Effects of vitamin D supplementation on the outcomes of patients with pulmonary tuberculosis: a systematic review and meta-analysis

Systematic review and meta-analysis of eight randomized trials in adults with active pulmonary tuberculosis receiving standard anti-tuberculosis therapy. The active intervention arms were compared with placebo controls across studies conducted in India, Mongolia, the United Kingdom, Bangladesh, Indonesia, Pakistan, Georgia, and Guinea.

Vitamin D supplementation, mainly as vitamin D3 or cholecalciferol, was used as adjunctive therapy to standard anti-tuberculosis treatment. Across the included trials, dosing varied widely: oral regimens ranged from 0.25 mg daily for 42 days to 7.5 mg bolus dosing over 3 to 4 months, and one trial used 15 mg intramuscular monthly for 2 doses; treatment durations ranged from 6 weeks to 8 months.

Vitamin D supplementation improved sputum conversion and several laboratory or radiographic measures, but it did not shorten time to conversion or improve mortality or adverse-event outcomes. It increased sputum smear conversion (OR 1.21, 95% CI 1.05 to 1.39, P = 0.007) and sputum culture conversion (OR 1.22, 95% CI 1.04 to 1.43, P = 0.02). Time to sputum smear conversion (HR 1.07, 95% CI 0.83 to 1.37, P = 0.62) and time to sputum culture conversion (HR 0.97, 95% CI 0.76 to 1.23, P = 0.77) were not significantly different. Serum 25(OH)D, plasma calcium, lymphocyte count, and chest radiograph findings improved, while TB score, BMI, MUAC, weight gain, CRP, ESR, other blood indices, non-serious adverse events, serious adverse events, and all-cause deaths did not differ meaningfully.

The included trials used heterogeneous vitamin D regimens, doses, routes, and treatment durations, which limits direct comparability. Several outcomes were inconsistently reported, and some subgroup results were based on small samples. More rigorous randomized trials are needed to refine optimal dosing and to assess whether factors such as disease severity or vitamin D receptor polymorphisms modify response.