Impact of Micronutrient Supplementation on Sputum Conversion Kinetics in Pulmonary Tuberculosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials Galley Proof

Abstract

Background: Tuberculosis (TB) remains a global health challenge, accounting for over 10 million incident cases and 1.6 million deaths annually as of 2021. The kinetics of sputum smear or culture conversion are critical determinants of patient infectiousness and long-term clinical prognosis. Although micronutrients—including vitamins A and D, and zinc—are known to modulate host immune responses, their specific efficacy in accelerating mycobacterial clearance remains a subject of academic debate.

Aims: This study aimed to systematically evaluate whether the adjunctive administration of micronutrient supplements alongside standard anti-tuberculosis therapy (ATT) significantly reduces the duration required for sputum smear or culture conversion in patients infected with Mycobacterium tuberculosis.

Methods: Following the PRISMA 2020 guidelines, a comprehensive search of PubMed, ScienceDirect, and the Cochrane library was executed for studies published through March 2025. Only randomized controlled trials (RCTs) comparing ATT micronutrient supplementation versus ATT alone were eligible for inclusion. The primary endpoint was the time to sputum smear or culture conversion. Data synthesis was performed using Review Manager (v 5.4.1), with outcomes expressed as mean differences (MD) and odds ratio (OR). Heterogeneity was addressed through fixed or random-effects modeling as appropriate.

Results: Twelve RCTs involving 3,377 participants met the inclusion criteria. Meta-analysis revealed that micronutrient supplementation significantly abbreviated the time to sputum conversion (M D = -4.48 days; 95% CI: –7.54 to –1.41; p = 0.004). Furthermore, the odds of achieving negative sputum status were significantly elevated by the second month of treatment (OR = 1.59; 95% CI: 1.03 – 2.46), although this effect was not observed at the one-month or three-month intervals. While vitamin D was the most frequently studied intervention, vitamin A, zinc, and multi-micronutrient formulations were also represented. Risk of bias was rigorously assessed using the Cochrane tool.

Conclusion: Adjunctive micronutrient therapy appears to modestly but significantly accelerate sputum conversion in TB patients. These findings suggest that nutritional fortification may serve as a viable auxiliary strategy to enhance standard treatment regimens. However, further investigation is warranted to outline the efficacy of specific nutrient combinations and their impact across diverse demographic populations.

Keywords: Tuberculosis; Micronutrient; Dietary supplements; Adjunctive Therapy; Sputum Conversion Kinetics.