Efficacy of Vitamin D Supplementation in Accelerating Sputum Conversion of Bacteriologically Diagnosed Tuberculosis Patients: A Meta-Analysis

Tuberculosis (TB) is a global pandemic disease whose first-line treatment is with a combination of four antimicrobials commonly abbreviated as HRZE (isoniazid, rifampin, pyrazinamide, and ethambutol). However, some consider the regimen inadequate, thus conducting numerous trials to search for adjunctive therapies, including vitamin D supplementation. Trials so far have led to mixed results. The present study aims to consolidate data on the effects of vitamin D supplementation on clinical outcomes, specifically rates of sputum culture conversion. PubMed databases were searched for peer-reviewed articles published in English between the years 2013 and 2023 that deal with human subjects, designed as randomized controlled trials (RCTs), utilizing vitamin D supplementation in addition to anti-TB therapy, with a measured outcome of the rate of sputum culture conversion at specific follow-up intervals. The risk of bias (RoB) was assessed using the Cochrane RoB 2 tool. Initially, 1,225 articles were found via database search, narrowed to six articles after screening and full-text reading. A significant difference was found between the vitamin D and control/placebo groups in rates of sputum culture conversion at eight weeks, with the intervention group having an increased odds of culture conversion by 1.63 (95% CI 1.13, 2.35, p < 0.01). The same was not found, however, at 16 weeks (OR = 0.99, 95% CI 0.71, 1.38, p > 0.05). Statistical heterogeneity was minimal, but the studies significantly differed in the dosing regimens of the intervention, populations included, and attrition rates. The RoB was also low, but there were concerns due to high attrition rates, lack of blinding, and the addition of unplanned post-hoc analysis. The beneficial effects of vitamin D supplementation, if any, involve eliciting an early response to treatment, reflected in improved culture conversion rates at earlier follow-up intervals. Possible factors mentioned in some studies that may lead to variations in the effect of vitamin D supplementation include vitamin D status (sufficiency/insufficiency/deficiency), presence of drug resistance, and genetic polymorphisms; these may be explored in future studies sufficiently powered to examine such a relationship.