Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials
PubMed 33798465 · doi:10.1016/S2213-8587(21)00051-6
What was done
Authors conducted an updated systematic review and random-effects meta-analysis of double-blind randomized controlled trials (searched through May 1, 2020) evaluating vitamin D supplementation (vitamin D3, D2, or 25-hydroxyvitamin D) versus placebo or low-dose control. The primary outcome was the proportion of participants experiencing one or more acute respiratory infections (ARIs). Subgroup analyses evaluated baseline 25(OH)D concentration, dosing regimen and frequency, study duration, age, and underlying airway disease. Serious adverse events and risk of bias were also evaluated.
What was found
Out of 46 eligible RCTs with 75,541 participants, primary outcome data across 37 studies showed vitamin D significantly lowered the odds of having one or more ARIs compared to placebo: 61.3% (14,332/23,364) versus 62.3% (14,217/22,802), corresponding to an OR of 0.92 (95% CI 0.86-0.99; I2=35.6%, p=0.018). Subgroup analyses found significant protective effects for daily dosing (OR 0.78, 95% CI 0.65-0.94; 19 studies), daily dose equivalents of 400-1000 IU (OR 0.70, 95% CI 0.55-0.89; 10 studies), trial durations of 12 months or less (OR 0.82, 95% CI 0.72-0.93; 29 studies), and ages 1.00-15.99 years (OR 0.71, 95% CI 0.57-0.90; 15 studies). No significant subgroup effects were found based on baseline 25(OH)D levels, and formal interaction tests between subgroups were not statistically significant. Serious adverse events did not differ between groups (OR 0.97, 95% CI 0.86-1.07; 36 studies).
Why it matters
This updated meta-analysis confirms that vitamin D supplementation provides a safe, modest reduction in acute respiratory infection risk across broad populations, with the clearest benefits observed with daily moderate dosing.
Limits
The overall absolute risk reduction was very small (approximately 1 percentage point). Significant heterogeneity existed among included trials. The analysis relied on aggregate study-level data rather than individual participant data, and pathogen-specific outcomes (including SARS-CoV-2) were not evaluated.
Cited by
- partial Vitamin D shortens the duration of infections and helps prevent cytokine storms, sepsis, and autoimmune diseases by modulating immune system overreactions.