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Original Investigation
June 19, 2019

Vitamin D Supplementation and Cardiovascular Disease Risks in More Than 83 000 Individuals in 21 Randomized Clinical Trials: A Meta-analysis

Author Affiliations
  • 1Department of Internal Medicine, Hurley Medical Center, Michigan State University, Flint
  • 2Department of Internal Medicine, Mutah University, Al-Karak, Jordan
  • 3Division of Cardiology, Hurley Medical Center, Michigan State University, Flint
  • 4Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts
JAMA Cardiol. 2019;4(8):765-775. doi:10.1001/jamacardio.2019.1870
Key Points

Question  Does vitamin D supplementation have any association with cardiovascular disease risk?

Findings  In this meta-analysis of randomized clinical trials that included more than 83 000 participants, vitamin D supplementation was not associated with reduced risks of major adverse cardiovascular events, myocardial infarction, stroke, cardiovascular disease mortality, or all-cause mortality compared with placebo.

Meaning  These results suggest that vitamin D supplementation may not confer cardiovascular protection and may not be indicated for this purpose.

Abstract

Importance  Observational studies have reported an association between low serum vitamin D levels and elevated risk of cardiovascular disease (CVD) events, but such studies cannot prove causation because of possible unmeasured confounding.

Objective  We conducted a meta-analysis of randomized clinical trials that tested the association of vitamin D supplementation with reduced CVD events and all-cause mortality.

Data Sources  Literature search through PubMed, the Cochrane Library, and Embase was completed by 2 reviewers from each database’s inception to December 15, 2018.

Study Selection  Inclusion criteria were randomized clinical trials that reported the effect of long-term (≥1 year) vitamin D supplementation on CVD events and all-cause mortality. Studies that did not include cardiovascular outcomes were excluded.

Data Extraction and Synthesis  Data were abstracted independently by 2 authors. Random-effects models were used to report the risk ratios (RRs) and 95% CIs.

Main Outcomes and Measures  Major adverse cardiovascular events was the primary outcome, and rates of myocardial infarction, stroke or cerebrovascular accident, CVD mortality, and all-cause mortality were the secondary end points.

Results  Twenty-one randomized clinical trials were included (including 83 291 patients, of whom 41 669 received vitamin D and 41 622 received placebos). The mean (SD) age of trial participants was 65.8 (8.4) years; 61 943 (74.4%) were female. Only 4 trials had prespecified CVD as a primary end point. Vitamin D supplementation compared with placebo was not associated with reduced major adverse cardiovascular events (RR, 1.00 [95% CI, 0.95-1.06]; P = .85) nor the secondary end points of myocardial infarction (RR, 1.00 [95% CI, 0.93-1.08]; P = .92), stroke (RR, 1.06 [95% CI, 0.98-1.15]; P = .16), CVD mortality (RR, 0.98 [95% CI, 0.90-1.07]; P = .68), or all-cause mortality (RR, 0.97 [95% CI, 0.93-1.02]; P = .23). 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.

Conclusions and Relevance  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.

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