Vitamin D supplementation was not associated with reduced risks of major adverse cardiovascular events (MACE), in new research published in JAMA Cardiology. The authors of the meta-analysis* said their results suggest that vitamin D supplementation might not confer cardiovascular protection and may not be indicated for this purpose.
They pointed out that previously, observational studies have suggested an inverse association between serum 25-hydroxyvitamin D levels and risk of cardiovascular disease (CVD) events – low vitamin D levels have been linked to an increased risk of myocardial infarction (MI), stroke, CVD mortality, and heart failure in case-control and other prospective epidemiologic studies. Furthermore, vitamin D receptors are expressed in vascular tissues, including the myocardium and vascular smooth muscle, directly influencing calcium influx, muscle relaxation, and diastolic function; and vitamin D also has effects on the renin-angiotensin-aldosterone system and parathyroid hormone and may influence endothelial function and arterial thrombogenesis.
Because of this, vitamin D supplementation has increased, particularly in the US. But, said the researchers, previous randomised clinical trials (RCT) assessing vitamin D supplementation and cardiovascular disease have been limited and inconclusive, so they conducted a meta-analysis of all 21 eligible RCTs to date that have tested the association of vitamin D supplementation with reduced CVD events and all-cause mortality – although only four had prespecified CVD as a primary endpoint. These 21 RCTs included a total of 83,291 patients (mean age nearly 66 years; three-quarters of them female), of whom 41,669 received vitamin D and 41,622 received placebo.
Their analysis found that vitamin D supplementation was not associated with a significantly reduced risk of MACE compared with placebo (relative risk, RR 1.00) nor with risk of the secondary end points of MI (RR 1.00), stroke (RR 1.06), CVD mortality (RR 0.98) or all-cause mortality (RR 0.97). They added that the results were generally consistent by sex, baseline 25-hydroxyvitamin D level, vitamin D dosage, formulation (daily vs bolus dosing), and presence or absence of concurrent calcium administration.
The study authors noted that in a previous meta-analysis of RCTs, vitamin D supplementation showed no benefit in reducing MI, but a potential benefit for heart failure was observed; however, their own meta-analysis confirms an absence of benefit for MI, as well as no reduction in stroke, CVD mortality, or a composite MACE endpoint.
They concluded: “In this updated meta-analysis, vitamin D supplementation was not associated with reduced major adverse cardiovascular events, individual CVD end points (myocardial infarction, stroke, CVD mortality), or all-cause mortality. The findings suggest that vitamin D supplementation does not confer cardiovascular protection and is not indicated for this purpose.”
They added: “Additional trials of higher-dose vitamin D supplementation, perhaps targeting members of older age groups and with attention to other CVD end points such as heart failure, are of interest.”
*Barbarawi M, Kheiri B, Zayed Y, et al. Vitamin D supplementation and cardiovascular disease risks in more than 83,000 individuals in 21 randomized clinical trials: a meta-analysis. JAMA Cardiol. Published online June 19, 2019. doi:10.1001/jamacardio.2019.1870.