Findings from a meta-analysis suggest that vitamin D supplementation may not provide cardiovascular protection and may not be appropriate for this purpose.
Published prospective and case-control studies have suggested that low vitamin D levels may increase the risk of myocardial infarction, stroke, cardiovascular disease (CVD) mortality, and heart failure. “Vitamin D supplementation has been thought to be beneficial for the cardiovascular system by lowering risk of key cardiovascular endpoints like myocardial infarction and stroke,” explains Mahmoud Barbarawi, MD. “This concept was supported by many studies, but most of these analyses were observational in nature.”
Assessment of vitamin D supplementation for CVD prevention has been a subject of growing interest in recent randomized clinical trials. However, data from these studies has been limited and inconclusive regarding the cardiovascular benefits of screening and treating asymptomatic low vitamin D in adults. In addition, the United States Preventive Services Task Force has not specifically recommended vitamin D supplementation to prevent CVD in its most recent guidance document.
Taking a More Comprehensive Look
In recent years, several large-scale trials have added to a substantial evidence base regarding the potential cardiovascular benefits of vitamin D supplements. In light of this new evidence, Dr. Barbarawi and colleagues published a meta-analysis of all RCTs to date in JAMA Cardiology in which they evaluated the efficacy of vitamin D supplementation in preventing CVD. They reviewed 21 randomized clinical trials that included more than 83,000 patients, nearly half of which received vitamin D supplementation while the other half received placebos. The primary outcome measure was major adverse cardiovascular events. Secondary endpoints included rates of myocardial infarction, stroke or cerebrovascular accident, CVD mortality, and all-cause mortality.
The study found that vitamin D supplements did not reduce risk of incident major adverse cardiovascular events as well as myocardial infarction, stroke or cerebrovascular accident, CVD mortality, or all-cause mortality (Table). The results were generally consistent across different variables, including sex, race and ethnicity, baseline 25-hydroxyvitamin D level, vitamin D dosage, formulation (daily vs bolus dosing), and the presence or absence of concurrent calcium administration.
“Vitamin D supplementation did not show a beneficial effect on cardiovascular endpoints or any-cause mortality,” says Dr. Barbarawi. “As such, vitamin D supplementation should not be prescribed for the purpose of CVD prevention. Our study was based on strong evidence and was powered to draw this conclusion.”
The study noted that most trials in the meta-analysis were not designed to assess CVD events as a primary prespecified outcome. Instead, these trials were more often designed to assess the effects of vitamin D on fractures or osteoporosis. The majority of studies also primarily included older patients and women who were postmenopausal. Just 4 of the 21 trials assessed in the meta-analysis focused on cardiovascular events as a primary prespecified endpoint. Of note, these 4 trials did not show cardiovascular or mortality benefits.
In light of the study findings, Dr. Barbarawi recommends clinicians change their way of thinking about use of these supplements when counseling patients. “Vitamin D deficiency should be treated with vitamin D supplementation because it is important vitamin to keep the electrolytes in equilibrium,” he says. “Patients should understand that vitamin D deficiency could be a cardiovascular risk factor but correcting levels of vitamin D with supplements will not provide a cardioprotective effect. Ultimately, vitamin D supplementation should not be given to prevent CVD.”
The study group reported that additional trials of higher-dose vitamin D supplementation are warranted to gain a better understanding of the relationship between these supplements and cardiovascular protection. They recommend studies be designed to target different age groups using a specifically defined endpoint of CVD protection. Future studies should also be conducted in which greater attention is paid to other CVD endpoints, such as heart failure.
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. 2019 Jun 19 [Epub ahead of print]. Available at: https://jamanetwork.com/journals/jamacardiology/fullarticle/2735646.
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. JAMA Cardiol. 2017;2(6):608-616.
Pekkanen MP, Ukkola O, Hedberg P, et al. Serum 25-hydroxyvitamin D is associated with major cardiovascular risk factors and cardiac structure and function in patients with coronary artery disease. Nutr Metab Cardiovasc Dis. 2015;25(5):471-478.
LeFevre ML; U.S. Preventive Services Task Force. Screening for vitamin D deficiency in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2015;162(2):133-140.