Vitamin D in Health & Disease: A Response to Recent Articles

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Vitamin D, an Essential Neurohormone
Russell Jaffe, MD, Ph.D., CCN
Fellow, Health Studies Collegium
Adjunct Faculty, George Washington University Medical School

Vitamin D Measurement Meaning and Value

Known as vitamin D, cholecalciferol, is converted by the liver and kidneys into a potent neurohormone that regulates cell growth and mineral balance. While levels of vitamin D are commonly low, the common deficit in the community is not an indication of adequacy. Further, common digestive issues such as enteropathy result in impaired intestinal uptake of vitamin D. Enteropathy means atrophy or impaired repair of the intestinal lining.

A current understanding of the global literature on vitamin D and our clinical experience confirm the importance of adequate vitamin D to reduce risk, promote long-term health including a healthy skeleton. Vitamin D is not a drug to be used alone. Vitamin D does not treat disease. Vitamin D is not a single agent suitable for pharmaceutical like double blind trials. A recent such clinical study of high dose vitamin D alone did not find heart healthy benefits.

In contrast, we include vitamin D as an important member of the essential or conditionally essential nutrients. Vitamin D improves cell communication at the molecular level. Vitamin D assures enough but not too many cells of each kind in their places within the body. Adequate vitamin D is one of a variety of essential factors needed for healthy bones, healthy cells and lifelong lower risk of chronic illness.

There are 20 essential nutrients needed for healthy bone formation and renewal. Vitamins are like members of an orchestra. Many different instruments are needed to perform a symphony properly. No single instrument can do what the interdependent musicians can do. By analogy, we find that when adequate vitamin D is taken in to achieve the least risk, best outcome range and combined with other essential nutrients then synergies of benefits emerge. Risks reduce. Quality of life improves.

A recent article from the New York Times presented a conclusion that vitamin D testing is rarely needed and that the low levels of most Americans are sufficient so that more than modest daily supplements are not needed. In essence the message in the newspaper is ‘take none a day’. The Health Studies Collegium Predictive Biomarkers working group analysis reaches the opposite conclusion.

Perspective is important. If you look at the world with the goal of treating or fighting diseases then you can conclude the vitamin D fails as a single agent to treat symptoms of disease. In contrast, if you look at the world with the goal of promoting health or reducing risks so that disease can be avoided or reversed then vitamin D is an essential member of the team of required nutrients for cell and system health.

While access to information expands geometrically, many people who have learned a particular perspective become selective about what they let into their personal reality. ‘Hardening of the categories’ is a way of understanding how otherwise intelligent, educated and engaged people selectively let in information that agrees with their view and exclude information that does not agree. In regard to biomedical sciences this is an increasing issue of concern. The curriculum of most medical schools is so heavily focused on disease treatments that health promotion and systems biology are increasingly excluded from the classrooms and the professional continuing education society meetings. Nature, nurture and wholeness have largely been replaced in professional education by knowledge of medications that treat specific ills. Physiology has been nudged aside to make more room for pharmacology. Most physicians believe they are doing what is best for the person for whom they care.

Too often the cause is left unknown while the signs and symptoms of disease are the primary focus of health professionals. Absence of disease is different from high-level health. Too often absence of evidence is taken as evidence of absence. Lack of large scale long term studies of combinations of essential nutrients is often taken as reason to restrict intake or lower the ‘safe upper limit’ for nutrients from vitamins to minerals to cofactors to essential fats, aminoacids and dietary fiber.

Based on the Health Studies Collegium review of the world literature, we suggest the best outcome least risk goal range for vitamin D is 50-80 ng/ml. The typical American has a value of less than 20. Of note, few studies have had enough subjects with levels in the goal range. This means possible benefits were not observed because people were not dosed to levels in the least risk, best outcome range. The difference substantially alters cancer, cardiovascular, autoimmune and inflammatory repair deficit risks. The preferred form of vitamin D to be measured is 25-OH Cholecalciferol (‘25 hydroxy D’).

Each of the issues raised in the recent news article about vitamin D are addressed below. In many cases, the news report did not include important, well-documented and widely reported beneficial effects of adequate vitamin D when used in combination with other nutrients. As happens commonly in news reports, vitamin D is viewed and evaluated as a drug rather than an essential neurohormone.

1. “Millions of people are popping supplements in the belief that vitamin D can help turn back depression, fatigue, muscle weakness, even heart disease or cancer. In fact, there has never been widely accepted evidence that vitamin D is helpful in preventing or treating any of those conditions.”The frame of this comment makes vitamin D a pharmaceutical. Based on inappropriate pharmaceutical criteria the writer finds inadequate large-scale long-term studies to allow a substantial degree of scientific agreement in support of vitamin D as a drug.Vitamin D is a neurohormone that plays many functional roles in cell regulation. None of these functions is a treatment for a disease. Many of these functions are essential for cell division, communication and mineral balance within cells. In all cases vitamin D acts as a member of a family of essential nutrients rather than a single agent.

2.One study with 5,108 participants, published this month in JAMA Cardiology, found that vitamin D did not prevent heart attacks.” and Another study found no cancer reduction at four years on vitamin D3 plus calcium. 2017 Mar 28;317(12):1234-1243. doi: 10.1001/jama.2017.2115.Testing the use of high dose vitamin D alone or in combination with calcium makes sense if it is a drug candidate; it makes no sense given the interdependent nature of this neurohormone in cell and animal physiology.In essence, vitamin D connects two adjacent cells. It is important in regulation of cell division. As a neurohormone, vitamin D tells the cells that a balance has been reached and only replacement of cells that wear out are needed. Lack of vitamin D can cause cells to over grow and increases cancer risks. Multiple nutrients or cofactors are all needed to observe the interactive and interdependent benefits of vitamin D at the molecular and cellular level.Other recent studies ( suggest an urgent need for investigation of the synergies of all needed factors including vitamin D and cardiovascular risks.

3. “Labs performing these tests are reporting perfectly normal levels of vitamin D — 20 to 30 nanograms per milliliter of blood — as “insufficient. As a consequence, millions of healthy people think they have a deficiency, and some are taking supplemental doses so high they can be dangerous, causing poor appetite, nausea and vomiting.”While pharmacologic doses of a synthetic analogue (vitamin D2) have raised questions about potential toxicity, the healthy cholecalciferol is not harmful according to both (cholecalciferol toxicity, human) as well as a similar search through addition, low levels in a population are statistically normal. Too often this statistical artifact is confused with adequate or healthy ‘normal’. While the usual and thus statistically normal range for vitamin D is a third of what we suggest is needed for best outcomes and least risks (see below).

4. “Vitamin D overdoses also can lead to weakness, frequent urination and kidney problems.”Actually it is the opposite: until there are kidney problems, uptake and conversion of healthy vitamin D3 precursors are self-regulated. When kidney function fails then issues arrive as a result, rather than cause of kidney damage.

5. “In 2007, Dr. Holick published a paper in The New England Journal of Medicine asserting that vitamin D levels now considered normal — 21 to 29 nanograms per milliliter of blood — were linked to an increased risk of cancer, autoimmune disease, diabetes, schizophrenia, depression, poor lung capacity and wheezing…. In 2011, a committee of the Endocrine Society, headed by Dr. Holick, came out with a recommendation that vitamin D levels be at least 30 nanograms per milliliter, which meant that most people were vitamin D deficient.”In personal communication, Dr Holick affirms that scientists are only slowly distinguishing the safety of nature’s forms of essential nutrients in contrast to synthetic analogues that in our experience do not work or the use of single nutrients as drugs when they are essential members of ‘team health’.Since 2011 more and more data supports a goal range or optimum range or least risk range of 50-80 ng/ml.

6. “…when the Institute of Medicine report proved critical of the vitamin D craze, Dr. Fairfield started telling healthy patients there was no reason for them to be tested. Many did not want to hear that advice. ‘People were used to vitamin D monitoring, like with cholesterol,’ Dr. Fairfield said. ‘They wanted to know what their number is.Although Dr. Fairfield stopped routine vitamin D testing, many others have not. Becky Rosen, 64, a nurse who is director of clinical services at a home health agency in Brunswick, ME., had a physical exam four years ago and was told she needed a vitamin D test. She declined.

Her next physical exam was in February, with a different doctor. Once again, the doctor wanted to test her vitamin D level. ‘I said, ‘I don’t think I need it,’ Ms. Rosen said. The doctor persisted, explaining that Maine is so far north that people may not be exposed to enough sunlight. Once again, Ms. Rosen politely but firmly declined.But she is a special patient: Her husband, Dr. Rosen, helped write the Institute of Medicine report that was critical of vitamin D supplements. ‘I can see other people getting persuaded,’ Ms. Rosen said.”

So ends the article in a prominent newspaper. Looking strictly from the lens of pharmaceutical sciences, the article and its conclusions are consistent.

As pointed out throughout this response, vitamin D is an essential neurohormone. With the best outcome, least risk range of 50-80 ng/ml it is our suggestion that enough vitamin D be taken to achieve the best outcome range. For the average American, this means tripling their vitamin D level.

Since we know the best outcome target range, functional integrative and comprehensive care practitioners guide therapy based on achieving best outcome least risk values or ranges of all predictive biomarkers of which vitamin D is one of eight. The predictive biomarkers cover epigenetics, the 92% of lifetime health and illness determined by habits of daily living while only 8% is genetic variance.

This is one of a series of articles that report on a recent scientific study in which an essential nutrients most common commercial form is used at high doses to treat a disease or to determine if such a regimen reduces risk in a specific group of people.Examples include the use of high dose beta-carotene rather than mixed carotenoids in people with a long history of smoking. Our experience is that the mixed natural forms of nutrients are consistently much safer than synthetic work-a-likes that in our experience do not work or have unexpected toxicities usually by unbalancing the family of compounds of which they are members.Another example is 800 IU of synthetic d-alpha tocopherol had a negative benefit in regard to heart and cardiovascular risks. Given that only the gamma form of vitamin E helps the heart, it is all too predictable that the higher the level of d-alpha the lower by dilution is the gamma form that is the only heart healthy form of vitamin E. Overlooked in both the scientific reports and news articles that flowed from it was the substantial work of the Shute brothers in Canada. For decades that followed large numbers of people who agreed to take high doses of natural vitamin E, from 1600-3600 IU. Reported outcomes included reduced cardiovascular diseases including stroke. Using nature’s mixed natural forms marked reduction in cardiovascular risks and enhancement in heart health were reported in the peer-reviewed scientific literature.Another example are multiple recent reports, often metaanalyses, that calcium supplementation or calcium with vitamin D is not sufficient to reduce osteopenia and osteoporosis risk; fracture risk reduction and bone density enhancement. In contrast, our comprehensive bone renewal program showed consistent new bone formation by DEXA after just two years of best efforts. This included supplementation with all 20 essential bone nutrients as part of an age and interests appropriate healthy life style.

My colleague Susan Brown and I published about this issue over a decade ago (Jaffe, R. Brown S. Acid-Alkaline balance and its Effect on Bone Health. Intl J Integrative Med 2000; 2(6): 7-18.)
We are in the process of publishing a more current review of the subject based on this physiology before pharmacology approach. Pre-prints available on request (

Others[1] have called attention to the same issue. Essential and conditionally essential nutrients are not single purpose medications. They are required for a high quality of life with low disease risks. They are needed in amounts based on biochemical individuality. Usually, too little and too much are unhealthy. Just right for the individual is associated with better physical renewal, flexibility, sleep, relationships and productivity.

In summary, it is safer and more effective to take teams of essential or conditionally essential nutrients sufficient to reach a best outcome goal value or range for each person’s validated predictive biomarker tests. The documented personalized proactive predictive primary prevention tests are just eight with vitamin D being one. The eight predictive biomarker tests cover all of epigenetics; all of the influences of habits of daily living on quality of life. According to the National institutes of Health, 92% of lifetime health quality and disease risk is epigenetic while 8% is genetic. While vitamins are not drugs they are required for health today and physiologic renewal tomorrow. Current scientific knowledge can guide individual and population healthcare based on physiology before pharmacology using incentives for healthier habits of daily living in age and culturally appropriate ways.

[1] Responses to the Institute of Medicine’s report on vitamin D and calcium along with selected papers that seemed to help steer the IOM’s decision

Prepared by William B. Grant, Ph.D.,

IOM (Institute of Medicine). 2011. Dietary Reference Intakes for Calcium and

Vitamin D. Washington, DC: The National Academies Press.

A summary of the IOM report

  1. Institute of Medicine (US) Committee to Review Dietary Reference Intakes forVitamin Dand Calcium; Ross AC, Taylor CL, Yaktine AL, Del Valle HB, editors. Dietary Reference Intakes for Calcium and Vitamin D. Washington (DC): National Academies Press (US); 2011.
  2. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA. The 2011 report on dietary reference intakes for calcium and vitamin D from theInstituteof Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011 Jan;96(1):53-8.
  3. Ross AC, Manson JE, Abrams SA, Aloia JF, Brannon PM, Clinton SK, Durazo-Arvizu RA, Gallagher JC, Gallo RL, Jones G, Kovacs CS, Mayne ST, Rosen CJ, Shapses SA. The 2011 dietary reference intakes for calcium and vitamin d: what dietetics practitioners need to know.J Am Diet Assoc. 2011 Apr;111(4):524-7.