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

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. Trials were conducted in community and institutional settings across multiple countries and compared vitamin D supplementation with placebo or no treatment.

Vitamin D supplementation was evaluated across randomized trials using varying regimens, including daily, weekly, and monthly bolus dosing. The comparison was placebo or no treatment, although some studies allowed low-dose personal vitamin D use in control groups and some active arms included calcium with vitamin D. Route and exact per-arm doses were not consistently reported in the provided packet.

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 trials to confirm the findings.

Most trials were relatively short, with a median follow-up of 1.2 years, which may limit detection of mortality effects. Dosing, route, and per-arm sample sizes were not consistently reported in the provided text, and some studies allowed additional low-dose vitamin D or used calcium with vitamin D, adding potential heterogeneity and indirectness. Baseline vitamin D status was often not deficient, which may limit generalizability to deficient populations.