An Updated Meta-Analysis of Randomized Controlled Trials on Vitamin D Supplement and Cancer Incidence and Mortality

Objectives: We synthesized the results of published randomized controlled trials, aiming to test the hypothesis that low vitamin D is associated with an increased risk of cancer incidence and mortality. Meanwhile, we explored potential sources of between-trial heterogeneity. Methods: Randomized controlled trials that explored the association between vitamin D and cancer incidence or mortality were identified by searching PubMed and EMBASE databases. Literature search, quality assessment and data extraction were performed in duplicate and independently. Results: Nine randomized controlled trials were pooled involving 55491 study participants. The incidence rate of cancer was 10.56% and 10.65% in vitamin D intervention group and placebo group, respectively, resulting in a nonsignificant relative risk (RR) (95% confidence interval [CI]) of 0.99 (0.93 to 1.05) (P=0.733). The mortality rate of cancer was 2.61% and 2.92% in vitamin D intervention group and placebo group, respectively, resulting in a significant reduction in risk prediction (RR=0.88, 95% CI: 0.80 to 0.98, P=0.016). 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-related mortality, especially in subpopulation with no history of cancer, extra use of vitamin D, or calcium supplement. Funding Statement: : This study was supported by the Fundamental Research Funds for the Central Universities (Grant No. 3332018170). Declaration of Interests: The authors declare that they have no conflict of interest.