Vitamin D supplementation for the prevention of total cancer incidence and mortality: An updated systematic review and meta-analysis

Introduction: Previous randomized controlled trials (RCTs) and meta-analyses of RCTs evaluating vitamin D supplementation for the prevention of cancer incidence and mortality have found inconsistent results and no meta-analysis has assessed the quality of the evidence available. We, therefore, aimed to perform an updated meta-analysis by including recent large-scale RCTs and assessing the quality of the pooled evidence.Methods: We searched several databases and trial registers from inception to April 2022. We used a random-effects model to estimate pooled risk ratios (RRs) and 95% confidence intervals (CIs). We used the Grades of Recom-mendation, Assessment, Development, and Evaluation (GRADE) considerations to evaluate the certainty of evidence.Results: We included 13 RCTs in our study. Vitamin D supplementation had no effect on the risk of total cancer incidence (RR 0.99, 95% CI: 0.94-1.04; I2 = 0%), total cancer mortality (RR 0.93, 95% CI: 0.84-1.03; I2 = 24%) and total mortality (RR 0.92, 95% CI: 0.82-1.04; I2 = 36%). The overall quality of evidence was high for all outcomes.Discussion: Vitamin D supplementation is ineffective in reducing total cancer incidence and mortality in largely vitamin D-replete older adult populations. Future research should be based on populations with a higher prev-alence of vitamin D deficiency and should involve more extended follow-up periods.Study protocol: PROSPERO database, CRD42021285401.