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

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, I²=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 D₃ supplementation than in trials with vitamin D₂ supplementation (P for interaction=0.04); neither vitamin D₃ nor vitamin D₂ 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 D₃ supplementation is associated with lower all cause mortality.

Study registration: PROSPERO registration number CRD42018117823.