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ESSENTIAL NUTRIENTS – SEVEN ARGUMENTS FOR NUTRITIONAL SUPPLEMENTS

Fred Liers PhD nutrients nutritional supplementsAlmost daily articles, reports, or studies appear claiming nutritional supplements are not effective. The claims vary, but the verdict is always there is little or no scientific evidence proving supplements (or the nutrients in supplements) work. Others assert that people who take supplements have the world’s most expensive urine. This is nonsense! The scientific evidence is clear, available, and it has been for a long time.

Among the many problems with these reports is bashing supplements based on studies using low dose or non-therapeutic levels of nutrients. There is frequently failure to consider the importance of synergy among nutrients. Often there is data manipulation via statistical methods (often in meta-analyses).

Well beyond the question of whether supplements support health are the factors in modern life that create a greater needs for supplementing with important vitamins, minerals, cofactors, and other nutrients.

This month we present “Seven Arguments for Nutritional Supplements.” As the title implies, there are at least seven solid arguments for nutritional supplementation. There are actually a lot more.

To preview these arguments in favor of taking supplements, they are: 1) reduced food quality, 2) nutrient density varies by location, 3) modern lifestyles and stress, 4) environmental pollution, 5) too low RDAs, and 6) promotion of health and delaying of aging, and 7) the human right to correct information.

essential nutrients fatty acids EFA supplement

Essential Fatty Acids (EFA) are one type of essential nutrient required for health.

We at HPDI re-publish articles from the Orthomolecular News Service  (OMNS) because the authors provide much needed truth. Truth the form of correcting the false assumptions of anti-supplement propagandists to clarify the benefits of nutritional supplements. This information can help people be healthier easily and at relatively low cost.

HPDI offers a full line of foundational nutritional supplements, including multivitamins, vitamin C and antioxidant formulas, essential fats, and high-RNA Rejuvenate! superfoods. We also offer nearly 100 other nutritional supplements from single nutrients to condition specific formulas. See our full product overview.

Enjoy this article from the Orthomolecular News Service (OMNS). ~

Seven Arguments for Taking Nutritional Supplements

by Dag Viljen Poleszynski, PhD

(OMNS Sept 12 2018)

One of the most vitamin-restrictive countries in the world is Norway. There, authorities limit potencies to only slightly higher than RDA (Recommended Dietary Allowance) levels for dietary supplements sold outside of pharmacies. The traditional reasoning is that most people receive the nutrients they need from a “balanced diet.” [1]

The authorities are also obsessively concerned that some vitamins and minerals are harmful in high doses. And, since an intake of water-soluble vitamins in excess of needs is excreted in the urine, Norwegian “experts” advise that taking supplements is a waste of money.

Accordingly, the argument goes, the public should be protected not only from possible harm, but also from wasting money on unnecessary nutrients. The official policies on nutritional supplements vary within OECD (Organization for Economic Cooperation and Development) countries. Some are more liberal, while others are even more restrictive.

The official view on the connection between nutrient intake and possible toxicity is illustrated by the Norwegian Food Authority in a graph. [2]

Perceived risk from intake of nutrients. (Source: Expert Group on Vitamins and Minerals. Safe upper limits for Vitamins and Minerals. May 2003: Food Standards Agency, UK.)

The graph illustrates the official view on nutrients, assuming that nutrients function in the same way as pharmaceuticals, which they do not. Supplements of most vitamins, but also minerals and other nutrients, do not have very serious side effects even when taken at very high levels – in contrast with most drugs. [3,4] The fact that most of the chemotherapeutic drugs used against cancer have none or even just marginal effects against most cancers [5], while at the same time cause a lot of serious side effects, is rarely up for discussion.

The idea that nutritional supplements are not safe has a legal underpinning in Norwegian Food Law, which in section 16 prohibits sale of any food which is not safe: “Any food shall be considered not to be safe if it is seen as detrimental to health or not fit for consumption.” [6]

However, the Norwegian authorities do admit that vitamin D supplements are needed during part of the year. [1] Only part of the year? One third of Norway is within the Arctic Circle. Norway has far too little sunshine (especially during winter months) to get adequate levels of vitamin D from UVB radiation on the skin.

The authorities also recommend that pregnant women take folic acid to prevent birth defects, and omega-3-fatty acids may be advisable for those who do not eat fish regularly. Norwegians have a long tradition of giving children cod liver oil, which in a daily tablespoon provides enough vitamin A and D and essential fatty acids to cover basic needs.

Essential and conditionally essential nutrients

There are thousands of dietary supplements on the market, including 40+ essential nutrients alone and in various combinations, i.e. vitamins, minerals, trace elements and fatty acids. However, a number of other nutrients are “conditionally essential”, meaning that the body normally can make these molecules, but some people do not make optimal amounts. Examples are L-carnitine, alpha-lipoic acid, the methyl donor betaine, [7] chondroitin sulfate, coenzyme Q10, choline, amino acids such as tyrosine or arginine, and “essential” sugars normally formed in the body. [8]

Healthy young people normally make sufficient amounts of conditionally essential molecules in the body, although the levels are not always optimal. With inadequate levels of minerals or vitamins, key enzymes in biochemical pathways may not function optimally.

Due to genetic mutations, some enzymes may have increased needs for certain cofactors (vitamins), which can prevent them from functioning optimally.[9] Some enzymes only function normally when supplied with cofactors in greater amounts than normally required.

If supplements of essential nutrients prove insufficient for optimal enzyme function, “conditionally essential” nutrients may be added as part of a comprehensive, therapeutic program.

Some reservations

Parents are advised to become familiar with the literature on essential nutrients, for instance by consulting the Orthomolecular News Service. Children should be given supplements in appropriate doses and in a suitable form. Pills should not be given before children can control the swallowing reflex. Multivitamin powder can be given dissolved in water or juice. Parents should not dose vitamin C so high that a child comes to school or kindergarten with loose bowels or diarrhea.

In high doses, niacin may cause unpleasant side effects such as flushing and itching lasting up to several hours. [10] Although this is not dangerous, it may cause a child to feel unwell and anxious. Starting niacin supplementation with a low dose and gradually increasing it will allow the body to adapt and avoid the niacin flush.

A multivitamin supplement containing moderate amounts of niacin is often adequate until a child is 8-10 years old. For younger children, the dosage should start with only a few tens of milligrams, and not increased to more than 50-100 mg/day. Adults may gradually get used to taking 1,000-1,500 mg/d divided into 3 doses per day.

When it comes to omega-3 fatty acids (omega = ω) such as EPA and DHA, children may be given cod liver oil and served fish and/or other seafood 2-3 times a week. It is important to check the dose of vitamin A supplied, as it can be toxic in high doses, especially for children. One problem with cod liver oil today is that vitamin D has been removed during processing, thus changing the natural ratio of the two vitamins so that we ingest relatively too much of vitamin A. [11]

Higher dosages may be given after having consulted a therapist who has measured the ratio of omega-6 to omega-3 fatty acids in relevant cell membranes (red blood cells). In most industrialized countries, many people get too much of the omega-6 fatty acids, and would therefore benefit from eating more seafood or taking supplements with omega-3 fatty acids derived from organisms low in the food chain (algae, krill).

Flax seeds contain a high level of the essential omega-3 fatty acid alpha-linolenic acid, and freshly ground flaxseed meal or flax oil can be mixed with breakfast cereals or smoothies. Note that it may be advisable to limit eating farmed fish to once per week, since their fodder contains less omega-3 fatty acids than the food eaten by wild fish, and possibly also contains more contaminants. [12] Some researchers even warn against letting children eat too much fish because of the content of environmental toxins. [13,14]

Reasons for high-dose supplements of micronutrients

I have identified a number of arguments in favor of supplementing the modern diet with essential nutrients, here summarized with seven headlines. Most people should consider taking a multivitamin supplement containing vitamins and minerals even if they eat a nutritionally balanced diet.

Additional nutrients may contribute to better health and, in some cases, can be of vital importance in our modern world. The arguments are presented in random order, i.e. the order does not reflect priority.

1. The agricultural revolution has reduced food quality

The transition from an existence as hunter and gatherers to urban agriculture around 10,000 years ago began an epoch when foods were mass-produced but had lower nutritional density, compared with the previous food eaten by our ancestors. The nutritional density in many foods has fallen significantly since human societies transformed from hunter-gatherers into resident farmers. This is especially true in the last 60-70 years after agriculture was changed from small, versatile ecologically driven family farms to large, chemical-based, industrial agriculture. [15]

The reduction of nutritional content in modern crops, compared with older varieties, is well documented. [16] It is a consequence of soil erosion, loss of essential minerals from continual heavy use, combined with breeding of new varieties, which has increased the size and growth rate of plants by increasing the content of sugar and water and decreasing their mineral content compared to ancient species. At the same time, the relative content of other macronutrients (fat, protein/amino acids) and antioxidants may have been reduced.

Reduced nutritional density in many foods, combined with the use of refined “foods” like sugar, white flour and refined oils, places a greater priority on eating the most nutritious foods.

Farm produce grown organically generally has higher levels of essential nutrients such as trace minerals because the soil contains higher levels of trace minerals and the produce grows slower and thus has more time to absorb nutrients from the soil. Examples of nutrient dense foods are sardines, wild salmon, shellfish, eggs, liver, kale, collards and spinach, sea plants (seaweed), garlic, blueberries, and dark chocolate. [17]

2. Nutritional content of food varies with geographical location

Nutritional density varies considerably geographically between different regions, even with the same agricultural methods. This was documented in the United States in 1948 by a researcher at Rutgers University in the so-called Firman Bear report. [18] At that time agriculture was little mechanized, and artificial fertilizers and pesticides were hardly used.

The analysis found large differences in the content of minerals in the same food. The largest variations were found for potassium, sodium, boron and iron in spinach, while the greatest differences in calcium, magnesium and copper content were found in tomatoes.

The soil in areas with relatively low rainfall may in some cases contain an extremely high concentration of minerals, which is reflected in the plants growing there. This was well documented 70 years ago in the book Tomorrow’s Food. [19] The dentist George W. Heard found that the soil in Hereford, Texas, was exceptionally rich in minerals.[20]

Hereford became known as the “town without a toothache” after a newspaper article from January 29, 1942, reported that Hereford had the lowest incidence of tooth decay of any city in the United States. [21] Dr. Heard found that people in Hereford had exceptionally few dental cavities and also that the soil locally was especially rich in minerals. He emphasized that the population in the county ate unprocessed food and was drinking raw milk. [19]

Recent research shows that differences in the content of the selenium in the soil can cause major differences in the concentration of selenium in meat. [22] For instance, since the soil in Finland is poor in selenium, the authorities decided in the early 1980s to add selenate to commercial fertilizers. A survey of selenium status among 108 healthy young people showed an increase in the blood selenium level of about 50 percent after four years. [23]

A similar problem with the level of minerals in the soil exists for the content of magnesium. Often when the soil gets depleted of magnesium from heavy use, this essential mineral is not included in soil amendment with fertilizers. Produce grown in soil with an adequate level of magnesium will contain more magnesium than produce grown in soil deficient in magnesium.

Perhaps as many as 70-80% of the US population is magnesium-deficient, which causes many health problems. [24] Magnesium supplements (chloride, malate or citrate) can provide an adequate level when vegetables grown in soil with adequate magnesium are not available.

3. Stress and the modern lifestyle increase the need for nutrients

Mental stress increases the excretion and hence the need for many nutrients. Among the most important are magnesium and vitamin C, both of which are used by the body in larger quantities during periods of physical and mental stress. [24,25] Compared with our past as hunters and gatherers, today´s stress is often of a more permanent nature. Instead of experiencing occasional situations where we had to fight or flee, many of us live with recurring stress day in and out.

Vitamin C protects the brain and nervous system from damage caused by stress because the synthesis and maintenance of chemical neurotransmitters such as adrenaline and noradrenaline requires adequate levels of vitamin C. [25]

Vitamin C is also needed to repair collagen which is essential for skin, blood vessels, bones and joints, and muscles. When these are damaged by physical stress, extra vitamin C is necessary.

A controlled trial of 91 adults who experienced increased anxiety and stress 2-3 months after an earthquake in New Zealand in 2011 was divided into three groups, two were given a broad spectrum supplement of micronutrients in low or higher doses. [26] The supplements were found to alleviate the experience of stress, with the biggest dose having the biggest effect.

Our sedate, modern lifestyle reduces the need for energy from food, which implies a lower food intake or obesity. Loren Cordain, PhD, and coworkers have estimated that hunter-gatherers had significantly higher energy needs than the typical modern office worker. [27]

A lower energy intake generally reduces the absolute intake of all nutrients, while the need for some nutrients is not always reduced proportionally with energy intake. Overall this suggests that more exercise along with a more nutritious diet, including supplements of essential nutrients and less carbohydrates, will help to prevent obesity and maintain health.

Processing of food reduces its nutritional content, and the finished products are often based on fractions of the original foods. One example is milling grain to make white flour, [1] which has a lower nutritional density than whole grain flour.

The reduction in nutritional value has accelerated since whole foods are now divided into pieces, for example, boneless chicken breast. When meat is injected with saline to increase the volume, the relative level of essential nutrients is reduced. In the United States, many supermarkets in low-income rural and inner city areas have a limited selection of nutrient-dense foods, compared with high-income areas. [28]

4. Environmental pollutants increase the need for nutrients

The need for efficient detoxification and excretion is greatly increased by environmental pollution from the chemical industry, herbicides and pesticides used by industrial agriculture, antibiotic treatment of animals, transport, and plastic packaging. [29]

In our polluted world, the increased toxic load may be compensated for by an increase in nutrients to promote detoxification. One can respond by taking large doses of supplements of essential nutrients, for example, antioxidants vitamin C and E, and an adequate dose of selenium, which help the body detoxify harmful chemicals. Also helpful is regularly taking sauna baths, fasting periodically, and eating an excellent diet that includes generous portions of dark green leafy vegetables and colorful vegetables and fruits. [30]

A recent study predicts that global warming may reduce the nutrient density in many foods worldwide. [31] Atmospheric CO2 is estimated to surpass 550 ppm in the next 30-80 years, leading to larger crops with lower content of protein, iron and zinc per energy unit.

Assuming that diets remain constant, while excluding other climate impacts on food production, the researchers estimated that elevated CO2 could cause an additional 175 million people to be zinc deficient and an additional 122 million people to be protein deficient in 2050. Anemia would increase significantly if crops lose even a small amount of iron. The highest risk regions – South and Southeast Asia, Africa, and the Middle East – are especially vulnerable, since they do not have the means and access to compensate using nutritional supplements.

5. The RDA for essential nutrients is too low

The recommended nutrient reference intake (NRI) has been defined by UK authorities and the EU Food Safety Agency as the dose that is adequate for 95 percent of the population. [32] These authorities have given recommendations for a total of 41 chemical substances, [33] including 13 vitamins, 17 minerals/trace elements, 9 amino acids and two fatty acids. The problem with such guidelines is that when using the same 0.95 fraction for just 16 of the essential nutrients, the fraction of the overall population that has their needs met with the RDA is less than half (0.9516 = 0.44).

Given the above assumption, the proportion of the population having all nutrient needs met falls below 25 percent for 30 nutrients (0.9530 = 0.21). These 25 percent will not necessarily get optimal amounts, just enough so that they probably will have no deficiencies in accordance with established standards. Each individual is different and has different biochemical needs, so we all need different doses of essential nutrients. Many vitamins and minerals can give additional benefit when taken at higher doses.

The need for several essential nutrients increases with age and sickness. This applies, for example, to vitamin C, vitamin D, magnesium, and iron. In 2017 the Norwegian Food Safety Authority proposed to revise the official maximum levels for vitamins and minerals in dietary supplements. [34]

Their proposal introduced four different age categories with separate maximum intakes. Initially, the agencies proposed to revise the daily doses allowed in dietary supplements for folic acid, magnesium, calcium, vitamin C and D. At the same time, maximum rates were temporarily suspended for vitamins A, E, K, thiamine (B1), riboflavin (B2), niacin (B3), pantothenate (B5), pyridoxine (B6), cobalamine (B12), biotin, and for phosphorus, iron, copper, iodine, zinc, manganese, selenium, chromium, molybdenum, sodium, potassium, fluoride, chloride, boron and silicon.

The upper limits for some nutrients may be changed in the future. Unfortunately, Norwegian nutrition “experts” will likely continue to limit allowable doses below those freely available in the US and even Sweden.

6. An optimal nutrient intake promotes health and delays aging

A spokesperson for optimal nutritional intake is the well-known biochemist Bruce Ames, who proposed the “triage theory of nutrients,” in which enzymes responsible for cell maintenance functions evolved to have lower affinity for the essential vitamin and mineral cofactors than the enzymes responsible for short-term survival, to preserve life during times of famine. [35]

Thus, higher levels of vitamins and minerals may delay mitochondrial aging, speed up the repair of large molecules such as DNA and collagen, and generally improve other cellular functions. This is an important rationale for taking higher doses of vitamins and minerals than recommended reference intakes.

Dietary supplements can slow the aging process, in part by reducing the harmful effects of free radicals, known to be involved in many diseases such as cardiovascular disease and cancer. [36]

Naturally occurring hormones and/or supplements of cofactors needed for optimal hormone production in the body can have a significant life-prolonging effect if the body produces less than optimal amounts. [37] This is especially relevant for those with a genetic predisposition for disease.

An optimum intake of all nutrients is difficult to achieve even for those who eat almost exclusively an excellent diet of nutrient dense foods, such as meat and innards, fish, shellfish, fowl, eggs, nuts, mushrooms, and vegetables, berries and nutritious fruits. Some nutrients such as folic acid or carotenoids in vegetables are absorbed better from processed than unprocessed foods.

Although vegetables are often considered to be a good source of vitamins, for example vitamin A from carrots, vitamin A is only found in animal products such as liver, egg yolk, fish cod and cod liver oil. Although eating raw vegetables is helpful for several reasons (vitamin C, fiber, microbiota), carotenoids (alpha/beta-carotene, lutein, lycopene) in vegetables are less well absorbed from raw than cooked food and better absorbed in the presence of added fat. [38,39].

Nutrients in vegetables are better absorbed when finely chewed, graded, or mashed [38], and cooking and grinding meat reduces the energy required to digest it [40] and increases nutrient absorption [41].

Orthomolecular pioneer Abram Hoffer and Orthomolecular News Service Editor Andrew W. Saul suggested this list of daily intakes of vitamins and minerals. [42] The Norwegian 2017 recommendations for adult men and women [43] are given in comparison. Individual needs may vary substantially from person to person and also with health status.

The figures for optimal intake are obtained from the Independent Vitamin Safety Review Panel of physicians, researchers and academics, who concluded:

“People are deceived in believing that they can get all the nutrients they need from a ‘balanced diet’ consisting of processed foods. To achieve an adequate intake of vitamins and minerals, a diet of unprocessed whole foods, along with intelligent use of dietary supplements is more than just a good idea: it is vital.” [44: 55]

A well-known example is vitamin C, which can effectively fight viral infections, prevent or reverse disease caused by bacteria, and help the body detoxify organic and inorganic toxins. [45] Vitamin C also reduces the risk for cancer, strengthens connective tissues (collagen), and counteracts stress by increasing the adrenal´s production of cortisol. The dose required is set according to the body’s need.

Nobel Price Laureate Linus Pauling suggested that an optimal daily intake of vitamin C could vary from at least 250 mg up to 20 grams per day. [46] Because unabsorbed vitamin C attracts water into the gut, some people may experience loose stools, gas and/or diarrhea by ingesting only 1-2 grams at a time, while others with a higher level of stress may tolerate 5-6 grams or more. The dose that causes loose stools is called the “bowel tolerance” for vitamin C. [47] To avoid the laxative effect of high doses, it is best to take vitamin C throughout the day in smaller divided doses.

When the body is stressed by disease, the gut will naturally absorb more vitamin C because the body needs more. To find the optimal dose, the intake should be increased until bowel tolerance is reached. Some people can tolerate more than 100,000 mg/d of vitamin C in divided doses during serious illness without having loose stool.

Liposomal vitamin C bypasses the normal bowel tolerance because it is absorbed directly through cell membranes, so higher doses can be tolerated without diarrhea.

7. A human right to receive correct information

Access to correct information about food and essential nutrients, including knowledge about the importance of food for health is a fundamental human right. Such information should not only provide a summary of the nutrient content of food, but in our opinion should also explain how dietary supplements can counteract deficiencies and prevent and reverse disease caused by nutrient deficiencies.

We should be free to purchase quality-controlled supplements of essential nutrients and to use them to counteract aging and damage from stress as part of a long-term health plan. The right to reject recommendations by doctors for symptomatic treatment with synthetic, some times life-threatening, drugs to alleviate symptoms should be included. [48,49]

I have not found any formulation of such rights from the Norwegian authorities. The role of parents and their right to receive correct health information is addressed in a book by lawyer Anne Kjersti C. Befring, a fellow at the University of Oslo since 2014. [50]

Summary

The use of dietary supplements is widespread. High doses of vitamins are thought to be helpful because they help the body recover from damage and maintain itself long-term. Many vitamins are not harmful in doses even 10 to 100-fold higher than officially recommended.

Some governments warn about possible negative side effects, even including increased mortality from “excessive” intake of certain supplements. However, supplements of essential nutrients have been available for more than 80 years. They are known to be safe, and the observed side effects are generally mild with few exceptions.

It is possible to ingest too much of certain vitamins and minerals (vitamin A, calcium, iron, copper, selenium) which may exacerbate an existing imbalance or lack of another mineral (magnesium, zinc). It is also important to balance intake of fatty acids in the omega-6 and omega-3 series, as most people get too much omega-6 and not enough omega-3.

Small children can be overdosed with adult doses of for example vitamin A or iron, and pills may be dangerous for babies or young children because they can get stuck in the throat. Therefore, I recommend consulting a doctor or nutritionist educated in orthomolecular medicine. Most people are likely to benefit from taking a broad-spectrum multivitamin/mineral supplement as a basic insurance against deficiencies.

Compared to pharmaceutical drugs, supplements of most essential nutrients are quite harmless. However, some supplements may have poor quality, or contain toxic metals such as lead or cadmium. Therefore, it is the duty of our authorities to ensure that potentially hazardous products or supplements of poor quality are not sold, and that consumers are offered fair prices in a free market.

An example where the Norwegian authorities do not follow up such basic duties is that pharmacies demand more than 1,600 Norwegian Kroner (about $190) per kg of vitamin C in powder form, which would cost less than $20 with free competition and no restrictions in permitted doses or outlets.

Those who want to use natural healing methods, such as the use of food and supplements of essential nutrients to prevent or reverse illness, should consult therapists who are qualified to give advice on how natural therapies can help.

I recommend that anyone interested in supplements read the references for this article as well as the archives of the Journal of Orthomolecular Medicine http://orthomolecular.org/library/jom/ and the Orthomolecular Medicine News Service http://orthomolecular.org/resources/omns/index.shtml . Both are free access online.

(Dag Viljen Poleszynski, PhD, is the editor of Helsemagasinet [Health Magazine] https://vof.no/arkiv/ . He has translated and published a large number of OMNS releases in Norwegian.)

 

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37. Hertoghe T. The hormone handbook. Copyright (c) 2006 Thierry Hertoghe. Surrey, UK: International Medical Publications, 2006.

38. Edwards AJ, Nguyen CH, You CS, et al. a- og ß-carotene from a commercial carrot puree are more bioavailable to humans than from boiled-mashed carrots, as determined using an extrinsic stable isotope reference method. Journal of Nutrition 2002; 132: 159-67. https://academic.oup.com/jn/article/132/2/159/4687130

39. Unlu NZ, Bohn T, Clinton SK et al. Carotenoid absorption from salad and salsa by humans is enhanced by the addition of avocado or avocado oil. The Journal of Nutrition 2005; 135: 431-6. https://www.ncbi.nlm.nih.gov/pubmed/15735074

40. Boback SM, Cox CL, Ott BD et al. Cooking and grinding reduces the cost of meat digestion. Comparative biochemistry and physiology. Part A, molecular & integrative physiology 2007; 148: 651-6. https://www.ncbi.nlm.nih.gov/pubmed/17827047

41. Carmody RN, Wrangham RW. Cooking and the human commitment to a high-quality diet. Cold Spring Harbor Symposium on Quantitative Biology 2009; 74: 427-34. https://www.ncbi.nlm.nih.gov/pubmed/19843593

42. Hoffer A, Saul AW. Orthomolecular medicine for everyone. Laguna Beach, CA: Basic Health Publications, Inc., 2008. ISBN-13: 978-1591202264

43. Hjartåker A, Pedersen JI, Müller H mfl. Grunnleggende ernæringslære. 3. utgave. [Basic nutrition] Oslo: Gyldendal Norsk Forlag AS, 2017.

44. Levy TE. Vitamin C, infectious diseases, & toxins. Curing the incurable. 3rd Edition. (c)Thomas E. Levy 2011. Medfox Pub. ISBN-13: 978-0977952021

45. Pauling L. How to live longer and feel better. New York: W. H. Freeman and Company, 1986. ISBN-13: 978-0870710964

46. Cathcart, RF III. The method of determining proper doses of vitamin C for the treatment of disease by titrating to bowel tolerance. Journal of Orthomolecular Medicine 1981; 10: 125-32. http://orthomolecular.org/library/jom/1981/pdf/1981-v10n02-p125.pdf

47. Lazarou J, Pomeranz BH, Corey PN. Incidence of adverse drug reactions in hospitalized patients. A meta-analysis of prospective studies. JAMA 1998; 279: 1200-5. https://jamanetwork.com/journals/jama/fullarticle/187436

48. Moore TJ, Cohen MR, Furberg CD. Serious adverse drug events reported to the Food and Drug Administration, 1998-2005. Archives of Internal Medicine 2007; 167: 1752-9. https://www.ncbi.nlm.nih.gov/pubmed/17846394 .

49. Hitchen L. Adverse drug reactions result in 250 000 UK admissions a year. BMJ 2006; 332: 1109. https://www.ncbi.nlm.nih.gov/pubmed/16690649 .

50. Befring AKC. Helse- og omsorgsrett. [Health and Care] Oslo: CappelenDamm AS, 2017.

Nutritional Medicine is Orthomolecular Medicine

Orthomolecular medicine uses safe, effective nutritional therapy to fight illness. For more information: http://www.orthomolecular.org

Find a Doctor

To locate an orthomolecular physician near you: http://orthomolecular.org/resources/omns/v06n09.shtml

The peer-reviewed Orthomolecular Medicine News Service is a non-profit and non-commercial informational resource.

Editorial Review Board:

Ilyès Baghli, M.D. (Algeria)
Ian Brighthope, M.D. (Australia)
Prof. Gilbert Henri Crussol (Spain)
Carolyn Dean, M.D., N.D. (USA)
Damien Downing, M.D. (United Kingdom)
Michael Ellis, M.D. (Australia)
Martin P. Gallagher, M.D., D.C. (USA)
Michael J. Gonzalez, N.M.D., D.Sc., Ph.D. (Puerto Rico)
William B. Grant, Ph.D. (USA)
Tonya S. Heyman, M.D. (USA)
Suzanne Humphries, M.D. (USA)
Ron Hunninghake, M.D. (USA)
Michael Janson, M.D. (USA)
Robert E. Jenkins, D.C. (USA)
Bo H. Jonsson, M.D., Ph.D. (Sweden)
Jeffrey J. Kotulski, D.O. (USA)
Peter H. Lauda, M.D. (Austria)
Thomas Levy, M.D., J.D. (USA)
Homer Lim, M.D. (Philippines)
Stuart Lindsey, Pharm.D. (USA)
Victor A. Marcial-Vega, M.D. (Puerto Rico)
Charles C. Mary, Jr., M.D. (USA)
Mignonne Mary, M.D. (USA)
Jun Matsuyama, M.D., Ph.D. (Japan)
Dave McCarthy, M.D. (USA)
Joseph Mercola, D.O. (USA)
Jorge R. Miranda-Massari, Pharm.D. (Puerto Rico)
Karin Munsterhjelm-Ahumada, M.D. (Finland)
Tahar Naili, M.D. (Algeria)
W. Todd Penberthy, Ph.D. (USA)
Dag Viljen Poleszynski, Ph.D. (Norway)
Jeffrey A. Ruterbusch, D.O. (USA)
Gert E. Schuitemaker, Ph.D. (Netherlands)
Thomas L. Taxman, M.D. (USA)
Jagan Nathan Vamanan, M.D. (India)
Garry Vickar, MD (USA)
Ken Walker, M.D. (Canada)
Anne Zauderer, D.C. (USA)

Andrew W. Saul, Ph.D. (USA), Editor-In-Chief
Editor, Japanese Edition: Atsuo Yanagisawa, M.D., Ph.D. (Japan)
Robert G. Smith, Ph.D. (USA), Associate Editor
Helen Saul Case, M.S. (USA), Assistant Editor
Ralph K. Campbell, M.D. (USA), Contributing Editor
Michael S. Stewart, B.Sc.C.S. (USA), Technology Editor
Jason M. Saul, JD (USA), Legal Consultant

Comments and media contact: drsaul@doctoryourself.com OMNS welcomes but is unable to respond to individual reader emails. Reader comments become the property of OMNS and may or may not be used for publication.

0

OMEGA-3 ESSENTIAL FATS REMAIN “ESSENTIAL” – A REBUTTAL FROM OMNS

Fred Liers PhD omega-3 essential fats plus e EFA formulaOmega-3 essential fatty acids (EFA) are critically important for health. That is the reason we at HPDI include them in our foundational supplements system in the form of our Essential Fats Plus E formula. Essential Fats Plus E provides a balanced ratio of 4:1 omega-3 EPA to omega-6 GLA fatty acids proven to optimally support health.

As important as Omega-3 fats are in good health, various studies conclude they are of little value. In order to help clarity the fallacies found in such studies, this month we re-print the recent article “Omega 3 Fatty Acids and Cardiovascular Disease” from the Orthomolecular News Service (OMNS).

BACKGROUND

Essential fats including Omega-3 and Omega-6 are so important to health that we consider them as foundational or “core” to basic nutrition as multivitamins, antioxidants/vitamin C formulas, and high-RNA superfoods, like Rejuvenate! Plus.

Many of today’s health problems relate to deficiencies in Omega-3 essential fatty acids rather than overabundance of it. It makes sense for everyone to supplement their diets with at least a minimum amount of essential fats. This is addition to consuming foods high in Omega-3 (and Omega-6) essential fats, including leafy greens, nuts, seeds, and seed oils. Also, small amounts of wild-caught fish from clean waters. Preferably these fish would come from low on the food chain, such as sardines, herring, or young mackerel, for example.

In December 2107, my father Hank Liers, PhD, wrote “The Truth about Essential Fatty Acids.” In his article, he delves into detail about why essential fatty acids are critical for health.

The diagram below from Dr. Hank’s article shows in detail the pathways for the production and use of fatty acids in the body. In the figure the metabolic pathways (running left to right) for four fatty acids types are shown (top – Omega-3, second – Omega-6, third – Omega-9, bottom – Omega-7). Notice that only the omega-3 and omega-6 oils are considered to be essential fatty acids because they cannot be made in the body. This means they must come from food.

omega-3 fats omega-6 fats

Furthermore, an additional diagram from Dr. Hank’s article shown below provides details of the omega-6 and omega-3 pathways. Pathway specifics indicate key eicosanoids (series 1 prostaglandins [anti-inflammatory], series 2 prostaglandins [pro-inflammatory], and series 3 prostaglandins [anti-inflammatory]), oil sources, and important nutrient cofactors that are needed for the reactions to take place.

omega-3 fats omega-6 fats

In particular, Dr. Hank discusses how superior benefits to health result from a balanced 4:1 ratio between Omega-3 eicosapentanoic acid (EPA) fatty acids and Omega-6 gamma linoleic acid (GLA).

Below we list some of the functions and benefits obtained when by diet or supplementation the correct ratios and amounts of essential fatty acids are consumed.

• Regulate steroid production and hormone synthesis
• Regulate pressure in the eyes, joints, and blood vessels
• Regulate response to pain, inflammation, and swelling
• Mediate Immune Response
• Regulate bodily secretions and their viscosity
• Dilate or constrict blood vessels
• Regulate smooth muscle and autonomic reflexes
• Are primary constituents of cellular membranes
• Regulate the rate at which cells divide
• Necessary for the transport of oxygen from the red blood cells to tissues
• Necessary for proper kidney function and fluid balance
• Prevent red blood cells from clumping together
• Regulate nerve transmission

Dr. Hank also discusses the fallacy of thinking that supplemental Omega-3 fats alone are sufficient to produce health. That is, despite the relative lack of Omega-3 essential fats and the prevalence of Omega-6 fats in modern diets, it is nevertheless the forms (EPA and GLA)—and the critical 4:1 ratio between them—that makes the difference in how they act synergistically for health. The result of Hank’s scientific understanding of essential fatty acids has resulted in his formulation of a balanced EFA product, Essential Fats Plus E.

Orthomolecular Medicine News Service Article “Omega 3 Fatty Acids and Cardiovascular Disease”

Regarding the Orthomolecular Medicine News Service article “Omega 3 Fatty Acids and Cardiovascular Disease” (republished below) rebutting the “Cochrane Database of Systematic Reviews” which relies on so-called “Evidence Based Medicine” (EBM) to distort truth on Omega-3 essential fatty acids, the fact that Omega-3 fats are under such false attack represents a huge disservice to the public.

While essential fatty acids may not generate profits for corporations—and in fact may lead to improved health outcomes that threaten the use of chemicals and drugs—essential fats nevertheless remain foundational for health.

Above we have shown the important reasons Omega-3 fats and other essential fatty acids are scientifically termed “essential.” And why people continue taking essential fats, and giving them to their families and children, for supporting health and well-being. Primary among these reasons is that you cannot be healthy without them. Hence, they are essential. Why believe anyone who says otherwise?

The bottom line: Omega-3 essential fatty acids are critical for health. Supplementing the diet with them is a good idea for nearly everyone. This is especially true because typical diets are proven to be most deficient in Omega-3 among essential fats.

Below we re-print in full the recent article “Omega 3 Fatty Acids and Cardiovascular Disease” from the Orthomolecular News Service (OMNS) for the benefit of our HPDI blog readers. ~

===

FOR IMMEDIATE RELEASE
Orthomolecular Medicine News Service, Aug 6, 2018

Omega-3 Fatty Acids and Cardiovascular Disease

Commentary by Damien Downing, MBBS, MSB and Robert G. Smith, PhD

The Cochrane Database of Systematic Reviews has just updated its own review: Omega-3 fatty acids for the primary and secondary prevention of cardiovascular disease [1]. Here’s our take on it.

Michael Pollan, the brilliant food writer, reckoned you could sum up what to do about nutrition and diets in 7 words; “Eat food, not too much, mostly plants.” That sums up both what’s best for humans and what’s best for the planet.

We reckon you can sum up what’s wrong with evidence-based medicine (EBM) in 10 words; “Evidence is a waste of data; systematic reviews are palimpsests.” You can use that as a knife to quickly dissect this study.

There are many things wrong with this review. Somebody’s PR department has spun the review’s “no clear evidence of benefit” into “evidence of no benefit” – absence of evidence becoming evidence of absence. And clearly the media were entirely happy to take that one and run with it.

Systematic reviews are palimpsests

What’s a palimpsest? Back when things got written on vellum, an animal skin, not on paper, you didn’t throw it away; you recycled it and wrote over the original. It was called a palimpsest.

A systematic review gives an opportunity to write over the conclusions of a whole list of papers with your new version of the truth. You do that by the way that you select and exclude them.

For instance there was a meta-analysis (that’s a systematic review with more numbers) in 2005 that concluded that vitamin E supplements significantly increased the risk of death [2]. The way they did that was to rule out any study with less than 10 deaths – when fewer deaths was exactly the outcome they were supposed to be looking for.

The reason they gave for doing that was “because we anticipated that many small trials did not collect mortality data.” We’re not buying it; they used it as a trick to enable them to get the negative result they wanted – to over-write the findings of a long list of original studies.

And here we have authors doing the very same thing in this omega-3 study – and upping the ante slightly. Now the threshold is 50 deaths. Fewer than that and your study is ruled out of the final, supposedly least biased, analysis . . on the grounds that it’s more biased.

We don’t know how they could keep a straight face while saying (our interpretation); “The studies with fewer deaths showed more benefit from omega-3s, so we excluded them.” At least that’s what happened back in 2004 when the first version of this came out.[3]

But this is the 8th update (we think) and they no longer bother to tell you about what they included or excluded in detail, so we can only assume that if they had changed that exclusion they would have told us.

The weird thing is that they are allowed to do it. Nutrition researcher Dr. Steve Hickey has shown that in systematic reviews there is generally control for bias in the included studies, but none for bias in the actual review and its authors.[4,5]

They found not one example of adequate blinding among 100 Cochrane reviews (like this one); they could all be palimpsests. Do we know that they are fake? No, but it doesn’t matter: what we do know is that we can’t trust them. Nor can we trust this Cochrane review. Things haven’t changed since 2004.

Evidence is a waste of data

Evidence is what lawyers and courts use to find someone Guilty or Not Guilty, and we all know how that can go wrong. It’s a binary system: you’re either one or the other. But at least if you’re on trial all the evidence should be about you and whether you did the crime.

In EBM the evidence is all about populations, not about individuals. When a doctor tells you “There’s a 1 in 3 chance this treatment will work” he is required to base that on big studies, or even systematic reviews. You don’t, and you can’t, know what that means for you because very likely you don’t fit the population profile.

As Steve Hickey (again) said, the statistical fallacy underlying all this states that you have one testicle and one ovary – because that’s the population average! The authors of this study update started off with about 2100 papers that looked relevant. They then excluded 90 per cent of them for various reasons – some of them good reasons, some not.

A smarter way to work would be to data-mine them and look for useful information about sub-groups and sub-effects in all the papers. Is there a particular reason omega-3s might work for you and not for others? Perhaps you can’t stand fish, or are allergic to them, and so are deficient in omega-3s.

But the review system doesn’t allow it, it insists on overall conclusions (about populations), and that’s a colossal waste of data. It also confounds the overall finding of the review – it biases it in fact.

Here’s an example: while most subgroups that made it to the final analysis showed a small reduction in risk from taking omega-3s in one form or another (pills, food, whatever), those who got it from supplemented foods, which we understand means stuff like margarine with added omega-3, showed a 4.3-fold death risk increase!

The problem here is that the effects of omega-3 fatty acids cannot be studied alone as if they were a drug. What counts are all the other components of the diet that affect a person’s health.

Processed foods and drinks that contain many unhealthy ingredients can’t be made healthy by adding small doses of vitamins, minerals, and omega-3 fatty acids. In fact, many processed foods that contain small doses of vitamins and other essential nutrients are unhealthy because they contain large doses of sugar, salt, and harmful ingredients such as preservatives, dyes, and other non-food items.

Why lipids are so important

Part of the problem is that lipids are truly complicated, and not many people, patients, doctors or even scientists, understand them well. You need a good understanding of lipid metabolism to appreciate the difference in metabolism and impact between alpha-linolenic acid (ALA, in food such as oily fish) and extracted oils such as EPA and DHA that are only found at high levels in omega-3 supplements.

At these levels they are effectively new to nature; nobody, indeed no mammal, was exposed to really high doses of DHA until we invented fish oil supplements [6]. Miss that fact and you miss the difference between having people eat fresh oily fish or just using omega-3 margarine!

We know from a variety of studies that a diet containing generous portions of green leafy and colorful vegetables and fruits, moderate portions of eggs, fish, and meat, and supplements of adequate doses of essential nutrients (vitamins and minerals) is effective at lowering the risk for cardiovascular disease.

Adequate doses of both omega-3 (in flax oil, walnuts, fish) and omega-6 (in seed oils such as canola, soybean, peanut) fatty acids are essential for health. Although essential, omega-6 fatty acids are thought to contribute to inflammation throughout the body whereas omega-3 fatty acids are anti-inflammatory.

Omega-3 fatty acids are essential for most body organs including the brain but are found in lower levels than omega-6 fatty acids in most vegetables. Risk for cardiovascular disease can be lowered by adequate doses of vitamins C (3,000-10,000mg/d), D (2,000-10,000 IU/d), E (400-1,200 IU/d), and magnesium (300-600 mg/d) in addition to an excellent diet that includes an adequate dose of omega-3 fatty acids.[7]

(Dr. Damien Downing is a specialist physician practicing in London, and President of the British Society for Ecological Medicine. Robert G. Smith is a physiologist and Research Associate Professor at the University of Pennsylvania Perelman School Of Medicine.)

 

References:

1. Abdelhamid, A, Brown TJ, Brainard JS, et al., (2018) Omega 3 fatty acids for the primary and secondary prevention of cardiovascular disease. Cochrane Database of Syst Rev. 7:CD003177. https://www.ncbi.nlm.nih.gov/pubmed/30019766
http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD003177.pub3/abstract

2. Miller ER, Pastor-Barriuso R, Dalal D, et al., (2005) Review Meta-Analysis?: High-Dosage Vitamin E Supplementation May Increase. Annals of Internal Medicine, 142(1), pp.37-46. Available at: http://annals.org/article.aspx?articleid=718049.

3. Hooper L, Thompson RL, Harrison RA, et al.. (2004) Omega 3 fatty acids for prevention and treatment of cardiovascular disease. Cochrane Database Syst Rev. (4):CD003177. http://cochranelibrary-wiley.com/doi/10.1002/14651858.CD003177.pub2/abstract

4. Hickey S, Noriega LA. Implications and insights for human adaptive mechatronics from developments in algebraic probability theory, IEEE, UK Workshop on Human Adaptive Mechatronics (HAM), Staffs, 15-16 Jan 2009.

5. Hickey S, Hickey A, Noriega LA, (2013) The failure of evidence-based medicine? Eur J Pers Centered Healthcare 1: 69-79. http://ubplj.org/index.php/ejpch/article/view/636

6. Cortie CH, Else, PL, (2012) Dietary docosahexaenoic acid (22:6) incorporates into cardiolipin at the expense of linoleic acid (18:2): Analysis and potential implications. International Journal of Molecular Sciences, 13(11): 15447-15463. http://www.mdpi.com/1422-0067/13/11/15447

7. Case HS (2017) Orthomolecular Nutrition for Everyone. Turner Publication Co., Nashville, TN. ISBN-13: 978-1681626574

Nutritional Medicine is Orthomolecular Medicine

Orthomolecular medicine uses safe, effective nutritional therapy to fight illness. For more information: http://www.orthomolecular.org

Find a Doctor

To locate an orthomolecular physician near you: http://orthomolecular.org/resources/omns/v06n09.shtml

The peer-reviewed Orthomolecular Medicine News Service is a non-profit and non-commercial informational resource.

Editorial Review Board:

Ilyès Baghli, M.D. (Algeria)
Ian Brighthope, M.D. (Australia)
Prof. Gilbert Henri Crussol (Spain)
Carolyn Dean, M.D., N.D. (USA)
Damien Downing, M.D. (United Kingdom)
Michael Ellis, M.D. (Australia)
Martin P. Gallagher, M.D., D.C. (USA)
Michael J. Gonzalez, N.M.D., D.Sc., Ph.D. (Puerto Rico)
William B. Grant, Ph.D. (USA)
Tonya S. Heyman, M.D. (USA)
Suzanne Humphries, M.D. (USA)
Ron Hunninghake, M.D. (USA)
Michael Janson, M.D. (USA)
Robert E. Jenkins, D.C. (USA)
Bo H. Jonsson, M.D., Ph.D. (Sweden)
Jeffrey J. Kotulski, D.O. (USA)
Peter H. Lauda, M.D. (Austria)
Thomas Levy, M.D., J.D. (USA)
Homer Lim, M.D. (Philippines)
Stuart Lindsey, Pharm.D. (USA)
Victor A. Marcial-Vega, M.D. (Puerto Rico)
Charles C. Mary, Jr., M.D. (USA)
Mignonne Mary, M.D. (USA)
Jun Matsuyama, M.D., Ph.D. (Japan)
Dave McCarthy, M.D. (USA)
Joseph Mercola, D.O. (USA)
Jorge R. Miranda-Massari, Pharm.D. (Puerto Rico)
Karin Munsterhjelm-Ahumada, M.D. (Finland)
Tahar Naili, M.D. (Algeria)
W. Todd Penberthy, Ph.D. (USA)
Dag Viljen Poleszynski, Ph.D. (Norway)
Jeffrey A. Ruterbusch, D.O. (USA)
Gert E. Schuitemaker, Ph.D. (Netherlands)
Thomas L. Taxman, M.D. (USA)
Jagan Nathan Vamanan, M.D. (India)
Garry Vickar, MD (USA)
Ken Walker, M.D. (Canada)
Anne Zauderer, D.C. (USA)

Andrew W. Saul, Ph.D. (USA), Editor-In-Chief
Editor, Japanese Edition: Atsuo Yanagisawa, M.D., Ph.D. (Japan)
Robert G. Smith, Ph.D. (USA), Associate Editor
Helen Saul Case, M.S. (USA), Assistant Editor
Ralph K. Campbell, M.D. (USA), Contributing Editor
Michael S. Stewart, B.Sc.C.S. (USA), Technology Editor
Jason M. Saul, JD (USA), Legal Consultant

Comments and media contact: drsaul@doctoryourself.com OMNS welcomes but is unable to respond to individual reader emails. Reader comments become the property of OMNS and may or may not be used for publication.

To subscribe to the Orthomolecular Medicine News Service (free): http://www.orthomolecular.org/subscribe.html

OMNS Archive: http://orthomolecular.org/resources/omns/index.shtml

To view this article on the OMNS website: http://www.orthomolecular.org/resources/omns/v14n17.shtml

0

PRO-C ANTIOXIDANT FORMULA UPDATE + VIDEO

Dr. Hank Liers, PhD pro-c™ pro-c super antioxidant formulaFred Liers PhD pro-c antioxidant vitamin c nrf2 formulaLooking for an advanced antioxidant formula? Already using or recommending vitamin C? Curious about cellular Nrf2 activation? Look no further than PRO-C™.

PRO-C™ is among the most effective antioxidant formulas available. It is an HPDI foundational supplement that works most effectively when used with multivitamins, essential fats, and superfoods. However, it is also an excellent standalone formula that can rapidly provide the body with extremely high protection from free radicals.

We ourselves have taken PRO-C daily for many years with excellent results. Our personal experience together with detailed feedback from health professionals and end-users affirms the effectiveness of PRO-C as a super-antioxidant–vitamin C-Nrf2 activator formula.

PRO-C provides 500 mg of buffered vitamin C per capsule (buffered with calcium, magnesium, and zinc) along with grape extract (seed, skin, pulp) and green tea extract (95% polyphenols). In addition, we include a special combination of the “network antioxidants” l-glutathione (reduced), n-acetyl-l-cysteine (NAC), r-lipoic acid, and selenium. Vitamin B2 and Vitamin B6 in coenzyme forms support the enzymatic effectiveness of the “network antioxidants”. The formula works so well because this combination of ingredients leverages the antioxidant power of vitamin C, grape extract, green tea extract, and the other nutrients to act synergistically in order to maximize effectiveness.

FORMULATION HISTORY AND THE SCIENCE BEHIND PRO-C™

What you may not know is the history of the development PRO-C and the scientific knowledge on which Dr. Hank Liers based his formulation of it.

Dr. Hank formulated his first product in 1989. It was a potent antioxidant formula he called PYC-C™ (sounds like “pixie”). PYC-C consisted of a combination of buffered Vitamin C (including magnesium, calcium, and zinc ascorbates) and pycnogenols from pine bark.

Much of the scientific research data Dr. Hank collected during the development of PYC-C regarding oligomeric proanthocyanidins (OPC) he later incorporated into an article (currently published on this blog) titled “Review of Scientific Research on Oligomeric Proanthocyanidins (OPC)” (rev. 2017)

By 1997 Dr. Hank had gathered a great deal of new scientific information regarding green tea catechins and the nutrients termed “network antioxidants” by Dr. Lester Packer, director of Packer Lab at University of California, Berkeley. Beyond this information, Dr. Hank studied additional research regarding how various nutrients worked together synergistically. At that point, he was ready to formulate the new, improved PRO-C™ super antioxidant formula.

PRO-C combines the ingredients of PYC-C (now known as OPC-C™) and uses grape pulp, skin, and seed extract with green tea extract (with high polyphenols >95% and EpiGalloCatechinGalate (EGCG) >45%), n-acetyl-l-cysteine (NAC), reduced glutathione (GSH), R-lipoic acid, selenium, and coenzyme Vitamins B2 and B6.

PRO-C super antioxidant formula 180 cap 90 cap

HPDI launched PRO-C™ in late 1997. It rapidly became one of our best-selling products. Our customers raved about how effective it was for them if they felt like they were “coming down with something” (like a cold, flu, virus, infection, etc.). Greater skin elasticity greatly helped pregnant women avoid stretch marks and episiotomies. Today, we highly recommend its use together with our other Foundational Supplements to ensure optimal health and anti-aging effects.

THE PRO-C™ SUPER ANTIOXIDANT FORMULA

PRO-C™ super antioxidant formula is extremely synergistic, especially in so far as it increases the body’s ability to quench free radicals in its aqueous (i.e., water-based) compartments. Because antioxidants may become free radicals themselves after they have done their job, the body has developed an elaborate system for recovery of oxidized antioxidants.

 

Dr. Lester Packer was the primary researcher investigating the synergistic character of antioxidants. He made this statement in his interview with Dr. Richard Passwater after publication of Packer’s The Antioxidant Miracle (1999):

[The major theme of] The Antioxidant Miracle is that antioxidants work in a coordinated manner. They interact with one another, and this interaction, which we like to call the antioxidant network, is very important to the overall antioxidant defense that we possess. The key members of the antioxidant network are vitamin E and vitamin C, but there are other participants in this network. These are thiol antioxidants, antioxidants that contain sulfur groups in the body. Glutathione perhaps is the best known of these, but there are other sulfur-containing antioxidants that also are very important.”

Dr. Packer continues:

“This whole antioxidant network works like an orchestra depending on individuals who have, of course, different complements of antioxidants depending upon their nutritional regimens and the individuality of their own body metabolisms. The idea behind having a network of antioxidants is that if one antioxidant happens to be deficient the others can compensate and still keep the antioxidant defense system strong.”

The following diagram shows some of the relationships in the antioxidant network and how they support each other.

Lester Packer antioxidant network diagram Figure 1 – Dr. Packer’s Antioxidant Network

We see, for example, reduced glutathione (GSH) has the ability to reduce oxidized Vitamin C back to its unoxidized state. Vitamin C reduces oxidized Vitamin E back to its unoxidized state, and both reduces glutathione and spares it for other important functions, including detoxification and immune enhancement.

Many polyphenols (e.g., oligomeric proanthocyanidins (OPCs), anthocyanidins and catechins) found in red grape and green tea extracts spare Vitamin C and glutathione in the body, as well as operate as powerful antioxidants, anti-inflammatories, and connective tissue strengtheners.

grapes grape extract antioxidant

Grapes provide antioxidant nutrients such as polyphenols, OPCs, anthocyans, and resveratrol.

R-Lipoic Acid (see abstracts below) operates as an antioxidant both in its oxidized and reduced states, reduces the oxidized forms of both Vitamin E and Vitamin C, and and has been shown to enhance glutathione levels. Because several of these substances are able to protect Vitamin E contained in cell membranes, this combination also has a significant beneficial effect on the fat soluble antioxidant status of the body!

The nutrients in PRO-C have been carefully selected and balanced to provide optimal effects, especially as related to free radical protection, detoxification, immune system enhancement, connective tissue strengthening, and reduction of inflammation. PRO-C therefore provides outstanding nutritional support in a wide variety of conditions of poor health, as well as acts to support and maintain a state of health and well-being.

It the last several years the research results on Nrf2 activators have become well known and products developed that take advantage of these nutrients. For details see our blog article Natural Phytochemical Nrf2 Activators for Chemoprevention. Researchers have been studying specifically how enzyme-activating substances such as OPCs and anthocyans activate a transcription factor known as Nrf2 that causes the body to endogenously produce higher levels of a wide variety of protective enzymes including superoxide dismutase (SOD), catalase, and glutathione peroxidase.

Although we did not know about Nrf2 activators in 1997 when we formulated PRO-C, we have subsequently learned that four of the ingredients in the formula have powerful Nrf2 activity. These include grape seed extract, green tea extract, NAC, and r-lipoic acid. With this knowledge, we now understand that PRO-C provides both powerful external antioxidants (with extremely high ORAC5.0 values) that support redox cycles within the body, but also provides ingredients that allow the body to endogenously produce powerful protective enzymes for even greater free-radical protection and health.

PRO-C™ ANTIOXIDANT FORMULA INGREDIENTS

PRO-C contains buffered vitamin C (in the form of powdered calcium, magnesium, and zinc ascorbates), high-potency grape extract (from grape pulp, skins, and seeds), green tea extract (with>95% polyphenols and >45% EGCG), reduced glutathione, N-Acetyl-L-Cysteine (NAC), R-lipoic acid, coenzyme forms of vitamin B2 (R5P) and vitamin B6 (P5P), and selenium.

Below we will discuss each ingredient and show some of the research that confirms its effectiveness.

VITAMIN C

Vitamin C typically is called l-ascorbic acid or ascorbate and is an essential nutrient for humans and other animal species. The term “vitamin C” refers to a number of vitamins that have vitamin C activity in animals, including ascorbic acid and its salts (e.g., magnesium ascorbate, calcium ascorbate, sodium ascorbate, etc.), and some oxidized forms such as dehydroascorbate and semidehydroascorbate.

Vitamin C is known to perform many critical functions within the body involving detoxification, tissue building, immune enhancement, pain control, and controlling or killing pathogenic organisms. It is also known to be helpful for wound and bone healing, healthy skin and eyes, fighting infections, stress control, toxic exposure, and repairing damaged tissue of all types. For much more information on the many benefits of Vitamin C see our blog article Vitamin C – An Amazing Nutrient.

Below are two abstracts that show some of the beneficial effects of Vitamin C when used with other network antioxidants:

ABSTRACT 1:
Exhaustive physical exercise causes oxidation of glutathione status in blood: prevention by antioxidant administration.
Sastre J, Asensi M, Gasco E, Pallardo FV, Ferrero JA, Furukawa T, Vina J
In: Am J Physiol (1992 Nov) 263(5 Pt 2):R992-5

We have studied the effect of exhaustive concentric physical exercise on glutathione redox status and the possible relationship between blood glutathione oxidation and blood lactate and pyruvate levels. Levels of oxidized glutathione (GSSG) in blood increase after exhaustive concentric physical exercise in trained humans. GSSG levels were 72% higher immediately after exercise than at rest. They returned to normal values 1 h after exercise. Blood reduced glutathione (GSH) levels did not change significantly after the exercise. We have found a linear relationship between GSSG-to-GSH and lactate-to-pyruvate ratios in human blood before, during, and after exhaustive exercise. In rats, physical exercise also caused an increase in blood GSSG levels that were 200% higher after physical exercise than at rest. GSH levels did not change significantly. Thus, both in rats and humans, exhaustive physical exercise causes a change in glutathione redox status in blood. We have also found that antioxidant administration, i.e., oral vitamin C, N-acetyl-L- cysteine, or glutathione, is effective in preventing oxidation of the blood glutathione pool after physical exercise in rats.

ABSTRACT 2:
The effect of glutathione and vitamins A, C, and E on acute skin flap survival.

Hayden RE, Paniello RC, Yeung CS, Bello SL, Dawson SM
In: Laryngoscope (1987 Oct) 97(10):1176-9

Vitamins A, C, and E act as antioxidants and as free radical scavengers in biological systems. Glutathione is involved in several reactions in vitamin metabolism and also plays an important role in cell membrane protection against lipid peroxidation by free radicals. We sought to use these natural defense mechanisms against oxygen free radicals formed during reperfusion of ischemic skin flaps. An acute axial random skin flap model was utilized in the rat. Vitamins or glutathione were administered by oral gastric tube or intravenously in the perioperative period, and survival of the flap was measured at 1 week. Glutathione, beta-carotene, ascorbic acid and alpha-D- tocopherol showed mean flap survival of 84% to 89%, each of which was significantly improved over saline controls (67% p less than .0005). The mechanisms and biochemistry of these vitamins, and their interactions with other vitamins and with glutathione, are discussed, along with clinical implications of free radical scavenging and skin flap survival.

GRAPE EXTRACT

Grape extract (seeds, skin, pulp) contain highly bioavailable bioflavonoid complexes that in research studies have been shown to have powerful antioxidant capability. The Oligomeric Proanthocyanidins (OPCs) in grape seed extract are able to strengthen collagen fibers in aging or damaged connective tissue and can act as a preventative against connective tissue degradation.

Some research indicates that anthocyans, which are found in extracts of grape skin and stems (but not in grape seed extract), can reduce oxidized glutathione while at the same time become reduced themselves. In addition, extracts of grape skin and stems (but not those of grape seed extract) contain a material called trans-resveratrol that has been shown to have chemopreventive effects.

Below we have provided some of the abstracts that are included in our broad list of relevant abstracts for PRO-C.

ABSTRACT 3:
Protective effects of grape seed proanthocyanidins and selected antioxidants against TPA-induced hepatic and brain lipid peroxidation and DNA fragmentation, and peritoneal macrophage activation in mice.
Bagchi D, Garg A, Krohn RL, Bagchi M, Bagchi DJ, Balmoori J, Stohs SJ
In: Gen Pharmacol (1998 May) 30(5):771-6

1. The comparative protective abilities of a grape seed proanthocyanidin extract (GSPE) (25-100 mg/kg), vitamin C (100 mg/kg), vitamin E succinate (VES) (100 mg/kg) and beta-carotene (50 mg/kg) on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced lipid peroxidation and DNA fragmentation in the hepatic and brain tissues, as well as production of reactive oxygen species by peritoneal macrophages, were assessed. 2. Treatment of mice with GSPE (100 mg/kg), vitamin C, VES and beta-carotene decreased TPA-induced production of reactive oxygen species, as evidenced by decreases in the chemiluminescence response in peritoneal macrophages by approximately 70%, 18%, 47% and 16%, respectively, and cytochrome c reduction by approximately 65%, 15%, 37% and 19%, respectively, compared with controls. 3. GSPE, vitamin C, VES and beta-carotene decreased TPA-induced DNA fragmentation by approximately 47%, 10%, 30% and 11%, respectively, in the hepatic tissues, and 50%, 14%, 31% and 11%, respectively, in the brain tissues, at the doses that were used. Similar results were observed with respect to lipid peroxidation in hepatic mitochondria and microsomes and in brain homogenates. 4. GSPE exhibited a dose-dependent inhibition of TPA- induced lipid peroxidation and DNA fragmentation in liver and brain, as well as a dose-dependent inhibition of TPA-induced reactive oxygen species production in peritoneal macrophages. 5. GSPE and other antioxidants provided significant protection against TPA-induced oxidative damage, with GSPE providing better protection than did other antioxidants at the doses that were employed.

ABSTRACT 4:
Clinical and capillaroscopic evaluation of chronic uncomplicated venous insufficiency with procyanidins extracted from vitis vinifera
Costantini A, De Bernardi T, Gotti A
In: Minerva Cardioangiol (1999 Jan-Feb) 47(1-2):39-46

BACKGROUND: The pharmacological treatment of non-complicated chronic venous insufficiency is a current and well-debated topic. The introduction of new products with action on the venous system, improved knowledge on the physiopathology of venous insufficiency and the possibility provided by new analytical instruments, have given new impulse to the consolidation of the clinical value of phlebotonics in this indication. METHODS: In light of this, 24 patients with non-complicated chronic venous insufficiency were treated with oral administration of Oligomeric Proanthocyanidins (Pycnogenols-OPC) 100 mg/day. To evaluate the therapeutic efficacy of the treatment, an instrumental evaluation by optical probe capillaroscope was employed in addition to the traditional subjective clinical parameters: swelling, itching, heaviness and pain. The videocapillaroscope examination was performed at the lower third of the leg and the first toe. Edema in the capillaroscopic field, the number of observable capillaries and the capillary dilatation were the parameter chosen to evaluate the efficacy of treatment. All patients completed the study with no reports of adverse events during the period of observation. RESULTS: The results obtained show a positive clinical response (improved or absent symptoms) in over 80% of patients, with significant improvement of symptoms already evident after the first 10 days of treatment. The mechanism of action of the OPCs explains the rapid reduction of the swelling of the lower limbs and correlated with this are the other evaluable symptoms: heaviness and itching. Particularly striking results were observed for itching and pain which completely disappeared during the course of therapy in 80% and 53% of the patients respectively. Noteworthy is the good correlation between the clinical and instrumental data, with improvement in a total of 70% of patients. CONCLUSIONS: The results obtained in the course of this clinical experience, with evident improvement already during the first weeks of treatment, the absence of adverse events added to the benefit of a once-a-day administration, justify the use of OPC in the treatment of non-complicated chronic venous insufficiency.

ABSTRACT 5:
Polymeric procyanidin fraction from defatted grape seeds protects HepG2 cells against oxidative stress by inducing phase II enzymes via Nrf2 activation.
Younghwa Kim, Youngmin Choi, Hyeonmi Ham, Heon-Sang Jeong, Junsoo Lee
Kim, Y., Choi, Y., Ham, H. et al. Food Sci Biotechnol (2013) 22: 485. https://doi.org/10.1007/s10068-013-0105-x

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important transcription factor that regulates antioxidant response element (ARE)-driven phase II detoxification enzymes. In this study, induction of phase II enzymes via Nrf2/ARE activation in the cytoprotective effect of crude polyphenol extract (CPE), oligomeric procyanidin fraction (OPF), and polymeric procyanidin fraction (PPF) from defatted grape seeds in HepG2 cells was evaluated. Among these treatments, the treatment with PPF significantly increased Nrf2 protein expression in the nuclear fraction. Treating the samples increased heme oxygenase-1 (HO-1) and NAD(P)H:quinone oxidoreductase 1 (NQO1) protein expression in a dose-dependent manner, and PPF significantly increased the levels of phase II enzymes. Cellular generation of reactive oxygen species (ROS) were effectively reduced by PPF. These results suggest that pretreatment with PPF shows a cytoprotective effect by inhibiting ROS production and inducing HO-1 and NQO1 expression via Nrf2 activation in HepG2 cells.

GREEN TEA EXTRACT

Green tea extract is obtained from the unfermented leaves of Camellia sinensis for which numerous biological activities have been reported including: antimutagenic, antibacterial, hypocholesterolemic, antioxidant, and protective against tumorigenesis. Below we have selected a few of the many abstracts we have on file showing the benefit of green tea extract.

Green tea antioxidant polyphenols catechins

Green tea leaves are high in antioxidant polyphenols and catechins.

ABSTRACT 6:
Enhancement of antioxidant and phase II enzymes by oral feeding of green tea polyphenols in drinking water to SKH-1 hairless mice: possible role in cancer chemoprevention.
Khan SG, Katiyar SK, Agarwal R, Mukhtar H
In: Cancer Res (1992 Jul 15) 52(14):4050-2

Following the oral feeding of a polyphenolic fraction isolated from green tea (GTP) in drinking water, an increase in the activities of antioxidant and phase II enzymes in skin, small bowel, liver, and lung of female SKH-1 hairless mice was observed. GTP feeding (0.2%, w/v) to mice for 30 days significantly increased the activities of glutathione peroxidase, catalase, and quinone reductase in small bowel, liver, and lungs, and glutathione S-transferase in small bowel and liver. GTP feeding to mice also resulted in considerable enhancement of glutathione reductase activity in liver. In general, the increase in antioxidant and phase II enzyme activities was more pronounced in lung and small bowel as compared to liver and skin. The significance of these results can be implicated in relation to the cancer chemopreventive effects of GTP against the induction of tumors in various target organs.

ABSTRACT 7:
INHIBITORY EFFECT OF SIX GREEN TEA CATECHINS AND CAFFEINE ON THE GROWTH OF FOUR SELECTED HUMAN TUMOR CELL LINES.
In: Anticancer Drugs (1996 Jun) 7(4):461-8
Institutional address: Department of Pharmacology and Toxicology College of Pharmacy University of Arizona Tucson 85721 USA.

Green tea is an aqueous infusion of dried unfermented leaves of Camellia sinensis (family Theaceae) from which numerous biological activities have been reported including antimutagenic, antibacterial, hypocholesterolemic, antioxidant, antitumor and cancer preventive activities. From the aqueous-alcoholic extract of green tea leaves, six compounds (+)-gallocatechin (GC), (-)-epicatechin (EC), (-)- epigallocatechin (EGC), (-)-epicatechin gallate (ECG), (-)- epigallocatechin gallate (EGCG) and caffeine, were isolated and purified. Together with (+)-catechin, these compounds were tested against each of four human tumor cells lines (MCF-7 breast carcinoma, HT-29 colon carcinoma, A-427 lung carcinoma and UACC-375 melanoma). The three most potent green tea components against all four tumor cell lines were EGCG, GC and EGC. EGCG was the most potent of the seven green tea components against three out of the four cell lines (i.e. MCF-7 breast cancer, HT-29 colon cancer and UACC-375 melanoma). On the basis of these extensive in vitro studies, it would be of considerable interest to evaluate all three of these components in comparative preclinical in vivo animal tumor model systems before final decisions are made concerning which of these potential chemopreventive drugs should be taken into broad clinical trials.

GLUTATHIONE AND N-ACETYL-L-CYSTEINE (NAC)

Glutathione and NAC (a major precursor of glutathione) both provide important protection against toxins and free radicals, and can strengthen the immune system. Glutathione is considered to be one of the most important protective substances in the human body with almost 60% of liver detoxification accounted for by this key substance. In addition, glutathione is one of the most potent anti-viral substances known.

Some research has indicated that glutathione may not be able to enter easily into certain types of cells, but NAC is able to enter these cells and be converted into glutathione once inside the cell. Thus, the combination of glutathione and NAC appear to be more potent than either alone.

Below we provide some of the key abstracts we have on file regarding NAC and glutathione.

ABSTRACT 8
GSH rescue by N-acetylcysteine.
Ruffmann R Wendel A
In: Klin Wochenschr (1991 Nov 15) 69(18):857-62

Reduced glutathione (GSH) is the main intracellular low molecular weight thiol. GSH acts as a nucleophilic scavenger and as an enzyme-catalyzed antioxidant in the event of electrophilic/oxidative tissue injury. Therefore, GSH has a major role as a protector of biological structures and functions. GSH depletion has been recognized as a hazardous condition during paracetamol intoxication. Conversely, GSH rescue, meaning recovery of the protective potential of GSH by early administration of N-acetylcysteine (NAC), has been found to be life-saving. Lack of GSH and electrophilic/oxidative injury have been identified among the causes of the adult respiratory distress syndrome (ARDS), idiopathic pulmonary fibrosis (IPF), and the acquired immunodeficiency syndrome (AIDS). Experimental and early clinical data (in ARDS) point to the role of NAC in the treatment of these conditions. Recently, orally given NAC has been shown to enhance the levels of GSH in the liver, in plasma, and notably in the bronchoalveolar lavage fluid. Rescue of GSH through NAC needs to be appreciated as an independent treatment modality for an array of different disease, all of which have one feature in common: pathogenetically relevant loss of GSH.

ABSTRACT 9
Cysteine and glutathione concentrations in plasma and bronchoalveolar lavage fluid after treatment with N-acetylcysteine.
Bridgeman MM Marsden M MacNee W Flenley DC Ryle AP
In: Thorax (1991 Jan) 46(1):39-42

N-acetylcysteine (600 mg/day) was given to patients by mouth for five days before bronchoscopy and bronchoalveolar lavage to determine whether N-acetylcysteine could increase the concentrations of the antioxidant reduced glutathione in plasma and bronchoalveolar lavage fluid. Bronchoalveolar lavage was performed 1-3 hours (group 2, n = 9) and 16-20 hours (group 3, n = 10) after the last dose of N-acetylcysteine and the values were compared with those in a control group receiving no N-acetylcysteine (group 1, n = 8). N-Acetylcysteine was not detected in plasma or lavage fluid. Plasma concentrations of cysteine, the main metabolite of N-acetylcysteine and a precursor of reduced glutathione, were greater in the groups receiving treatment (groups 2 and 3) than in group 1. Cysteine concentrations in lavage fluid were similar in the three groups. Concentrations of reduced glutathione were greater in both plasma and lavage fluid in group 2 than in group 1. These data suggest that N-acetylcysteine given by mouth is rapidly deacetylated to cysteine, with resulting increases in the concentrations of cysteine in plasma and of reduced glutathione in plasma and the airways, which thus temporarily increase the antioxidant capacity of the lung.

R-LIPOIC ACID / ALPHA-LIPOIC ACID

R-Lipoic Acid is normally made at low levels in the human body, where it functions primarily as an important metabolic nutrient in the conversion of pyruvic acid into acetyl coenzyme A. As such, it plays a crucial role in the metabolism of both fats and carbohydrates into energy. In addition, r-lipoic acid functions as an extremely powerful antioxidant capable of trapping many different types of free radicals in the body.

Because it is both water and fat soluble, lipoic acid is able to operate in a broader range of body tissues than most other antioxidants. Its small size allows lipoic acid to enter areas of the body not easily accessible to many other substances; this allows lipoic acid, for example, to enter the cell nucleus and prevent free-radical damage to DNA.

Because it is such a powerful antioxidant and can easily function as such in both a reduced and oxidized state, lipoic acid is able to protect other important antioxidants such as glutathione, Vitamin E, and Vitamin C. R-lipoic acid is also able to chelate heavy metals such as lead, cadmium, mercury, free iron, and free copper out of the body.

Below we provide relevant scientific abstracts from our database regarding R-Lipoic acid.

ABSTRACT 10:
Alpha-Lipoic acid as a biological antioxidant.
Packer L Witt EH Tritschler HJ
In: Free Radic Biol Med (1995 Aug) 19(2):227-50

alpha-Lipoic acid, which plays an essential role in mitochondrial dehydrogenase reactions, has recently gained considerable attention as an antioxidant. Lipoate, or its reduced form, dihydrolipoate, reacts with reactive oxygen species such as superoxide radicals, hydroxyl radicals, hypochlorous acid, peroxyl radicals, and singlet oxygen. It also protects membranes by interacting with vitamin C and glutathione, which may in turn recycle vitamin E. In addition to its antioxidant activities, dihydrolipoate may exert prooxidant actions through reduction of iron. alpha-Lipoic acid administration has been shown to be beneficial in a number of oxidative stress models such as ischemia-reperfusion injury, diabetes (both alpha-lipoic acid and dihydrolipoic acid exhibit hydrophobic binding to proteins such as albumin, which can prevent glycation reactions), cataract formation, HIV activation, neurodegeneration, and radiation injury. Furthermore, lipoate can function as a redox regulator of proteins such as myoglobin, prolactin, thioredoxin and NF-kappa B transcription factor. We review the properties of lipoate in terms of (1) reactions with reactive oxygen species; (2) interactions with other antioxidants; (3) beneficial effects in oxidative stress models or clinical conditions.

ABSTRACT 11:
Regeneration of glutathione by α-lipoic acid via Nrf2/ARE signaling pathway alleviates cadmium-induced HepG2 cell toxicity.
Zhang J, Zhou X, Wu W, Wang J, Xie H, Wu Z.
In: Environ Toxicol Pharmacol. 2017 Apr;51:30-37. doi: 10.1016/j.etap.2017.02.022. Epub 2017 Feb 27.

Alpha-lipoic acid (α-LA) is an important antioxidant that is capable of regenerating other antioxidants, such as glutathione (GSH). However, the underlying molecular mechanism by which α-LA regenerates GSH remains poorly understood. The current study aimed to investigate whether α-LA regenerates GSH by activation of Nrf2 to alleviate cadmium-induced cytotoxicity in HepG2 cells. In the present study, we found that cadmium induced cell death by depletion of GSH through inactivation of Nrf2. Addition of α-LA to cadmium-treated cells reactivated Nrf2 and regenerated GSH through elevating the Nrf2-downstream genes γ-glutamate-cysteine ligase (γ-GCL) and GR, both of which are key enzymes for GSH synthesis. However, blocking Nrf2 with brusatol in the cells co-treated with α-LA and cadmium reduced the mRNA and the protein levels of γ-GCL and GR, thus suppressed GSH regeneration by α-LA. Our results indicated that α-LA activated Nrf2 signaling pathway, which upregulated the transcription of the enzymes for GSH synthesis and therefore GSH contents to alleviate cadmium-induced cytotoxicity in HepG2 cells.

SELENIUM

Selenium has been shown by clinical research to be a key mineral in the body’s defenses against free radicals and has been shown to be a major factor in reducing the symptoms of HIV infections and in the prevention of tumors. Selenium is used in conjunction with glutathione to form the powerful enzyme glutathione peroxidase that is responsible for detoxification of peroxides formed during the process of aerobic metabolism in humans and other animals.

ABSTRACT 12
Serum selenium concentrations in rheumatoid arthritis.
In: Ann Rheum Dis (1991 Jun) 50(6):376-8

O’Dell JR, Lemley-Gillespie S, Palmer WR, Weaver AL, Moore GF, Klassen LW

Selenium is a trace element and an essential part of the enzyme glutathione peroxidase, which protects cells from oxidative damage. Selenium has been shown to have antiproliferative, anti-inflammatory, antiviral, and immune altering effects. Serum selenium concentrations in 101 patients with seropositive rheumatoid arthritis were found to be significantly lower than those in 29 normal, healthy controls (mean (SD) 148 (42) v 160 (25) micrograms/l) and also lower than those in eight patients with fibrositis (148 (42) v 166 (25) micrograms/l). It is speculated that serum selenium concentrations may modulate the effect of viral or other infections in subjects with the appropriate genetic background and in this way enhance the development or progression of rheumatoid arthritis.

ABSTRACT 13
Studies on selenium in top athletes.
Dragan I, Ploesteanu E, Cristea E, Mohora M, Dinu V, Troescu VS
In: Physiologie (1988 Oct-Dec) 25(4):187-90

The authors performed a controlled trial in 18 top athletes (9 weight lifters and 9 rowers, girls) in order to make evident some chronic and acute effects (antioxidant) of selenium. Nonprotein–SH (essential glutathione), lipid peroxides (MDA-malondialdehyde), glucose-6-phosphate dehydrogenases (G-6-PDH) and fructose-1,6- diphosphate aldolase in serum, have been recorded initially on basal conditions, after 3 weeks of treatment (100 micrograms/day selenium or placebo) and again after 3 weeks of treatment, also on basal conditions, when crossing over the groups (between a free interval of 10 days). In another trial we registered these parameters on basal conditions and after two hours of hard training accompanied by a per oral administration of 150 micrograms selenium (respectively placebo). The results show significant changes under selenium treatment of the peroxides, G-6-PDH and light changes, not significant of the nonprotein–SH, changes which could suggest an antioxidant effect of this element.

VITAMINS B2 and B6 IN COENZYME FORMS

Vitamin B2 as coenzyme riboflavin-5-phosphate is a key vitamin that supports the regeneration of glutathione (via glutathione reductase). Vitamin B6 as coenzyme pyridoxal-5-phosphate is a key vitamin that supports the ability of glutathione to combine with toxic substances (via glutathione transferase) in the process of eliminating them from the body. They are especially effective in their coenzyme forms which allows them to be directly utilized by the body starting in the intestinal tract.

MAGNESIUM, CALCIUM, AND ZINC

Magnesium, zinc, and calcium synergistically work with (and enhance the effects of) the other ingredients in PRO-C. Minerals are especially needed as active components of enzymes that drive metabolic activity. For example, magnesium is required in the functioning of more than 325 types of enzymes.

PRO-C™ SUPER ANTIOXIDANT FORMULA BENEFITS

HIGHLY EFFECTIVE VITAMIN C FORMULA PLUS ANTIOXIDANTS. A complete vitamin C formula, a powerful antioxidant Formula, and Nrf2 activator combined in a single advanced supplement!

POWERFUL, SYNERGISTIC FREE-RADICAL QUENCHING FORMULA. PRO-C™ components work together to quench free radicals in your body. Vitamin C enables grape seed extract to function more effectively, and conversely grape seed extract potentiates vitamin C. Green tea extract boosts ORAC (Oxygen Radical Absorbance Capacity) value.

PROVIDES SIGNIFICANT AMOUNTS OF POWERFUL NRF2 ACTIVATORS (from Grape Extract, Green Tea Extract, NAC, and R-Lipoic Acid) that stimulate the production of the body’s own protective antioxidants including superoxide dismutase, catalase, glutathione peroxidase, and heme oxygenase.

SUPERIOR, BUFFERED (NON-ACIDIC) FORM OF VITAMIN C. Mineral Ascorbates never acidify your body, keeping you pH balanced. Staying alkaline is an important element in maintaining a healthy body.

RAPID ASSIMILATION. Capsule form ensures rapid uptake and assimilation in the body. You may also empty capsule contents into water, food, or directly Into mouth, if desired. Good, mildly tart taste!

COMPOSITION OF PRO-C™ SUPER ANTIOXIDANT FORMULA

One (1) vegetarian capsule of PRO-C provides the following percentages of the Daily Value:

NUTRIENT AMOUNT % Daily Value
Vitamin C (from mineral ascorbates) 500 mg 833%
BioVin® Grape Extract 30 mg *
Green Tea Extract 30 mg *
Calcium (from calcium ascorbate) 23 mg 2.3%
Magnesium (from magnesium ascorbate) 23 mg 5.7%
L-Glutathione (reduced) 20 mg *
N-Acetyl-L-Cysteine (NAC) 15 mg *
R-Lipoic Acid 5 mg *
Zinc (from zinc ascorbate) 2 mg 13%
Vitamin B2 (from riboflavin-5′-phosphate) 1 mg 118%
Vitamin B6 (from pyridoxal-5′-phosphate) 1 mg 50%
Selenium (from l-selenomethionine) 10 mcg *

* No established Daily Value

DIRECTIONS: As a dietary supplement take 1–3 capsules or more daily in divided doses (i.e., spread out over the day), or as recommended by a health care professional. It initially may be useful to take up to 6 capsules per day in divided doses for one week. The contents of the capsule may be emptied into juice or food, as needed.

INGREDIENTS: PRO-C™ SUPER ANTIOXIDANT FORMULA contains only the highest-quality USP grade magnesium ascorbate, USP grade calcium ascorbate, BioVin® grape extract (greater than 75% polyphenols, 93% OPC, greater than 3.5% anthocyanidins from grape pulp, skins, and seeds, and a small amount of trans resveratrol), green tea extract (95% min. polyphenols and 45% min. EGCG), l-glutathione (reduced), USP grade n-acetyl-l-cysteine, USP grade zinc ascorbate, r-(+)-lipoic acid, riboflavin-5′-phosphate, pyridoxal-5′-phosphate, l-selenomethionine, the smallest amounts of microcrystalline cellulose and silica in a vegetarian capsule.

PRO-C™ does not contain wheat, rye, oats, corn antigen, barley, gluten, soy, egg, dairy, yeast, sugar, sulfates, phosphates (other than coenzyme forms), fats, chlorides, GMOs, wax, preservatives, colorings, or artificial flavorings.

Click here to order PRO-C™.

SOURCES & RESOURCES

BOOKS

The Antioxidant Miracle. Lester Packer, PhD, and Carol Coleman. New York: John Wiley and Sons, 1999.

How to Live Longer and Feel Better. Dr. Linus Pauling. Corvallis, OR: Oregon State University Press, 2006.

ARTICLES

Review of Scientific Research on Oligomeric Proanthocyanidins (OPC)” (rev. 2017) by Hank Liers, PhD

“Vitamin C – An Amazing Nutrient” by Hank Liers, PhD

PRO-C™ and Ultimate Protector™ – Comparison by Hank Liers, PhD

“Antioxidant Cocktail Update: Part 1: The Take Home Message is to Use Antioxidant Supplements”
(An interview of Dr. Lester Packer by Richard A. Passwater, PhD, Whole Foods Magazine 1999)

ABSTRACTS

PRO-C™ / Vitamin C Abstracts

Catechin Abstracts

N-Acetyl-L-Cysteine (NAC) Abstracts

Lipoic Acid Abstracts

WEBSITES

Orthomolecular.org
(Therapeutic Nutrition Based Upon Biochemical Individuality)

PRODUCTS

PRO-C™Super Antioxidant Formula

Ultimate Protector™Nrf2 Activator Formula

OPC-C™

HPDI Vitamin C Products

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THE NEED FOR IODINE SUPPLEMENTATION

Dr. Hank Liers PhD iodine supplementationFred Liers PhD iodine supplementationThe Orthomolecular Medicine News Service (OMNS) published on June 12 “The Need for Iodine Supplementation.” We believe strongly in the need for iodine supplementation, especially given the fact that more than 90% of the US population is iodine deficient. For this reason we make available both Nascent Iodine and Lugol’s Iodine Solution 2 to our customers.

We present the full OMNS article (below), as a source of valuable information to our resellers and Creating Health Naturally readers. The factors contributing to massive-scale iodine deficiency remain virtually unchanged over decades. This has led to a greater need for educating health professionals and individuals about the critical importance of iodine supplementation.

Another useful article discussing the benefits of iodine supplementation was published August 2 by Dr. Mark Sircus, OMD: “Iodine, Thyroid and Low Body Temperature.” ~

The Need for Iodine Supplementation

by Wojciech Rychlik, PhD

(OMNS, June 12, 2017) Feeling tired, having low energy or depression, gaining weight, memory problems, having dry skin, dry mouth, or immune system issues? There is good chance your body needs iodine supplementation. Why iodine? Because this essential to human health element has been singled out as dangerous, for several obscure reasons, and it has been gradually eliminated from our diet, and even worse, replaced by its antagonist, bromine. This trend has been termed, iodophobia (1). It is a cause of widely occurring hypothyroidism in many developed countries.

Iodine: How Much?

Iodine deficiency is associated with (2, 3, 4):

  • Fibrocystic breast disease leading to breast cancer and stomach cancer
  • Goiter (enlarged thyroid)
  • Mental issues from reduced alertness, lowered IQ, autism to cretinism, lack of iodine for the fetus leads to cretinism, and in milder cases to autism and ADHD
  • Slow metabolism, leading to tiredness, sluggishness, fatigue, apathy, depression, and insomnia
  • Inability to produce saliva, dry skin, and lack of sweating
  • Lack of optimal detoxification, especially of bromides, fluorides, and heavy metals
  • Sensitivity to temperature changes, and cold hands and feet
  • Muscle pain, fibrosis, and fibromyalgia
  • Erectile dysfunction, infertility and miscarriages, and low sex drive
  • Overweight
  • High blood pressure, and increased incidence of heart attacks and strokes

The Food and Agriculture Organization (FAO) of the United Nations has published probable safe upper limits for dietary intake of iodine (5). They range from 150 micrograms (mcg) per kilogram (kg) per day in newborn infants to 30mcg/kg/day in adults. That is 2 milligrams (2,000 micrograms) daily for a 146-pound adult. The safe upper limit is higher during pregnancy and lactation (40 mcg/kg/day).

Treatments for Hypothyroidism

The simplest method to deal with an underactive thyroid is proper supplementation with iodine, called orthoiodosupplementation. If the thyroid is damaged, then supplementation with thyroid hormones, thyroxine (T4) and triiodothyronine (T3, the main biologically active hormone) may be necessary. Supplementation (6). with these hormones should be done under close supervision of a medical professional. However, supplementation with inorganic iodine is generally much safer, as the body “knows” how much T4 and T3 need to make. There are also drugs that change physiology of iodine metabolism, but this subject is beyond the scope of this article. Pharmaceutical companies pressure doctors to avoid inexpensive orthoiodosupplementation, so you won’t likely get a prescription for inexpensive Lugol’s solution from a mainstream practitioner.

One caveat to supplementation with iodine is the autoimmune illness called Hashimoto’s disease, or chronic lymphocytic thyroiditis, which is one of the potential causes of hypothyroidism. Unfortunately, when hypothyroidism is diagnosed, the possibility that Hashimoto’s disease underlies this condition has not always been properly tested. Therefore, Hashimoto’s disease has often been misdiagnosed. Doctors usually treat this condition with hormone replacement therapy, and some believe that excessive iodine intake may trigger it in susceptible people (7). Always ask your doctor if iodine supplements are right for you.

History of Iodine Usage and “Iodophobia”

This subject has been covered in detail by Dr. Guy E. Abraham (8,9,10). The iodine element was discovered in 1811 by B. Courtois. In 1850–1853 A. Chatin noted that goiter and cretinism are rare in geological zones rich in iodine and frequent where iodine is in short supply, and that goiter can be prevented by iodine supplementation. In 1895 E. Baumann proposed that iodine is the active element in the thyroid gland.

By the time Bauman identified large concentrations of iodine in the thyroid gland in 1895, pharmaceutical and apothecary preparations containing iodine, excluding thyroid extracts, were widely used as a panacea.

To quote Kelley: (11) “The variety of diseases for which iodine was prescribed in the early years is astonishing – paralysis, chorea, scrofula, lacrimal fistula, deafness, distortions of the spine, hip-joint disease, syphilis, acute inflammation, gout, gangrene, dropsy, carbuncles, whitlow, chilblains, burns, scalds, lupus, croup, catarrh, asthma, ulcers, and bronchitis – to mention only a few. Indeed, tincture of iodine, iodoform, or one of the iodides, was applied to almost every case that resisted the ordinary routine of practice; and between 1820 and 1840 there appeared a remarkable series of essays and monographs testifying to the extraordinary benefits to be achieved by this new and potent remedy.”

Unfortunately, these monographs have virtually disappeared from US medical libraries. In the mid-1800s, iodine treatments of some diseases called for ingestion of gram (1,000 mg) amounts per day. However, most treatments were from 5 to 50 mg daily. The recommended daily amount of iodine by Dr. G. E. Abraham is 0.1-0.3 ml Lugol containing 12.5-37.5 mg elemental iodine. This is the amount of iodine needed for whole body sufficiency, based on a recently reported iodine/iodide-loading test (12). Thyroid gland sufficiency for iodide is achieved with a lower dose.

Lugol's iodine supplementation

The first iodophobic authority emerged in early 1900s. Prof. T. Kochler reported that he suffered from overactive thyroid following ingestion of iodide (just a single individual case, not a statistical research study!) Despite this, the number of applications grew. In an International Index published in 1956, and devoted exclusively to iodine pharmaceuticals, no less than 1,700 approved iodine-containing products were listed. In 1948 Wolff and Chaikoff published that a serum inorganic iodide level at a concentration of 1 µM blocks (one micromolar) the synthesis of thyroid hormones, resulting in hypothyroidism and goiter in rats. But this conclusion was erroneous as they even did not measure thyroid hormones in the rats studied, and of course, hypothyroidism and goiter were not observed in those rats. Many organic forms of iodinated drugs were quite poisonous. Unfortunately, medical establishment did not make a distinction between organic and inorganic forms of iodine, and iodophobia became more popular.

Decades ago, iodine was added to bread so that one slice contained 150 mcg of iodine (the current recommended daily allowance). In the 1980s, bromine replaced iodine in bread. Since bromide is an antagonist to iodine (it is goitrogenic), it worsened iodine deficiency in the US. Moreover, a big push to remove salt from our diet (the only grocery item still supplemented with iodine) exacerbated the problem. The only developed nation that resisted iodophobia is Japan, statistically the healthiest and longest living nation on the planet. Their average daily consumption of iodine is around 5 mg, with various reports ranging from 1 mg to 18 mg. In a study of reported daily iodine intake versus total number of clinical symptoms, an intake of approximately 1 mg per day correlated with the lowest number of reported symptoms, that is, the highest level of health (13). Recent popularization of bromides in our food supplies likely increased this amount.

According to Dr. Abraham, (14) “proper amounts of iodine in the food supply should be considered one of a nation’s greatest assets. Removing iodine from the food supply is a major mistake. Supplying a daily intake of iodine sufficient for the whole body (100-400 times the RDA) gives protection against goitrogens and radioactive iodine/iodide fallout; improves immune functions, resulting in an adequate defense system against infection; decreases singlet oxygen formation which is the major cause of oxidative damage to DNA and macromolecules, resulting in an anticarcinogenic effect in every organ; results in a detoxifying effect by increasing urinary excretion of the toxic metals lead, mercury, cadmium, and aluminum, as well as the goitrogens fluoride and bromide; normalizes hormone receptor functions resulting in improved response to thyroid hormones both endogenous and exogenous; and results in better control of blood sugar in diabetic patients; stabilizes cardiac rhythm, obviating the need for the toxic sustained release form of iodine, amiodarone; and normalizes blood pressure without medication in hypertensive patients. Iodine deficiency is the major cause of cognitive impairment, worldwide.”

The Iodine-Cancer Connection

The body requires iodine to metabolize both omega-3 and omega-6 fatty acids. A substance called delta-iodolactone, a derivative of arachidonic acid, which is produced in the thyroid gland and breast tissue, prostate, colon, and the nervous system, is a regulator of a process called cellular apoptosis (“cell death”). Ascorbic acid is required to stimulate intracellular hydrogen peroxide synthesis that, in turn, provides the energy to make iodine free radicals necessary for this reaction. When the level of delta-iodolactone is high enough, the process of apoptosis can then kill cancer cells. (15)

Unfortunately, the recommended daily allowance (RDA) for iodine — about 150 mcg per day — will not allow delta-iodolactone to be efficiently formed in the thyroid gland. The thyroid requires higher iodine concentrations to efficiently produce it. Researchers have found that 100 times the RDA amount of iodine is optimal to produce delta-iodolactone. That equates to taking about 15 mg of iodine per day (15,16). These findings are important because they imply that there are some biochemical reactions that require much larger amounts of iodine than the current RDA. The mechanism by which delta-iodolactone induces cell death may be an important pathway for curing some types of cancer.

Forms of Iodine

Inorganic iodine exists in 6 oxidative states, from -1 to +7. The most reduced form (with most electrons) is iodide (I); an example is potassium iodide. The diatomic form of elemental iodine I2, has no electrical charge. Monoatomic iodine also has no electrical charge, but is unstable and highly reactive (free radical, labeled as an I with a dot, I* ). It can be produced by exposing I2 to ultraviolet light. Electric and magnetic fields won’t do it, as is sometimes incorrectly suggested. More oxidized forms of iodine are: hypoiodite (I+1), iodite (I+3), iodate (I+5), and periodate (I+7). The body’s metabolism may convert (reduce) these forms to biochemically available iodide, but at the cost of depleting its antioxidants. All forms of positively charged iodine are relatively poisonous, with established lethal doses (LD50) in the range of 35 to 2100 mg/kg. Elemental iodine (I2) and iodides (I) are non-poisonous. However, a bad “antiseptic” non-culinary taste of iodine (I2) suggests to our senses that this is not so good choice for supplementation.Nascent iodine supplementation

Despite that adverse taste, almost all the research on iodine supplementation has been done using Lugol’s Solution (17). The original solution is called 5% Lugol’s Iodine, but in reality it consists of 12.5% iodide/iodine or (I/[I3]) ions. Two drops of Lugol’s Solution (0.1 ml) contain 12.5 mg iodine/iodide mix. Iodine tablets that are a solid form of Lugol’s solution, were created to mask the taste and make the doses more precise for dietary supplementation.

I should mention a few points about Edgar Cayce’s atomidine. This famous visionary wrote several articles about the best form of iodine supplement (18). Some claim that this was iodine trichloride, but that cannot be true as this compound is toxic by ingestion and damaging to mucous membranes. It decomposes to ICl and poisonous gas Cl2 at 77 degrees C and also in water at room temperature (19). Most likely Cayce’s atomidine was simply a 1% iodine solution (I2) in 95% ethanol. I am surprised that there are educated people, even medical doctors who claim that “elemental monoatomic iodine” preparations (Atomidine, Nascent Iodine etc.) are the best forms of iodine supplements. May be it has something to do with efficient marketing? Elemental Iodine (I2) is soluble in glycerin. Replacement of ethanol with glycerol indeed makes these supplements more consumption-friendly, so they are sold by some vendors as superior products to Cayce’s ethanol-formulated one. Personally, I think glycerol-based I2 supplements are inferior to iodides; however, they are excellent antiseptics.

To defend the validity of Cayce’s vision, in thyroid, I ion and amino acid tyrosine react through a short intermediate step by forming monoatomic I* free radical (selenium and hydrogen peroxide are involved) to make monoiodotyrosine. Diiodotyrosine is formed analogical way, and finally, two of these molecules combine to produce thyroxine. All those steps are carried by the enzyme thyroid peroxidase, which is normally attached to the protein thyroglobulin. So, yes, monoatomic iodine I* exists in human bodies, and it directly reacts with tyrosine, but no, it wouldn’t be healthy to consume iodine free radicals as their high reactivity would prevent safe transport throughout the body.

In the mid-1930s the thyroid hormone thyroxine became available on the market. This was a blessing for people who had damaged their thyroid. Unfortunately, doctors started to prescribe this hormone to just about anybody with hypothyroidism, thinking that they can control better thyroid hormone levels than our bodies can. And, the “iodine is iodine, no matter what form” mentality became a dangerous trend, because most medical professionals do not fully appreciate the difference between the raw nutrient (iodine) and its product (hormone).

The pharmaceutical industry came up with lots of organic forms of iodine (NB: organic, meaning that iodine is bound to a carbon-atom-containing molecule and NOT meaning it’s grown in a pesticide-free environment), all relatively toxic and certainly not to be used without strict medical supervision. Only inorganic forms of iodine, I and I2, are safe for supplementation (20,21). Further, high doses of these supplements should still be supervised by your doctor.

Iodine Uses

Iodine plays critical role in human metabolism. Many researchers believe the RDA value of 150 mcg for iodine is too low, especially when this element is commonly substituted with competing element bromine. Therefore, the main use of iodine in dietary supplementation is to enable optimal thyroid function. There are a number of medical conditions where iodine is either essential or helpful. For best results, iodine/iodide should be supplemented with selenium, magnesium, copper (there is usually enough of it in tap water as copper is widely used in plumbing), vitamin B2 (riboflavin) and B3 (niacin). Ask your doctor before taking any iodine supplements, especially if you are on medications.

Elemental iodine (I2) is antibacterial and antifungal, so iodine or iodine/iodide solutions are commonly used topically to sterilize wounds, or internally to fight infections, such as vaginitis and sore throat, and also to sanitize drinking water. Because iodine is antibacterial, drinking it may cause friendly bacterial flora to suffer and result in diarrhea and stomach cramps (the same applies to Lugol’s solution, but to a lesser extent as it contains iodides as well).

Ingestion of iodides prevents the incorporation of destructive radioactive iodine into the body (mainly by the thyroid) in case of nuclear accidents. It also may help flushing already incorporated radioactive iodine from the thyroid, although too much iodine inhibits secretion of T4/T3 from the gland.

Common-Sense Cautions

Overdosing any of the iodine supplements can lead to swollen salivary glands, metallic aftertaste and skin rash and itching (that are usually due to rapid process of detoxification from heavy metals fluorides and bromides), faster heartbeat or palpitations and diarrhea. When supplementation is stopped, these symptoms will usually disappear quickly, often within one day. Iodine stabilizes thyroid hormone production, so it is an adaptogen, but in rare cases, such as acquired allergy to iodine (Hashimoto’s disease), it may actually misbalance it. In some cases, iodine supplementation can cause hypothyroidism, so it’s important to get checked by your doctor to make sure that your thyroid function is not worsened by supplementation. Some authors advising caution are Alan Christianson (22), Jeffrey Dach, (23) and Alan Gaby (24). Testing of levels of thyroid hormones along with testing and supplementation of mineral nutrients such as selenium, zinc, copper, magnesium calcium, and other trace minerals may prevent problems in cases where high doses of iodine/iodide might tend to cause Hashimoto’s disease. (23)

Inorganic Iodine Availability

The most common form of iodine supplement is Lugol’s solution (17). The original solution contains 5% of iodine and 10% iodide. Solid pill forms of Lugol’s solution are sold under several brand names. Potassium iodide (KI), my favorite iodine supplement, is available as tablets as well. Various products with kelp or other seaweed extracts contain iodides as well. Check the label when you buy as some of them are very diluted.

It is difficult to find inexpensive elemental iodine (I2) solution in alcohol. You can buy iodine crystals online and make the proper solution by yourself very easily (using either alcohol or glycerol). The monoatomic iodine concept is simply a marketing gimmick that has been created to inflate the price several fold. Note that if the monoatomic claims were really true, few would really want to drink free radicals, the only monoatomic form that exists. Iodine free radicals are not transported freely in our bodies because they are too reactive. Elemental iodine preparations, including iodine dissolved in glycerol, may be helpful products for external antiseptic use rather than a supplement.

Another form of iodine supplement includes a mixture of algae and thyroid extract in glycerin, water and ethanol. This is likely not harmful because it contains T3 and T4 only in very small amounts, and the recommended serving size is also small. Other complex formulae that contain elemental iodine are a useful antiseptic, but not a good supplement. Iodine trichloride should be avoided as a supplement because it is too toxic.(19)

Summary

The established RDA allowance for iodine (150 mcg/day) is inadequate for many individuals. In order to maintain optimum health, adults need 2-5 mg of iodide daily. Actually, this is in line with the upper safe limit of dietary intake of iodine established by FAO (30 mcg/kg/day). In case of a dysfunctional thyroid or other illnesses, such as fibrocystic breast disease or cancer, 15-50 mg daily may be needed. Ask your doctor about the alternatives to hormone therapy or taking iodine-containing organic drugs, because inexpensive orthoiodosupplementation would usually not be his/her first choice.

The best and safest form of iodine supplementation for a healthy adult is iodide. Iodides are naturally produced in larger quantities by various seaweeds.

Please consult your doctor about iodine supplementation, as in your particular case it may be contraindicated.

References:

1. Abraham GE. The History of Iodine in Medicine Part III: Thyroid Fixation and Medical Iodophobia. http://optimox.com/pics/Iodine/IOD-16/PUB_16.htm

2. Dommisse J. MD Best Kept Secret (2009) http://www.westonaprice.org/modern-diseases/best-kept-secret/#sthash.vdrKPaJw.dpuf

3. http://theiodineproject.webs.com/addadhdautism.htm

4. Hamza RT1, Hewedi DH, Sallam MT. (2013) Iodine deficiency in Egyptian autistic children and their mothers: relation to disease severity. Arch Med Res. 44(7):555-61. http://www.ncbi.nlm.nih.gov/pubmed/24120386

5. http://www.fao.org/docrep/004/y2809e/y2809e0i.htm

6. Abraham GE. The Concept of Orthoiodosupplementation and Its Clinical Implications. https://www.optimox.com/pics/Iodine/IOD-06/IOD_06.htm

7. http://www.webmd.com/women/hashimotos-thyroiditis-symptoms-causes-treatments#1

8. Abraham GE. The History of Iodine in Medicine Part I: From Discovery to Essentiality. http://optimox.com/pics/Iodine/IOD-14/PUB_14.htm

9. Abraham GE. The historical background of the Iodine Project. http://www.optimox.com/pics/Iodine/IOD-08/IOD_08.htm

10. Abraham GE. The History of Iodine in Medicine Part II: The Search for and the Discovery of Thyroid Hormones. http://optimox.com/pics/Iodine/IOD-15/PUB_15.htm

11. Kelly FC. “Iodine in medicine and pharmacy since its discovery , 1811-1961.” Proc R Soc Med, 1961; 54:831-836. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1869599/

12. Abraham GE. “The safe and effective implementation of orthoiodosupplementation in medical practice.” The Original Internist, 2004; 11(1):17-36. http://www.hakalalabs.com/Research/Abraham_OI_Mar04.pdf

13. Fallon Morell S. The Great Iodine Debate (2009) The WestonA. Price Foundation, http://www.westonaprice.org/modern-diseases/the-great-iodine-debate/

14. Abraham GE. The Wolff-Chaikoff Effect: Crying Wolf? https://www.optimox.com/pics/Iodine/IOD-04/IOD_04.html

15. Brownstein D. The Cancer-Iodine Connection, (2015) http://www.newsmax.com/Health/Dr-Brownstein/iodine-cancer-cell-death-fish-oil/2015/06/10/id/649877/

16. 6-Iodolactone, key mediator of antitumoral properties of iodine, M. Nava-Villalba, C. Aceves, (2014) Prostaglandins & Other Lipid Mediators 112, 27-33. https://www.researchgate.net/publication/263856609_6-Iodolactone_key_mediator_of_antitumoral_properties_of_iodine

17. Bacteriological Analytical Manual, R40 Lugol’s Iodine Solution (2001), http://www.fda.gov/Food/FoodScienceResearch/LaboratoryMethods/ucm062245.htm

18. Review of Atomidine, International Wellness Directory, http://www.mnwelldir.org/docs/reviews/atomidine.htm

19. Material safety data sheet, http://www.mnwelldir.org/docs/history/Iodine_Trichloride.pdf

20. Abraham GE. The historical background of the Iodine Project http://www.optimox.com/pics/Iodine/IOD-08/IOD_08.htm

21. Abraham GE and Brownstein D. A Rebuttal of Dr. Gaby’s Editorial on Iodine. (2005) Townsend Letter, The Examiner of Alternative Medicine, http://www.townsendletter.com/Oct2005/gabyrebuttal1005.htm

22. Christianson A. http://www.integrativehealthcare.com/why-i-discourage-high-dose-iodine/

23. Dach J. http://jeffreydachmd.com/iodine_is_safe

24. Gaby A. http://www.townsendletter.com/AugSept2005/gabyiodine0805.htm

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