Vitamin D and risk of cause specific death: systematic review and meta-analysis of observational cohort and randomised intervention studies

Systematic review and meta-analysis of observational cohort studies and randomized intervention trials assessing mortality outcomes related to circulating 25-hydroxyvitamin D and vitamin D supplementation. The randomized trials included 30,716 participants in total across active and control groups, with older adults studied in Europe, North America, and the Asia-Pacific region.

In the randomized trials, vitamin D was given orally as tablets, mainly as daily vitamin D3 (cholecalciferol) at 10 to 6000 IU/day or daily vitamin D2 (ergocalciferol) at 208 to 4500 IU/day. Follow-up ranged from 0.38 to 6.8 years, and the active supplement was compared with control in 22 trials.

Overall vitamin D supplementation did not significantly reduce all-cause mortality across all trials, with a pooled risk ratio of 0.98 (0.94 to 1.02). In subgroup analyses, vitamin D3 was associated with lower all-cause mortality, RR 0.89 (0.80 to 0.99), whereas vitamin D2 showed no benefit, RR 1.04 (0.97 to 1.11). The intervention arm recorded 2527 all-cause deaths versus 2587 in control across the pooled trials. The review concluded that vitamin D3 may reduce mortality in older adults, but the overall evidence does not support a clear mortality benefit for vitamin D supplementation as a whole.

The randomized evidence was heterogeneous in vitamin D form, dose, duration, and trial quality, which limits direct comparison and makes the pooled estimate less definitive. Per-arm sample sizes, sex distribution, and several participant characteristics were not reported, and the included trials were largely in older adults, limiting generalizability. Follow-up was relatively short in some studies, ranging from 0.38 to 6.8 years.