Vitamin D: Best Evidence of Primary Prevention

Frank J. Domino, MD

Review

Chowdhury, R., et al. “Vitamin D and Causes of Death: Best Evidence to Date.” BMJ 2014; 348:g1903.

Vitamin D has appeared in the media frequently with correlation touting its use in many disease states. This paper summarizes the best data to date.

Study Methods

Observational cohort studies and randomized controlled trials were included in this systematic review and meta-analysis. After extensive evaluation, 73 cohort studies (covering over 800,000 participants), and 22 randomized controlled trials (covering 30,000 participants) were included for review.

Results and Outcomes

Best data from observational studies found patients with the lowest 1/3 of baseline 25-hydroxy vitamin D levels had a relative risk of death of 1.35 from cardiovascular disorders, 1.14 for death from cancer, 1.30 for death from “non-vascular/non-cancer” causes, and 1.35 for all cause mortality.

From the randomized controlled trial data of vitamin D3 supplementation, the relative risk for all-cause mortality was 0.89. There was a non-significant increase in relative risk when evaluated for vitamin D2 supplementation, but the authors note the vitamin D2 studies were of low dose and shorter duration, concluding D2 provided no negative implications of use.

Commentary

This systematic review and meta-analysis helps clarify much of the media hype and confusion around vitamin D supplementation. What it strongly suggests is having a low 25-hydroxy vitamin D level can lead to increased risk of mortality.

This study was extremely well done and does explore a number of issues. The supplementation of vitamin D (using D3, and likely vitamin D2 as well) seems to lower all-cause mortality risk. Contrast this with having a low serum 25 OH vitamin D level inducing an all-cause mortality increased risk (relative risk increase of 1.35 (1.22-1.49). This combination implies a benefit to supplementation that is likely beyond lifestyle based confounders

A systematic review and meta-analysis recently published in the British Medical Journal (Theodoratou, E., et al. BMJ 2014; 348:g2035) found a number of conditions benefit from vitamin D supplementation. These included improved birth weight based upon maternal vitamin D status or supplementation and reduced dental caries in children. This data supports the American Academy of Pediatrics recommendation that all infants receive 400 IU per day starting within a few days of birth (Pediatrics 2010; 125(4):627-632). Supplementation also supported a relationship between parathyroid hormone concentrations in patients on dialysis for chronic kidney disease and improved outcomes.

The current data from this study also found limited evidence to support the use of vitamin supplementation alone for bone mineral density improvement or decreasing the risks of falls and fractures. This finding is in contrast to a Cochrane systematic review (and US Preventive Services Task Force recommendation), which did demonstrate a benefit of vitamin D supplementation for fracture risk, primarily in an older, female population.

Patients most likely to benefit from Vitamin D supplementation include pregnant women, newborns and those with no sun exposure. This last group requires all of their serum vitamin D to be derived from food sources or supplementation.

How much Vitamin D is appropriate for an individual? The Institute of Medicine found vitamin D supplementation between 800 to 4,000 IU per day was safe. The risks of taking vitamin D supplementation are very few. None are severe or serious, and the cost of implementing a large population-based vitamin D supplementation is extremely low.

What supplementation benefits beyond a reduced all-cause mortality is currently under evaluation, and results should be published by early 2016. As more randomized controlled data appears over the next 18 months, expect greater media attention, and hopefully, better answers.

About the Author

Frank J. Domino, MD, is Professor and Pre-Doctoral Education Director for the Department of Family Medicine and Community Health at the University of Massachusetts Medical School in Worcester, MA. Domino is Editor-in-Chief of the 5-Minute Clinical Consult series (Lippincott Williams & Wilkins).

Additionally, he is Co-Author and Editor of the Epocrates LAB database, and author and editor to the MedPearls smartphone app. He presents nationally for the American Academy of Family Medicine and serves as the Family Physician Representative to the Harvard Medical School’s Continuing Education Committee.