Primary Research · 2017
Vitamin D supplementation to prevent acute respiratory tract infections: systematic review and meta-analysis of individual participant data
Martineau AR, Jolliffe DA, Hooper RL, et al. · BMJ, 2017
Key finding
Individual-participant meta-analysis of 25 RCTs (n=10,933) found vitamin D supplementation reduced risk of acute respiratory tract infection, with greatest benefit in baseline-deficient participants and daily/weekly (not bolus) dosing.
Abstract
PubMed · PMID 28202713 →Objectives To assess the overall effect of vitamin D supplementation on risk of acute respiratory tract infection, and to identify factors modifying this effect.Design Systematic review and meta-analysis of individual participant data (IPD) from randomised controlled trials.Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, ClinicalTrials.gov, and the International Standard Randomised Controlled Trials Number registry from inception to December 2015.Eligibility criteria for study selection Randomised, double blind, placebo controlled trials of supplementation with vitamin D3 or vitamin D2 of any duration were eligible for inclusion if they had been approved by a research ethics committee and if data on incidence of acute respiratory tract infection were collected prospectively and prespecified as an efficacy outcome.Results 25 eligible randomised controlled trials (total 11 321 participants, aged 0 to 95 years) were identified. IPD were obtained for 10 933 (96.6%) participants. Vitamin D supplementation reduced the risk of acute respiratory tract infection among all participants (adjusted odds ratio 0.88, 95% confidence interval 0.81 to 0.96; P for heterogeneity <0.001). In subgroup analysis, protective effects were seen in those receiving daily or weekly vitamin D without additional bolus doses (adjusted odds ratio 0.81, 0.72 to 0.91) but not in those receiving one or more bolus doses (adjusted odds ratio 0.97, 0.86 to 1.10; P for interaction=0.05). Among those receiving daily or weekly vitamin D, protective effects were stronger in those with baseline 25-hydroxyvitamin D levels <25 nmol/L (adjusted odds ratio 0.30, 0.17 to 0.53) than in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (adjusted odds ratio 0.75, 0.60 to 0.95; P for interaction=0.006). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted odds ratio 0.98, 0.80 to 1.20, P=0.83). The body of evidence contributing to these analyses was assessed as being of high quality.Conclusions Vitamin D supplementation was safe and it protected against acute respiratory tract infection overall. Patients who were very vitamin D deficient and those not receiving bolus doses experienced the most benefit.Systematic review registration PROSPERO CRD42014013953.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions. Abstract sourced from PubMed, a database of the U.S. National Library of Medicine. Displayed in the authors’ own words for context; our critique is in the sections below.
B
76/100
Moderate evidence
Reasonable design with one or two notable limitations. The finding is credible but less certain than an A-grade result.
Strengths
- ✓Large sample size
- ✓Real-world outcome
- ✓Independent funding
Limitations
No major methodological limitations flagged.
Critique
Individual-participant meta-analysis across 25 RCTs is a strong design — it re-analyses raw subject data rather than just pooling summary statistics, which handles heterogeneity better than conventional meta-analysis. The overall effect is modest (NNT ~33) and the pooled estimate hides substantial variation between trials in dose, population, seasonal timing, and baseline vitamin D status. A cleaner read of the data is that vitamin D meaningfully helps people who are deficient; evidence of benefit in already-replete individuals is weaker.
What would be more convincing
A single large pre-registered RCT restricting enrollment to baseline 25(OH)D below 20 ng/mL, using daily (not bolus) dosing, would resolve the heterogeneity question and settle the 'does deficiency matter' framing that the current evidence only hints at.
Reviewed 2026-04-21 · Opinion based on verifiable facts in the published paper.
What these flags mean for you
Each flag on this study comes with a plain-English breakdown of why it matters and how it should change the confidence you place in the result.
Large sample size
What it means
The trial enrolled enough participants to detect realistic effect sizes with high statistical power.
Why it matters
Large samples shrink the role of chance. A positive finding in thousands is much less likely to be a fluke than the same finding in dozens.
How to read around it
Gives you more confidence the reported effect size is close to the true effect — but still doesn't prove the study is well-designed in other ways.
Real-world outcome
What it means
The trial measured something a patient would actually notice — symptoms, function, quality of life, hospitalization, mortality.
Why it matters
Real-world outcomes skip the surrogate-endpoint problem entirely. If symptoms improved, symptoms improved.
How to read around it
Higher translational value than biomarker trials. What the trial measured is closer to what you'd get from taking the supplement.
Independent funding
What it means
Funded by a public agency, university, or philanthropic grant with no commercial stake in the outcome.
Why it matters
Removes the financial incentive that skews industry-funded results. Independent trials historically show smaller effect sizes — closer to the truth.
How to read around it
Weight independent results more heavily. When independent and industry-funded trials disagree, the independent result is usually closer to reality.
About the supplement
Vitamin D
Dose · mechanism · evidence grade · safety →
Read the full paper
How to read a study like this
The same questions worth asking about any research paper, not just this one. Worth a minute even if you trust the grade.
Who was studied, and do you resemble them?
Supplement effects often depend on baseline status. Vitamin D helps people who are deficient; iron helps people who are anemic. A result in people unlike you may not apply to you.
What was measured, and does it matter in daily life?
A study that shows a blood marker moved isn't the same as a study that shows people felt or functioned better. Ask what the outcome means in practice.
How large was the effect — not just whether it was significant.
'Statistically significant' only means the effect is unlikely to be zero. It doesn't tell you the effect is large enough to notice. Look for effect sizes, not just p-values.
Who paid for the trial, and what did they stand to gain?
Industry-funded trials are several times more likely to report positive results than independent ones. It's not usually fraud — it's subtle design and reporting choices. Weight accordingly.
Has anyone else replicated this?
Single positive trials are hypotheses. Replication by independent groups is what turns a hypothesis into reliable evidence. If the only positive trial is the one you're reading, wait.
Does the dose in the trial match what's being sold?
Supplement marketing routinely cites trials that used 5–10× the dose in the product. If the effective dose was 2 g/day and the capsule has 200 mg, expect roughly no effect.
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