For many years various nutrients have been touted as beneficial in amounts well in excess of their current RDA. Back in the 1970s Linus Pauling, PhD touted high doses of vitamin C as a treatment for everything from the common cold to preventing and even treating colon cancer. Eventually, researched showed vitamin C well in excess of the RDA for vitamin C were not beneficial and could also have adverse or toxic effects (1). As that fad died out other antioxidant nutrients became popular fads. vitamin E was being touted as an antioxidant that could help prevent everything from atherosclerosis and heart attacks to cancer and even slow the aging process. Then beta-carotene was touted as another antioxidant nutrient that could help prevent cancer and other ills. Eventually the enthusiasm for large doses of all these nutrients and many more when taken well in excess of what the body required according the RDAs were all shown to lack efficacy but in most cases to produce toxic effects including an increased risk of cancer, especially lung cancer in smokers for beta-carotene (2), or dying from all causes combined in the case of vitamin E supplements well in excess of the RDA (3).The most recent example of what appears to be irrational exuberance for a vitamin supplement involves high doses of vitamin D. Michael Holick, MD at Boston University perhaps is playing the role of top guru. Dr. Holick has claimed the RDA for vitamin D is inadequate. According to Dr. Holick vitamin D deficiency is pandemic. He claims an insufficient level of vitamin D plays a role in causing not only metabolic bone disease (osteoporosis in adults and rickets in children), but also increases the risk of developing preeclampsia, common deadly cancers, schizophrenia, infectious diseases including TB and influenza, autoimmune diseases including type 1 diabetes and multiple sclerosis, type 2 diabetes, stroke and heart disease.[https://www.bumc.bu.edu/busm/profile/michael-holick/]. There is no doubt low tissue stores of vitamin D leads to not only weakened bones and may well impair other tissues too. However, Dr. Holick criticism of the RDA and claims the recommended intake for vitamin D was far too low to maintain optimal tissue stores to prevent numerous illnesses is questionable (4).Who is Deficient in Vitamin D?Well, this depends on how one determines what an adequate level of 25-OH-D (a metabolite of vitamin D that best reflects the body’s store of vitamin D) is.According to Dr. Holick, people need about 50,000 IUs per week of vitamin D orally to maintain optimal tissue levels of 25-OH-D (5). Dr. Holick suggested an “optimal” level of 25-OH-D is 100-150nmol/L with a “sufficient” level of 25-OH-D being 75-99nmol/L or 30ng/ml to <40ng/ml (6). The RDA of 400IU for those under 70 and 600IU for those 70y and older is inadequate to maintain such high tissue stores of 25-OH-D in adults who are not getting a lot of sun exposure without sunscreen.A study examined the impact of vitamin D supplements of 400, 4000 and 10,000 IUs on 311 subjects 55 to 70y who’s initial 25-OH-D levels of 30 to 125nmol/L were at least “sufficient”. They were randomized to receive vitamin D supplementation for 3 years to determine if even higher levels of 25-OH-D improved bone density and/or strength. Study subjects were scanned on high?resolution peripheral quantitative computed tomography (HR?pQCT) to measure total volumetric BMD at baseline and after 6, 12, 24 and 36 months of vitamin D supplementation. Balance, physical function, and clinical biochemistry parameters were also assessed. 25-OH-D levels of 76.3, 76.7, and 77.4 nmol/L were observed in those receiving only the 400IU RDA level supplements. For those receiving 4000IU daily 25-OH-D levels increased to 81.3, 115.3, and 132.2; and for those receiving 10,000IUs daily 78.4, 188.0, and 144.4 (10,000). There were significant time?by?treatment and group?by?sex interactions for BMD at the radius (p=0.002) and tibia (p=0.005). Supplemental vitamin D of 4000 or 10,000 IU compared to 400 IU resulted in significantly greater BMD losses in females. After three years, women receiving 400IU lost an average of 1.8% of their BMD. Those receiving 4000IUs lost an average of 3.8% and those receiving 10,000IUs lost an average of 5.5% of their initial BMD. In men the average loss of BMD with the RDA supplement (400IU) was 0.9%. Men receiving 4000IU supplemental vitamin D lost 1.3% of their initial BMD and for men receiving the highest supplemental vitamin D (10,000IU) BMD declined on average 1.9% at the radius. At the tibia, losses in BMD were smaller, but followed a similar trend. BMD trends were similar for both men and women they were not statistically significant for the men.Vitamin D supplementation with 4000 or 10,000 IU, compared with the RDA of 400 IU daily, resulted in greater losses of BMD over three years in healthy vitamin D?sufficient females, with similar but not statistically significant trends in men. The authors conclude: “These results are clinically relevant, as vitamin D supplementation is widely administered to postmenopausal females for osteoporosis prevention. Our findings do not support a benefit of high?dose vitamin D supplementation for bone health and raise the possibility of harm for females” (7).Bottom Line: The results of this study and others suggests those taking high doses of vitamin D well in excess of current RDA levels actually tend to have more bone fractures, fall more frequently, sleep less well, and die sooner than those with lower levels. For those with a 25-OH-D level of 20 ng/mL, it now appears likely they will not benefit from taking a supplement. For those with a 25-OH-D levels above 35 ng/ml, it now seems likely they will see more rapid loss of BMD and other ill effects from taking supplements to push their 25-OH-D levels even higher. A 25-OH-D level of at least 20 ng/mL should be considered "sufficient”. It now appears Dr. Holick’s enthusiasm for high-dose vitamin D supplements is likely misguided.By James J. Kenney, PhD, FACNReferences:

1. https://www.medscape.com/answers/819426-102384/what-are-the-signs-and-symptoms-of-vitamin-c-toxicity
2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6636175/
3. https://ebn.bmj.com/content/8/3/82
4. https://khn.org/news/how-michael-holick-sold-america-on-vitamin-d-and-profited
5. Holick MF: Vitamin D deficiency. N Engl J Med. 2007, 357: 266-281. 10.1056/NEJMra070553
6. https://www.hindawi.com/journals/dm/2015/864370
7. https://asbmr.onlinelibrary.wiley.com/doi/abs/10.1002/jbmr.4152