Meta-analysis of randomized controlled trials on vitamin D supplement and cancer incidence and mortality

Objectives: We aimed to meta-analyze the results of published randomized controlled trials to test the hypothesis that low vitamin D supplement is associated with an increased risk of cancer incidence and mortality. Methods: Randomized controlled trials that explored the association between vitamin D supplement and cancer incidence or mortality as primary outcomes were identified through searching the PubMed and EMBASE. Literature search and data extraction were performed independently and in duplicate. Results: Ten randomized controlled trials pooled in 81362 participants. The incidence rate of cancer was 9.16% (3716 cases) and 9.29% (3799 cases) in vitamin D intervention group and placebo group, respectively, resulting in a nonsignificant relative risk (RR) (95% confidence interval (95% CI)) of 0.99 (0.94–1.03) (P=0.532). The mortality rate of cancer was 2.11% (821 cases) and 2.43% (942 cases) in vitamin D intervention group and placebo group, respectively, resulting in a significant reduction in risk (RR = 0.87, 95% CI: 0.79–0.95, P=0.003). There was no observable heterogeneity or publication bias. Subgroup analyses revealed that history of cancer, extra use of vitamin D and calcium supplement were potential sources of heterogeneity. Conclusions: Our findings support a beneficial effect of vitamin D supplement on lowering cancer mortality, especially in subpopulations with no history of cancer, extra use of vitamin D, or calcium supplement.