BACKGROUND: Vitamin D metabolites support innate immune responses to Mycobacterium tuberculosis. METHODS: We randomly assigned children who had negative results for Mycobacterium tuberculosis infection, using the QuantiFERON-TB Gold In-tube assay (QFT), to receive a weekly oral dose of 14,000 IU vitamin D3 or placebo over 3 years. The primary outcome was the proportion of children having a positive QFT result at 3 years. Secondary outcomes included end-study vitamin D status and incidence of tuberculosis disease, acute respiratory infections and adverse events. RESULTS: 8851 participants underwent randomization (4418 to vitamin D, 4433 to placebo), of whom 95.6% had baseline serum 25-hydroxyvitamin D concentrations <20 ng/mL. Mean end-study 25-hydroxyvitamin D concentration in participants randomized to vitamin D vs. placebo was 31.0 vs. 10.7 ng/mL (95% CI for difference, 19.9 to 20.6 ng/mL), and 147 participants in the vitamin D group vs. 134 participants in the placebo group tested positive by QFT (adjusted risk ratio [aRR] 1.10, 95% CI 0.87 to 1.38, P=0.42). Tuberculosis disease was diagnosed in 21 children in the vitamin D group and 25 children in the placebo group (aRR 0.87, 95% CI 0.49 to 1.55). 29 participants randomized to vitamin D and 34 randomized to placebo were hospitalized for treatment of acute respiratory infections (aRR 0.86, 95% CI 0.52 to 1.40). Incidence of adverse events did not differ significantly between study arms. CONCLUSIONS: Vitamin D supplementation did not reduce risk of tuberculosis infection, tuberculosis disease or acute respiratory infections among vitamin D-deficient schoolchildren in Mongolia
