, Osteo: osteoblastic, osteoregulator in its relationship with peripheral metabolism; CV: improves cyanosis in shock, GI: portal decongestant, aids digestion, digestive astringent, GU: Spermatozoic, Drainage: Pelvic decongestant (venous stimulation) Use: Endo: Pituitary: all conditions in which there is h­ yper-, hypo- or inconsistent pituitary function across endocrine axes: failure to thrive, wasting, sarcopenia, infertility, amenorrhea, dysmenorrhea, etc. Corticotropic: Any disorder of adrenal insufficiency: asthma, immune dysfunction (hypo- hyper- or autoimmunity), allergies, all infectious conditions; Chronic fatigue: Men: 4:3:1 Quercus pedunculata GM + Ribes nigrum GM + Sequoia gigantea GM, and for drainage: Juniperus communis GM, Women: 1:3:3 Quercus pedunculata GM + Ribes nigrum GM + Sequoia gigantea GM, and for drainage: Juniperus communis GM, Gonadotropic/GU: low libido, premature ejaculation (+ Ylang ylang EO Topical + Turnera diffusa MT), uterine prolapse, anal prolapse, vaginal atony, BONE: fracture (+ Betula ssp. GM), osteoporosis (+ Sequoia gigantea GM + Rubus fruticosus GM + Betula ssp. GM); Metab: malnutrition, ONC: active or postcancer terrains in which bone remodeling is elevated, risk of, or, current bone metastasis of tumors, bone marrow suppression (+ Cornus sanguinea GM, Tamarix gallica GM); GI: constipation (+ Rosmarinus officinalis GM), CV: shock (high dose + Crocus sativa 6x + Pyrogenium 6c-9c), early hepatic fibrosis (+ Secale cereale GM + Betula pendula GM high dose), ID: Herpes (+ Ulmus campestre GM, Rosa canina GM, + liver drainage), CV: Hypotension (+ Crataegus oxyacantha GM), Derm: Furuncles (+ Arctium lappa), periodontitis, psoriasis (+ Fragaria vesca MT, Poterium sanguisorba MT + Malva sylvestris MT + Viola tricolor MT).

Raphanus niger (Black radish) Essence: #1 prespring adaptation and detoxifier, disorders of digestive-pulmonary stasis Part used: root Galenic forms: MS, MT, DE Actions: NB: rich in sulfur, sulferated compounds, vitamin C, Mg, K, Na, Ca, P, Fe; GI: cholagogue, choleretic (volume and fluidity), hepatobiliary drainer, hepatic detoxifier (inhibits phase 1, activates phase 2 enzymes i.e., GSH peroxidase, augments excretion of xenobiotics) digestive antispasmodic, mild laxative (via biliary flow); Pulm: ­mucolytic,

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fluidifies mucous, augments bronchial excretions, bronchial antiseptic; ID: Antibacterial; Tropism against H. pylori, Staph aureus, antifungal; Immune: immune stimulant, antioxidant; Derm: antiinflammatory (topical application), cicatrizing, vulnerary; Renal: diuretic, antilithiatic; Endo: Thyro: Increase TRH, TSH endocrine activity, but may reduce production of T4. Use: Best used for short periods of time, Cosmobiologic: change of seasons, especially prespring from February 21 to March 4, as long as March 18th if needed; GI: disorders of a hepatobiliary nature: cirrhosis, hepatitis, sclerosing cholangitis (+ Carduus marianus ± Acer campestre GM), cholecystitis, adjuvant for chemotherapy toxicity (+ Juniperus communis GM), siderosis, hepatoprotection (alcohol, drugs, xenobiotics), food poisoning, gastritis with delayed gastric emptying from biliary dyskinesia, gastric ulcers, etc.; Disorders requiring good sulfur activity and hepato-biliary drainage: Pulm: acute sinusitis, acute bronchitis, MS: rheumatoid arthritis (inflammatory phase), arthrosis, Derm: psoriasis, urticaria, eczema, acne, furuncles, anthrax; Endo: Thyrotropic: Disorders benefitting from reduction of peripheral thyroid activity: Grave’s disease, functional hyperthyroidism; ID: whooping cough; Neuro: abdominal migraine; Metab: obesity with oxidative insufficiency; Vitiligo (as simple syrup or juice). Method: Mother tincture: no more than 2 mL TID; Juice (fresh): 1–2 oz before main meal (add olive or flax oil or honey to reduce risk of heart burn; Simple syrup: slice a whole black radish in fine slices. Layer in a pot alternating with crystallized sugar. Let sit for 24 h, strain and refrigerate. Take 4–6 tbsp per day in divided doses. Contra: biliary obstruction; Relative: latent or frank hypothyroidism. Precautions: Gastritis.

Rhodiola rosea (Goldenroot) Essence: a true adaptogen across the lifecycle for survival, reproduction and durability Parts used: root Galenic: MT, DE, BH Actions: Neuro: serotonergic, dopaminergic, cholinergic, noradrenergic; Endo: General: adaptogen of the centralperipheral vertical endocrine feedforward mechanisms, particularly corticotropic and gonadotropic function and cortico-gonadotropic coupling,23, 52–56 Corticotropic: Augments adrenal cortex’s capacity to produce all metabolic lines of hormones, Gonadotropic: estrogen receptor modulator: downregulates number of receptors related to nongenomic activity, facilitates nuclear-response element binding to estrogen for genomic activity of estrogens’ regulation of cellular metabolic activity, Thyrotropic: augments

thyroid glands’ efficient of production of calcitonin and thyroxine, diminishes penetration and adhesion of thyroid antibodies; Immune: thymic support: improves maturation of T-cells by facilitating cytokine signaling and quality of TSH diffusion into the gland, antioxidant; CV: myotrophic, cardioprotectant, antiarrhythmic: direct through stabilization of Purkinje fibers and indirectly through central regulation, GU: emmenagogue, improves sexual function related to the sequential activity of stimulation, sustain, orgasm and recovery; ONC: anticarcinogenic, antimetastatic, antimutagenic; Heme: leukocytogen. Use: General/Corticotropic: States of fatigue from asthenia (+ Eleutherococcus senticosus + Ribes nigrum GM + Satureja hortensis EO) or overexcitation (+ Passiflora incarnata + Sequoia gigantea GM ± Fraxinus excelsior GM + Lavandula angustifolia EO), Gonadotropic: Amenorrhea, oligomenorrhea, polymenorrhea, metrorrhagia, Thyrotropic: Hashimoto’s thyroiditis, Grave’s disease (Melissa officinalis MT + Lycopus europaeus MT + TRH inhibitor: Leonurus cardiaca MT if tachycardia or dysrhythmias, otherwise, Fabiana imbricata MT); ID: all states of infection, acute or chronic, all locations of infection; Psych: Depression (+Crocus sativa MT, Ribes nigrum GM); mental retardation (+ Melissa officinalis MT + Sambucus nigra leaf MT), ADHD (+ Ginkgo biloba MT, Salvia officinalis MT or EO ± Menyanthes trifoliata); Heme: Leukopenia (Matricaria recutita MT + Rosmarinus officinalis EO > GM); ONC: cancer, general support, CV: myocardial remodeling postinfarction (+ Panax ginseng MT + Coenzyme Q10, D-ribose). Contra: can worsen bipolar disorder or high-strung people if they have low beta-sympathetic and elevated and unregulated TRH.

Ribes nigrum (Cassis) Essence: the most versatile corticotropic regulator. A ­cortico-tissular adaptogen rooted in the natural ease of the flow of Life Parts used: bud, leaf, fruit Galenic: GM, MT, DE, BH Fruit Rich in vitamin C; Endo: Corticotropic: general support of adrenal cortex organotissular activity; CV: capillary tonic, capillary vasoconstrictor. Leaves Actions: Mucosal/Derm: astringent to mucosal surfaces, antiexudative at the level of the tissues, cicatrizing; GI: intestinal antiseptic; Immune: antiinflammatory, glucocorticoid-like activity, antiallergic; febrifuge, antiinflammatory (arteries, bronchus, mucocutaneous, digestive, urinary, joints), ID: antiinfectious (ENT, pulmonary), Metabolic: antigout,

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h­ ypoglycemant, regulator of cellular and tissue metabolism; Rheum: antirheumatic, antiarthritic; CV: phlebotonic, antihypertensive, venous and capillary vasoconstrictor; Heme: antihemorrhagic; ANS: β-sympathomimetic; Neuro: analgesic, antimyalgic, antineuralgic; Renal: Diuretic (azoturic, uricosuric). Use: Mucosal: GI: acute infectious diarrhea, postinfectious dyspepsia, gastric and duodenal ulceration, inflammatory bowel disease, irritable bowel disease; Derm: psoriasis, eczema, dermatitis, etc.; ID: infectious; Rheum: Arthroses, arthropathies, arthritis; CV: stasis, pedal edema, hypertension. Buds Actions: Endo: General: endocrine adaptogen, Corticotropic: adrenal cortex stimulant by regulating pituitary action, cortisol analogue that favors inhibition of ACTH by classical feedback; Allergies: best corrector of the allergic terrain; Immune: febrifuge, antiinfectious (ENT, pulmonary), antiinflammatory (arteries, bronchus, mucocutaneous, digestive, urinary, joints), antiexudative at the level of the tissues, Drainage: drains the extracellular matrix (+ Alnus glutinosa GM + Juniperus communis GM), permissive effect on general drainage of all emunctories. Use: Endo: General: adaptogen (+ Rhodiola rosea, Eleutherococcus senticosus); Allergies: environmental, sun, drug, food allergies, respiratory…, Immune: general and acute phase inflammation (+ Betula pubescens GM + Alnus glutinosa GM), chronic inflammation (+ Menyanthes trifoliata MT, Curcuma longa, Rosmarinus officinalis EO, Lavandula angustifolia EO, etc.); ID: ENT: parotitis (+ Rubus fruticosus GM, Ficus carica GM, Thymus vulgaris EO), sinusitis, tonsillitis, laryngitis, croup, allergic rhinitis; Respiratory: Acute bronchitis in Adults: (Ribes nigrum GM, Populus nigra GM, Satureja montana EO, Cinnamomum zeylanicum), Pediatric bronchitis: (Ribes nigrum GM Populus nigra GM, Inula helenium MT 40 mL + Eucalyptus smithii); Pulm: asthma, emphysema, pneumonia, Wegener’s granulomatosis;. Derm: Acne, Urticaria (+ Plantago major, Juglans regia GM, Zinc oligoelement), Dry eczema (+ Cedrus libani GM), Oozing, infected eczema (+ Fragaria vesca MT + Ulmus campestre GM + Arctium lappa MT), Dermatitis, GI: Colitis, Crohn’s disease, chronic pancreatitis, chronic hepatitis (+ Secale cereale GM + Corylus avellana GM); Joints: antirheumatismal, coxarthrosis, gonarthrosis, bursitis, arthritis, psoriatic arthritis, osteoporosis, ligament stiffness (+ Sequoia gigantea GM + Fraxinus excelsior GM), ankylosing spondylitis, Peyronie’s disease, Dupuytren’s contracture (+ Betula pubescens GM + Viscum album GM), chronic back pain (+ Pinus sylvestris GM + Eschscholzia californica MT), acute neck pain; Metabolic: Gout (+ Betula ssp. GM);

Renal: chronic renal failure (+ Fagus sylvatica GM + Anthemis nobilis EO), poststreptococcal nephritis (+ Vitis vinifera GM), glomerulonephritis, GU: chronic prostatitis, uterine fibroids, ovarian cysts. ONC: Chemo-protective, postchemotherapy (+ Juniperus communis GM + Betula pubescens GM); GYN: Amenorrhea, Oligomenorrhea (+ Inula helenium MT, Salvia sclarea MT), Dysmenorrhea, chronic fatigue, CV: Giant cell arteritis, Kawasaki’s disease, thrombotic disorders, hypovolemic hypotension; Occular: Retinopathy, photophobia, myopia, optic neuritis, optic nerve atrophy, retinal detachment, retinitis pigmentosa (+ liver drainage), diabetic retinopathy (+ Vaccinium myrtillus MT + alpha-lipoic acid); Neuro: Delirium and psychosis with hazy thinking: + Alnus glutinosa GM + Betula pubescens, Valeriana officinalis MT + Lavandula angustifolia EO).

Rosa canina (Dog rose) Essential: an essential revitalizer and nourisher in the vector of persistence of Life. An excellent sympathetic-­corticotropic support in children and cases of asthenia, especially with comorbidities of ENT illnesses and/or food allergies Galenic: GM Actions: Endo: Corticotropic: adrenal cortex stimulant favoring production of adrenal androgens, ANS: β-sympathomimetic, Drainage: drains tonsils and adenoids, ID: Antiinfectious (ENT). Use: Endo: Corticotropic: physical or sexual asthenia, fatigue with lack of stamina or endurance, recurrent ENT ­infections—esp. when elevated cortisol suppresses immune activity and there is insufficient anabolic adrenal activity, failure to thrive, recurrent ENT disorders, asthma, allergies, eczema, ID: chronic sinusitis (+ Juglans regia + Hepar sulf 9c), enlarged tonsils and/or recurrent tonsillitis (+ Plantago major). Note: use during day for stamina, use in evenings for restoration and reparative actions; May cause excitation in evenings in some patients.

Rosmarinus officinalis (Rosemary) Essence: polyvalent plant offering a freshness to the organism through the return of hyperfunctioning and deficient states to equilibrium. Used in patients with allergic or autoimmune disorders with inflammation rooted in adrenal cortex insufficiency Parts used: flower, young shoots Galenic forms: EO, GM, MT, DE, HL, BH EO, Tisane, Decoction, GM Actions: GI: eupeptic, hepatoprotector, intestinal antispasmodic, antiulcer, choleretic > cholagogue; CV: inotrope

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+, ­chronotrope + (weak), dromotrope −; Immune: antiallergic; ID: Bacteriostatic, fungistatic, antiviral, GM Only: antiinfectious: biliary, pulmonary, urinary tropism; Metab: EO only: antioxidant (reduces free radicals); Pulm: antitussive, mucolytic, antispasmodic, decongestant; Endo: Corticotropic: adrenal cortex stimulant; Neuro: spasmolytic (bronchial, digestive), cerebral stimulant (short term memory, spatial memory), cholinergic, GM only: mild euphoric; Heme: GM only: leukocytogenic, erythrocytogenic; Osteo: antalgic, antiinflammatory; Derm: antiseptic, cicatrisant, epitheliogenic; ONC: antitumoral, antimutagenic; Renal: Diuretic: volumetric, uricosuric. Use: Internal: GI: Digestive troubles due to hepato-biliary insufficiency: loss of appetite, abdominal cramps, intestinal colic, dyspepsia, burping, flatulence, constipation (+ Quercus pedunculata GM); GU/GI: Infectious and inflammatory maladies: Intestinal inflammation (+ Vitis vinifera GM + Vaccinium vitis idaea GM), cholecystitis, hepatitis, colitis, cystitis, acute bronchitis, acute sinusitis; chronic allergies, Rheumatoid arthritis, rheumatic affectations; Heme: bone marrow insufficiency (leukopenia: + Thymus vulgaris decoction, erythropenia: + Tamarix gallica GM and/or Corylus avellana GM) anemia + Tamarix gallica GM and/or Corylus avellana GM, and, Ficus carica GM if due to intestinal blood loss) Neuro: memory disturbance with adrenal insufficiency, certain neuro-degenerative disorders, depression (+ Ribes nigrum GM), frigid infertility (EO); Topical: joint pain, myositis, muscle spasms, alopecia, fungal skin disease. Method: EO, internal (chemotype 1,8 cineole or ­verbenone): don’t exceed 300 mg/day, hydrolat: 1–3 tsp. BID to TID; EO external (chemotype camphor): musculoarticular 2%–10% (2–10 drops/5 mL carrier); EO ­external (chemotype 1,8 cineol): pulmonary: 2%–10% (2–10 drops/5 mL carrier); Tisane: 5–10 gm/1 L water, 15 min. steep, 1–3 cups/day; Bath: EO: 10–20 drops in excipient, Bath Decoction: 50 g/1 L, decoct 10 min, add to bath water (avoid before bed). Contraindications (EO primarily): chemotypes verbenone and camphor in: pregnancy, small children, and epileptics; Beware of possible risk of adrenal-overstimulation. Precautions (EO): GI irritation, nephritis, dermatitis, allergic reactions

Rubus fruticosus (Blackberry) Essence: a plant that regulates the consequences of somatopancreatic oversolicitation and hyperfunction Parts used: shoots, leaf, fruit Galenic: GM, MT, DE Actions: Rich in manganese Endo: Somatotropic: antihyperglycemiant, hypoglycemiant,57 indirect antidiabetic, ­pancreatic

drainer; Immune: antiinflammatory, ID: antibacterial (Group-B streptococcus), antiinfectious (ENT, pulmonary): antifungal, antiviral (Varicella), ENT: tonsillar decongestant, Osteo: antiarthrosis, CV: capillary tonic, hemostatic, venotonic; Derm/Mucosal: astringent (rich in tanins: cutaneous, digestive, ENT, pulmonary),58 Renal: diuretic (volumetric). Use: ID: any ENT, inflammatory or exudative disorders where exocrine or endocrine pancreatic dysfunction is implicated: diabetes, recurrent tonsillitis (+Rosa canina GM), gastritis, sinusitis, colitis, varicella (+ Acer campestre GM), Metab: diabetes (+ Olea europaea GM, Juglans regia, Myrtillus communis, etc.) Derm: acne, abscesses (+ Arctium lappa MT + Fragaria vesca MT), furoncles, weeping eczema (+ Cedrus libani GM); Rheum: spondylitis, Osteo: osteoarthritis (Ribes nigrum GM + Pinus sylvestris GM + Fraxinus excelsior GM + Betula pubescens GM), osteoporosis (+ Sequoia gigantea GM + Betula ssp. GM + Abies balsamea EO), balances osteoblastic and osteoclastic activity; GI: Celiac disease (+ vagosympatholytics) Method: Decoction of leaf: 2 tsp./1 c water, decoct 3 min, then infuse 10 min, drink; Compress: decoct 1 tbsp/ cup water; apply to skin or add to bath. Contraindications: Hypoglycemia states.

Salvia officinalis (Sage) Essence: a nearly perfect plant for central and peripheral neuroendocrine and emunctory regulation ensuring longevity and clarity of mind Parts used: leaf Galenic: EO, MT, DE, BH Actions: Mucosal: astringent, GI: choleretic, hepatoprotective,59–62 stimulates exocrine hepatic activity, dual pancreatrope: stimulates endocrine and exocrine pancreas (MT contains Zinc, nickel and cobalt which aids in production of digestive enzymes), Endo: Corticotropic: adrenal cortex stimulant favoring permissive activity, Gonadotropic: estrogenic (thus inhibiting FSH), Thyrotropic: thyroid stimulant, Somatotropic: antihyperglycemic, hypoglycemant thus indirectly reducing Thyro-somatotropic axis; ANS: sympathomimetic, Neuro: central cholinergic; ONC: antimitotic (anticancer)63–74; Heme: depurative; Immune: antiinflammatory, antipruritic; ID: fungicidal (antimycosic), genital infections; Rheum: antiarthrosic; Renal: volumetric diuretic. Use: GI: all disorders rooted in hepatic injury or hepatobiliary insufficiency: autotoxicity, gall stones, cancers (solid or blood) ENT infections, acne, etc. all disorders related to exocrine or endocrine pancreatic oversolicitation and/or insufficiency and/or deficiency: diabetes: all

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types, ENT infections, all adenoidal and cystic growths: tonsils, breast, prostate, etc.; Endo: Corticotropic: general dysadaptability rooted in insufficient permissive adrenal cortex activity, adrenal insufficiency, especially due to chronically elevated adaptive cortisol activity, fatigue, Gonadotropic: all conditions of hyper-FSH due to insufficient estrogen response and feedback: Crohn’s disease, psoriasis, mucosal edema, etc., all conditions of estrogen insufficiency: amenorrhea, oligomenorrhea, metrorrhagia, infertility, acne, etc., Thyrotropic: thyroid insufficiency or deficiency (absolute), insufficient gonado-thyrotropic linking (low genito-thyroid), etc., Somatotropic: all cases of prolonged growth hormone activity installing insulin resistance and/or oversolicitation of the pancreas: diabetes mellitus type 2a, adenoidal hypertrophy, chronic recurrent ENT infections, lymphatic stasis, etc., ID: ENT infections (+ Avena sativa MT + Rubus fruticosus GM in children, or, Plantago major MT: all ages), dysbiosis (+ Artemisia dracunculus EO), fungal infections (+ Cinnamomum zeylanicum, Satureja montana, Thymus vulgaris, Syzygium aromaticum, Origanum majorana, Juglans regia, Triticum repens), mumps (+ Avena sativa), ONC: general support of tumors—used with caution in estrogen-sensitive tumors; Rheum: arthroses, arthropathies, arthritis, Psych: central depression, dysthymia, melancholy, Neuro: memory impairment, focus, concentration. Caution: possible interaction with certain antiepileptic medications, may exacerbate hypertension, especially with arteriosclerosis.

Salvia sclarea (Clary sage) Essence: a neuroendocrine harmonizer and deep-acting polyendocrine revitalizer Parts used: whole plant Galenic: EO, DE, FE, BH, MT Actions: Neuroendocrine: harmonizer by regulation of hypothalamic stimulation of pituitary, and, regulation of hypothalamic synapsing with hippocampus and amygdala; ANS: parasympatholytic (vagolytic), alpha-sympatholytic, betamimetic; Neuro: neurologic antispasmodic, neurotonic, antidepressant, cerebral stimulant; Endo: Corticotropic: adrenal cortex stimulant: slightly favors cortisol and aldosterone, Gonadotropic: FSH inhibitor, Estrogen-mimetic (more estrogenic that Salvia officinalis), Thyrotropic: Thyroid stimulant: accelerates the rate of iodination and increases fullness of the metabolic capacity of the thyroid, Somatotropic: Prolactin inhibitor; GU: pelvic decongestant, emmenagogue, antigalactogenic, aphrodisiac; GI: Eupeptic, stomachic, astringent, choleretic, increases flow of exocrine pancreatic secretions, Drainage: pancreas, pelvis; CV: arteriotrope, phlebotonic, vascular antioxidant and antiinflammatory; Metabolic: hypolipemant,

­hypoglycemant; Immune: antiinfectious: broad spectrum for genital, urinary, ENT spheres, antiinflammatory; ONC: antimitotic, antitumoral; Muco-Cutaneous: Antisudoral, astringent, cicatrizant, antiinfectious, antiinflammatory; Renal: Volumetric diuretic. Use: Adaptability: use in all states in which there is central overactivity, hypothalamic oversolicitation of the pituitary with peripheral insufficiency in a single or multiple endocrine axes: asthenia: mental (+ Citrus aurantium amara EO or hydrolat), emotional (Rosa damascena hydrolat or EO), physical (+ Pine pollen), emotional lability (with anger: Matricaria recutita, with grief or sadness: Crocus sativa, Rosa damascena hydrolat or EO), rumination on past events (+ Viburnum lantana GM) posttraumatic stress with peripheral insufficiency, fatigue, hypothyroidism, migraines, seizures (+ Ilex aquifolium GM, Betula pubescens GM), peripheral depression (+ S-adenosyl methionine 200 mg in AM), asthma, etc.; ANS: All disorders rooted in functional spasmophilia: seasonal adaptation, seasonal affective disorder, genital recycling disorders with genital insufficiency, gastro-esophageal reflux, muscular spasms in which the patient responds to physical therapies for only a brief time, etc., Endo: Corticotropic: all states of global adrenal insufficiency, permissive function > adaptive: recurrent infections, atopic disease: eczema, allergies, asthma (intrinsic and extrinsic), central > peripheral depression, fatigue, etc.; Gonadotropic: all states of estrogen insufficiency: Children: cradle cap (topical, EO), failure to thrive, Females pubescent to Menopause: delayed puberty (adrenarche, thelarche or menarche), delayed parturition, acne, amenorrhea, oligomenorrhea, metrorrhagia, infertility, vaginismus, sexual frigidity, low libido, Postmenopausal: vaginal dryness, menopause, hot flashes, osteoporosis; Male pubescent onward: acne, seborrhea, orchiditis, prostate enlargement, prostate cancer (certain types); CV: hypertension, Reynaud’s syndrome, atherosclerosis; ID: all types of infections, with special tropism for: Genital: bacterial vaginosis, vaginal candidiasis, prostatitis, etc., Urinary: nephritis, cystitis, interstitial cystitis, ENT: sinusitis, rhinitis, pharyngitis, tracheitis, otitis media, Neuro: Migraines precipitated by emotional distress or lack of sleep, dementia related to cerebral sclerosis; Metab: prediabetes, hyperlipidemia, Derm: hyperhidrosis, frostbite, alopecia (associated with hypoestrogenism), stomatitis, gingivitis, wounds, ONC: Prostate cancer. Method: Tisane: 5–10 g/L water; infuse 10–15 min, drink in 3–4 divided doses daily; EO, internal: 2–6 drops/ day in divided doses; EO, external: 5%–10% applied to affected area 1–2 times per day. Contra: hyperestrogen states, estrogen-dependent cancers, pregnancy (except after 37 weeks gestation), lactation; use caution with children ages 6–7 during the end of the thyroid tissue growth phase.

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Satureja montana (Winter savory) Essence: an advocate for stamina, perseverance and adaptability in the face of aggressions Parts used: leaf and flower Galenic: EO, BH Actions: Adaptability: all conditions requiring stamina and/or endurance during an adaptation demand, and/or for timely recovery and restoration; Endo: Corticotropic: Adrenal cortex stimulant (general) improves permissive cortisol action but adrenal androgen production: (1) facilitates ACTH diffusion preferentially into zona reticularis, (2) when co-located with ACTH, upregulates transcription of 17αhydroxylase, 17, 20 lyase, and 17β-hydroxysteroid dehydrogenase, upregulating adrenal androgen production without detracting from cortisol production per se, Gonadotropic: increases circulating testosterone by reducing binding to testosterone binding globulin; ANS: sympathomimetic beta > alpha; Neuro: Neuralgic; Immune: Immunostimulant; ID: Antibacterial: gram +, gram −, antifungal, antiviral, antiparasitic, antiprotozoal; Osteo: Antirheumatic; GI: eupeptic, carminative, astringent, rebalances intestinal flora. Use: Endo: Corticotropic: all disorders of general adrenal cortex or medullary insufficiency: adrenal fatigue, lassitude, dysadaptability, lack of stamina, asthma, cosmobiologic affections, Neuro: all structural and functional spasmophilias from adolescence onward, Psycho-Neuro: neurasthenia, peripheral > central depression, esp. with psycho-motor retardation and recurrent infections; ID: General: all infectious disorders in all places, especially GI: Spasmodic Colitis, dysbiosis, gastroenteritis, diarrhea, intestinal candidiasis, parasitic infections, etc.; Rheum: rheumatic disorders. Method: EO: PO: 0.5–5 drops per day diluted in tincture, optimal: 15 US drops (750 μL) per 125 mL due to phenolic compounds, Topical: mix with other EO’s, dilute and use in localized areas only; Hydrolat: PO 1–3 tsp. bid, as gargle, nebulized, compress; Tisane: 1–2 tsp. in ¾ c. water, infuse 10 min, 2–3 cups per day. Contra: pregnancy, nursing, hemorrhoids, hemorrhagic disorders, Crohn’s (esp. rectal EO), Relative: Adrenal overstimulation, hypertension, gastritis, hepatic failure. Note: rich in phenols such as carvacrol, thymol, etc. which can be muco-irritating in moderate to high doses.

Secale cereale (Rye) Essence: a hepatobiliary-pancreatic restorative Parts used: rootlets Galenic: GM Actions: Liver: hepatoregenerator, antijaundice, Pancreas: substitutive protease and amylase activity.

Use: GI: Liver: acute and chronic hepatitis (+ Betula ssp. GM, Juniperus communis GM), hepatic overload, pediatric grow deficiency with hepato-pancreatic components of insufficiency (+ Agrimonia eupatoria + Rosa canina GM), Derm: Psoriasis (+ Ulmus campestre GM).

Sequoia gigantea (Sequoia) Essence: a revitalizer founded on the durability and persistence of Life in the face of adverse or decline. Parts used: young shoots Galenic: GM Actions: Endo: Corticotropic: an adrenal cortex stimulant favoring adrenal androgens. “It reduces cortisol and aldosterone by shifting adrenal metabolism towards Adrenal androgens. It inhibits ACTH by negative feedback. It promotes osseous reconstruction by assuring androgen availability and blocking estrogen receptors, therefore useful for assuring the foundation structure. It prevents estrogen insufficiency by invoking activity of growth factors and estrogen precursors.” (Christian Duraffourd, unpublished); MS: relaxes muscles and ligaments. Use: Endo: General: Revitalizer, tonic (+ Betula pubescens GM), antisenescent (+ Panax ginseng + Gingko biloba), Corticotropic: chronic fatigue syndrome (+Passiflora incarnata MT + Fraxinus excelsior GM + Arnica montana MT or Malva sylvestris MT + Lithium orotate 5 mg if serum TSH is also low); ID: cortisol-induced dysfunctional immunit; Osteo: osteoporosis; MS: muscular and ligamentous tension (+ Uncaria tomentosa (Cat’s claw) + Magnesium 500 mg qHS).

Taraxacum officinale (Dandelion) Essence: a superb drainer in conditions involving excess heat and dysmetabolic conditions Parts used: whole plant Galenic: MT, FE, GM, DE, BH, SWFP Actions: Drainage: liver, gallbladder, kidney; GI: cholagogue, choleretic, laxative; Renal: diuretic (volumetric, azoturic); Metag: hypocholesterolemiant, hypolipemiant by hepatorenal drainage (superb, but so powerful that can quickly become toxic); Immune: antiallergic (especially in arthroses); Endo: Corticotropic: inhibits vasopressin. Use: Drainage: use in all conditions requiring hepatobiliary, hepatorenal or renal drainage: atopic disease (allergies, eczema, asthma), infectious diseases, signs and symptoms of hepatobiliary insufficiency, constipation, dysbiosis rooted in biliary congestion, history of gallstones, renal calculi,

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arthroses, arthropathies, rheumatic conditions, etc.; Metab: atherosclerosis, hyperlipidemia; Immune: allergic conditions; Endo: Corticotropic: conditions in which central vasopressin is overactive in the face of elevated cortisol: chronic fatigue, fibromyalgia, peripheral depression, etc. Caution: Can increase the effects of antihypertensives, diuretic and hypoglycemiant75 medications.

Thymus vulgaris (Thyme) Essence: #1 immuno-adrenal support for vagotonics with atopia, infectious or digestive complications Parts used: stem and flowers Galenic forms: EO, BH, MT Actions: Immune: antiinfectious (ENT, pulmonary, intestinal, pharyngeal, urinary, genital, cutaneous), antifungal, antibacterial (gram +, gram −), antiviral, antiherpetic, anthelminthic, vermifuge; immune stimulant; antioxidant, antiinflammatory; febrifuge; Pulmonary: Mucolytic, expectorant; Digestive: neurotropic digestive carminative, eupeptic, choleretic, antigastritis; ANS: Parasympatholytic (strong vagolytic); Endo: Corticotropic: adrenal cortex stimulant; Gonadotropic: Emmenagogue, binds to estrogen, progesterone receptors; Neuro: Analgesic Neuromuscular: Spasmolytic; Renal: volumetric diuretic. Use: General: all disorders in vagotonic individuals, hyper parasympathetic states, adrenal insufficiency or infections; Spasmophilia: all chronobiologic spasmophilias, structuro-functional spasmophilias where improvement of cortisol activity regulates estrogens, of childhood; All spasmophilic disorders of vagotonics: depression, asthma, migraines (certain types), etc.; ID: All infectious disorders due to regulation of ANS-corticotropic function; sinusitis, pharyngitis, tonsillitis, otitis media, parotitis, bronchitis (wet), nephritis, cystitis, infected dermatitis, especially weeping or wet, gingivitis, dental carries; GU: Dysmenorrhea, amenorrhea (certain types); Psych: paralytic fear, anticipatory anxiety, depression; CV: hypotension; GI: digestive disorders: gastroesophageal reflux rooted in compensatory alpha from hypervagal states, dysbiosis, infectious colitis, etc.; Rheum: rheumatic disorders, especially topical application of essential oil; Heme: neutropenia. Methods: EO: topical, internal (PO) Acute: 2 drops TID; Nonacute: 0.5–2 drops/day; EO-rectal: 0.1%; Tisane (general use): ½ tsp./cup water, infuse 5 min; Neutropenia: 2 tsp. of Thymus vulgaris herb in 6 cups water (Consultation Boucicaut, Christian Duraffourd, unpublished). Boil 7 min, steep 7 min. Drink throughout the day. Compress, Oral rinse: 1 tbsp/1 cup water; Bath: 1 cup in 4 L water; add to bath. Contradictions: pregnancy, HTN, Glaucoma, hyposecretory states.

Tilia tomentosa (Linden tree) Essence: a gentle plant of downregulation, and clearance of accumulated toxins, emotional or physical in nature Parts used: bud, leaf, flower Galenic: BH, H, FE, DE, O, EO, MT Actions: ANS: Sympatholytic; Neuro: central nervous system sedative, moderate benzodiazepine agonist,76 neurologic antispasmodic; Musc: uterine antispasmodic, digestive antispasmodic, GI: choleretic (cordata), Drainage: hepatobiliary, renal; CV: bathmotrope negative; Heme: reduces blood hypercoagulability, anticoagulant, inhibits platelet aggregation; Renal: volumetric diuretic (stem); Metabolism: hypolipemiant (by renal drainage), Immune: mildly antimicrobial: antibacterial, antifungal, antiviral; increases lymphocyte proliferation, favors lymphocyte liberation from lymph nodes by stimulating peripheral GABA receptors and reducing alpha-sympathetic constriction. Use: Neuro: all childhood structural spasmophilias: children prone to comportmental issues: temper tantrums, breath holding, anger outbursts, insecurity with clingy attitude to caregivers, etc., insomnia, migraines, neuropathies, weaning off benzodiazepines (+ Passiflora incarnata MT + Lavandula angustifolia EO) CV: atrial fibrillation (+ Leonurus cardiaca + Lithium oligoelement), edema, atherosclerosis, risk of stroke; Metab: hypercholesterolemia, ID: mild catarrhal infections, UTI (supplement + Avena sativa), Heme: hypercoagulable states, GU: preterm labor, uterine spasms.

Urtica dioica, root (Nettle) Essence: a depurative that regulates peripheral gonadal androgen metabolism and associated factors Parts used: root Galenic: MT, DE, BH Actions: Endo: Gonadotropic: blocks growth factors at level of prostate, prevents binding of testosterone and DHT to SHBG, Inhibits aromatase activity (reduces conversion of testosterone to estrogen), Inhibits 5-α-reductase (reduces conversion testosterone to dihydrotestosterone),77 GU: Pelvic decongestant; Immune: antiproliferative78–82; antiinflammatory, stimulates T-cells; Rheum: antirheumatic (inhibits formation of inflammatory agents); Renal: Diuretic (volumetric, chloruretic, uricosuric); Detox: purifier, astringent; CV: antihypertensive (mild: inotrope (−), increases nitric oxide release.83, 84 Use: Endo: Gonadotropic: GU: prostatic hypertrophy, prostate cancer, uterine fibroids, fibrocystic lesions of breasts; Derm: androgenic alopecia, acne;, CV: hypertension,

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­congestive heart failure; Rheum: rheumatic congestions; ID: states of immune deficiency; Peds: precocious puberty. Method: BH: 3–5 tbsp dry root in 4 c water; decoct 3 min AND steep 10 min, drink in 3 even doses/day.

Urtica dioica, leaf (Nettle) Essence: an antiallergic, antiinflammatory that revitalizes tissues Parts used: leaf Galenic: MT, DE, BH Actions: Immune: antiallergic (inhibits mast cell degranulation, COX-1, COX-2 and prostaglandins),85, 86 Metabolic [SIPF, powder only]: Revitalizing (Fe, Si, Mg, Ca, Cu, Zn, K, S, B2, B5, Folic acid), stimulates growth of hair and nails; Derm: purifier of skin; Endo: Somatotropic: galactogogue, stimulates secretion of insulin87, 88; GI: hepatoprotectant; Metabolic: hypoglycemant89; Renal: Diuretic (volumetric, chloruretic, uricosuric).90 Use: Derm: hair and nail weakness, acne; Immune: allergies, autoimmune conditions with active inflammation, Metab: diabetes (types 1 and 2), Osteo: osteoporosis, Rheum: osteochondritis, juvenile arthritis. Method: Fresh plant: decoct 10 min in 4 c. water, drink in 3–6 even doses/day).

Vaccinium myrtillus (Bilberry) Essence: a firm and dependable tonifier and circulato Parts used: berry, leaf Galenic: DE, FE, A, GM, BH, MT Actions: Leaf and Gemmo: Metabolic: hypoglycemant (contains chromium), hypolipemant (Triglycerides); Leaf OR Berry: Immune: febrifuge, antidysentery, antifungal, bactericidal (enterococcus), antiinfectious (intestinal and urinary); GI: astringent, antigastric (increases gastric mucous secretion). intestinal drainer, pancreatic drainer; CV: vasculoprotective, capillary tonic (repairs capillary integrity), platelet antiaggregant; Renal: diuretic (volumetric, azoturic); Ocular: protects against neovascularization. Use: Metab: Diabetes, Ocular: eye disease, retinitis pigmentosa (+Corylus avellana GM + Citrus limon EO + Vinca minor MT); GI: intestinal ulcers; ID: general support of other antiinfectious treatments, intestinal infections, urinary tract infections; CV: vascular disease, esp. when diabetes is a co-morbidity, hypertriglyceridemia. Method: Berry Decoction: 3 tbsp in 3 c. water, boil 10 min, drink in 4–6 doses/day; Leaf tisane: 1 tbsp in 4 c water, steep 10 min, drink in 2–3 even doses/day

Valeriana officinalis (Valerian) Essence: #1 plant for acute spasmophilia and chronic regulation of spasmophilic terrain Parts used: rhizome, roots, stolons Galenic forms: BH, EO, DE, MT Actions: Neuro: GABAergic, Serotonergic, Melatonergic, sedative hypnotic, anxiolytic, antiepileptic soporific, duel spasmolytic: neurotropic and musculotropic; ANS: Sympatholytic, Vagolytic; CV: hypotensor, (−) bathmotrope; GI: digestive antispasmodic. Use: Spasmophilia: all spasmophilic states, structuro-­ functional or adaptive, all areas and systems; Neuro: anxiety, insomnia (+ Passiflora incarnata MT, Leonurus cardiaca MT, Lavandula angustifolia EO), hysteria (+Eschscholzia californica), hyperesthesia (+ Eschscholzia californica + Cannabis sativa (CBD oil)), somnambulism, seizures, migraines; CV: tachycardic hypertension, palpitations; Pulm: Asthma, spasmodic cough; GI: abdominal spasms, abdominal colic esp. with great discomfort and emotional reactivity, spasmodic colitis; GU/Women: hot flashes (+ Eleutherococcus senticosus MT, Medicago sativa MT, Lepidium meyenii MT), menstrual cramps. Method: Tisane: 2.5 g root (1 heaping tsp.) per 150 mL water, 10–15 min steep; 1–4 cups per day; Cold maceration: same recipe, let sit 12 h; Bath: 100 g (3.5 oz = 3/4 c.) root/2 L water, steep 15 min, add to a hot bath and rest 10– 15 min; EO: 8 gtt in1 tsp. sesame oil, mix and add to bath; Compress; 100 g root/1 L water, steep 10 min, apply to contusions and sore joints. Precautions: Valerian has a strong smell, which may limit its use with sensitive patients; Bath: acute exacerbation of eczema, psoriasis, etc.; fevers, congestive heart failure, hypertonia; Pregnancy and nursing (United Kingdom, none noted for rest of Europe), may cause somnolence and GI irritation in higher doses, may augment the effects of other hypnotic plants or benzodiazepines.

Vinca minor (Periwinkle) Essence: a regulator of spasmophilic, and neurologic dysfunction rooted in vasculo-pancreatic dysfunction Parts used: Petals Galenic: MT, FE, DE, BH Actions: Neuro: antispasmodic (musculotrope and neurotrope), cerebral hypotensor, improves oxygenation at cerebral level (+ Passiflora incarnata); GI: Pancreas: endocrine and exocrine pancreatrope,91 possible beta-islet cell regenerator,91 Liver: secondary support of hepatic function through its improvement of pancreatic function; CV: vascolotrope, vasoregulator, coronarodilator, capillary protector, ­circulatory

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drainer, antilactation, Endo: Gonadotropic: FSH stimulant, ANS: sympatholytic, vagolytic. Use: Neuro: all spasmophilic disorders expressing in the mental, cardiac or digestive spheres: Anxiety, apoplexy, panic attacks, migraines (with strong vascular component), Reynaud’s crisis (+ Tilia tomentosa GM, Crocus sativa MT, Passiflora incarnata MT), cerebral palsy, poststroke, pancreatic insufficiency, COPD, Prinzmetal’s angina, atherosclerosis, hypertension, etc.; Metab: Diabetes mellitus (types 1 and 2), GU: postpartum mastitis, Endo: hypoestrogenic states rooted in FSH insufficiency (+ Inula helenium): amenorrhea, oligomenorrhea, metrorrhagia, infertility, etc. Caution: avoid in lactating women.

Viscum album (Mistletoe) Essence: reestablishes buffering capacity in the face of pain and hyper vigilance Parts used: leaf, bud Galenic: GM, DE, BH Actions: ANS: sympatholytic, parasympathomimetic, Neuro: supports serotonin, antinociceptive: augments β-endorphin production; Immune: stimulates immunity at the thymus level, antiinflammatory, stabilizes DNA; antisclerotic, antioxidant, antiinflammatory; ONC: antineoplastic92: increases apoptosis and necrosis, augments activity of T helper, natural killer cells and TNFα release, antineoangiogenic, potentiates cytotoxicity of chemotherapy (in  vitro), stabilizes and improves DNA repair; Heme: hematopoietic; CV: dromotrope negative, hypotensive; Renal: Diuretic (volumetric, azoturic). Use: GM: Neuro: vertigo, tinnitus (+ Viburnum lantana GM, Sorbus domestica GM), neuralgia and pain syndromes— esp. with history of multiple traumas, or cancer metastasis (+ Syzygium aromaticum EO + Eschscholzia californica), fibromyalgia; Immune: T-cell deficiency (+ Rhodiola rosea), natural killer cell deficiency (+ Usnea lichen spagyric); ONC: metastatic phase of tumoral growth (+ Poterium sanguisorba or Mercurialis annua + Fabiana imbricata); improving tolerance for chemotherapy (+ Juniperus communis GM), DNA fracture (+ Viburnum lantana GM); Metab: fibrocystic disease (+ Mn-Cu oligoelement); uterine fibroids, postsurgical scarring; renal sclerotic disease (+ Fagus sylvatica GM, Betula pendula GM); Psych: psychiatric disorders rooted in hyperfunctioning from insufficient endorphins: fugue states, mania, peripheral depression, etc. (+ Eschscholzia californica) CV: hypertension, ventricular hypertrophy; Heme: anemia. Contra: pregnancy, nursing, chronic infections (Tuberculosis, AIDS), cerebral tumors, lymphoma, and leukemia.

Note: can augment the effect of central nervous system depressants and antihypertensive medications. High doses: diarrhea, vomiting, anemia, leukopenia, purpura; berries are toxic. Chemotherapy dosing may need to be reduced if used simultaneously.

Viola tricolor (Wild pansy) Essence: #1 antiallergic polyvalent therapeutic: use in all cases of allergy and poly-emunctorial congestion Parts used: flower Galenic: MT, BH Actions1, 2, 93–97: Immune: antiinflammatory (salicylates): skin, bronchopulmonary, genito-urinary; Drainage: General Depurative, skin: #1 cutaneous drainer, liver, intestines, kidneys; Renal: Kidneys: volumetric diuretic; Derm: keratolytic, cicatrisant; Infectious: antiinfectious; Pulm: antiinflammatory, expectorant; CV: veinotrope, anticoagulant, inhibits platelet aggregation; GI: mild laxative (mucilage). Use: Immune: all atopic disorders: allergic, asthma, eczema; Derm: all inflammatory and infected dermatoses: eczema, psoriasis, urticaria, acne; CV: varicose ulcers, venous insufficiency with pruritus of lower extremities; Pulm: bronchitis, wet with inspissated mucous. Method: Tisane or Compress: Infuse 1 tsp. in 8 oz water 10 min, drink TID before meals or apply to affected area.

Vitex agnus castus (Chaste tree) Essence: #1 plant for regulation of neuro-gonadotropic excess: diminishes peripheral and central gonadotropic activity but favors catabolic thyroid activity to support peripheral gonadotropic factors Parts used: berry, flowering tops Galenic forms: MT, FE, MS, Bulk herb, Actions1, 2: ● Neuro: sedative, dopamine agonist (inhibiting Prolactin)98, 99; ANS: α-sympatholytic; Endo: Central: inhibits the general relaunching of Hypothalamic and Pituitary hormones98, 99; Gonado: Follicular: Inhibits FSH (risk relaunching ACTH by blocking FSH), inhibits estrogen uptake at peripheral receptors (ERα ERβ98, 99 ); Luteal: diminishes serum testosterone, (favors progesterone through altering LH activity99–118); Thyro: increases T4/T3 ratio; Somato: Low doses: relaunches Prolactin; Higher doses: Reduces prolactin by stimulation of D2 dopaminergic receptors, reduces prolactin sensitivity to TRH stimulation99, 119; GU: uterine antispasmodic, regulator of menstrual cycle; Derm: Antiseptic, vulnary; ONC: antitumoral.

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Use: GU: all disorders of gonadotropic imbalance affecting genital structures: PMS, mastodynia, fibromas, polycystic ovarian syndrome, polycystic ovaries, endometrial hyperplasia, menorrhagia, uteritis (+ Alchemilla vulgaris MT 30 mL, Achillea millefolium MT 30 mL, Achillea millefolium macerate oil 30 mL + Cinnamomum zeylanicum EO 2 mL, Syzygium aromaticum EO 2 mL, Lavandula angustifolia EO 2 mL: vaginal infusion OR topical friction rub, Improve lactation (low dose: 1 capsule/day); Neuro: Insomnia (esp. in hyperluteal women with elevated alpha) Derm: Acne; ONC: Breast cancer; Psych: Frigidity, low libido (3DH to 30CH). Contra (Standard and high dose): pregnancy, nursing, conditions in which relaunching of ACTH is undesirable. ●

Zea mays (Corn) Essence: a hepatorenal drainer for inflammatory disorders Parts used: rootlets (GM), Silk (FE, BH, MT) Galenic: GM, BH Actions: Endo: Thyrotropic: TSH antagonist; Immune: Directly: antiinflammatory (salicylates), Indirect: by inhibition of TSH helps re-establish timing of insulin sensitivity; Drainage: hepatorenal drainer, diuretic (volumetric, azoturic, chloruric, natriuric and uricosuric); MS: Antirheumatic (contains salicylates and by hepatorenal drainage); Digestive: cholagogue, choleretic; Metabolic: hypolipemant by means of hepatorenal drainage; Cognitive: Improves connectivity of unilateral and cross-lateral hemispheric function; CV/Heme: inhibits platelet aggregation, strengthens the arterial wall (GM). Use: ENDO: all inflammatory disorders rooted in low serum TSH and/or elevated cortisol: Chronic fatigue and Brain fog related to Thyro-somatotropic dysfunction (low serum TSH, elevated Insulin and/or low insulin resistance + elevated inflammation and/or harmful free radicals), All disorders involving inflammation rooted in Thyrosomatotropic dysfunction, e.g., Cysts (+ Fragaria vesca leaf + Lithospermum officinale + Lycopus europaeus), tumors at risk of metastasis (+ Poterium sanguisorba + Fabiana imbricata), Neurodegenerative and demyelinating disorders; Neuro: impaired cognitive function (especially memory) or dementias rooted in somatotropic desynchronization, abnormal QEEG’s, PTSD with brain fog and elevated cortisol; Metab: hyperlipidemia; CV: Aneurysms, Atherosclerosis, stroke risk (+ Citrus limon EO).

Zingiber officinale (Ginger) Essence: an effective restorative and revitalizer of multiple endocrine axes

Parts used: root Galenic: EO, DE, FE, MT, O, BH Actions: GI: antiinflammatory, febrifuge, aperitif, eupeptic, antiulcerative, digestive cicatrizant, increases digestive enzyme production with chronic use, improves insulin activity12; Endo: Cortico: adrenal cortex stimulant, Gonado: stimulant of testicular androgens, Thyro: stimulant of T4 (strong); Heme: augments effects of anticoagulants. Use: Endo/Chronobiologic: Transitional states of chronobiology: delayed puberty, primary amenorrhea, prenatal hyperemesis, diminished fetal growth, late third trimester and postpartum states of fatigue, hypothyroidism, depression; perimenopausal and andropausal states with fatigue and/or demand for more androgens (muscle loss, lack of ambition in life); Cortico: Adrenal insufficiency (low cortisol, low adrenal androgens or both); Gonado: Infertility (certain types), Thyro: Grave’s thyroiditis, thyroid nodules in euthyroid states with elevated TRH/TSH; GI: Dyspepsia, gastric and duodenal ulcers, post-Crohn’s disease and postUlcerative colitis with residual intestinal bleeding; CV: Stroke risk (+ Citrus limon EO).

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105.

Doll M. The premenstrual syndrome: effectiveness of Vitex agnus castus. Med Monatsschr Pharm. 2009;32(5):186–191. 106. He Z, Chen R, Zhou Y, et al. Treatment for premenstrual syndrome with Vitex agnus castus: a prospective, randomized, multi-center placebo controlled study in China. Maturitas. 2009;63(1):99–103. 107. Imai  M, Kikuchi  H, Denda  T, Ohyama  K, Hirobe  C, Toyoda  H. Cytotoxic effects of flavonoids against a human colon cancer derived cell line, COLO 201: a potential natural anti-cancer substance. Cancer Lett. 2009;276(1):74–80. 108. Daniele C, Thompson Coon J, Pittler MH, Ernst E. Vitex agnus castus: a systematic review of adverse events. Drug Saf. 2005;28(4):319–332. 1 09. Halaska  M, Beles  P, Gorkow  C, Sieder  C. Treatment of cyclical mastalgia with a solution containing a Vitex agnus castus extract: results of a placebo-controlled double-blind study. Breast. 1999;8(4):175–181. 1 10. Chopin Lucks  B. Vitex agnus castus essential oil and menopausal balance: a research update [Complementary Therapies in Nursing and Midwifery 8 (2003) 148-154]. Complement Ther Nurs Midwifery. 2003;9(3):157–160. 1 11. Atmaca M, Kumru S, Tezcan E. Fluoxetine versus Vitex agnus castus extract in the treatment of premenstrual dysphoric disorder. Hum Psychopharmacol. 2003;18(3):191–195. 1 12. Xu H, Fabricant DS, Piersen CE, et al. A preliminary RAPD-PCR analysis of Cimicifuga species and other botanicals used for women's health. Phytomedicine. 2002;9(8):757–762. 1 13. Gorkow C, Wuttke W, Marz RW. Effectiveness of Vitex agnus-castus preparations. Wien Med Wochenschr. 2002;152(15-16):364–372. 1 14. Schellenberg R. Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo controlled study. BMJ. 2001;322(7279):134–137. 1 15. Berger D, Schaffner W, Schrader E, Meier B, Brattstrom A. Efficacy of Vitex agnus castus L. extract Ze 440 in patients with pre-menstrual syndrome (PMS). Arch Gynecol Obstet. 2000;264(3):150–153. 1 16. Bergmann J, Luft B, Boehmann S, Runnebaum B, Gerhard I. The efficacy of the complex medication Phyto-Hypophyson L in female, hormone-related sterility. A randomized, placebo-controlled clinical double-blind study. Forsch Komplementarmed Klass Naturheilkd. 2000;7(4):190–199. 1 17. Loch EG, Selle H, Boblitz N. Treatment of premenstrual syndrome with a phytopharmaceutical formulation containing Vitex agnus castus. J Women's Health Gend Based Med. 2000;9(3):315–320. 1 18. Halaska  M, Raus  K, Beles  P, Martan  A, Paithner  KG. Treatment of cyclical mastodynia using an extract of Vitex agnus castus: results of a double-blind comparison with a placebo. Ceska Gynekol. 1998;63(5):388–392. 1 19. Milewicz A, Gejdel E, Sworen H, et al. Vitex agnus castus extract in the treatment of luteal phase defects due to latent hyperprolactinemia. Results of a randomized placebo-controlled double-blind study. Arzneimittelforschung. 1993;43(7):752–756.

Further Reading 120.

Hedayat  KM. Essential oil diffusion for the treatment of persistent oxygen dependence in a three-year-old child with restrictive lung disease with respiratory syncytial virus pneumonia. Explore. 2008;4(4):264–266.

Index Note: Page numbers followed by f indicate figures and t indicate tables.

A

Abdominal pain, 244 Abies pectinata (Balsam fir), 269–270 Achalasia treatment, 198 Achillea millefolium (Yarrow), 270–271 Acid-base balance, 27 Acidity, 202–203 Acne in adolescent, 175–176 alimentary advice, 180–181 ANS, 170 biology of functions, 178–181 blood evaluation, 171–172 case study, 176–177 cellular nutrition, 180–181 classification, 165 critical terrain, 166–168 definitions, 165 diet, 177 endocrine, 166–168 epidemiology, 166t face mask recipe, 174 facial scrub recipe, 174 hygiene, 174 localization, neuroendocrine determinates, 171t mechanism of formation, 170–171 medical history, 177 pathophysiology, 166–175 peripheral luteal insufficiency, 166 physical examination, 171, 177 procedures, 172 severity, 165 skin physiology, 165–166 somatotropic axis, 180 thyrotropic axis, 169–170 at time of presentation, 178 treatment, 181 ages of patients with, 175t clay, 172 decoctions, 174 diet, 175, 181 essential oils, 174 lifestyle, 175 oligoelements, 174–175 oral, 174, 175t pharmaceutical, 172 tincture, 181 tisanes, 174 topical and symptomatic, 172–174 yoghurt, 172 Adaptive immunity, 1 Adenoma, prostate

aggressor, 154 biology of functions, 146–147, 155 case study in prevention, 141 chronic, 150 clinical evaluation, 145–146 corticotropic regulation, 148t, 151 coupled endocrine relationships in, 147t critical terrain, 154–155 devolution, 145 diet, 150 evaluation, 155–160 evolution, 144–145 gonadotropic regulation, 147t, 151–152 hyperimmune terrain, 154 hyperinflammatory terrain, 154–155 past critical terrain, 140–141 pharmacologic treatment, 147–150 precritical terrain, 140 somatotropic index, 148t, 153 symptomatic treatment, 150 thyrotropic regulation, 153 treatment of terrain, 151–154 Adrenal cortex, 1 permissive activity, 3, 3t Adrenocorticotropic hormone (ACTH), 238, 243 alpha stimulation, 5f cortisol response to, 97–98 horizontal stimulation, 97–98 hyperfunctioning, 3, 242, 259 metorrhagia, 95 stimulation, 258f vertical inhibition, 43 Agrimonia eupatoria (Agrimony), 271 Agrimony (Agrimonia eupatoria), 271 Alchemilla vulgaris (Lady’s mantle), 98, 271 Alfalfa (Medicago sativa), 152, 286 Alimentary advice acne, 175, 177, 181 adenoma, prostate, 150 asthma, 35 constipation normal transit, 228 slow transit, 230 Crohn’s disease, 239 menstrual cycle disorders, 120 ulcerative colitis, 258 Allergens, 1 airborne, 6 dietary, 6 exposure, 3 sensitization, 4f

Allergic disorders airborne, 6 classification, 1, 2t corticotropic, 3 cutaneous, 8–14 (see also Eczema) dietary, 6 extrinsic asthma (see Extrinsic (allergic) asthma) gonadotropic, 5 manifestation of, 4f somatotropic, 5–6 thyrotropic, 5 topology, 9t type 1, 6–7 IgE mediated hypersensitivity, 2–6 by location, 6–7 by metabolite and physiologic process, 7–8 Allergic rhinitis, 44–45 Alnus glutinosa (Black alder), 271–272 Althaea officinalis (Marshmallow), 272 Anal fissures treatment, 229 Ananas (Ananassa sativa), 272 Ananassa sativa (Pineapple), 272 Androgens, 139t acne, 179 genomic effects, 55 gonadotropic axis, 55 normal menstrual cycle, 73 nongenomic effects, 56 prostate enlargement, 154 prostatitis, 137, 142f theca cells, 73 TSH, 138 types, 56, 57t Androstenedione corpus luteum, 73–75 granulosa cells, 73 Angelica (Angelica archangelica), 272 Angelica archangelica (Angelica), 272 Anthemis nobilis (Roman chamomile), 272–273 Antiallergics, 11, 12–13t medicinal plants for, 12–13t Antigen presenting cells (APC), 4f Antihistamines insomnia, 11 therapy, 19 Antihistaminics allergy, 11, 12–13t with intestinal tropism, 231 medicinal plants, 12t Antiinflammatory support, 41, 260–261 Antipruritic treatment, 11 Antrum, gastric, 201

303

304  Index

Arctium lappa (Burdock), 12, 15, 174, 273 Arnica (Arnica montana), 252–254, 273 Arnica montana (Arnica), 252–254, 273 Artemisia dracunculus (Tarragon), 274 Artichoke (Cynara scolymus), 279 Asthma, 7–8 acute adaptive response, 42–44 in adults, 38–39 allergic (see Extrinsic asthma) antiinflammatory support, 41 beta-adrenergic support, 42–43 biology of functions, 38–39 clinical classification, 40–41t comorbidities, 38 corticotropic axis, 43–44 diet, 35 emunctory support, 44 endocrine system, 26 epidemiology, 36 essential oils, therapeutic, 41–42 internal, 42 nebulizer, 41–42 topical, 42 extrinsic (see Extrinsic asthma) factors, 34–36 gastroesophageal reflux disease and, 36 genetics, 34–35 intrinsic (see Intrinsic asthma) latent class analysis, 34–35 long-term complications, 34 lungs emunctory function, 26–27 psychosomatic relationships, 26 non-allergic (see Intrinsic (non-allergic) asthma) parasympathetic, etiology, 36 parasympathetic inhibition, 42 pathogenesis, 34f pediatric, 25, 38 pharmaceutical agents classification, 40 phenotypes, 28 pulmonary histology, 26, 26t pulmonary teleology, 23 quantitative evaluations, 38 rhinitis, 36 secondary treatments alimentation, 46 exercise therapy, 46 lifestyle, 46–47 mineral supplementation, 46 vitamin, 46 sinusitis, 36 symptomatic nonpharmaceutical therapy, 40–41 thyrotropic axis, 44 treatment, 44, 49 Atopy, 7–8, 7t extrinsic asthma, 31 presence of, 28 Autonomic nervous system (ANS), 1, 10, 132, 232 allergies, 3, 4t asthma, 23–25 Crohn’s disease, 264

diarrhea, 225 digestive tract, 190–193, 192–193t enteric nervous system, 190–193 extrinsic asthma, 32 lower urinary tract obstruction (LUTO), 139–140 malabsorption diarrhea, 221, 223 menstruation menstrual disorder, 109 normal transit constipation, 226 prostate, 138, 153 prostate enlargement, 158t rapid transit diarrhea, 224–225 regulation, 191–192 and salivary secretion, 195–196 slow transit constipation, 230t ulcerative colitis, 259t Autophagy, 18, 248 cellular, physiology, 262 definition, 248 index 2, 248 index, adjusted, 248 Avena sativa (Milky oat), 96–97, 274

B

Balsam fir (Abies balsamea/pectinata), 269–270 Benign prostatic enlargement (BPE), 139–140 allergic-terrain, 155, 160 corticotropic and immunity indexes, 159t edematous corticotropic and immunity indexes in, 158t endocrine relationships in, 156t gonadotropic indexes in, 157t nosologic classification, 154 somatotropic indexes in, 157t symptomatic treatment, 158t symptoms and signs, 156t thyrotropic index in, 157t endobiogenic terrain, 155–160 inflammatory, 155 terrain, 160 lifestyle guidance, 153t lower urinary tract obstruction (LUTO), 160 pharmacologic strategies, areas of action, 149f symptomatic treatment, 155 treatment options, 159t Benign prostatic hypertrophy (BPH), 139–140 Beta-agonists (BA), 39–40 Beta-sympathetic function, 91 Betula pubescens (Birch), 274–275 Bilberry (Vaccinium myrtillus), 297 Bile, 206 Biology of functions, diagnosis of acne, 178–181 allergic terrain, critical, 7 asthma in adults, 38–39 in children, 38 atopic disease, 7 chronic eczema, recurrent worsening, 15–19 critical allergic terrain, 6t, 7 critical, precritical vs. suppressed critical, 245t

colitis, Crohn’s disease, 245t colitis, ulcerative, 260–263 eczema, 10, 11t gonadotropic axis, 63–66, 65t menstrual cycle disorders, 118–120 oligomenorrhea, 108–109 polymenorrhea, 112t prostatitis, 146–147 prostate enlargement, adenoidal, 146–147, 155 prostate enlargement, inflammatory, 154–155 somatotropic axis, 126–133 type 2c metrorrhagia, 98t Biology of functions, indexes acceptance contentment, 249, 263 adaptation entrainment score adjusted, 245–247 adrenal yield, 261 autophagy index, 248 central gonadotropic activity, 64t closed off to receiving, 249 critical tendency score, 249, 263 free radical index, 248 frustration index, 249 genito-thyroid, 17–18 insulin resistance index, 132 peripheral gonadotropic activity, 65t permeability adjusted index, 249 traumatic memory index, 249 vitamin D adaptation index, 261–262 Birch (Betula pubescens), 274–275 Black alder (Alnus glutinosa), 271–272 Blackberry (Rubus fruticosus), 293 Black pepper (Piper nigrum), 198 Black poplar (Populus nigra), 289 Black radish (Raphanus niger), 290–291 Black walnut (Juglans regia), 283 Bladder outlet obstruction (BOO), 139–140 Bogbean (Menyanthes trifoliata), 150, 288 Borage (Borago officinalis), 102–105, 174, 275 Borago officinalis (Borage), 102–105, 174, 275 Borborygmus treatment, 204t Bowel habits, 244 Bronchial-associated lymphatic tissue (BALT), 25 Bronchial secretions, 33 Bronchodilators, 40 Burdock (Arctium lappa), 174, 273

C

Cajeput (Melaleuca leucadendron), 286 Caraway (Carum carvi), 276 Carbohydrates absorption, 207 Carbon dioxide excess load, 27t Carduus marianus (Milk thistle), 275–276 Carica papaya (Papaya), 276 Carum carvi (Caraway), 276 Cassis (Ribes nigrum), 43, 291–292 Cell membrane activity, 180–181, 180t Cephalic-oral phase, 194 Cervix, secretion development days 1–4, 78 days 15–20, 83 days 21–24, 84 Chaste tree (Vitex agnus castus), 104, 298–299 Chicory (Cichorium intybus), 276

Index  305

Chronic fatigue syndrome, 132–133 Cichorium intybus (Chicory), 276 Cinnamomum zeylanicum (Cinnamon), 198, 276–277 Cinnamon (Cinnamomum zeylanicum), 198, 276–277 Citrus limon (Lemon), 277 Clary sage (Salvia sclarea), 294 Colon absorption processes, 210 comparative anatomy, 209–210 innervation, 210 motility of, 210 stool, 210–211 Connective tissue disorders, 233 Constipation, 225 behavioral causes, 233 cleansing diets, 228 demulcents, 229 fermented foods, 227–228 fibro-sclerosis tincture, 233 fructose for, 227, 228t fruits for, 228t functional causes, 232–233 high fiber foods treatment, 227t honey for, 227 hydroelectrolyte, 234 metabolic causes, 233 metalotherapy, 234 neuro-lymphatic tincture, 233 normal transit, 226–229 nosologic categorization, 225f oils for, 228 pathophysiology, 225–226, 233 prescription medication causing, 234 probiotic organisms, 228 secondary causes, 232–234 slow transit, 229–232 structural causes, 232 Copper-manganese. See Oligoelements Corn silk (Zea mays), 299 Corpus luteum, 73–75, 84 Corticotropic axis, 91–92 adenoma, prostate, 148t, 151 allergic terrain, 3, 20t asthma, 43–44 benign prostatic enlargement, 159t chronic eczema, recurrent worsening, 17t Crohn’s disease, 246t gonadotropic axis, 91–92 menstrual cycle, 71 menstruation disorders, 91–92 metrorrhagia, 95 Cortisol, 132 Cortisol binding globulin (CBG), 71–72 Corylus avellana (Hazelnut bud), 277–278 Crataegus oxyacantha (Hawthorn), 278 C-reactive protein (CRP), 245 Creatine phosphokinase (CPK), 179–180 Critical terrain acne, 166–168 adenoma, prostate, 154–155 past critical terrain, 140–141 precritical terrain, 140

Crohn’s disease, 245t eczema, 8 intrinsic (non-allergic) asthma ANS, 47 emunctory, 48 endocrine, 47–48 lower urinary tract obstruction, 154 tendency score, 249, 263 ulcerative colitis, 258–259, 258f, 259t Crohn’s disease (CD), 237, 239 anatomical distribution, 243–244 by central endocrine receptors on intestines, 230 biology of functions, 245t critical vs. precritical vs. suppressed critical terrains, 245t clinical presentation, 244 critical terrain, 245t epidemiology and risk factors, 239 gonadotropic axis, 246t, 247, 252, 255, 255–256t medicinal plants, 253t, 254 pathophysiology, 239–243, 243f physical examination, 244–249 precritical terrain, 239–243, 241f, 243f psychological indexes, biology of functions, 248–249, 248t, 257t review of systems, 244 skip lesions, 243, 244f somatotropic axis, 247t, 248, 252, 256, 257t structural factor of initiation (SFI), 240f thyrotropic axis, 247–248, 247t, 252, 256, 256t treatment, 249 critical terrain physiology, 254–256 standard of care, 249–250 suppressive and symptomatic, pharmacologic, 250–256, 251t symptomatic, endobiogenic, 264 Cupressus sempervirens (Cypress), 278–279 Cynara scolymus (Artichoke), 279 Cypress (Cupressus sempervirens), 278–279

D

Dandelion (Taraxacum officinale), 295–296 Diabetes mellitus type 2, 132 Diarrhea acute, 218–220 causes, 215 chronic case study, 220–221 treatment, 220 definition, 215 duration, 217 infectious, neuroendocrine factors, 216, 217t malabsorption, 221–224 clinical assessment, 222 etiology, 221 pathophysiology, 221–222 postviral gastroenteritis, 223–224 symptoms, 222t treatment, 222–224 osmotic, 221 in pediatrics, 215t

rapid transit, 224–225 seasonality of, 216 secretory, 215–221 acute diarrhea, 215 characteristics, 218t chronic infectious, 215–216 clinical presentation, 216–217 laboratory evaluation, 217 medicinal plants, 219t, 220 pathophysiology, 216 therapeutics, 219t treatment, 217–221 in summertime, 220 Diatomaceous earth (Illite clay), therapeutic uses, 218, 250, 254, 265 Dietary interventions for disorders acne, 175, 177, 181 adenoma, prostate, 150 asthma, 35 menstrual cycle disorders, 120 normal transit constipation, 228 slow transit constipation, 230 ulcerative colitis, 258 Digestion autonomic on, 193–194 hormonal interaction on, 193–194 neurotransmitter on, 193–194 purpose of, 186 stages of, 194–196 Digestive tract (DT) autonomic nervous system in, 192–193t, 193–194 cephalic-oral phase, 194 defensive nature, 187 endocrine regulation of, 194 energy exchange management, 186 esophageal peristalsis, 199 esophageal varices, 198 evolutionary requirement, 185–186 function, 185 gastroesophageal reflux disease (GERD), 199–200 histamine, 202–203 histological aspects, 188–189 hormonal interaction, 193–194 microbiota distribution, 187 motility, 204 muscle fibers, 188 nervous organization, 190 neurotransmitter, 193–194 oral phase, 197 organism management, 187 pancreatic enzymatic activity, 206t parasympathetic, 191 parotid-pancreas-parasympathetic triad, 196–197 small intestine, 203–206, 203t submandibular glands-liver-alpha sympathetic triad, 197 sympathetic, 191 walls of, 187–188 intestinal epithelium, 187–188, 188t mucosal lining, 188 structure and purpose, 187

306  Index

Dihydrotestosterone (DHT), 56, 73, 137–138, 138f Distal colon, obstructive disorders, 232 Dog rose (Rosa canina), 43, 292 Dopamine, 99–100 Drainage colon, 264 hepatobiliary-intestinal drainage, 12 menorrhagia, 107 menstrual cycle disorders, 90t skin, 12–14 Dysbiosis, 220 Dyspnea symptoms, 37 Dysuria, acute, 150

E

Eczema, 7–14 agent, 8 alimentation, 14 biology of functions, diagnosis of, 10, 11t chronic, recurrent worsening biology of functions, 15–19 in children, 14–15 corticotropic axis, 17t gonadotropic axis, 18t somatotropic axis, 18t thyrotropic axis, 18t definition, 8 desquamation, 10 etiologic treatment, 11–14, 13t evolution, 10 neuroendocrine topology, 10 oozing, 10 phases of, 10t precritical terrain, 8 presentation, 8 pruritic erythema, 10 rational treatment, 20t symptomatic treatment, 11 topology, 9t, 19t vesicular, 10 Edematous benign prostatic enlargement corticotropic and immunity indexes in, 158t endocrine relationships in, 156t gonadotropic indexes in, 157t nosologic classification, 154 somatotropic indexes in, 157t symptomatic treatment, 158t symptoms and signs, 156t thyrotropic index in, 157t Elecampane (Inula helenium), 282–283 Eleuthero (Eleutherococcus senticosus), 152–153, 242, 255, 279 Eleutherococcus senticosus (Eleuthero), 152–153, 242, 255, 279 Emunctories asthma, 31, 44 exocrine pancreas, 89 gallbladder, 89 intestine, 89 kidney, 26–27 liver, 89 lungs, 26–27

menstruation disorder, 85 skin, 3–6, 166 Endocrine axis acne, 166–168 asthma, 26 corticotropic, 3, 32 coupling, 245–247 digestive tract, 194 eczema, 10 edematous benign prostatic enlargement, 156t extrinsic asthma, 32 gonadotropic, 5 histamine, 4t infectious diarrhea, 216, 217t malabsorption diarrhea, 222 menorrhagia, 94f menstrual cycle, 78 pancreas, 89, 125 prostate, 136t prostate adenoma, 147t pulmonary histology and, 26 somatotropic axis, 5–6, 123–126 thyrotropic, 5 ulcerative colitis, 259–260 Endocrine pancreas, 89, 125 Endometrium, menstrual cycle days 1–4, 78 days 5–10, 80 days 11–14, 81 days 15–20, 83 days 21–24, 84 days 25–menstruation, 84 Enemas, 231 Enteric nervous system, 190 Eructation treatment, 204t Erythema desquamation, 10 oozing, 10 pruritic, 10 vesicular, 10 Esophageal peristalsis, 199 Esophageal varices, 198 treatment using medicinal plants, 198t Essential fatty acids (EFAs), 104 Essential oils, therapeutic asthma, nebulizer, 41–42 external, 105 internal, 42, 105 polyvalent, 162t rectal administration, 162 topical, 106 Estrogens, 239–240, 248 acne, 179 allergies, 3 corpus luteum, 73–75 granulosa cells, 73 gonadotropic axis, 55 insufficiency, 92–100 menstrual cycle, 78–79 metrorrhagia, 92–100 predominance, 102 production site, 66f, 66t receptor, 56 somatotropic axis, 123

Estro-progestive imbalance, 101–106 Eucalyptus ssp. (Eucalyptus species), 279–280 Eucalyptus species. (Eucalyptus ssp.), 279–280 Exercise-induced asthma, 50 Exercise therapy, 46 Exocrine pancreas (EP), 44 allergies, 2, 15 emunctories, 137–138 intervention, 205 medicinal plants with, 44, 206t pancreato-pulmonary relationship, 27 and PAP, 144 role in menstrual physiology, 89 secretion, 205 thyro-somatotropic role, 138 Extrinsic (allergic) asthma airway obstruction, 35t allergens, 31 alpha-sympathetic, 30 ANS response, 32 bronchial hyperreactivity, 35t bronchial secretions response, 33 causes of emunctories, 31 hyperimmunity, 31 type 1, 28–31 diagnosis, 36–38 emunctories response, 33–34 endocrine response, 32 epigenetics, 31 inflammation, 35t mechanisms in, 34, 35t mucous production response, 32 onset and severity in patient, 31–32 order of treatment, 39–40 parasympathetic, 30 past medical history, 37 physical examination, 37–38 prescriptions for, 44–46 protective factors against, 31 symptoms, 36–37 treatment, 39–40

F

Fabiana imbricata (Pichi), 280 Fat-soluble vitamin, 208–209 Fatty acids, 209t Fertility, 69–70, 70t, 78 Fibromyalgia, 132 Ficus carica (Fig), 280–281 Fig (Ficus carica), 280–281 Flatus treatment, 204t Follicle-stimulating hormone (FSH), 55, 63, 70–71, 80 biology of function indexes, 63 corpus luteum, 73–75 Crohn’s disease, 239–240, 240f gonadotropic axis, 5, 55 granulosa cells, 73 menstrual cycle, 78 metrorrhagia, 92–93 oligomenorrhea, 108 time of, 78

Index  307

Follicular metrorrhagia, 93 Follicular phase, menstrual cycle, 78 days 1–4, 78 days 5–10, 78–80 days 11–14, 80–82 days 21–24, 83–84 days 25–menstruation, 84 Food allergies, 1, 7, 7t Food sensitivities, 233–234 Fragaria vesca (Strawberry leaf), 104, 281 Free radicals index, 133 Fructose foods, 223t FSH. See Follicle-stimulating hormone (FSH) Fumaria officinalis (Fumitory), 281 Fumitory (Fumaria officinalis), 281 Fundus, gastric, 201–202

G

Gallbladder, 89, 206 Gamma linoleic acid, 104–105, 105f Gastric regulation, 202. See also Stomach regulation Gastroesophageal reflux disease (GERD) and asthma, 36 treatment using medicinal plants, 199–200, 200t type 1, lower esophageal sphincter, 199–200 type 2, pyloric sphincter, 201 Gastrointestinal tract, 185–186. See also Digestive tract (DT) allergic disorder, 6 autonomic control, 192–193 Genito-thyroid index, 17–18 German chamomile (Matricaria recutita), 94, 286 Ginger (Zingiber officinale), 299 Gipsywort (Lycopus europaeus), 285 Glucagon, 123, 125t Glycyrrhiza glabra (Licorice), 44, 281–282 Goldenroot (Rhodiola rosea), 291 Gonadotropic axis, 17–18, 18t acne, 168–169 actions, 55–56 allergic terrain, 5, 21t alpha-sympathetic, 91 beta-sympathetic, 91 biology of functions, 63–66, 64t corticotropic, 91–92 Crohn’s disease, 246t, 247, 252, 255, 255–256t genital spasmolytics, 91 immunity, 92 parasympathetic, 91 pathophysiology, 56–58 peripheral hormones, 55 pulsatility, 56f signs, 58 of abdomen and genitals, 59–60t adiposity, 63t of breasts and areola, 59–60t in hair, 59–60t of head and neck, 59–60t of muscles and ligaments, 63t by observations, 59–60t on skin, 59–60t

somatotropic, 92 symptoms, 58, 58–59t thyrotropic, 92 ulcerative colitis, 263, 263t Gonadotropin releasing hormone (GnRH), 70–71 Granulosa cells, 73 Green Illite clay, 218 Growth hormone (GH), 18, 123 action by location and endobiogenic mechanism, 124t growth score index, 207f pediatric growth, 207 Gut-associated lymphoid tissue (GALT), 25, 187

H

Hamamelis virginiana (Witch hazel), 90, 282 Hawthorn (Crataegus oxyacantha), 278 Hazelnut bud (Corylus avellana), 277–278 HEENT (head, ear, eye, nose and throat), endobiogenic physical examination, 37–38, 245 Hemorrhagic colitis, 259. See also Ulcerative colitis (UC) Histamine allergic terrain, 3 ANS-endocrine mediators, 4t biology of function, index, 7 digestive tract, 202–203 hypersensitivity, 2 receptor, 3, 5f, 33f Holly (Ilex aquifolium), 282 Honey, therapeutic usage, 227 Hops (Humulus lupulus), 282 Human choriogonadotropin hormone (hCG), 84 Humulus lupulus (Hops), 282 Hydrochloric acid (HCl), 201–202

I

IgE. See Immunoglobulin E (IgE) Ileocecal zone, 237–238, 238t Ilex aquifolium (Holly), 282 Immune disorders, 233 cellular and humoral elements, 2t classification, 2t Immunoglobulin E (IgE), 3 antibody, 6 mediated hypersensitivity, 2–6 (see also Type 1 IgE mediated hypersensitivity) mediated response, 4f Inflammatory bowel diseases (IBDs), 237–239. See also Crohn’s disease (CD); Ulcerative colitis (UC) Inhaled corticosteroids (ICS), 40 Insulin, 125 conservative effects, 125t index, 208f resistance, 18 resistance index, 132 Insulin-like growth factor, 123, 124t actions and effects, 123, 124t IGF-1, 73, 137

Interstitial cells of Cajal (ICC), 190 Intestines. See also Crohn’s disease (CD); Ulcerative colitis (UC); Small intestine asthma, emunctory support, 44 brush border of, 187f drainage, 188 as emunctory support, 44 epithelium, 187–188 large intestines, 238 muscular outer structures, 189f role in menstrual physiology, 89 Intrinsic (non-allergic) asthma acute adaptative response, 49 agents of, 48 causes, precritical terrain ANS, 47 emunctory, 48 endocrine, 47–48 definition, 47 emotional shock, 49–50 emunctories, 49 endobiogenic classification, 48t exercise-induced asthma, 50 mechanisms, 48 prescriptions, 50 response, 48 symptomatic treatment, 49 treatment, 49 Inula helenium (Elecampane), 282–283 Islet cells, 123

J

Juglans regia (Black walnut), 283

L

Lactate dehydrogenase (LDH), 179–180 Lady’s mantle (Alchemilla vulgaris), 98, 271 Lamium album (White deadnettle), 252, 283–284 Large intestines, 238 Larynx, 23–25 Lavandula angustifolia (Lavender), 42, 94, 284 Lavender (Lavandula angustifolia), 94, 284 Lemon (Citrus limon), 277 Lemon balm (Melissa officinalis), 287 Leonurus cardiaca (Motherwort), 95, 284 Leukotriene receptor antagonists (LTRA), 40 Licorice (Glycyrrhiza glabra), 44, 281–282 Linden tree (Tilia tomentosa), 296 Lipids absorption, 208 glucagon in management of, 125t 5-Lipoxygenase inhibitors, 40 Lithospermum officinale (Stoneseed), 284–285 Liver, 44, 89, 206 drainage, 254 as emunctory, 6 immune elements, fabrication, 2 menstrual cycle, 89 Liver-gallbladder-pancreas, 206 Lower esophageal sphincter (LES), 199–200

308  Index

Lower urinary tract obstruction (LUTO), 139–140 allergic-terrain, 160 blood tests, 145–146 clinical evaluation, 145–146 inflammatory terrain, 160 pharmacologic strategies, areas of action, 149f physical examination, 145 precritical terrain, 154 surgical intervention, 153–154 urogenital system, 145 Lower urinary tract, stages and symptoms, 140t LTRA. See Leukotriene receptor antagonists (LTRA) Lungs atopy, 28 carbon dioxide excess load causes, 27t clinical presentation, 28 clinical response, treatment, 28 as emunctory, 26–27 endobiogeny, 28 histology, 26, 26t pancreato-pulmonary relationship, 27 phenotypes, 28 psychosomatics of, 26 pulmonary teleology, 23 pulmonary unit, 23–25, 24f reno-pulmonary relationship, 27 role, 23 structure, 24f Luteal metrorrhagia BoF findings, 101t hypoestrogenism, 100–101 predominance, 101 treatment, 101 type 4-progesterone predominance with absolute hypoestrogenism, 100–101 Luteal phase, menstrual cycle, 82–85 Luteinizing hormone (LH), 55, 56f, 63, 70–71, 242 benign prostatic enlargement, 154, 157t biology of function index, 63 corpus luteum, 73–75 gonadotropic axis, 63–66 granulosa cells, 73 late follicular phase, 80 premenstrual disorder, 113–114 prolactin stimulation, 71 prostatic adenoma, 145 theca cells, 73 Lycopus europaeus (Gipsywort), 285

M

Malabsorption diarrhea dietary modification, 222 endocrine, 222 medicinal plants, 223, 224t neuroendocrine factors, 223 pathophysiology, 221–222 serotonin, 221 vitamins, 221 Mallow (Malva sylvestris), 254, 273, 285 Malva sylvestris (Mallow), 254, 273, 285

Marshmallow (Althaea officinalis), 272 Mast cell stabilizers, 40 Mastication, 194 Materia medica, 269 Abies balsamea/pectinata (Balsam fir), 269–270 Achillea millefolium (Yarrow), 270–271 Agrimonia eupatoria (Agrimony), 271 Alchemilla vulgaris (Lady’s mantle), 271 Alnus glutinosa (Black alder), 271–272 Althaea officinalis (Marshmallow), 272 Ananassa sativa (Pineapple), 272 Angelica archangelica (Angelica), 272 Anthemis nobilis (Roman chamomile), 272–273 Arctium lappa (Burdock), 273 Arnica montana (Arnica), 273 Artemisia dracunculus (Tarragon), 274 Avena sativa (Milky oat), 274 Betula pubescens (Birch), 274–275 Borago officinalis (Borage), 275 Borago officinalis (Borage oil), 275 Carduus marianus (Milk thistle), 275–276 Carica papaya (Papaya), 276 Carum carvi (Caraway), 276 Cichorium intybus (Chicory), 276 Cinnamomum zeylanicum (Cinnamon), 276–277 Citrus limon (Lemon), 277 Corylus avellane (Hazelnut, noisette), 277–278 Crataegus oxyacantha (Hawthorn), 278 Cupressus sempervirens (Cypress), 278–279 Cynara scolymus (Artichoke), 279 dosing for children, 270t of tinctures, 270t Eleutherococcus senticosus (Eleuthero), 279 Eucalyptus spp., 279–280 Fabiana imbricata (Pichi), 280 Ficus carica (Fig), 280–281 Fragaria vesca (Strawberry), 281 Fumaria officinalis (Fumitory), 281 Glycyrrhiza glabra (Licorice), 281–282 Hamamelis virginiana (Witch hazel), 282 Humulus lupulus (Hops), 282 Ilex aquifolium (Holly), 282 Inula helenium (Elecampane), 282–283 Juglans regia (Black walnut), 283 Lamium Album (White deadnettle), 283–284 Lavandula angustifolia (Lavender), 284 Leonurus cardiaca (Motherwort), 284 Lithospermum officinale (Stoneseed), 284–285 Lycopus europaeus (Gipsywort), 285 Malva sylvestris (Mallow), 273, 285 Matricaria recutita (German chamomile), 286 Medicago sativa (Alfalfa), 286 Melaleuca leucadendron (Cajeput), 286 Melilotus officinalis (Yellow sweet clover), 287 Melissa officinalis (Lemon balm), 287 Mentha piperita (Peppermint), 287–288

Menyanthes trifoliata (Bogbean), 288 Passiflora incarnata (Passionflower), 288 Pectinata (Balsam fir), 269–270 Pinus sylvestris (Pine), 288–289 Plantago major (Plantain), 289 Populus nigra (Black poplar), 289 Poterium sanguisorba (Salad burnet), 289–290 Quercus pedunculata (Oak), 290 Raphanus niger (Black radish), 290–291 Rhodiola rosea (Goldenroot), 291 Ribes nigrum (Cassis), 291–292 Rosa canina (Dog rose), 292 Rosmarinus officinalis (Rosemary), 292–293 Rubus fruticosus (Blackberry), 293 Salvia officinalis (Sage), 293–294 Salvia sclarea (Clary sage), 294 Satureja montana (Winter savory), 295 Secale cereale (Rye), 295 Sequoia gigantea (Sequoia), 295 Taraxacum officinale (Dandelion), 295–296 Thymus vulgaris (Thyme), 296 Tilia tomentosa (Linden tree), 296 Urtica dioica (Nettle), 296–297 Vaccinium myrtillus (Bilberry), 297 Valeriana officinalis (Valerian), 297 Vinca minor (Periwinkle), 297–298 Viola tricolor (Wild pansy), 298 Viscum album (Mistletoe), 298 Vitex agnus castus (Chaste tree), 298–299 Zea mays (Corn silk), 299 Zingiber officinale (Ginger), 299 Matricaria recutita (German chamomile), 94, 286 Medicago sativa (Alfalfa), 152, 286 Medium-chain triglycerides (MCT), 222, 223t Melaleuca leucadendron (Cajeput), 286 Melilotus officinalis (Yellow sweet clover), 287 Melissa officinalis (Lemon balm), 287 Menorrhagia alpha with alphasympatholytics, 94 menstrual phase and endocrine origin, 94f treatment of, 106–112 Menstrual cycle disorders biology of functions, 118–120 diet, 120 estrogen insufficiency, 92–100 follow-up, 120 gonadotropic activity, 91–92 history, 114–116 lifestyle, 120 luteal metrorrhagia, 100–101 menorrhagia, 106–112 oligomenorrhea, 107–110 polymenorrhea, 110–112 premenstrual disorder, 113–114 premenstrual syndrome, 101–106 review of systems, 114 treatment, 118 regulation ages of life, 70t axes of, 70–73 central-peripheral corticogonadotropic, 71–72

Index  309

central-peripheral gonadotropic, 71 central-peripheral thyrosomatogonadotropic, 72–73 corticogonadotropic activity, 70–71 corticogonadotropic function, 70–71 days 1–4, 78 days 5–10, 78–79 days 11–14, 80–81 days 15–20, 83 days 21–24, 83–84 days 25–menstruation, 84 fertility and, 69, 70t follicle stimulating hormone variability, 70f follicular phase, 78 luteal phase, 82–85 luteinizing hormone variability, 70f neuroendocrine activity, 69–70 ovarian production, 73–75 phases, 70t qualitative action, 77–78 rhythmicity, 69, 75, 76t serum vs. functional endocrine assessment, 75–78 stages, 70t thyro-somatotropic activity, 71 variability, 76–77 Mentha piperita (Peppermint), 287–288 Menyanthes trifoliata (Bogbean), 150, 288 Methylxanthines, 40 Metrorrhagia, 92–100 ACTH horizontal stimulation, 97–98 adrenal cortex, 95 alpha, 94–95 cortico-gonadotropic, 96 corticotropic axis, 95 dopamine, 99–100 follicular, 93 type 1-reduced serum estrogen availability, 93 type 2-reduced estrogen production, 96–98 type 3-early switch from FSH to LH, 99–100 insufficient estrogen production, 99 luteal, 100–101 (see also Luteal metrorrhagia) type 4-progesterone predominance with absolute hypoestrogenism, 100–101 medicinal plants, 99t sympathetico-corticotropic adaptation, 93 thyro-somato-gonadotropic, 98 treatment, 93 Milk thistle (Carduus marianus), 275–276 Milky oat (Avena sativa), 274 Minerals, absorption of, 209 Mistletoe (Viscum album), 298 Mitochondropathy, 133 Motherwort (Leonurus cardiaca), 95, 284 Motilin role, 205 Mucous layer, 188–189 lining, 188 role, 206 Muscle fibers, 188

N

Nettle (Urtica dioica), 153, 296–297 Neuro-corticotropic axis Crohn’s disease (CD), 245–247, 246t, 252, 255t ulcerative colitis (UC), 259–260, 261t, 264 Neuroendocrine axis, malabsorption diarrhea, 223 Normal transit constipation (NTC), 226. See also Constipation case study, 229 dietary approach, 228 dietary factor, 226 endobiogenic treatment of terrain, 226–229 etiology, 226 glycerin suppositories, 226 history, 226 laxatives, 229 lifestyle modification, 228 medicinal plants, 228 physical examination, 226 soluble fiber, 226–227 stimulant laxatives, 226 symptomatic treatment, 226 treatment, 226

O

Oak bud (Quercus pedunculata), 43, 290 Obstructive disorders, distal colon, 232 Oligoelements acne, 145–146 allergic rhinitis, 44–45 antiinflammatory support, 41 copper, 221 copper-gold-silver, 41 magnesium, 41, 174 manganese, 14 manganese-copper, 14 manganese-copper-cobalt, 14, 174 prostatitis, 153 selenium, 41, 46, 175 sulfur, 14, 41, 46, 174 wound healing, 14 zinc, 14 zinc-copper, 98, 101, 175 zinc-nickel-cobalt, 175 Oligomenorrhea agent, 108 biology of function indexes, 108–109, 109t critical terrain, 108 definition, 107 mechanisms, 108 polyvalent neuroendocrine regulators, 113t precritical terrain, 107–108 prescriptions, 109–110, 111t treatment, 109–110, 110t Oligosaccharidases, 207 Omega-6 oils, 104 Osmotic diarrhea, 221 Ovarian activity, menstrual cycle days 1–4, 78 days 5–10, 78–79 days 11–14, 80–81

days 15–20, 83 days 21–24, 83–84 days 25–menstruation, 84 follicle development from uterine life to, 79f peripheral gonadic hormones, 73–75 spontaneous, 82f Oxygen exchange, 23–25, 29–30 insufficiency, 23

P

Pancreato-pulmonary relationship, 27 Papaya (Carica papaya), 276 Parasympathetic nervous system, 191 Para-sympatholytics, intestinal tropism, 231 Parathyroid hormone (PTH) index, 248 Parietal cells, 201–202 Parotid-pancreas-parasympathetic activity, 196–197 Passiflora incarnata (Passionflower), 94, 288 Passionflower (Passiflora incarnata), 94, 288 Pelvic circulation medical plants, menstrual physiology, 90t role in menstrual physiology, 89–90 Pelvic floor dysfunction, 232 Peppermint (Mentha piperita), 287–288 Pepsin, 202 Pepsinogen-HCl functional pairing, 202 Periwinkle (Vinca minor), 297–298 Permeability index, adjusted, 248t, 249 Pichi (Fabiana imbricata), 280 Pine (Pinus sylvestris), 43, 288–289 Pineapple (Ananassa sativa), 272 Pinus sylvestris (Pine), 43, 288–289 Piper nigrum (Black pepper), 198 Plantago major (Plantain), 289 Plantain (Plantago major), 289 Polymenorrhea agent, 111 biology of function indexes, 111–112, 112t definition, 110 mechanisms, 111 polyvalent neuroendocrine regulators, 113t precritical terrain, 110 prescriptions, 112 treatment, 112, 113t Populus nigra (Black poplar), 289 Postviral gastroenteritis malabsorption, 223–224 Poterium sanguisorba (Salad burnet), 289–290 Precritical terrain asthma, intrinsic, 47–48 Crohn’s disease, 239–243, 241f, 243f eczema, 8 lower urinary tract obstruction (LUTO), 154 oligomenorrhea, 107–108 polymenorrhea, 110 prostatitis, 140 ulcerative colitis, 258–259, 258f, 259t Premenstrual syndrome (PMS), 101–106, 103t, 113–114 chronic menstrual dysfunction with, 113–114 estrogen predominance, 102

310  Index

Premenstrual syndrome (PMS) (Continued) estro-progestive symptoms, 106 with menorrhagia, 107 progesterone predominance, 101–102, 103t Progesterone, 56, 57t, 75 corpus luteum, 73–75 granulosa cells, 73 predominance, 101–102, 103t theca cells, 73 Progestins, 55 Prolactin (PL), 5–6, 71 actions by location, 124t biology of function index, 132 in menstrual cycle, 78–79 somatotropic axis, 123 Prostate adenoma aggressor, 154 biology of functions, 146–147, 155 case study in prevention, 141 chronic, 150 clinical evaluation, 145–146 corticotropic regulation, 148t, 151 coupled endocrine relationships in, 147t critical terrain, 154–155 devolution, 145 diet, 150 evaluation, 155–160 evolution, 144–145 gonadotropic regulation, 147t, 151–152 hyperimmune terrain, 154 hyperinflammatory terrain, 154–155 past critical terrain, 140–141 pharmacologic treatment, 147–150 precritical terrain, 140 somatotropic index, 148t, 153 symptomatic treatment, 150 thyrotropic regulation, 153 treatment of terrain, 151–154 anatomy, 135–136 autonomic nervous system, 138 embryology, 136t endocrine influence, 136t endocrinology, 137–138 enlargement, 156t histology, 136 intrinsic function, 135 pathology, 136t physical examination, 161 physiology, 136–139 zonal anatomy, 136f Prostate-specific antigen (PSA), 137, 144 Prostatic acid phosphatase (PAP), 137, 144 Prostatic enlargement, benign. See Benign prostatic enlargement (BPE) Prostatitis, 135 acute, 161 anatomic structural and functional elements, 160t chronic, 161 evaluation, 161 metabolic structuro-functional and functional elements, 160t microbial agents, 161

pathophysiology, 160 physical examination, 161 treatment antibiotics, 161 endobiogenic approach, 162 oral, 162 rectal, 162 Proteins absorption, 208 digestion, 202

Q

Quercus pedunculata (Oak bud), 43, 290

R

Raphanus niger (Black radish), 290–291 Rapid transit diarrhea (RTD), 224–225. See also Diarrhea disorders of, 215 neurology, 224 pathophysiology, 224–225 treatment, 225 Recto-hemorrhagic colitis, 237. See also Crohn’s disease (CD); Ulcerative colitis (UC) Respiration, afferent input, 25f Rhodiola rosea (Goldenroot), 291 Ribes nigrum (Cassis), 43, 291–292 Roman chamomile (Anthemis nobilis), 272–273 Rosa canina (Dog rose), 43, 292 Rosemary (Rosmarinus officinalis), 292–293 Rosmarinus officinalis (Rosemary), 292–293 Rotavirus diarrhea, 220 Rubus fruticosus (Blackberry), 293 Rye (Secale cereale), 295

S

Sage (Salvia officinalis), 293–294 Salad burnet (Poterium sanguisorba), 289–290 Saliva, 194–195 Salivary glands autonomic nervous system and, 195–196 functional pairing, 196–200 pairs of, 194, 195f Salvia officinalis (Sage), 293–294 Salvia sclarea (Clary sage), 294 Satureja montana (Winter savory), 295 Secale cereale (Rye), 295 Secretory diarrhea. See also Diarrhea endobiogeny, 216 medicinal clay, 218 medicinal plants, 219t, 220 neuroendocrine factors, 216 pathophysiology, 216 treatment hydration, 217–218 Selenium, 46 Semen composition, 137t motility, 137 Sequoia (Sequoia gigantea), 295 Sequoia gigantea (Sequoia), 43–44, 295

Serum hormone testing, 171–172 Sex hormone binding globulin (SHBG), 71–72, 169–170 Short-chain fatty acids (SCFA), 222, 223t Skin physiology, 165–166 Skip lesions, 243, 244f Slow transit constipation (STC), 226, 229. See also Constipation beta-mimetics, 231 case study, 231–232 cognitive behavioral therapy (CBT), 230 dietary approach, 230 insoluble fiber, 230 lifestyle modification, 230 mineral, 231 pathophysiology, 229–230 physical exam, 230 treatment, 230–231 Small intestine, 237 activity of, 204 enzymatic absorption of nutrients, 206–209 functional considerations, 203–209, 203t migration motility complex, 204–205 motility, 204 Somatotropic axis, 92 acne, 170, 180 allergic terrain, 5–6, 21t biology of function, 126–133 cellular metabolic activity, 133t central integration, 125–126 central somatotropic activity, 130t Crohn’s disease, 247t, 248, 252, 256, 257t endocrine function, 123–126 features, 123 function review, 123–126 metabolic effects of, 131t pathophysiology, 126, 126t peripheral integration, 125–126 peripheral somatotropic activity, 131t signs, 126 abdomen, 130t back, 130t bones, 130t chest and breast, 129t dermatologic, 128t extremities, 130t head, 128t mouth, 129t temperament, 128t symptoms, 126, 127t ulcerative colitis, 260, 262, 262t, 264 Spasmophilia, 23, 28 Sperm, 137 Splanchnic congestion, 216 Stomach regulation anatomy and function antrum, 201 fundus, 201–202 pepsin and protein digestion, 202 gastric phases, 201 gastric regulation, 202 dynamics of, 202 gastric volume, 201 Stoneseed (Lithospermum officinale), 284–285

Index  311

Stool characteristics, 210–211 quality of, 217 test, characteristics, 217, 218t Strawberry leaf (Fragaria vesca), 104, 281 Structural factor of initiation (SFI), 239–240 Submandibular glands-liver-alpha sympathetic activity, 197 Sulfur. See Oligoelements

T

Taraxacum officinale (Dandelion), 295–296 Tarragon (Artemisia dracunculus), 274 Testosterone, 56, 137–138, 138f Theca cells, 73 Theory of Endobiogeny, 238–241, 248–249, 257–258 Thryotropin-releasing hormone (TRH), 242 alpha stimulation, 5, 5f benign prostatic enlargement, 154, 157t Crohn’s disease, 242 histamine stimulation, 33f late follicular phase, 80 premenstrual disorder, 113–114 prolactin stimulation, 71 prostatic adenoma, 145 Thyme (Thymus vulgaris), 296 Thymus vulgaris (Thyme), 42, 296 Thyroid efficiency index, 248 Thyroid-stimulating hormone (TSH), 138 asthma in children, 25 menstrual cycle, 92 oligomenorrhea, 108 prostate, adenomatous hypertrophy, 138 Thyro-somatotropic activity, 71 Thyrotropic axis, 17–18, 18t, 92, 93t acne, 169–170, 179–180 allergic terrain, 5, 21t asthma, 44 Crohn’s disease, 247–248, 247t, 252, 256, 256t lungs, 26–27 menstrual cycle disorders, 109–110 ulcerative colitis, 259–262, 261t, 264

Thyrotropic-exocrine pancreas, 138 Tilia tomentosa (Linden tree), 296 Transurethral prostatectomy (TURP), 153–154 Type 1 IgE mediated hypersensitivity, 2–6 agent, 3 emunctory, 6 hyperimmunity allergic terrain, 7 precritical, 2–3 response, 3–6

U

Ulcerative colitis (UC), 237, 257 acceptance-contentment index, 263 aggressor and critical terrain, 259 anatomical distribution, 260 autonomic nervous system, 259t closed off from receiving index, 262–263 comorbidities, 258 critical tendency score, 263 critical terrain, 258–259, 258f, 259t diet, 258 endocrine response, 259–260 epidemiology, 257–258 gonadotropic axis, 263, 263t laboratory studies, 260 neuro-corticotropic axis, 259–260, 261t, 264 pathophysiology, 258–259 permeability adjusted index, 262–263 physical examination, 260 precritical terrain, 258–259, 258f, 259t psychological stressors, 258 risk factors, 257 somatotropic axis, 260, 262, 262t, 264 thyrotropic axis, 259–262, 261t, 264 traumatic memory index, 262–263 treatment, 263–264 sample treatment, 265 standard of care, 263–264 symptomatic treatment, 264 Upper esophageal sphincter (UES), 199 Urtica dioica (Nettle), 153, 296–297

V

Vaccinium myrtillus (Bilberry), 297 Valerian (Valeriana officinalis), 297 Valeriana officinalis (Valerian), 297 Vinca minor (Periwinkle), 297–298 Viola tricolor (Wild pansy), 14, 174, 298 Viral gastroenteritis, 223–224 Viscum album (Mistletoe), 298 Vitamin absorption, 209 asthma treatment, 46 malabsorption diarrhea treatment, 221 Vitamin A sources, 264, 264t ulcerative colitis treatment, 258 Vitamin D, 264 adaptation index, 248, 261–262 Vitamin E, 105–106, 106t sources and servings, 264t, 265 Vitex agnus castus (Chaste tree), 104, 298–299

W

Water, absorption of, 209 Water-soluble vitamin absorption, 209 White deadnettle (Lamium album), 252, 283–284 Wild pansy (Viola tricolor), 14, 174, 298 Winter savory (Satureja montana), 295 Witch hazel (Hamamelis virginiana), 90, 282 Wound healing, 14

Y

Yarrow (Achillea millefolium), 270–271 Yellow sweet clover (Melilotus officinalis), 287 Yoghurt, acne therapeutic treatment, 172

Z

Zea mays (Corn silk), 299 Zinc, 98. See also Oligoelements Zingiber officinale (Ginger), 299