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JAMA Cardiol. 2019 Jun 19. doi: 10.1001/jamacardio.2019.1870. [Epub ahead of print]

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

Author information

Department of Internal Medicine, Hurley Medical Center, Michigan State University, Flint.
Department of Internal Medicine, Mutah University, Al-Karak, Jordan.
Division of Cardiology, Hurley Medical Center, Michigan State University, Flint.
Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.



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.


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.


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.

[Available on 2020-06-19]

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