Researchers have found in a new study that Vitamin D supplementation did not result in a lower risk of tuberculosis infection or tuberculosis disease. The study has been published in the New England Journal of Medicine.

Vitamin D metabolites support innate immune responses to Mycobacterium tuberculosis. Data from phase 3, randomized, controlled trials of vitamin D supplementation to prevent tuberculosis infection are lacking.

Vitamin D supplementation has been proposed as an intervention to reduce the risk of acquiring latent tuberculosis infection in populations in which deficiency is prevalent.It has been estimated that approximately 1.7 billion persons worldwide have latent tuberculosis infection,and about 10% of these persons will have progression to tuberculosis disease in their lifetime.

The investigations hypothesized that vitamin D supplementation would reduce the risk of tuberculosis infection and tuberculosis disease in populations in which both vitamin D deficiency and tuberculosis are prevalent. They tested this hypothesis in a phase 3, double-blind, randomized, placebo-controlled trial of vitamin D supplementation in schoolchildren living in Mongolia, with development of M. tuberculosis infection as the primary outcome and the incidence of active tuberculosis and acute respiratory infection as secondary outcomes.

In the study the children who had negative results for M. tuberculosis infection were randomly assigned according to the QuantiFERON-TB Gold In-Tube assay (QFT) to receive a weekly oral dose of either 14,000 IU of vitamin D3or placebo for 3 years.

The primary outcome was a positive QFT result at the 3-year follow-up, expressed as a proportion of children. The secondary outcomes included the serum 25-hydroxyvitamin D (25[OH]D) level at the end of the trial and the incidence of tuberculosis disease, acute respiratory infection, and adverse events.

The researchers randomized a total of 8851 children out of which 4418 were assigned to the vitamin D group, and 4433 to the placebo group; 95.6% of children had a baseline serum 25(OH)D level of less than 20 ng per milliliter. Among children with a valid QFT result at the end of the trial, the percentage with a positive result was 3.6% (147 of 4074 children) in the vitamin D group and 3.3% (134 of 4043) in the placebo group (adjusted risk ratio, 1.10; 95% confidence interval [CI], 0.87 to 1.38; P=0.42). The mean 25(OH)D level at the end of the trial was 31.0 ng per milliliter in the vitamin D group and 10.7 ng per milliliter in the placebo group (mean between-group difference, 20.3 ng per milliliter; 95% CI, 19.9 to 20.6). Tuberculosis disease was diagnosed in 21 children in the vitamin D group and in 25 children in the placebo group (adjusted risk ratio, 0.87; 95% CI, 0.49 to 1.55).

A total of 29 children in the vitamin D group and 34 in the placebo group were hospitalized for treatment of acute respiratory infection (adjusted risk ratio, 0.86; 95% CI, 0.52 to 1.40). The incidence of adverse events did not differ significantly between the two groups.

The researchers concluded that weekly oral supplementation with 14,000 IU of vitamin D3 for 3 years was effective in safely elevating 25(OH)D levels in a very large population of vitamin D–deficient schoolchildren in Mongolia. However, this intervention did not result in a lower risk of primary tuberculosis infection, as indicated by QFT conversion at the threshold value for the interferon-γ level of 0.35 IU per milliliter, than placebo.

Vitamin D supplementation did not result in a lower risk of tuberculosis infection, tuberculosis disease, or acute respiratory infection than placebo among vitamin D–deficient schoolchildren in Mongolia, the authors noted.

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N Engl J Med 2020; 383:359-368

DOI: 10.1056/NEJMoa1915176