Clinical Edge

Summaries of Must-Read Clinical Literature, Guidelines, and FDA Actions

Does High-Dose Vitamin D Supplementation Prevent CVD?

JAMA Cardiol; ePub 2017 Apr 5; Scragg, et al

In the general population, monthly high-dose vitamin D supplementation does not prevent cardiovascular disease (CVD), a recent study found. In the Vitamin D Assessment Study, 5,110 participants were randomized to receive vitamin D3 (n=2,558) or placebo (n=2,552). Interventions included oral vitamin D3 in an initial dose of 200,000 IU, followed a month later by monthly doses of 100,000 IU, or placebo, for a median of 3.3 years. Primary outcome was the number of participants with incident CVD and death. Researchers found:

  • There were 5,108 participants in the analysis.
  • Mean (SD) baseline deseasonalized 25-hydrovitamin D (25(OH)D) concentration was 26.5 (9.0) ng/mL, with 1,270 participants (24.9%) being vitamin D deficient.
  • In a sample of 438 participants, the mean-follow-up of 25(OH)D level was >20 ng/mL higher in the vitamin D group vs the placebo group.
  • The primary outcomes of CVD occurred in 303 (11.8%) participants in the vitamin D group and 293 (11.5%) participants in the placebo group.


Scragg R, Stewart AW, Waayer D, et al. Effect of monthly high-dose vitamin D supplementation on cardiovascular disease in the Vitamin D Assessment Study. A randomized clinical trial. [Published online ahead of print April 05, 2017]. JAMA Cardiol. doi:10.1001/jamacardio.2017.0175.


Observational trials have shown a correlation between low vitamin D levels and many diseases, including cardiovascular disease, asthma, and diabetes.1 For some time, it seemed like vitamin D might be the simple fix to many of life’s ills. Over the last 5 years, however, we have seen randomized trials that do not support a causal relationship between vitamin D and various outcomes. Specifically, randomized trials have shown no decrease in either asthma exacerbations or the development of diabetes with vitamin D supplementation.2,3 The trial reviewed above reminds us that while observational trials are helpful, we need to be cautious about inferring causality from correlations seen in them and need randomized trial evidence before forming therapeutic plans. —Neil Skolnik, MD

  1. Schöttker B, Jorde R, Peasey A, et al. Vitamin D and mortality: meta-analysis of individual participant data from a large consortium of cohort studies from Europe and the United States. BMJ. 2014;348:g3656.
  2. Castro M, et al. Effect of vitamin D3 on asthma treatment failures in adults with symptomatic asthma and lower vitamin D levels. The VIDA Randomized Clinical Trial. JAMA. 2014;311(20):2083-2091. doi:10.1001/jama.2014.5052.
  3. Davidson M, et al. High-dose vitamin D supplementation in people with prediabetes and hypovitaminosis D. Diabetes Care. 2013;36(2):260-266. doi:10.2337/dc12-1204.