Twenty-two RCTs (30,716 participants) and 73 cohort studies (849,412 participants) were included in the review. The average follow-up period ranged from 0.38 to 6.75 years in the RCTs, and 0.3 to 29 years in the observational studies. Fourteen RCTs reported adequate allocation concealment and blinding in participants and carers. Eight studies were considered to be at low risk of bias, 41 at medium risk, and 24 at high risk of bias.
RCTs: Participants receiving vitamin D3 supplementation showed significant reductions in risk of all cause mortality compared to control groups, but this was only just statistically significant (RR 0.89, 95% CI 0.80 to 0.99; 14 RCTs; Ι²=10.2%). There were no statistically significant differences in risk of all cause mortality between participants receiving D2 and control (RR 1.04, 95% CI 0.97 to 1.11; eight RCTs; Ι²=7.2%).
Subgroup analyses by participant (with or without existing disease) did not significantly alter the findings. Meta-regression analyses indicated that effects differed for vitamin D2 supplementation based on intervention dose, intervention period and risk of bias.
There was no evidence of publication bias.
Observational studies: Pooled adjusted risk ratios for participants in the bottom versus top thirds of the population distribution of baseline circulating vitamin D supplementation were 1.43 (95% CI 1.25 to 1.64; 29 studies) for death from cardiovascular disease, 1.25 (95% CI 1.10 to 1.43; 17 studies) for death from cancer; 1.34 (95% CI 1.13 to 1.60; 10 studies) for death not related to cancer or cardiovascular disease and 1.44 (95% CI 1.34 to 1.55; 68 studies) for all cause mortality. Results were also reported separately for primary and secondary prevention studies. Findings from other association were reported in the review.