Vitamin D supplementation and total cancer incidence and mortality by daily vs. infrequent large-bolus dosing strategies: a meta-analysis of randomised controlled trials

BACKGROUND: Efficacy of vitamin D supplementation may vary by dosing strategies and adiposity. To address such heterogeneity, we performed a meta-analysis of randomised controlled trials of vitamin D supplementation and total cancer outcomes. METHODS: PubMed and Embase were searched through January 2022. Summary relative risk (SRR) and 95% confidence interval (CI) were estimated using the DerSimonian–Laird random-effects model. RESULTS: For total cancer incidence (12 trials), the SRR for vitamin D supplementation vs. control group was 0.99 (95% CI, 0.94–1.03; P = 0.54; I²= 0%). No significant association was observed regardless of whether the supplement was given daily or infrequently in a large-bolus. Yet, among trials testing daily supplementation, a significant inverse association was observed among normal-weight individuals (SRR, 0.76; 95% CI, 0.64–0.90; P = 0.001, I²= 0%), but not among overweight or obese individuals (P_{heterogeneity}= 0.02). For total cancer mortality (six trials), the SRR was 0.92 (95% CI, 0.82–1.03; P = 0.17; I²= 33%). A significant inverse association emerged (SRR, 0.87; 95% CI, 0.78–0.96; P = 0.007; I²= 0%) among studies testing daily supplementations but not among studies that testing infrequent large-bolus supplementations (P_{heterogeneity}= 0.09). CONCLUSIONS: For vitamin D supplementation, daily dosing, but not infrequent large-bolus dosing, reduced total cancer mortality. For total cancer incidence, bolus dosing did not reduce the risk and the benefits of daily dosing were limited to normal-weight individuals.