By Joseph E. Scherger, MD, MPH

Core Faculty, Eisenhower Health Family Medicine, Residency Program, Eisenhower Health Center, La Quinta, CA; Clinical Professor, Keck School of Medicine, University of Southern California, Los Angeles

Dr. Scherger reports no financial relationships relevant to this field of study.

SYNOPSIS: Blood levels of vitamin D in the mid-normal range have been associated with several benefits, including healthy bones and better outcomes with COVID-19 infections. A recent study revealed vitamin D levels higher than normal from high-dose supplementation are harmful to bone health.

SOURCE: Billington EO, Burt LA, Rose MS, et al. Safety of high-dose vitamin D supplementation: Secondary analysis of a randomized controlled trial. J Clin Endocrinol Metab 2020;105:dgz212.

A randomized, controlled trial conducted at the University of Calgary, Alberta, Canada, included 373 healthy adults ages 55 to 70 years. Subjects received vitamin D supplements over three years. Participants were randomly assigned to taking vitamin D3 at 400 IU, 4,000 IU, or 10,000 IU. Researchers initiated calcium supplementation if the dietary calcium was less than 1,200 mg/day.

Each dose carried a similar safety profile. Those who took the higher dosages of vitamin D3 exhibited greater loss of total bone mineral density. Investigators observed this negative outcome started in participants who were taking daily doses of vitamin D3 of 4,000 IU and higher. Taking 10,000 IU of vitamin D3 was harmful to bone health.

COMMENTARY

Vitamin D is a prohormone that affects many areas of the body, including bone health, cell growth, neuromuscular and immune function, and inflammation severity.1-3 Dietary sources of vitamin D are limited. Most of the vitamin is acquired through the skin by the interaction of ultraviolet light with cholesterol. Several factors result in humans absorbing less vitamin D than our evolutionary ancestors, including living indoors, sun protection, eating less organ meats, and living longer. The World Health Organization and others have cited a widespread deficiency in vitamin D.4,5 Epidemiologic evidence suggests low vitamin D levels may cause premature aging, autoimmune disease, cancer, and cardiovascular disease.2,3,6 In one study, the authors observed those with the lowest vitamin D levels died more often.7 Recent evidence shows lower vitamin D levels are associated with a worse outcome from COVID-19 infection.8 Evolution is based on the successful reproduction of the species. I tell seniors that evolution does not care how long humans live. Aging skin does not convert sunlight to vitamin D as well as younger skin.9,10

The paradox of vitamin D is that despite its many health benefits, randomized, controlled trials have failed to show a beneficial effect of testing for vitamin D levels and supplementation in the general population.1,11-12 These have been single-variable studies and may fail to capture the benefit of vitamin D supplementation. Often unrealistic outcomes are tested for vitamin D supplementation (e.g., fracture prevention).

The “normal” range of vitamin D in the body is considered to be between 30 ng/mL and 100 ng/mL. Some suggest levels as low as 20 ng/mL are safe. The National Academy of Medicine recommends a daily intake of 600 IU for young adults and 800 IU for seniors.1 The Endocrine Society suggests supplementation of 1,500 IU to 2,000 IU of vitamin D3 daily, which could result in optimal vitamin D levels in the blood (i.e., 40 ng/mL to 60 ng/mL).13 This is what I recommend for adult patients, especially seniors.

New evidence for vitamin D and its importance seems to come out daily. I recommend keeping an eye out for more information about this important supplement, especially for older patients.

REFERENCES

  1. National Institutes of Health. U.S. Department of Health & Human Services. Vitamin D: Fact sheet for health professionals. Updated Oct. 9, 2020.
  2. Gallagher JC. Vitamin D and aging. Endocrinol Metab Clin North Am 2013;42:319-332.
  3. Meehan M, Penckofer S. The role of vitamin D in the aging adult. J Aging Gerontol 2014;2:60-71.
  4. Naeem Z. Vitamin D defiency — an ignored epidemic. Int J Health Sci (Qassim) 2010;4:V-VI.
  5. Palacios C, Gonzalez L. Is vitamin D deficiency a major global health problem? J Steroid Biochem Mol Biol 2014;144 Pt A:138-145.
  6. Holick MF. Sunlight and vitamin D for bone health and prevention of autoimmune diseases, cancers, and cardiovascular disease. Am J Clin Nutr 2004;80:1678S-1688S.
  7. Zhang Y, Fang F, Tang J, et al. Association between vitamin D supplementation and mortality: Systematic review and meta-analysis. BMJ 2019;366:14673.
  8. Weir EK, Thenappan T, Bhargava M, et al. Does vitamin D deficiency increase the severity of COVID-19? Clin Med (Lond) 2020;20:e107-e108.
  9. MacLaughlin J, Holick MF. Aging decreases the capacity of human skin to produce vitamin D3. J Clin Invest 1985;76:1536-1538.
  10. Montagna W, Carlisle K. Structural changes in aging human skin. J Invest Dermatol 1979;73:47-53.
  11. LeFevre ML, LeFevre NM. Vitamin D screening and supplementation in community-dwelling adults: Common questions and answers. Am Fam Physician 2018;97:254-260.
  12. US Preventive Services Task Force. Vitamin D, calcium, or combined supplementation for the primary prevention of fractures in community-dwelling adults: Preventive medication. April 17, 2018.
  13. Seaborg E. Just right: How much vitamin D is enough? Endocrine News. November 2014.