Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of stratified aggregate data
Bibliographic record
Abstract
ABSTRACT Background A 2021 meta-analysis of 37 randomised controlled trials (RCTs) of vitamin D supplementation for prevention of acute respiratory infections (ARI) revealed a statistically significant protective effect of the intervention (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.86 to 0.99). Since then, 6 eligible RCTs have completed, including one large trial (n=15,804). Methods Updated systematic review and meta-analysis of data from RCTs of vitamin D for ARI prevention using a random effects model. Sub-group analyses were done to determine whether effects of vitamin D on risk of ARI varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration, dosing regimen or age. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Web of Science and the ClinicalTrials.gov were searched between May 2020 (previous search) and April 2024. No language restrictions were imposed. Double-blind RCTs supplementing vitamin D for any duration, with placebo or low-dose vitamin D control, were eligible if approved by Research Ethics Committee and if ARI incidence was collected prospectively and pre-specified as an efficacy outcome. Aggregate data, stratified by baseline 25(OH)D concentration and age, were obtained from study authors. The study was registered with PROSPERO (no. CRD42024527191). Findings We identified 6 new RCTs (19,337 participants). Data were obtained for 16,086 (83.2%) participants in 3 new RCTs and combined with data from 48,488 participants in 43 previously identified RCTs. For the primary comparison of any vitamin D vs. placebo, the intervention did not significantly affect overall ARI risk (OR 0.94, 95% CI 0.88 to 1.00, P=0.057; 40 studies; I 2 26.4%). Pre-specified subgroup analysis did not reveal evidence of effect modification by age, baseline vitamin D status, or dosing regimen. Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (OR 0.96, 95% CI 0.90 to 1.04; 38 studies; I 2 0.0%). A funnel plot showed left-sided asymmetry (P=0.002, Egger’s test). Interpretation This updated meta-analysis yielded a similar point estimate for the overall effect of vitamin D supplementation on ARI risk to that obtained previously, but the 95% CI for this effect estimate now spans 1.00, indicating no statistically significant protection. Funding None Research in context Evidence before this study We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and the ClinicalTrials.gov registry from 1 st May 2020 (date of our previous search) to 30 th April 2024 for randomised Controlled Trials and meta-analyses of randomised Controlled Trials evaluating effectiveness of vitamin D supplementation for the prevention of acute respiratory infections. Our previous meta-analysis of 43 randomised Controlled Trials (RCTs) of vitamin D supplementation for prevention of acute respiratory infections (ARI) conducted in 2021 revealed a statistically significant protective effect of the intervention (OR 0.92, 95% CI 0.86 to 0.99). A further 6 eligible RCTs, contributing data from 19,337 participants have now completed, including one large trial (n=15,804). Added value of this study Our meta-analysis of aggregate data from 64,086 participants in 46 randomised controlled trials, stratified by baseline 25(OH)D concentration and age, provides an updated estimate of the protective effects of vitamin D against acute respiratory infection overall (OR 0.94, 95% CI 0.88 to 1.00), and in sub-groups defined by baseline vitamin D status, age, and dosing frequency, amount and duration. Implications of all the available evidence Updated meta-analysis including the latest available RCT data shows no statistically significant protective effect of vitamin D supplementation against ARI, either overall or in sub-group analyses.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".