Sandra Miller PhD ( McGill University ) Echinacea cancer cure -- mcgill university and carol bower immunity cancer cure echinacea , astragalus, burdock -- immunity cancer cure

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1/23/24, 2:17 PM

Immunity Cancer Cure - About Sandra C. Miller and Carol E. Bower

   

Let your food be medicine and your medicine be food. ~Hippocrates, the Father of Western Medicine

HOME | THE DIET | RECIPES | Q & A | ABOUT US | CONTACT US         SANDRA C. MILLER Biographical Info Publications CAROL E. BOWER Biographical Info Publications

About Us Sandra C. Miller, PhD is a Professor in the Department of Anatomy and Cell Biology, Faculty of Medicine, at McGill University in Montreal, Quebec. She has taught and conducted research at McGill for since 1978. She also has conducted research at two distinguished medical schools in the United States (see Biographical Information).  Sandra's research focus for more than 30 years has been the cells of the body's immune system, especially natural killer (NK) cells. NK cells are instrumental in seeking out and destroying newly formed cancer cells. She formulated "the immunity cancer cure"--her cancerfighting eating regimen, as an outgrowth of her studies on enhancement of the immune system in the presence of cancer by using substances derived from plants. She has published numerous research papers in medical and scientific journals (see Publications), edited a textbook on Echinacea, and she has received several awards for excellence in education and research. Sandra's work was featured in the March, 2007 issue of Cancer Monthly. Sandra's father died of pancreatic cancer at the age of 66, long before anyone knew about treating cancer with biologically active plant products. Carol E. Bower, BSc is medical writer and editor, currently working in public health research and planning.  Previously, she directed aquatic chemistry, parasitology, and toxicology laboratories, and conducted research in the Department of Tropical Public Health at Harvard School of Public Health. Carol has authored three books. Her other publications include educational guides, peer-reviewed research papers on human and animal health, and many reports on population health. She served on  the Board of Directors of the Connecticut Cancer Partnership, from 2002 to 2009 and was editor of its web site.  Carol's father died of lung cancer in 1967 at the age of 48. Her mother was diagnosed with non-Hodgkin lymphoma in late 2005. She refused to have conventional treatments, and with her oncologist's consent, began following the cancer-fighting diet since February, 2006. One year later, she was declared cancer free. In July, 2013 she celebrated

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Immunity Cancer Cure - About Sandra C. Miller and Carol E. Bower

her 91st birthday, and is presently in fine health with no detectable cancer. She still takes all the supplements every day.

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Let your food be medicine and your medicine be food. ~Hippocrates, the Father of Western Medicine

HOME | THE DIET | RECIPES | Q & A | ABOUT US | CONTACT US



The Cancer-fighting Diet >> How to Do It WHAT IT IS

The Eating Regimen Before you begin the diet, please be sure you read and understand the Key Concepts of the eating regimen and the section on Forbidden Foods.

The Story What It Is, and What It's Not

The 6 "eating times" described below replace the 3 meals a day you're accustomed to eating. These are the times you take specific supplements with certain foods.

Conventional Medical Treatments



HOW IT WORKS

The eating times should be spaced out, so that you eat something every 3 to 4 hours throughout the day. Times that work well for many people are 7- 8 a.m., 11 a.m.-noon, 2-3 p.m., 5-6 p.m., 8-9 p.m., and just before bed. As you'll see, the amounts of food and supplements you take get smaller as the day goes on.

The Immune System and Cancer Foods & Supplements



You can eat as much or as little as you like, as long as you have at least a little bit of each of the specified foods. How often you eat is far more important than how much you eat. If you're not a "morning person," for example, your first foods of the day could be a few spoonsful of Cheerios with half a banana, a few spoons of yogurt, and a few ounces of V8 vegetable juice. You do not have to eat large amounts of the specified foods.

HOW TO DO IT Key Concepts Forbidden Foods The Eating Regimen Toolkit

If you get hungry between scheduled times (which is not very likely) feel free to snack on anything you like, except, of course, the forbidden foods. Nuts, especially walnuts and almonds, are excellent snacks when you're on the cancer-fighting diet. And if you get the urge for sweets, we recommend dark chocolate, which is loaded with antioxidants and other cancer-fighting substances. This is not a "mega-vitamin" diet, so there is no need for concern about overdosing on the supplements. Where supplement dosages are not specified, take the lowest dosage you can buy. High dosages of most supplements are not needed, and excess amounts simply get washed out. Nearly all the supplements are available as capsules or gels. Those who follow the diet find these forms easier to swallow than dry, uncoated tablets, and they can easily be opened and added to foods like applesauce if you have difficulty swallowing them. NOTE: The strict eating regimen outlined below is for persons who currently have tumors diagnosed as cancer. It is designed to maximize absorption of specific substances when specific immune cells can best use them. People who have no detectable tumors (after surgery or other conventional treatment to prevent cancer from recurring, or for general prevention) can follow a simplified version of the diet -- Observe the dietary guidelines about what foods to eat and what foods to avoid, and take all the supplements over the course of the day. Printable Food Reference on Index Cards (PDF) Printable List of Supplements (PDF) How to Set Up One Week of Supplements (PDF) FIRST Eating Time (approx. 6 a.m. to 9 a.m.) Foods: Oat-based cereal (not bran or wheat), such as cooked oatmeal, Cheerios, Heart to Heart, oatmeal muffins, etc., with low-fat or fat-free milk Sprinkle a spoonful of ground flax seed over the cereal. V8 vegetable juice or V8 Fusion (but not plain tomato juice or fruit juice) At least half a banana

Yogurt (plain or flavored, as long as it contains Acidophilus) Finish with a cup of green tea Supplements: 1 Echinacea tablet* 1 Multivitamin (any good brand) 1 Vitamin C (500 mg) 1 Vitamin E (gamma-E, not alpha-E, 400 IU)** 1 NAC (N-acetylcysteine) 600 mg 1 Bilberry 1 Biotin 1 Folic acid 1 Zinc (low dose) 1 Calcium & Magnesium with Vitamin D*** [Take highest Calcium dose available. These are usually large tablets, which can be difficult to swallow, so you might want to substitute a few capsules of lower dosage, or add powdered calcium/magnesium to your food or a glass of milk.] * Bioforce Echinaforce, an extract manufactured by A. Vogel, is recommended ** Alpha tocopherol is the most common form of Vitamin E, but this form is NOT effective against cancer. Buy only "mixed tocopherols" containing the gamma and delta forms. In the US, we recommend Jarrow Gamma-E or any other brand that contains mostly gamma-tocopherol. *** Natrol Calcium-Magnesium with Vitamin D are in gel caps that are easier than tablets to swallow.

SECOND Eating Time (approx. 10 a.m. to 12 noon) Foods: Salad containing a variety of vegetables Add any kind of beans (Black beans, kidney beans, a little 5-bean salad, etc.) A small amount of vegetarian chile would work here also.) Any soy product (Tofu, Edamame, or Soy Nuts) Tofu is delicious stir-fried in olive oil with garlic and mushrooms, or boiled and used in place of a chopped hard boiled egg in a sandwich with celery, onion, and canola mayonnaise. Edamame (ed-uh-MA-mee) is the name of whole soybeans, which you probably never heard of until now. You can find them (in or out of their shells) in the freezer section in the "natural foods" area of your supermarket. They taste like fresh peas, and are delicious uncooked (thaw them in a strainer under running water), lightly steamed, or sautéed in olive oil. Use olive oil and your favorite spices as dressing Dessert (if desired)--dark chocolate with nuts; Nutella on whole wheat crackers Green tea, low-fat milk, or soy milk Supplements: 1 Vitamin C (500 mg) 1 B-100 complex vitamin 1 Omega-3 fish oil capsule* 1 Alpha lipoic acid 1 Coenzyme Q10 (50 mg for most people, 100 mg or more for people who take statins such as Lipitor, Zocor, or Mevacor to control their cholesterol) 1 Beta carotene (low dosage) 1 Astragalus (350 mg)--Not to be taken by people with autoimmune disorders such as rheumatoid arthritis 1 Burdock (540 mg)-- Not to be taken by people with diabetes who are taking insulin 1 Cranberry capsule * Not all "fish oil" capsules are equal. Their content of "omega-3 fatty acids" is what to look for. We recommend Carlson's Elite Omega Gems, which contain about twice as much omega-3 as other brands. They are extremely pure, and have no fishy smell or taste.

THIRD Eating Time (between 1 p.m. and 4 p.m.) Foods: Salad containing a variety of fruits Pasta with tomato sauce or Hard-boiled egg (could be part of the salad or eaten as an egg salad sandwich

on multigrain or oat bread) Dessert if desired (see #1) Low-fat or fat-free milk, soy milk, or green tea Supplements: 1 Vitamin C (500 mg) 1 Vitamin E (400 IU-- see notes under "First Eating Time") 1 Lycopene 1 Vitamin D3 (1,000 IU) FOURTH Eating Time (between 5 p.m. and 7 p.m.) Foods: Chicken or seafood (As much as you like, broiled, baked, sautéed, or stir-fried in olive oil.) Vegetables (Raw is most nutritious except for carrots, which are more nutritious after light cooking to release beta carotene. Lightly steamed broccoli, green beans, etc. would be fine here, too. Just don't boil them to death.) Sprinkle a spoonful of ground flax seed over the vegetables Dessert if desired (see #1) or some fruit salad Low-fat or fat-free milk, soy milk, or green tea Supplements: 1 Selenium 1 Folic Acid 1 Resveratrol, 100 mg 1 Omega-3 (fish oil) capsule, 1,000 mg* * Strict vegetarians may substitute 1 flaxseed oil capsule. See notes under "First Eating Time."

NOTE: Post-menopausal women, women with estrogen-receptorpositive [ER+] breast cancer, and men over 65 years of age should add: 1 Lactoferrin, 100 mg This is especially important for breast cancer survivors who are taking Tamoxifen or Arimidex FIFTH Eating Time (betwen 8 p.m. and 10 p.m.) Foods: A small amount of anything that you ate previously in the day. Yogurt Add another spoonful of ground flax seed Green tea only Supplement: 1 Multivitamin SIXTH Eating Time (Just before going to sleep) Food: A little yogurt or a few dry whole wheat crackers Green tea only Supplement: 1 Echinacea tablet * * Bioforce/Echinaforce, an extract manufactured by A. Vogel, is recommended



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Let your food be medicine and your medicine be food. ~Hippocrates, the Father of Western Medicine

HOME | THE DIET | RECIPES | Q & A | ABOUT US | CONTACT US



Medical Advice Notice The Immunity Cancer Cure web site is intended to help people with cancer, their caregivers, families, and friends to become better informed about how cancer can be controlled through enhancement of the immune system with phytocompounds. We do not sell any information or products, nor do we provide medical advice, diagnosis, or treatment. T he content of this web site, such as text, graphics, and images, is for your private use and informational purposes only. Always seek the advice of your physician or other qualified health provider with questions regarding your medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on the Immunity Cancer Cure web site. If you have a medical emergency, do not rely on this information to treat your condition; call your doctor or go to a hospital immediately. Reliance on the content of this web site or any other information provided by any of its employees, agents, authors or others providing content on the web site is solely at your own risk.

Copyright © 2014 by immunitycancercure.org. All rights reserved. Address inquiries to the web site editor.

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Let your food be medicine and your medicine be food. ~Hippocrates, the Father of Western Medicine

HOME | THE DIET | RECIPES | Q & A | ABOUT US | CONTACT US



The Cancer-fighting Diet>> How to Do It

Forbidden Foods WHAT IT IS The Story What It Is, and What It's Not Conventional Medical Treatments



HOW IT WORKS The Immune System and Cancer

"Forbidden" may seem like a strong word, but your first months on the cancer-fighting diet are the most critical. This is when you need to focus all your body's resources on strengthening your immune system to fight your cancer, while keeping the rest of your body in optimal health. So it's especially important to avoid anything that reduces the absorption or beneficial effects of the foods and supplements, or prevents them from doing their work. Many of the foods listed below have been linked to an increased risk of getting cancer. While it's important for people to avoid these foods to lower their chances of getting cancer, it's especially important to keep them out of your diet if you already have cancer.

Foods & Supplements



Red Meat

HOW TO DO IT Key Concepts Forbidden Foods The Eating Regimen

Pork Products Processed Meats Margarine, Butter, Shortening, Trans Fats, Vegetable Oils

Toolkit

Coffee Laxatives Sugary Foods Red Meat Beef, veal, lamb, and other red meats should not be eaten for three reasons. They all contain saturated animal fats. These fats coat the lining of the digestive system and the walls of the blood vessels, and block the absorption of nutrients your body needs to fight cancer. Cancer-causing chemicals called nitrosamines are formed in meats during hightemperature cooking (frying, grilling and broiling). Even lean red meats cooked at lower temperatures (baked or stir-fried) take up space in your digestive system that could otherwise be filled with foods that are valuable for fighting cancer. Although red meat is an important source of iron, the iron in the foods and multivitamins you'll consume will meet your body's needs. Pork Products Pork, ham, bacon, sausage, and other products of pigs also contain saturated animal fats (see Red Meat, above). Ham, bacon, and sausage are even worse for people fighting cancer, because they are heavily salted and contain preservatives called nitrites that cause cancer (see below). Processed Meats Hot dogs, coldcuts and luncheon meats, pepperoni, corned beef, pastrami, and other processed meats are especially harmful to people with cancer. First, even "low fat" and "all beef" processed meats commonly are more than 50% fat! (Read the amounts of "calories" and "fat calories" on the Nutrition Facts labels. Don't be surprised to find that 140 calories or more of each 190-calorie slice of meat comes from fat.) Cancer-causing chemicals are produced during the salting of meat. Nitrites are added to meats because they prevent the growth of bacteria. They combine with a protein in meat to produce the "desirable" dark red or pink color typical of ham, hot dogs, corned beef, pastrami, and coldcuts. Very high concentrations of nitrites, by themselves, cause cancer. But during cooking, nitrites combine with other substances in meats to form additional carcinogenic substances. The last thing a person fighting cancer needs to consume is more carcinogens!

Margarine, Butter, Shortening, Trans Fats, Vegetable Oils Margarine, butter, shortening (e.g., Crisco), and other oils and spreads made of saturated animal fats, polyunsaturated vegetable oils, and trans fats (listed on nutrition labels as "hydrogenated" and "partially hydrogenated" oils) should not be used at all during the first months. They keep cancer-fighting nutrients from being absorbed into your body. They also may make existing cancers grow faster. These types of fats and oils can raise levels of "bad" (LDL) cholesterol, lower levels of "good" (HDL) cholesterol, and increase the risk of heart disease and stroke. Animal fats and many vegetable oils contain omega-6 fatty acids, which form inflammatory substances when broken down in the body. Inflammation may play an important role in the development of cancer. Only extra virgin olive oil (EVOO) and canola oil should be used for cooking an in salad dressings. EVOO is loaded with antioxidants and also raises levels of HDL cholesterol. Olive and canola oils, along with fish oil, and oils in nuts, contain omega-3 fatty acids, which curb inflammation and may slow the growth and spread of cancer. Fried Foods All deep-fried foods (meats, poultry, seafood, French fries, potato chips, taco chips, etc.) are strictly off limits, because they are cooked with unhealthy fats and oils. More important, the high temperatures reached during frying creates carcinogens. While frying is out, sautéeing poultry, fish, and vegetables in olive oil is fine. You won't believe it until you try it, but chicken, shrimp, scallops, and vegetables sautéed in a high-quality extra virgin olive oil taste almost exactly the same as when cooked in butter. Vegetables also are delicious when tossed with olive oil and a little salt and roasted (see Recipes). Coffee Although drinking a few cups a day of caffeinated coffee may have some health benefits, such as lowering the risk of diabetes and Parkinson's disease, people on the cancer-fighting diet should not drink coffee. Coffee is a diuretic (increases the flow of urine), and it complexes with calcium and accelerates its eliminationfrom the body. The whole point of Dr. Miller's diet is to maximize absorption of cancer-fighting nutrients, and calcium is a key nutrient. Another important reason not to drink coffee is that it does nothing to fight cancer, and it keeps you from drinking something that may prevent or slow the formation of tumors (low fat milk, soy milk, green tea) . Laxatives By now, you probably have figured out why laxatives should not be used: they prevent absorption of the food and supplements that are key to boosting your immune system to combat cancer. Sugary Foods Sugar is not entirely off-limits in the cancer-fighting diet. In fact, some sweet foods, such as fruits and dark chocolate, are important parts of the regimen. Big bursts of sugar--what you get from a can of Coke (9 teaspoons of sugar!) or a candy bar can rapidly raise the level of sugar in your blood. There is new evidence that sugar-sweetened beverages increase the chances of getting colorectal cancer, prostate cancer, and endometrial cancer, and possibly other cancers. More important, high levels of blood sugar cause Natural Killer (NK) cells--the main cancer fighters of the immune system--to leave the bloodstream. While they are away, it means that the "cancer police" are not patrolling for and destroying cancer cells. The idea is to boost levels of NK cells, so sugar consumption should be limited mostly to sugars found in natural foods.

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immunitycancercure.org is intended to provide information about enhancing the immune system with plant products to fight cancer. See additional information. xxxxxxxxx



Let your food be medicine and your medicine be food. ~Hippocrates, the Father of Western Medicine





HOME | THE DIET | RECIPES | Q & A | ABOUT US | CONTACT US





The Immunity Cancer Cure web site has three main areas. (Some of them are still being developed, but the critical ones are complete.) What It Is How Dr. Sandra Miller's research led to the development of the cancer fighting diet. How the diet differs from other "alternative cancer treatments." How it differs from conventional medical treatments like chemotherapy and radiation therapy.



How to Do It Key concepts about the diet. What to eat and when. The few foods that you must NOT eat. Checklists, step-by-step directions, and other tips and aids that make the diet easier to follow.



3 Q & A (Questions & Answers) Answers to questions from people who have used the cancer-fighting diet. The list is still growing, so please contact us with your own questions. They could help others.









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Let your food be medicine and your medicine be food. ~Hippocrates, the Father of Western Medicine

HOME | THE DIET | RECIPES | Q & A | ABOUT US | CONTACT US



Welcome to Immunity Cancer Cure WHAT IT IS The Story What It Is, and What It's Not Conventional Medical Treatments



HOW IT WORKS The Immune System and Cancer Foods & Supplements



HOW TO DO IT Key Concepts Forbidden Foods The Eating Regimen

This web site contains information about a cancer-fighting nutritional regimen. The regimen ("diet") was developed by Sandra C. Miller, PhD for adults with cancer. It also can be followed by healthy individuals to lower their chances of getting cancer. It works in several ways, most importantly by enhancing the immune system-the body's natural defense against cancer--without harming normal, healthy cells. It is a carefully defined regimen, in which specific food supplements are taken at specific time help to ensure that the body absorbs the most cancer-fighting nutrients, and when they are taken aligns with the growth cycles of various cell types in the immune system. It is grounded in scientific evidence. It integrates findings from hundreds of studies published in peer-reviewed journals on the effects of phytochemicals (substances derived from plants), vitamins, minerals, and other supplements on the immune system and on cancer development and tumor growth. It can be used against any kind of cancer at any stage, either as the first and only treatment, or after surgery, chemotherapy, or other conventional medical treatments have been completed.

Toolkit

Important Note: The cancer-fighting eating regimen will not be effective during chemotherapy or extensive radiation (both of which harm the immune system). It also will not work if disease or prior treatments with radiation or chemotherapy have caused major, irreversible to any vital organs (heart, brain, lungs, liver). All the information about the cancer-fighting eating regimen is free. We do not sell or promote any books, brands or distributors of supplements, or counseling or treatment facilities, nor are we affiliated with any commercial ventures. Occasionally, we recommend specific brands for reasons of quality and efficacy. None of the foods or supplements in the eating regimen is proprietary or requires a prescription. They all can be found at many drugstores and health food shops, or can be purchased online (typically at a much lower cost) from the source of your choice. Sometimes we mention specific web sites that we have found have the lowest prices. We encourage you explore this web site and learn more about the cancer-fighting eating regimen (see How to Use This Web Site). It could save your life or the life of someone you care about who has cancer. It will always improve quality of life for a cancer survivor, and will lower anyone's chance of getting cancer.

Copyright © 2014 by immunitycancercure.org. All rights reserved. Address inquiries to the web site editor.

immunitycancercure.org is intended to provide information about enhancing the immune system with plant products to fight cancer. See additional information. xxxxxxxxx



Let your food be medicine and your medicine be food. ~Hippocrates, the Father of Western Medicine

HOME | THE DIET | RECIPES | Q & A | ABOUT US | CONTACT US



The Cancer-Fighting Diet>> How to Do It WHAT IT IS

Key Concepts 1. This is not a "lose weight diet." It is a "save-your-life" diet. Be sure you

The Story

understand the difference.

What It Is, and What It's Not

2. Humans were originally grazers and foragers, eating small amounts of

food here and there throughout the day. Eating three meals a day is known as "bolus eating" (consuming large volumes in one sitting). No other creature on earth intentionally "bolus eats" the way humans do. In the cancer-fighting diet, the words, breakfast, lunch, and dinner are meaningless and are not used.

Conventional Medical Treatments



HOW IT WORKS The Immune System and Cancer

3. You will eat specified foods with specified vitamins and other

supplements 6 times per day (as described in The Eating Regimen) for 23 months, then go back to your oncologist to check on the status of your cancer.

Foods & Supplements



HOW TO DO IT

4. The foods in each of the 6 “eating times” were planned with the indicated

vitamins and herbals in carefully defined combinations (see Rationale for Foods & Supplements). The combinations are based on:

Key Concepts Forbidden Foods

a. The timing of daily growth and reproductive phases of the different cells of your immune system; and

The Eating Regimen Toolkit

b. "Molecular bonding" of the supplements with the foods, to ensure that they are absorbed. 5. For these reasons, do not exchange #1, 2, 5, or 6 with one another or any

other. You may switch “# 3” with “# 4,” but make sure to switch both the foods and supplements. Our physiology is governed by circadian rhythms (bio-rhythms) of biological processes throughout a 24-hour daily cycle, and this diet is timed to correspond with those bio-rhythms. 6. For the first 2-3 months, NEVER eat any of the following foods and

NEVER use laxatives (see Forbidden Foods for explanation): a. Red meat (beef, veal, lamb, etc.) b. Ham, pork, bacon, or other pork products c. Processed meats such as hot dogs, lunch meats, or coldcuts (even turkey) c. Coffee d. Margarine, shortening, and foods containing trans fats. (Trans fats are identified as "hydrogenated" or "partially hydrogenated" oils. READ FOOD LABELS CAREFULLY.) 7. Although sugar is not entirely off-limits, you'll also want to go easy on

sugary foods (see Forbidden Foods). [Lists of preferred food and foods to avoid are given under xxx.] 8. When your oncologist determines with an MRI, CT scan, or PET scan that

your cancer has not spread and your tumors have shrunken, continue the diet for another 2 months, then get evaluated again. The amount of time it will take for your cancer to be eliminated depends on many things, such as they type of cancer and how far it has progressed when you begin the diet. Another important factor is your age. The older you are, the longer it takes to build up your immune system (see The Immune System and Cancer). 9. Even when there is no sign of remaining cancer, continue to

maintain some level of the diet. Remember that one single, completely undetectable cancer cell is all it takes to begin growing another tumor. Sustained enhancement of your immune system with the recommended foods and supplements will ensure that not even one cancer cell can survive and go on to form a tumor.

Copyright © 2014 by immunitycancercure.org. All rights reserved. Address inquiries to the web site editor.

immunitycancercure.org is intended to provide information about enhancing the immune system with plant products to fight cancer. See additional information. xxxxxxxxx





Let your food be medicine and your medicine be food. ~Hippocrates, the Father of Western Medicine

HOME | THE DIET | RECIPES | Q & A | ABOUT US | CONTACT US



SANDRA C. MILLER Biographical Info Publications CAROL E. BOWER Biographical Info Publications

About Sandra C. Miller, BSc, MSc, PhD Current Academic Position Professor, Department of Anatomy and Cell Biology McGill University Faculty of Medicine, Montreal, Quebec Postdoctoral Study Baylor College of Medicine, Houston, Texas Topic: Microenvironmental governance over the development of cells of the hematopoietic and immune system Sabbatical Study Stanford University, Howard Hughes Medical Institute, Palo Alto, California Topic: The dynamics of development and maturation of cells mediating innate immunity. Education BSc: Sir George Williams University MSc: McGill University PhD: McGill University Publications and Presentations Sandra has published more than 60 peer-reviewed papers in 30 medical journals. She edited the 2004 book, Echinacea: The Genus Echinacea (see Sandra's publications), and also contributed 2 chapters to the volume. In 2005-2006, she critiqued and contributed to the updated knowledge of at least a dozen herbs, vitamins, and minerals for a Canadianhealthy living web site, www.passeportsante.net .She has made numerous presentations nationally and internationally throughout her career, including many by invitation. Read the book Echinacea: The Genus Echinacea online (free) Research Interests Sandra has been studying various aspects of the immune system for more than 30 years. Her early research interests concerned the development of the various cells of the immune system, and she authored what still stands as the definitive study of the dynamics of natural killer cells. Since the late 1990's, her research has focused on enhancement of the immune system in the treatment of cancer, especially with phytocompounds (substances derived from plants). Awards Sandra has won numerous awards both for medical education and for research. They include the Murray Barr Award of the Canadian Association of Anatomists for excellence in research; the Honors List for Educational Excellence, McGill University Faculty of Medicine; and the Canadian Association of Medical Educators' Merit Award, for her valuable contributions to medical education. Professional Memberships Sandra has membership in the following professional societies: ~ Canadian Association for Anatomy ~ Canadian Society for Immunology ~ American Association of Anatomists ~ Natural Health Products Research Society of Canada ~ Society for Integrative Oncology

Copyright © 2014 by immunitycancercure.org. All rights reserved. Address inquiries to the web site editor.

immunitycancercure.org is intended to provide information about enhancing the immune system with plant products to fight cancer. See additional information. xxxxxxxxx



Let your food be medicine and your medicine be food. ~Hippocrates, the Father of Western Medicine

HOME | THE DIET | RECIPES | Q & A | ABOUT US | CONTACT US



The Story behind the Cancer-Fighting Diet WHAT IT IS The Story What It Is, and What It's Not Conventional Medical Treatments



HOW IT WORKS The Immune System and Cancer Foods & Supplements



HOW TO DO IT Key Concepts Forbidden Foods The Eating Regimen Toolkit

Despite the billions of dollars poured into public and private cancer research each year throughout the world, the number of new cancer cases continues to increase each year. In developed countries, cancer is expected to surpass cardiovascular disease as the leading cause of death by 2010. It is already the leading cause of death for some minority groups in the United States. Most conventional cancer treatments add only months to life, and for the more successful treatments, "complete remissions" (but rarely cures) can be expected for a "5-year survival increment." The trouble with most treatments, particularly chemotherapy and radiation therapy, is their damaging side effects. It is becoming increasingly evident, especially with childhood cancers, that conventional treatments increase the risk of developing other cancers at a later age, often by as much as 2 to 8 times. Numerous experimental and clinical studies have demonstrated beyond a doubt that the immune system can be mobilized to combat cancer. Several approaches to "immunotherapy" are being studied (anti-tumor vaccines, monoclonal antibodies, cytokines, etc.), but all have limited success. The cancer-fighting diet is a safe, effective, and inexpensive method of treating and curing cancer by stimulating the immune system. Why, didn't someone think of it before? The answer is that it took a unique scientist--an immunologist with extensive knowledge about cancer--to "put two and two together." [Add material about the fallacy of "spontaneous remission." Also add explanation of why clinical trials are not likely.] Dr. Sandra Miller has been studying the the immune system for more than 35 years. In her early research on combating cancer by enhancing the immune system, she focused on a family of molecules called cytokines. Cytokines, which include interferons and interleukins, are chemical messengers produced by the cells and organs of our own immune system. They interact with target cells in the immune system to produce biochemical reactions that stimulate or inhibit various activities. Some cytokines can stimulate the immune system to fight cancer, but large doses are needed to fight cancer effectively, and these high doses cause side effects such as high fevers and rupturing of tiny blood vessels. Although cytokines are manufactured in biotechnology laboratories, they too expensive for widespread use, and the manufactured ones don't always work as well own own "home-grown" varieties. In the late 1970's, Sandra began to pay increasing attention to newly discovered cells in the immune system called natural killer (NK) cells. NK cells are one of the oldest and most primitive types of immune system cells. They are found in all animals with backbones, including reptiles, amphibians, and fish, and even insects have immune systems with NK-like activity. NK cells have a starring role in the story of the cancerfighting diet, because they are the body's first line of defense against all foreign invaders, and they are the primary defender against cancer. [Continue story here.]

Copyright © 2014 by immunitycancercure.org. All rights reserved. Address inquiries to the web site editor.

immunitycancercure.org is intended to provide information about enhancing the immune system with plant products to fight cancer. See additional information. xxxxxxxxx



Let your food be medicine and your medicine be food. ~Hippocrates, the Father of Western Medicine

HOME | THE DIET | RECIPES | Q & A | ABOUT US | CONTACT US



About Conventional Cancer Treatments WHAT IT IS The Story What It Is, and What It's Not Conventional Medical Treatments



HOW IT WORKS The Immune System and Cancer Foods & Supplements



HOW TO DO IT Key Concepts Forbidden Foods The Eating Regimen Toolkit

Despite advances in the understanding of cancer biology, conventional treatments have remained fundamentally unchanged for decades. Treatments generally still involve surgery, often preceded or followed by drugs (chemotherapy) and/or radiation--all in an effort to kill the cancer before the cancer or the "therapy" kills the patient. The shortcomings of these three approaches, along with those of some new and experimental biological methods, are discussed briefly below. Surgery Surgery is the oldest method of cancer treatment. It is most effective when cancers are diagnosed early, before they have spread. Surgery still has serious risks and side effects, including complications of anesthesia, bleeding, damage to blood vessels and internal organs, pain, infections, and blood clots. Intravenous fluids, given during and after surgery, can raise blood pressure, and this can raise the chances of heart attack and stroke, especially among the elderly. Surgery, itself, is also stressful to the body, and stress suppresses the immune system. Chemotherapy

"It seems that far too often, we physicians are vendors of suffering, infusing toxic chemicals when we know it's not only futile but, in the realm of ethics, wrong." ~ Paul Roussea, MD, Journal of the American Medical Association, August 8, 2007

The drugs and chemicals used for cancer chemotherapy typically attack cancer cells when they are reproducing, so they are most effective against fast-growing cancers. The trouble is that the chemo drugs cannot distinguish between cancerous and normal cells. The most vulnerable normal cells are those that multiply rapidly and have a good blood supply--in hair follicles, eyes, lining of the stomach and intestines, bone marrow, liver, kidneys, heart, and lungs. The inability of chemotherapy drugs and chemicals to tell the difference between cancer cells and normal cells results in its devastating "side effects": hair loss; dry eyes; mouth sores and ulcers; nausea, vomiting, and diarrhea; stomach or intestinal bleeding; anemia; damage to the heart and other organs; and a severely weakened immune system. Chemotherapy often destroys the immune system by killing white blood cells as they are manufactured in the bone marrow. These cells are the body's first defense system against bacteria, viruses and, ironically, cancer. Their destruction opens to door to a range of secondary, opportunistic infections that can lead to death. In addition to immediate side effects, many chemotherapy drugs cause permanent damage that appears and persists long after treatment has ended. These effects, which are well documented in the scientific literature, include damage to organs (weakening of the heart muscle, toxic damage to the liver, kidneys, and bladder), fatigue, "chemobrain" (problems with memory and concentration), infertility, hearing loss, "peripheral neuropathy (a sensation of numbness or burning in the hands and feet), bone loss, and scarring of the lungs. Many chemotherapy drugs cause damage to DNA. As a result, chemotherapy actually increases the chance that new cancers will develop in the future, and is a major problem, especially for survivors of childhood and adolescent cancers.

"As a practicing oncologist for the past 20 years, I have seen that chemotherapy has been overused, and many times potential toxic effects should have deterred the oncologist from persisting in various "protocols" in the name of killing the last cancer cell. There should be more emphasis on supplemental use of alternative therapies... to improve the quality of life rather than ending up in a total avoidable disaster in many of advanced cancer cases." (April, 2011) ~ Arvind Kulkarni, MD, former Medical Director. Integrated Medical Program, Allegheny General Hospital, Pittsburgh, PA

Radiation Therapy

Radiation therapy uses high-energy particles, rays, or waves to damage cancer cells, making them die or slowing their reproduction. All the side effects of chemotherapy can also happen with radiation, except the physical damage is usually limited to the areas directly under the radiation beam. Radiation treatment of head and neck cancer, for example, often causes substantial and permanent hearing loss.* A 2011 study of women with early-stage breast cancer suggested that surgery followed by radiation decreased cancer recurrence compared to surgery alone; but when breast cancer did recur after radiation, it was more likely to be invasive.¥ Also, it is well known that incidental exposure of the heart during radiation therapy can increase the risk of subsequent heart disease.+ Like chemotherapy, radiation therapy also can cause long-term damage to the body. The severity and type of damage depends on the the site of the cancer and how much of the body was exposed. Some common harmful effects are damage to the heart (after breast cancer), anal and rectal problems (after prostate cancer), hearing loss and problems with memory and concentration (after brain cancer), and increased chances of developing other cancers. Biological Treatments Experimental biological therapies for treating cancer, such as anti-tumor vaccines, gene therapy, and monoclonal antibodies recently have come into use, but their success has been limited. Cancer cells mutate regularly, selecting out those that reproduce and spread the best. Biological therapies also can have harmful side effects, and their effectiveness depends the individual patient and type of cancer. More importantly, cancer cells ultimately develop ways to evade or thwart the treatments, so complete cures rarely are achieved.

Why the Cancer-Fighting Diet is Different Unlike the conventional treatments that kill both cancerous and healthy cells, including those of the immune system, the cancer-fighting diet contains naturally occurring substances that stimulate the immune system's ability to fight cancer. This is the key to its effectiveness: it enables the immune system to destroy cancer cells without harming normal, healthy cells. This is how it keeps the cancer from spreading to new places in the body. In addition the enhancing the immune system, the diet also contains substances that: 1) cut off the food supply to existing tumors by inhibiting the growth of new blood vessels to the tumors (anti-angiogenesis); 2) make cancer cells revert to normal behavior-- they lose their ability to grow out of control into tumors, and they die (apoptosis); prevent the formation of "free radicals" that can damage cells and lead to cancer; and increase the ability of cells to repair damage that has already occurred. (See The Diet for a detailed discussion of the benefits of this method of treating cancer.) * Schultz, C. et al. 2010. Hearing loss and complaint in patients with head and neck cancer treated with radiotherapy. Archives of Otolaryngology, Head and Neck Surgery 136(11):1065-9. ¥ Janie Weng Grumley, M.D., fellow, breast oncology, University of Southern California Keck School of Medicine; presentation, American Society of Breast Surgeons meeting, Washington, DC, April 29, 2011. + Taylor, C., and Darby, SC. JAMA Internal Medicine. Published online, October 28, 2013. doi:10. 1001/ jamainternmed.2013.9131.

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Let your food be medicine and your medicine be food. ~Hippocrates, the Father of Western Medicine

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The Diet: What It Is, and What It's Not What It Is WHAT IT IS The Story What It Is, and What It's Not Conventional Medical Treatments



HOW IT WORKS The Immune System and Cancer Foods & Supplements



HOW TO DO IT Key Concepts Forbidden Foods The Eating Regimen Toolkit



It is a highly specific dietary regimen (eating program) for adults with diagnosed cancers, who are not currently receiving chemotherapy or radiation therapy or who have completed surgery or other medical treatments. It requires normal (not "mega") dosages of several vitamins, minerals, and herbal supplements, in combination with certain foods, taken at specific times of the day. The objective is to maximize the absorption of the critical nutrients and active substances that can shrink existing tumors and prevent the formation of new ones. It is based on scientific studies that have been published in reputable journals. It contains foods and supplements that act in six different ways to help eliminate existing tumors and to keep new ones from forming. 1) It enhances and restores the immune system with biologically active substances derived from plants. 2) It improves the body's natural ability to prevent cancer-causing damage to cells. 3) It helps to repair damage to cells that has already occurred and has the potential to become cancer. 4) It slows or stops the growth of new blood vessels to feed existing tumors. 5) It prevents existing cancer from spreading (metastasizing) to other tissues and other parts of the body. 6) It causes cancer cells in existing tumors to "commit suicide" by inducing a process called apoptosis. This process ends with the death of cells and occurs as a normal and controlled part of all living things' growth or development. It is blocked in cancer cells, which enables them to grow out of control and form tumors. It can be used to fight any kind or stage of cancer, either as a first and only treatment or after conventional medical therapy (chemotherapy, radiation) is finished. It is free and based on open information, all of which is provided on the web site. Everything you need to take-- all the foods and all the supplements-- can be found at most drugstores and health food stores. We do not sell anything. It will not work, however if: The person with cancer is currently being treated with chemotherapy or extensive radiation therapy. Because the eating regimen destroys existing tumors and stops cancer from spreading largely by restoring and enhancing the immune system, it cannot work during these treatments, which weaken or destroy the immune system. The cancer is so extensive, or prior medical treatments were so damaging, that a vital organ or organ system has failed irreversibly. Vital organs are those that are essential for the body's existence, such as the brain, heart, liver, lungs, kidneys, and pancreas. What It's Not It is not a "complementary" therapy. Complementary therapies are used in combination with conventional treatments, such as chemotherapy and radiation. These treatments weaken the immune system and prevent the diet from working (see Conventional Cancer Treatments). It can, however, be used after such treatments, to help restore the immune system and to prevent new tumors from forming. (NOTE: There is growing scientific evidence that certain food

supplements make chemotherapy and radiation work better against cancer cells, while protecting normal cells from damage and reducing other common side effects. A section about these nutrients will be added to this web site soon.) It is not a list of general guidelines for lowering cancer risk. It is not a weight-loss diet. It is not a "macrobiotic" diet. It does not require "mega-doses" of vitamins and other supplements; in fact, in most cases, it calls for the lowest available dosage of each supplement. It does not involve any proprietary powders or pills, enzymes, extracts, glandular concentrates, electrical charges, or "frequency generators," or any other substances or devices that have not been studied by qualified researchers and documented by publication in reputable scientific journals. It does not require body cleansing, fasting, or enemas. It does not "make the body alkaline." It does not poison cancer cells. It is not based on religious, spiritual, or mystical beliefs, or blood or body types.

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Let your food be medicine and your medicine be food. ~Hippocrates, the Father of Western Medicine

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The Recipes section is still being developed. Please contact Carol with your questions about foods and meal preparation.

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Let your food be medicine and your medicine be food. ~Hippocrates, the Father of Western Medicine

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Has This Diet Been Proven Effective in Clinical Studies? Question: Has the effectiveness of this dietary regimen been proven in clinical trials? Answer: There is no simple answer to this question. Everything in the cancer-fighting diet-- the foods and individual supplements-- has been studied scientifically, reported in scientific our medical journals, and is included because it has the ability to fight cancer or keep it from developing. More important, they foods and supplements are safe and not harmful under most circumstances. Some of the studies have been conducted with cancer cells grown outside the body in cultures, some have been done with laboratory animals (such as Dr. Miller's own studies on Echinacea and ginseng), and others have involved human subjects. "Randomized controlled clinical trials" are considered the gold standard for demonstrating the effectiveness of a treatment. They are experiments involving people selected according to specific criteria and then randomly placed in a group that receives one or the other of the treatments being studied. These studies are extremely complex, typically cost millions of dollars, and take several years to complete. They test a single intervention-- one drug or treatment-- rather than a complex regimen such as the cancer-fighting diet. Although some randomized trials are sponsored by non-profit organizations or government agencies, most are funded by the health care industry and pharmaceutical companies. Businesses are unlikely to invest such time and money to study foods and food supplements, when there is no promise of future profits. (For example, the drug Avastin, used to treat colorectal and lung cancers, costs $5,000 a month, and Gleevec, used to treat leukemia, costs $92,000 a year. In contrast, food supplements can be bought for a few dollars at any grocery store or drugstore.) So it is not likely that the diet or many of its components every will be tested in randomized controlled clinical trials. Is this a drawback? Not at all. As stated simply but eloquently by George Ebers, MD, Professor of Neurology and specialist in Genetic Epidemiology and Immunology at the University of Oxford, United Kingdom: "It's all very nice to have a randomized trial, but they are not the be all and end all. If we needed a randomized clinical trial, then we still wouldn't recognize that smoking caused lung cancer and contaminated water caused cholera." (Medscape Medical News, from the 29th Congress of the European Committee for Treatment and Research in Multiple Sclerosis, October 3, 2013)

Can Certain Foods Be Substituted for Others? Low-fat Dairy Products Question: I am lactose intolerant. What can I substitute for low-fat milk and yogurt in your dietary regimen? Answer: Almond milk or soy milk may be substituted for low-fat milk. Note: Although some doctors think that soy mimics estrogen and could make some breast cancers grow faster, there is no evidence that this is true. If you cannot eat yogurt take a good probiotic supplement containing a mix of different bacteria (especially Lactobacillus and Bifidobacterium). Probiotics help maintain a healthy balance of microorganisms in the digestive system and reduce the growth of harmful bacteria. They may help to control diarrhea and prevent infections, and also could help control inflammation related to irritable bowel syndrome and colorectal cancer. Oatmeal Question: I am on a gluten-free diet. What can I eat instead of oatmeal, wheat bread, and wheat crackers? Answer: Oats are included in the diet mainly because they minimize cholesterol accumulation, but oatmeal is not essential. Feel free to substitute quinoa or brown rice for oatmeal, and rice crackers and any gluten-free breads and crackers for regular breads and crackers.

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SANDRA C. MILLER Biographical Info Publications CAROL E. BOWER Biographical Info Publications

About Us Sandra C. Miller, PhD is a Professor in the Department of Anatomy and Cell Biology, Faculty of Medicine, at McGill University in Montreal, Quebec. She has taught and conducted research at McGill for since 1978. She also has conducted research at two distinguished medical schools in the United States (see Biographical Information). Sandra's research focus for more than 30 years has been the cells of the body's immune system, especially natural killer (NK) cells. NK cells are instrumental in seeking out and destroying newly formed cancer cells. She formulated "the immunity cancer cure"--her cancer-fighting eating regimen, as an outgrowth of her studies on enhancement of the immune system in the presence of cancer by using substances derived from plants. She has published numerous research papers in medical and scientific journals (see Publications), edited a textbook on Echinacea, and she has received several awards for excellence in education and research. Sandra's work was featured in the March, 2007 issue of Cancer Monthly. Sandra's father died of pancreatic cancer at the age of 66, long before anyone knew about treating cancer with biologically active plant products. Carol E. Bower, BSc is medical writer and editor, currently working in public health research and planning. Previously, she directed aquatic chemistry, parasitology, and toxicology laboratories, and conducted research in the Department of Tropical Public Health at Harvard School of Public Health. Carol has authored three books. Her other publications include educational guides, peer-reviewed research papers on human and animal health, and many reports on population health. She served on the Board of Directors of the Connecticut Cancer Partnership, from 2002 to 2009 and was editor of its web site. Carol's father died of lung cancer in 1967 at the age of 48. Her mother was diagnosed with non-Hodgkin lymphoma in late 2005. She refused to have conventional treatments, and with her oncologist's consent, began following the cancer-fighting diet since February, 2006. One year later, she was declared cancer free. In July, 2013 she celebrated her 91st birthday, and is presently in fine health with no detectable cancer. She still takes all the supplements every day.

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Let your food be medicine and your medicine be food. ~Hippocrates, the Father of Western Medicine

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How to Contact Us General Comments and Suggestions We are using this web site to share with you what Dr. Sandra C. Miller has learned from her research on cancer and the immune system, and Carol E. Bower's practical experience with the cancer-fighting diet, from the standpoint of a caregiver and counselor to those who use it. Because this is our first use of the Internet to publish information about the cancerfighting diet, we still have much to learn about how best to address the concerns of people with cancer, their caregivers, loved ones, and friends. Please let us know what you think of this site and how we can make it better. The best ideas come from you, so please share with us your suggestions, recipes, and experiences. Thanks for your help! Questions for Dr. Sandra C. Miller and Carol E. Bower Please check the Questions & Answers page before asking us specific questions about the cancer-fighting diet. We'll try our best to answer each question personally, if time permits, and add it to the published list. Please be patient, as we do this as a free service and hold other full-time jobs. Also, please remember that we are not medical doctors and do not give medical advice, diagnosis, or treatment. Sandra can answer technical questions about the immune system and cancer, how the diet works, and food substitutions. Carol can answer questions about logistics, food preparation, sources of supplements, and recipes. Send your questions to: [email protected] [email protected] Technical Problems For problems with this web site (missing pages, broken links, dreaded typos, etc., please send your e-mails to: [email protected]

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Let your food be medicine and your medicine be food. ~Hippocrates, the Father of Western Medicine

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The Cancer-Fighting Diet: How to Do It

WHAT IT IS

Key Concepts 1. This is not a "lose weight diet." It is a "save-your-life" diet. Be sure you

The Story

understand the difference.

What It Is, and What It's Not

2. Humans were originally grazers and foragers, eating small amounts of

Conventional Medical Treatments

food here and there throughout the day. Eating three meals a day is known as "bolus eating" (consuming large volumes in one sitting). No other creature on earth intentionally "bolus eats" the way humans do. In the cancer-fighting diet, the words, breakfast, lunch, and dinner are meaningless and are not used.



HOW IT WORKS The Immune System and Cancer

3. You will eat specified foods with specified vitamins and other

Foods & Supplements

supplements 6 times per day (as described later) for at least 2-3 months, then go back to your oncologist to check on the status of your cancer.



HOW TO DO IT

4. The foods in each of the 6 “eating times” were planned with the indicated

Key Concepts

vitamins and herbals in carefully defined combinations (see Rationale for Foods & Supplements). The combinations are based on: 1) the timing of daily growth and reproductive phases of the different cells of your immune system; and 2) on "molecular bonding" of the supplements with the foods, which ensures that they are absorbed by your body.

Forbidden Foods The Eating Regimen Toolkit

For these reasons, although you may switch “# 3” with “# 4,” be sure you do so in its entirety--both the foods and supplements. DO NOT, however, change “# 5” and “# 6” with each other or anything else. Our body functions are governed by "biological clock" throughout a 24-hour daily cycle, and this diet is timed to correspond with those bio-rhythms. 5. For the first 2-3 months, NEVER eat any of the following foods and

NEVER use laxatives (see Forbidden Foods for explanation): a. Red meat (beef, veal, lamb, etc.) b. Ham, pork, bacon, or other pork products c. Processed meats such as hot dogs, lunch meats, or coldcuts (even turkey coldcuts) c. Coffee d. Margarine, shortening, vegetable oils (except olive and canola oils), and foods containing trans fats. (Trans fats are identified as "hydrogenated" or "partially hydrogenated" oils. READ FOOD LABELS CAREFULLY.) 6. Although sugar is not entirely off-limits, you'll also want to go easy on

sugary foods. [Lists of preferred food and foods to avoid are given under xxx.] 7. When your oncologist determines with an MRI, CT scan, or PET scan that

your tumors are shrinking and the cancer has not spread, continue to follow the diet strictly for another 4-6 months, then get evaluated again. The amount of time it will take for your cancer to be eliminated depends on many things, such as they type of cancer and how far it has progressed when you begin the diet. Another key factor is your age. The older you are, the longer it takes to work.* 8. Even when there is no sign of remaining cancer, continue to maintain

some level of the diet. Remember that one single, completely undetectable cancer cell is all it takes to begin growing another tumor. Keeping the immune system healthy and strong with the recommended foods and supplements will ensure that not even one cancer cell can survive and form a tumor. * Our immune systems decline as we age. For people in their 70's and older, it may take several months to rebuild the immune system, then even longer for their immune systems to fight the cancer.



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Let your food be medicine and your medicine be food. ~Hippocrates, the Father of Western Medicine

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WHAT IT IS The Story What It Is, and What It's Not Conventional Medical Treatments

About the Immunity Cancer Cure When you learn you have cancer, everything seems frightening and confusing, whether it is the first time it has been diagnosed or if it has returned after months or years. Even without leaving the bounds of conventional medicine, the choices you must make can be overwhelming--choices that could determine how long you live and the quality of your life. On the one hand, medical doctors offer surgery, chemotherapy, radiation, or experimental treatments.



HOW IT WORKS

On the other hand, well-meaning people bombard you with information about alternative therapies--enzymes, extracts, chemicals, electronic devices, or other "magic bullets"--and their suggestions only add to your confusion.

The Immune System and Cancer Foods & Supplements



HOW TO DO IT Key Concepts Forbidden Foods The Eating Regimen

How you choose to fight your cancer may be the most important personal decision you will ever make. As you weigh your choices, we hope you will explore this web site and learn about Dr. Miller's dietary regimen. It might save your life, or the life of someone you love.

Toolkit

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Let your food be medicine and your medicine be food. ~Hippocrates, the Father of Western Medicine

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Welcome to Immunity Cancer Cure WHAT IT IS The Story What It Is, and What It's Not Conventional Medical Treatments



HOW IT WORKS The Immune System and Cancer Foods & Supplements



HOW TO DO IT Key Concepts Forbidden Foods The Eating Regimen

This web site contains information about a cancer-fighting nutritional regimen. The regimen ("diet") was developed by Sandra C. Miller, PhD for adults with cancer. It also can be followed by healthy individuals to lower their chances of getting cancer. It works in several ways, most importantly by enhancing the immune system-the body's natural defense against cancer--without harming normal, healthy cells. It is a carefully defined regimen, in which specific food supplements are taken at specific time help to ensure that the body absorbs the most cancer-fighting nutrients, and when they are taken aligns with the growth cycles of various cell types in the immune system. It is grounded in scientific evidence. It integrates findings from hundreds of studies published in peer-reviewed journals on the effects of phytochemicals (substances derived from plants), vitamins, minerals, and other supplements on the immune system and on cancer development and tumor growth. It can be used against any kind of cancer at any stage, either as the first and only treatment, or after surgery, chemotherapy, or other conventional medical treatments have been completed.

Toolkit

Important Note: The cancer-fighting eating regimen will not be effective during chemotherapy or extensive radiation (both of which harm the immune system). It also will not work if disease or prior treatments with radiation or chemotherapy have caused major, irreversible to any vital organs (heart, brain, lungs, liver). All the information about the cancer-fighting eating regimen is free. We do not sell or promote any books, brands or distributors of supplements, or counseling or treatment facilities, nor are we affiliated with any commercial ventures. Occasionally, we recommend specific brands for reasons of quality and efficacy. None of the foods or supplements in the eating regimen is proprietary or requires a prescription. They all can be found at many drugstores and health food shops, or can be purchased online (typically at a much lower cost) from the source of your choice. Sometimes we mention specific web sites that we have found have the lowest prices. We encourage you explore this web site and learn more about the cancer-fighting eating regimen (see How to Use This Web Site). It could save your life or the life of someone you care about who has cancer. It will always improve quality of life for a cancer survivor, and will lower anyone's chance of getting cancer.

Copyright © 2014 by immunitycancercure.org. All rights reserved. Address inquiries to the web site editor.

immunitycancercure.org is intended to provide information about enhancing the immune system with plant products to fight cancer. See additional information. xxxxxxxxx



Let your food be medicine and your medicine be food. ~Hippocrates, the Father of Western Medicine

HOME | THE DIET | RECIPES | Q & A | ABOUT US | CONTACT US



Welcome to Immunity Cancer Cure WHAT IT IS The Story What It Is, and What It's Not Conventional Medical Treatments



HOW IT WORKS The Immune System and Cancer Foods & Supplements



HOW TO DO IT Key Concepts Forbidden Foods The Eating Regimen

This web site contains information about a cancer-fighting nutritional regimen. The regimen ("diet") was developed by Sandra C. Miller, PhD for adults with cancer. It also can be followed by healthy individuals to lower their chances of getting cancer. It works in several ways, most importantly by enhancing the immune system-the body's natural defense against cancer--without harming normal, healthy cells. It is a carefully defined regimen, in which specific food supplements are taken at specific time help to ensure that the body absorbs the most cancer-fighting nutrients, and when they are taken aligns with the growth cycles of various cell types in the immune system. It is grounded in scientific evidence. It integrates findings from hundreds of studies published in peer-reviewed journals on the effects of phytochemicals (substances derived from plants), vitamins, minerals, and other supplements on the immune system and on cancer development and tumor growth. It can be used against any kind of cancer at any stage, either as the first and only treatment, or after surgery, chemotherapy, or other conventional medical treatments have been completed.

Toolkit

Important Note: The cancer-fighting eating regimen will not be effective during chemotherapy or extensive radiation (both of which harm the immune system). It also will not work if disease or prior treatments with radiation or chemotherapy have caused major, irreversible to any vital organs (heart, brain, lungs, liver). All the information about the cancer-fighting eating regimen is free. We do not sell or promote any books, brands or distributors of supplements, or counseling or treatment facilities, nor are we affiliated with any commercial ventures. Occasionally, we recommend specific brands for reasons of quality and efficacy. None of the foods or supplements in the eating regimen is proprietary or requires a prescription. They all can be found at many drugstores and health food shops, or can be purchased online (typically at a much lower cost) from the source of your choice. Sometimes we mention specific web sites that we have found have the lowest prices. We encourage you explore this web site and learn more about the cancer-fighting eating regimen (see How to Use This Web Site). It could save your life or the life of someone you care about who has cancer. It will always improve quality of life for a cancer survivor, and will lower anyone's chance of getting cancer.

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THE “IMMUNITY CANCER CURE” CANCER-FIGHTING DIET Summary of Daily Foods & Drinks

The following pages contain short versions in “index card” format of what to eat and drink at each of the 6 consumption occasions. You might find it helpful to print them on heavy paper, cut each sheet in half into cards, and keep the cards on your kitchen counter for reference until you become more familiar with the diet. The specific supplements are not listed, because they’ll already be set up in numbered pill containers (as described in Dispensing Supplements). Remember that the important thing when you’re fighting an existing cancer is how often you eat, not how much you eat. You need to eat a little something and take your supplements every 3-4 hours throughout the day, to make sure that your immune system is always being stimulated with something good for it.

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FIRST (About 8-9 a.m.) Oat-based cereal sprinkled with 1 Tbsp. ground flax seed with low-fat milk (Oatmeal, Cheerios, Heart to Heart, oatmeal muffins, oat waffles) Banana (at least ½) Low fat yogurt with acidophilus V-8, V-8 Fusion, or other vegetable juice (not tomato juice or plain fruit juice) Supplements #1 Green tea ----------------------------------------------------------------------------------------------

SECOND (About 11 a.m.-Noon) Salad with variety of veggies, with olive oil dressing Tofu (can be stir-fried in olive oil w/ mushrooms or other vegetables, or substituted for egg on an egg-salad sandwich) or/ edamame beans or/ soy nuts Beans (5-bean salad, black beans, etc.) Use edamame beans if no tofu or soy is eaten. Dark chocolate or nutella on crackers(if desired for dessert) Supplements #2 Green tea, low-fat milk, or soy milk

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THIRD (About 2-3 p.m.) Fruit salad Pasta with tomato sauce or/ hard-boiled egg Dark Chocolate or Nutella on wheat crackers for dessert if desired Supplements #3 Green tea, low-fat milk, or soy milk

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FOURTH (About 5-6 p.m.) Chicken or seafood (can be prepared/seasoned any way you like,except fried). Examples: chicken or tuna salad with Hellman’s canola mayonnaise; baked, broiled, or sautéed chicken, shrimp, or fish; chicken parmesan Vegetables or salad (raw are best except for carrots, but lightly steamed OK too) with 1 Tbsp. ground flax seed Fruit salad or chocolate (Nutella) for dessert if desired Supplements #4 Green tea, low-fat milk, or soy milk

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FIFTH (Snack) (About 8 p.m.) A small amount of any food from 1st thru 4th consumptions earlier in the day Add 1 Tbsp. ground flax seed to whatever you eat Yogurt Supplement #5 (one multivitamin) Green tea

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SIXTH (Just before bed) A small amount of food (dry crackers or a little yogurt) Supplement #6 (one Echinacea tablet) Green tea only

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Supplement List * (To be taken with specified foods. Times are approximate.) First Eating Time (6 a.m. to 9 a.m.) 1 Echinacea tablet (Use only a standardized extract. We recommend Bioforce Echinaforce by A. Vogel) 1 Multivitamin (Any good brand, but we use "Solaray Twice Daily Multivitamins") 1 Vitamin C with bioflavonoids (500 mg) ** 1 Vitamin E (400 IU) 1 NAC (N-acetylcysteine) capsule (600 mg) (Twinlabs brand has no unpleasant odor.) 1 Bilberry capsule 1 Biotin capsule 1 Folic acid (400 mcg) 1 Zinc (low dose) ** 1 Calcium/Magnesium with Vitamin D (These are quite large. Schiff makes a gel cap that’s easy to swallow.) Second Eating Time (10 a.m. to Noon) 1 Vitamin C with bioflavonoids (500 mg) 1 B-100 Vitamin B complex vitamin 1 Alpha lipoic acid ** 1 Coenzyme Q-10 (50 mg for most people; 100 mg or more for people who take statins to control cholesterol) 1 Astragalus (350 mg) Not to be taken by people with autoimmune disorders such as rheumatoid arthritis) 1 Burdock capsule (540 mg) Not to be used by people who are taking insulin 1 Cranberry capsule 1 Beta Carotene capsule Third Eating Time (1 p.m. to 4 p.m.) 1 Vitamin C with bioflavonoids (500 mg) 1 Vitamin E (400 IU) 1 Lycopene (10 mg) 1 Vitamin D (2,000 IU) Fourth Eating Time (5 p.m. to 7 p.m.) 1 Selenium 1 Folic acid 1 Resveratrol (100 mg) 1 Omega-3 fish oil capsule (Carlson's Elite Omega or Nordic Naturals Pro-Omega brands recommended) 1 Lactoferrin, 250 mg (For women with estrogen-receptor positive breast cancer, especially if they are taking Tamoxifen, Arimidex, or other estrogen blocking drugs. Jarrow brand recommended. Lactoferrin is so safe and has so many beneficial functions-- anti-inflammatory, antimicrobial, stimulates bone growth and replacement, anti-cancer) that we recommend it for all people, esp. all postmenopausal women.) Fifth Eating Time (8 p.m. to 10 p.m.) 1 Multivitamin 6ixth Eating Time (Just before bed) 1 Echinacea tablet * Unless dosage is specified, take lowest dosage available ** Natrol now makes a produced called Easy C Regenerating Complex, a capsule which contains 500 mg vitamin C, bioflavonoids, 50 mg alpha lipoic acid, and 19 mg zinc. This may be substituted for the 3 individual supplements (vitamin C, alpha lipoic acid, and zinc) and taken during the first eating time.

Supplement List (In alphabetical order)

Alpha lipoic acid Astragalus Beta Carotene Bilberry Biotin Burdock Calcium/Magnesium with Vitamin D Coenzyme Q-10 (Co Q-10) Cranberry Echinacea Folic acid Lactoferrin Lycopene Multivitamin N-acetylcysteine (NAC) Omega-3 fish oil Resveratrol Selenium Vitamin B complex (B-100) Vitamin C with bioflavonoids Vitamin D Vitamin E Zinc

Notes: To ensure quality products, avoid store brands and stick with name brands such as Natures Way (for all herbal supplements except Echinacea) and Solaray, Solgar, Twinlabs, NOW, Natrol, Schiff, and Jarrow for vitamins, minerals, and other supplements. When ordered online from discount web sites (such as www.luckyvitamin.com or www.vitacost.com), the supplements (all brand names) cost about $80 a month. They are 40-60% more expensive when purchased at retail stores. You also can find certain brand-name supplements at good prices at Sam’s Club, BJ’s, and Costco. Order capsules instead of tablets, as they are much easier to swallow. Carol will gladly share the list of specific products she orders for her mother. Feel free to e-mail her at [email protected].

THE CANCER-FIGHTING DIET: DAILY / WEEKLY SUPPLEMENT SET-UP (C.E. Bower, September, 2007)

For the cancer-fighting food program, you’ll need to take vitamins, minerals, and herbal supplements with specific foods 6 times throughout each day. Because 19 different supplements are involved (a few taken two or three times a day) you’ll need to get organized. Organization is especially important when you are a caregiver for someone with cancer, and you will not be around every time the person eats. This is the system I worked out to help my mother, after she was diagnosed with non-Hodgkin lymphoma. A. GET AND PREPARE CONTAINERS FOR STORING SUPPLEMENTS

1. At first, I put the tablets and capsules into individual plastic snack bags or new plastic pill bottles (which my pharmacist kindly gave me at no charge). Then I discovered it was faster and easier to set up a week’s worth of supplements in advance, in pill organizers. After the initial steps are done (labeling the containers and supplement bottles), it takes only about 15 minutes to set out a full week of supplements. Then they’re ready to take, with no further thought or bother. 2. Many different kinds of pill containers are available. A few are shown below. You can find them at any drugstore or online (search for “pill organizer”). Whatever kind you choose, make sure that each compartment is large enough to hold 10 tablets or capsules.

3. I chose the “VitaMinder Seven Day Vitamin Pack” (MEDPort, LLC, Providence, RI), shown in photos below. I like them because they are unmarked, so you can label them however you wish, and the interior compartments close separately. I bought mine at a health food store for $2.99 each, but later found them online for less (The lowest price I found was $1.79 each at House of Nutrition Online http://hono.stores.yahoo.net/vitaminder.html Shipping is a flat $5.95 per order). HON also sells vitamins, but they don’t discount them as much as some other sellers do.

4. If you choose to use pill organizers, get at least 7 of them (one for each day of the week) with at least 6 compartments in each (for each of the 6 times you will eat each day). I bought 2 extra ones, in case I am late doing a set up.

B. LABEL THE CONTAINERS 1. Label the outside of the containers. Using a permanent marker, stickers, masking tape, or a label maker, write the days of the week on the outside of the pill containers—one day per container. If you bought extras, label them “Extra”.

2. Label the compartments inside each container. Using a permanent marker, tape, or labels, number the inside compartments from 1 through 6. Leave any extras blank.

C. LABEL THE SUPPLEMENT BOTTLES I found that it was easier to label the bottles of supplements with numbers corresponding to the eating times when they were needed, rather than trying to sort through them looking for certain ones by name. Refer to the Supplement Checklist in the instructions for the cancer-fighting diet, to see what supplements are taken at each of the 6 eating times. 1. Mark the bottles. Using a permanent marker, sticker, or tape, mark the “eating time” number or numbers (1, 2, 3, 4, 5, or 6) on the cap of each supplement bottle. (Use a sticker if the bottle cap is dark.) For example, because folic acid is taken in the morning (#1) and late afternoon (#4), write “1, 4” or “1+4” on the cap of the folic acid bottle. When you’re finished labeling the bottles, you’ll have something that resembles the assortment below.

2. Store the supplement bottles when not in use. Store the labeled supplement bottles in a cool dry place (not in a bathroom). I keep them in an cardboard box at the top of the basement stairs, but a plastic storage container would probably work better.

C. HOW TO DISPENSE THE SUPPLEMENTS A WEEK AT A TIME 1. Remove the supplement bottles from the storage container, and arrange them in rows on a table, with the highest numbers in the back and the lowest numbers in the front. If a bottle has more than one number, go by the highest number. I do this at the kitchen table.

2. Open the pill containers and interior compartments, and lay them out next to the supplements.

3. Beginning with the bottles with the highest numbers on the labels, dispense the supplements into the compartments with the corresponding numbers. (For example, first take the bottle of Echinacea (“1, 6” on cap) and put one tablet in compartment 6 and one tablet in compartment 1 of each pill container. Close the bottle and return it to the storage box. (I keep the empty box on the floor and drop in the bottles as I go through them, to get them out of the way.) 4. After a compartment has been completed (all supplements added to it, even if it only contains one tablet or capsule) close the compartment. This will help keep you organized and lower the chances of putting supplements into the wrong compartments. 5. Continue dispensing supplements, matching up the numbers on the bottle caps with the numbers on the compartments. Close each compartment when filled, and remove each supplement bottle from the table after you’re finished with it. 6. If you take any supplements other than those on the cancer-fighting diet, they can be labeled and added to the containers also. (For example, I put glucosamine/chondroiton capsules for joint pain in compartments 4, and 5 in the picture below.) Note that the most supplements are taken earlier in the day (at eating times 1 and 2), and fewer are taken as the day goes on.

7. After all the supplements have been dispensed, close all the lids and put the daily containers away. My mother stores here in a kitchen cabinet, takes out one container each morning, and leaves it on the kitchen counter, so she’ll have it handy each time she eats.

When you get low on a particular supplement, label a new bottle and replace the empty one. I always order supplements for 3 or 4 months at a time, to avoid running out and getting stuck paying much higher prices at local stores.

PUBLICATIONS OF SANDRA C. MILLER    Full Papers In Peer‐Reviewed Journals, 1973‐2013    Miller, S.C. and Osmond, D.G. (1973) The proliferation of lymphoid cells in guinea pig bone marrow. Cell  Tissue Kinet. 6: 259‐269.    Osmond, D.G., Miller, S.C. and Yoshida, Y. (1973) Kinetic and hemopoietic properties of lymphoid cells in  the bone marrow. Haemopoietic Stem Cells. CIBA Foundation Symposium (Wolstenholme, G.E.W. and  M. O=Connor, eds.) ASP, Elsevier/North Holland Press, Amsterdam, pp. 131‐156.    Miller, S.C. and Osmond, D.G. (1974) Quantitative changes with age in bone marrow cell populations of  C3H mice. Exp. Hemat. 2: 227‐236.    Miller, S.C. and Osmond, D.G. (1975) Lymphocyte populations in mouse bone marrow: quantitative  kinetic studies in young, pubertal and adult C3H mice. Cell Tissue Kinet. 8: 97‐110.    Miller, S.C. and Osmond, D.G. (1976) Quantitative studies of lymphocytes and other cell populations in  the bone marrow of neonatally thymectomized mice.  Anat. Rec. 184: 325‐333.    Miller, S.C. , Kaiserman, M. and Osmond, D.G. (1977) Small lymphocyte production and lymphoid cell  proliferation in mouse bone marrow. Experientia 134: 129‐131.    Yang, W.C., Miller, S.C. and Osmond, D.G. (1978) maturation of bone marrow lymphocytes. II.  Development of Fc and complement receptors and surface immunoglobulin studies by rosetting and  radioautography. J. Exp. Med. 148: 1251‐1270.    Kanamaru, A. Durban, E. Gallagher, M.T., Miller, S.C. and Trentin, J.J. (1980) Augmentation of erythroid  burst formation by the addition of thymocytes and other myelo‐lymphoid cells. J. Cell Physiol. 104: 187‐ 197.    Miller, S.C. (1981) Failure to demonstrate morphologically the presence of colostral or milk cells in the  wall of the gastrointestinal tract of the suckling neonatal mouse.  J. Reprod. Immunol. 3: 187‐194.    Miller, S.C. (1981) Genetic resistance to transplantation of xenogeneic bone marrow lin mice of various  strains: influence of an interferon inducer and age. Scand. J. Immunol. 14: 515‐532.    Miller, S.C. (1982) Production and renewal of murine natural killer cells in the spleen and bone marrow.  J. Immunol. 129: 2282‐2286.    Miller, S.C. (1983) Genetically determined resistance to foreign bone marrow transplantation:  characteristics of the effector cells. J. Immunol. 131: 92‐97.    Miller, S.C. (1984) Life history of cells mediating natural resistance to tumor cells and bone marrow  transplants: The respective roles of cell lineage commitment and host environment in determining strain  characteristics of natural resistance to foreign marrow grafts. Amer. J. Anat. 170:367‐376.   

Nassiry, L. and Miller, S.C. (1987) Renewal of natural killer cells in mice having elevated natural killer cell  activity. Nat. Immun. Cell Growth Reg. 6: 250‐259.    Miller, S.C., Galley, D. and Nguyen, D. (1988) Inhibition of natural killer cell mediated lysis of tumor cells  by normal and regenerating bone marrow. Immunobiol. 177: 82‐90.    Miller, S.C., Nguyen, D. and Bird, I. (1988) The effect of bearing tumors on the ability of mice to reject  bone marrow transplants. Scand. J. Immunol. 27: 427‐432.    Miller, S.C. and Poirier, L. (1988) Characteristics of cells mediating spontaneous resistance to bone  marrow allografts.  Immunobiol. 178: 191‐202.    Miller, S.C. and Christopher, F.L. (1989) Altered production and renewal of natural killer cells in B  lymphocyte‐deficient CBA/N mice.  Nat. Immun. Cell Growth Reg. 8: 245‐254.    Christopher, F.L. and Miller, S.C. (1991) Effects of low pathogen environment on natural killer cells of  normal and B lymphocyte‐deficient mice. Nat. Immun. Cell Growth Reg. 10: 216‐225.    Miller, S.C. and Shatz, A. (1991) Relationship between large and small tumor‐binding cells in the spleen  and bone marrow. Nat. Immun. Cell Growth Reg. 10: 320‐326.  .  Christopher, F.L., Dussault, I. and Miller, S.C. (1991) Population dynamics of natural killer cells in the  spleen and bone marrow of normal and leukemic mice during in vivo exposure to interleukin‐2.   Immunobiol. 184: 37‐59.    Miller, S.C., Christopher, F.L. and Dussault, I. (1992) Population dynamics of natural killer cells and T  lymphocytes in murine spleen and bone marrow during the development of erythroleukemia: The effect  of indomethacin.  Nat. Immun. 11: 78‐92.    Miller, S.C. (1992) Age‐related differences in the effect of in vivo administration of indomethacin on  hemopoietic cell lineages of the spleen and bone marrow of mice. Experientia 48: 674‐678.    Dussault, I. and Miller, S.C. (1993) Stimulation of natural killer cell numbers but not function in leukemic  infant mice: A system primed in infancy allows survival in adulthood. Nat. Immun. 12: 66‐78.    Miller, S.C., Fleming, W.H., Zsebo, K.M. and Weissman, I.L. (1993) The in vivo effects of stem cell factor  on hemopoietic and natural killer lineage cells in murine spleen and bone marrow. Nat. Immun. 12: 293‐ 301.    Miller, S.C. (1994) The development of natural killer (NK) cells from Thy‐1 lo Lin‐ Sca‐1+ stem cells:  Acquisition by NK cells of the homing receptor MEL‐14 and the integrin Mac‐1.  Immunobiol. 190: 385‐ 398.    Dussault, I. and Miller, SC. (1994) Decline in natural killer cell‐mediated immunosurveillance in aged  mice: A consequence of reduced cell production and tumor binding capacity. Mechan. Ageing & Dev. 75:  115‐129.    Dussault, I. and Miller, S.C. (1995) Suppression of natural killer cell activity in infant mice occurs after  target cell binding. Nat. Immun. 14: 35‐43.   

Dussault, I. and Miller, S.C. (1995) Effectiveness of immunotherapy in aged leukemic mice. Gerontology  41(4): 195‐204.    Giboda M., Jacobs, P., Smith, J.M. and Miller, S.C. (1995) Immune response of mice infected with  Schistosoma mansoni is modulated by antifibrotic treatment. Annals of Trop. Med. Parasit. 89(4): 415‐ 424.    Dussault, I. and Miller, S.C. (1996) The effect on leukemia cell numbers of  in vivo administration of  immunotherapeutic agents is age dependent. Oncology 53: 241‐246.    Miller, S. C. and Kearney, S.L. (1997) Effect of in vivo administration of trans retinoic acid on the  hemopoietic cell populations of spleen and bone marrow: Profound strain differences between A/J and  C57Bl/6J mice.  Lab. An. Sci. 48(1): 74‐80.    Whyte, A.L. and Miller, S.C. (1998) Strain differences in natural killer cell‐mediated immunity among  mice: A possible mechanism for the low natural killer cell activity of A/J mice. Immunobiol. 199: 23‐38.    Currier, N.L. and Miller, S.C. (1998) Influence of an interferon inducer on bone marrow transplant  reconstitution in irradiated, leukemic mice: Elevated natural killer cell numbers and improved life span.  Nat. Immun. 16: 6‐17.    Mahoney, M.X., Currier, N.L. and Miller, S.C. (1998) Natural killer cell levels in older mice are gender  dependent: Thyroxin is a gender independent natural killer cell stimulant.  Nat. Immun. 16: 165‐174.    Sun, L.Z‐Y., Currier, N.L. and Miller, S.C. (1999) The American coneflower: A prophylactic role involving  non‐specific immunity. Jour. Alt. & Comp. Med. 5 (5): 437‐446.    Currier, N.L., Sun, L. Z‐Y. and Miller, S.C. (2000) Exogenous melatonin: Quantitative enhancement in vivo  of cells mediating non‐specific immunity. Jour. Neuroimmunol. 104:101‐108.    Yu, Q., Miller, S.C. and Osmond, D.G. (2000) Melatonin inhibits apoptosis during early B cell  development in mouse bone marrow. Jour. Pineal Res. 29: 86‐93.    Currier, N.L. and Miller, S.C. (2000) Natural killer cells from aging mice treated with extracts from  Echinacea purpurea are quantitatively and functionally rejuvenated. Exp. Gerontol. 35(5): 627‐639.    Currier, N.L. and Miller, S.C. (2001) TNF‐α further augments natural killer cells when co‐administered  with an interferon inducer to irradiated, leukemic, bone marrow‐transplanted mice. Cancer  Chemotherapy & Pharmacology . 47(2): 185‐188.    Currier, N.L. and Miller, S.C. (2001)   E. purpurea and melatonin augment natural killer cells in leukemic  mice and prolong life span. J. Alt. & Comp. Med. 7(3): 241‐251.    Currier, N.L., Sicotte, M. and Miller, S.C. (2001) Deleterious influence of Echinacea purpurea and  melatonin on cells of the myeloid lineage in the spleen and bone marrow of mice. Jour. Leukocyte Biol.  70: 274‐277.    Currier, N.L. and Miller S.C. (2002) The effect of immunization with killed tumor cells, with/without  feeding of E. purpurea in an erythroleukemic mouse model. J. Alt. & Comp. Med. 8(1): 49‐58.   

Miller, S.C. (2002) Hemopoietic reconstitution of irradiated, stem cell injected mice: Dynamics of  restoration of various cell lineages of the spleen and bone marrow. Jour. Hematother. Stem Cell Res.  11(6): 965‐970.    Currier, N.L., Lejtenyi, D. and Miller, S.C. (2003) The effect with time of administration in vivo, of the  polysaccharide, arabinogalactan, on the immune and hemopoietic cell lineages in murine spleen and  bone marrow. Phytomedicine 10(2‐3): 145‐153.    Lejtenyi, D., Osmond, D.G. and Miller, S.C. (2003) Natural killer cells and B lymphocytes in L‐selectin and  Mac‐1/LFA‐1 knockout mice: Marker dependent but not cell lineage dependent changes in the spleen  and bone marrow. Immunobiology 207: 129‐135.    Miller, S.C. (2004) Echinacea in vivo: A prophylactic agent in normal mice and a therapeutic agent in  leukemic mice.  In: Medicinal and Aromatic Plants ‐ Echinacea: The Genus Echinacea (ed: Miller, S.C.)  CRC Press, Boca Raton, FL, p. 153‐162.    Miller, S.C. (2004) Two immunoenhancers are not better than one. In: Medicinal and Aromatic Plants ‐  Echinacea: The Genus Echinacea (ed: Miller, S.C.) CRC Press, Boca Raton, FL, p. 219‐230.    Brousseau, M. and Miller, S.C. (2005) Enhancement of natural killer cells and increased survival of adult  mice fed daily Echinacea root extract from youth. Biogerontology 6: 157‐163.    Miller, S.C. (2005) Echinacea: A miracle herb against aging and cancer? Evidence  in vivo, in mice. eCAM:  Evidence‐based Complementary and Alternative Medicine 2(3): 309‐314.    Delorme, D. and Miller, S.C. (2005) Dietary consumption of the herb, Echinacea, by mice afflicted with  autoimmune (type I) diabetes: The effect on their hemopoietic and immune cells is feeding duration  dependent. Autoimmunity 38(6): 453‐461.     Srinivasan, V., Maestroni, G.J.M., Cardinali, D.P., Esquifini, A.I., Pandi‐Perumal, S.R., and Miller, S.C.(2005)  Melatonin, immune function and aging.  Immunity & Ageing 2:17‐ 49. HIGHLY ACCESSED status at  http://www.biomedcentral.com     Chow, G., T. Johns and Miller, S.C. (2006) Dietary Echinacea purpurea during murine pregnancy: Effect on  maternal hemopoiesis and fetal growth Biology of the Neonate 89: 133‐138.    Miller, S.C., Pandi, P.S.R., Esquifino, A.I., Cardinali, D.P. and Maestroni, G.J.M. (2006) The role of  melatonin in immuno‐enhancement: potential application in cancer. Jour. Exp. Path. 87(2): 81‐87.    Brousseau, M. and Miller, S.C. (2007) The effects of Echinacea root extract in plasmacytoma‐bearing  mice: Enhancement of non‐specific immunity. Jour. Herbs & Med. Plants 13(2):11‐23 .    Miller, S.C., Delorme, D. (2008) An extract of North American ginseng, Panax quinquefolius, stimulates  spontaneous immunity in infant mice: Sustained, augmented immunity in adulthood long after  withdrawal of the extract. Jour. Comp. Int. Med. 5(1): 1‐16.    Miller, S.C., Delorme, D. and Shan, J. (2009) CVT‐E002, a proprietary extract of Panax quinquefolius,  stimulated the immune system and significantly extends the life span of leukemic mice: Analysis of the  hemopoietic and immune cells in vivo.  Journal of the Society for Integrative Oncology 7(4):127 – 136.   

Miller, S.C., Delorme, D.,Shan, J.J. A proprietary extract of North American ginseng (Panax Quinquefolius),  administered to leukemic, juvenile mice extends their life span in a does‐dependent manner. Journal of  Complementary and Integrative Medicine 8(1): article 10. DOI: 10.2202/1553‐3840.1315    Miller, S.C., Ti, L., and Shan, J. (2011) The sustained influence of short term exposure to a proprietary  extract of North American ginseng on the hemopoietic cells of the bone marrow, spleen, and blood of  adult and juvenile mice. Phytotherapy Research, published online – Wiley Online Library. DOI:  10.1002/ptr.3626.    Miller, S.C., Ti, L., Shan, J.J. (2011) Dietary supplementation with an extract of North American ginseng in  adult and juvenile mice increases Natural Killer cells.  Immunological Investigations, published online –  Informa Healthcare USA, Inc. DOI: 10.3109/08820139.2011.59909087.    Miller, S.C. (2012) Can herbs be useful in cancer therapy? A review of studies on the influence of  Echinacea on cells of the immune system and on tumor amelioration. Biomedical Research, 23:9‐16.  Durairaj, P. and Miller, S.C. (2012) Inhibition/prevention of primary liver tumors in mice given a daily  dietary extract of North American ginseng (Panax quinquefolius) following a hepatoma‐inducing agent.  Biomedical Research, 23(3): 429‐436.  Durairaj, P. and Miller, S.C. (2013) Neoplasm prevention and Immuno‐enhancement mediated by daily  consumption of a proprietary extract from North American Ginseng by elderly mice of a Cancer‐prone  strain. Phytotherapy Research . DOI: 10.1002/ptr.4880; 27:1339‐1344.   Durairaj, P., Breda, M. and Miller, S.C. (2013) Quantitative augmentation of immune cells in elderly,  normal mice by short‐term, daily consumption of an extract of North American ginseng (Panax  quinquefolius). Biomedical Research, 24(2): 199‐205. 

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Review

Echinacea: a Miracle Herb against Aging and Cancer? Evidence In vivo in Mice Sandra C. Miller Department of Anatomy and Cell Biology, McGill University, Montreal, Quebec, Canada Echinacea has been viewed as an immunoenhancing herb since it became commercially available several years ago. Indeed, its medicinal significance is responsible for billions of dollars in worldwide sales annually. Unfortunately, most of the ‘evidence’ for the purported medicinal efficacy of Echinacea has been anecdotal and, moreover, to this day, there is no formal proof on how to achieve the best results—whether it should be consumed daily throughout life as a prophylactic; consumed by either young or old; or consumed after diseases, such as cancer, have taken hold. Our work over the past 5 years has led to conclusive answers to some of these questions, at least in mice. Our results have shown that daily consumption of Echinacea is indeed prophylactic, extends the life span of aging mice, significantly abates leukemia and extends the life span of leukemic mice. Given that humans are 97% genetically common with mice and that virtually all our basic physiology is identical, it is neither unjustified to extrapolate these observations to humans nor would it be an arduous task to perform many of these studies in humans, thus establishing viable scientific evidence replacing the anecdotal. Keywords: Echinacea – hemopoiesis – immunology – leukemia – NK cells

Introduction Natural Killer Cells and Echinacea: a Harmonious Duo The herb, Echinacea, after making its debut on the world’s commercial markets more than a decade ago, has become one of the top-selling herbs of all time. Many of its ingredients are powerful immune system stimulators. Its contents include high molecular weight polysaccharides, essential oils, alkylamides such as echinacein, isobutylamides such as pentadecadienes and hexadecadienes, polyacetylene, tannins, inulin, heteroxylan, flavonoids and vitamin C. Indeed, the biochemistry and content definition of Echinacea and most other herbs has taken place decades before the medicinal value of the phytochemicals they contain ever merited investigation. Some of the contents of Echinacea are natural killer (NK) cell stimulants while others (the alkylamides) inhibit the endogenous suppressors of NK cells, i.e. the prostaglandins. NK cells are the first line of defense in cancer immunosurveillance, and For reprints and all correspondence: Sandra C. Miller, PhD, Department of Anatomy and Cell Biology, McGill University, 3640 University Avenue, Montreal, Quebec, Canada H3A 2B2. Tel: þ1-514-398-6358; Fax: þ1-514-398-5047; E-mail: [email protected]

consequently any agent that will either stimulate these fundamental cells or remove any negative influence on them would be clearly of medicinal value. In spite of the manifold functions of the prostaglandins in vivo, it is clear that at least one member of the prostaglandin family is detrimental to NK cells. The alkamide family of compounds within Echinacea inhibits the production of 5-lipoxygenase and cyclooxygenase, which are enzymes needed for the production of prostaglandins (1,2). Thus, reducing or eliminating this negative influence should result in an absolute and functional increase in NK cells (Fig. 1). Indeed, this is what we found some years ago when the drug indomethacin, an inhibitor of these key enzymes in prostaglandin formation, was administered in vivo to leukemic mice. This drug in vivo resulted in statistically significant increases in NK cell numbers and function in leukemic mice (3,4). Unfortunately, indomethacin, as with most exogenously administered drugs/factors, is beset with significant undesirable side effects that necessarily restrict its long-term use. Furthermore, there is considerable evidence suggesting that other phytochemicals in Echinacea might have the capacity to reduce tumors and virus infections (5–10). Among the polysaccharides contained within Echinacea, the complex carbohydrate group known as the arabinogalactans are particularly

Ó The Author (2005). Published by Oxford University Press. All rights reserved. The online version of this article has been published under an open access model. Users are entitled to use, reproduce, disseminate, or display the open access version of this article for non-commercial purposes provided that: the original authorship is properly and fully attributed; the Journal and Oxford University Press are attributed as the original place of publication with the correct citation details given; if an article is subsequently reproduced or disseminated not in its entirety but only in part or as a derivative work this must be clearly indicated. For commercial re-use, please contact [email protected]

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Figure 1. Contained within Echinacea root extract is a family of complex polysaccharides known as arabinogalactans. These sugars directly stimulate macrophages to produce three cytokines that, in turn, directly stimulate NK cells. The latter respond by means of new NK cell production/numbers and/ or increased lytic functional capacity. On the other hand, contained also within Echinacea root extract are a group of molecules known as the alkamides, some of which interact with two key enzymes essential to the production of prostaglandin E2 (PGE2). Normally, PGE2 is suppressive to NK cells. Consequently, when the fundamental enzymes are blocked, PGE2 levels are negligible and NK cells, now free of their suppressors, become increased in numbers and function. Thus, via these two different avenues, i.e. stimulation indirectly through macrophages, and release from suppressor factors (PGE2), whole Echinacea is a powerful NK cell stimulant. The diagram of the Echinacea plant is reproduced with permission from The Herbal Drugstore, LB White & S Foster, Rodale Inc., 2000.

significant (5,11,12). Macrophages upon stimulation by arabinogalactans (Fig. 1) release, in turn, a host of NK cell stimulants (11,13–16). Consequently, any agent that contains these two valuable compounds, both so beneficial to those cells acting at the first line of defense, i.e. the NK cells, is worthy of investigation for its prophylactic potential and its therapeutic value. It was against this background, i.e. the medicinal potential of Echinacea in NK cell enhancement, that we undertook an in-depth in vivo study of this herb in (i) aged mice and (ii) mice afflicted with leukemia, under controlled laboratory conditions. Virtually all that was known about the medicinal potential of Echinacea had been established in vitro. Our first study, in contrast, was conducted in vivo
5 years ago, and at that time we investigated the effect on hemopoietic and immune cells of daily dietary intake of this herb for 2 weeks (17). After 2 weeks, we analyzed quantitatively the absolute changes in all the hemopoietic and immune cells in both the spleen and the bone marrow, the latter being the organ of de novo generation of all hemopoietic and immune cells. The spleen, on the other hand, is a major repository for all these cells since this organ is on the blood circulatory highway. In the spleen there are cells

that reside and function therein, i.e. the cells mediating specific (adaptive) immunity (T and B lymhocytes), as well as NK cells and monocytes—both types being responsible for nonspecific, spontaneous and non-adaptive immunity. Other cells involved in the disease defense process, i.e. the mature and maturing cells of the granulocyte lineages (eosinophils, neutrophils and basophils) also either function in the spleen or pass through it en route elsewhere. In our analysis of the effect of Echinacea on the abovementioned cells, everything was standardized. The mice were inbred and of identical age, weight and gender (male). Moreover, housing conditions were identical between cages of mice consuming Echinacea and those consuming untreated diet. The quantity and quality of food and water were also standardized among all cages—those receiving the herb in the diet and those not given the herb (controls). It is obviously of fundamental importance that Echinacea itself, as with any agent given either prophylactically or therapeutically, is not deleterious to the host. In the case of Echinacea, there appears to be no in vivo toxic level, i.e. overdose level, as defined by several assays and criteria (6,18,19). The immunostimulating effects of Echinacea in vivo are exclusive to cells mediating spontaneous immunity and their accessory cells, i.e. NK cells and monocytes (17). While Echinacea appears to be tailor-made for its highly positive influences on this arm of the immune system, there are instances, in vivo, where use of this herb may be contraindicated. For example, individuals demonstrating allergy to members of the Family Asteraceae, to which Echinacea belongs, would clearly be ill-advised to consume this herb for any reason (20,21). Moreover, there is very little available information concerning the potential for detrimental interactions of Echinacea with either other herbs or pharmaceuticals (22). Another problem pertains to the choice of the most effective source of Echinacea as NK stimulant—not an insignificant problem since there is extremely wide variation in the quality of Echinaceas from assorted commercial sources. For our experiments, we chose a product from a commercial supplier, which we proved was consistent in quality and NK stimulating potency, and revealed in dose–response analyses, a progressive increment in NK cell numbers up to a maximum (plateau) beyond which no further increase in NK cells occurred. It was this dosage that we have used throughout our experiments to date, including those reported in this review. Should Echinacea be Taken When Healthy? When healthy young adult mice consumed Echinacea daily in their diet for 7 days, we found significantly more NK cells, identified by our standard immunoperoxidase labeling methods, in their bone marrow than in the bone marrow of mice consuming untreated diet (P < 0.01), while the spleens of mice consuming Echinacea had 25% more NK cells, which is a clear elevation in number although not yet statistically significant (17). By 2 weeks, however, those mice consuming the

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herb had significantly more NK cells in their spleens and bone marrow (P < 0.01). The early (7 days) elevation in absolute numbers of NK cells in the bone marrow necessarily indicated that actual generation of new NK cells was underway in that organ under the influence of Echinacea. The 25% increment in the spleen simply reflected the increased new NK cell production, since it is well established that the spleen is major site to which virtually all newborn, bone marrow-derived NK cells unidirectionally migrate (via the blood). NK cells do not recirculate back to the bone marrow (23–25). However, during 2 weeks of daily Echinacea exposure, the elevating levels of new NK cell production by the bone marrow resulted in a supernormal export of these additional NK cells to the spleen, such that there was indeed a statistically significant increase in the numbers of NK cells in the spleen by 2 weeks as well. Also of considerable interest was the observation that the ‘helper’, or accessory, cells for NK cells, i.e. the monocytes, were
25% more numerous in both the bone marrow and the spleen of mice consuming the herb for 7 days, and were statistically more numerous in both organs (P < 0.01) after 14 days of the dietary herb (17). To our surprise, mature granulocytes and their precursors, as well as all other lymphocytes (T and B), and the red blood cell precursors remained steadfastly at control levels (mice consuming untreated diet) in both the spleen and the bone marrow, irrespective of whether mice had consumed Echinacea for 7 days or 14 days. Moreover, we have consistently shown in all our previous studies that all mice on Echinacea-containing diets were clinically no different from littermates and cage mates consuming untreated chow, with respect to body weight, coat texture and level of activity. Our administration to mice of daily dietary doses of this herb of 0.45 mg per 25 gm body weight was indeed derived from the average recommended dose for adult humans (averaged as 125 lb), indicated on the labels of Echinacea containers provided by several different suppliers. Since our murine studies were carried out under highly controlled conditions (above), with the only variable being the presence or absence of dietary Echinacea, then the singularly positive influence on NK cells and their accessory cells (monocytes) must have resulted only from the presence of Echinacea. A major observation of this finding is that Echinacea appears able to influence new cell generation in the NK/monocyte systems, as evidenced by the significant bone marrow increments in these cell types. Thus, the elevated numbers of these cells observed in the spleen is the direct result of the increased cell proliferation in the bone marrow with subsequent dissemination via the blood in the presence of Echinacea. Two corollaries may extend from this study. First, the fact that these observations were made in normal, healthy adult mice indicates that the presence of Echinacea in vivo may have a prophylactic role, resulting in a sustained elevation in the available supply of NK cells/monocytes—both well-established and vitally important cell lineages in the maintenance of spontaneous, non-adaptive defenses against

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virus-mediated diseases and developing neoplasms. Second, since Echinacea is able to stimulate new NK cell generation in the bone marrow, could it also do so in aging and elderly animals, where these cells are in progressive, age-mediated decline and thus rejuvenate this potent disease (cancer)defense mechanism? Can Echinacea be Growing in the Fountain of Youth? It has been known for some years that NK (and T) cells decline with age (26–31), and correspondingly, cancers of assorted types increase with age in both mice and humans. Believing that this inverse relationship between NK cell presence and cancer was more than coincidental, we set out to investigate some years ago, first, the mechanism whereby NK cells decline with age, and secondly, to see if there was any way that NK cells could be brought back to their levels in young adulthood. We found (27) that the decline in NK cells with age was the result of (i) reduced new NK cell production in the bone marrow and (ii) reduced efficiency of the few mature NK cells that were produced to bind to their target cells, hence preventing subsequent killing of the offensive target. With the success of our studies with Echinacea (above) in healthy, young adult mice, we conducted the same sort of experiments as in these mice, except we used healthy, elderly mice (32). We demonstrated in these healthy, elderly mice, that it is not only possible to increase the absolute numbers of NK cells in their normal bone marrow generating site by feeding daily (P < 0.004) Echinacea via the diet for 14 days but also to resurrect the functional capacity (target cell binding/lysis) of these new Echinacea-generated NK cells. Indeed, this herb in the diet returned the numbers and function of NK cells in these elderly animals to the levels of the young adult. In the spleens of these Echinacea-consuming elderly mice, NK cell numbers rose to levels 30% greater than those of their control cage mates not consuming Echinacea. The lytic capacity of this newly produced army of NK cells in these Echinaceaconsuming elderly mice (32) also returned to levels equivalent to those of the young adult. These levels were statistically significantly higher (P < 0.03–0.001) than the killing capacity of identically treated elderly mice not consuming Echinacea for 14 days. These observations appear to apply uniquely to this herb since we could never rejuvenate the NK cell-mediated component of the immune system in elderly mice by any of the other typical NK cell enhancers. For instance, we had previously found in such healthy, elderly mice that neither the cytokines IL-2 nor the drugs indomethacin was able to stimulate NK cell numbers or function in aging mice (27), in spite of the fact that both these agents are potent stimulators of NK cell numbers and function in the young adult mouse. Furthermore, in elderly humans, immunostimulating cytokines such as the NK-stimulating IL-2 are significantly impaired with respect to production levels and with respect to a decreased ability of several types of immune cells from aged humans to utilize IL-2 (31,33,34). Paralleling our observations

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with young adult mice consuming Echinacea for 14 days (17), we did not find in these healthy elderly mice, any influence of dietary Echinacea on the mature or precursor granulocytes, the precursors to red blood cells or the other immune cells (T and B lymphocytes) in either the spleen or bone marrow, again indicating the unique role of Echinacea in stimulating the non-adaptive limb of the immune response, i.e. NK cells and their accessory cells, the monocytes. Nevertheless, in spite of our observations of these positive influences of Echinacea consumption in aging mice, it must be borne in mind that similar controlled experiments have not been, or can they really ever be, conducted on human subjects simply because of the variability among humans even of identical age and gender. One reason for this, of course, is that precisely identical, lifelong life styles can never be achieved with the precision and control readily achievable for laboratory animals. Are the Parts as Good as the Whole? In a subsequent study (35), we injected arabinogalactan intraperitoneally daily for 7 days or 14 days into elderly mice. Since this complex polysaccharide is contained in whole Echinacea, it was hypothesized that this component might have as good an effect on NK cells as did the extract of whole herb. However, we found that in contrast to whole product, this component was not effective in stimulating NK cell numbers in the elderly mouse bone marrow or spleen. Arabinogalactan was not effective in altering the levels of any other hemopoietic or immune cell populations in either spleen or bone marrow. However, when we injected arabinogalactan into young adult mice the NK cell levels of the bone marrow were decreased after 7 days and returned to control (shaminjected) levels for that organ only after 14 days of daily administration of the polysaccharide. In the spleen, arabinogalactan administration for 7 days produced no change in the numbers of NK cells, and only after 14 days of daily exposure to this agent did the levels of splenic NK cells rise significantly (P < 0.004) above control levels. From these findings, it appears that at least from a prophylactic standpoint, it is more efficacious to administer whole Echinacea rather than isolated compounds contained within the herb. As discussed above (see Introduction), in the case of Echinacea at least, the whole product acts via two different mechanisms to stimulate NK cells since the whole product contains both arabinogalactans and alkamides. With respect to other herbs of known medicinal value, the whole product may similarly contain many compounds that may act additively or even synergistically to produce, collectively, the best effects in vivo. The possibility that the collective whole may be better than any single extracted compound, is supported by already available circumstantial evidence (15,36). Is it Possible to Get Too Much of a Good Thing? We elected next to study the influence of daily consumption of Echinacea throughout life beginning in youth, i.e. 7 week of

age (puberty), until early ‘old age’ (13 months) in inbred mice (37). There is considerable controversy concerning the duration/frequency with respect to human consumption of Echinacea. For example, the common label advice when purchasing Echinacea over the counter indicates that Echinacea should be taken for short spurts of time and then terminated for several days/weeks before resuming intake. The untested reasoning is that perhaps chronic overstimulation of the immune system via daily, long-term exposure to Echinacea could result in dependency, or worse, that immune system activity may fall to very low levels, rendering it incompetent to ward off even minor infections. Thus, in an effort to dispel or prove this theory, we fed young mice, from 7 weeks of age until 13 months, our standard, daily dose of Echinacea, previously shown to be NK-enhancing, in the chow—all other parameters strictly controlled (husbandry, gender, age, water/ food intake quantity, etc.) as in our previous studies. Our results (37), for the first time, provided concrete evidence that chronic (long-term) intake of Echinacea was not only not detrimental but also distinctly prophylactic. Mice in control cages eating untreated chow had a 79% survival by 10 months of age, while mice living under identical conditions, with the one variable being Echinacea in the daily chow, were still 100% alive by 10 months of age. By 13 months of age, control mice were 46% still alive, while those consuming Echinacea were 74% alive. Furthermore, in the Echinaceaconsuming mice, NK cells were statistically significantly elevated in absolute numbers at every sampling period, in both their bone marrow generating site and their site of maximum accumulation, the spleen (37). Given that the key immune cells acting as the first line of defense against developing neoplasms in mice and humans are NK cells, it is not difficult to conclude that sustained enhancement of NK cells alone, throughout life, could readily account for the reduced frequency in deaths with advancing age. Spontaneous neoplasms, clinically undetectable, are well known to increase with advancing age in humans and mice. Thus, the logical corollary from this study indicates that chronic daily intake of Echinacea, is clearly not detrimental to the immune system, but rather prophylactic. Will Echinacea ‘Work’ Once a Tumor is in Progress? Since the debut of NK cells, leukemias and lymphomas have been known to be targets for NK cytolysis. Indeed, NK cells were, decades ago, established as the first line of defense against these types of neoplasms (38–40). The concept that herbal compounds can enhance NK cells has recently gained considerable attention and indeed, excellent reviews on the roles of NK cells in tumor combat and the role of such compounds in modifying antitumor responses, have been provided by Takeda and Okumura (41) and Cooper (42). Therefore, we hypothesized that significantly enhancing NK cells, even after leukemia has taken hold, may lead to actual elimination of these tumor cell ‘targets’. Thus, we induced leukemia in mice via injection of a dose of leukemia cells known to consistently result in death 3.5 weeks later, and on the same day

eCAM 2005;2(3)

as leukemia induction, Echinacea was added to their diet. Control leukemia-injected mice consumed regular diet. All other parameters of these experiments were identical, as usual (above). The results were most encouraging (43). NK cell numbers by 9 days after tumor onset were very significantly elevated over control (P < 0.000007). Three months after leukemia onset—long after all control (untreated chow) leukemic mice had died—NK cells were recorded at more than twice the numbers present in normal mice of identical age, strain and gender. Furthermore, all the other hemopoietic and immune cell lineages in both bone marrow and spleen in these long-term, Echinacea-consuming, originally leukemic mice were indistinguishable from the corresponding populations of cells in normal mice. Life span analysis indicated that not only had Echinacea extended life span (43) but also the survival advantage provided to leukemic mice by consuming Echinacea daily was statistically significant (P < 0.022). One-third of all Echinacea-consuming mice that survived until 3 months after leukemia onset went on to live a fulllife. We believe that further manipulation of Echinacea dose/ frequency/duration regimens could allow many more if not the other full two-thirds to go on to live a full life. The mechanism by which Echinacea mediates its antineoplastic activity is well known (see Introduction). It acts exclusively via the immune system and has no influence on the tumor cells themselves, the latter being highly unstable and continuously cloning out their most virulent cells to produce frank neoplasm. However, by stimulating the first line of defense, i.e. NK cells, which are so effective in detecting and lysing tumor cells immediately upon detection, the value of Echinacea can be readily seen. Thus, the medicinal value of phytochemicals contained in Echinacea is clearly evident and indicates that these agents, as well as phytochemicals not yet discovered in other herbs, may be valuable tools to combat tumor. The therapeutic value of Echinacea can now be added to its prophylactic potential (above) and indicates that herbal therapy may soon see its debut alongside—or indeed in place of—conventional therapy, especially since virtually all chemo-‘therapy’ is so toxic to all other renewing systems in the body, that its administration (dose/frequency/duration) must necessarily be very limited, and as such are not successful in achieving complete lifelong tumor eradication, i.e. cure. Combination Therapy in Leukemia Combat— Echinacea Helps Out Again There is another powerful NK stimulant called melatonin, which the mammalian body makes in the pineal gland, and ‘its role is to act as a neuroimmunomodulator (44–48). When we gave the combination of Echinacea and melatonin (43), via the diet, daily to leukemic mice (leukemia induced as above), not only did we find the usual significant elevation in NK cells but also the long-term survival increased to 40%, compared with the one-third of the leukemic mice when Echinacea alone was given (above). Thus, at least for this

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tumor, the two NK stimulants together were indeed better than one. In another type of combination therapy, we immunized mice 5 weeks beforehand, with killed leukemia cells (49) before injecting live cells and daily dietary Echinacea. We observed that the combination of immunization and dietary Echinacea was substantially more therapeutic than either alone. Immunization alone produced a survival rate and life span increment similar to that achieved by giving leukemic mice dietary Echinacea alone. Life span increment via combination therapy has reached 60%. Moreover, when NK cells were measured at 3 months after leukemia injection (onset), it was found that the absolute numbers of NK cells in their bone marrow birth site was three times that of immunized mice not consuming Echinacea (P < 0.003), and the numbers of NK cells in the spleens of immunized mice consuming daily dietary Echinacea rose to almost twice (P < 0.001) the numbers found in immunized mice not receiving the herb. In true ‘Echinacea style’, the stimulatory effect of this herb was directed toward NK cells. Consequently, by 3 months, the presence of this herb in the diet of leukemic mice had no influence on the lymphocytes, red blood cell precursors, mature granulocytes or their precursors in either spleen or bone marrow, again demonstrating the uniquely positive influence of this herb on non-adaptive immunity. Therefore, it appears that combination therapy in which one agent is Echinacea and the other, a non-toxic and nonimmunosuppressive agent (thus eliminating virtually all modern chemotherapeutic laboratory-derived concoctions) has great advantage at least in leukemia treatment. Given that humans and mice are
97% genetically common, with similar physiology in virtually every organ, it is not unjustifiable to extrapolate these collective findings to humans. Studies such as these investigations with mice warrant assessment at the clinical level especially since both Echinacea and melatonin, and a host of other herbal products, are already in the market place. Unless formal clinical studies follow, to establish regulatory guidelines, it is very conceivable that leukemia patients (and others) could begin to self-medicate—with potentially disasterous results (22).

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27. Dussault I, Miller SC. Decline in natural killer cell-mediated imunosurveillance in aged mice—a consequence of reduced cell production and tumor binding capacity. Mech Ageing Dev 1994;75:115–29. 28. Ghoneum M, Suzuki K, Gollapud S. Phorbol myristate acetate corrects impaired NK function of old mice. Scand J Immunol 1991;34:391–8. 29. Hanna N. The role of natural killer cells in the control of tumor growth and metastasis. Biochim Biophys Acta 1985;780:213–26. 30. Krishnaraj R. Immunosenescence of human NK cells: effects on tumor target recognition, lethal hit and interferon sensitivity. Immunol Lett 1992;34:79–84. 31. Cheung TH, Twu S,Jr, Richardson A. Mechanism of age-related decline in lymphocyte proliferation: role of IL-2 production and protein synthesis. Exp Gerontol 1983;18:451–60. 32. Currier NL, Miller SC. Natural killer cells from aging mice treated with extracts from Echinacea purpurea are quantitatively and functionally rejuvenated. Exp Gerontol 2000;35:627–39. 33. Chouaib S, Chatenoud L, Klatzman D, Frandelizzi D. The mechanisms of inhibition of human IL-2 production. II. PGE2 induction of suppressor T lymphocytes. J Immunol 1984;132:1851–7. 34. Gillis S, Kozak R, Durante M, Weksler ME. Decreased production of and response to T cell growth factor by lymphocytes from aged humans. J Clin Invest 1981;67:837–42. 35. Currier NL, Lejtenyi D, Miller SC. Effect over time of in-vivo administration of the polysaccharide arabinogalactan on immune and hemopoietic cell lineages in murine spleen and bone marrow. Phytomedicine 2003;10:145–53. 36. Voaden DJ, Jocobson M. Tumor inhibitors. 3. Identification and synthesis of an oncolytic hydrocarbon from American coneflower roots. J Med Chem 1972;15:619–23. 37. Brousseau M, Miller SC. Enhancement of natural killer cells and increased survival of aging mice fed daily Echinacea root extract from youth. Biogerontology 2005;6:157–63. 38. Kasai M, Yoneda T, Habu S, Maruyama Y, Okumura K, Tokunaga T. In vivo effect of anti-asialo GM1 antibody on natural killer activity. Nature 1981;291:334–5. 39. Keissling R, Klein E, Pross H, Wigzell H. Natural killer cells in the mouse. II. Cytotoxic cells with specificity for mouse Moloney leukemia cells: characteristics of the killer cell. Eur J Immunol 1975;5: 117–21. 40. Lotzova E, Savary CA, Lowlachi M, Murasko DM. Cytotoxic and morphologic profile of endogenous and pyrimidinone-activated murine NK cells. J Immunol 1986;136:732–40. 41. Takeda K, Okumura K. CAM and NK cells. eCAM 2004;1:17–27. 42. Cooper EL. Commentary on CAM and NK cells by K. Takeda and K. Okumura. eCAM 2004;1:29–34. 43. Currier NL, Miller SC. Echinacea purpurea and melatonin augment natural killer cells in leukemic mice and prolong life span. J Altern Complement Med 2001;7:241–51. 44. Demas GE, Nelson RJ. Exogenous melatonin enhances cell-mediated, but not humoral, immune function in adult male deer mice (Peromyscus maniculatus). J Biol Rhythms 1998;13:245–52. 45. Liebmann PM, Wolfler A, Felsner P, Hofer D, Schauenstein K. Melatonin and the immune system. Int Arch Allergy Immunol 1997;112:203–11. 46. Maestroni GJ, Hertens E, Galli P, Conti A, Pedrinis E. Melatonin-induced T-helper cell hematopoietic cytokines resembling both interleukin-4 and dynorphin. J Pineal Res 1996;21:131–9. 47. Poon AM, Liu ZM, Pang CS, Brown GM, Pang SF. Evidence for a direct action of melatonin on the immune system. Biol Signals 1994;3: 107–17. 48. Yu Q, Miller SC, Osmond DG. Melatonin inhibits apoptosis during early B-cell development in mouse bone marrow. J Pineal Res 2000;2: 86–93. 49. Currier NL, Miller SC. The effect of immunization with killer tumor cells, with/without feeding of Echinacea purpurea in an erythroleukemic mouse model. J Altern Complement Med 2002;8:49–58. Received October 12, 2004; accepted July 29, 2005

Ó Springer 2005

Biogerontology (2005) 6:157–163 DOI 10.1007/s10522-005-7951-8

Research article

Enhancement of natural killer cells and increased survival of aging mice fed daily Echinacea root extract from youth Me´lanie Brousseau & Sandra C. Miller* Department of Anatomy and Cell Biology, McGill University, 3640 University Ave, H3A 2B2, Montreal, QC, Canada; *Author for correspondence (e-mail: [email protected]) Received 11 November 2004; accepted in revised form 14 February 2005

Key words: aged, Echinacea, hemopoiesis, immunity, life span Abstract In spite of Echinacea-based products being among the best-selling herbs in the world to date, to allay assorted ailments, the debate is still on-going with respect to the efficacy of ingesting the herb intermittently, continuously, or only at the beginning of an affliction. We sought, therefore, to find out if mice, receiving dietary Echinacea daily, throughout life, from youth until late middle-age, demonstrated any longevity/survival differences, and/or any differences in their various populations of immune/ hemopoietic cells. Sustained and/or high levels of these cells are crucial for longevity. Some mice were maintained on a regular chow diet to which was added Echinacea purpurea daily (2 mg/mouse), from puberty (7 week) until just beyond 13 months of age (late middle-age in mice). Control mice, identically housed and maintained, received identical chow without the herb. Mice consuming untreated diet had a 79% survival by 10 months of age, while those consuming Echinacea daily in the diet were still 100% alive by 10 months. At approximately 13 months of age, mice consuming untreated diet had a 46% survival rate while those consuming Echinacea, were 74% alive at this time. Moreover, the key immune cells, acting as the first line of defense against developing neoplasms in mice and humans, i.e., natural killer (NK) cells, were significantly elevated in absolute number both in their bone marrow production site, as well as in the major organ to which they traffic and function, i.e., the spleen. The cells of the myeloid/granulocyte lineages remained steadfastly at control levels in both the bone marrow and spleen in Echinacea-consuming mice. Thus, it appears that regular intake of Echinacea may indeed be beneficial/ prophylactic, if only for the reason that it maintains in an elevated state, NK cells, prime elements in immunosurveillance against spontaneous-developing tumors, a phenomenon which increases in frequency with progressive aging.

Introduction That many phytochemicals, i.e., plant/herb derivatives, have the capacity to alleviate a wide variety of pathological conditions accounts for the explosive growth in the nutraceutical industry within the last decade. We have already studied one such product, i.e., root extract of the plant

w This project was supported by a grant from the Cancer Research Society, Inc.

Echinacea purpurea (Sun et al. 1999) and found that daily dietary administration, throughout 14 days, to young adult mice, had the capacity to stimulate a specific kind of immune cell, the natural killer (NK) cell, which is responsible for combating virus-mediated afflictions as well as certain tumors. We elected subsequently, to assess the role of E. purpurea in mice during late middle-age, a period in life in both animals and humans, where NK cells are moderately to profoundly reduced. Correspondingly, and more than co-incidentally,

158 it is also a time when there is a great increase in the frequency of developing tumors of assorted types. We had previously shown that the mechanism for such age-related reduction in NK cells was (i) a reduction in production of new NK cells in the bone marrow, (ii) a defect in the ability of NK cells to bind tumor cells, an event which must precede NK cell-mediate lysis of the cell (Dussault and Miller 1994). Moreover, these agents had no effect on leukemia abatement in elderly mice, since sustained administration of either/both resulted in no change in the absolute numbers of leukemia cells counted in either the bone marrow or the spleen (Dussault and Miller 1996). We had also demonstrated that neither the cytokine, IL)2, nor the drug, indomethacin which are both powerful stimulants of NK cell production/function in young adult mice, were completely unable to stimulate these parameters in elderly mice (Dussault and Miller 1994). By contrast, we subsequently demonstrated, that by administering to aged mice (15–16 months), daily dietary E. purpurea for 14 days, we were able to rejuvenate their NK cell populations such that at the conclusion of 14 days, NK cell absolute numbers, NK cell lytic functions, and NK cell production, thereby generating more new NK cells, in these old mice, had returned to the level of that of the young adult mouse (Currier and Miller 2000). Based on this collective body of knowledge, we hypothesized that frequent dosing with this immuno-enhancing herb, from youth to late adulthood, may be prophylactic. That is, sustained elevated levels of those specific immune cells, known to be most active against tumors, may be adequate to allay the progressive increase in frequency of spontaneously developing neoplasms known to occur in animals and humans with advancing age. Thus, we administered, via the diet daily, E. purpurea, to mice from puberty until late middle-age. Indeed, we found that not only were age-related deaths significantly delayed in time in Echinacea-consuming mice, but the numbers of healthy, active Echinacea-consuming mice, about to enter old age, was almost twice that of mice consuming the standard diet.

Materials and methods Mice BALB/cByJ male mice were purchased at 5 week of age from Jackson Laboratories (Bar Harbor, Maine, USA). Male mice of this strain have a life span of 18–20 months with a maximum life span of approximately 2 years (Myers 1978; Jackson Laboratories, Bar Harbor, ME). Upon arrival in the McGill University Animal Care Facility, all mice were housed three per cage, under specifically pathogen-free conditions in autoclaved micro-isolator cages (Allentown Caging, Inc., New Jersey, USA) and provided autoclaved food and water ad libidum. Temperature and humidity were constant throughout as was a fixed 12 h light/dark cycle. All mice were allowed a 10 day adjustment period after arrival in the facility prior to their use in any experimental protocol. From the commencement of this study (age: 7 week), until its conclusion (13 month) all mice under experimental and control protocols were identically treated in terms of their husbandry/living conditions.

The dietary additive – Echinacea purpurea A commercially available extract of Echinacea purpurea root was obtained from Sante´ Naturelle (AG) Lte´e, LaPrairie, QC, Canada. From doseresponse analysis previously done in our laboratory, this agent, in the dose used for dietary administration, has been proven non-toxic (no abnormal findings in several clinical parameters), and effective as a stimulant of non-specific immunity mediated primarily by NK cells (Sun et al. 1999; Currier and Miller 2001, 2002). Standard mouse chow (LabChow, Agribrands, Inc.), ±Echinacea, was provided fresh daily. From youth until old age, mice regularly consumed approximately 6 g total chow/day with/without 2 mg Echinacea purpurea. A dose of this herb, many times greater than this, has nevertheless been demonstrated to be non-toxic (Weiss 1988; Mengs et al. 1991; Ernst 2002). Finally, given the

159 long term nature of this study, the logical assumption was that any minor variations in food and/or herb consumption per day, among mice in any one group, or between control (untreated chow), and experimental (Echinaceacontaining chow) groups, would have been canceled, or averaged over the long period of this study (7 week 13 month). Mouse sampling When mice were just beyond 13 month of age, they were euthanized by asphyxiation in a CO2 chamber, and their spleen and both femurs (bone marrow source) were removed, placed in ice-cold MEM (Minimal Essential Medium) pH 7.4 containing 10% millipore-filtered fetal bovine serum (FBS). The organs were prepared for single cell analysis by methods in standard use in our laboratory (Dussault and Miller 1994; Miller and Kearney 1997; Mahoney et al. 1998; Whyte and Miller 1998; Sun et al. 1999). Ultimately, from the washed, single cell suspensions of hemopoietic cells, from both organs, the total numbers of viable, hemopoietic cells per organ per mouse were obtained by means of a hemocytometer. Immunoperoxidase labelling of natural killer cells NK cells were identified by means of their ASGM)1 surface marker, by methods in standard use in our laboratory (Miller et al. 1992; Dussault and Miller 1993, 1995). The ASGM)1 surface molecule is present on 100% of mature and maturing NK cells (Kasai et al. 1980; Young et al. 1980; Beck et al. 1982). NK cells are progressively tagged, by a primary antibody when cells are in suspension followed by a secondary antibody, also administered to the NK cells while they are in suspension. Spleen and bone marrow suspensions are then cytospotted such that all cells lie in a monolayer on glass slides, which are then subjected to the final NK cell tag, i.e., a chromogenic agent (diaminobenzidine), thus enabling their ready distinction from other lymphocytes (T and B). The microscope slides, containing now discernable NK cells, are dried, and are finally counterstained with a hematologic tetrachrome stain (Wright–Giemsa). Collectively, the combination of stains reveals the identity,

not only of NK cells, but also of all the other lineages of hemopoietic and immune cells including their precursor (proliferating) and mature forms. Differential analysis of hemopoietic cells In both organs (spleen and bone marrow) cells were, thus, morphologically identified and recorded as belonging to one of five distinct categories: NK cells, lymphocytes, granulocytic cells (mature and precursors), nucleated erythroid cells, monocytes by means of well-established methods in use in our laboratory (references above). Differential counts of 1000–2000 cells/organ/mouse were performed and the percentages of each cell type were determined. The resulting percentages obtained for each cell type/organ/ mouse, were then converted, via the known total organ cellularity (hemocytometer-obtained), to the absolute number of cells/organ/mouse. Statistical analysis Student’s t-test (two-tailed) was used to compare the differences for each organ between the corresponding means of Echinacea-consuming and control mice. Values of P < 0.05 were considered statistically significant. Significant differences in survival data were ascertained by means of the Kaplan–Meier Survival Analysis Statistics, Mann–Whitney U-test, and the VassarStats Program of trend analysis.

Results Normal mice, consuming daily Echinacea throughout life were profoundly affected with respect to many of their immune/hemopoietic cells as well as their life expectancy. The numbers of bone marrow-based lymphocytes, myeloid/granulocytic cells and monocytes, in Echinacea-consuming mice, remained at or near the numbers found in control mice, consuming untreated, regular (R) chow (Figure 1a). However, the absolute numbers of nucleated erythroid cells (precursors of blood-borne red cells responsible for O2/CO2 exchange) were significantly increased in the bone marrow of Echina-

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Figure 1. (a) Total numbers of hemopoietic and immune cells in the bone marrow of mice, with and without daily dietary Echinacea from youth (7 week) until later middle-age (>13 month). Mean ± SE. Control: n = 17; Echinacea: n = 19. *P < 0.02, **P < 0.01. (b) Total numbers of hemopoietic and immune cells in the spleens of mice, with and without daily dietary Echinacea from youth (7 week) until late middle-age (>13 month). Mean ± SE. Control: n = 17; Echinacea: n = 19. *P < 0.01, **P < 0.007, ***P < 0.004, ****P < 0.001.

cea-consuming mice (Figure 1a). By contrast, lymphocytes, monocytes and nucleated erythroid cells were significantly reduced in the spleens of mice on Echinacea-containing diets (E) vs. mice consuming untreated, regular (R) chow (Figure 1b). As in the bone marrow, the absolute numbers of myeloid/granulocytic cells remained unchanged from control levels in the spleen (Figure 1b). NK cells were the only cells to be significantly enhanced in numbers in both their bone marrow production site as well as in the spleen, the site to which mature, NK cells traffic and function (Figure 1a and b). Finally, Figure 2

reveals that mice consuming Echinacea from youth until late middle-age (>13 month), showed a delayed onset in age-related deaths, and moreover, the number of mice alive, healthy and about to enter the final segment of their life (old age), was almost twice that of mice consuming regular, untreated chow.

Discussion This study has shown, for the first time in any species, that daily dietary exposure to Echinacea,

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Figure 2. Life span alterations in mice consuming daily dietary Echinacea (n = 30) vs. mice consuming control (standard, untreated) chow (n = 30). In the former group, deaths due to aging/‘natural causes’ were not observed until 4 months after the first deaths were observed in the control group. At >13 months of age, 74% of all the ‘starting mice’ were still alive in the Echinacea-consuming group vs. 46% in the control group.

throughout a large proportion of the life span (puberty through late middle-age), produces a significant and sustained enhancement of tumor-lytic NK cells. Indeed, it is the unique role of Echinacea as an immuno-stimulant, which gives this herb it’s considerable medicinal value. One known action of Echinacea is to inhibit (via the contained alkylamides), two enzymes fundamental to prostaglandin production, i.e., cyclooxygenase and lipooxygenase, and consequently, the ultimate levels of prostaglandins (Wagner et al. 1989; Muller-Jakic et al. 1994; Raso et al. 2002). Prostaglandins are well demonstrated suppressors/inhibitors of NK cells (Kendall and Targan 1980; de Tracey and Adkinson 1980; Rappaport and Dodge 1982; Lala et al. 1986). Moreover, a decrease in prostaglandins also favors the IL)1-mediated stimulation of monocytes–macrophages (Kendall and Targan 1980; Lala et al. 1986), which then secrete interferons and other direct stimulants of NK cells. Echinacea, in vivo, results in an increase in other cytokines which favor NK cell production/lytic function, i.e., TNF-alpha, IFN-beta (Leuttig et al. 1989; Roesler et al. 1991; Barak et al. 2002). A second molecular mechanism by which

Echinacea exerts an immune stimulatory function, is via its contained family of polysaccharrides known as arabinogalactans. Macrophage uptake of these sugars, also results in release of specific cytokines (IL)1, TNF-alpha, IFN-beta 2) which directly stimulate NK cells. In aging, normal mice of another strain (DBA/ 2), we found that only 2 weeks of daily dietary administration of Echinacea, to these mice when they were 15–16 months of age, resulted in a rejuvenation of NK cell production, NK cell numbers and an increase in NK cell-mediated, tumor-lytic function – all comparable to levels seen in the young adult mouse (Currier and Miller 2000). Given that NK cells renew rapidly and have a short functional life span (Miller 1982; Zoller et al. 1982; Pollack and Rosse 1987; Miller and Shatz 1991), it is not surprising that only 2 weeks of daily Echinacea consumption, would have revved up these cells (Currier and Miller 2000). Moreover, it has been well demonstrated that increase in NK cell numbers parallels the tumor-lytic functional activity in the host (Keissling et al. 1975; Hanna and Burton 1981; Biron et al. 1983; Lala et al. 1985; Christopher et al. 1991; Miller et al. 1992; Brittenden et al. 1996). The absolute numbers of nucleated erythroid cells in the bone marrow of mice fed the Echinacea-containing diet was increased, and represents an enhanced production of these cells. However, the increase in absolute numbers of these cells by the bone marrow was almost precisely canceled out by the downward shift in the number of these cells found in the spleen. Nothing is known conclusively about the mechanism by which Echinacea influences erythropoiesis, however some conclusions may be drawn from what is known. For instance, TNF-alpha, interferons, and IL)1 are inhibitory to erythropoiesis (Feelders et al. 1998; Goicoechea et al. 1998; Allen et al. 1999). These are precisely the cytokines which are produced by monocytes–macrophages following exposure to Echinacea. By contrast, it has been shown that these cytokines can stimulate the earliest erythropoiesis progenitors (BFU-E), while inhibiting the growth of later progenitors (CFUE) (Trey and Kushner 1995; Means 1999; Barany 2001). Furthermore, the stromal microenvironment which governs erythropoiesis in the bone marrow and spleen, may also be susceptible to

162 the presence of enhanced levels or types of circulating cytokines in the presence of dietary Echinacea. Irrespective of the dynamics of interplay (negative/positive feedback) between the two organs with regard to erythropoiesis, it may well be that the normal, whole-body, steady state levels of nucleated erythroid cells in Echinacea-consuming mice have been maintained, since the arithmetic total of nucleated erythroid cells from the bone marrow and spleen in these mice, is very similar to the arithmetic total of these cells from the bone marrow and spleen of mice consuming untreated chow. In the present study, wherein no animals had died by ‘middle age’ (10 month) in the Echinaceaconsuming group, from ‘natural’ (age-related) causes (undetected spontaneous tumors, etc.), it appears probable that the sustained high levels of NK cells up to this time at least, were adequate to ward off any early – but clinically undetectable – life-threatening neoplasms, which increase in frequency in all mammals with increasing age. Thus, life-long consumption of this herb appears to have prophylactic advantage in this regard. Nevertheless, survival advantage cannot be indisputably related to tumor paucity in the Echinacea-consuming mice, since other disease conditions of aging, often gene-based, also increase with age in both humans and mice. References Allen DA, Breen C, Yagoob MM and Macdougall IC (1999) Inhibition of CFU-E colony formation in uremic patients with inflammatory disease: role of IFN-gamma and TNFalpha. J Invest Med 47: 204–211 Barak V, Birkenfeld S, Halperin T and Kalickman I (2002) The effect of herbal remedies on the production of human inflammatory and anti-inflammatory cytokines. Israel Med Assoc J 4: 919–922 Barany P (2001) Inflammation, serum C-reactive proteins, and erythropoietin resistance. Nephrol Dialysis Transplant 16: 224–227 Beck BN, Gillis S and Henney CS (1982) Display of the neutral glycolipid ganglio-N-tetraosylceramide (asialo GM1) on cells of the natural killer and T lineages. Transplantation 33: 118–122 Biron CA, Turgiss LR and Welsh RM (1983) Increase in NK cell number and turnover rate during acute viral infection. J Immunol 131(3): 1539–1545 Brittenden J, Heys SD, Ross J and Eremin O (1996) Natural killer cells and cancer. Cancer 77(7): 1226–1243

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