A randomized controlled trial of over 5,000 participants published in the Journal of American Medical Association found that vitamin D supplementation did not prevent cardiovascular disease (CVD).
In 1981, researchers first proposed the hypothesis that sunlight may protect against CVD through a mechanism involving vitamin D. Observational studies have supported this hypothesis, showing that people with low vitamin D status have an increased risk of CVD.
Confirmation of this hypothesis requires proof from randomized controlled trials, comparing the effects of vitamin D supplements to placebo. However, RCTs have produced conflicting results. The Women’s Health Initiative study found that daily supplementation of 400 IU did not lead to any benefits against CVD. These results came as no surprise, because the dose was very low. Another RCT found that 100,000 IU of vitamin D3 for four months led to a non-significant 10% reduction in CVD incidence. Finally, a secondary analysis of a RCT on fractures determined that 800 IU daily did not prevent heart attacks or strokes but decreased the incidence of heart failure by 25%.
Due to the mixed results on vitamin D and CVD, researchers recently conducted a large RCT with over 5,000 adults between the ages of 50 to 84 years. A total of 2,558 adults were randomly assigned to receive an initial dose of 200,000 IU of vitamin D3, followed a month later by monthly doses of 100,000 IU. The other 2,252 participants were given a matching placebo. The intervention lasted an average of 3.3 years.
The average vitamin D levels were 26.5 ng/ml before the intervention, with nearly a quarter of the participants being considered vitamin D deficient (<20 ng/ml). After six months, one year, two years and three years, the researchers evaluated the vitamin D levels among a random sample of 438 participants. The vitamin D group’s average vitamin D levels were 54.1 ng/ml after three years. Whereas, those given the placebo had an average vitamin D status of 26.4 ng/ml after three years.
CVD occurred in 303 participants in the vitamin D group and 293 participants in the placebo group. Similar results were observed when the researchers performed a sub-analysis of those with vitamin D deficiency at study entry and for other outcomes such as angina, heart failure, hypertension, heart attack and stroke.
The researchers concluded,
“The results of this large population-based RCT indicate that vitamin D supplementation given in the dose and frequency we used does not prevent CVD…”
The researchers go on to point out the study’s main limitation, the use of monthly dosing. “However, it remains possible that monthly doses of vitamin D are less effective in preventing disease than daily or weekly doses,” the study stated.
The researchers explained that the recommendation for vitamin D dosage changed during their study. Bolus dosing used to be the typical recommendation, but recent reviews have concluded that vitamin D is more accessible for cells before it becomes hydroxylated into 25(OH)D. In this study, vitamin D would have only been in the blood circulation for several days after each monthly dose.
The study proposes another reason for the surprising findings. Perhaps, another component of sunlight is responsible for the observed relationship between low vitamin D levels and increased risk of CVD.
While media headlines may claim that vitamin D does not help cardiovascular health, the researchers stated that it’s too soon to draw such a definitive conclusion.
They stated,“We caution against closure of this topic, given the descriptive epidemiologic findings on inverse associations between solar radiation and CVD with regard to season, latitude, and altitude.”
The effects of daily or weekly vitamin D supplementation on CVD prevention require further investigation.
Tovey, A. & Cannell, JJ. New study suggests monthly high-dose vitamin D supplementation does not prevent heart disease. The Vitamin D Council Blog & Newsletter, April 13, 2017.
Scragg, R. Stewart, A. 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. JAMA Cardiology, 2017.