Vitamin D supplementation to prevent tuberculosis infection and disease: systematic review and individual participant data meta-analysis of randomised controlled trials

Background: Several randomised controlled trials of vitamin D supplementation for prevention of tuberculosis infection and disease have been conducted, but no individual participant data (IPD) meta-analysis has been conducted. Methods: We conducted a systematic review, one-stage and two-stage IPD meta-analysis (PROSPERO CRD420251173446) of double-blind, placebo-controlled randomised trials of vitamin D supplementation for prevention of tuberculosis infection or disease. We searched MEDLINE, Embase, Scopus, Cochrane and ClinicalTrials.gov from inception to October 29, 2026. The co-primary outcomes were incident tuberculosis infection (evidenced by tuberculin skin test or Interferon Gamma Release Assay conversion) and incident tuberculosis disease. Mixed-effects models estimated adjusted odds ratios (aORs), accounting for trial and prespecified covariates. Prespecified subgroup analyses investigated effect modification by sex and age, body-mass index, vitamin D status, and BCG vaccination status. Findings: Four trials contributed IPD for 14,619 participants. Vitamin D did not reduce risk of incident tuberculosis infection (9,557 participants; aOR 0.97, 95% CI 0.81-1.18; p=0.79) or incident tuberculosis disease (14,533 participants; aOR 0.78, 95% CI 0.56-1.10; p=0.15). There was no evidence of effect modification by participant characteristics investigated in sub-group analyses, including in participants with 25-hydroxyvitamin D <25 nmol/L (infection: aOR 0.95, 95% CI 0.67-1.34; disease: 1.01, 0.45-2.30). Serious adverse events and mortality were unaffected. Interpretation: Vitamin D supplementation did not reduce the risk of incident tuberculosis infection or disease in the populations studied, either overall or within sub-groups. The 95% confidence interval of the effect estimate for prevention of tuberculosis disease remains compatible with a potentially important benefit, and further trials for this indication may be warranted.