Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data.
Level 1 - systematic review of randomized trials
Systematic review and individual participant data meta-analysis of randomized controlled trials
PubMed 28202713 · doi:10.1136/bmj.i6583
What was done
A systematic review and individual participant data meta-analysis of randomized, double-blind, placebo-controlled trials evaluating vitamin D3 or D2 supplementation of any duration. Searches across Medline, Embase, Cochrane CENTRAL, Web of Science, ClinicalTrials.gov, and ISRCTN from inception to December 2015 identified trials where acute respiratory tract infection incidence was prospectively collected and prespecified as an efficacy outcome.
What was found
Across 25 eligible trials (11,321 participants, aged 0 to 95 years), individual participant data were obtained for 10,933 participants (96.6%). Vitamin D supplementation reduced overall acute respiratory tract infection risk (adjusted odds ratio [aOR] 0.88, 95% CI 0.81 to 0.96; P for heterogeneity <0.001). Subgroup analysis showed protection from daily or weekly dosing without boluses (aOR 0.81, 95% CI 0.72 to 0.91) but not from regimens containing bolus doses (aOR 0.97, 95% CI 0.86 to 1.10; P for interaction = 0.05). Among those on daily or weekly regimens, protection was substantially stronger in participants with baseline 25-hydroxyvitamin D <25 nmol/L (aOR 0.30, 95% CI 0.17 to 0.53) than in those ≥25 nmol/L (aOR 0.75, 95% CI 0.60 to 0.95; P for interaction = 0.006). Serious adverse events were similar between groups (aOR 0.98, 95% CI 0.80 to 1.20, P = 0.83).
Why it matters
This review provides high-level evidence that regular daily or weekly vitamin D supplementation safely reduces acute respiratory infections, particularly in individuals with severe baseline deficiency.
Limits
There was significant statistical heterogeneity among included trials (P < 0.001). Individual participant data were unavailable for 3.4% of eligible participants, and the abstract does not report specific pathogen types, exact optimal dosing amounts, or clinical severity of the infections.
Cited by
- partial A British Medical Journal meta-analysis by Martineau and colleagues showed that vitamin D supplementation significantly reduced acute respiratory tract infections by 50%.
- supports A meta-analysis led by Martineau found that daily or weekly vitamin D supplementation protected against acute respiratory tract infections, but monthly bolus doses did not.