Vitamin D as Adjunctive Host-Directed Therapy in Tuberculosis: A Systematic Review

Vitamin D plays an important role in innate defenses against intracellular pathogens. Seasonal vitamin D insufficiency (VDI) due to reduced sun exposure far from the equator increases tuberculosis risk. Eight randomized controlled trials examined vitamin D as adjunctive therapy during tuberculosis treatment. The studies varied substantially regarding patient genetic backgrounds, the extent of baseline VDI, the administered dose, the study endpoints, and the quality of the reported data. One carefully performed study in which moderately large vitamin D doses were given to markedly VDI patients found a benefit sufficient to support shortening treatment from 6 to 4 months, although other similar studies did not. Vitamin D is thought to have anti-inflammatory effects. However, 2 studies reported 3 vitamin D recipients with severe paradoxical inflammatory reactions. Future studies of vitamin D in tuberculosis in patients with specific genetic backgrounds must monitor these events closely to determine their risks and underlying mechanisms.