Efficacy and safety of vitamin D supplementation in treating pulmonary tuberculosis: a systematic review and meta-analysis

This study endeavors to assess the efficacy and safety of vitamin D (VD) supplementation among pulmonary tuberculosis (PTB) adults receiving standard anti-tuberculosis (TB) therapy. This systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Studies evaluating VD supplementation as an adjunct to standard therapy in patients with drug-susceptible TB were included. Eligible studies compared clinical outcomes between patients receiving VD supplementation regardless of formulation or route of administration (RoA) and those receiving standard therapy alone. The number of included studies and participants varied across outcomes. Data on study design, participant characteristics, VD regimens, and outcome measures were systematically extracted. Risk ratio (RR) was calculated for dichotomous outcomes, and standardized mean difference (SMD) was used for continuous outcomes. Statistical heterogeneity was assessed using the I² statistic. Publication bias was evaluated using funnel plots and Egger’s test. Sensitivity analyses and predefined subgroup analyses (e.g., by treatment duration and RoA) were performed. The certainty of evidence was assessed using the GRADE framework. Adjunctive VD supplementation significantly increased the sputum smear conversion (SSC) rate (RR: 1.12; 95% confidence interval (CI): 1.05–1.19; P = 0.0001; high GRADE certainty; I²=46%, P = 0.06) and reduced mean TB severity scores (SMD: -1.20; 95% CI: -2.18 to -0.21; P = 0.02; low GRADE certainty; I²=96%, P < 0.0001). No significant effect was observed on sputum culture conversion (SCC) (RR: 1.08; 95% CI: 0.95–1.22; P = 0.25; low GRADE certainty; I²=67%, P = 0.05). VD supplementation was related to a significant reduction in adverse events (AEs) (RR: 0.54; 95% CI: 0.40–0.74; P = 0.0001; high GRADE certainty; I²=0%, P = 0.43) and an increase in serum calcium levels (SMD: 0.31; 95% CI: 0.14–0.49; P = 0.0006; high GRADE certainty; I²=26%, P = 0.25). Subgroup analyses indicated that treatment durations of ≥ 12 weeks and injectable RoAs were related to more consistent benefits for SSC. Substantial heterogeneity was observed across several outcomes. Additional findings included significant increases in serum VD and hemoglobin (Hgb) levels, whereas no significant effects were detected for white blood cell (WBC) count, erythrocyte sedimentation rate (ESR), or C-reactive protein (CRP). Adjunctive VD supplementation in the treatment of drug-susceptible TB is related to improved SSC and a favorable safety profile, including a reduction in AEs. These findings support the use of VD as an adjunctive therapy, particularly among VD-deficient patients. However, evidence for other clinical outcomes remains inconclusive due to substantial heterogeneity and lower certainty of evidence. Further well-designed, adequately powered, and standardized randomized controlled trials (RCTs) are warranted to determine optimal dosing strategies, RoAs, and treatment durations, and to strengthen the overall evidence base. Not applicable.