Optimal methods of vitamin D supplementation to prevent acute respiratory infections: a systematic review, dose-response and pairwise meta-analysis of randomized controlled trials.

ABSTRACT

BACKGROUND: Vitamin D supplementation may prevent acute respiratory infections (ARIs). This study aimed to identify the optimal methods of vitamin D supplementation. METHODS: PubMed, Embase, Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry were searched from database inception through July 13, 2023. Randomized-controlled trials (RCTs) were included. Data were pooled using random-effects model. The primary outcome was the proportion of participants with one or more ARIs. RESULTS: The analysis included 43 RCTs with 49320 participants. Forty RCTs were considered to be at low risk for bias. The main pairwise meta-analysis indicated there were no significant preventive effects of vitamin D supplementation against ARIs (risk ratio [RR] 0.99, 95% confidence interval [CI] 0.97 to 1.01, I2 = 49.6%). The subgroup dose-response meta-analysis indicated that the optimal vitamin D supplementation doses ranged between 400-1200 IU/day for both summer-sparing and winter-dominant subgroups. The subgroup pairwise meta-analysis also revealed significant preventive effects of vitamin D supplementation in subgroups of daily dosing (RR 0.92, 95% CI 0.85 to 0.99, I2 = 55.7%, number needed to treat [NNT] 36), trials duration < 4 months (RR 0.81, 95% CI 0.67 to 0.97, I2 = 48.8%, NNT 16), summer-sparing seasons (RR 0.85, 95% CI 0.74 to 0.98, I2 = 55.8%, NNT 26), and winter-dominant seasons (RR 0.79, 95% CI 0.71 to 0.89, I2 = 9.7%, NNT 10). CONCLUSION: Vitamin D supplementation may slightly prevent ARIs when taken daily at doses between 400 and 1200 IU/d during spring, autumn, or winter, which should be further examined in future clinical trials.