Impact of Micronutrient Supplementation on Sputum Conversion Kinetics in Pulmonary Tuberculosis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
Copyright © 2026 Farida Anggraini Soetedjo, Johanes Aprilius Falerio Kristijanto, Nur Khamidah
This work is licensed under a Creative Commons Attribution 4.0 International License.
- Attribution — You must give appropriate credit, provide a link to the license, and indicate if changes were made.
- No additional restrictions — You may not apply legal terms or technological measures that legally restrict others from doing anything the license permits.
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 (MD = -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
How to Cite
Afzal, A., Rathore, R., Butt, N. F., & Randhawa, F. A. (2018). Efficacy of Vitamin D supplementation in achieving an early sputum conversion in smear positive Pulmonary Tuberculosis. Pakistan Journal of Medical Sciences, 34(4). https://doi.org/10.12669/pjms.344.14397 DOI: https://doi.org/10.12669/pjms.344.14397
Bagcchi, S. (2023). WHO’s Global Tuberculosis Report 2022. The Lancet Microbe, 4(1), e20. https://doi.org/10.1016/S2666-5247(22)00359-7 DOI: https://doi.org/10.1016/S2666-5247(22)00359-7
Daley, P., Jagannathan, V., John, K. R., Sarojini, J., Latha, A., Vieth, R., Suzana, S., Jeyaseelan, L., Christopher, D. J., Smieja, M., & Mathai, D. (2015). Adjunctive vitamin D for treatment of active tuberculosis in India: a randomised, double-blind, placebo-controlled trial. The Lancet Infectious Diseases, 15(5), 528–534. https://doi.org/10.1016/S1473-3099(15)70053-8 DOI: https://doi.org/10.1016/S1473-3099(15)70053-8
Ganmaa, D., Munkhzul, B., Fawzi, W., Spiegelman, D., Willett, W. C., Bayasgalan, P., Baasansuren, E., Buyankhishig, B., Oyun-Erdene, S., Jolliffe, D. A., Xenakis, T., Bromage, S., Bloom, B. R., & Martineau, A. R. (2017). High-Dose Vitamin D-3 during Tuberculosis Treatment in Mongolia. A Randomized Controlled Trial. American Journal of Respiratory and Critical Care Medicine, 196(5), 628–637. https://doi.org/10.1164/rccm.201705-0936OC DOI: https://doi.org/10.1164/rccm.201705-0936OC
Gombart, A. F., Pierre, A., & Maggini, S. (2020). A Review of Micronutrients and the Immune System–Working in Harmony to Reduce the Risk of Infection. Nutrients, 12(1), 236. https://doi.org/10.3390/nu12010236 DOI: https://doi.org/10.3390/nu12010236
Hasanain, A. F. A., Zayed, A. A.-A. H., Abd-ellatief, R. B., & Nafee, A. M. A. (2019). Efficacy and safety of cholecalciferol-augmented anti-tuberculosis therapy for treatment of naïve patients with pulmonary tuberculosis: A randomized, controlled, clinical study. Indian Journal of Tuberculosis, 66(1), 111–117. https://doi.org/10.1016/j.ijtb.2018.06.004 DOI: https://doi.org/10.1016/j.ijtb.2018.06.004
Higgins, J. P. T., Altman, D. G., Gotzsche, P. C., Juni, P., Moher, D., Oxman, A. D., Savovic, J., Schulz, K. F., Weeks, L., & Sterne, J. A. C. (2011). The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ, 343(oct18 2), d5928–d5928. https://doi.org/10.1136/bmj.d5928 DOI: https://doi.org/10.1136/bmj.d5928
Iskandar, D., Suwantika, A. A., Pradipta, I. S., Postma, M. J., & van Boven, J. F. M. (2023). Clinical and economic burden of drug-susceptible tuberculosis in Indonesia: national trends 2017–19. The Lancet Global Health, 11(1), e117–e125. https://doi.org/10.1016/S2214-109X(22)00455-7 DOI: https://doi.org/10.1016/S2214-109X(22)00455-7
Kim, E. W., De Leon, A., Jiang, Z., Radu, R. A., Martineau, A. R., Chan, E. D., Bai, X., Su, W.-L., Montoya, D. J., Modlin, R. L., & Liu, P. T. (2019). Vitamin A Metabolism by Dendritic Cells Triggers an Antimicrobial Response against Mycobacterium tuberculosis. MSphere, 4(3). https://doi.org/10.1128/mSphere.00327-19 DOI: https://doi.org/10.1128/mSphere.00327-19
Lai, Y.-J., Chang, H.-S., Yang, Y.-P., Lin, T.-W., Lai, W.-Y., Lin, Y.-Y., & Chang, C.-C. (2021). The role of micronutrient and immunomodulation effect in the vaccine era of COVID-19. Journal of the Chinese Medical Association, 84(9), 821–826. https://doi.org/10.1097/JCMA.0000000000000587 DOI: https://doi.org/10.1097/JCMA.0000000000000587
Similar Articles
- Quality Evaluation and Storage Stability of Low-Fat Chin-Chin Formulated with Wheat-Soybean Residue (Okara) Flour Blends
- Chemical risk assessment of conventionally and organically grown tomatoes in Côte d'Ivoire
- Physicochemical characteristics and nutritional value of safflower oil: A potential sustainable crop for Egypt
- Comparative Nutritional Characterization of a Novel Formulated Composite Milk Alternative and a Conventional Infant Formula
- Food profile and its effect on the occurrence of diabetes in patients living with HIV: A cross-sectional study at the Nylon district hospital, Cameroon
- Understanding Bread Consumption and Waste Patterns in Algeria and Tunisia: Insights into Consumer Practices and Challenges
- Nutritional Status, Muscle Mass, and Body Fat Percentage in Patients with Breast Cancer Undergoing Adjuvant Chemotherapy
- Bioactive compounds and antioxidant potential of soft wheat and oat bran on the Algerian market
- A UV-Visible spectrophotometric approach to quantify caffeine and carbohydrates in Dhaka's chocolate and candy selection, Bangladesh
- Proximate analysis of selected agricultural waste for their nutritional potential
You may also start an advanced similarity search for this article.
NAJFNR is licensed under 