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

<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Objective</jats:title> <jats:p>To investigate whether vitamin D supplementation is associated with lower mortality in adults.</jats:p> </jats:sec> <jats:sec> <jats:title>Design</jats:title> <jats:p>Systematic review and meta-analysis of randomised controlled trials.</jats:p> </jats:sec> <jats:sec> <jats:title>Data sources</jats:title> <jats:p>Medline, Embase, and the Cochrane Central Register from their inception to 26 December 2018.</jats:p> </jats:sec> <jats:sec> <jats:title>Eligibility criteria for selecting studies</jats:title> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Main outcome measures</jats:title> <jats:p>All cause mortality.</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p> 50 trials with a total of 74 655 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 <jats:sup>2</jats:sup> =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 (0.85, 0.74 to 0.97, 0%). In subgroup analyses, all cause mortality was significantly lower in trials with vitamin D <jats:sub>3</jats:sub> supplementation than in trials with vitamin D <jats:sub>2</jats:sub> supplementation (P for interaction=0.04); neither vitamin D <jats:sub>3</jats:sub> nor vitamin D <jats:sub>2</jats:sub> was associated with a statistically significant reduction in all cause mortality. </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p> 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 15%. Additional large clinical studies are needed to determine whether vitamin D <jats:sub>3</jats:sub> supplementation is associated with lower all cause mortality. </jats:p> </jats:sec> <jats:sec> <jats:title>Study registration</jats:title> <jats:p>PROSPERO registration number CRD42018117823.</jats:p> </jats:sec>