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

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 Register from their inception to 26 December 2018.

Eligibility criteria for selecting studies

Randomised controlled trials comparing vitamin D supplementation with a placebo or no treatment for mortality were included. Independent data extraction was conducted and study quality assessed. A meta-analysis was carried out by using fixed effects and random effects models to calculate risk ratio of death in the group receiving vitamin D supplementation and the control group.

Main outcome measures

All cause mortality.

Results

52 trials with a total of 75 454 participants were identified. Vitamin D supplementation was not associated with all cause mortality (risk ratio 0.98, 95% confidence interval 0.95 to 1.02, I ²=0%), cardiovascular mortality (0.98, 0.88 to 1.08, 0%), or non-cancer, non-cardiovascular mortality (1.05, 0.93 to 1.18, 0%). Vitamin D supplementation statistically significantly reduced the risk of cancer death (0.84, 0.74 to 0.95, 0%). In subgroup analyses, all cause mortality was significantly lower in trials with vitamin D ₃ supplementation than in trials with vitamin D ₂ supplementation (P for interaction=0.04); neither vitamin D ₃ nor vitamin D ₂ was associated with a statistically significant reduction in all cause mortality.

Conclusions

Vitamin D supplementation alone was not associated with all cause mortality in adults compared with placebo or no treatment. Vitamin D supplementation reduced the risk of cancer death by 16%. Additional large clinical studies are needed to determine whether vitamin D ₃ supplementation is associated with lower all cause mortality.

Study registration

PROSPERO registration number CRD42018117823.