Effects of Immune-Modulatory Nutrients as Host-Directed Therapy in Pulmonary Tuberculosis Patients: A Systematic Review and Meta-Analysis.

CONTEXT: Tuberculosis (TB) remains the leading cause of death from a single infectious agent worldwide, and treatment outcomes remain suboptimal. Host-directed therapies, including immunonutrients, have gained attention for their potential to support immune function and modulate inflammation.

OBJECTIVE

To determine the effects of adjunct immunonutrients (omega-3 long-chain polyunsaturated fatty acids [n-3 LCPUFAs]; vitamins A, C, D, and E; selenium; zinc; arginine; glutamine; iron; and nucleotides) on early sputum conversion (sputum smear or culture negative at 4-8 weeks); and culture time to conversion, inflammation, mortality, and TB score in adults (aged ≥15 years) with drug-sensitive pulmonary TB.

DATA SOURCES: Scopus, Web of Science, Cochrane, and PubMed were searched from March 19, 2024, to May 2026. The review was performed according to Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). guidelines and was registered on PROSPERO.

DATA EXTRACTION: Two authors independently screened articles, extracted data, and assessed risk of bias using RoB 2.0. Certainty of evidence was assessed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) methodology. The review included 44 randomized controlled trials (RCTs) and 1 quasi-experimental trial.

DATA ANALYSIS: Vitamin D lowered TB scores at 8 weeks (standardized mean difference [SMD], -0.83; 95% CI, -1.09 to -0.57; P < .001), and C-reactive protein (CRP) at 6 weeks (SMD, -0.43; 95% CI, -0.83 to -0.03; P = .03), but did not improve sputum smear conversion (odds ratio [OR], 1.05; 95% CI, 0.99-1.10; P = .098). Arginine and vitamin C pooled effects on sputum smear conversion were not robust in sensitivity analyses or based on only 2 trials. Arginine reduced CRP at 8 weeks (OR, 0.55; 95% CI, 0.40-0.75; P < .001). Vitamin A, zinc, and their combination showed no significant effects. Certainty of evidence was low to very low.

CONCLUSIONS

These findings suggest a potential but unconfirmed benefit of selected adjunct immunonutrients, most notably vitamin D. Routine supplementation cannot be recommended. Large, well-designed RCTs with standardized dosing and outcomes are needed, including for those with no eligible trials identified (vitamin E, selenium, n-3 LCPUFAs, nucleotides, iron, and glutamine).

SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration No. [CRD42024567237].