Effects of zinc and vitamin A supplementation on prognostic markers and treatment outcomes of adults with pulmonary tuberculosis: a systematic review and meta-analysis

Introduction Undernutrition is a major risk factor for tuberculosis (TB), which is estimated to be responsible for 1.9 million TB cases per year globally. The effectiveness of micronutrient supplementation on TB treatment outcomes and its prognostic markers (sputum conversion, serum zinc, retinol and haemoglobin levels) has been poorly understood. This study aimed to determine the effect of zinc and vitamin A supplementation on prognostic markers and TB treatment outcomes among adults with sputum-positive pulmonary TB. Methods A systematic literature search for randomised controlled trials (RCTs) was performed in PubMed, Embase and Scopus databases. Meta-analysis with a random effect model was performed to estimate risk ratio (RR) and mean difference (MD), with a 95% CI, for dichotomous and continuous outcomes, respectively. Results Our search identified 2195 records. Of these, nine RCTs consisting of 1375 participants were included in the final analyses. Among adults with pulmonary TB, zinc (RR: 0.94, 95% CI: 0.86 to 1.03), vitamin A (RR: 0.90, 95% CI: 0.80 to 1.01) and combined zinc and vitamin A (RR: 0.98, 95% CI: 0.89 to 1.08) supplementation were not significantly associated with TB treatment success. Combined zinc and vitamin A supplementation was significantly associated with increased sputum smear conversion at 2 months (RR: 1.16, 95% CI: 1.03 to 1.32), serum zinc levels at 2 months (MD: 0.86 mu mol/L, 95% CI: 0.14 to 1.57), serum retinol levels at 2 months (MD: 0.06 mu mol/L, 95% CI: 0.04 to 0.08) and 6 months (MD: 0.12 mu mol/L, 95% CI: 0.10 to 0.14) and serum haemoglobin level at 6 months (MD: 0.29 mu g/dL, 95% CI: 0.08 to 0.51), among adults with pulmonary TB. Conclusions Providing zinc and vitamin A supplementation to adults with sputum-positive pulmonary TB during treatment may increase early sputum smear conversion, serum zinc, retinol and haemoglobin levels. However, the use of zinc, vitamin A or both was not associated with TB treatment success. PROSPERO registration number CRD42021248548.