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

Eight randomized, double‑blind, placebo‑controlled trials enrolling adults with newly diagnosed active pulmonary tuberculosis on initial anti-tuberculosis therapy; participants >16 years; both genders; conducted in eight countries; total N=1787 (898 vitamin D, 889 placebo).

Vitamin D3 (cholecalciferol) regimens varied by trial: Daley 2015 (India): oral 2.5 mg bolus, biweekly for 4 doses (total 10 mg), duration 6 weeks. Ganmaa 2016 (Mongolia): oral 3.5 mg bolus, biweekly for 4 doses (13.5 mg), duration 8 weeks. Martineau 2011 (UK): oral 2.5 mg bolus, biweekly for 4 doses (10 mg), duration 8 weeks. Mily 2015 (Bangladesh): oral 0.875 mg bolus, weekly for 8 doses (7 mg), duration 8 weeks. Nursyam 2006 (Indonesia): oral 0.25 mg daily for 42 doses (10.5 mg), duration 6 weeks. Salahuddin 2013 (Pakistan): intramuscular 15 mg monthly for 2 doses (30 mg), duration 8 weeks. Tukvadze 2015 (Georgia): oral 1.25 mg bolus, triweekly for 3 doses and weekly for 3 doses (7.5 mg total), duration 16 weeks. Wejse 2009 (Guinea): oral cholecalciferol 2.5 mg every 4 months for 3 doses (7.5 mg total), duration 8 months.

Vitamin D3 supplementation increased the proportion of sputum smear conversion (OR 1.21; 95% CI 1.05–1.39) and culture conversion (OR 1.22; 95% CI 1.04–1.43). It did not shorten time to conversion (sputum smear HR 1.07; 95% CI 0.83–1.37; culture HR 0.97; 95% CI 0.76–1.23). Secondary outcomes showed rises in serum 25(OH)D (MD 103.36, 95% CI 84.20–122.53), plasma calcium (MD 0.09, 95% CI 0.03–0.14), and lymphocyte counts (SMD 0.26, 95% CI 0.15–0.37); chest radiograph improvement (MD −0.33, 95% CI −0.57 to −0.08). No significant differences in adverse events, mortality, TB score, BMI, mean MUAC, weight gain, CRP, ESR, or other blood indices. Authors conclude vitamin D3 can be considered a safe, cost‑effective adjunct therapy for PTB; more rigorous RCTs are needed to define optimal dose, duration, and the role of host genetics.

Dosing regimens, treatment durations, and follow‑up varied across trials; heterogeneity observed for several outcomes; some trials had unclear risk of bias; analyses had limited power for some outcomes; data were insufficient to assess genetic modifiers (e.g., VDR polymorphisms).