Association between vitamin D supplementation and mortality: systematic review and meta-analysis
What this study found
Vitamin D supplementation did not reduce all-cause mortality, cardiovascular mortality, or non-cancer, non-cardiovascular mortality. Pooled estimates were null for all-cause mortality (RR 0.98, 95% CI 0.95 to 1.02), cardiovascular mortality (RR 0.98, 0.88 to 1.08), and non-cancer, non-cardiovascular mortality (RR 1.05, 0.93 to 1.18). Cancer mortality was lower with vitamin D (RR 0.84, 95% CI 0.74 to 0.95), with the benefit seen in vitamin D3 rather than vitamin D2. Longer follow-up was associated with greater all-cause mortality benefit, and the authors called for additional large randomized…
- Study & population
- This was a systematic review and meta-analysis of 52 randomized controlled trials enrolling 75,454 adults aged 18 years and older with various health conditions.
- Intervention
- Vitamin D supplementation was evaluated across randomized trials using varying regimens, including daily, weekly, and monthly bolus dosing.
- Key limitation
- Most trials were relatively short, with a median follow-up of 1.2 years, which may limit detection of mortality effects.
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Open PDFOriginal 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 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.