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New research suggests that vitamin D supplementation may reduce the incidence of major cardiovascular (CV) events, particularly myocardial infarction (MI) and coronary revascularization, in older adults.1

Findings were published online June 28, 2023, in The BMJ.

Vitamin D supplementation might reduce the risk of major cardiovascular events, although the absolute risk difference was small and the confidence interval was consistent with a null finding,” wrote first author Bridie Thompson, PhD, postdoctoral researcher in the Population Health Program, QIMR Berghofer Medical Research Institute in Herston, Queensland, Australia, and colleagues. “Further evaluation is warranted, particularly in people taking statins or other cardiovascular disease drugs.”1

Thompson and colleagues conducted the current analysis using data from their original randomized placebo-controlled D-Health Trial, which they conducted to determine if monthly vitamin D supplementation can improve health outcomes in the general population of older adults. D-Health enrolled 21 315 participants aged 60-84 years compared with placebo.1

A previous analysis of the D-Health cohort showed that vitamin D supplementation did not reduce all-cause mortality, which was the primary outcome, or mortality due to cardiovascular disease.2 The effect of monthly vitamin D supplementation on incidence of major CV events, however, has not been analyzed, according to Thompson and coauthors.1

The primary outcome for the current study was the occurrence of a major CV event, including MI, stroke, and coronary revascularization, according to the study.1

Participants were assigned 60 000 IU per month of vitamin D (n=10 658), or placebo (n=10 644) taken orally for up to 5 years. At 5 years, follow-up was completed by 80.2% of the vitamin D group and 77.6% of the placebo group. Also, the majority of participants in both the vitamin D group (84%) and placebo group (82%) reported taking at least 80% of the study tablets.1


At 5 years, researchers observed a major CV event in 6.0% of the vitamin D group and 6.6% of those in the placebo arm.1

Results showed that compared with the placebo group, the rate of major CV events was lower in the vitamin D arm (hazard ratio [HR] 0.91, 95% CI 0.81-1.01), “although the upper bound of the confidence interval is consistent with there being no effect,” wrote investigators.1

Overall, the difference in standardized cause-specific cumulative incidence of major CV events at 5 years was –5.8 events per 1000 participants (95% CI, –12.2 to 0.5), which translated to a number needed to treat of 172 to avoid one major CV event, according to researchers.1

In addition, compared with the placebo group, the vitamin D group had lower rates of MI (HR 0.81, 95% CI 0.67-0.98) and coronary revascularization (HR 0.89, 95% CI 0.78-1.01), but not stroke (HR 0.99, 95% CI 0.8-1.23).1

These findings differ from previous clinical trials of vitamin D supplementation, such as the VITAL and ViDA studies, which showed no CV benefit associated with vitamin D supplementation.1

“If the effect on myocardial infarction observed in the D-Health Trial is a true effect, and not due to chance, the reasons for the lack of consistency across studies are unclear. The discrepancy with VITAL might partly be caused by differences in study design and adherence,” wrote authors.1

Investigators concluded that the protective effect of vitamin D supplementation demonstrated in the current study, “could be more marked in those taking statins or other cardiovascular drugs at baseline. Subgroup analyses in other large trials might help to clarify this issue. In the meantime, these findings suggest that conclusions that vitamin D supplementation does not alter risk of cardiovascular disease are premature.”1


  1. Thompson B, Waterhouse M, English DR, et al. Vitamin D supplementation and major cardiovascular events: D-Health randomised controlled trial.BMJ. Published online June 28, 2023. doi:10.1136/bmj-2023-075230.
  2. Neale RE, Baxter C, Duarte Romero B, et al. The D-Health Trial: A randomised controlled trial of the effect of vitamin D on mortality. Lancet Diabetes Endocrinol. 2022;10:120-8.