Association between vitamin D supplementation and mortality: systematic review and meta-analysis

The BMJ
Aug 2019
Citations:302
Influential Citations:10
Systematic Reviews / Meta-Analyses
88
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Methods
Adults aged 18 years and older with any health condition; randomized controlled trials comparing vitamin D supplementation with placebo or no treatment; systematic review and meta-analysis (including quasi-randomized and cluster randomized trials).
Intervention
Vitamin D supplementation; dosing varied across trials (daily, weekly, monthly, or bolus dosing); included both vitamin D3 and vitamin D2; some high-dose monthly regimens used in ongoing large trials (e.g., 60,000 IU/month).
Results
Vitamin D supplementation did not reduce all-cause mortality in adults (RR 0.98; 95% CI 0.95–1.02). No significant effect on cardiovascular mortality (RR 0.98; 95% CI 0.88–1.08) or non-cancer, non-cardiovascular mortality (RR 1.05; 95% CI 0.93–1.18). Cancer mortality was reduced by 15% (RR 0.85; 95% CI 0.74–0.97), primarily with vitamin D3; vitamin D2 showed no significant reduction. Longer follow-up was associated with a greater reduction in all-cause mortality. Conclusion: Vitamin D supplementation does not lower all-cause mortality overall; there is potential reduction in cancer mortality, especially with vitamin D3, which requires confirmation by further large trials.
Limitations
Mortality reporting was secondary in most trials and may be subject to selective reporting; wide heterogeneity in dosing regimens, populations, and trial designs; many trials used calcium co-supplementation or hydroxylated vitamin D, limiting generalizability; baseline vitamin D status often not low and exposure in control groups varied, complicating interpretation; unable to determine an optimal dose.

Abstract

Abstract Objective To investigate whether vitamin D supplementation is associated with lower mortality in adults. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Medline, Embase, and the Cochrane Central Regis...