Vitamin D Supplements for Prevention of Tuberculosis Infection and Disease.

Randomized placebo-controlled trial in vitamin D-deficient schoolchildren aged 6-13 years in 18 public schools in Ulaanbaatar, Mongolia. Latent tuberculosis infection was excluded at baseline, and the vitamin D group was stratified by school of attendance.

Vitamin D3 was given orally at 14,000 IU (0.35 mg) once weekly for 3 years. The active arm was compared with identical placebo capsules; 4418 participants were randomized to vitamin D3 and 4074 had valid end-of-trial QFT results for the primary outcome.

Weekly vitamin D3 markedly increased 25(OH)D but did not reduce Mycobacterium tuberculosis infection, tuberculosis disease, or acute respiratory infection versus placebo. For the primary endpoint, positive QFT at end occurred in 3.6% (147 of 4074) of the vitamin D group versus 3.3% (134 of 4043) of the placebo group, with an adjusted risk ratio of 1.10 (95% CI 0.87 to 1.38; P = 0.42). Tuberculosis disease was rare and similar between groups: 21 of 4401 (0.5%) versus 25 of 4418 (0.6%), adjusted RR 0.87 (95% CI 0.49 to 1.55); acute respiratory infection hospitalization was also similar at 29 of 4401 (0.66%) versus 34 of 4418 (0.77%), adjusted RR 0.86 (95% CI 0.52 to 1.40). End-of-trial 25(OH)D was 31.0±9.1 ng/mL in the vitamin D group versus 10.7±5.3 ng/mL in placebo, and the trial was considered safe and well tolerated.

The main outcomes were uncommon, especially tuberculosis disease, which limits power to detect modest effects. End-of-trial QFT data were not available for all randomized participants, and the primary outcome remained null despite a large rise in 25(OH)D levels. Generalizability is mainly to vitamin D-deficient schoolchildren in urban Mongolia.