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. 2019 Aug 12;366:l4673.
doi: 10.1136/bmj.l4673.

Association Between Vitamin D Supplementation and Mortality: Systematic Review and Meta-Analysis

Free PMC article

Association Between Vitamin D Supplementation and Mortality: Systematic Review and Meta-Analysis

Yu Zhang et al. BMJ. .
Free PMC article


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.

Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at and declare: support from the National Natural Science Foundation of China and the National Key R&D Program of China; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.


Fig 1
Fig 1
Search strategy and final included and excluded studies
Fig 2
Fig 2
Forest plot of all cause mortality of trials evaluating vitamin D3 and vitamin D2 supplementation
Fig 3
Fig 3
Forest plot of cancer mortality, cardiovascular mortality, and non-cancer, non-cardiovascular mortality of trials evaluating vitamin D supplementation

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    1. Chowdhury R, Kunutsor S, Vitezova A, et al. Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies. BMJ 2014;348:g1903. 10.1136/bmj.g1903 - DOI - PMC - PubMed
    1. Wang TJ. Vitamin D and cardiovascular disease. Annu Rev Med 2016;67:261-72. 10.1146/annurev-med-051214-025146 - DOI - PubMed
    1. Grandi NC, Breitling LP, Vossen CY, et al. Serum vitamin D and risk of secondary cardiovascular disease events in patients with stable coronary heart disease. Am Heart J 2010;159:1044-51. 10.1016/j.ahj.2010.03.031 - DOI - PubMed
    1. Yin L, Ordóñez-Mena JM, Chen T, Schöttker B, Arndt V, Brenner H. Circulating 25-hydroxyvitamin D serum concentration and total cancer incidence and mortality: a systematic review and meta-analysis. Prev Med 2013;57:753-64. 10.1016/j.ypmed.2013.08.026 - DOI - PubMed
    1. Autier P, Mullie P, Macacu A, et al. Effect of vitamin D supplementation on non-skeletal disorders: a systematic review of meta-analyses and randomised trials. Lancet Diabetes Endocrinol 2017;5:986-1004. 10.1016/S2213-8587(17)30357-1 - DOI - PubMed

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