Nutrition Principles and Applications

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NUTRITION Principles and Applications Amandio V. Vieira

Canadian Edition

© copyright 2021 Amandio Vieira, all rights reserved. No part of this work may be reproduced or used in any form, including electronic and mechanical, without permission of the author About the author: Amandio V. Vieira, PhD, completed the Bachelor of Science program in biochemistry at the University of Calgary, and the doctoral program on the topics of vitamin A, lipids, and lipoproteins, at the University of Alberta and the University of Vienna. He was a postdoctoral researcher at the Scripps Research Institute, California. He has published research articles in major international scientific journals. Current, nutrition-related research interests include nutrient transport into cells, epigenetic regulation by nutrients, as well as bioactivities of phytochemicals and xenobiotics.

NUTRITION: Principles and Applications

TABLE OF CONTENTS Chapter 1 : Introduction to Nutrition

2

Chapter 2 : Dietary recommendations and assessments

16

Chapter 3 : Fats and lipids

25

Chapter 4 : Carbohydrates

35

Chapter 5 : Proteins and amino acids

46

Chapter 6: Plant foods and phytochemicals

57

Chapter 7: Vitamins

62

Chapter 8: Minerals and water

77

Chapter 9: Food safety and technology

89

Chapter 10: Life-cycle nutrition

99

REFERENCES

113

INDEX

128

Appendix A: Dietary Reference Intakes, DRI Tables

135

Appendix B: Example of Dietary Assessment

149

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Chapter 1 Introduction to Nutrition

1.1 Basic definitions The term nutrition can refer to a process: the process by which nutrients and foods contribute to body function. Nutrition can also refer to the study of nutrients and foods. Foods are generally defined as what people eat and drink; foods contain nutrients and other factors. Nutrients are typically classified into six groups: carbohydrates, lipids or fats, protein, vitamins, minerals, and water. The first three (carbohydrates, fats, protein) are referred to as macronutrients because we typically require them in large quantities (macro means large). Vitamins and minerals are typically referred to as micronutrients because they are needed in relatively smaller quantities (micro means small). The term malnutrition refers to a chronically poor diet that results in illness. Undernutrition and overnutrition, as the names imply, refer to situations where nutrient 2

intake is insufficient (under) or excessive (over) relative to the body's needs.

1.2 Food choices Many factors can influence a person’s food choices. The appearance of the food, its smell, flavor, and texture, are important for most people. But there are many other factors that can influence food choices, e.g., ethnic background, convenience, availability and cost, social networks, media and advertising, knowledge of nutrition, and also more fundamental factors such as genetics, age, level of physical fitness, as well as childhood experiences. Over years and decades, food choices can have a major influence on health, and risk of developing some chronic diseases. Many diseases, including the two major causes of death in most societies—cardiovascular diseases and cancers—can have diet-related risk factors in addition to genetic risk factors (more details in section 1.3, Nutrigenomics), and other risk factors such as level of physical activity and smoking.

We can prevent some illnesses and improve our overall health by eating a variety of foods as part of a balanced diet. Poor nutrition can increase the risk of morbidity and mortality from chronic illnesses.

1.3 Nutrigenomics Nutrigenomics is a term that relates the influence of genetic and epigenetic factors to diet and disease risk. An example of how genetics and epigenetics can contribute to disease risk is shown in FIGURE 1.3.1, and explained as follows: (A) shows that a genetic mutation (x) in a gene (DNA) can result in production of a mutant protein by the cells. (B) The mutant protein may contribute to increased risk of disease. For example, in some families there are mutations in the LDL receptor gene that are passed from one 3

generation to another and can greatly increase the risk of a heart attack due to an abnormal LDL receptor protein (coronary heart disease, CHD; more details in chapter 3). (C) There are also genetic mutations that occur outside of the proteincoding sequence of a gene and such mutations, while not affecting the structure of a protein, can greatly increase or decrease the levels of a protein. (D) Such abnormal levels of a protein may also increase risk of a disease.

FIGURE 1.3.1 Comparison of genetic (downward arrows A and C) and epigenetic (upward arrow E) effects on gene expression and risk of disease (arrows D and B). See main text for full explanation.

(E) Epigenetic factors can also result in abnormal levels of a protein and may increase disease risk. Whereas genetics is concerned with DNA sequence (i.e., sequence of the AGTC bases of a person’s genes), epigenetics involves chromatin. Chromatin includes the DNA genetic material as well as its accessories such as histones and other cellular components that interact with DNA. With genetics, changes in the DNA sequence (mutations) can influence disease risk. In comparison, with epigenetics there are different chemical modifications of the chromatin 4

(shown as F, G, H) that can affect the expression of a gene and thereby affect disease risk. More than 100 different epigenetic chemical modifications have been identified to date.8 Diet and other environmental factors can change the chemical modifications of chromatin: a process that can be called nutriepigenetics.

1.4 Energy balance in the body Energy balance refers to the relative input of energy into the body and output of energy from the body. More specifically, it refers to the energy metabolism that occurs in the cells. If a person expends more energy than they consume, it’s a negative balance and results in weight loss; if energy intake is greater than energy expended, that is a positive balance and contributes to weight gain. Energy input refers to the calories that people obtain from the foods they eat. Three macronutrients provide energy for the body: about 4 kilocalories per gram of carbohydrate consumed, about 4 kilocalories per gram of protein, and about 9 kilocalories per gram of fat. Another potential source of calories is alcohol which can provide about 7 kilocalories per gram. In terms of energy output, the ways by which the body uses energy are typically classified into three categories: (1) Resting energy expenditure, REE, and basal energy expenditure, BEE, both refer to the minimal amount of energy needed by the body when it's in an awake state, resting, fasting, and in a low stress, warm, and quiet environment. REE (or BEE) accounts for most of the daily energy used by adults, typically about 2/3 of all the energy used by the body.9 The main differences between REE and BEE are the conditions that must be met for their measurements, typically more stringent conditions for BEE; for example, BEE requires about 12 hours of fasting, but only about 4 hours is required for REE measurements. (2) The thermic effect of food component, TEF, accounts for approximately 1/10th of the total energy output by the adult body. TEF refers to the acute increase in energy expenditure associated with the consumption of a meal; it is the increase in energy expenditure above the basal energy expenditure that occurs when food is consumed. This extra energy is required for the

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Energy input and output are two components of energy balance that people can control to some extent. In terms of input, dietary protein, fat, carbohydrates, provide about 4, 9, 4 kcal/g, respectively

eating process, digestion of the food, as well as transport of nutrients throughout the body. (3) The third output component, physical activity or exercise, is highly variable among individuals. Some people are very sedentary, others very physically active. On average, in the adult population, it has been estimated that the physical activity component accounts for about 1/4 of all the energy expended by the body. Kilocalorie (kcal) is the unit of energy used in this book, 1 kcal = 1 Calorie (the SI unit for energy is the Joule, 1 kcal = 4.2 kJ). If one knows the energy value of the macronutrients—4 kcal/g of carbohydrate, 4 kcal/g of protein, 9 kcal/g of fat—dietary energy calculations can be performed using those energy values. For example, if a sandwich contains 20 grams of fat, 15 grams of protein, and 30 grams of carbohydrate, those macronutrient energy values can be used to calculate the total kilocalories of the sandwich: 360 kcal (20 x 9 = 180 kcal from fat, 15 x 4 = 60 kcal from protein, 30 x 4 = 120 kcal from carbohydrates). The percentage of the total calories that comes from fat can then be calculated: 180 kcal from fat/360 total kcal = 0.5, or 50% of all calories in the sandwich come from fat. There are equations that can be used to calculate a person’s estimated daily energy requirement (EER, equation for normal-weight adults given below).1 Such calculations are based on age, weight, height, and estimated physical activity level (PA). APPENDIX A provides additional details for the PA factors, and EER equations for different ages and conditions such as pregnancy.

Men EER = 662 – (9.53 x age [y]) + PA x { (15.91 x weight [kg]) + (539.6 x height [m]) } Women EER = 354 – (6.91 x age [y]) + PA x { (9.36 x weight [kg]) + (726 x height [m]) } The PA factors range from 1.00 (sedentary, typical activities of daily living DL), to 1.12 (low-level active, DL plus about 30 minutes of moderate-intensity exercise per day (MA), e.g., walking 5 km), to 1.26 (active, DL plus 1 hour of MA), and up to about 1.47 (very active, DL plus 1 hour MA, plus either 1 hour of vigorous exercise/day or 2 hours MA).

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Example: a 20 year-old woman, 60 kg weight, 160 cm height, who is physically active (PA, 1.26) has an EER = 354 – (6.91 x 20) + 1.26 [(9.36 x 60) + (726 x 1.6)] = 2387 kcal/day. This should be her approximate daily energy intake.

1.5 Essential nutrients and nutrient deficiencies Before examining the individual nutrients in subsequent chapters, the following are some general properties of the nutrients. Essential nutrients can be defined as those nutrients that either are not produced in the body, or not produced in sufficient quantities to meet body needs. These nutrients, which must be obtained from the diet, have specific and important functions in the body, in the cells; and health problems will develop if there is a chronic (long-term) deficiency. In terms of nutrient recommendations, there is a general term referred to as dietary reference intakes, DRI. Under this DRI umbrella term, there are other, more specific terms related to nutrient recommendations; for example, the recommended dietary allowance, RDA, is widely used in dietary planning and will be examined in more detail, along with other DRI terms, in chapter 2. Nutrient deficiencies can occur when there is low intake, lower than what the body needs, over a prolonged period of time; this problem is referred to as a primary deficiency. A secondary nutrient deficiency can occur when a person is consuming the recommended amount, e.g., consuming the RDA amount, but there is a metabolic abnormality in the body or other physiological problem that causes the person to require a higher than normal intake. Nutrient density is another commonly used term that refers to the amount of a particular nutrient in a serving of food relative to the total calories in that same serving of food. For example, consider two meat sandwiches, A and B; the only difference between them is that A contains butter and B does not. The nutrient density for iron, a nutrient present only in the bread and meat, is higher in B than A; butter contributes calories but does not contribute any iron. Deficient or excessive intake of some nutrients can result in health problems. For most people, consuming the recommended amounts, such as the RDA, can prevent these health problems. Many people, however, are slightly deficient in some nutrients; and even if intake is enough to avoid major symptoms of deficiency, this slightly deficient intake may 7

increase the risk of health problems in the long term.2 In the vitamins and minerals chapters (ch. 7 and ch. 8, respectively), some examples of this potentially problematic suboptimal intake will be considered.

FIGURE 1.5.1 A spectrum of nutrient intakes, from deficient to excessive. The middle of the spectrum represents the recommended intake (e.g., RDA or AI). See main text for additional details.

1.6 Nutrient supplements Terms such as dietary supplements, nutraceuticals, and functional foods are commonly used, and sometimes subject to different definitions. Dietary supplements typically refer to dry powders, pills or liquid extracts that are taken to promote health but are not in a food form, for example, multi-vitamin pills or omega-3-rich fish oil capsules. Nutraceuticals often refers to a subgroup of dietary supplements where the potentially active component is present at high doses for a possible pharmacological or physiological effect (beyond the basic nutritional effect), for example, high dose vitamin C pill taken with the goal of trying to prevent the common cold (in this case, however, vitamin C has not been scientifically proven to prevent such respiratory illnesses). In contrast to dietary supplements, functional foods are those foods, often enriched with a vitamin or mineral, that are consumed with the purpose of promoting health, beyond the basic nutritional value of the food, for example, an iron-fortified breakfast cereal for a person who is iron deficient, or frequent consumption of tofu (a soy food) for potential health benefits; functional foods are in a normal food form, not a pill form. Some common recommendations for supplements are the following: (a) the vitamin folate and the mineral iron are often recommended as supplements in relation to pregnancy; (b) supplements of vitamins D and 8

B12 are often recommended for the elderly; (c) vitamin and mineral supplements may be recommended for children who have inadequate food consumption and lack variety in their diets. One of the most common problems associated with the use of nutrient supplements is that the supplements may give the person a false sense of security3 and lower their motivation for consuming more fruits and vegetables, for increasing their physical activity, or for changing potentially harmful habits such as smoking and high alcohol consumption. With supplement use (compared to obtaining nutrients from foods) there is also increased risk of toxicity from excessive intake of some vitamins or minerals or other nutrients.

1.7 Food digestion and nutrient absorption This section is a brief overview of digestion, absorption, storage, transport, and functions of nutrients. Many factors affect food digestion and absorption of nutrients, and some apply before the eating process begins; for example, the length of time and temperature at which the food is cooked can affect digestion and nutrient absorption. In subsequent chapters, details of digestion and absorption for the carbohydrates, protein, fats, vitamins, and minerals will be examined. Once the nutrients are absorbed in the gastrointestinal tract (GI, mostly in the small intestine, SI in FIGURE 1.7.1), they can be transported throughout the body via the bloodstream. From the blood, they can pass through the capillaries and into the extracellular fluid that bathes the tissues and cells. Many nutrients have carrier proteins (or lipoproteins, complexes of lipids and protein) that participate in this transport; and on the cell surfaces, at the cell membrane, there are receptors that recognize the nutrients or the nutrient carriers, and participate in the process that brings the nutrients into the cells. Inside the cells, the nutrients may be chemically modified or metabolized into active forms that can then function in the cell. Modification of nutrients in cells can also result in the production of breakdown products to be excreted from the body by the kidneys, in the urine.

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Cross section through a capillary tube showing a red blood cell (erythrocyte) inside. This type of capillary is lined with fenestrated endothelial cells. Source: Dr. L. Howard, Darthmouth, USA

MO ES LV

ST PA

LI

SI

FIGURE 1.7.1 The human digestive tract (gastrointestinal tract, GI) showing the mouth (MO), esophagus (ES), stomach (ST), small intestine (SI), large intestine (LI, also called colon), liver (LV, and gall bladder shown as the blue spot with the liver), and pancreas (PA). A blood capillary network (right image) is also shown where nutrients for cells, and waste compounds from cells, exchange. Arterial blood enters from the arterioles (1, red arrows). The blood plasma exits the blood vessels (2, yellow arrows) into the interstitial fluid that bathes tissues; it delivers oxygen, water, glucose, vitamins, minerals, and other nutrients to the cells through spaces between the cells lining the capillary wall. Waste products from the cells including uric acid, creatinine, lactic acid, carbon dioxide, along with water then enter the capillaries and move into venules (3, blue arrows), ultimately into the veins.

1.8 Overview of nutrient functions and metabolism Nutrients, or their active conversion products (metabolites), can have many functions in the body and inside our cells. For example, some nutrients participate in the production of body proteins or other body components. Other nutrients (carbohydrates, fats, and protein) are sources of energy for the body. Some of the B vitamins are not direct sources of energy but can participate in energy metabolism, and help the body obtain energy from the macronutrients. Metabolites of vitamins A and D can function in the nucleus of the cell, and help control the expression of genes. Metabolites of some nutrients help control many body processes by acting like signals in the cell or hormones in the circulation, e.g., forms of vitamin D. Water is essential for almost all body functions, including its critical role in the regulation of body temperature. Some of the minerals such as calcium and phosphorus are important 10

components of body structure and the skeletal system. Other nutrients such as vitamins C and E, function as antioxidants and help protect cells from oxidative stress. These and many other functions of nutrients will be considered in more detail in subsequent chapters. Metabolism refers to the many chemical reactions that occur in the body; some of these involve nutrients and other dietary components. As illustrated in FIGURE 1.8.1, metabolic reactions (metabolism) may be divided into two groups: (a) anabolic reactions (anabolism) that involve production of larger components from smaller units, also referred to as synthesis. For example, inside the cells there is a process called protein synthesis by which amino acids, the building blocks of proteins, are linked together to form body proteins such the proteins needed to form muscles. (b) The other types of metabolic reactions involve breakdown of larger components into their units (catabolism). For example, when a person consumes foods that contain protein, the process of digestion breaks that dietary protein down into its component amino acids which can then be delivered to the cells. Some of the enzymes that catalyze metabolic reactions require ‘helpers’ for their activities. These co-enzyme helpers (shown in the figure as CoE) may be nutrients; for example, derivatives of many of the B vitamins act as co-enzymes in our cells.

FIGURE 1.8.1 Schematic representation of anabolic (build-up, green arrow, two units being linked together) and catabolic (break-down, red arrow, two linked units being broken apart) reactions catalyzed by enzymes. Typically energy is required for anabolic reactions, and released in catabolic reactions. CoE represents enzyme helpers, coenzymes; many B vitamins function as coenzymes.

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1.9 Nutrition research Nutrition research can cover a wide spectrum of areas from medicine and biology, to anthropology and psychology, and the food industry. The research is based on the scientific method which typically begins with an observation or question, a problem to be solved. Based on comparisons with similar problems and the results of related past research, a hypothesis is formulated. This is a possible solution to the problem, an educated guess. Then the hypothesis must be tested; for nutrition research, this may involve testing of nutrients or diets in animal models or human intervention studies. Double-blind placebo-controlled intervention studies are considered most reliable in this respect. Double blind means that neither the participants nor those directly working with the participants know which participants are part of the intervention group (receiving the potentially active food or substance) and which participants are part of the placebo group (not receiving the potentially active food or substance). The results of the study may be incorporated into a larger theory when combined with the results of similar studies; or the results may indicate that a new hypothesis must be formulated and tested. The results of nutrition research (and other scientific research) are published in peer-reviewed journals. Peer review means that other experts in the field have examined the study in detail, and approved it for publication. Typically, for a hypothesis or theory to become established and widely accepted among scientists, there should be results from different researchers, usually from different research laboratories, perhaps different countries, and there should be results from different kinds of experiments or studies. FIGURE 1.9.1 shows the home pages of two large databases of published scientific research including nutrition research. PubMed is a database related to health and medicine: https://pubmed.ncbi.nlm.nih.gov/ Google Scholar is a more general scientific database that covers all scientific topics; the advanced search option (shown in the figure) allows for a more directed search: https://scholar.google.com/ When one searches these databases to find peer-reviewed articles related to nutrition, terms that are as specific as possible should be used. These databases contain both original-research articles which detail a specific 12

study, as well as more general review articles that cover multiple research articles. There are many publications on the internet that have not been put through a reliable scientific peer review, e.g., commercial and organization websites, or research journals and other publications outside of the scientific mainstream. There are many websites related to nutrition, and many claims are made about nutrients and foods, especially in relation to human health. In terms of evaluating information about nutrition and health, it's useful to ask a range of questions: Is the proposed diet balanced, and does it include a variety of foods? Are there many forbidden foods, and attempts to frighten people with claims of toxic nutrients and foods? Most, if not all sites, that propose detoxification solutions with foods or supplements are not considered reliable. Is there an attempt to lead a person to purchase ‘unique’ supplements, often expensive? Is there information that you recognize as false? Does the website propose a rapid solution to a complex problem such as obesity? Is the case being presented unbalanced, very one-sided? Is it based on personal claims or testimonials, rather than upon articles in established, peer-reviewed scientific journals?

Example Study: Beta-carotene supplements and lung cancer To end this first chapter, an example of nutrition research is presented (summarized at the end of this chapter). It is a summary of studies on betacarotene and cancer, and the testing of the hypothesis that beta-carotene supplements can lower the risk of lung cancer among smokers.4-7 For many decades, biochemical research in the laboratory had indicated that beta-carotene, a component of many fruits and vegetables, is a powerful antioxidant. This information, combined with knowledge that oxidative damage to DNA can increase cancer risk, and population-level studies that suggested a lower lung cancer risk among smokers who consume more fruits and vegetables, led to these studies with betacarotene supplements.

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FIGURE 1.9.1 Home pages of two major sources (databases) for nutrition-related research articles, PubMed (upper) and Google Scholar (lower). See main text for webpage addresses.

In this double-blind, placebo-controlled intervention study, smokers were divided into two groups: one received a pill containing beta-carotene, the other received the placebo pill. As the results were analyzed, it was found that the beta-carotene pills did not lower the risk of lung cancer among smokers, relative to the placebo group.6,7 In fact, a small increase in lung cancer risk was seen among those smokers taking the beta-carotene pill. The conclusion from this study is that the isolated beta-carotene in the pill form—i.e., this beta-carotene taken out of its normal food context (it is

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one of the many components of some fruits and vegetables)—does not provide protection against lung cancer and may slightly increase the risk. Note that this study does not disprove a possible cancer-protective role of beta-carotene when consumed as part of the fruits and vegetables that contain it. Fruits, vegetables, and other plant foods typically contain hundreds of substances—phytochemicals (‘phyto’ means plant; this topic of phytochemicals will be examined further in chapter 6). When the whole plant food is consumed, there are potential synergies among these phytochemicals; and such synergies cannot occur if a person takes a supplement that contains only one or a few isolated substances instead of consuming the whole food.

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Chapter 2 Dietary recommendations and assessments

2.1 Introduction and main questions The second unit is focused on dietary planning: dietary and nutritional recommendations as well as assessments of nutritional status will be considered. The following are some of the main questions for this chapter: ● What are the different categories of food and nutrient recommendations? ● How is nutritional status assessed, and how can problematic nutritionrelated behavior be corrected?

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2.2 Food guides and food groups A healthy diet is possible within the food context of different countries, cultures, ethnic groups, and different food preferences. Most countries have food guides that emphasize variety and balance in the diet. These national guides typically recommend a variety of foods from within each food group, and a balance of foods from the different food groups. Variety and balance help ensure adequacy of all the required nutrients. Moderation is also typically emphasized, especially in terms of total caloric intake. With the food guides, it's important to keep in mind that not all foods classified in the same group have equal health benefits. Some foods, for example, may have healthier types of fats compared to other foods that are in the same group. Also, different varieties of the same vegetable can have different nutrient densities for vitamins and minerals; for example, two types of lettuce, Romaine and iceberg, are not nutritionally equivalent.1 Romaine typically has a higher nutrient density for several vitamins and minerals. The same can apply to grain products, two types of breads, even though they are in the same food group food, can have different nutrients densities for vitamins and mineral, and different amounts of dietary fibre. Serving sizes are also important components of food guides. If food servings are too large, it becomes more difficult to achieve variety and balance in the diet. Serving sizes are examined further in the section on food labels (2.4). Overall, national food guides are attempts to provide simple and important information, and facilitate the planning of healthy diets by a large population. FIGURE 2.2.1 provides examples of national food guides from around the world, Asia, Africa, Europe, and North America. For adults, the new Canada Food Guide, for example, recommends that most daily food should come from the vegetables and fruit group, water should be the main daily drink, whole grain foods should be chosen as carbohydrate sources rather than high sugar foods, and also emphasizes the need to include protein rich foods which can be from animal or plant sources (FIGURE 2.2.1 below).2

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FIGURE 2.2.1 National food guides from around the world: China, India, South Africa, USA, UK. Additional details are given for the Canada food guide (bottom picture).2

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2.3 Nutrient recommendations Nutrient recommendations are made to avoid health problems due to long-term (chronic) deficiencies and to avoid possible toxicity due to chronic excessive intake. Recommendations for nutrients and energy depend on gender, age, and can also be influenced by level of physical activity, health status, pregnancy, and other factors. Nutrient supplements are not generally recommended; the recommendation is typically to try to get all the necessary nutrients from foods.6,7 In some specific situations, however, supplements may be recommended, for example, (a) supplements of micronutrients (vitamins and minerals) for an adult who is on a very-low calorie diet as part of a weight-loss program; typically, if caloric intake is below about 1500 kilocalories per day, micronutrient supplements are recommended because it’s difficult to get all vitamins and minerals with such low food intake.3,4 (b) Vitamin B12 supplements can be recommended for some vegans (type of vegetarianism) or for elderly people. (c) Supplements of the vitamin folate and the mineral iron are often recommended during pregnancy. Dietary reference intake DRI is a collection of recommendations based on the available scientific evidence for nutrient needs. Recommended dietary allowance RDA is the nutrient intake that meets the needs of 97% of the population. Estimated average requirement EAR meets the needs of 50% of the population. When there is insufficient data available to establish an EAR or RDA, available scientific evidence is used to set an adequate intake AI. Daily values DV are reported on food labels and they are a percent of the DRI (e.g., RDA or AI) in a serving of a given food. Acceptable macronutrient distribution range AMDR represents the percent of recommended total daily calories from a macronutrient, i.e., fat, protein, and carbohydrate. An upper limit UL is an intake that represents the limit in terms of possible toxic effects of a nutrient; intakes above the UL over a period of time are likely to be toxic to the body. Dietary reference intakes are given in Appendix A. Why don't we all have exactly the same nutrient requirements? FIGURE 2.3.1 is a graph that represents the requirement for a nutrient (call it nutrient x), on the X axis, and number of people in the population on the Y axis. We see that the curve presenting the requirement is a normal distribution; in the middle at about the 50% requirement level is the estimated average requirement (EAR). At about the 97% requirement level 19

is the RDA. Under the curve, ABC represent three individuals in the population. These are three individuals with very different requirements for nutrient x. They have different requirements because of their genetic and epigenetic differences; each one is unique. Note that the RDA for this nutrient meets the needs of all three of these people A, B, and C. But if they were following the EAR instead of the RDA, however, person C would develop a deficiency of this nutrient x over time.

FIGURE 2.3.1 A graph to illustrate nutrient recommendations and requirements, and needs of three different individuals in the population, A, B, and C. Main text provides an explanation.

2.4 Food labels Food labels provide much information about the food. Information about main components is typically found in the ingredients list. Added natural and artificial colors and flavors, or fortification with vitamins and minerals, can also be mentioned in the ingredients. In terms of macronutrients, the quantity and types of fats and carbohydrates, and protein, is given. Serving sizes, i.e., how many grams are in a typical serving of the food, are also given along with the contents of other nutrients and Calories per serving. Often the country of origin is stated; and if it's an organic food, this information is also present on the food label with the appropriate organic certification symbols. But food labels don't necessarily include all the 20

Example of a “Nutrition Facts” food label. Table 2.4.1 states the minimal, required nutrients; additional nutrients can be listed on this label.

components in the food. Cooking and processing of food can result in new substances being formed through chemical reactions, and such substances are not mentioned on the food label. Health claims may also be mentioned on the food label; but there are government-level regulations on what can be stated in the health claims. There are also regulations in terms of the use of specific words for nutrient contents, words such as fat free, low in sugar, lean meat, reduced in salt, high in calcium, or source of fibre. TABLE 2.4.1 contains more specific information on the regulation of these nutrient content words, as well as health claims; and a list of the nutrients that must be reported on the food label is also shown. Table 2.4.1 Regulations related to food labels. Canadian food labels currently define “a lot” of a nutrient as 15% or more of the daily value, and “a little” as 5% or less of the daily value.

There are some foods that don't require any labeling in terms of ingredients; for example, spices, alcoholic drinks, foods that are made to

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be consumed in the short term such as deli sandwiches don't require an ingredients list and nutrition facts label.

2.5 Assessments of nutritional status After following a dietary plan, an assessment may be done to determine if nutrient needs are being met. If they are not being met, then the dietary plan should be revised. A variety of methods can be used to assess nutritional status. One of the most common is a dietary assessment whereby a person records all the foods they have consumed over a period of time (for example, over three days). Then the nutrient content of each food is determined; there are a variety of databases and other tools that report nutrient contents of most of the common foods. By determining total daily nutrient intakes, a person can then compare their own intakes with the recommendations, for example, with the RDAs and AIs. APPENDIX B provides an example of a dietary assessment based on a three-day food intake recall. Anthropometric measurements are body measurements such as weight, height, waist circumference, body mass index (BMI), and can also be used for assessing nutritional status; for example, these measurements can be used for assessing whether caloric intake has been sufficient or excessive. BMI is a person’s weight (kg) divided by their height squared (m2); for example, a person of height 175 cm who weighs 75 kg has a BMI of 24.5 [75 ÷ (1.75 x 1.75) = 24.49]. Clinical assessments by a health care provider may also provide an indication of nutritional status and nutritional deficiencies; but often problems identified in clinical assessments (e.g., skin conditions) can have many causes in addition to nutrition deficiencies. There are also many laboratory tests, biochemical analyses that can measure nutrient levels in the body and identify possible deficiencies or excesses. Some laboratory tests measure the nutrient directly, others are indirect; for example, vitamin B status can be measured directly through a blood test for pyridoxal phosphate (PLP, discussed further in chapter 7 on vitamins), an active B6 metabolite in the body, or measured indirectly through a urine test for 4-pyridoxic acid (PA), a catabolite of B6 that is excreted from the body in the urine. The FIGURE at right shows urine test strips that are dipped into a patient’s urine sample and can help a doctor to diagnose an illness; they change colors depending on levels of different urine components. A strip that is 22

positive for nitrite in the urine, may indicate that the patient has a urinary tract infection (UTI) with coliform bacteria. A strip that is positive for protein in the urine may indicate a problem with kidney function. Ketones and glucose in the urine may be indicative of diabetes (discussed further in chapter 4 on carbohydrates).

2.6 Changing nutrition-related behavior If problems are identified in the assessments, the question becomes how to solve them, how to change nutrition related behaviors? Typically, advice is given to improve the person's knowledge of nutrition and health, and to help them develop a better dietary plan. There are also psychological models that can be used to change food related behaviors. FIGURE 2.6.1 summarizes three main steps in terms of solving a problem. In the context of nutrition, the example here is for a type 2 diabetic (diabetes is a topic of chapter 4). A variety of laboratory tests such as blood glucose measurements are used to assess the problem, in this case to assess the level of diabetes. Based on this assessment, a strategy is developed to try to improve the health of the diabetic. Dietary changes are typically recommended along with increased physical activity, and perhaps also a prescription of glucoselowering drugs. After a period of time (e.g., three months), an evaluation of the strategy is done to determine if there has been a satisfactory improvement in the problem. In the case of the diabetic, after a period of about 3 months of trying the suggested changes to diet and physical activity (and perhaps also medication), the person would be assessed again, laboratory tests, etc. 5 Did the strategy result in a satisfactory improvement of blood glucose control by the body? If not, then the strategy can be modified, perhaps additional dietary changes, more physical activity, and addition of other glucose lowering drugs for the diabetic in this example.

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FIGURE 2.6.1 Overview of a strategy to try to change nutrition-related behaviors and improve the health of a type 2 diabetic adult. See main text for details.

The chapters that follow on the nutrients (macronutrients, and micronutrients) have the same overall structure: (a) different types of the nutrients are introduced, followed by the (b) best food sources of the nutrient(s). How are they (c) digested, transported and absorbed by the body is the third focal point. Then (d) some functions of the nutrient(s) are examined along with (e) some problems and diseases associated with them.

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Chapter 3 Fats and other lipids

Kalamata olives (Greece)

3.1 Introduction and main questions The lipids group of macronutrients is examined in this first chapter on nutrients. There are many types of lipids, and they all have a common property: very low solubility in water; i.e., they do not readily dissolve in water. Two general categories of lipids considered in this chapter are the oils and fats. Oils are those lipids that are liquid at room temperature, for example, olive oil or other plant oils. Fats are those that are solid at room temperature, for example, butter or lard (animal fat). In the last part of this chapter on problems and diseases associated with lipids and lipoproteins, cardiovascular diseases, mainly coronary heart disease, CHD (heart attack), will be examined. The following are some of the main questions for this chapter: 25

· · · · ·

What are some of the different types of lipids? What are the best food sources for lipids? How are lipids digested, transported, and absorbed by the body? How do they function in the body? What are some problems and diseases associated with lipids?

3.2 Fatty acids Fatty acids are the first group of lipids to be considered in this chapter. Commonly used terms such as saturated fats, or omega-3 fats, or transfats, refer to different fatty acid structures. The fatty acids are characterized by three main parameters: (i) First is the number of carbons in the carbon chain that makes up most of their structure. There are long chain (14 or more carbons), short chain (6 or fewer carbons), and in between those lengths are the medium chain, fatty acids. (ii) Second, fatty acids can be characterized by the presence of carbon-carbon double bonds (C=C) in the chain. If there are no such bonds, the fatty acid is called saturated or SFA. If there is at least one C=C double bond in the carbon chain, it's called unsaturated. If there is only one C=C, it’s a mono-unsaturated fatty acid (MUFA); and if there’s more than one, it's a polyunsaturated fatty acid (PUFA). (iii) A third characterizing parameter applies to the unsaturated fatty acids—the location of the first C=C double bond. Omega-3 fatty acids have their first C=C double bond on the third carbon from the end (omega is the end). Omega 6 fatty acids have their first C=C double bond on the sixth carbon from the end, and omega-9 on the nineth.

9 6 Structure of alpha-linolenic acid, an unsaturated fatty acid (three double bonds between the carbons, at positions 3, 6, and 9); it’s an omega-3 fatty acid because the first double bond is at position 3. It has a total 18 carbons, and can be designated as C18:3 (where 3 refers to the 3 C=C double bonds)

There are two groups of essential fatty acids, both unsaturated; i.e., they have double bonds between the carbons: (a) Omega 3, e.g., alpha-linolenic acid, and (b) Omega-6, e.g., linoleic acid. Trans fatty acids can occur naturally in foods such as meats and dairy, or originate from man-made industrial processes, e.g., partial hydrogenation of plant oils. High dietary intake of trans fats can have a negative impact on health, and the exact reasons for this are a current topic of research in nutrition and health. A fatty acid is trans, if it has at least one C=C double bond between the carbons and an abnormal linear shape. Normal unsaturated non-trans fatty acids have a bent (crooked) shape: the C=C double bond introduces a bend in the chain; that is the normal structure (called cis; cis is the opposite of trans). Thus, the trans fat is a kind of 26

Structure of two C18:1 (only 1 C=C double bond) fatty acids, both are omega-9. Oleic acid (upper, main component of olive oil) has a bend at the location of the C=C double bond (cis structure). Elaidic acid (lower) also has a C=C double but is linear; such a structure is called trans.

hybrid, abnormal in that it contains a C=C double bond but does not have a bent structure; its structure is linear, similar to that of a saturated fatty acid.

3.3 Triglycerides, cholesterol, and other types of lipids There are hundreds of different kinds of lipids in the body; for example, phospholipids are very abundant in our body because they are main components of cell membranes and of lipoproteins (FIGURE 3.4.1). Some other lipids such as glycolipids are conjugates of a lipid with a sugar (or saccharide).

Figure 3.3.1 A mixed triglyceride showing the glycerol backbone (left, red- framed) and three fatty acids: palmitic (top, saturated, C:18:0), oleic (middle, unsaturated, C:18:1), and alpha-linolenic (bottom, unsaturated, C18:3, first C=C double bond is at the third carbon from the omega (w) end). In this book, the omega designation is used; but there is another numbering system that starts at the alpha (a) end of the fatty acid. Note that the middle and bottom saturated fatty acids are shown as linear, but their natural shape is bent (cis, not trans).

Triglycerides are structures composed of three fatty acids linked together via a glycerol backbone (FIGURE 3.3.1). Triglycerides (TG) are the main form of storage fats in the body; TG is stored in fat cells, called adipocytes (illustrated in section 3.8). Cholesterol is a type of lipid called a sterol (an isoprenoid, similar in structure to vitamin D) that is important for the normal function of the cells in the body. Excessive cholesterol in the blood (plasma or serum, as LDL

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Steroidal structure of cholesterol. Many factors contribute to a person’s plasma cholesterol level, e.g., diet and heredity (genetics)

cholesterol), however, is a strong risk factor for cardiovascular diseases such as CHD or heart attack (examined in section 3.9).

3.4 Lipoproteins Lipoproteins are aggregates, or complexes, of lipids and proteins. Four different classes of lipoproteins are considered here; they are defined based on their density, and commonly abbreviated as: CM, VLDL, LDL, and HDL. Lipoproteins can greatly impact our risk of some cardiovascular diseases.

Apo

CE TG (hydrophobic core)

Apo

PL Ch

Figure 3.4.1 Lipoprotein structure. In this sphere cross-section model the more hydrophobic (lipophilic) components such as triglycerides (TG) and cholesteryl esters (CE) are in the core of the particle. Phospholipids (PL), cholesterol (Ch) and other compounds with hydrophilic parts form the surface of the particle. Lipoproteins in the circulation can carry many different lipids including the lipid-soluble vitamins such as vitamins A, D, E, and K (Chapter 7). The protein components (labelled as Apo, with parts protruding from the surface of the lipoprotein) are called apolipoproteins, and have many functions such as lipoprotein interactions with cells, with extracellular enzymes, and with other lipoproteins.

Chylomicrons, CM, are the lipoproteins that form in gut cells (enterocytes) during the digestive process, and eventually enter the circulation with the dietary lipids that were consumed in the meal. Very low density lipoproteins, VLDL, are produced and secreted by liver cells; VLDL particles are assembled from different pools of lipids in the 28

liver. Both CM and VLDL are composed mainly of triglycerides (but can contain many other types of lipids). In the circulation, VLDL is broken down to smaller particles that, ultimately, have a density range defined as low density lipoprotein or LDL. The main component of LDL is cholesterol, and LDL delivers cholesterol (and other lipids) to the cells in the body. High-density lipoprotein HDL can pick up (or accept) excess cholesterol from many of the cells in the body; and thus protect them from accumulating too much cholesterol. In artery cells, excess cholesterol accumulation can contribute to a pathological process known as atherosclerosis which, in turn, contributes to risk of CHD and stroke.

3.5 Synthetic fats and fat substitutes A variety of synthetic fats or fat substitutes have been developed by the food industry. The objective is to create substances that have the taste and mouth-feel of fat, but fewer calories than fat. Microparticulated protein is one example of a fat substitute, and one of its commercial formulations is called Simplesse®. Microparticulated proteins are based on milk protein 29

(whey) or egg white protein. The protein source is put through a mechanical (blending) process that generates tiny particles. These microparticles create a consistency and taste similar to fat, but only have 1-3 kilocalories per gram, depending on the formulation and percentage of water (compared to 9 kcal/g for fats).

3.6 Food sources of lipids and intake recommendations Major sources of lipids in the Canadian diet include plant oils, butter and margarines, mayonnaises and salad dressings, nuts, cheese and dairy, meats and eggs. The omega-3 and Omega 6 essential fatty acids can be obtained from plant oils; canola oil, for example, is a source of both, about 10% alpha-linolenic omega-3, and about 20% linoleic acid omega-6. Fish and seafood are also sources of other omega-3 fatty acids known as DHA and EPA (docosahexaenoic acid and eicosapentaenoic acid, respectively). Plant oils are often classified based on their most abundant fatty acids. Olive oil and canola oil are referred to as monounsaturated because their main components are monounsaturated fatty acids (mainly oleic acid). As presented in chapter 2, there are regulations regarding the use of terms such as low fat or low saturated fat. For a food to be labeled as ‘low fat’ it should contain 3 grams or less of total fat per serving. To be labeled ‘low in saturated fat’ a food should have 2 grams or less of saturated fat and trans fat combined, as well as less than or equal to 15% of the total calories per serving from saturated and trans fat combined. A fat-free food is one that contains less than 0.5 gram of fat per serving. Current recommended fat intake for adults is 20 to 35 % of total daily calories (AMDR). The majority of fats consumed should be monounsaturated, up to about 20 %. Approximately 5 to 10% should be polyunsaturated, including good sources of omega-3, and avoiding excessive omega-6. For saturated fats, the recommendation is less than about 10% of daily calories, with an emphasis on minimizing saturated fats from animal products such as dairy and meats. The recommendation for trans fat is that it should be as low as possible, less than 1% of total daily calories. For cholesterol, the current recommendation is 300 milligrams per day or less; a medium sized egg, for example, contains about 200 milligrams of cholesterol.

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Common dietary plant oils (top) include canola, olive, corn, peanut. Butter and margarines (bottom) are also common sources of fat. Others include avocado and cheese (not shown)

3.7 Lipid digestion During the digestive process after a meal, bile is secreted from the gallbladder and serves to emulsify or dissolve the dietary lipids. The pancreas secretes enzymes into the small intestine to help with fat digestions, e.g., lipase enzymes that breakdown triglycerides. The lipids are then absorbed by the cells lining the small intestine (enterocytes); most of the bile is recycled, returns to the gallbladder. The intestinal cells assemble chylomicron lipoprotein particles (CM) from the dietary lipids, and secrete them; ultimately, they enter the circulation. In the blood, CM are broken down (fatty acids released from TG by lipases in the capillary wall) to produce CM remnants. The CM remnants are then taken out of the circulation, mainly by the liver. In the cells of the liver, another lipoprotein is assembled, very low-density lipoprotein VLDL, and secreted into the blood. As with CM, VLDL is also broken down in the circulation, and one of the breakdown products is LDL, low density lipoprotein. LDL is cholesterolrich and can deliver cholesterol to cells throughout the body. Most cells have another source of cholesterol (other than LDL delivery) and that source is the internal production of cholesterol. High density lipoprotein HDL does the opposite of LDL, it accepts or picks up excess cholesterol (and some other lipids) from the cells. HDL is considered a protective lipoprotein (sometimes called the ‘good cholesterol’) in terms of cardiovascular disease risk because it protects cells against accumulating excess cholesterol. In contrast, LDL (‘bad cholesterol’) has the potential to overload cells with cholesterol. An excessive cholesterol accumulation in cells can contribute to the pathological process of atherosclerosis in the arteries.

3.8 Functions of lipids in the body There are hundreds of different kinds of lipids in the body, in the cells and in the circulation, and they can have many functions. One major function of the fatty acids is to provide energy for the body. The human body is efficient at storing fatty acids in the form of triglyceride, in the adipocytes of the fat tissues (see FIGURE at right). As a source of energy, fats are important to support body growth during childhood, and many other processes that occur in the body at all stages of the life cycle. Derivatives of the essential fatty acids have regulatory functions in the body; they can 31

White adipose tissue (WAT) is the main energy storage depot of the body. Subcutaneous WAT is shown.

Source: Medical gallery of Blausen Medical 2014

affect multiple cell functions. Lipids are also important structural components of cells. Cholesterol, phospholipids, and other lipids, are critical components of the outer membrane of cells, as well as components of the membranes inside the cell (surrounding intracellular organelles).

3.9 Problems and diseases associated with lipids As an example of problems and diseases related to lipids, coronary heart disease or CHD (also known as a heart attack) will be examined. CHD is a type of cardiovascular disease that involves pathological processes of atherosclerosis, inflammation, and thrombosis (description of the pathological process is given in FIGURE 9.3.1). Atherosclerosis refers to the buildup of plaque in the artery that eventually leads to a block in the blood flow (block may be caused by a blood clot, thrombosis); and if this plaque buildup occurs in the heart, it can lead to a heart attack. Atherosclerosis, inflammation, thrombosis, these pathological processes involved in CHD are affected by many factors, risk factors include older age, male gender, genetics (heredity), hypercholesterolemia (high LDL cholesterol), hypertriglyceridemia (high fasting triglycerides), low HDL cholesterol, obesity (especially with high intra-abdominal fat storage), hypertension, diabetes, physical inactivity, smoking, psychological stress, and diet.1,5 If a person is at very high risk of CHD based on blood (plasma or serum) lipid measurements, diet and exercise recommendations alone may not be enough to lower risk; and medications may be prescribed, for example, drugs such as statins that lower plasma cholesterol levels.1,2,12 TABLE 3.9.1 provides information on some risk categories for plasma lipid levels. The major dietary recommendations to lower CHD risk are the following (A-E): 2-4,6-9,12 (A) lower intake foods that are high in saturated and trans fat, especially animal products such as meats; (B) lower caloric intake to help achieve a healthy body weight; (C) increase intake of fruits, vegetables, and whole grain products; these are typically low in saturated and trans fats, and rich in vitamins, minerals, and dietary fiber; (D) increase intake of omega-3 foods; for example, replace a serving of meat with fish, an omega-3-rich food.

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Walnuts (shown in the growth phase on the tree) are rich sources of linoleic acid (~60% of lipid content), as well as alpha-linolenic acid and oleic acid (~15% each). They also contain a wide range of polyphenols and other phytochemicals (topic of chapter 6).

Table 3.9.1 Blood lipid levels and risk* of atherosclerosis/CHD in adults over age 30.

FIGURE 3.9.1 The pathological process of atherosclerosis in an artery. (1) Normal, healthy artery. (2) Plaque build-up typically occurs over decades, and the early stages are called fatty streaks. (3, 4) The lesion builds as macrophages and cholesterol-loaded foam cells promote inflammation, and smooth muscle cells secrete fibrous proteins to form a fibrous cap (4, 5). Platelets also aggregate and contribute to the fibrous cap and narrowing of the artery. The increased pressure can contribute to rupture of the cap and formation of a blood clot that completely blocks the artery (6, causing a heart attack, or stroke in the brain) and may also contribute to rupture of the artery (7). Plaques that become loose in one location can break free and cause a blockage in another arterial location, e.g., in a narrow arteriole of the brain. Source: Npatchet 2015, creative commons

5

6

7 1

2

3

4 33

Dependent on a person's risk of CHD, (E) other dietary recommendations may be made; for example, keep saturated fat intake under 7% of total daily calories, or include dietary plant sterols that are known to lower LDL cholesterol, or emphasize some types of plant foods to increase intake of other potentially beneficial phytochemicals. There is ongoing research on different components of plant foods (phytochemicals, discussed further in chapter 6) that may have benefits in terms of lowering risk of CHD and other chronic diseases. One of the most common dietary recommendations for lowering CHD risk is to lower consumption of high saturated fat animal products.2,9-12 In this case, the dietician provides some specific suggestions based on the patient’s food preferences. Common advice is to choose low-fat meats such as poultry, and low-fat cheeses and dairy products. If the person regularly consumes prepared frozen foods such as ready-to-heat pasta dinners, they are given advice to read the food labels carefully because there are large differences in terms of the saturated fat content, usually related to the quantities of meat and cheese. Another specific example is pizza, a very common food. A meat pizza with a typical amount of cheese contains about twice as much fat as a vegetarian pizza with a bit less cheese; and most of that fat in the meat pizza is saturated fat from the animal products—meat and cheese.

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Common recommendations to lower risk of CHD include increased consumption of vegetables and fish.

Chapter 4 Carbohydrates

4.1 Introduction and main questions In this chapter, dietary carbohydrates and their functions in the body are examined, along with related topics such as artificial sweeteners, dietary fibres, glycemic index of foods, and an introduction to diabetes. The following are some of the main questions for this chapter: · What are the different types of carbohydrates? · What are the best food sources for carbohydrates? · How are carbohydrates digested and absorbed by the body? · How do carbohydrates function in the body? · What are some of the problems and illnesses associated with carbohydrate metabolism?

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4.2 Simple sugars (saccharides): monosaccharides, disaccharides, and oligosaccharides Monosaccharides are the single carbohydrate units, the most simple sugars. Glucose is one of these monosaccharides; and it's also the main carbohydrate source of energy in our body. Problems with the control of blood (plasma) glucose levels are characteristic of diabetes (topic of section 8.6). The monosaccharides glucose, galactose, and fructose are hexoses (hex=6; they contain 6 carbons in their chemical structure). Combinations of two monosaccharides are called disaccharides; these are also simple sugars. If glucose and fructose are linked together, they form sucrose, also known as common table sugar. If glucose and galactose are linked together that disaccharide is called lactose, milk sugar. Two glucose units linked together form the disaccharide maltose. Oligosaccharide is a less-commonly used term; it refers to chains containing a few linked monosaccharides. For example, 6 or 7 fructose units linked together is called a fructo-oligosaccharide (FOS). Many vegetables contain FOS, and it can help promote the growth of beneficial bacterial in the large intestine (prebiotic, topic of section 4.7); FOS is often considered as type of soluble dietary fibre.

Glucose (top, a monosaccharide), sucrose (middle, common table sugar) a disaccharide of glucose and fructose, and lactose (bottom, milk sugar), a disaccharide of glucose and galactose are shown; note the different ways to draw the chemical structure of glucose.

4.3 Polysaccharides Polysaccharides are long chains of monosaccharides (typically >9 single sugars linked together, usually several 100 or a few 1000 linked together); these chains can be linear or branched. The starches are long chains of glucose made by plants: amylose is a linear chain starch; and amylopectin is a branched chain starch. Glycogen is the highly branched glucose polysaccharide that is made in the body; it’s stored in the liver and muscle. Dietary fibers are sometimes called non-starch polysaccharides (NSP). They can be soluble in water, for example, pectins, or insoluble, for example, hemicellulose. Dietary fibers can be partly digested (fermented) by bacteria in the large intestine; and these digestion products can help maintaining a healthy gastrointestinal tract (examined further in chapter 6).

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Structure of amylopectin starch showing a branch in the glucose chain

4.4 Food sources of carbohydrates and dietary fibres The major dietary sources of carbohydrates are cereal products and starchy foods such as potatoes, rice, and bread. Also, major sources are the sweetened foods, drinks and baked goods, and fruits, and fruit juices. Carbohydrate intake recommendation, in terms of AMDR, is 45 to 65% of total daily calories. Most of these carbohydrate calories should come from complex carbohydrates (whole grain foods); intake of simple sugars should be as low as possible, about 10% or less of total daily carbohydrate intake.4 The recommended dietary allowance (RDA) for carbohydrates is about 130 grams a day; most Canadian adults consume much more than the RDA. For dietary fibre, the recommendation for adults (AI) is about 30 grams per day, and should include sources of soluble fiber. A food that is labeled as a high source of fiber must have at least 4 grams per serving. Examples of dietary fibers and their sources are given in TABLE 4.4.1.

TABLE 4.4.1 Some food sources of soluble and insoluble dietary fibres. * exoskeleton of invertebrates; ** pasta and potatoes that have been cooked and cooled before eating, e.g., potato salad, also some legumes, cereals, unripe bananas SOLUBLE

INSOLUBLE

Pectins (apple skin, vegetables)

Cellulose (most plant foods)

Alginates & Carrageenan (Algae)

Lignins (cereals, e.g, rye)

Psyllium

Chitin (‘skin’ of shrimp/insects*)

Inulin (some plant foods)

Resistant starches**

Raffinose (legumes)

Hemicellulose (cereals, legumes)

4.5 Sweeteners Sweeteners can be classified as natural versus man-made (artificial or synthetic), or classified by caloric content. The full calorie sweeteners, 4 kilocalories per gram, include table sugar (sucrose), honey, and corn syrup. Honey and corn syrup are not recommended for infants; as will be 37

discussed in chapter 9, this is because of safety issues due to possible contamination with bacterial spores. Sweeteners that provide no energy, 0 kcal/g include artificial (man-made) sweeteners such as saccharin and sucralose, and also the natural sweeteners stevia derived from the leaves of the South American Stevia plant. Relative to sucrose (sweetness value of 1), the three sweeteners are about 300, 500, and 200 times sweeter, respectively. Acceptable daily intake values (ADI) are available for most of these sweeteners. For example, Health Canada sets the ADI for these sweeteners at 5, 15, and 4 mg/kg of body weight, respectively.

Stevia plant, bag of dried leaves

Aspartame is an artificial sweetener that typically makes a negligible energy contribution because it is very sweet and extremely small amounts are used to sweeten foods and drinks. Aspartame is a dipeptide, two amino acids linked together; when it’s digested by the body it has the protein energy value of 4 kilocalories per gram. But because very small amounts are needed to sweeten a food/drink, its energy contribution to the diet is negligible. Aspartame breaks down under heat; it is not useful as a sweetener for baking/cooking. Acesulfame or sucralose or stevia can be used for cooking and baking. Aspartame also is only stable for longer than a few days at lower pH (below 7); it’s ideal for soft-drinks such as colas that have a low pH (its half-life is almost a year in a cola drink of about pH 4). The ADI for aspartame is 40 mg/kg of body weight. Aspartame has a relative sweetness of 200 (i.e., 200 times more sweet than table sugar). Sweeteners such as xylitol, mannitol, sorbitol, are sugar alcohols that provide fewer than 4 kilocalories per gram due to lower absorption efficiency in the small intestine; typically, they provide only about 2 kilocalories per gram. These sweeteners are used, for example, in sugarfree chewing gum because they do not promote tooth decay (unlike sugar, honey, or corn syrup). Very high intake of sugar alcohols can cause diarrhea and bloating because of their passage into the large intestine. The relative sweetness values for the three sugar alcohols mentioned above are about 1.0, 0.5, and 0.5. Allulose (also called psicose) is a natural compound found at low levels in plant foods (e.g., figs, jackfruit, raisins) with a sweetness close to that of sucrose (about 2/3 of the sweetness of sucrose) but negligible caloric value (about 0.2 kcal/g). Allulose can also lower activity of some enzymes involved in carbohydrate digestion (e.g., amylase, and disaccharidases such as maltase) and decrease glucose absorption. Thus, it may be beneficial in terms of blood glucose control and decreasing risk of 38

Sucralose (top) is a man-made chlorinated sucrose, about 2.5 times sweeter than aspartame (middle). Aspartame is a man-made dipeptide, two amino acids linked together (aspartate linked to phenylalanine, a methyl ester); it’s about 200 times sweeter than sucrose. Allulose (bottom) is a natural compound with a sweet-ness close to that of sucrose.

hyperglycemia; but allulose may cause discomfort (flatulence, diarrhea) at high doses because the undigested and unabsorbed carbohydrates pass into the colon and are fermented by bacteria.

4.6 Carbohydrate digestion Carbohydrate digestion begins in the mouth during the chewing process with the production of salivary amylase. This enzyme begins the starch breakdown process. The pancreas secretes another amylase into the small intestine, and the pancreatic enzymes continue the digestion of starch polysaccharides and oligosaccharides to the smaller mono- and disaccharide sugars. In the small intestine another group of enzymes called the disaccharidases further breakdown disaccharides into monosaccharides; for example, lactase is a disaccharidase that breaks down the milk sugar lactose into its two component monosaccharides, galactose and glucose. Sucrase, another example of a disaccharidase, breaks down sucrose into glucose and fructose monosaccharides. The sugars are absorbed by the gut cells and ultimately transported to the liver and delivered throughout the body via the bloodstream. The liver (and muscle) can store some glucose as glycogen. Carbohydrates that are not absorbed in the small intestine pass into the large intestine where they can be broken down (fermented) by bacteria. Excessive passage of some carbohydrates into the large intestine can result in the production of gas, bloating, and abdominal discomfort; these are symptoms of intolerance to lactose (discussed further in section 4.8).

4.7 Functions of carbohydrates and dietary fibres There are many different types of carbohydrates in the body and they can have many different functions. Glucose is a major energy source for the body. If a person does not get enough carbohydrates from their diet, the body is able to make glucose (gluconeogenesis, explained further below). If a person gets too much carbohydrate from their diet, glucose can be converted to fatty acids; thus, the extra carbohydrate energy can be stored as fat in the adipocytes (fat cells). If carbohydrate intake is very low, the body can mobilize large amounts of fat from the fat stores to be used as energy (this also occurs in a diabetic 39

Glucose in an important energy source for the body. But there is not much storage capacity for glucose (glycogen) in the body compared to fat storage capacity

who is not controlling the disease well, discussed further in section 4.9). When this large fat mobilization occurs, ketones (also called ketone bodies) are usually produced. Ketones result the from incomplete use of fat for energy; e.g., when fat is mobilized at high rates from the fat stores, it cannot be completely metabolized for energy, and the partial breakdown products that result are the ketones. With very low carbohydrate intake (or metabolic problems such as diabetes, or prolonged exercise or fasting), and once the glycogen stores have been depleted, the body has to make glucose in order to maintain blood plasma glucose levels. A person cannot survive if blood glucose levels are too low. The process that occurs in the body (mostly in the liver) of making glucose from non-carbohydrates is called gluconeogenesis. Fatty acids mobilized from fat stores, or some amino acids derived from protein breakdown (e.g., muscle protein breakdown), can be used to make (genesis) new (neo) glucose, gluconeogenesis. Normally, the insulin secreted by the pancreas after consumption of foods that contain carbohydrate prevents gluconeogenesis; i.e., the body does not need to produce glucose because it’s available from the diet. But with insulin resistance (type 2 diabetes, metabolic syndrome, obesity, topic of section 4.9), gluconeogenesis continues and contributes to abnormally high blood plasma glucose levels. Some drugs such as metformin, used by type 2 diabetics, can help prevent excessive gluconeogenesis. Carbohydrates can have many regulatory functions in cells. Carbohydrate structures on the cell surface are responsible for the different human blood groups A, AB and O (see FIGURE at right). The health benefits of dietary fibers (soluble and insoluble) include their prebiotic effect to promote the growth of beneficial bacteria in the large intestine, and also their contribution to satiety which can result in lower energy intake and better weight management. Insoluble fibers increase the rate of transit through the colon and, along with fluid, help to prevent constipation. Soluble fibers can lower the absorption rates of some nutrients such as glucose (possible benefit for diabetics);7,8 and they can lead to lower LDL cholesterol, for example, by decreasing the absorption of cholesterol and bile acids in the gut.7,8 Some more controversial, possible benefits of dietary fibers may include lower risk of colorectal cancer and lower risk of diverticulosis; both of these potential benefits, however, are suggestions from some studies and not yet scientifically proven.

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The ABO blood is based on cellsurface carbohydrate structures (hexagon shapes). The blood types shown are O (top left), A (top right), B (bottom left), and AB (bottom right). Source: Invictahog 2006

4.8 Potential problems associated with carbohydrates In terms of potential problems and diseases associated with carbohydrates, a few will be examined in this section, and in the next section on diabetes. Lactose intolerance is due to deficiency of the lactase enzyme in the small intestine. The lactase enzyme normally breaks down the milk sugar lactose into its component monosaccharides, glucose and galactose, which are then absorbed by the cells of the small intestine. If there are low levels of lactase in the small intestine, the lactose will continue into the large intestine where it will be fermented by bacteria; this results in production of gas, bloating, and the abdominal discomfort associated with lactose intolerance. Many low lactose dairy products are available for people with lactose intolerance.

ctose ct se en me

cose ctose (norm sit on)

o ct se en me in ctose into er nce res ts in more ctose ferment on cteri in the co on

Figure 4.8.1 Lactose intolerance. See main text for explanation

Another potential problem with dietary carbohydrates is the consumption of too many simple sugars. Some foods such as soft-drinks, e.g., sugarsweetened sodas such as colas, don't contain any nutrients except for sugar and water. This empty calories problem is especially of concern for children who consume large quantities of sugar-sodas or fruit juices because it can lead to excessive energy intake and low intake of other nutrients required for body growth, e.g., protein and fats, as well as some 41

vitamins and minerals that are not present in these drinks. High sugar diets also greatly increased the risk of dental caries, especially from foods that stick to the teeth and result in higher levels of dental acid. Very low carbohydrate diets or ketogenic diets are currently under research for potential health benefits and problems. Some of these diets, for example, have carbohydrate intake well under 25% of total daily calories; the AMDR for carbohydrates is 45 to 65% of total daily calories. Possible health benefits under research include a potential for better blood glucose control in diabetics. Ketogenic diets have already been proven to be of benefit to some epileptics in terms of helping to control the frequency of their seizures. Potential problems of these diets include low intake of fruits and vegetables, one of the food groups with many health benefits. People who follow these very low carb diets are more likely to have high intake of saturated fats from animal products, potentially leading to increased cardiovascular disease risk over the long term. Depending on the level of ketosis, a person following one of these very low carb diets may also experience unpleasant symptoms such as fatigue, dizziness or headache, constipation due to increased dehydration, insomnia, and possibly nausea (see also possible negative effects on kidneys in the calcium section of chapter 8).

4.9 Diabetes Early in Type 2 diabetes disease there is typically an excess of insulin production (hyperinsulinemia), an attempt by the body to compensate for growing resistance to insulin action. But over time (years/decades), insulin production decreases due to pancreatic beta-cell dysfunction and loss of beta-cell mass. Eventually, type 2 diabetics may also require insulin injections to help control blood glucose levels. Insulin injections are required in type 1 diabetes because type 1 diabetics do not produce insulin (or produce extremely low amounts). Type 1 diabetes is often diagnosed in childhood, but can also develop later in life. Most of the diabetics in Canada, and worldwide, are type 2 diabetics, over 90%. There are also other types of diabetes, more rare types including some type 1/2 hybrid forms, and gestational diabetes associated with pregnancy.1,2 There is evidence that both genetic and environmental factors are involved in type 2 and type 1 diabetes. 1,2,6 For type 1, the factors that contribute to autoimmune destruction of insulin-producing 42

pancreatic beta-cells are currently not well understood. For type 2, obesity (especially with visceral adiposity) and low physical activity are major factors, as well as older age. The main objective in the management of type 2 diabetes is to try to keep blood glucose levels as close to normal as possible. Other objectives include controlling atherogenic dyslipidemias such as high serum cholesterol, high serum fasting triglycerides, and other cardiovascular risk factors such as hypertension.3,5,9 Two of the most common recommendations are to increase physical activity and to decrease caloric intake; both of these will help promote weight loss.5,6,10 Because of the increased risk of cardiovascular diseases, there are also common recommendations to decrease intake of saturated fats from animal products, and increase foods containing omega-3, as well as increase consumption of plant foods.6,9,12 Often the diabetic is also instructed to distribute carbohydrate-rich foods over several daily meals, rather than combining them into one or two meals. Other dietary recommendations include avoiding foods that contain simple sugars, especially drinks such as sugar-sweetened sodas and fruit juices;4 the recommendation, which applies both to diabetics and the general population, is for complex carbohydrates. The diabetic may also be instructed about the glycemic index (GI, section 4.10) of foods, and given information on low GI foods and an overall low glycemic load. Overall, the nutritional recommendations for a type 2 diabetic adult are not very different from those for the general Canadian adult population.

4.10 Glycemic index of foods Glycemic index and glycemic load both relate to the potential of a food to increase blood glucose after it is consumed. Glycemic index GI is a measure of the extent to which consumption of a food can increase blood glucose. More technically, GI is defined as the relative area under the curve (AUC) of glucose concentration after food intake. The figure shows a graph of plasma glucose concentration on the Y axis, and time in hours on the X axis. The red curve represents a high glycemic index food, and the green curve represents a low glycemic index food. The colored area is the AUC that is used to calculate the glycemic index. GI is a relative index because it involves comparison of a food-serving that contains 50 grams of digestible carbohydrate with 50 grams of a standard food, which is typically either glucose or white bread. Foods with glycemic indexes 43

Glycemic index for two foods represented by red (high GI) and green (low GI) curves. There is a greater increase in plasma glucose concentration about 45 minutes after consumption of the high GI food (e.g., white bread) compared to consumption of the low GI food (e.g., beans).

around 55 and lower are considered low GI foods; and those 70 or higher are considered high GI foods. Glycemic load GL is a combination of the GI and the amount of carbohydrate in a food. For example, a slice of bread has a GI of 70 and contains about 15 grams of carbohydrate. The glycemic load is calculated by multiplying 70 by 15 (and dividing by a constant factor, 100). The GL for a slice of bread, thus, is about 10.5; and for two slices, it would be double, 21. Different varieties of the same plant food can have different GI numbers; for example, white bread is typically classified as a high GI food, whole wheat bread as intermediate GI, and a heavy rough-grain bread as a low GI food (TABLE 4.10.1). Similar differences in GI are found for different types of rice (e.g., short-grain vs. long-grain) and potato varieties (e.g., Russet baking potatoes vs. red-skin potatoes).

TABLE 4.10.1 Examples of glycemic indices for some common foods. Low GI is 55 or less; 70 or greater is classified as high GI. 55 or less 56-69 70 or more rough-grain bread

whole-wheat bread

white bread (highly refined flour)

converted (parboiled) rice

basmati/brown rice

short-grain or instant rice

legumes

Banana (depends on ripeness)

watermelon

plain yogurt

Popcorn, red-skin potatoes

Russet potatoes

yams

pineapple

doughnuts

There are some problems and controversies associated with glycemic index. One of the issues is that the GI scale applies to single foods, and not to the food combinations that are typical of meals where interactions 44

Fresh figs (right) and dried figs (left) have a glycemic index of about 50 and 60, respectively.

among different foods could potentially affect the GI and GL. Another issue is the variability among different individuals in terms of how the same food can affect blood glucose levels. Glycemic indexes represent averages from studies done on different subjects. Another potential problem may occur if a diabetic is too focused on GI and ignores other important dietary recommendations such as total caloric intake, dietary fiber, or intake of some types of fats that could increase risk of cardiovascular disease; this distraction may also represent a problem for some people.

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Chapter 5 Dietary Protein, amino acids, and functions of body proteins

Some rich sources of protein: meats, fish, and nuts

5.1 Introduction and main questions In this chapter, dietary protein and its digestion to amino acids is examined. The amino acids are then used by the cells to make body proteins. A few of the many functions of body proteins are also examined. The following are some of the main questions for this chapter: · What are amino acids and which ones are essential nutrients? · What are the best food sources for protein? · How is protein digested by the body? · How are proteins made in the cells and how do they function in the body? · What are some problems and diseases associated with amino acids and proteins? 46

5.2 Amino acids Proteins are chains of amino acids, also called polypeptides; hundreds of amino acids may be linked together. The term peptide typically refers to shorter sequences of amino acids. A tripeptide, for example, is three amino acids linked together. In the body, there are about 20 standard amino acids used as building blocks in the production of proteins (and other amino acids that are not proteinogenic). Nine of these 20 proteinogenic amino acids are classified as essential nutrients; i.e., they cannot be made in sufficient quantities to meet body needs and must be obtained from the diet. These nine essential amino acids are isoleucine, leucine, methionine, phenylalanine, tryptophan, valine, threonine, lysine, and histidine. The other eleven amino acids can be made by the body, typically in quantities that are sufficient to meet body needs; but a deficiency of essential amino acids or some other metabolic problems and diseases can turn a nonessential amino acid into an essential one.

FIGURE 5.1 Protein primary structure is the sequence of amino acids in a polypeptide chain. Each amino acid differs in the composition of the R group. Structurally, the two most simple amino acids are glycine (Gly, G, R=H) and alanine (A, Ala, R=CH3)

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The linear chain of amino acids is referred to as the primary structure of the protein. This linear chain sometimes adopts a helical conformation (or other 2-dimensional conformations, see margin Figure in section 5.6) that is referred to as secondary structure. The tertiary structure of a protein is its 3-dimensional configuration: the folding of the secondary structures as well as bonds and covalent linkages between amino acids (examples in section 5.6). Each amino acid has a common structure consisting of a central carbon linked to an amino group, to a carboxylic acid group, to a hydrogen, and to an R group (Figure 5.1.1).

5.3 Food sources of protein and recommended intakes Foods that are rich in protein include animal products such as fish, meat, dairy, and plant products such as nuts, beans (legumes). Recommended daily protein intake for adults is about 0.8 grams per kilogram of body weight (RDA). During periods of body growth, the requirement for protein is higher; for example, it may be about 1.5 g/kg of body weight for a 6month infant. The AMDR (acceptable macronutrient distribution range) for protein is 10 to 35% of total daily calories. The TABLE 5.1 provides some examples of the approximate protein content of selected foods.

TABLE 5.3.1 Approximate protein content of some common foods. Not all protein sources provide the amino acids in the optimal proportions needed by the body; this is the issue of protein quality (section 5.4).

FOOD

PROTEIN (g)

Egg (one, large size chicken egg)

8

Bread (two slices, 75 g)

5

Beans (one serving, 125 mL)

7

Fish (Tuna or Salmon, 100 g)

20

Meat (100 g, chicken breast or beef steak)

30

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Invertebrate animals such as insects and seafood (e.g., shellfish, shrimp) are a source of protein in parts of the world. Fried worms (silkworm larvae, bottom left) and grilled squid (top) are shown here. Cheeses are rich sources of protein (and typically also of fat, saturated fats, bottom right)

Rice or Pasta (100 g dry)

10

Nuts or seeds (100 g)

12

Milk (one cup, 250 mL)

8

Cheese (30 g serving)

7

Tofu (100 g)

8

5.4 Protein quality In terms of meeting body needs for protein, one has to consider not only the quantity of protein consumed but also the quality of protein. Protein quality is a measure of the extent to which the dietary protein meets the body’s needs, and can be obtained and used by the body; to meet body needs, dietary protein must contain all the essential amino acids in the necessary quantities. Different scales or measures of protein quality have been developed over the years. TABLE 5.4.1 shows two such measures, PDCAAS and DIAAS, and the rating of some typical protein food sources.

TABLE 5.4.1 Digestible Indispensable Amino Acid Score (DIAAS) and Protein digestibility-corrected amino acid score (PDCAAS) are two ways of rating protein quality; they involve calculations that take into account the quantities of essential amino acids in foods, and amino acid availability from the digestion of foods. This table shows approximate scores for some foods (DIAAS not available for all).

Food

PDCAAS

Co ’s mi k

1.0

Whey

1.0

Egg

1.0

Beef

0.9

Wheat

0.4

DIAAS

0.4 49

Protein from animal foods typically has a high quality score. (Dried fish shown in picture)

Rice

0.4

Soy

0.9

0.9

Pea

0.9

0.8

Peanut

0.5

Black bean

0.7

0.6

Some foods, especially plant foods, contain low levels of one or more essential amino acids. If those foods are frequently consumed and become major protein sources in the diet, one can avoid deficiency of essential amino acids by specific combinations of such foods to achieve amino acid complementation. Amino acid or protein complementation occurs when two or more foods together in the diet, but not individually, meet the body's needs for essential amino acids. For example, rice is low in the amino acid lysine, but relatively rich in methionine and cysteine; peas are relatively rich in lysine but low in methionine and cysteine. If a person consumes rice with peas, either together or in meals throughout the day, then risk of deficiency of these amino acids is decreased. As shown in TABLE 5.4.2, similar complementation can occur with oats and peas, or rice and beans.

TABLE 5.4.2 The combinations of foods that are limiting in different essential amino acids provide amino acid complementation, and are especially important for vegans to ensure intake of all the essential amino acids in the necessary quantities. Rice with either beans or peas, or peas with either rice or oats, are examples of such complementation from this table.

FOOD

Limiting amino acid(s)

oats

lysine

rice

lysine

black beans

methionine +cysteine

peas

methionine+cysteine 50

Dietary amino acid complementation: two or more foods that together in the diet, but not individually, can meet the body’s needs for essential amino acids. Oats and beans are one such combination.

5.5 Protein digestion The breakdown of dietary protein begins in the acidic environment of the stomach through the action of stomach acid and catalyzed by the pepsin enzyme. Subsequently, other enzymes known as proteases and peptidases produced by the pancreas are secreted into the small intestine; these pancreatic enzymes further breakdown the polypeptides and oligopeptides into smaller pieces. On the surfaces of the cells lining the small intestine there are other peptidases that continue the digestion process, breaking down oligopeptides into smaller peptides, and dipeptides and tripeptides into amino acids. These single amino acids, along with dipeptides and tripeptides, are then internalized by the cells (enterocytes) of the small intestine where further breakdown of small peptides occurs. Ultimately, amino acids obtained from dietary protein are secreted into the bloodstream and available to cells throughout the body for protein synthesis (shown in FIGURE 5.6.1). Protein from the diet is digested (broken down) to its amino acid components. Ultimately, these components end up in the amino acid pools of cells, and can be used by the cells for building body proteins. Alternatively, some of those amino acids in the cells can be used to generate energy, or for glucose production, or for synthesis of fatty acids. All our body proteins are also under constant turnover; some have longer half-lives than others, but ultimately each body protein is broken down to its component amino acids, and then synthesized anew (translation process in FIGURE 5.6.1) from the amino acid pools within the cell. The cell’s amino acid pool is illustrated in FIGURE 5.5.1; the amino acids are represented by different geometric shapes. There are about 21 different amino acids that can be incorporated into body proteins; these are called the proteinogenic amino acids.

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FIGURE 5.5.1 Protein catabolism (breakdown, red arrow) and anabolism (buildup, green arrow) is catalyzed by enzymes in the cells of the body. Dietary protein is digested and the dietary amino acids ultimately enter the amino acid pools within cells of the body (thick red arrow); breakdown of body proteins (thin red arrow) is always occurring, and most of those amino acids can also be salvaged. The cells use the pools of amino acids to build new body proteins (thick green arrow). Amino acids can also be used for other purposes (blue arrow) such as energy production or synthesis of nitrogen-containing metabolites.

5.6 Functions of body proteins The proteins made by the body (the ones synthesized in the cells) can have a range of different functions. Protein structure is very important for many of these functions. If the protein does not adopt a normal 3-dimensional structure, its function may be compromised. Some functions of body proteins include (a) enzymatic and (b) hormonal activities, (c) structure, (d) growth, and (e) maintenance of the body, (f) immune activities and (g) blood clotting, (h) acid base and (i) fluid balance in the body, (j) muscle contraction and body movement, (k) transport of nutrients such as vitamins, minerals, and lipids in the bloodstream. (l) Amino acids can also be sources of energy for cells. The sequence of amino acids in the protein chain is ultimately dependent on the information coded in our genes (DNA). FIGURE 5.6.1 shows transcription of the genetic information from DNA to messenger RNA (mRNA). The codons (three base sequences) in the mRNA are then translated by the ribosome to form the polypeptide. Each three-base 52

3D structure of the circulatory vitamin A carrier protein: the red helix and yellow arrows represent protein secondary structures; vitamin A is the solid bubble shape inside the protein

codon is recognized by a transfer RNA (tRNA, not shown in the figure) that carries with it a specific amino acid; the ribosome links the amino acids that are sequentially brought in by the tRNAs. The polypeptide chain grows based on the mRNA sequence until the mRNA is fully translated; then all the amino acids will have been added to the protein chain. The protein is then released from the ribosome, and undergoes folding into its normal 3dimensional structure, and possible post-translational modifications, in the cell. The result is the mature protein, and it may be exported from the cell as shown in the figure. Functional complexes of different proteins may form; this is referred to as the quaternary structure level. If there is a genetic mutation, an abnormal base in the DNA sequence, that mutation will be transcribed to the mRNA and may result in the wrong amino acid being incorporated into the protein structure during translation. Such a mutant or abnormal protein may not fold properly, and may not have normal function. In the last part of this chapter, some examples related to this problem will be presented.

FIGURE 5.6.1 Protein synthesis in the cells of the body. The genetic information is transcribed and translated to yield a polypeptide chain of amino acids. The linear amino acid sequence (primary structure) is ultimately based on the sequence of AGTC bases in the genes (DNA).

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5.7 Problems and diseases associated with proteins and amino acids There are many problems and diseases associated with proteins and amino acids, and a few of these are summarized in this section. In terms of protein intake, very high or very low intakes can be problematic as detailed below. One interesting aspect of current research on dietary protein is the relationship between energy balance and the dietary ratios of essential amino acids.2 With very high protein intake, there may be problems related to (a) excessive calcium loss from the body, (b) potential stress on the kidneys, especially for long term diabetics, and especially in cases where people take protein and or amino acid supplements (as opposed to obtaining all protein from foods), and (c) over the long term, increased risk of some cardiovascular and other chronic diseases if the high protein intake involves high meat animal product consumption.4-6 Very low protein intake may increase bone loss and loss of muscle; this is an area of current research. In developing countries, there are cases of severe protein-energy malnutrition. Two examples of this are kwashiorkor and marasmus. Kwashiorkor refers to severe protein deficiency coupled with a mild energy deficiency; there is some fat storage in the body from the carbohydrate and fat intake.1 Marasmus is a severe deficiency of both protein and energy; the body is emaciated, and fat stores depleted.1 Both kwashiorkor and marasmus impair body growth in children, and increase risk of infections and of a range of other health problems. A more moderate deficiency of essential amino acids, especially in early childhood, is a relatively common, global nutritional deficiency.7 In phenylketonuria, PKU, genetic mutations result in the loss of function of an enzyme, phenylalanine hydroxylase, that normally catalyzes the conversion of phenylalanine to tyrosine; tyrosine becomes an essential amino acid. These genetic mutations result in abnormal enzyme structures which cannot efficiently catalyze the conversion of phenylalanine to tyrosine; and as a result, phenylalanine and toxic metabolites of phenylalanine build up in the body.3 If an infant with a PKU genetic mutation is not given a phenylalanine-reduced diet, these toxic metabolites will damage the brain and may result in a range of problems including severe intellectual disability and epileptic seizures. 54

Fast-foods such as hamburgers and hot dogs are rich sources of protein, but are also high in saturated fats

Children with Kwashiorkor (left) and marasmus (right) Source: Center for Disease Control and Prevention, USA: L. Conrad 1960s (left), D. Eddins 1972 (right)

A common feature of PKU is microcephaly, an abnormally small head. Source: National Institutes of Health, USA, 2008

The final example of the importance of normal protein structure for the function of our body and our cells is sickle cell anemia. In this disease, there are genetic mutations that result in an abnormal hemoglobin protein. Hemoglobin is the oxygen carrier protein in our red blood cells (erythrocytes). The mutant hemoglobin does not adopt a normal protein structure, and results in an abnormal shape of the red blood cells that are filled with hemoglobin. People with sickle cell anemia experience many health problems related to lysis or breakage of red blood cells, and to obstruction of blood vessels by the sickle-shaped red blood cells.

55

FIGURE 5.7.1 Sickle cell anemia is due to genetic mutations that affect hemoglobin structure and, thus, affect red blood cell (erythrocyte) shape. Source: National Heart, Lung, and Blood Institute, USA (NHLBI 2011).

56

Chapter 6 Plant foods and phytochemicals

Plant foods including the spices shown above are sources of phytochemicals

6.1 Introduction and main objectives This chapter covers the topics of plant foods and vegetarianism, as well as some of the non-nutrient substances in plants that may have health benefits—the phytochemicals. The following are some of the main objectives for this chapter: ● Understand the different types of vegetarianism and their related health benefits as well as possible concerns. ● Become familiar with some dietary phytochemicals and their related health benefits, as well as possible concerns such as antinutrient activity.

57

6.2 Vegetarianism Vegetarianism refers to a dietary emphasis on plant foods. A person may be a vegetarian because of their ethnic and cultural background, or for health-improvement reasons, or for ethical reasons, or a combination of these. In terms of potential health benefits, diets that are rich in plant foods have been associated with lower risk of several chronic diseases including cardiovascular and some types of cancer.20-23,25 The reasons for this association between plant foods and health are under research. Possible health benefits of vegetables, fruits, spices, teas and other plant foods include increased nutrient density for many minerals and vitamins, increased dietary fiber intake, lower intake of saturated fats and meats, and the possible benefits of many phytochemicals present in plant foods, as well as the products of phytochemical fermentation or metabolism by gut bacteria (see Kimchi FIGURE in section 6.5). Typically, several different species of beneficial bacteria and other microbes live in the adult large intestine (colon); this is a major part of the body’s microbiome. The action of these gut bacteria upon food components (fermentation) can lead to the production of potentially beneficial substances, especially the fermentation of plant food components. For example, some dietary fibers are fermented to yield short-chain fatty acids that can be absorbed into the body and may have health benefits.1,7-9,24 Other potentially beneficial substances produced by gut bacteria include vitamin K and several B vitamins including biotin and folate.

Bacteria in the colon (a major part of the gut microbiome) can ferment (metabolize) food components, e.g., convert glucosinolates (abundant in cabbage, broccoli) into sulforaphane (S, upper chemical), or convert dietary fibre into butyrate (B, lower chemical) and other shortchain fatty acids. There is evidence for health benefits of both S and B in the body.

There are different types of vegetarianism. The strictest form is veganism; a person who is vegan does not consume any products of animal origin. Semi-vegetarianism can include some animal products but typically does not include meats; for example, a lacto-ovo-vegetarian consumes mostly plant foods but also includes dairy products (lacto) and eggs (ovo). In terms of some nutrient deficiencies, vegans are most at risk, especially if they do not take supplements or foods enriched in some vitamins and minerals (typically those vitamins and minerals that are most abundant in animal products). Vegans are at higher risk of deficiency for minerals such as zinc, calcium, and iron, and for vitamins such as B12 and D, and for the longer forms of omega-3 fatty acids: DHA and EPA.2,10-13,26 Vegans should also emphasize high protein plant foods such as legumes, nuts, and especially those with high protein-quality such as soy. Vegans should choose food combinations that provide complementation of essential 58

A pescatarian is a vegetarian who also includes fish and seafood, two rich sources of DHA and EPA omega-3 fatty acids

amino acids, for example, beans and rice, peas and rice, corn and beans (as discussed in the chapter on protein). These considerations in terms of micronutrient and protein sufficiency are especially important during periods of growth, e.g., for children, adolescents, and during pregnancy and lactation.

6.3 Phytochemicals Phytochemicals are substances produced by plants, phyto means plant. This term is most often used to refer to non-nutrient components of plants and plant foods that may have health benefits. Thousands of different phytochemicals are known at present, and some of them are currently under research for possible health benefits.3-7 At the molecular and cellular level, in the body, some phytochemicals can influence hormone action, others have antioxidant activity; current research suggests that many different cell functions can be affected by phytochemicals. The results of some laboratory biochemical and cellular studies, however, may not necessarily be applicable to the human whole-body context (to human physiology and pathology) because some phytochemicals are not efficiently absorbed in the digestive tract; i.e., some phytochemicals have low bio-availability and, even if absorbed, maybe be rapidly metabolized or eliminated from the body. How can a person increase dietary intake of phytochemicals? The main recommendation is to increase consumption of plant foods: fruits and vegetables, legumes, grain products, herbs and spices, teas and other plant-based drinks. Use of supplements (e.g., pill form) is less often recommended.14,15 There is a greater risk of toxicity with some supplements (especially hepatotoxicity with some herbal supplements), and possible interference with prescription drugs. For example, Saint John’s wort is a plant commonly available as a herbal supplement that some people take for mental well-being, e.g., as an antidepressant; it's possible benefits in this context are still under research, but it may cause serious health problems because it is known to interfere with a wide range of other, physician-prescribed medications. Also, in the preparation of some extracts of the plants, some phytochemicals may be lost; i.e., more phytochemicals are present in the whole plant or whole food compared to an extract. There are many plant supplements and phytochemical extracts available in pharmacies, supermarkets, specialty stores and also online; but many of the claims made about their health benefits have not been 59

To increase intake of phytochemicals and benefit from their possible health effects, intake from plant foods is often recommended over the use of supplements

Anthocyanins are a type of flavonoid abundant in some berries, e.g., blueberries (top left) and aronia, also in other red-purple plant foods such as red cabbage (top right), purple corn, black rice, eggplant, red grapes. Anthocyanindin structure is shown.

scientifically proven, e.g., not verified through double-blind placebocontrolled human intervention studies. Some examples of phytochemical groups are shown, as well as some research directions for these phytochemicals. The phytoestrogens are a group of phytochemicals that can be derived from multiple sources. The isoflavone class of phytoestrogens is abundant in soy and products (more details in section 6.4) such as tofu; the lignan class of phytoestrogens is especially abundant in some types of seeds such as sesame and flax. The flavonoids are a large class of phytochemicals widely distributed among plant foods; some flavonoids are abundant in red purple fruits such grapes, blueberries and other berries (see margin FIGURE on previous page). There are also many different types of carotenoids in plant foods. The red color of tomatoes is due to the carotenoid lycopene; and beta-carotene is responsible for the orange color of many fruits and vegetables such cantaloupe, carrots, and pumpkin. Beta-carotene is also a potential source of vitamin A (examined in the chapter on vitamins). Organosulfur compounds are abundant in the garlic-onion family (includes chives, and shallots) and in the cabbage family (includes also kale, broccoli, cauliflower, bok choi, rapini, and mustard greens) of plant foods. Glucosinolates and their microbiome conversion products such as sulforaphane are shown in the margin FIGURE of section 6.2.

Rapini (above) is a member of the cabbage family, and a source of many vitamins and minerals, especially rich in vitamin K. Sea buckthorn berries (lower, Hyppophae rhamoides) are consumed in some parts of northern Europe and Asia. Oils can be extracted from the berries; the seed oil is rich in omega-3 fatty acids (alpha-linolenic acid).

6.4 Soy Soy foods can be sources of phytoestrogens, phytochemicals that may have health benefits.3 Research is ongoing into possible health benefits of soy foods, e.g., in terms of lower risk of some cardiovascular diseases and perhaps also protection against some types of cancer. Another potential benefit is that soy foods are typically a rich source of high-quality protein. Very high consumption of soy products can have some possible negative effects; for example, some of the substances in soy foods can interfere with absorption of mineral micronutrients (antinutrients, a topic examined further in section 6.5). With very high intake, some other soy components can interfere with normal thyroid function;16 and very high intake is not recommended for women who have breast cancer because the phytoestrogens may increase the growth of some types of breast cancer cells; although this issue remains controversial.17-19 Soy can also induce an allergic reaction in some people. 60

Genistein (top) and daidzein (middle) are two phytoestrogens abundant in soy and other legumes. Some people have bacterial species as part of their gut microbiome that can convert daidzein into equol (lower structures), with possible health benefits.

6.5 Antinutrients Antinutrients are substances that interfere with nutrient absorption. Some examples of antinutrients in plant foods are as follows. Phytic acid (also called phytate, structure in FIGURE at right) is abundant in many different plant seeds, for example, soy and other legumes; it can bind some minerals such as calcium, iron, zinc, magnesium, and prevent their absorption. 2 Oxalic acid (oxalate) can also bind some minerals such as calcium and lower absorption from foods such as spinach, rhubarb, and members of the cabbage family including broccoli and cauliflower. Some plant foods especially legumes have enzyme inhibitors that can decrease the enzymatic digestion of starches and proteins, for example, amylase and protease inhibitors, respectively. Lectins, carbohydrate-binding proteins that are wide-spread in many plant foods, may interfere with absorption of nutrients including some minerals. Other examples of antinutrients include the egg white protein avidin which binds the vitamin biotin very tightly and prevents its absorption (i.e., avidin is an anti-vitamin); glucosinolates abundant in cabbage family (see section 6.2) foods can lower iodine absorption; flavonoids, widespread in fruits and vegetables, tea and other plant foods (see section 6.3), can lower absorption of some minerals such as iron and zinc, and also interfere with enzymatic digestion.

Phytic acid found in foods such as oats, beans, and cereals, legumes (plants seeds) can lower the absorption of dietary minerals.

Food traditions in some cultures involve fermentation of plant foods such as soy and other legumes, cabbage, and cassava; such fermentation can lower levels of some antinutrients,1 and decrease the risk of developing nutrient deficiencies. Fermentation by microbes such as bacteria and fungi may also produce some beneficial phytochemicals. Toxins may also be produced especially if harmful strains of microbes get established during the fermentation process. Kimchi is a fermented cabbage product, and a source of probiotics— bacteria and other microbes that are potentially beneficial for gut health.

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Chapter 7 Vitamins

7.1 Introduction and main questions The micronutrients will now be examined, beginning with vitamins. Vitamins were discovered in the first half of the 20th century; they are organic (made from carbon; in contrast, minerals are referred to as inorganic) micronutrients required for reproduction, development, growth, and maintenance of many body functions. Deficiency of vitamins can increase the risk of some chronic diseases. Towards the end of this chapter there will be a brief presentation of nutrition and cancer risk. The following are some of the main questions for this chapter: ● For each vitamin, what are some of the best food sources? what are some of the main physiological functions? what can happen with chronic deficiency? what can happen with excessive intake? Vitamins help control many processes in the body. They can help regulate the expression of genes, and can function as coenzymes to help enzymes carry out their catalytic functions. Often the form of the vitamin that 62

performs biological activities in the cell is not the same as the food form of the vitamin; chemical changes (metabolism) to the vitamin structure may be required for activation. Vitamins are often divided into two categories: (a) the fat-soluble (lipophilic) vitamins A, D, E, K, and (b) the water-soluble (hydrophilic) vitamin C, and the B vitamins. Many of the B vitamins are important for energy production and their requirement (DRIs such as RDA or AI) can be expressed per 1000 kilocalories consumed; these B vitamins are not themselves sources of energy but are required for cells to get energy from the macronutrients. Recommended intakes for the vitamins are given in APPENDIX A.

FIGURE 7.1.1 Schematic representation of the transport and metabolic events that some vitamins undergo during the conversion of their food forms to their active forms which can affect many functions of cells.

7.2 Vitamin A Vitamin A was the first vitamin to be discovered. Different forms of vitamin A can be referred to as retinoids; for example, retinol is typically the form that is most often called vitamin A. Other retinoids include retinal and retinoic acid; the possible conversions among these three retinoids are shown in the figure along with the structure of retinol. In addition to retinoids, Vitamin A can also be derived from some carotenoids such as beta-carotene; these can be converted in the human gut to retinoids but typically the conversion is not very efficient. In terms of the intakes for vitamin A, typically 700 to 900 retinol activity equivalents, RAE, are recommended for women and men, respectively. One RAE equals one microgram of retinol, and about 12 micrograms of beta-carotene.

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Oxidation of retinol to retinal and further to retinoic acid. Structure of retinol is shown

Major dietary sources of beta-carotene and other provitamin A carotenoids include plant foods such as carrots sweet potatoes, pumpkin (figure at right), cantaloupe, apricots, and green leafy vegetables such as spinach and some types of cabbage such as kale. Dietary retinoids, in contrast, are derived mainly from animal products including meats and especially organ meats such as liver, eggs, and fortified milk and other fortified dairy products. The Canadian diet is typically sufficient in vitamin A especially if a person includes some of the fortified foods and carotenoid rich foods; deficiency is rare. The conversion and absorption of dietary carotenoids depend on the bodies need for vitamin A; absorption from cooked foods is more efficient because the heat helps to release carotenoids from the plant foods.

FIGURE 7.2.1 Overview of the processes of retinoid transport and conversion. Provitamin A carotenoids present in foods can be converted to retinol in the gut; and the retinol as well as retinyl esters (retinol linked to a fatty acid, R-FA) are loaded into chylomicrons along with other dietary lipids. Most of these chylomicron retinoids are delivered to the liver for storage. The liver releases retinoids into the circulation bound to specific carrier proteins as well as VLDL lipoproteins. Cells throughout the body can take up the retinol and convert it to other bioactive retinoids such as retinoic acid and retinal.

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Biologically active forms of vitamin A include retinal which is important for light absorption and the process of vision in the eye, and retinoic acid which can help control the expression of many genes. Regulation of gene expression accounts for many effects of retinoids related to health and disease. Vitamin A deficiency can result from chronic low intake, a problem that has been observed in some developing countries especially with children. Secondary deficiency Vitamin A can occur even with normal dietary intake if there is a problem with storage or mobilization of the vitamin, for example with some liver diseases. Vitamin A deficiency contributes to diseases such as xerophthalmia (dry eye) which may increase risk of infections and lead to blindness, mainly observed in developing countries. Many other problems can result from vitamin A deficiency including lower immune function, abnormal structure and function of epithelial tissues such as skin and mucous membranes that line the gastrointestinal tract, as well as problems related to reproduction and embryonic development.20,21 Toxic effects of high vitamin A intake include developmental malformations of the fetus during pregnancy;16-17 this has been observed with high intake of the retinoid form Vitamin A, not the carotenoids (the body controls carotenoid to retinoid conversion depending on the need for vitamin A). Intake above the upper limit UL (3000 micrograms of retinol/day) can be toxic to the liver, skin, bone, and other organs.

7.3 Vitamin D Vitamin D (calciferols, D2 and D3 forms) is sometimes called the sunshine vitamin because we can make it (D3) in our skin if we are exposed to sunlight; in Canada, there is most potential for vitamin D production in sunexposed skin between April and August. There are not many natural dietary sources of vitamin D; fish such as salmon, tuna, sardines, are one of the richest natural sources (D3). Some mushrooms can be a source of vitamin D (mainly the D2, some D3) if they are exposed to ultraviolet light during growth. The other main dietary sources in the typical Canadian diet are vitamin D-fortified foods (D3), foods to which vitamin D has been added, such as margarine, butter, milk, yogurt, and other dairy products.

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Cholecalciferol, vitamin D3 (structure, lower figure). Milk is usually fortified with vitamins D and A (milk food label shown above); one serving provides 45% and 10%, respectively.

FIGURE 7.3.1 Vitamin D3, cholecalciferol, is our main source of vitamin D from foods and from sun/UV light exposure. In the body D3 undergoes hydroxylation, a kind of chemical activation, in the liver and in the kidneys; dihydroxy D3 is the form with most biological activities.

Vitamin D can function in the body as a hormone. It can help regulate the expression of many genes in the cell; and this action is responsible for many of its functions in the body including roles in maintaining the health of the nervous system, immune system, and skeletal system. Many of these functions are currently under research. Vitamin D is very important for maintaining bone health and can promote increased calcium absorption in the gut. Deficiency of vitamin D Can result in bone diseases such as rickets in children, and osteomalacia in adults (soft bones). Deficiency can develop if there is low dietary intake and low sun exposure. Sunscreens contain chemicals that block UV light, for example SPF 15 blocks about 99% of UV light; while this can help lower the risk of skin cancer, it also prevents vitamin D production in the skin. People with darker skin produce less vitamin D upon similar exposure to sunlight compared to a light-skinned person. Dietary vitamin D is absorbed with other dietary lipids and deficiency can result from very-low-fat diets. Deficiency can also occur in people who have some types of liver disease that effects activation of vitamin D3. Excessive intake of vitamin D3 (most likely to occur from supplements) can be toxic to the body; at extremely high levels it can result in calcification 66

Rickets image from 1920 showing bowing of the femur in two of the children

and damage to many tissues and organs in the body including the kidneys. The adult UL tolerable upper intake level in most countries is about 100 micrograms per day.

7.4 Vitamin K Vitamin K is widespread among plant foods and especially abundant in green leafy vegetables such as spinach, kale and other members of the cabbage family. These plant foods contain mainly the K1 phylloquinone form; and typically only about 10 or 20% of the K1 present in these foods is absorbed by the body. Animal products such as meats, cheeses and other dairy, eggs, seafood, and others contain the K2 or menaquinone form; K2 is also produced by bacteria in the large intestine. Vitamin K can have multiple functions and some of these are currently under research. The best-known function of vitamin K is its participation in the complex process of blood clotting. Deficiency of vitamin K increases risk of hemorrhage (abnormal bleeding). Deficiency, however, is rare because it is widespread in foods and because it is recycled and reused in cells. Newborns are at greatest risk of deficiency and hemorrhage because of the low transfer of vitamin K to the fetus during gestation and the low levels of vitamin K available to the infant in breast milk. Also, the large intestine of newborns is not yet colonized by bacteria; and, hence, that potential source is not available.

Vitamin K1, phylloquinone

Vitamin K is necessary for blood clotting; deficiency increases risk or haemorrhage

7.5 Vitamin E Vitamin E is a term that refers to several different forms of tocopherols and tocotrienols. The RDA for vitamin E is expressed in milligrams (not micrograms), 15 milligrams per day for adults. Major dietary sources of vitamin E are the plant oils (about 10-40 mg/100 g), as well as nuts and whole grain foods, avocados, and some vegetables such as spinach and cauliflower. Compared to these two vegetables, animal products such as fish, butter, eggs have about the same amount (1-2 mg/100 g). Gammatocopherol form of vitamin E is the most abundant in the typical Canadian diet; alpha-tocopherol, also abundant in the diet, is the form with the highest vitamin E activity. 67

Vitamin E: tocopherols (saturated side chain, general structure shown at top, different R-group forms: e.g., RRR alpha-tocopherol (middle) with 3 chiral points - - - -) and tocotrienols (unsaturated side chain, forms differ in the R-group, bottom structure)

Vitamin E functions as an antioxidant in lipid environments such as lipoproteins and cell membranes (FIGURE 7.5.1); it can neutralize free radicals and prevent some of the damage they can cause in the body. Vitamin E may have other functions through its effects on gene expression and enzyme activity under research. Vitamin E deficiency can result in increased oxidative damage. Vitamin E supplementation has been studied in the context of lowering risk for some diseases such as cancer, Alzheimer's and dementias, coronary heart disease, and some eye diseases; but the research has not produced conclusive evidence of benefit. There is some evidence of the benefit of supplementation in cases of non-alcoholic fatty liver diseases (NAFLD).

FIGURE 7.5.1 Upper figure shows vitamin E in the cell membrane where it can neutralize free radicals and prevent damage to membrane lipids. Lower figure shows vitamin E neutralizing a free radical (X● neutralized to HX). In this process, tocopherol itself becomes a free radical (tocopheryl radical as indicated by O●). Vitamin C (and other antioxidants, e.g., vitamin A and ubiquinol CoQ10) can regenerate tocopherol as shown.

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Vitamin E toxicity appears to be low; high intake levels, 20 times RDA, may be problematic for people taking some medications. The recent trend of vaping has resulted in some cases of serious injury to the lungs; and high levels a vitamin E acetate added to the vaping liquids may be involved in this lung injury.

7.6 Vitamin C Vitamin C is the first of the water-soluble vitamins to be examined in this chapter. Vitamin C is also an antioxidant and it protects the aqueous or water environments of the body such as the cytoplasm of the cell and the blood plasma. The major dietary sources of vitamin C are fruits and vegetables such as red sweet peppers, kale and other members of the cabbage family, some berries such as blackcurrants, and oranges and other citrus fruits.

FIGURE 7.6.1 Vitamin C is also known as ascorbic acid; this is the reduced form. When ascorbic acid, for example, reactivates vitamin E (changes the tocopheryl radical back to tocopherol, as shown in FIGURE 7.5.1) it becomes converted to dehydroascorbic acid; this oxidized form can then be converted in the body back to ascorbic acid. Smoking increases oxidative stress and lowers ascorbic acid levels; thus, the recommended intake for smokers is higher (see note in Appendix A).

Vitamin C can function as an antioxidant and also as a coenzyme (enzyme helper) in other body processes such as collagen formation (FIGURE 7.6.2), and production of dopamine (neurotransmitter) and carnitine (for fatty acid metabolism), both essential factors for normal body function. Although vitamin C is one of the most common dietary supplements, its role in possible protection against cardiovascular diseases, cancers, dementia, and the viruses that cause common colds, is not proven. 69

Vitamin C helps maintain structure of connective tissue (collagen), and severe long-term deficiency results in poor wound healing, bleeding gums, and other symptoms of scurvy. Source: Center for Disease Control and Prevention, USA

James Lind in 1753 showed that citrus fruits could prevent scurvy, one of the first controlled experiments in the world (medical)

Vitamin C toxicity appears to be low; excess can be excreted in the urine. Currently, the adult tolerable upper intake level is about 2 grams (2000 milligrams) per day; some studies, however, suggest possible problems with intakes above 500 milligrams per day (under research). As will be examined in the chapter on minerals, Vitamin C helps keep some minerals in a form (reduced) in which their absorption is most efficient; thus, for example, high intake can contribute to iron overload in the body (more details in chapter 8).

FIGURE 7.6.2 Among other functions, vitamin C promotes the synthesis and crosslinkage of collagen fibrils (as shown in this figure) that is necessary for normal structure of scar tissue, blood vessels, cartilage (connective tissues).

7.7 Oxidative stress and antioxidants After examining two antioxidant vitamins, C and E, this section provides more general information on oxidative stress and antioxidants. As shown in the margin FIGURE at right, the body is always producing free radicals and other reactive chemical species, e.g., reactive oxygen species (ROS), as part of energy metabolism (step 1 in figure). Environmental exposure to smoke, radiation (including UV light), heavy metals and some other contaminants can increase ROS production. ROS and other highly reactive chemicals can cause oxidative damage in the cells and tissues of the body. Such damage over the long term can increase risk of some chronic diseases, and contributes to aging.9,10 The body has several lines of defense against this damage: dietary antioxidants such as vitamins C and E, as well as flavonoids and other phytochemicals, can help decrease some of the damage cause by ROS and other reactive chemicals (step 2 in figure); there are also endogenous antioxidants made by the body such as glutathione, and various proteins including the blood iron-carrier transferrin (more details in the chapter on minerals) and intracellular selenium-enzymes such as glutathione peroxidase, that can help lower some of this damage (step 3 in figure). 70

Despite all these antioxidants, damage cannot be fully prevented; and there is another line of defense that can help lower the risk of some health problems related to this damage: repair of damage (step 4 in figure), e.g., repair of DNA, the genetic material in the cells of the body.

Oxygen in the air causes browning (oxidation) of an apple over time (bottom part), compare with the white, freshly cut part (top). Oxidation reactions also occur in the body

7.8 Thiamine and Riboflavin Thiamine (vitamin B1) is found in foods such as whole grain products and enriched cereals, pork and other meats, as well as some vegetables and fruits. Thiamine pyrophosphate (TPP) is the active form, a coenzyme for many metabolic reactions in the body. TPP is necessary for cells to obtain energy from dietary carbohydrates. Thiamine deficiency is rare in Canada; chronic deficiency results in beriberi, a fatal disease characterized by muscle weakness (including cardiac insufficiency) and degeneration of the nerves.

A person suffering from beriberi, a form of severe thiamine deficiency. Source: People and Food (1951) A. Virtanen, P. Roine.

FIGURE 7.8.1 Structure of a thiamin riboswitch. This complex of RNA and TTP (central structure between RNA strands) can regulate gene expression in many organisms

Riboflavin (vitamin B2, usually examined with the water-soluble group of vitamins despite low water solubility) is abundant in many plant foods such as green leafy vegetables, legumes and nuts, and many animal products including dairy. Flavin adenine dinucleotide, FAD, and flavin mononucleotide, FMN, are two active forms of riboflavin; they also participate in many metabolic reactions as coenzymes, for example, energy production in the cells. Deficiency of riboflavin compromises cellular energy production, and is characterized by neurological and dermatological symptoms. Deficiency of riboflavin is rare in Canada.

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FAD (shown) is a coenzyme involved in many redox metabolic reactions, e.g., conversion of retinol to retinoic acid, and oxidized to reduced glutathione. FMN is also a coenzyme for many reactions, e.g., activation of vitamin B6 (pyridoxal phosphate)

7.9 Niacin Niacin (vitamin B3) is abundant in foods such as peanuts, mushrooms, wheat bran, sunflower seeds, salmon and other fish, poultry and other meats, and fortified foods such as breads and cereals. Nicotinamide adenine dinucleotide (NAD+, and its phosphorylated form NADP+) are active forms of this vitamin that participate as coenzymes in hundreds of metabolic reactions in the body; for example, they are necessary for energy (ATP) production in cells. Chronic niacin deficiency results in skin lesions (FIGURE at right), and neurological symptoms including cognitive dysfunction and dementia; these are characteristic of the disease pellagra. Supplementation with high doses of niacin has been reported to have potentially beneficial effects on plasma lipids, for example, lowers triglycerides and LDL cholesterol; but its use in this respect is limited by potentially harmful side effects including liver toxicity and glucose intolerance. Supplementation with niacinamide has fewer reported harmful side effects, but also does not have the potentially beneficial effects on plasma lipids; niacinamide has been used to treat pellagra and acne. Some niacin can be made in the body from the essential amino acid tryptophan, but typically not enough to meet body needs. A diet highly dependent on corn (maize) increases risk of niacin deficiency because corn has a low tryptophan content and the niacin that is present has low digestibility; alkali treatment of ground corn, a tradition in some cultures when making corn tortillas, increases niacin bioavailability.

Active forms of niacin (top) participate in hundreds of metabolic reactions as coenzymes. Nicotinamide (bottom) also has many of the niacin functions, and fewer toxic side effects when used as a supplement, e.g., to treat pellagra or acne.

Skin lesions on the hands of a person with pellagra.

Source: Dr. J. Babcock (c. 1900), Medical University of South Carolina, USA

7.10 Vitamin B6 Vitamin B6 (pyridoxine and other forms) is abundant in foods such as meats, dairy and other animal products, bananas, watermelon and other fruits and vegetables, dark chocolate and nuts, yeast products and fortified foods such as cereals. Pyridoxal phosphate, PLP, is the active form and functions as a coenzyme, for example, in the synthesis of amino acids, hemoglobin (cf. top margin FIGURE next page), neurotransmitters such as dopamine and adrenaline, production of the vitamin niacin from the amino acid tryptophan, gluconeogenesis, and other metabolic reactions including those involving the dietary mineral selenium and production of selenoproteins in the cells. 72

PLP is a coenzyme for many metabolic reactions in cells, e.g., production of niacin, and in the use of dietary selenium (from selenomethionine, and production of selenoproteins)

Chronic deficiency of Vitamin B6 has many deleterious effects in the body including dermatitis, neurological dysfunction (nerve damage), microcytic hypochromic anemia, and immunodeficiency. Interestingly, long term use of high-dose B6 supplements has also been reported to cause nerve damage.

Human red blood cell (erythrocyte, left), and white blood cell (leukocyte, right). A platelet (thrombocyte) is also shown. Red blood cell are about 7 micrometers wide and each contains more than 200 million oxygen-carrying hemoglobin proteins. Source: National Cancer Institute, USA

7.11 Biotin and Pantothenic acid Deficiency of biotin (vitamin B7) is rare because it’s found in many different foods, and very small amounts are needed for health (about 30 micrograms/day). Some of the foods that are richest in biotin include egg yolks, peanuts and other nuts, liver, cheese, yeast foods, avocado. Biotin can also be produced by the bacteria in the human large intestine; but at present, the extent to which that biotin is available to the cells of the body is not known. Biotin is active when bound to the amino acid lysine in a form called biocytin. As a coenzyme, biotin participates in many metabolic reactions, for example, production of fatty acids, gluconeogenesis, breakdown of carbohydrates and fat for energy, and the metabolism of some branched-chain amino acids. Deficiency of biotin can occur in a few rare genetic diseases, or with the use of medications such as some types of anti-epileptic drugs. The symptoms of deficiency include neurological and dermatological problems.

FIGURE 7.11.1 Structure of coenzyme A, pantothenic acid parts are pantoic acid (3) and beta-alanine (4)

Pantothenic acid (vitamin B5) is also widespread among many food sources both of plant and animal origin. Deficiency is very rare. Pantothenic acid is needed for the production of coenzyme A (CoA) which

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Structures of biotin (top) and biocytin (biotin linked to the amino acid lysine

participates in numerous metabolic reactions; e.g., it's necessary in order to obtain energy from the macronutrients.

7.12 Folate Folate (vitamin B9) is present in foods such as peanuts and other nuts, green leafy vegetables, orange juice, and other fruits and vegetables, also abundant in sunflower seeds, legumes, fish, cheese, poultry and other meats, and especially in animal livers. Folate is a common supplement for women planning pregnancy and in the early stages of pregnancy. Folate deficiency has been associated with an increased risk of birth defects such as spina bifida (incomplete closure of the neural tube) during development.12-15 The recommended intake is about 50% higher for women in the early stages of pregnancy compared to the normal adult RDA (600 micrograms per day versus the normal 400). It's difficult to consume enough foods that will provide the 600 micrograms per day; liver, one of the richest natural food sources, is not a recommended food for frequent consumption during pregnancy because it contains high levels of vitamin A retinoid form, and also accumulates toxins to which the animal may have been exposed. Thus, supplements or folate-fortified foods are recommended in early pregnancy. Tetrahydrofolic acid THFA is the biologically active form of folate, and functions as a coenzyme in many metabolic reactions. THFA, for example, is important for the synthesis of the genetic material DNA and for cell division. Chronic folate deficiency results in slow or defective DNA synthesis and cell division; and this can lead to megaloblastic anemia in which abnormally large immature red blood cells form in the bone marrow; and abnormal cells can be detected in the circulation. Potential toxicity of high doses of folate is under current research and not yet well understood. Animal experiments suggest that very high doses of folate (beyond UL) may also increase risk of birth defects. Moreover, folate supplements may prevent the detection of pernicious anemia, a potentially fatal problem due to long-term vitamin B12 deficiency (more details in section 7.13).

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Structure of folic acid above shows its three parts: glutamic acid (triangle), PABA (circle), and pteridine (rectangle). The folates contain multiple glutamate amino acids (shown below)

Figure 7.12.1 Folate deficiency early in pregnancy can increase risk of birth defects such as spina bifida (neural tube defect as shown in picture). Source: Centers for Disease Control and Prevention, USA

7.13 Vitamin B12 Vitamin B12 is represented by the cobalamins such as methylcobalamin and adenosylcobalamin, the two active forms. Methylcobalamin is important for the production of bioactive folate (THFA) and, hence, also participates in DNA synthesis and cell division; deficiency can result in the folate type of megaloblastic anemia. Chronic vitamin B12 deficiency can result in loss of nerve cell integrity and function, a fatal disease if not treated with vitamin B12. This may be due to insufficient B12 intake, or due to a condition called pernicious anemia that results from loss of intrinsic factor (IF) production. This factor is important for the absorption of vitamin B12 by the cells (enterocytes) of the small intestine. Vitamin B12 is found in most foods of animal origin. B12 can only be produced by bacteria-like organisms; such bacteria colonize the gut of animals and produce the B12 that is found in meats and other animal products (bacteria in the human colon can also produce it but most, if not all, of it is excreted from the body). Deficiency of B12 is not a problem for people who include animal products in their diet. Strict vegetarians such as vegans are at high risk of deficiency; they can decrease this risk by taking B12 supplements or consuming B12-fortified foods or including nutritional yeast in their diet.11 B12 supplements are also often recommended for elderly people because absorption from supplements is more efficient than from foods; and the elderly typically have more problems with stomach acid production (helps release B12 from foods) as well as production of IF.10---7

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Methylcobalamin, an active form of vitamin B12.

FIGURE 7.13.1 Vitamin B12, digestion and absorption.

7.14 Diet and cancer risk The last part of this chapter on vitamins is a brief overview of diet and cancer risk. Cancer is a group of diseases characterized by cells that have escaped normal growth and death controls. These abnormal cells have high rates of cell division (proliferation) and often invade other tissues in the process of metastasis. The development of many cancers—a process also known as carcinogenesis—is influenced both by genetics (heredity, family history of cancer), and by environmental factors including diet. In general, with relation to diet, cancer risk may be influenced by deficiencies of protective nutrients and phytochemicals, and by excesses of harmful substances known as carcinogens. Current research is examining dietary factors that may help decrease the risk of cancer.1-4 People who consume more fruits and vegetables likely have lower risk of some types of cancer.5-8 In terms of specific nutrients, some of the research suggests that ensuring sufficiency of vitamins such as B12 and folate, A and D, C and E, and others, as well as some dietary minerals, phytochemicals, and dietary fiber, may lower risk of some cancers. Harmful substances in the diet may increase the risk of some cancers, 18,19 and this is in the context of genetic factors and family history of cancer. High caloric intake and excessive body fat likely increase risk of some 76

Cancerous lesion of the stomach (adenocarcinoma, upper). Histological analyses of biopsies can differentiate this cancer from a benign stomach ulcer (lower). Risk of most adulthood cancers is influenced by genetic and environmental factors. Source: Ed Uthman MD

cancers. Diets that are high in fat, especially from animal products, as well as high consumption of red meats have also been associated with increased risk. Chronic high alcohol consumption is known to increase the risk of oral, esophageal, and stomach cancers. High temperature cooking methods such as frying and flame grilling, especially of meats and fish (high protein animal foods), are known to produce substances such as polyaromatic hydrocarbons (PAHs) and heterocyclic amines that are potential carcinogens. For example, PAHs are potential carcinogens that may contribute to cancer risk. Some PAHs can act at the initiation phase (mutation); other PAHs act mainly in the promotion phase of cancer cell growth (see FIGURE 7.14.1).

FIGURE 7.14.1 (Left) Some of the steps involved in the process of cancer development, also know as carcinogenesis. This pathological process involves 77

genetic mutations, perhaps 5 to 10 different mutations, that result ultimately in a metastatic cancer. (Right) The cancer cells can (spread form their primary site to other body tissues and organs; a cancer that has progressed to the metastatic stage becomes very difficult to treat. Sources: National Cancer Institute, USA (left); Häggström, Mikael (2014, right).

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Chapter 8 Minerals and water

8.1 Introduction and main questions In this chapter, some of the functions of water and minerals in the body will be examined, first the major minerals—the ones most abundant in the body—and then some of the minor or trace minerals. The absorption efficiency of dietary minerals is dependent on many factors both in the foods and in the body, and these will be detailed with specific minerals (cf. antinutrients section of chapter 6). The following are some of the main questions for this chapter: ● What are some major functions of water in the body? ● For each mineral, what are the best dietary sources? what are the physiological functions? what are the results of deficiency, and who is most at risk? what are potential risks with excessive intake? 79

8.2 Water Water is the major constituent of the body; it accounts for almost 2/3 of body weight. Water can be obtained both from drinks (including water itself, teas, juices, sodas, milk), and from the foods we eat. Some foods such as fresh fruits and vegetables contain much water (typically about 8095% of their weight), while others such as cheese, bread, and dried fruits and jams are low in water content (typically about 30-40%); cooked meats are intermediate in water content (typically about 60%). In addition to food and drink, the body also obtains water from its internal metabolism. It is estimated that a person needs about 30 milliliters of water per kilogram of body weight, or about one milliliter per kilocalorie consumed. Water is critical for body function and we cannot survive more than a few days without it. It's important for body temperature regulation; it can prevent fatal overheating during prolonged exercise especially in hot environments. Water is also the main component of body fluids, and the medium for chemical reactions metabolism in the body. Many catabolic reactions involve hydrolysis: the addition of water to break apart larger structures into smaller units, for example, hydrolysis of starches (which ultimately yield glucose for the body) by salivary and pancreatic alphaamylases, and hydrolysis of ATP in the cells to yield energy. Many anabolic reactions in the body involve release of water (dehydration reactions), for example, the production of triglycerides (storage fat in the body) from fatty acids and glycerol. The brain generates a thirst sensation in response to signals such as decrease in blood volume and the resultant increase in concentrations of 80

Water output (top) and input (bottom). Most water loss from the body occurs (major to minor) in urine, evaporation from skin and lungs, feces. Most water input into the body (major to minor, typically) comes from fluids, solid foods, metabolism.

blood components (solutes, including sodium). Thirst signals help restore water balance in the body. Typically, as people age, the thirst signal threshold increases; i.e., a 70 or 80 year old person is at greater risk of dehydration5,6 because they have to lose relatively more body water in order to feel the same thirst sensation compared to a 20 or 30 year old. The body is always losing water, for example, in the urine and feces, and with evaporation from the skin and lungs; water loss cannot be prevented. Water loss is greater with fever, diarrhea, and vomiting. When the body becomes severely dehydrated, rehydration must involve not only water but also minerals. Rehydration salts (e.g., also called electrolytes, sold in pharmacies) include sodium and smaller amounts of potassium (and other components); they are mixed with water and taken for rehydration (called ORT, oral rehydration therapy).

The color of a person’s urine is often indictive of their level of hydration

8.3 Sodium and potassium Sodium is a major mineral involved in electrolyte and fluid balance in the body; it's the major positively charged ion (cation, Na+) in the extracellular fluid, ECF (FIGURE at right). The major dietary sodium source is table salt that is commonly added to foods. Sodium is critical for the body, and it’s roles include nerve conduction and heart function. Sodium depletion can occur with severe vomiting, diarrhea, extreme perspiration. Deficiency can occur with a very low sodium diet, but this is rare because for most people sodium intake is excessive, not deficient. Symptoms of sodium deficiency include muscle cramps, dizziness, nausea; severe sodium depletion can be fatal. Moderate excesses of sodium can usually be well tolerated by adults with healthy kidneys; extremely high body sodium, for example with severe dehydration, can be fatal. Many people are sodium sensitive in terms of high blood pressure (hypertension); thus, salt restriction is a common recommendation for those with high blood pressure. Potassium is also important for water and electrolyte balance in the body; it's the major cationic mineral (K+) of the intracellular fluid, ICF (FIGURE at right). Potassium is important for nerve conduction and cardiovascular function. Major dietary sources of potassium are the plant foods (fruits and vegetables and plant-based drinks such as coffee and tea), also milk and other animal products; it's widely distributed and deficiency due to diet is rare. Low potassium intake is associated with increased risk of hypertension. Potassium depletion can occur with severe vomiting and 81

The body’s fluid compartments can be divided into two parts: intracellular and extracellular

diarrhea, or with the use of some diuretic medications. Potassium excess and toxicity from dietary intake is very unlikely especially with normal kidney function. If high potassium levels build up in the body, for example, due to the use of some medications or kidney malfunction, it can be a serious problem, especially for the heart, e.g., increase risk of cardiac arrhythmias.

8.4 Hypertension Hypertension (high blood pressure) is a major health problem in many countries of the world especially among the older adult population. Chronic hypertension contributes to many diseases because it affects many organs, e.g., increases risk of heart disease and stroke, and kidney disease. Risk factors for hypertension include genetic factors (family history of hypertension), and environmental factors such as high sodium and alcohol intake, smoking; obesity and lack of physical activity are two major risk factors. Dietary recommendations to help control hypertension include lower sodium intake, calorie reduction to help achieve and maintain a healthy body weight, increased consumption of fruits and vegetables. There are also many pharmacological treatments available for people suffering from hypertension.

8.5 Phosphorus, magnesium, chloride, sulfur Chloride is another major mineral that people typically get along with dietary sodium as part of table salt (NaCl, sodium chloride. Chloride is important for fluid, electrolyte, and acid base balance in the body; it's the major negatively charged ion (anion) in the extracellular fluid. Chloride is also important for nerve conduction and is part of stomach acid, hydrochloric acid. Sulfur is another major mineral that people typically get along with dietary protein. Sulfur is a component of the vitamins biotin and thiamine, and of alpha-lipoic acid (a coenzyme for several metabolic reactions) and of glutathione (redox balance regulator, endogenous antioxidant), and is part of some potentially beneficial dietary organosulfur compounds especially abundant in the cabbage and garlic families of plants. Disulfide bonds, based on sulfur, are important for stabilizing protein structure. In the 82

Hypertension is a major global health problem with many possible causes. Maintaining a healthy body weight is a major way to reduce the risk of hypertension.

process of sulfation, a sulfo group is added to substances for their elimination from the body, for example, added to drugs and other xenobiotics. Phosphorus is part of many biomolecules of the body; for example, it's part of adenosine triphosphate (ATP) which is the energy currency of the cell, and part of cell membrane phospholipids and of the genetic material DNA. In the phosphate form, it's the major intracellular anion, important for fluid balance. Phosphate is also a major component of bones and teeth; it's deposited in these structures along with calcium. Major dietary sources of phosphate include dairy products, meats, and is widely distributed among both plant foods and animal products. Magnesium is also abundant in many food sources including whole grain cereals, vegetables, dairy products, and mineral waters. Magnesium is important for many metabolic reactions; it's required by hundreds of enzymes as a cofactor. It stabilizes polyphosphate structures including DNA, and is a functional part of ATP. Magnesium is important for the function of nerves, heart, and skeletal muscle; and deficiencies will affect these functions. Magnesium excess in the body due to diet is rare, especially for adults with normal kidney function; but excess is more likely with overuse of supplements or magnesium rich antacids. Tolerable upper intake level (UL) for magnesium has been set for supplements and medications, not for magnesium from foods.

ATP is the major energy currency of the body. Energy is stored and released from the phosphate bonds. Magnesium is a part of the structure of functional ATP

8.6 Calcium Calcium is a major mineral of the body, the main structural component of bones and teeth. It also has many regulatory functions in the body, for example, helps to control blood clotting, muscle contraction, nerve function, stabilizes protein and membrane structures, and activates many enzymes. Deficiency of calcium is more likely if there is also a vitamin D deficiency. Blood calcium levels are maintained through mobilization of the vast reserves in bones. Parathyroid hormone, PTH, is central to calcium homeostasis; PTH helps mobilize calcium from bone, promotes vitamin D activation by the kidneys, and reduces calcium loss in the urine. Excessive calcium accumulation in the circulation (hypercalcemia) can cause symptoms such as nausea, muscle weakness, bone pain, and upset stomach. If very high levels develop, for example, with excessive vitamin D supplementation, it could become a serious problem, interference with 83

Calcium can be mobilized from the bones as needed by the body’s cells

heart and kidney function and calcification of organs in extreme cases. Major dietary sources of calcium include milk and dairy products, fish, and green leafy vegetables. Absorption of dietary calcium may be decreased by competition from some mineral supplements such as magnesium; oxalates present in some vegetables such as spinach and rhubarb, fiber and phytates present in legumes and other plant foods, can bind calcium and decrease its availability for absorption (see antinutrients section in chapter 6). Vitamin D deficiency results in lower gut absorption of dietary calcium.

8.7 Osteoporosis Osteoporosis is a disease characterized by abnormally low bone mass; it results in fragile, porous bones that are at increased risk of fracture, especially at the wrist, hip, and spine. Risk factors for osteoporosis include old age and low body weight; genetic factors are also involved, and risk is higher for those of European and Asian ethnicity. Women are at higher risk for osteoporosis than men, especially with early menopause. Low levels of physical activity also greatly increased risk, as do smoking and excessive alcohol intake. In terms of diet, low calcium intake and low vitamin D levels may increase risk. These and other dietary factors are under research for their contribution to risk, and possible to help control of osteoporosis development. Pharmacological and hormone treatments are available for those older adults who are most at risk.

Spine wedge fractures (arrow) are characteristic of osteoporosis. Source: Glitzyqueen00 released to public domain (2008)

8.8 Iron The first of the trace minerals to be considered is iron, a nutrient required by all cells. Dietary iron can be obtained from many foods especially meats, also plant foods including beans, cereals, and vegetables; and there are many iron-fortified foods available. Absorption of dietary iron is strongly dependent on the body's need for iron. Some properties of foods can affect iron absorption:1-4 a] heme iron from animal products is more efficiently absorbed than non-heme iron from plant foods (animal products contain both heme and non-heme iron); b] vitamin C can increase iron absorption from foods; c] iron absorption from foods can be competed by calcium and magnesium (and other divalent cations, 2+) especially from supplements; d] tannins and phytates in some plant foods can lower iron absorption (see also antinutrients section in chapter 6). 84

The structure of heme with iron (Fe2+) in the centre bound to the four nitrogen atoms

Dietary iron is absorbed by gut epithelial cells (enterocytes) and transported in the circulation bound to the protein transferrin. Transferriniron is delivered to cells throughout the body including liver cells for storage, and bone cells for the production of hemoglobin and red blood cells (see FIGURE 8.8.1). Iron can be lost from the body through blood loss, e.g., menstruation, normal shedding of gut enterocytes (minute quantities lost), and some cancers such as colon cancer. Iron has many functions in cells; a major function is to carry oxygen throughout the body as part of hemoglobin in red blood cells, and myoglobin muscle cells. Iron is also part of some enzymes as a cofactor, for example, part of the antioxidant catalase enzyme that converts hydrogen peroxide to water.

1

5

2

3 4

FIGURE 8.8.1 Dietary iron is absorbed by enterocytes (gut epithelial cells, 1) and transported in the circulation (2) bound to transferrin (TF). TF-iron is delivered to cells throughout the body, including liver (storage) and bone (3). In the bone marrow, iron becomes part of hemoglobin (Hb) and Hb is then loaded into erythrocytes (4). Iron is lost from the body with blood loss and shedding of enterocytes (5).

Deficiency of iron can occur, for example, in infants with a prolonged milk diet; and vegans (strict vegetarians) are at increased risk mainly due to lower iron absorption from plant foods.1,4 Iron deficient anemia is called microcytic hypochromic because it's characterized by small red blood cells (microcytic) with a pink (rather than the normal deep red) color (hypochromic); such anemia results in a decrease of the oxygen carrying capacity of blood. Iron overload and toxicity can occur if a person, especially a child consumes, too many iron pills or other nutrient supplements containing iron. Hemochromatosis is a genetic disease which results in excessive accumulation of body iron; such iron overload is damaging to most organs, 85

for example, the liver and heart. Iron excess increases oxidative damage, and may increase the risk of some types of cancer and other chronic diseases.

8.9 Zinc and Selenium Zinc is also widely distributed among plant and animal foods; levels in plant foods often depend on zinc levels in the soil. Absorption of dietary zinc can be decreased by dietary factors such as phytates (cf. antinutrients), as well as consumption of iron and calcium supplements. Zinc functions as a cofactor for hundreds of enzymes in the body (important for normal metabolism) including the antioxidant enzyme superoxide dismutase SOD. Zinc also participates in the regulation of gene expression with hundreds of different transcription factors. Overall, zinc is important for immune function, reproductive development, bone and body growth, function of the nervous system, and many other body tissues and organs.11 Zinc deficiency is most commonly associated with protein malnutrition; it can also occur with some diseases. Deficiency affects body growth, sexual maturation and reproduction, hair and skin health, neurological and immune function, and can alter the senses of taste and smell. Zinc supplements can decrease absorption of dietary iron and copper; and excessive zinc accumulation can be toxic to body cells; but such accumulation is less likely than excessive iron accumulation (especially in men and post-menopausal women) because excess zinc can be eliminated in pancreatic digestive secretions (unless intake is greatly excessive).

FIGURE 8.9.1 Selenium is a cofactor for GPX (glutathione peroxidase) enzymes which remove potentially damaging peroxides from the body cells.

Selenium is found in many animal products, mushrooms, and in plant foods such as nuts and cereals; the level in plant foods depends on soil selenium levels. Selenium is a cofactor for several enzymes in the body including glutathione peroxidase that helps neutralize reactive peroxides 86

Pumpkin seeds are a rich source of minerals such as zinc

(lipid peroxides and hydrogen peroxide) and controls the damage they can cause. Selenium is also a cofactor for iodinases, enzymes that participate in the activation of thyroid hormones.12 Deficiency of selenium is characterized by muscle weakness and possibly increased levels of oxidative stress. Deficiency is most common in parts of the world where soil selenium levels are low. Selenium supplements can interfere with dietary absorption of other minerals such as zinc, and vice versa. Overload with selenium can contribute to hair and skin problems, fatigue, as well as serious neurological and gastrointestinal damage.

8.10 Copper and Iodine Copper is a trace mineral that is widespread among foods, for example, plant seeds, e.g., whole grain foods, beans and nuts, as well as seafood and other animal products. Dietary copper absorption can be competed by some mineral supplements such as iron and magnesium. Copper is a cofactor for several enzymes including superoxide dismutase, and antioxidant enzyme that helps remove superoxide free radicals produced during energy metabolism. Copper is also important for collagen production and the integrity of the connective tissues, and for iron mobilization and utilization; it also has a role in normal immune function. Deficiency of copper is rare with most diets; but can occur with some rare genetic diseases such as Menkes disease, due to inefficient copper transport into cells. The results of deficiency are poor body growth in children, and anemia. Excessive copper in the body can be highly toxic; but this is usually a result of overconsumption of supplements not foods. Toxic accumulation can also occur with the rare genetic Wilson's disease in which there is an overload of copper due to inefficient copper transport into the bile, an important step that can lead to the elimination of excess copper from the body. The final trace mineral that will be examined is iodine. Its major dietary sources are iodized table salt that is commonly added to foods; marine foods including some types of seafood are a source of iodine as are some plant foods if the plants are grown on iodine-rich soils. Dietary iodine, ultimately in the form of iodide (anion) is taken up by the thyroid and incorporated into the protein TG, thyroglobulin. TG is broken down to release thyroid hormones T3 and T4 into the circulation; carrier proteins in the blood deliver thyroid hormones to cells. Inside the cells, thyroid hormones can have many regulatory functions, for example, at the level of 87

A person suffering from goiter, severe deficiency of iodine. Source: People and Food (1951) A. Virtanen, P. Roine.

the mitochondria they help regulate basal metabolic rate (BMR), energy expenditure. Thyroid hormones can also participate in the control of protein synthesis. With long-term deficiency of iodine, a type of goiter (thyroid problem) can develop as the thyroid gland grows in the attempt to capture more iodine. A different type of goiter can develop with chronic high intake of iodine because such excessive intake can lower formation of iodinated TG. Iodine deficiency is an important global nutrient deficiency, with severe consequences upon brain development and learning (cognitive function).7-10

The incorporation of dietary iodide into thyroglobulin (TG) and thyroid hormones (T3, T4) which affect energy metabolism in the body (BMR, basal metabolic rate)

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Chapter 9 Food safety and technology

9.1 Introduction and main questions In this chapter food contamination and toxicity—e.g., due to harmful microbes and chemicals—will be examined, as well as safety recommendations to minimize the risk of foodborne illnesses. Related topics will also be introduced such as organic foods, food additives, allergies, alcohol toxicity, and genetically modified (GM) foods as an example of food technology. The following are some of the main questions for this chapter: ● How can food contamination be prevented? ● What are some of the microbes and parasites that lead to food-borne illnesses? ● What are some of the natural and synthetic food chemicals that can cause illness? ● Are there advantages to organic foods? ● What are the toxic effects of alcohol? ● What are some of the chemical food additives? ● What are food allergies and the common allergens? ● Are there risks associated with genetically modified foods? 89

9.2 General rules for food safety Major rules to lower the risk of food-borne illnesses (also called food poisoning) are summarized in this section; they relate to safe food handling.1-3,12 Main recommendations include avoiding raw animal products and unpasteurized dairy products and juices, and avoiding foods from defective packages, e.g., canned products if the can is bulging or defective. In terms of handling and preparing food, it is important to wash hands with soap before and after food preparation, and ensure clean surfaces when preparing food. Thorough cooking is one of the most important recommendations for making a food microbiologically safe; bacteria, viruses, parasites, and other microbes are destroyed by high temperatures. Prolonged storage of foods should be avoided. Leftover cooked foods should be promptly refrigerated or kept hot, and thoroughly cooked before eating. A general rule is that leftover cooked foods should not be kept at room temperature for longer than about 2 hours. Frozen foods should be thawed in the refrigerator, or thawed quickly, for example, in a microwave oven; they should not be thawed for several hours or overnight at room temperature.

Safe food handling rules include washing and cleaning hands, foods, tools, and surfaces (lower picture), and using different cutting boards for raw foods such as vegetables and animal products such as meats and fish (upper picture) to avoid cross-contamination.

The danger zone for microbial growth and contamination, e.g., temperatures at which bacteria can multiply rapidly is about 4 to 60 oC, and especially 15 to 50 oC. Internal cooking temperature for foods should reach over 70 oC.

9.3 Types of food contamination Food contamination may be physical (for example, particles of plastic or metal), chemical (for example, pesticides and other agricultural chemicals), or biological (for example, bacteria, viruses, molds). In terms of biological contamination, we will begin by examining a few of the many bacteria that can cause foodborne illnesses. Salmonella and campylobacter are two of the most common causes of food poisoning in the world. Clostridium botulinum and E. coli O157:H7 are rare causes of food poisoning but, when they occur, can be very dangerous or fatal. 90

Microbial contamination is one type of food contamination. Source: People and Food (1951) A. Virtanen, P. Roine, drawing by O. Renkonen

9.4 Some bacteria that can cause foodborne illnesses There are many strains of Salmonella that can contaminate food and cause food poisoning. Salmonella is the most common bacterial cause of food poisoning in Canada and many other countries. Common food sources of salmonella are undercooked eggs and animal products such as meats, unpasteurized milk and juices, raw produce, and contaminated water; it can get on foods through handling of pets and other animals such as birds, reptiles and mammals, or if a person infected with salmonella handles food. Prevention of salmonellosis (the food-borne illness caused by salmonella) is thorough cooking of the food and safe food handling as mentioned earlier. Food poisoning with salmonella typically begins to show symptoms between about eight hours and up to about three days after exposure. Symptoms include vomiting, diarrhea, fever, headache, and abdominal cramps. As with many other food poisonings, children are at greater risk of illness due to their smaller body size, as are the elderly and immuno-compromised.

Salmonella bacteria. Source: Health Canada

Campylobacter is another common cause of food poisoning. Typical food sources of campylobacter include unpasteurized milk, raw or undercooked animal products, especially poultry and other meats and shellfish, also raw vegetables, and untreated drinking water. Prevention recommendations include thorough cooking of the food and safe food handling. Food poisoning with campylobacter typically begins to show symptoms two to five days after exposure. The symptoms include diarrhea, abdominal pain, fever, and vomiting; for some people, there may be more serious longer lasting symptoms, e.g., arthritis. E. coli strain O157:H7 is a relatively rare but potentially very dangerous cause of food poisoning.14 Common food sources include undercooked meats, especially undercooked ground beef. Ground meat (hamburger meat) is most problematic because of its large surface area; all the parts or strings of meat that are used to produce the hamburger patty have a large combined surface area, which increases risk of contamination in the meat processing plants. Other potential sources include sprouts and raw produce, unpasteurized milk and juices, and contaminated water. Prevention recommendations include thorough cooking of the food, and safe food handling procedures (section 9.2). Illness with this strain of E. coli typically begins one to six days after exposure. Symptoms often include bloody diarrhea; it can be fatal, or the person may be left blind, paralyzed, 91

Ground meat (image of hamburger sandwich) is at greater risk of microbial contamination because of the large surface area, and increased possibility of contamination below the surface, in the center of the meat patty

or with kidney disease depending on the toxin levels in the body. The risk is higher for children due to their smaller body size. Clostridium botulinum is a very rare but potentially fatal cause of foodborne illness, botulism. Food sources include vacuum-packed foods such as fish, canned meats or vegetables, especially non-acidic vegetables such as green beans, beets, peppers, and mushrooms. Home canning can be a problem if the equipment is not working properly and if high enough temperatures are not reached in the process. For prevention of botulism, it is recommended to avoid abnormal food packages, for example, cans that are bulging or otherwise defective. For infants, the recommendation is to avoid giving them honey because it may contain Clostridium botulinum spores. Such spores are more problematic for infants because their large intestine is not fully colonized by normal bacterial species. Botulism typically develops between about 8 to 72 hours after exposure. Symptoms include vomiting, diarrhea and, depending on the toxin levels in the body, muscle paralysis; such paralysis begins typically with blurred vision, difficulty swallowing and speaking, and can be fatal if the breathing muscles are affected. Listeria infection can be very serious for some people; for example, it can be fatal for immuno-compromised people and for the fetus during pregnancy. Food sources such as unpasteurized milk, cheeses and dairy products, raw animal products, raw salads, and vacuum-packed fish have increased risk for listeria contamination (Listeriosis). These bacteria can grow at typical refrigerator temperatures. Pasteurization and thorough cooking of food as well as safe food handling practices can minimize Listeria contamination.

Listeria bacterium, magnified about 40000X. Source: E. White, Centers for Disease Control and Prevention, USA

Many other bacteria can cause foodborne illness, for example, Staphylococcus, Yersinia, Shigella, and others listed in TABLE 9.4.1. Thorough cooking and safe food handling can minimize risk of illness caused by all these bacteria.

TABLE 9.4.1 Some of the many bacteria that can cause foodborne illness (in addition to the ones discussed in the main text of this chapter)

Bacteria Staphylococcus Yersinia Shigella Vibrio

Foods with highest risk (remarks) eggs, meats, salads, cakes (e.g., cough contamination) water, raw produce (can grow at refrigerator temperatures) water, salads, produce (e.g., fecal contamination) water, raw seafood and other foods (e.g., poor sanitation)

Snails for sale at a food market. These invertebrates are considered a delicacy in some countries; but if not thoroughly cooked, they can be sources of harmful microbes.

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9.5 Parasites and other organisms that can cause foodborne illnesses Thorough cooking and safe food handling can also minimize risk of infection by foodborne parasites.10 The following are some protozoan parasites that can be present on contaminated foods and cause illness. Toxoplasma are one group of such parasites that a person can get from undercooked meat or fecal contamination foods especially contamination with cat excrement. Many people infected with toxoplasma are asymptomatic; but infection can be very serious during pregnancy and can result in abortion of the fetus. Giardia parasites have been reported for contaminated water, especially in cities of the world with poor municipal water treatment; undercooked animal products and raw foods can also be a source of Giardia. Cryptosporidium parasites can also be present in contaminated water; and this protozoan has high resistance to chlorine treatment. In places where there is a risk of contaminated tap or other drinking water, boiling of the water eliminates the risk of contamination by Cryptosporidium, Giardia, amoebas, Cyclosporiasis, and other parasites. Amoebic dysentery (ameobiasis, caused by Entamoeba hystolytica) is relatively common especially from contaminated food and water in developing countries. Some Entamoeba-infected people are asymptomatic, but most develop typical foodborne illness symptoms such as diarrhea; for some people, such infection can be fatal.

Entamoeba histolytica (trophozoite life cycle stage). The internal dark spots are red blood cells that have been ingested. Source: Centers for Disease Control and Prevention, USA

Other foodborne parasites can cause illness, for example, worms such as roundworms (e.g., Trichinella) and tapeworms (e.g., Taenia and Diphyllobothrium). The infection cycle of Diphyllobothrium is shown in the figure; infection risk can be minimized by avoiding raw meats, and especially raw fish. Again, thorough cooking and safe food handling can minimize infection risk. Paralytic shellfish poisoning (PSP) can be caused by different microorganisms such as Dinoflagellates, cyanobacteria, and microalgae. These organisms produce heat resistant toxins that can accumulate in shellfish, e.g., clams, mussels; if the dose of such toxins is high enough, it can lead to respiratory paralysis, and can be fatal.

9.6 Viruses and Prions 93

Dinoflagellates. Source:

Encyclopedia Britannica, 1911

There are also several types of viruses that can cause foodborne illness; and thorough cooking along with safe food handling (section 9.2) can minimize infection risk.11 The norovirus (also called Norwalk virus) is the most common cause of foodborne illness in the world with hundreds of millions of cases each year. Typically the symptoms of diarrhea and vomiting disappear about one to three days after exposure; serious complications are not common with this virus. Norovirus can be found in contaminated water and ice, or foods contaminated with such water. Hepatitis A is another virus that can be obtained from contaminated water, and from undercooked foods such as shellfish harvested from such waters. Symptoms of hepatitis A infection include nausea, fatigue, and jaundice from temporary dysfunction of the liver; long-term liver damage is rare for hepatitis A, but possible.

Noroviruses, bar = 50 nm. Source: Environmental Protection Agency, USA

Yellow color of the sclera (white of the eye) that is characteristic of jaundice. Source: Centers for Disease Control and Prevention, USA

Finally, a rare and invariably fatal illness is believed to be caused by infectious, contagious proteins called prions (PrPSc, misfolded forms of the normal PrPC protein; superscript C refers to cellular, and Sc refers to the disease scrapie). Prions can resist cooking, and are found in some products obtained from infected animal such as a cow, especially products that include parts of brain and nerve tissue. There is ongoing research examining the possibility that transmission of prions (PrPSc) can occur from the excrement or dead bodies of infected animals. Prions can cause fatal neurodegenerative diseases in humans and other animals; for example, they can cause Creutzfeld-Jakob-type diseases, kuru, and familial spongiform encephalopathy in humans, scrapie in sheep and goats, mad cow disease in cattle, feline spongiform encephalopathy in cats, chronic wasting disease in moose and some species of deer.13

9.7 Synthetic chemicals and environmental contaminants Some chemicals can also cause foodborne illnesses. Both natural and manmade (anthropogenic) chemicals can be problematic in this respect. Environmental contaminants such as mercury, lead, and other heavy metals, and agricultural chemicals such as pesticides, herbicides, and veterinary drugs including antibiotics, can be ingested with foods and may cause health problems.5,7,8

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Vacuoles (holes) in the brain of a prion-infected cow. Source: Dr. A. Jenny, USDA.gov, USA

Methylmercury is an environmental contaminant that can cause illness and is especially harmful to the developing fetus during pregnancy. There are both natural and synthetic (anthropogenic) sources of methylmercury. In terms of diet, contaminated fish can be a major source of this poison.4,5 The risk is highest for consumption of larger older fish the typically eat other fish (size of M in picture at right relates to mercury accumulation levels in fish), for example, shark swordfish king mackerel, large tuna, and pike, due to bioaccumulation along the food chain; and there is also high risk for fish from contaminated waters such as methylmercury contaminated lakes near mining sites or other industries. Pesticides are sprayed on crops to prevent damage by insects and other organisms and increase yields. Some pesticides may have harmful effects in the body, especially if ingested at high levels. Based on the results of the environmental working group of the US Department of Agriculture (USDA), some fruits and vegetables have been identified as typically containing the highest levels of pesticides: apples, strawberries, grapes, peaches, celery, spinach, cherry tomatoes, nectarines, cucumbers, sweet peppers, snap peas, potatoes. These have been called the dirty dozen.15 Thus, to minimize pesticide exposure, one should consider organic varieties of some of these plant foods, particularly if one consumes them frequently.

M

M

Arial spraying of pesticides on an agricultural field. Souce: C. O’Rear, USDA, USA

9.8 Organic foods Organic foods are grown without synthetic chemicals, and their consumption results in less exposure to such chemicals including pesticides and herbicides. Most studies that have compared organic and non-organic plant foods, however, do not provide strong evidence that organic foods are nutritionally superior in terms of their macronutrient and micronutrient contents. Organic foods, as with non-organic foods, are susceptible to microbial contamination and must be handled safely as discussed previously in section 9.2. Organic foods may have a higher risk of contamination with some microbes because of the organic or manure fertilizers that are used in their cultivation.

9.9 Naturally-occurring toxins

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Apples, strawberries (not shown), and grapes often have the most pesticide residues of all nonorganic fruits

There are also many naturally occurring toxins or chemicals that can cause foodborne illnesses. In addition to some of the microbe toxins that have already been discussed, there are toxic substances produced by plants, fungi, and animals. Some of these can be fatal, for example, hepatotoxins from some Amanita mushrooms (top image at right), neurotoxins from puffer fish (image at right) and jellyfish (lower image at right; see also PSP, paralytic shellfish poisoning in section 9.5). Solanine is a neurotoxic chemical found in the nightshade family of plants (potatoes, tomatoes, eggplant). Potatoes (image at right) that have turned greenish in color are likely to have the highest solanine levels.9

Some jellyfish and mushrooms are edible, others are deadly toxic. Historical illustrations of Amanita mushroom, puffer fish, jellyfish, and potatoes shown above.

9.10 Alcohol Alcohol (ethanol) is also a potentially toxic substance, and especially toxic to the developing fetus. It is recommended that pregnant women do not consume any alcohol. Chronic high intake of alcohol damages many organs of the body including liver, pancreas, and brain; high intake over time can increase the risk of some types of cancer, for example, oral, esophageal, and breast.6 Chronic high intake also increases the risk of several vitamin deficiencies including thiamin B1, biotin B5, folate B9, and vitamins D, A, and B12. Many alcoholics have poor diets and are at high risk of multiple nutrient deficiencies. Low-level, moderate consumption of alcoholic drinks, e.g., red wine may lower the risk of some atherosclerotic cardiovascular diseases such as heart attack (coronary heart disease, CHD), especially for men.

Liver damage (cirrhosis) is a common result of chronic high alcohol intake. Source: Encyklopedia Powszechna Ultima Thule 1931

9.11 Food preservatives, colors, and other additives Many chemicals have been approved for use as food additives by national health agencies of most countries. These include food preservatives, colors, flavors and flavor enhancers, antioxidants, sequestrants, texturizers, and humectants. Foods can also be fortified through the addition vitamins, minerals, dietary fiber, and other nutrients. TABLE 9.11.1 provides some examples of these. Note that countries can have differences in their lists of approved food additives.

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Tartrazine (yellow #5, often used to color sweets such as fruit jellies above) can cause allergic reactions, and must be stated on food labels; tartrazine is not allowed in some European countries.

TABLE 9.11.1 List of some food additivies

Food example Sausages, cured meats Soups and many other foods Colas and other soft-drinks Candies, cakes, many other foods Juices, soft-drinks, other foods Breakfast cereals (packaging), also added to some foods Ice cream, cured meats Mayonnaise, salad dressings Dairy products Colas, candies, other foods Breads Breads, cured meats, and many other foods Drinks, sweets

Additive Nitrite Glutamate (MSG) Benzoate Tartrazine Sucralose (BHT) butylated hydroxytoluene Carrageenan EDTA (binds iron) Vitamin D Caramel Propionate Ascorbate Allyl hexanoate

Reason for addition Antimicrobial (preservative) Flavor enhancer Antimicrobial (preservative) Color (artificial) Sweetener (artificial) Antioxidant (artificial) Texturizer (algal product) Antimicrobial, antioxidant Nutrient (fortification) Color (heated sugar) Antimicrobial (preservative) Antioxidant, nutrient (vitamin C) Fruit flavor (occurs naturally in pineapples)

9.12 Food allergies Food allergies are reactions of the body's immune system to one or more components (antigens) in a food. Allergies contrast with food intolerances; the latter are non-immune reactions to a food, for example, lactose intolerance. Food allergies are most common in the childhood years, and typically become less prominent or disappear completely by adulthood. Many symptoms are possible in an allergic reaction to food, for example, fatigue, headache, nausea, diarrhea, and very commonly skin reactions such as rashes. Typically, the most allergenic foods are protein rich, for example, eggs, cow’s milk and dairy products, seafood, peanuts and other nuts. There are various tests to identify the food that is causing an allergic reaction; once identified, the treatment is to minimize or eliminate exposure to that food antigen.

9.13 Genetically modified foods 97

An allergic reaction shown as a skin rash on the back (top). Skin prick test (lower picture) is common but not very reliable in terms of identifying an allergen. Source for upper image: DL double E public domain (2008)

Genetically modified (GM) foods are those that have been subjected to genetic manipulation, for example, the introduction of a gene from one species into another species, or introduction of modified genetic material back into the same species; and typically, the genetic change can be passed on to future generations. There are many possible reasons for genetic modification of foods; these include increasing yield and storage time of a fruit or vegetable, increasing nutrient content, or decreasing the level of potential toxins naturally present in the food. For example, some GM plant foods are made more resistant to plant viruses and bacteria, to agricultural chemicals such as herbicides, and to environmental conditions such as frost and prolonged storage. At present, there is no good evidence that GM foods pose a risk to human health; possible negative long-term consequences, however, cannot be ruled out completely at present.

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Some plums are genetically modified to be resistant to a virus that is normally transmitted from aphids to the plum tree.

Chapter 10 Overview of nutrition during the life cycle

The following sections provide an overview of nutrition during stages of the human life cycle, from prenatal development to birth, infancy, childhood, and the teenage years. Nutrition of the fetus and mother during pregnancy is also examined. Adulthood nutrition is divided into elderly and 99

pre-elderly (middle age) stages. The nutritional recommendations presented below are derived mostly from the tables for the different age groups in Appendix A.

Old man in a painting by Ditlev Blunck (1789-1853)

10.1 Nutrition and aging, recommendations for the elderly The proportion of elderly people in the Canadian population, as well as in many other countries of the world, is increasing greatly. The elderly age group exhibits more variability in terms of health, physiology and metabolism, as well as physical abilities1 relative to younger adults or children. Aging leads to loss of function for many of the body’s organs and systems including musculoskeletal, sensory, nervous system, gastrointestinal (GI), renal, immune, endocrine, and cardiovascular. Increased oxidative stress and inflammation contribute to some of these age-related functional losses.2-4 Because of the changes that occur with aging, nutritional requirements for the elderly may be different compared to those for pre-elderly adults. Typically, energy recommendations for the elderly are about 300 to 600 kilocalories per day lower than those younger adults; but this is highly dependent on the level of physical activity. Reasons for lower energy requirements among the elderly include lower basal metabolic rate (BMR), and also typically a lower level of physical activity.

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In terms of protein, at present, such recommendations are similar for elderly and pre- elderly adults. Very low protein diets among the elderly may increase the risk of sarcopenia and bone loss, and may affect disease outcomes:5 for example, contribute to a longer or deficient recovery from an illness. Very high protein intake may place additional stress on the kidneys especially for elderly diabetics, and especially if protein and amino acid supplements are being used. The requirement for calcium is higher among the elderly; and reasons for this include increased rates of bone loss as well as lower intake and absorption of calcium.5,6 The current recommendation is for a 20 % increase in calcium intake for men over age 70 and women over age 50, relative to younger adults of the same gender. The intake recommendations for some vitamins are higher among the elderly. For those over age 70, the vitamin D intake recommendation is 25 % higher compared to pre-elderly adults; reasons for this include decreased activation a vitamin D in the liver and kidneys (see Vitamins chapter),6 and lower sun exposure among the elderly especially those that are in a senior’s care home or otherwise institutionalized. For vitamin B6, the recommendation is about 20% higher for those over age 50, and this is mainly due to decreased absorption and activation of the vitamin (cf. vitamin D). For vitamin B12, the current recommendation is similar among elderly and pre-elderly adults; but the elderly are advised to obtain more B12 from supplements and fortified foods to achieve higher absorption of this vitamin. Gastritis and other problems of the gastrointestinal tract (e.g., lower intrinsic factor production) among the elderly make it more difficult to absorb sufficient B12 from food sources.7 Higher intake of water is recommended for the elderly because of their decreased thirst response, i.e., increased thirst threshold; more water must be lost from the older person’s body to achieve the same thirst sensation relative to a younger person. Typically, among the elderly there is also decreased reabsorption of water by the kidneys, more water loss.8,9 Risks for dehydration that are particularly applicable to the elderly include being unable to drink without assistance (e.g., in cases of dysphagia or Alzheimer’s), and use of medications such as diuretics.

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Alzheimer’s disease (AD) is a relatively common neurodegenerative illness that affects primarily the elderly population. At present, there is no good evidence for dietary factors in the prevention or progression of AD.

10.2 Adulthood nutrition Nutritional recommendations during adulthood, in the pre-elderly years, are aimed primarily at lowering the risk of major chronic diseases such as cancer, cardiovascular diseases, as well as type 2 diabetes and related metabolic disorders (these topics have been in the nutrient chapters).10 A major nutritional recommendation for adults is to increase intake of vegetables, fruits, and other plant foods; these foods typically have high nutrient density for vitamins, minerals, dietary fiber, and contain other phytochemicals with potential health benefits. Another major recommendation is to change some of the types of fats and carbohydrate in the diet, for example, to decrease saturated fats from animal products an increase omega-3 rich food sources, and to replace simple sugars with whole grain foods and others that contain complex carbohydrates. In general, it is recommended that people should get the nutrients they need from foods rather than dietary supplements;40 but if consuming sufficient foods, and a variety of foods, is difficult to achieve, then supplements may be recommended to avoid deficiencies that could increase risk of diseases over the years and decades.

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10.3 Nutrition during pregnancy This section provides information on the nutritional recommendations for the health of the mother and fetus during pregnancy. Nutrients and other factors are necessary for normal fetal development and are transferred from the maternal to the fetal circulation. If there is a nutrient deficiency, it may interfere with development, result in malformation of the fetus, or termination of pregnancy. Such harmful effects can also occur with exposure to toxic substances such as alcohol, drugs, viruses and other infectious agents, mercury and other metals, as well as industrial compounds and other pollutants. General nutritional recommendations during pregnancy include ensuring sufficient macronutrients (especially protein) and micronutrients, and avoiding all alcohol and drugs, and many types of prescription and overthe-counter medications. The following nutrient recommendations are for a pregnant woman relative to a non-pregnant, non-lactating woman of the same age and pre-pregnancy BMI. In terms of energy intake (kilocalories), the recommendation is for about 15 to 20 % increase for a pregnant woman in the second half of the pregnancy. This extra energy is needed to support growth of the fetus and the placenta, and for many metabolic processes including nutrient transport to the fetus and others that require energy. In terms of protein intake, the recommendation is for a 50 % increase with a single pregnancy, higher for twins and other multiple pregnancies. This extra protein supports the protein synthesis that is required for new maternal and fetal tissues.

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For vitamin B6, the recommendation is also a 50 % increase with pregnancy. This extra B6 helps support in the increased need for protein synthesis and especially for production of non-essential amino acids; B6 also supports production of the vitamin niacin from the amino acid tryptophan. An increase of about 30 % is recommended for the intake of vitamins B1, B2, and B3, thiamin, riboflavin, and niacin, respectively. These B vitamins participate in many metabolic processes; for example, they are important to obtain energy from the macronutrients—dietary fats, protein and carbohydrates. The pregnancy-related recommendation for folate, vitamin B9, is a 50% increase; folate supports DNA synthesis and cell division in maternal and fetal tissues, and is especially critical very early in the pregnancy, e.g., within the first month. Folate deficiency can may increase risk of premature birth or low birth weight infants, and also may increase the risk of birth defects, especially spina bifida, a defect in the closure of the neural tube during development (see also Vitamins chapter).11-15 To meet the increased intake for folate, supplements are often recommended because it is difficult to achieve high folate intake through natural food sources alone. Recommended natural food sources include legumes, leafy vegetables such as spinach and cabbage, and citrus fruits; fortified foods are also often recommended, for example, folate-fortified pastas and cereals. Recommended vitamin A intake for a pregnant woman is similar to that for a non-pregnant woman. Very high doses of vitamin A in the retinoid form (not the carotenoid form, see Vitamins chapter) can increase the risk of developmental abnormalities and birth defects.16,17 Pregnant women are advised to avoid high vitamin A supplements, and avoid frequent consumption of some vitamin A-rich foods (retinoid-rich, animal products) such as liver. Such increased risk of developmental abnormalities has not been associated with consumption of foods that are rich in provitamin A carotenoids, e.g., orange-colored plant foods such as carrots, pumpkin, squash, and cantaloupe. With pregnancy, a 50 % increase in iron intake is recommended to meet increased production of maternal red blood cells, and for the fetal blood and placenta. Iron supplements are often recommended to meet the needs of the pregnant woman; it's difficult to achieve the recommended intake with foods alone. Iron-fortified foods such as cereals, breads, and pastas are often recommended during pregnancy. Natural iron-rich 104

Pumpkin and squash are good sources of beta-carotene, a carotenoid form of vitamin A

sources include meats and other animal products as well as legumes. Animal products contain both non-heme-iron and heme-iron; plant foods don’t contain the heme-iron form. Heme-iron is more readily absorbed compared to non-heme iron.18,19 For zinc an increase of about 40 % is recommended for pregnant women. Zinc participates in hundreds of metabolic reactions in the body. Typically, with the use of some mineral supplements such as iron, less zinc is absorbed from the diet; thus, zinc-rich foods are emphasized during pregnancy, for example, meats, fish, eggs, dairy, whole-grain products, legumes, nuts, and other seeds such as sesame, pumpkin, sunflower. An increase of about 50 % is recommended for iodine during pregnancy. Iodine deficiency is a relatively common cause of neurological and developmental deficiencies in infants and children in some developing countries.20-23 Food recommendations during pregnancy typically follow from the nutrient recommendations, for example, increased dairy products and other high protein foods; dairy products are also rich sources of calcium, calories, and are usually fortified with vitamin D. Meats and fish are also good sources of protein, and can be good sources of iron. Organ meats such as liver are typically not recommended during pregnancy because of high vitamin A content and possible accumulation of toxins. Fish is also a good source of omega-3 fatty acids such as DHA and EPA; the recommendation is to consume fish that are typically low in mercury content, for example, salmon and sardines. Plant foods such as legumes and green leafy vegetables are recommended as good sources of folate and other vitamins and minerals, as well as dietary fiber.

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Heme-iron present in meats is usually more efficiently absorbed compared to elemental iron. Plant foods contain only the latter.

Woman and infant, painting by Kitamara Utagaro (c. 1790)

10.4 Nutrition during lactation This section provides information on the nutritional recommendations for the health of the mother and infant during lactation. For the infant, some benefits of breastfeeding include decreased risk of infections and decreased risk of allergic reactions. For the infant, breast feeding has also been associated with lower risk of diabetes, asthma, and some types of leukemias later in life.24,25 Breast milk is nutritionally well balanced for the infant, and there is a lower risk of overfeeding compared to formulas. For the mother, benefits include a possible lower risk of breast and ovarian cancers later in life.24,25 The levels of many nutrients in breast milk depend on the mother's diet, for example, minerals such as selenium and zinc, vitamins such as B6 and D, as well as omega-3 fatty acids, DHA and EPA.26,27 Some other milk components are not greatly affected by the mother's diet, for example, cholesterol and calcium; the latter is mobilized as needed from the mother's skeletal system. For energy, the recommendation during the first 12 months of breastfeeding is for an increase of about 300 to 400 kilocalories per day; this extra energy helps support milk production. For protein, the recommendation is for an increase of about 50 % during breastfeeding; this is the source of protein for the breastfeeding infant, also helps support milk production. A 50 % increase in the daily intake of the mineral zinc is recommended during breastfeeding; and for the mineral iodine the recommendation is for an increase of about 90 % (Appendix A). Sufficient iodine in the breast milk is important for the cognitive development of the infant. 106

Vitamins A and C have recommended intake increases of about 90 and 80 percent, respectively. For the B vitamins, the recommended increased intake is in the range of about 20 % for B12 and folate, 20 to 40% for niacin (B3), thiamin (B1), and riboflavin (B2), and about 50% increase for vitamin B6. These B vitamins support various cellular and metabolic functions; B1, B2 and B3 are especially important for obtaining energy from the metabolism of macronutrients. Increased intake of essential fatty acids, omega-3 and omega 6, is also recommended during breastfeeding. The longer chain omega-3 fatty acids, DHA (docosahexaenoic acid) and EPA (eicosapentaenoic acid), are important for normal fetal and infant development.

10.5 Infancy In addition to rapid increases in body weight and body length, infancy is a time of rapid physiological, psychological, and social changes,28,29 The stage of maturation, especially the development of the kidneys and gastrointestinal tract, determine the readiness to progress toward solid foods. Infants drink only breast milk or formula at birth, and typically progress to a diet that includes many finger foods and table foods, from all food groups, near the end of their first year. Note that cow’s milk is not recommended30 before the age of 1 year.

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Sufficient energy intake is critical to maintain normal, rapid growth; and insufficient energy may be detected using growth charts. Infants are generally able to adjust their intake, whether of mothers’ milk or formula, to their energy needs. Carbohydrates typically supply about 40-50 % of the energy during infancy. Lactose is the main carbohydrate source during the milk-dominated period of feeding. Sufficient intake of high-quality protein (high relative percentage of essential amino acids) is critical to maintain normal, rapid growth. The recommendations for protein intake, per kg of body weight, are typically higher in infancy than they will ever be again. Human milk is an adequate source of protein during the first six months, but other sources are usually required thereafter. A deficiency of essential amino acids in the early years of life is one of the most prevalent nutritional deficiencies, with major global consequences for child health.31 Infants require a diet rich in fat, at least 30 g or 270 kcal per day, or close to half of all daily energy intake. It is often a mistake for parents to limit the fat intake of young children, especially if they attempt to do this by emphasizing skim milk. Sufficient intake of the longer chain omega-3 fatty acids, DHA and EPA, is important during childhood.32

Human milk is typically the best food for a newborn. Formulas attempt to simulate the composition of human milk, even though most formulas are based on modified cow’s milk. Infants who do not tolerate a formula based on cow’s milk are usually offered a soy or hydrolyzed casein formula. Note 108

that soy formula is not the same as the more common soy beverages found in most supermarkets. Semi-solid foods are typically first introduced around the age of five or six months. Iron-fortified rice cereal is typically added first because iron is the first nutrient needed, and rice is a cereal that is not likely to be allergenic.

Children at play in a painting by Xia Kui (c. 1500, Ming dynasty)

10.6 Childhood Nutritional needs during childhood reflect physical growth and development, as well as activity level. The influence of peers and media increases as the child becomes more independent of the family. Inadequate nutrition during childhood and the teen years can retard growth and perhaps also impair learning ability.29 Sufficient energy and high-quality protein are critical to allow for optimal growth rates in children. The DRIs for estimated energy requirements can be calculated using formulas such the ones APPENDIX A. Daily energy requirements depend not only on rates of growth but also on the level of physical activity (or kcal used in physical activity per day). Protein recommendations per kg of body weight are typically higher for younger children compared to older children (specific numbers given in APPENDIX A). The recommended total amount of protein per day increases from infancy to early childhood, to the teen years; this parameter should 109

not be confused with recommendations made per kg of body weight. Children with food allergies, eating disorders, or those on vegan diets are typically most at risk for protein deficiency. Not all protein is of the same value for the body; high quality protein (e.g., contains more of the essential amino acids) is more abundant in animal product-based foods and is best for optimal body growth. Iron deficiency is one of the most common dietary deficiencies in North America for children under the age of four. Maintaining rapid growth rates requires an adequate supply of all essential nutrients, with special emphasis on those micronutrients whose deficiencies are most often noticed in children: e.g., iron, zinc, calcium, vitamin D. Use of multi-vitamin-mineral supplements is common among children. Supplements are especially useful in children with problems that make it difficult to eat a healthy diet, or other problems such as those related to the digestion and absorption of nutrients. Most national health agencies emphasize that people should try to get their nutrient requirements from foods and not pills, and also that it is much easier to get excessive or toxic amounts of nutrients (e.g., iron or vitamin A) from pill supplements than from foods. Toxicity may be especially problematic for children because of their smaller bodies and because they can confuse the sweet, fruity supplement pills with candy. Vitamin D requirements usually have to be met by consuming fortified foods (e.g., vitamin D-fortified milk) or taking supplements. The requirement for this vitamin also depends on factors such as sunlight exposure, geographic location, and skin color; children with darker skin produce less vitamin D upon sun exposure (see also Vitamins chapter). In addition to iron and protein deficiencies (mentioned above), deficiency of the mineral iodine is a global problem of childhood nutrition, especially in developing countries, and especially in the inland geographic regions, far from the sea—marine foods are good sources of iodine—and countries where use of iodized table salt is not common. It has been estimated that a few hundred million school-age children in the world have insufficient iodine intake which may contribute to learning problems and intellectual disability.33,34 The rapidly increasing number of overweight and obese children is a major national public health problem. The prevalence and severity of childhood obesity continues to increase. Obesity in childhood is known to greatly increase the risk of adulthood obesity. In general, strategies for dealing 110

with overweight problems in children involve dietary changes aimed at reducing the rate of weight gain, and not typically aimed at weight loss. A major component of such strategies is increased physical activity for the children.

10.7 Adolescence

Adolescent in a painting by Ditlev Blunck (1789-1853)

Adolescence can be a challenging stage of the life cycle in many ways, physically, mentally, socially. It is also nutritionally challenging; and during this time some lifelong nutrition-related and health-related behaviors may become set. Adolescence is a time for heightened concerns regarding body image and increased risk of disordered eating, e.g., bulimia nervosa and anorexia nervosa. Sufficient energy and high-quality protein (sufficient essential amino acids) are critical for body growth, and support the accelerated growth that occurs during early adolescence. APPENDIX A provides information on energy and protein requirements. A growing problem among teens is excessive energy intake, mainly from foods with added sugar (e.g., candy and soft drinks) and added fat (e.g., snacks and fried foods such as chips); these foods also typically have low levels of many essential nutrients. Adequate intake of essential fatty acids is also important for normal growth.31 The DRIs (AIs in this case) for linoleic and alpha-linolenic are given in APPENDIX A. As is the case for many adults, an upper limit of 10% of total calories from saturated fatty acids is recommended for adolescents. The adolescent DRIs for various vitamins and minerals are also given in APPENDIX A. For example, calcium recommendations (mg/day) are highest for the teenage years; much of it is needed for deposition in bone during the growth spurt. In this context, sufficient vitamin D intake, e.g., obtained through consumption of vitamin D-fortified dairy products, is also important; low calcium intake is becoming more of a problem as teens replace milk with soft-drinks (sweetened sodas).35,36 Iron, zinc, folic acid are other important micronutrients emphasized for adolescents. Irregular meals and consumption of high fat and sugar snacks or fast foods can increase the risk of nutrient deficiencies, and are especially common 111

Potato chips (also called crisps) are typically high in fat and salt.

problems among adolescents.37 Strict vegetarian diets may increase risks of nutrient deficiencies, e.g., vitamin B12, omega-3 fatty acids such as EPA and DHA, calcium, vitamin D, zinc, and iron, nutrients that are important for growth during adolescence.38,39 Problems may be avoided in these cases by choosing nutrient-fortified vegetarian foods or taking nutrient supplements.

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REFERENCES and further reading

Chapter 1

1. Institute of Medicine 2005. Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein, and Amino Acids. Washington, DC: The National Academies Press. 2. Ames, BN. Optimal micronutrients delay mitochondrial decay and ageassociated diseases. Mechanisms of Ageing and Development, 2010, 131 (7– 8):473-479. 3. Gascon-Barré M, Mongeau E, Dubuc MB. Use of vitamin and mineral supplements by urban school children: prevalence and justification. Can J Public Health. 1973 Nov-Dec;64(6):537-47. 4. Druesne-Pecollo N, Latino-Martel P, Norat T, Barrandon E, Bertrais S, Galan P, Hercberg S. Beta-carotene supplementation and cancer risk: a systematic review and meta analysis of randomized controlled trials. Int J Cancer. 2010 Jul 1;127(1):172-84. 5. Goodman GE, Thornquist MD, Balmes J, Cullen MR, Meyskens FL Jr, Omenn GS, Valanis B, Williams JH Jr. The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements. J Natl Cancer Inst. 2004 Dec 1;96(23):1743-50. 6. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group (Finland). N Engl J Med 1994;330: 1029 –35. 7. Omenn GS, Goodman G, Thornquist M, Grizzle J, Rosenstock L, Barnhart S, et al. The beta-carotene and retinol efficacy trial (CARET) for chemoprevention of lung cancer in high risk populations: smokers and asbestos-exposed workers. Cancer Res 1994;54 (7b Suppl): 2038s –2043s. 8. Li, S., Yang, D., Gao, L., Wang, Y., Peng, Q. Epigenetic regulation and mechanobiology. Biophys Rep 6, 33–48 (2020). 9. Wang Z, Heshka S, Gallagher D, Boozer CN, Kotler DP, Heymsfield SB. Resting energy expenditure-fat-free mass relationship: new insights provided by body composition modeling. Am J Physiol Endocrinol Metab. 2000 Sep;279(3):E53945.

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Chapter 2

1. Kim MooJung, Moon YouYoun, Kopsell DA, Park SueJin, Tou JC, Waterland NL. Nutritional value of crisphead 'Iceberg' and romaine lettuces (Lactuca sativa L.). Journal of Agricultural Science. 2016; 8(11):1-10. 2. Canada’s Food Guide. Health Canada. Government of Canada. 2020. https://food-guide.canada.ca/en/ 3. Dwyer JT, Allison DB, Coates PM. Dietary supplements in weight reduction. J Am Diet Assoc. 2005 May;105(5 Suppl 1):S80-6. 4. Chandra RK, Imbach A, Moore C, Skelton D, Woolcott D. Nutrition of the elderly. CMAJ. 1991 Dec 1;145(11):1475-87. 5. WHO package of essential noncommunicable (PEN) disease interventions for primary health care. Geneva: World Health Organization; 2020. 6. Huang HY, Caballero B, Chang S, Alberg AJ, Semba RD, Schneyer CR, Wilson RF, Cheng TY, Vassy J, Prokopowicz G, Barnes GJ 2nd, Bass EB. The efficacy and safety of multivitamin and mineral supplement use to prevent cancer and chronic disease in adults: a systematic review for a National Institutes of Health state-of-the-science conference. Ann Intern Med. 2006 Sep 5;145(5):372-85. 7. Gascon-Barré M, Mongeau E, Dubuc MB. Use of vitamin and mineral supplements by urban school children: prevalence and justification. Can J Public Health. 1973 Nov-Dec;64(6):537-47.

Chapter 3

1. WHO package of essential noncommunicable (PEN) disease interventions for primary health care. Geneva: World Health Organization; 2020. 2. Global Atlas on Cardiovascular Disease Prevention and Control. Mendis S, Puska P, Norrving B editors. World Health Organization, Geneva 2011. 3. Swanson D, Block R, Mousa SA. Omega-3 fatty acids EPA and DHA: health benefits throughout life. Adv Nutr. 2012 Jan;3(1):1-7 4. Nelson JR, Raskin S. The eicosapentaenoic acid:arachidonic acid ratio and its clinical utility in cardiovascular disease. Postgrad Med. 2019 May;131(4):268277.

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5. Wolf D, Ley K. Immunity and Inflammation in Atherosclerosis. Circ Res. 2019 Jan 18;124(2):315-327. 6. Wang X, Ouyang Y, Liu J, Zhu M, Zhao G, Bao W, Hu FB. Fruit and vegetable consumption and mortality from all causes, cardiovascular disease, and cancer: systematic review and dose-response meta-analysis of prospective cohort studies. BMJ. 2014 Jul 29;349:g4490. 7. Simonetto M, Infante M, Sacco RL, Rundek T, Della-Morte D. A Novel AntiInflammatory Role of Omega-3 PUFAs in Prevention and Treatment of Atherosclerosis and Vascular Cognitive Impairment and Dementia. Nutrients. 2019 Sep 23;11(10):2279. 8. Threapleton DE, Greenwood DC, Evans CE, Cleghorn CL, Nykjaer C, Woodhead C, Cade JE, Gale CP, Burley VJ. Dietary fibre intake and risk of cardiovascular disease: systematic review and meta-analysis. BMJ. 2013 Dec 19;347:f6879. 9. Brouwer IA, Wanders AJ, Katan MB. Effect of animal and industrial trans fatty acids on HDL and LDL cholesterol levels in humans--a quantitative review. PLoS One. 2010 Mar 2;5(3):e9434. 10. Guay V, Lamarche B, Charest A, Tremblay AJ, Couture P. Effect of short-term low- and high-fat diets on low-density lipoprotein particle size in normolipidemic subjects. Metabolism. 2012 Jan;61(1):76-83. 11. Fats and fatty acids in human nutrition: report of an expert consultation. FAO Food and Nutrition Paper 91. Rome: Food and Agriculture Organization of the United Nations; 2010. 12. Diet, nutrition and the prevention of chronic diseases: report of a Joint WHO/FAO Expert Consultation. WHO Technical Report Series, No. 916. Geneva: World Health Organization; 2003.

Chapter 4

1. Classification of diabetes mellitus. Geneva: World Health Organization; 2019 2. WHO package of essential noncommunicable (PEN) disease interventions for primary health care. Geneva: World Health Organization; 2020. 3. Sarwar N, Gao P, Seshasai SR, Gobin R, Kaptoge S, Di Angelantonio E, Ingelsson E, Lawlor DA, Selvin E, Stampfer M, Stehouwer CD, Lewington S, Pennells L, Thompson A, Sattar N, White IR, Ray KK, Danesh J. Diabetes mellitus, fasting blood glucose concentration, and risk of vascular disease: a collaborative meta-analysis of 102 prospective studies. Emerging Risk Factors Collaboration, Lancet. 2010 Jun 26;375(9733):2215-22. 115

4. Guideline: Sugars intake for adults and children. Geneva: World Health Organization; 2015. 5. Diet, nutrition and the prevention of chronic diseases: report of a Joint WHO/FAO Expert Consultation. WHO Technical Report Series, No. 916. Geneva: World Health Organization; 2003. 6. Rao Kondapally Seshasai S, Kaptoge S, Thompson A, Di Angelantonio E, Gao P, Sarwar N, Whincup PH, Mukamal KJ, Gillum RF, Holme I, Njølstad I, Fletcher A, Nilsson P, Lewington S, Collins R, Gudnason V, Thompson SG, Sattar N, Selvin E, Hu FB, Danesh J; Emerging Risk Factors Collaboration. Diabetes mellitus, fasting glucose, and risk of cause-specific death. N Engl J Med. 2011 Mar 3;364(9):829841. 7. Ahmed F, Sairam S, Urooj A. In vitro hypoglycemic effects of selected dietary fiber sources. J Food Sci Technol. 2011 Jun;48(3):285-9. 8. Hartley L, May MD, Loveman E, Colquitt JL, Rees K. Dietary fibre for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2016 Jan 7;2016(1):CD011472. 9. Chiu THT, Pan WH, Lin MN, Lin CL. Vegetarian diet, change in dietary patterns, and diabetes risk: a prospective study. Nutr Diabetes. 2018 Mar 9;8(1):12. 10. Emadian A, Andrews RC, England CY, Wallace V, Thompson JL. The effect of macronutrients on glycaemic control: a systematic review of dietary randomised controlled trials in overweight and obese adults with type 2 diabetes in which there was no difference in weight loss between treatment groups. Br J Nutr. 2015 Nov 28;114(10):1656-66. 12. Rienks J, Barbaresko J, Nöthlings U. Association of isoflavone biomarkers with risk of chronic disease and mortality: a systematic review and metaanalysis of observational studies. Nutr Rev. 2017 Aug 1;75(8):616-641.

Chapter 5

1. Pham TP, Alou MT, Golden MH, Million M, Raoult D. Difference between kwashiorkor and marasmus: Comparative meta-analysis of pathogenic characteristics and implications for treatment. Microb Pathog. 2021 Jan;150:104702. 2. Xiao F, Guo F. Impacts of essential amino acids on energy balance. Mol Metab. 2021 Nov 14:101393. 3. van Spronsen FJ, Blau N, Harding C, Burlina A, Longo N, Bosch AM. Phenylketonuria. Nat Rev Dis Primers. 2021 May 20;7(1):36. 116

4. Brouwer IA, Wanders AJ, Katan MB. Effect of animal and industrial trans fatty acids on HDL and LDL cholesterol levels in humans--a quantitative review. PLoS One. 2010 Mar 2;5(3):e9434. 5. Fats and fatty acids in human nutrition: report of an expert consultation. FAO Food and Nutrition Paper 91. Rome: Food and Agriculture Organization of the United Nations; 2010. 6. Diet, nutrition and the prevention of chronic diseases: report of a Joint WHO/FAO Expert Consultation. WHO Technical Report Series, No. 916. Geneva: World Health Organization; 2003. 7. Semba RD, Shardell M, Sakr Ashour FA, Moaddel R, Trehan I, Maleta KM, Ordiz MI, Kraemer K, Khadeer MA, Ferrucci L, Manary MJ. Child Stunting is Associated with Low Circulating Essential Amino Acids. EBioMedicine. 2016 Apr;6:246-252.

Chapter 6

1. Dimidi E, Cox SR, Rossi M, Whelan K. Fermented Foods: Definitions and Characteristics, Impact on the Gut Microbiota and Effects on Gastrointestinal Health and Disease. Nutrients. 2019 Aug 5;11(8):1806. 2. Menzie CM, Yanoff LB, Denkinger BI, McHugh T, Sebring NG, Calis KA, Yanovski JA. Obesity-related hypoferremia is not explained by differences in reported intake of heme and nonheme iron or intake of dietary factors that can affect iron absorption. J Am Diet Assoc. 2008 Jan;108(1):145-8. 3. Rienks J, Barbaresko J, Nöthlings U. Association of isoflavone biomarkers with risk of chronic disease and mortality: a systematic review and meta-analysis of observational studies. Nutr Rev. 2017 Aug 1;75(8):616-641. 4. Meeran, S. M., Patel, S. N., & Tollefsbol, T. O. Sulforaphane causes epigenetic repression of hTERT expression in human breast cancer cell lines. PLoS ONE. 2010;5(7). 5. Ou CC, Tsao SM, Lin MC, Yin MC. Protective action on human LDL against oxidation and glycation by four organosulfur compounds derived from garlic. Lipids. 2003 Mar;38(3):219-24. 6. Djuric Z, Chen G, Doerge DR, Heilbrun LK, Kucuk O. Effect of soy isoflavone supplementation on markers of oxidative stress in men and women. Cancer Lett. 2001;172(1): 1–6. 7. Chambers ES, Viardot A, Psichas A, Morrison DJ, Murphy KG, Zac-Varghese SE, MacDougall K, Preston T, Tedford C, Finlayson GS, Blundell JE, Bell JD, Thomas 117

EL, Mt-Isa S, Ashby D, Gibson GR, Kolida S, Dhillo WS, Bloom SR, Morley W, Clegg S, Frost G. Effects of targeted delivery of propionate to the human colon on appetite regulation, body weight maintenance and adiposity in overweight adults. Gut. 2015;64(11):1744-54. 8. Hartley L, May MD, Loveman E, Colquitt JL, Rees K. Dietary fibre for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2016 Jan 7;2016(1):CD011472. 9. Kasubuchi M, Hasegawa S, Hiramatsu T, Ichimura A, Kimura I. Dietary gut microbial metabolites, short-chain fatty acids, and host metabolic regulation. Nutrients. 2015;7(4):2839-49. 10. Rudloff S, Bührer C, Jochum F, Kauth T, Kersting M, Körner A, Koletzko B, Mihatsch W, Prell C, Reinehr T, Zimmer KP. Vegetarian diets in childhood and adolescence : Position paper of the nutrition committee, German Society for Paediatric and Adolescent Medicine (DGKJ). Mol Cell Pediatr. 2019 Nov 12;6(1):4. 11. Van Winckel M, Vande Velde S, De Bruyne R, Van Biervliet S. Clinical practice: vegetarian infant and child nutrition. Eur J Pediatr. 2011 Dec;170(12):1489-94. 12. Ekman M, Reizenstein P. Comparative absorption of ferrous and heme-iron with meals in normal and iron deficient subjects. Z Ernahrungswiss. 1993 Mar;32(1):67-70. 13. Björn-Rasmussen E, Hallberg L, Isaksson B, Arvidsson B. Food iron absorption in man. Applications of the two-pool extrinsic tag method to measure heme and nonheme iron absorption from the whole diet. J Clin Invest. 1974 Jan;53(1):24755. 14. Huang HY, Caballero B, Chang S, Alberg AJ, Semba RD, Schneyer CR, Wilson RF, Cheng TY, Vassy J, Prokopowicz G, Barnes GJ 2nd, Bass EB. The efficacy and safety of multivitamin and mineral supplement use to prevent cancer and chronic disease in adults: a systematic review for a National Institutes of Health state-of-the-science conference. Ann Intern Med. 2006 Sep 5;145(5):372-85. 15. Gascon-Barré M, Mongeau E, Dubuc MB. Use of vitamin and mineral supplements by urban school children: prevalence and justification. Can J Public Health. 1973 Nov-Dec;64(6):537-47. 16. Otun J, Sahebkar A, Östlundh L, Atkin SL, Sathyapalan T. Systematic Review and Meta-analysis on the Effect of Soy on Thyroid Function. Sci Rep. 2019 Mar 8;9(1):3964. 17. Guha N, Kwan ML, Quesenberry CP Jr, Weltzien EK, Castillo AL, Caan BJ. Soy isoflavones and risk of cancer recurrence in a cohort of breast cancer survivors:

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the Life After Cancer Epidemiology study. Breast Cancer Res Treat. 2009 Nov;118(2):395-405. 18. Fritz H, Seely D, Flower G, Skidmore B, Fernandes R, Vadeboncoeur S, Kennedy D, Cooley K, Wong R, Sagar S, Sabri E, Fergusson D. Soy, red clover, and isoflavones and breast cancer: a systematic review. PLoS One. 2013 Nov 28;8(11):e81968. 19. Zhu J, Pouillot R, Kwegyir-Afful EK, Luccioli S, Gendel SM. A retrospective analysis of allergic reaction severities and minimal eliciting doses for peanut, milk, egg, and soy oral food challenges. Food Chem Toxicol. 2015 Jun;80:92-100. 20. Key TJ. Fruit and vegetables and cancer risk. Br J Cancer. 2011 Jan 4;104(1):6-11. 21. Bradbury KE, Appleby PN, Key TJ. Fruit, vegetable, and fiber intake in relation to cancer risk: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC). Am J Clin Nutr. 2014 Jul;100 Suppl 1:394S-8S. 22. Chiu THT, Pan WH, Lin MN, Lin CL. Vegetarian diet, change in dietary patterns, and diabetes risk: a prospective study. Nutr Diabetes. 2018 Mar 9;8(1):12. 23. Chuang SY, Chiu TH, Lee CY, Liu TT, Tsao CK, Hsiung CA, Chiu YF. Vegetarian diet reduces the risk of hypertension independent of abdominal obesity and inflammation: a prospective study. J Hypertens. 2016 Nov;34(11):2164-71. 24. Cryan JF, O'Riordan KJ, Sandhu K, Peterson V, Dinan TG. The gut microbiome in neurological disorders. Lancet Neurol. 2020 Feb;19(2):179-194. 25. Chiu THT, Chang HR, Wang LY, Chang CC, Lin MN, Lin CL. Vegetarian diet and incidence of total, ischemic, and hemorrhagic stroke in 2 cohorts in Taiwan. Neurology. 2020 Mar 17;94(11):e1112-e1121. 26. Watanabe F, Yabuta Y, Tanioka Y, Bito T. Biologically active vitamin B12 compounds in foods for preventing deficiency among vegetarians and elderly subjects. J Agric Food Chem. 2013 Jul 17;61(28):6769-75

Chapter 7

1. WHO package of essential noncommunicable (PEN) disease interventions for primary health care. Geneva: World Health Organization; 2020. 2. Wild CP, Weiderpass E, Stewart BW, editors (2020). World Cancer Report: Cancer Research for Cancer Prevention. Lyon, France: International Agency for Research on Cancer

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3. Kushi LH, Doyle C, McCullough M, Rock CL, Demark-Wahnefried W, Bandera EV, Gapstur S, Patel AV, Andrews K, Gansler T; American Cancer Society 2010 Nutrition and Physical Activity Guidelines Advisory Committee. American Cancer Society Guidelines on nutrition and physical activity for cancer prevention: reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J Clin. 2012 Jan-Feb;62(1):30-67 4. Byers T, Nestle M, McTiernan A, Doyle C, Currie-Williams A, Gansler T, Thun M; American Cancer Society 2001 Nutrition and Physical Activity Guidelines Advisory Committee. American Cancer Society guidelines on nutrition and physical activity for cancer prevention: Reducing the risk of cancer with healthy food choices and physical activity. CA Cancer J Clin. 2002 Mar-Apr;52(2):92-119. 5. Vieira AR, Abar L, Vingeliene S, Chan DS, Aune D, Navarro-Rosenblatt D, Stevens C, Greenwood D, Norat T. Fruits, vegetables and lung cancer risk: a systematic review and meta-analysis. Ann Oncol. 2016 Jan;27(1):81-96 6. Miller AB, Altenburg HP, Bueno-de-Mesquita B, Boshuizen HC, Agudo A, Berrino F, Gram IT, Janson L, Linseisen J, Overvad K, Rasmuson T, Vineis P, Lukanova A, Allen N, Amiano P, Barricarte A, Berglund G, Boeing H, ClavelChapelon F, Day NE, Hallmans G, Lund E, Martinez C, Navarro C, Palli D, Panico S, Peeters PH, Quirós JR, Tjønneland A, Tumino R, Trichopoulou A, Trichopoulos D, Slimani N, Riboli E. Fruits and vegetables and lung cancer: Findings from the European Prospective Investigation into Cancer and Nutrition. Int J Cancer. 2004 Jan 10;108(2):269-76 7. Key TJ. Fruit and vegetables and cancer risk. Br J Cancer. 2011 Jan 4;104(1):611. 8. Bradbury KE, Appleby PN, Key TJ. Fruit, vegetable, and fiber intake in relation to cancer risk: findings from the European Prospective Investigation into Cancer and Nutrition (EPIC). Am J Clin Nutr. 2014 Jul;100 Suppl 1:394S-8S. 9. Bektas A, Schurman SH, Sen R, Ferrucci L. Aging, inflammation and the environment. Exp Gerontol. 2018 May;105:10-18. 10. Sims-Robinson C, Hur J, Hayes JM, Dauch JR, Keller PJ, Brooks SV, Feldman EL. The role of oxidative stress in nervous system aging. PLoS One. 2013 Jul 2;8(7):e68011. 11. Watanabe F, Yabuta Y, Tanioka Y, Bito T. Biologically active vitamin B12 compounds in foods for preventing deficiency among vegetarians and elderly subjects. J Agric Food Chem. 2013 Jul 17;61(28):6769-75. 12. Molloy AM, Kirke PN, Brody LC, Scott JM, Mills JL. Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant, and child development. Food Nutr Bull. 2008 Jun;29(2 Suppl):S101-11.

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13. Hovdenak N, Haram K. Influence of mineral and vitamin supplements on pregnancy outcome. Eur J Obstet Gynecol Reprod Biol. 2012 Oct;164(2):127-32 14. Czeizel AE, Dudás I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med. 1992 Dec 24;327(26):1832-5. 15. Greenberg JA, Bell SJ, Guan Y, Yu YH. Folic Acid supplementation and pregnancy: more than just neural tube defect prevention. Rev Obstet Gynecol. 2011 Summer;4(2):52-9. 16. Bastos Maia S, Rolland Souza AS, Costa Caminha MF, Lins da Silva S, Callou Cruz RSBL, Carvalho Dos Santos C, Batista Filho M. Vitamin A and Pregnancy. Nutrients. 2019 Mar 22;11(3):681. 17. Lammer EJ, Chen DT, Hoar RM, Agnish ND, Benke PJ, Braun JT, Curry CJ, Fernhoff PM, Grix AW Jr, Lott IT, et al. Retinoic acid embryopathy. N Engl J Med. 1985 Oct 3;313(14):837-41. 18. LoConte NK, Brewster AM, Kaur JS, Merrill JK, Alberg AJ. Alcohol and Cancer: A Statement of the American Society of Clinical Oncology. J Clin Oncol. 2018 Jan 1;36(1):83-93. 19. Jägerstad M, Skog K. Genotoxicity of heat-processed foods. Mutat Res. 2005 Jul 1;574(1-2):156-72. 20. Li Z, Shen J, Wu WK, Wang X, Liang J, Qiu G, Liu J. Vitamin A deficiency induces congenital spinal deformities in rats. PLoS One. 2012;7(10):e46565. 21. Clagett-Dame M, DeLuca HF. The role of vitamin A in mammalian reproduction and embryonic development. Annu Rev Nutr. 2002;22:347-81.

Chapter 8

1. Björn-Rasmussen E, Hallberg L, Isaksson B, Arvidsson B. Food iron absorption in man. Applications of the two-pool extrinsic tag method to measure heme and nonheme iron absorption from the whole diet. J Clin Invest. 1974 Jan;53(1):24755. 2. Menzie CM, Yanoff LB, Denkinger BI, McHugh T, Sebring NG, Calis KA, Yanovski JA. Obesity-related hypoferremia is not explained by differences in reported intake of heme and nonheme iron or intake of dietary factors that can affect iron absorption. J Am Diet Assoc. 2008 Jan;108(1):145-8. 3. Gaitán D, Flores S, Saavedra P, Miranda C, Olivares M, Arredondo M, López de Romaña D, Lönnerdal B, Pizarro F. Calcium does not inhibit the absorption of 5

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milligrams of nonheme or heme iron at doses less than 800 milligrams in nonpregnant women. J Nutr. 2011 Sep;141(9):1652-6. 4. Ekman M, Reizenstein P. Comparative absorption of ferrous and heme-iron with meals in normal and iron deficient subjects. Z Ernahrungswiss. 1993 Mar;32(1):67-70. 5. Hommos MS, Glassock RJ, Rule AD. Structural and Functional Changes in Human Kidneys with Healthy Aging. J Am Soc Nephrol. 2017 Oct;28(10):28382844. 6. Hooper L, Bunn D, Jimoh FO, Fairweather-Tait SJ. Water-loss dehydration and aging. Mech Ageing Dev. 2014 Mar-Apr;136-137:50-8. 7. Hovdenak N, Haram K. Influence of mineral and vitamin supplements on pregnancy outcome. Eur J Obstet Gynecol Reprod Biol. 2012 Oct;164(2):127-32 8. Darnton-Hill I, Mkparu UC. Micronutrients in pregnancy in low- and middleincome countries. Nutrients. 2015 Mar 10;7(3):1744-68. 9. Zhao W, Li X, Xia X, Gao Z, Han C. Iodine Nutrition During Pregnancy: Past, Present, and Future. Biol Trace Elem Res. 2019 Mar;188(1):196-207. 10. Zimmermann MB, Jooste PL, Pandav CS. Iodine-deficiency disorders. Lancet. 2008 Oct 4;372(9645):1251-62. 11. Uriu-Adams JY, Keen CL. Zinc and reproduction: effects of zinc deficiency on prenatal and early postnatal development. Birth Defects Res B Dev Reprod Toxicol. 2010 Aug;89(4):313-25. 12. Hofstee P, Bartho LA, McKeating DR, Radenkovic F, McEnroe G, Fisher JJ, Holland OJ, Vanderlelie JJ, Perkins AV, Cuffe JSM. Maternal selenium deficiency during pregnancy in mice increases thyroid hormone concentrations, alters placental function and reduces fetal growth. J Physiol. 2019 Dec;597(23):55975617.

Chapter 9

1. Charlebois S, Juhasz M, Music J, Vézeau J. A review of Canadian and international food safety systems: Issues and recommendations for the future. Compr Rev Food Sci Food Saf. 2021 Sep;20(5):5043-5066. 2. Dharod JM, Perez-Escamilla R, Bermudez-Millan A, Segura-Perez S, Damio G. Influence of the Fight BAC! food safety campaign on an urban Latino population in Connecticut. J Nutr Educ Behav. 2004 May-Jun;36(3):128-32.

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3. Trepka MJ, Newman FL, Dixon Z, Huffman FG. Food safety practices among pregnant women and mothers in the women, infants, and children program, Miami, Florida. J Food Prot. 2007 May;70(5):1230-7. 4. Stratakis N, Conti DV, Borras E, Sabido E, Roumeliotaki T, Papadopoulou E, Agier L, Basagana X, Bustamante M, Casas M, Farzan SF, Fossati S, Gonzalez JR, Grazuleviciene R, Heude B, Maitre L, McEachan RRC, Theologidis I, Urquiza J, Vafeiadi M, West J, Wright J, McConnell R, Brantsaeter AL, Meltzer HM, Vrijheid M, Chatzi L. Association of Fish Consumption and Mercury Exposure During Pregnancy With Metabolic Health and Inflammatory Biomarkers in Children. JAMA Netw Open. 2020 Mar 2;3(3):e201007. 5. Solan TD, Lindow SW. Mercury exposure in pregnancy: a review. J Perinat Med. 2014 Nov;42(6):725-9. 6. LoConte NK, Brewster AM, Kaur JS, Merrill JK, Alberg AJ. Alcohol and Cancer: A Statement of the American Society of Clinical Oncology. J Clin Oncol. 2018 Jan 1;36(1):83-93. 7. Wild CP, Weiderpass E, Stewart BW, editors (2020). World Cancer Report: Cancer Research for Cancer Prevention. Lyon, France: International Agency for Research on Cancer 8. Wild CP, Weiderpass E, Stewart BW, editors (2020). World Cancer Report: Cancer Research for Cancer Prevention. Lyon, France: International Agency for Research on Cancer 9. Barceloux DG. Potatoes, tomatoes, and solanine toxicity (Solanum tuberosum L., Solanum lycopersicum L.). Dis Mon. 2009 Jun;55(6):391-402 10. Li J, Wang Z, Karim MR, Zhang L. Detection of human intestinal protozoan parasites in vegetables and fruits: a review. Parasit Vectors. 2020 Jul 29;13(1):380 11. Bosch A, Gkogka E, Le Guyader FS, Loisy-Hamon F, Lee A, van Lieshout L, Marthi B, Myrmel M, Sansom A, Schultz AC, Winkler A, Zuber S, Phister T. Foodborne viruses: Detection, risk assessment, and control options in food processing. Int J Food Microbiol. 2018 Nov 20;285:110-128. 12. McEvoy JD. Emerging food safety issues: An EU perspective. Drug Test Anal. 2016 May;8(5-6):511-20. 13. Onodera T, Sakudo A. Introduction to Current Progress in Advanced Research on Prions. Curr Issues Mol Biol. 2020;36:63-66. 14. Söderqvist K, Rosberg AK, Boqvist S, Alsanius B, Mogren L, Vågsholm I. Season and Species: Two Possible Hurdles for Reducing the Food Safety Risk of Escherichia coli O157 Contamination of Leafy Vegetables. J Food Prot. 2019 Feb;82(2):247-255. 123

15. Nguyen TT, Rosello C, Bélanger R, Ratti C. Fate of Residual Pesticides in Fruit and Vegetable Waste (FVW) Processing. Foods. 2020; 9(10):1468.

Chapter 10

1. J. O. Hooper, FH Hooper, K Colbert, R. McMahan. Cognition, memory, and personality in elderly students. Edu Gerontol. 1986 Feb;12(3):219-229. 2. Sims-Robinson C, Hur J, Hayes JM, Dauch JR, Keller PJ, Brooks SV, Feldman EL. The role of oxidative stress in nervous system aging. PLoS One. 2013 Jul 2;8(7):e68011. 3. Barcelos IP, Haas RH. CoQ10 and Aging. Biology (Basel). 2019 May 11;8(2):28. 4. Bektas A, Schurman SH, Sen R, Ferrucci L. Aging, inflammation and the environment. Exp Gerontol. 2018 May;105:10-18. 5. Fagundes Belchior G, Kirk B, Pereira da Silva EA, Duque G. Osteosarcopenia: beyond age-related muscle and bone loss. Eur Geriatr Med. 2020 Oct;11(5):715724. 6. Bhattarai HK, Shrestha S, Rokka K, Shakya R. Vitamin D, Calcium, Parathyroid Hormone, and Sex Steroids in Bone Health and Effects of Aging. J Osteoporos. 2020 Jun 17;2020:9324505 7. Watanabe F, Yabuta Y, Tanioka Y, Bito T. Biologically active vitamin B12 compounds in foods for preventing deficiency among vegetarians and elderly subjects. J Agric Food Chem. 2013 Jul 17;61(28):6769-75. 8. Hommos MS, Glassock RJ, Rule AD. Structural and Functional Changes in Human Kidneys with Healthy Aging. J Am Soc Nephrol. 2017 Oct;28(10):28382844. 9. Hooper L, Bunn D, Jimoh FO, Fairweather-Tait SJ. Water-loss dehydration and aging. Mech Ageing Dev. 2014 Mar-Apr;136-137:50-8. 10. WHO package of essential noncommunicable (PEN) disease interventions for primary health care. Geneva: World Health Organization; 2020. 11. Molloy AM, Kirke PN, Brody LC, Scott JM, Mills JL. Effects of folate and vitamin B12 deficiencies during pregnancy on fetal, infant, and child development. Food Nutr Bull. 2008 Jun;29(2 Suppl):S101-11. 12. Hovdenak N, Haram K. Influence of mineral and vitamin supplements on pregnancy outcome. Eur J Obstet Gynecol Reprod Biol. 2012 Oct;164(2):127-32

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13. Czeizel AE, Dudás I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med. 1992 Dec 24;327(26):1832-5. 14. Greenberg JA, Bell SJ, Guan Y, Yu YH. Folic Acid supplementation and pregnancy: more than just neural tube defect prevention. Rev Obstet Gynecol. 2011 Summer;4(2):52-9. 15. Darnton-Hill I, Mkparu UC. Micronutrients in pregnancy in low- and middleincome countries. Nutrients. 2015 Mar 10;7(3):1744-68. 16. Bastos Maia S, Rolland Souza AS, Costa Caminha MF, Lins da Silva S, Callou Cruz RSBL, Carvalho Dos Santos C, Batista Filho M. Vitamin A and Pregnancy. Nutrients. 2019 Mar 22;11(3):681. 17. Lammer EJ, Chen DT, Hoar RM, Agnish ND, Benke PJ, Braun JT, Curry CJ, Fernhoff PM, Grix AW Jr, Lott IT, et al. Retinoic acid embryopathy. N Engl J Med. 1985 Oct 3;313(14):837-41. 18. Ekman M, Reizenstein P. Comparative absorption of ferrous and heme-iron with meals in normal and iron deficient subjects. Z Ernahrungswiss. 1993 Mar;32(1):67-70. 19. Björn-Rasmussen E, Hallberg L, Isaksson B, Arvidsson B. Food iron absorption in man. Applications of the two-pool extrinsic tag method to measure heme and nonheme iron absorption from the whole diet. J Clin Invest. 1974 Jan;53(1):24755. 20. Chittimoju SB, Pearce EN. Iodine Deficiency and Supplementation in Pregnancy. Clin Obstet Gynecol. 2019 Jun;62(2):330-338. 21. Zhao W, Li X, Xia X, Gao Z, Han C. Iodine Nutrition During Pregnancy: Past, Present, and Future. Biol Trace Elem Res. 2019 Mar;188(1):196-207. 22. Hovdenak N, Haram K. Influence of mineral and vitamin supplements on pregnancy outcome. Eur J Obstet Gynecol Reprod Biol. 2012 Oct;164(2):127-32 23. Darnton-Hill I, Mkparu UC. Micronutrients in pregnancy in low- and middleincome countries. Nutrients. 2015 Mar 10;7(3):1744-68. 24. Westerfield KL, Koenig K, Oh R. Breastfeeding: Common Questions and Answers. Am Fam Physician. 2018 Sep 15;98(6):368-373. 25. Binns C, Lee M, Low WY. The Long-Term Public Health Benefits of Breastfeeding. Asia Pac J Public Health. 2016 Jan;28(1):7-14. 26. Bravi F, Wiens F, Decarli A, Dal Pont A, Agostoni C, Ferraroni M. Impact of maternal nutrition on breast-milk composition: a systematic review. Am J Clin Nutr. 2016 Sep;104(3):646-62.

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27. Mosca F, Giannì ML. Human milk: composition and health benefits. Pediatr Med Chir. 2017 Jun 28;39(2):155. 28. Alderman H, Fernald L. The Nexus Between Nutrition and Early Childhood Development. Annu Rev Nutr. 2017 Aug 21;37:447-476. 29. Black MM, Pérez-Escamilla R, Rao SF. Integrating nutrition and child development interventions: scientific basis, evidence of impact, and implementation considerations. Adv Nutr. 2015 Nov;6(6):852-9. 30. Ziegler EE. Adverse effects of cow's milk in infants. Nestle Nutr Workshop Ser Pediatr Program. 2007;60:185-199. 31. Semba RD, Shardell M, Sakr Ashour FA, Moaddel R, Trehan I, Maleta KM, Ordiz MI, Kraemer K, Khadeer MA, Ferrucci L, Manary MJ. Child Stunting is Associated with Low Circulating Essential Amino Acids. EBioMedicine. 2016 Apr;6:246-252. 32. Basak S, Vilasagaram S, Duttaroy AK. Maternal dietary deficiency of n-3 fatty acids affects metabolic and epigenetic phenotypes of the developing fetus. Prostaglandins Leukot Essent Fatty Acids. 2020 Jul;158:102109. 33. Zhao W, Li X, Xia X, Gao Z, Han C. Iodine Nutrition During Pregnancy: Past, Present, and Future. Biol Trace Elem Res. 2019 Mar;188(1):196-207. 34. Zimmermann MB, Jooste PL, Pandav CS. Iodine-deficiency disorders. Lancet. 2008 Oct 4;372(9645):1251-62. 35. McGartland C, Robson PJ, Murray L, Cran G, Savage MJ, Watkins D, Rooney M, Boreham C. Carbonated soft drink consumption and bone mineral density in adolescence: the Northern Ireland Young Hearts project. J Bone Miner Res. 2003 Sep;18(9):1563-9. 36. American Academy of Pediatrics Committee on School Health. Soft drinks in schools. Pediatrics. 2004 Jan;113(1 Pt 1):152-4. 37. Liberali R, Kupek E, Assis MAA. Dietary Patterns and Childhood Obesity Risk: A Systematic Review. Child Obes. 2020 Mar;16(2):70-85. 38. Rudloff S, Bührer C, Jochum F, Kauth T, Kersting M, Körner A, Koletzko B, Mihatsch W, Prell C, Reinehr T, Zimmer KP. Vegetarian diets in childhood and adolescence : Position paper of the nutrition committee, German Society for Paediatric and Adolescent Medicine (DGKJ). Mol Cell Pediatr. 2019 Nov 12;6(1):4. 39. Van Winckel M, Vande Velde S, De Bruyne R, Van Biervliet S. Clinical practice: vegetarian infant and child nutrition. Eur J Pediatr. 2011 Dec;170(12):1489-94.

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40. Huang HY, Caballero B, Chang S, Alberg AJ, Semba RD, Schneyer CR, Wilson RF, Cheng TY, Vassy J, Prokopowicz G, Barnes GJ 2nd, Bass EB. The efficacy and safety of multivitamin and mineral supplement use to prevent cancer and chronic disease in adults: a systematic review for a National Institutes of Health state-of-the-science conference. Ann Intern Med. 2006 Sep 5;145(5):372-85.

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INDEX

A ACCEPTABLE DAILY INTAKE VALUES 38 ACCEPTABLE MACRONUTRIENT DISTRIBUTION RANGE 19 ADENOSINE TRIPHOSPHATE 83 ADENOSYLCOBALAMIN 75 ADEQUATE INTAKE 19 ADIPOCYTES 31 ADOLESCENCE 111 ADRENALINE 72 ADULTHOOD NUTRITION 102 AGING 100 AI 19 ALCOHOL 77, 84 ALCOHOL 96 ALCOHOLICS 96 ALLERGIES 97 ALLULOSE 38 ALLYL HEXANOATE 97 ALPHA-LINOLENIC ACID 26 ALPHA-TOCOPHEROL 67 ALZHEIMER’S 101 AMDR 19 AMEOBIASIS 93 AMINO ACIDS 47 AMOEBIC DYSENTERY 93 AMYLASE 39 AMYLASES 80 AMYLOPECTIN 36 AMYLOSE 36 ANABOLISM 11 ANEMIA 85 ANTHROPOGENIC 94 ANTIGENS 97 ANTINUTRIENTS 61 ANTIOXIDANT 68, 69 APOLIPOPROTEIN 28 APOPROTEIN 28 ASCORBATE 97

ASCORBIC ACID 69 ASPARTAME 38 ASSESSMENTS OF NUTRITIONAL STATUS 22 ATHEROSCLEROSIS 32 ATP 72, 83 AVIDIN 61 B B VITAMINS 63 B12 SUPPLEMENTS 75 B6 SUPPLEMENTS 73 BAD CHOLESTEROL 31 BASAL ENERGY EXPENDITURE 5 BASAL METABOLIC RATE 88 BEE 5 BENZOATE 97 BERIBERI 71 BETA-CAROTENE 63 BETA-CAROTENE SUPPLEMENTS 13 BHT 97 BIOCHEMICAL ANALYSES 22 BIOCYTIN 73 BIOTIN 73, 82 BIRTH DEFECTS 74 BLOOD CLOTTING 67 BLOOD GROUPS 40 BLOOD LIPID LEVELS 33 BLOOD VOLUME 80 BMI 22 BMR 88 BODY MASS INDEX 22 BOTULISM 92 BRANCHED-CHAIN AMINO ACIDS 73 BREAKDOWN OF BODY PROTEINS 52 BUTYLATED HYDROXYTOLUENE 97 C CABBAGE

60

128

CALCIFEROLS 65 CALCIUM 83 CALCIUM, ELDERLY 101 CAMPYLOBACTER 91 CANADA FOOD GUIDE 17 CANADIAN FOOD LABELS 21 CANCER 96 CANCER 76 CAPILLARIES 9 CARAMEL 97 CARBOHYDRATE DIGESTION 39 CARCINOGENESIS 76 CARCINOGENS 76 CARNITINE 69 CAROTENOIDS 60 CARRAGEENAN 97 CATABOLISM 11 CATALASE 85 CATION 81 CELL DIVISION 74 CELL MEMBRANES 68 CHD 32 CHEWING GUM 38 CHILDHOOD 109 CHLORIDE 82 CHOLESTEROL 27 CHYLOMICRON 31 CHYLOMICRONS 28 CLOSTRIDIUM BOTULINUM 92 CM 28 COA 73 COENZYME A 73 CO-ENZYMES 11 COLLAGEN 69, 87 COLON 58 COLON CANCER 85 COMPLEMENTATION 50 CONNECTIVE TISSUES 70 COPPER 87 COQ10 68 CORN 72 CORN SYRUP 37 CORONARY HEART DISEASE 32 CREUTZFELD-JAKOB-TYPE DISEASES 94 CRYPTOSPORIDIUM 93 CYANOBACTERIA 93 CYCLOSPORIASIS 93 CYTOPLASM 69

D DAILY VALUES 19 DATABASES OF PUBLISHED SCIENTIFIC RESEARCH 12 DEHYDRATION 80 DIAAS 49 DIABETES 42 DIET AND CANCER RISK 76 DIETARY ASSESSMENT 22 DIETARY FIBERS 36 DIETARY RECOMMENDATIONS TO LOWER CHD RISK 32 DIETARY REFERENCE INTAKE 19 DIETARY REFERENCE INTAKES 7 DIETARY SUPPLEMENTS 8 DIGESTIBLE INDISPENSABLE AMINO ACID SCORE 49 DINOFLAGELLATES 93 DIPHYLLOBOTHRIUM 93 DISACCHARIDASES 38 DISULFIDE BONDS 82 DNA 83 DOPAMINE 69, 72 DOUBLE-BLIND PLACEBO-CONTROLLED INTERVENTION 12 DRI 7 DV 19 E E. COLI STRAIN O157:H7 91 EAR 19 ECF 81 EDTA 97 EER 6 ELDERLY 100 ELECTROLYTES 81 EMPTY CALORIES PROBLEM 41 ENERGY BALANCE 5 ENERGY VALUE OF THE MACRONUTRIENTS 6 ENERGY, ELDERLY 100 ENERGY, PREGNANCY 103 ENTAMOEBA HYSTOLYTICA 93 ENTEROCYTES 51, 75, 85 ENZYME INHIBITORS 61 EPIGENETICS 3 EPITHELIAL CELLS 85 ERYTHROCYTES 55, 85

129

ESSENTIAL AMINO ACIDS 47 ESSENTIAL FATTY ACIDS 26 ESSENTIAL NUTRIENTS 7 ESTIMATED AVERAGE REQUIREMENT19 ESTIMATED DAILY ENERGY REQUIREMENT 6 ETHANOL 96 EVALUATING INFORMATION ABOUT NUTRITION 13 EXTRACELLULAR FLUID 9, 81 F FAD 71 FAMILIAL SPONGIFORM ENCEPHALOPATHY 94 FAT FREE 21 FAT SUBSTITUTES 29 FAT TISSUE 31 FATS 25 FATTY ACIDS 26 FERMENTATION 58, 61 FLAVIN ADENINE DINUCLEOTIDE 71 FLAVIN MONONUCLEOTIDE 71 FLAVONOIDS 60, 61, 70 FMN 71 FOLATE 74 FOLATE, PREGNANCY 104 FOOD ADDITIVES 96 FOOD ALLERGIES 97 FOOD CHOICES 3 FOOD CONTAMINATION 90 FOOD DIGESTION AND NUTRIENT ABSORPTION 9 FOOD GUIDES 17 FOOD INTOLERANCES 97 FOOD LABELS 20 FOOD POISONING 90 FOOD RECOMMENDATIONS, PREGNANCY 105 FOOD RELATED BEHAVIORS 23 FOOD SAFETY 89 FOOD SOURCES OF PROTEIN 48 FOOD SOURCES OF CARBOHYDRATES 37 FOOD SOURCES OF LIPIDS 30 FOOD SOURCES OF SOLUBLE AND INSOLUBLE DIETARY FIBRES 37 FOOD TECHNOLOGY 89 FOOD-BORNE ILLNESSES 90

FOODS FREE RADICAL FRUCTO-OLIGOSACCHARIDE FRUCTOSE FUNCTIONAL FOODS FUNCTIONS OF BODY PROTEINS FUNCTIONS OF CARBOHYDRATES FUNCTIONS OF LIPIDS

2 68 36 36 8 52 39 31

G GALACTOSE 36 GAMMA-TOCOPHEROL 67 GARLIC 60 GASTROINTESTINAL TRACT 9 GENES 52 GENETIC MANIPULATION 98 GENETICALLY MODIFIED FOODS 97 GENETICS 3 GI 9 GIARDIA 93 GLUCONEOGENESIS 40, 72, 73 GLUCOSE 36 GLUCOSINOLATES 61 GLUCOSINOLATES 60 GLUTAMATE 97 GLUTATHIONE 82 GLUTATHIONE PEROXIDASE 70, 86 GLYCEMIC INDEX 43 GLYCEMIC LOAD 44 GLYCOGEN 36 GLYCOLIPIDS 27 GM PLANT FOODS 98 GOITER 88 GOOD CHOLESTEROL 31 GOOGLE SCHOLAR 12 GROUND BEEF 91 GUT BACTERIA 58 H HAMBURGER MEAT 91 HDL 29, 31 HEALTH BENEFITS OF DIETARY FIBERS 40 HEART ATTACK 32 HEME 84 HEMICELLULOSE 36 HEMOCHROMATOSIS 85 HEMOGLOBIN 55, 85

130

HEMORRHAGE HEPATITIS A HEPATOTOXINS HERBICIDES HETEROCYCLIC AMINES HIGH BLOOD PRESSURE HIGH PROTEIN INTAKE HIGH-DENSITY LIPOPROTEIN HONEY HONEY HYDROGEN PEROXIDE HYDROLYSIS HYPERCALCEMIA HYPERTENSION

67 94 96 95 77 82 54 29 92 37 85, 87 80 83 82

I ICF IMMUNE SYSTEM IMMUNODEFICIENCY INFANCY INFLAMMATION INGREDIENTS LIST INTRACELLULAR FLUID INTRINSIC FACTOR IODIDE IODINASES IODINE IRON IRON DEFICIENT ANEMIA IRON OVERLOAD IRON, PREGNANCY

81 97 73 107 32 20 81 75 87 87 87 84 85 70 104

J JAUNDICE JELLYFISH

94 96 K

KETOGENIC DIETS KETONES KILOCALORIE KURU KWASHIORKOR

42 23, 40 6 94 54 L

LABORATORY TESTS LACTATION LACTOSE

22 106 36

LACTOSE INTOLERANCE LARGE INTESTINE LDL LDL RECEPTOR LECTINS LINOLEIC ACID LIPASES LIPID DIGESTION LIPID PEROXIDES LIPIDS LIPOIC ACID LIPOPROTEINS LISTERIA LISTERIOSIS LONG CHAIN LOW DENSITY LIPOPROTEIN LOW IN SATURATED FAT LOW IN SUGAR LOW PROTEIN LUNG CANCER

41 58 29, 31 3 61 26 31 31 87 25 82 28 92 92 26 29 30 21 54 13

M MACRONUTRIENTS 2 MAD COW DISEASE 94 MAGNESIUM 83 MALNUTRITION 2 MALTASE 38 MANAGEMENT OF TYPE 2 DIABETES 43 MANNITOL 38 MARASMUS 54 MEDIUM CHAIN FATTY ACIDS 26 MEGALOBLASTIC ANEMIA 74 MEMBRANE 68 MEMBRANE OF CELLS 32 MENAQUINONE 67 MENKES DISEASE 87 MERCURY 94 METABOLISM 11 METHYLCOBALAMIN 75 METHYLMERCURY 95 MICROALGAE 93 MICROBIOME 58 MICROCYTIC HYPOCHROMIC 85 MICROCYTIC HYPOCHROMIC ANEMIA 73 MICRONUTRIENTS 2, 62 MICROPARTICULATED PROTEIN 29 MINERALS, PREGNANCY 105

131

MONO-UNSATURATED FATTY ACID 26 MRNA 53 MSG 97 MUFA 26 MUTATION 3, 77 MYOGLOBIN 85 N NAD NATIONAL FOOD GUIDES NATURALLY OCCURRING TOXINS NEURAL TUBE NEUROTOXINS NIACIN NIACIN NIACINAMIDE NICOTINAMIDE ADENINE DINUCLEOTIDE NITRITE NON-STARCH POLYSACCHARIDES NOROVIRUS NUTRACEUTICALS NUTRIENT DEFICIENCIES NUTRIENT DENSITY NUTRIENT FUNCTIONS NUTRIENT SUPPLEMENTS NUTRIENTS NUTRIENTS IN BREAST MILK NUTRI-EPIGENETICS NUTRIGENOMICS NUTRITION NUTRITION DURING ADOLESCENCE NUTRITION DURING CHILDHOOD NUTRITION DURING INFANCY NUTRITION DURING LACTATION

72 17 96 74 96 72 72 72 72 97 36 94 8 7 7 10 19 2 106 5 3 2 111 109 107 106

O OBESITY, CHILDHOOD AND ADOLESCENCE OILS OLIGOSACCHARIDE OMEGA 6 FATTY ACIDS OMEGA-3 FATTY ACIDS ORGANIC FOODS ORGANOSULFUR COMPOUNDS OSTEOMALACIA OSTEOPOROSIS OVERNUTRITION

111 25 36 26 26 95 60 66 84 2

OXALATE OXALATES OXIDATIVE DAMAGE OXIDATIVE STRESS

61 84 86 70

P PAH 77 PANTOTHENIC ACID 73 PARALYTIC SHELLFISH POISONING 96 PARALYTIC SHELLFISH POISONING 93 PARASITES 93 PARATHYROID HORMONE 83 PDCAAS 49 PECTINS 36 PEER REVIEW 12 PELLAGRA 72 PEPTIDASES 51 PESTICIDES 95 PHENYLALANINE 54 PHENYLKETONURIA 54 PHOSPHATE 83 PHOSPHOLIPIDS 27, 83 PHOSPHORUS 83 PHYLLOQUINONE 67 PHYSICAL ACTIVITY 6 PHYTATE 61 PHYTATES 84 PHYTOCHEMICALS 59 PHYTOESTROGENS 60 PKU 54 PLANT OILS 30 PLP 72 POLYAROMATIC HYDROCARBONS 77 POLYPEPTIDES 47 POLYPHOSPHATE 83 POLYSACCHARIDES 36 POLYUNSATURATED FATTY 26 POTASSIUM 81 POTENTIAL CARCINOGENS 77 PREGNANCY 65, 74, 103 PRESERVATIVES 96 PRIMARY STRUCTURE 48 PRIONS 94 PROPIONATE 97 PROTEASES 51 PROTEIN COMPLEMENTATION 50 PROTEIN DIGESTIBILITY-CORRECTED AMINO ACID SCORE 49

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PROTEIN DIGESTION 51 PROTEIN IN THE URINE 23 PROTEIN QUALITY 49 PROTEIN, ELDERLY 101 PROTEIN, PREGNANCY 103 PROTEINOGENIC AMINO ACIDS 51 PROTEINS 47 PROVITAMIN A CAROTENOIDS 64 PSICOSE 38 PSP 93, 96 PTH 83 PUBMED 12 PUFA 26 PYRIDOXAL PHOSPHATE 22 PYRIDOXAL PHOSPHATE 72 PYRIDOXINE 72 R RAE 63 RASHES 97 RDA 19 REACTIVE OXYGEN SPECIES 70 RECOMMENDED DIETARY ALLOWANCE 19 RED BLOOD CELLS 55, 85 REDUCED IN SALT 21 REE 5 REGULATION OF HEALTH CLAIMS 21 REGULATION OF THESE NUTRIENT CONTENT WORDS 21 REHYDRATION 81 REPAIR OF DAMAGE 71 REPAIR OF DNA 71 RESTING ENERGY EXPENDITURE 5 RETINOIC ACID 63 RETINOL 63 RETINOL ACTIVITY EQUIVALENTS 63 RIBOFLAVIN 71 RIBOSOME 53 RICKETS 66 ROS 70 ROUNDWORMS 93 S SACCHARIN SAFE FOOD HANDLING SAINT JOHN’S WORT SALMONELLA

38 90 59 91

SALMONELLOSIS 91 SATURATED 26 SCIENTIFIC METHOD 12 SCRAPIE 94 SECONDARY STRUCTURE 48 SELENIUM 86 SELENOPROTEINS 72 SERVING SIZES 17 SFA 26 SHELLFISH 93 SHIGELLA 92 SHORT CHAIN 26 SHORT-CHAIN FATTY ACIDS 58 SICKLE CELL ANEMIA 55 SIMPLESSE 29 SKIN LESIONS 72 SOD 86 SODIUM 81 SODIUM SENSITIVE 81 SOLANINE 96 SORBITOL 38 SOURCE OF FIBRE 21 SOY FOODS 60 SPINA BIFIDA 74 SPORES 92 STAPHYLOCOCCUS 92 STARCH 36 STATINS 32 STEVIA 38 STOMACH ACID 75 STORAGE OF FOODS 90 STRATEGY TO TRY TO CHANGE NUTRITION-RELATED BEHAVIORS 24 SUCRALOSE 38 SUCRALOSE 97 SUCRASE 39 SUCROSE 36 SUGAR ALCOHOLS 38 SUGARS 36 SULFATION 83 SULFORAPHANE 60 SULFUR 82 SUNSCREENS 66 SUPEROXIDE DISMUTASE 86 SUPPLEMENTS 59, 83 SUPPLEMENTS, CHILDHOOD NUTRITION 110 SUPPLEMENTS, DIETARY 102 SWEETENERS 37

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SYNTHETIC FATS

29 T

TAENIA TAPEWORMS TARTRAZINE TEENAGERS TEF TERTIARY STRUCTURE TETRAHYDROFOLIC ACID TG THERMIC EFFECT OF FOOD COMPONENT THFA THIAMINE THIAMINE THIAMINE PYROPHOSPHATE THIRST THROMBOSIS THYROGLOBULIN THYROID THYROID HORMONES TOCOPHEROLS TOCOTRIENOLS TOXIN TOXOPLASMA TRANS FATTY ACIDS TRANSCRIPTION TRANSFERRIN TRANSLATION TRICHINELLA TRIGLYCERIDES TRNA TRYPTOPHAN TYPE 1 DIABETES TYPE 2 DIABETES TYROSINE

93 93 97 111 5 48 74 27 5 74, 75 82 71 71 80 32 87 60, 87 87 67 67 92 93 26 52 70, 85 53 93 27 53 72 42 42 54

U UBIQUINOL UL ULTRAVIOLET LIGHT UNDERNUTRITION UPPER LIMIT URINE TEST STRIPS

68 19 65 2 19 22

V VACUUM-PACKED FOODS 92 VAPING 69 VEGAN 58 VEGANS 75 VEGETARIANISM 58 VERY LOW DENSITY LIPOPROTEIN 28 VIBRIO 92 VIRUSES 94 VITAMIN A 63 VITAMIN B1 71 VITAMIN B12 75 VITAMIN B2 71 VITAMIN B3 72 VITAMIN B5 73 VITAMIN B6 72 VITAMIN B7 73 VITAMIN B9 74 VITAMIN C 69 VITAMIN D 65 VITAMIN D3 66 VITAMIN E 67 VITAMIN K 67 VITAMINS 62 VITAMINS, ELDERLY 101 VITAMINS, PREGNANCY 104 VLDL 28, 31 W WATER WATER, ELDERLY WILSON'S DISEASE WORMS

80 101 87 93 X

XENOBIOTICS XEROPHTHALMIA XYLITOL

83 65 38 Y

YERSINIA

92 Z

ZINC ZINC, PREGNANCY

86 105

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APPENDICES APPENDIX A Dietary Reference Intakes (DRI) Source: Government of Canada, Health Canada division, Food and Nutrition section

The following groups of tables are included:

A. B. C. D. E.

Reference Heights and Weights Equations to estimate energy requirement (EER) Reference Values for Vitamins Reference Values for Minerals (elements) Reference Values for Macronutrients

APPENDIX B Example of Dietary Assessment A step-by-step guide based on 3-day food recall

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APPENDIX A DRI Tables and related information, source: Health Canada Unit definitions and conversions (continue on next page)

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DRI tables for nutrients (with footnotes; AI/RDA values are for a typical individual consuming both plant foods and animal products) Estimated Average Requirements (EARs) in italics, Recommended Dietary Allowances (RDAs) in bold, Adequate Intakes (AIs) marked with an asterisk (*), Tolerable Upper Intake Levels (ULs) in shaded columns (ND, not determined).

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** New values for 2010 replace older values from 1997. 1 Retinol Activity Equivalents (RAE). 2 DRIs not established for carotenoids including beta-carotene. 3 UL is for preformed vitamin A (retinoids). 138

4 Vitamin D DRIs are set under the assumption of minimal sun (UV) exposure. 5 Vitamin E RDA, AI, EAR apply to alpha-tocopherol only. 6 Vitamin E UL is only for supplements and fortified foods (not the natural forms present in regular foods). 7 ULs not established for vitamin K; but adverse effects of high intakes are possible

8 Vitamin C requirement for smokers is 35 mg/day higher than for non-smokers of the same age and gender. 139

9 ULs not established for thiamin and riboflavin; but adverse effects of high intakes are possible. 10 Niacin Equivalents (NE). 11 Niacin UL is only for supplements and fortified foods (not the natural forms present in regular foods). a. infants 0-6 months, RDA is for preformed niacin (not NE).

12 Dietary Folate Equivalents (DFE) 13 Folate UL is only for supplements and fortified foods (not the natural forms present in regular foods). 140

14 ULs not established for vitamin B12, biotin, and pantothenate; but adverse effects of high intakes are possible. 15 uncertain whether dietary choline is necessary for all ages; sufficient quantities may be made by the body at some ages. b women planning pregnancy should take a daily folic acid supplement of 400 µg in addition to their folate intake from foods c women should continue taking 400 µg folic acid until pregnancy is confirmed, typically at least the first month of pregnancy. d people over age 50 should include vitamin B12 supplement or B12 fortified foods to meet their RDA.

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** New values for 2010 replace older values from 1997. 16 Arsenic UL not determined; however, it should not be added to foods or supplements. 17 ULs not established for arsenic and chromium; but high intakes can have adverse effects.

18 vegetarians, especially vegans, should consume about 1.8 times more iron. 142

19 Magnesium UL is only for supplements and pharmacological agents (not from natural water and foods). e Iron EAR and RDA values are based on the assumption that girls over age 13 menstruate (iron loss), and women over 50 are postmenopausal.

20 There is no justification for the addition of silicon to foods or supplements. 143

21 ULs not established for sulfate, potassium, and silicon; but high intakes can have adverse effects. 22 Vanadium is obtained naturally from foods; there is no justification for the addition of it to foods and supplements. There is not enough data to set a vanadium UL for children. 23 vegetarians, especially vegans, should consume about 1.5 times more zinc. 24 Potassium should be obtained only from foods; plant foods are rich sources. Supplements are potentially dangerous and must be medically supervised. 25 One g sodium is 2.53 g salt (sodium chloride) 26 Sodium and chloride are typically obtained together from salt (sodium chloride). 27 Sulfate AI is typically met if a person consumes the recommended amount of protein.

28 Macronutrients do not have a set UL, but long-term excessive intake can cause health problems. 144

29 vegetarians, especially vegans, should emphasize protein complementation 30 (amount of protein needed per kg body weight) x (reference weight) is the amount shown 31 value represents total dietary fibre 32 Total dietary fibre AI is 14 g/1000 kcal consumed, and based on CSFII 1994-1996, 1998 data of median typical energy intake 33 Total water, from all sources including solid foods f protein EAR and RDA during pregnancy are only applicable to the first and second trimester (no change for the first, relative to non-pregnancy situation)

34 pregnancy and lactation included 35 DHA and EPA can contribute up to 10 percent of this AMDR

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EER is the estimated energy requirement that meets typical daily caloric (energy) needs and helps maintain a normal energy balance and body weight. Below the EER equations is a table for estimating the PA (physical activity) component.

146

147

Reference weights (kilograms or pounds) and heights (meters or inches) from NCHS/ CDS (USA) growth charts data. For ages beyond 30, the 19-30 values can be used as reference

REFERENCES for DRIs Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride (1997); Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (1998); Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids (2000); Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc (2001); Dietary Reference Intakes for Energy, Carbohydrate, Fiber, Fat, Fatty Acids, Cholesterol, Protein and Amino Acids (2002); Dietary Reference Intakes for Water, Potassium, Chloride, and Sulfate (2004).

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APPENDIX B

Dietary Assessment Based on 3-day Food Recall A step-by-step guide 1. Record what you eat, all foods and drinks, for a typical 3-consecutive-day period that includes one weekend day. Also, include dietary supplements (if any). For example, food intake can be recorded on a spreadsheet as shown in Table 1 (29 columns in this example, shown as multiple parts of one wide table) Table 1 (columns 1-6):

Table 1 continued (columns 7-13):

Table 1 continued (columns 14-22):

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Table 1 continued (columns 23-29):

2. For each food, record the quantities, if any, of the 27 nutrients and energy (columns 2-29 in Table 1). Do this for all the foods consumed over the three days. Then determine an average daily intake for each nutrient in Table 1 by summing all intakes for a nutrient (represented by a single column) and dividing the total by 3 (three days). The following are possible sources for the nutrient composition of foods. If the composition of a food is not available, you may separate out the different food components or substitute the composition of a similar food. Food labels can also help you with this task of determining the nutrient composition of each food. i. Canada food guide database: https://food-nutrition.canada.ca/cnf-fce/index-eng.jsp ii. The USDA Food Database: http://www.nal.usda.gov/fnic/foodcomp/search/ iii. Australia-New Zealand food composition database: https://www.foodstandards.gov.au/science/monitoringnutrients/afcd/Pages/foodsear ch.aspx iv. UK food composition website (requires registration): https://quadram.ac.uk/UKfoodcomposition/login-register/ 3. Calculate your daily estimated energy requirements (EER, kcal) by using the following equations for male or female (from textbook, Chapter 2, and APPENDIX A): Men: EER = 662 – (9.53 x age) + (PA x [(15.91 x weight] + (539.6 x height)]) Women: EER = 354 – (6.91 x age) + (PA x [(9.36 x weight] + (726 x height)]) Units for the parameters: Age (years); Weight (kg); Height (m). Choose the most appropriate physical activity (PA, more details in textbook Chapter 2 and APPENDIX A) factor from the following list (for men, first number) [for women, second number]: Sedentary, (1.0) [1.0]; Active, low-level, (1.11) [1.12]; Active, moderate, (1.25) [1.27]; Active high-level, (1.48) [1.45]. 4. Calculate your percent recommended intakes (DRI) for all the nutrients and energy. For example, this can be done using a spreadsheet as shown in Table 2. Note that total protein, total carbohydrate, and total fat recommendations are based on AMDR (percentages of total daily energy intake). Unit definitions are given in APPENDIX A, for example, converting micrograms of retinol or beta-carotene to RAE vitamin A units.

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Table 2 DRIs are for male (m) and female (f) adults, 19-30 years of age. Appendix A includes DRIs for other age groups, and for conditions such as pregnancy.

5. The following are some questions to consider in terms of analyzing your dietary assessment: a. What are main problems in your diet in terms of nutrient excesses or deficiencies, the greatest deviations from the DRIs? b. Is your energy intake appropriate based on the EER calculation (step 3)? c. For saturated and trans fat, the recommendations are ≤ 10% and < 1%, respectively, of total daily energy intake; how does your intake compare? d. For omega-3 and omega-6 fats, the recommendations are 0.6-1.2% and 5-10%, respectively, of total daily energy intake; how does your intake compare? e. For simple sugars, the recommendation is < 25% of total daily energy intake, and as low as possible; how does your intake compare? f. What dietary (food consumption) changes could you make to help correct some of the major excesses or deficiencies? g. If your excesses or deficiencies remain uncorrected over the long-term, what are possible consequences in terms of disease risk? h. What are some disadvantages and advantages of this type of dietary analysis?

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