Vitamin D and Respiratory Tract Infections: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

Background: Low levels of 25-OH vitamin D are associated with respiratory tract infection (RTI). However, results from randomized controlled trials are inconclusive. Therefore, we performed a systematic review and meta-analysis to assess the preventive effect of vitamin D supplementation on RTI.

Methods: Randomized, controlled trials of vitamin D for prevention of RTI were used for the analysis. The risks of within-trial and publication bias were assessed. Odds ratios of RTI were pooled using a random-effects model. Heterogeneity was assessed using Cochran's Q and I(2). Meta-regressions and subgroup analyses were used to assess the influence of various factors on trial outcome. The pre-defined review protocol was registered at the PROSPERO international prospective register of systematic reviews, registration number CRD42013003530.

Findings: Of 1137 citations retrieved, 11 placebo-controlled studies of 5660 patients were included in the meta-analysis. Overall, vitamin D showed a protective effect against RTI (OR, 0.64; 95% CI, 0.49 to 0.84). There was significant heterogeneity among studies (Cohran's Q p<0.0001, I(2) = 72%). The protective effect was larger in studies using once-daily dosing compared to bolus doses (OR = 0.51 vs OR = 0.86, p = 0.01). There was some evidence that results may have been influenced by publication bias.

Interpretation: Results indicate that vitamin D has a protective effect against RTI, and dosing once-daily seems most effective. Due to heterogeneity of included studies and possible publication bias in the field, these results should be interpreted with caution.

Figure 1. Flowchart for selection of eligible studies.

Figure 2. Efficacy of vitamin D for prevention of respiratory tract infections.

Error bars indicate 95% confidence intervals.

Figure 3. Subgroup analyses.

Error bars indicate 95% confidence intervals of OR in subgropus of randomized trials. Subgroups were based on RTI being a primary or secondary endpont, trial participants being patients or healthy individuals, children or adults, and vitamin D-sufficient or insufficient, and vitamin D being adminstered daily or as bolus doses. Numbers indicate number of trials in each subgroup and p-values refer to between-group differences in random effects meta-regressions performed separately for each pair of subgroups.

Figure 4. Random effects meta-regressions.

Dotted lines indicate 95% confidence intervals of regression lines (solid lines). Sizes of dots are proportional to the weight of each trial in the regression model.