FOR IMMEDIATE RELEASE
Orthomolecular Medicine News Service, April 15, 2021

Vitamins and minerals for lowering risk of disease: Adding to the evidence.

by Robert G. Smith, PhD, Associate Editor

(OMNS Apr 15, 2021) There is still a huge suppression of information about the vitamin C, D, magnesium, zinc, and selenium protocol for reducing risk of Covid-19. [1] For example, this suppression has been perpetuated by doctors who didn't study nutrition in medical school, and government agencies that have promoted nutrient supplements only to prevent outright deficiencies like scurvy. People are saying this protocol is not effective because there are no randomized, double-blind studies showing its efficacy. That type of study has not been done for many reasons, including the prevailing scientific method that only studies one nutrient at a time, the paucity of funding available for testing nutrient protocols -- since most funding for medical treatments comes from drug companies, and the politics of the medical establishment. [1] It would be helpful to organize a properly-done study that tests the efficacy of a supplementation protocol to prevent infection, hospitalization, and mortality. If the doses that we know are safe could be shown to be effective in a randomized double-blind study, then prophylactic supplementation could be supported by the authorities. How can the Orthomolecular Medicine field organize such a study? With the coronavirus evolving into new variants, such a study would continue to be helpful for saving lives. And a properly organized study focused on adequate levels of essential nutrients can also test for reduction in risk for a wide variety of other diseases.

Efficacy

Clinical studies, case histories, and direct experience over many decades have shown the importance of adequate doses of essential nutrients in preventing and reversing disease. This needs to come into the public spotlight in the current COVID-19 pandemic. Nutrition therapy is firmly based on sound biological principles and established biochemical knowledge accumulated over the last century. For example, it is known that adequate doses of vitamin C, higher than the RDA, can prevent viral infection, and further can ameliorate recovery from infection and provide many other health benefits. [1-56] In severe pneumonia caused by COVID-19 infection, vitamin C levels can drop precipitously, in effect causing local scurvy. [1-4] Vitamin D is essential for a wide variety of hormone-like signaling in the body, and beyond its function in supporting bone health is necessary for a strong immune system. Vitamin D is known from a variety of studies to reduce the risk of viral infections such as flu and common cold, as well as COVID-19, and low levels of vitamin D are known to be a risk for worse hospital outcomes. [54-68] Magnesium is essential for proper functioning of hundreds of biochemical pathways in the body, including many of those related to the function of vitamin D in the immune system and recovery from illness. [69-73] Zinc and selenium are known to be important in the recovery from inflammation, infection, and sepsis. [55, 74, 75] And a protocol that includes all of these essential nutrients and others known to be important for health is likely to provide even greater synergistic benefits in supporting health and lowering the risk of disease. [7-9, 23-25, 58, 76]

Safety

Although clinically effective doses of vitamins and minerals are higher than the RDA, they are known to be safe for the overwhelming majority of the adult population. Vitamin C taken a dose of 1000-3000 mg per day in divided doses is safe and well tolerated by most people. [6,20] Vitamin D taken at a dose of 5,000 - 10,000 IU per day is safe. [58] Magnesium at a dose of 400 - 600 mg per day in a readily absorbable form is safe for individuals except those with severely impaired kidney function, heart block, bowel obstruction, and myasthenia gravis. [73] Zinc is safe at a dose of 20 - 50 mg per day in most individuals. Selenium is safe at a dose of 200 mcg per day in most individuals. A protocol comprising at least these doses of essential nutrients can help to prevent and reverse viral infections.

How it's done

Although randomized double-blind interventional studies are required to test the safety and efficacy of a potential new drug in lowering risk of infection, [77] a study of a nutritional protocol comprising essential nutrients differs in several ways. First, since everyone requires all the essential nutrients, our bodies already contain some of each nutrient. Therefore it is necessary to take into account the existing levels and adjust doses accordingly for each individual in the study. Individuals who have adequate levels will likely not improve much, because the interventional doses will not decrease their risk as much as it will for others who are deficient. Also, the most effective protocols include several essential nutrients because they are symbiotic, so studies of one nutrient (as performed for drugs) will miss a large portion of the full efficacy. Thus the doses of all the nutrients in a study must be varied to test their combinations. Further, the absorption of nutrients from the diet or a specific protocol of supplements may differ between individuals for a variety of reasons, including lifestyle, age, normal diet, and genetic factors. Therefore, the study must determine the existing nutrient levels of each individual before and as a result of taking the vitamin and mineral protocol. [78,79]

Second, many studies of essential nutrients that are not performed according to a randomized double-blind (RCT) protocol, for example, environmental or epidemiological studies, are often observational. These do not comprise an interventional treatment, but carefully study the effect of an essential nutrient in the diet, taking into account other factors that might affect a risk. An observational study can determine the association of reduction in risk with living in a specific environment where a nutrient is present, for example, the benefit of living at a sunny equatorial latitude where vitamin D levels are generally higher. Although observational studies are often larger and more diverse, comprising more individuals and different environments or countries, they are widely considered not to be a valid test of a treatment's efficacy, because no treatment is given and causality ostensibly cannot be determined.

However, observational studies can build on known biochemical knowledge to provide a likely cause for an observed effect. For example, since both vitamin C and vitamin D are known to be essential for the immune system, this supports findings of observational studies that these vitamins in adequate doses can lower risk of infection and ameliorate recovery. This knowledge also supports studies that show deficiencies of vitamin C and D, magnesium, zinc, and selenium in patients with severe pneumonia and/or sepsis. [1-75] Moreover, observational studies can extend the scientific knowledge relevant to a randomized double-blind study. For example, groups included in a RCT can be determined according to prior knowledge gathered from observational studies -- in essence, testing whether the association proven by the wider observational studies is incidental or causal.

Ethics

Another important difference between studies of essential nutrients and drugs is that since the nutrients are known to be essential, it is unethical to allow individuals in a study to succumb to nutrient depletion. Therefore, any benefit of essential nutrients shown by prior studies must be taken into account. For example, the control group in a RCT that studies the effect of essential nutrients must receive at least the minimum daily intakes, from their normal diet and/or from supplementation, that are known to be essential. However, after testing of nutrient levels, each individual could in principle give permission to be blindly assigned into a control group that does not receive the highest doses. But those who have read up on optimal nutrient levels would likely not choose to be included in such a study that might assign lower nutrient levels. Therefore, an observational study that does not assign doses, but merely measures their levels, may be considered the most ethical. The exact methods used to set up the different control and treated groups, and the doses provided will require careful consideration.

Other conditions

Further, since excellent nutrition is widely known to enhance health, a study that tests the effect of a nutritional protocol on preventing infection could usefully be extended beyond its original intent. For example, if performed over a longer duration than 12 months, it could verify the doses required to reduce the risk of a variety of progressive diseases associated with aging, body mass index, or diet. Although small doses of essential nutrients are known to be beneficial, an interventional study testing different doses could be extended to test what reduction in risk of cardiovascular disease, diabetes, or cancer can be obtained with adequate, safe, higher doses.

The study must:

1. Test the efficacy of the protocol using a dosing (i.e. interventional) paradigm for lowering risk of infection, need for hospitalization, and mortality. This is compatible with other forms of protection, e.g. vaccination, social distancing, and wearing masks.
2. Be a double-blind, randomized controlled trial (RCT) study with several different dosage combinations, along with placebo controls.
3. Measure and take into account the existing vitamin and mineral levels in the incoming study groups.
4. Be of sufficient duration, preferably 6-12 months or more, that any incoming deficiencies of vitamins and minerals can be relieved. Notably, both vitamin D and magnesium are known to require in some cases several months of supplementation to achieve adequate levels when an individual is deficient.
5. Be run with a sufficient number of individuals to show statistical significance.
6. Include groups that differ in their status with respect to the condition of disease. Some groups should be in excellent health without symptoms, but other groups should include individuals with a variety of known risk factors. For example, groups comprising elderly or obese individuals, or groups that have symptoms, or who have been hospitalized.
7. Test groups of several different populations, including different ethnic groups, in different countries, different geographic regions and climates.
8. Include groups that have not been vaccinated for Covid-19.
9. Check infection rates for different variants of the coronavirus.

How to organize

Since large clinical studies are generally very expensive, the study could start with several small groups comprising, for example, several hundred individuals. It could be funded by a public online funding campaign that is set up and publicized by a consortium of integrative and orthomolecular medical organizations. [e.g. 25, 80-83] Its methodology can be checked and verified by an independent group of nutrition-aware medical researchers who have experience from involvement in previous studies. The health status of participants will need to be checked upon entry by a team of medical professionals, to test existing nutrient levels and identify risk factors and potential disease conditions. An online website and phone and email hotlines can provide the support needed to answer questions about doses and complications. A sub-committee of integrative and orthomolecular medicine scientists and doctors can implement an outreach program to publicize the study for enrollment and fund-raising. It might even be possible to allow individuals to sign up for the study (as one category of included groups) after they have supported the study by donating funds at an online website.

Conclusion

The widespread use of a vitamin and mineral protocol can lower risk of virus infection and pneumonia, and can assist in stopping the pandemic. This can provide a tremendous boost in health worldwide. The protocol is safe. It does not require the type of clinical trial that establishes efficacy and safety of a new drug. Yet a double-blind randomized controlled clinical trial seems essential -- if only to silence the doubt that currently exists about nutrition therapy. With a sound plan for organizing and funding a trial of this type of nutrition therapy, we can proceed to test its efficacy in fighting a variety of diseases, including viral infections.

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Albert G. B. Amoa, MB.Ch.B, Ph.D. (Ghana)
Seth Ayettey, M.B., Ch.B., Ph.D. (Ghana)
Ilyès Baghli, M.D. (Algeria)
Ian Brighthope, MBBS, FACNEM (Australia)
Gilbert Henri Crussol, D.M.D. (Spain)
Carolyn Dean, M.D., N.D. (USA)
Ian Dettman, Ph.D. (Australia)
Damien Downing, M.B.B.S., M.R.S.B. (United Kingdom)
Ron Ehrlich, B.D.S. (Australia)
Hugo Galindo, M.D. (Colombia)
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)
Claus Hancke, MD, FACAM (Denmark)
Tonya S. Heyman, M.D. (USA)
Suzanne Humphries, M.D. (USA)
Ron Hunninghake, M.D. (USA)
Bo H. Jonsson, M.D., Ph.D. (Sweden)
Felix I. D. Konotey-Ahulu, MD, FRCP, DTMH (Ghana)
Jeffrey J. Kotulski, D.O. (USA)
Peter H. Lauda, M.D. (Austria)
Thomas Levy, M.D., J.D. (USA)
Alan Lien, Ph.D. (Taiwan)
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)
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)
Zhiyong Peng, M.D. (China)
Isabella Akyinbah Quakyi, Ph.D. (Ghana)
Selvam Rengasamy, MBBS, FRCOG (Malaysia)
Jeffrey A. Ruterbusch, D.O. (USA)
Gert E. Schuitemaker, Ph.D. (Netherlands)
T.E. Gabriel Stewart, M.B.B.CH. (Ireland)
Thomas L. Taxman, M.D. (USA)
Jagan Nathan Vamanan, M.D. (India)
Garry Vickar, M.D. (USA)
Ken Walker, M.D. (Canada)
Raymond Yuen, MBBS, MMed (Singapore)
Anne Zauderer, D.C. (USA)

Andrew W. Saul, Ph.D. (USA), Editor-In-Chief
Associate Editor: Robert G. Smith, Ph.D. (USA)
Editor, Japanese Edition: Atsuo Yanagisawa, M.D., Ph.D. (Japan)
Editor, Chinese Edition: Richard Cheng, M.D., Ph.D. (USA)
Editor, French Edition: Vladimir Arianoff, M.D. (Belgium)
Editor, Norwegian Edition: Dag Viljen Poleszynski, Ph.D. (Norway)
Editor, Arabic Edition: Moustafa Kamel, R.Ph, P.G.C.M (Egypt)
Editor, Korean Edition: Hyoungjoo Shin, M.D. (South Korea)
Assistant Editor: Helen Saul Case, M.S. (USA)
Technology Editor: Michael S. Stewart, B.Sc.C.S. (USA)
Legal Consultant: Jason M. Saul, JD (USA)

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