Protective effects of vitamin D supplementation against acute respiratory infection are greatest in those with the lowest baseline vitamin D status

Background: Aggregate data meta-analysis of randomised controlled trials (RCTs) of vitamin D supplementation to prevent acute respiratory infection (ARI) reveals modest net protective effects. We hypothesised that these protective effects may be more marked in individuals with the lowest baseline vitamin D status. Objective: To conduct an individual patient data (IPD) meta-analysis to determine whether the degree of vitamin D-induced protection against ARI varies according to baseline vitamin D status. Methods: We used a one-step logistic regression with random effects, adjusting for age, sex, study duration and clustering by study, to meta-analyse IPD from 22 RCTs of vitamin D enrolling a total of 10,425 participants of any age, where data on incidence of ARI had been collected prospectively and pre-specified as an efficacy outcome. Sub-group analysis was performed to determine whether the effect of vitamin D on risk of ARI varied in sub-groups defined by a 25 nmol/L cut-off for serum 25-hydroxyvitamin D (25[OH]D) concentration. Results: IPD meta-analysis of data from all participants demonstrated a modest protective effect of vitamin D against ARI (aOR 0.86, 95% CI 0.79 to 0.95). Sub-group analysis revealed a strong protective effect among individuals with baseline circulating 25(OH)D Conclusions: Protective effects of vitamin D supplementation against ARI are modified by baseline vitamin D status, with very deficient individuals experiencing substantial benefit.