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Meta-Analysis
. 2019 Aug 1;4(8):765-776.
doi: 10.1001/jamacardio.2019.1870.

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

Mahmoud Barbarawi  1 , Babikir Kheiri  1 , Yazan Zayed  1 , Owais Barbarawi  2 , Harsukh Dhillon  1 , Bakr Swaid  1 , Anitha Yelangi  1 , Saira Sundus  1 , Ghassan Bachuwa  1 , Mohammad Luay Alkotob  3 , JoAnn E Manson  4
Affiliations
Meta-Analysis

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

Mahmoud Barbarawi et al. JAMA Cardiol. .

Erratum in

  • Errors in Table 1 and Figures 2 and 3.
    [No authors listed] [No authors listed] JAMA Cardiol. 2020 Jan 1;5(1):112. doi: 10.1001/jamacardio.2019.4472. JAMA Cardiol. 2020. PMID: 31693055 Free PMC article. No abstract available.

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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Conflict of interest statement

Conflict of Interest Disclosures: Dr Manson received funding from the US National Institutes of Health to conduct the Vitamin D and ω-3 Trial (VITAL). Vitamin D study pills were donated by Pharmavite LLC and Omega-3 supplements were donated by Pronova BioPharma and BASF. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. The Study Selection Strategy
Figure 2.
Figure 2.. Forest Plot Illustrating the Results of the Primary and Secondary End Points, Part 1
Figure 3.
Figure 3.. Forest Plot Illustrating the Results of the Primary and Secondary End Points, Part 2
See this image and copyright information in PMC

Comment in

References

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