Comparative Effectiveness of Zinc Supplementation Combined with Probiotic Therapy Versus Zinc Alone in Reducing Acute Diarrhea Duration, Severity, and Recurrence Rates in Pediatric Populations: A Meta-Analysis

Wasiq Raza; Talat Mahmood; Lyaba Atta; Sualeh Hassan; Sami Ullah; Shahid Ali; Mian Muhammad; Nigar Ahmad

doi:10.70749/ijbr.v2i02.256

Authors

Wasiq Raza Department of Paediatric, Lady Reading Hospital (MTI), Peshawar, KP, Pakistan.
Talat Mahmood Department of Paediatric, Lady Reading Hospital (MTI), Peshawar, KP, Pakistan.
Lyaba Atta Department of Paediatrics, Lady Reading Hospital, Peshawar, KP, Pakistan.
Sualeh Hassan Department of Pathology, Khyber Girls Medical College, Peshawar, KP, Pakistan.
Sami Ullah Department of Paediatrics, Lady Reading Hospital, Peshawar, KP, Pakistan.
Shahid Ali Department of Paediatrics, Lady Reading Hospital, Peshawar, KP, Pakistan.
Mian Muhammad Department of Paediatrics, Lady Reading Hospital, Peshawar, KP, Pakistan.
Nigar Ahmad Department of Paediatric, Lady Reading Hospital (MTI), Peshawar, KP, Pakistan.

DOI:

https://doi.org/10.70749/ijbr.v2i02.256

Keywords:

Zinc Supplementation, Probiotic Therapy, Acute Diarrhea, Pediatric Populations, Meta-Analysis

Abstract

Background: Diarrhea remains a significant concern for children under five, particularly in developing countries. While zinc supplementation is a standard intervention for managing diarrheal diseases, the potential role of probiotics in restoring gut flora is gaining recognition. However, limited research has compared the efficacy of zinc alone versus zinc combined with probiotics. Objective: This meta-synthesis aimed to evaluate evidence from comparative studies to determine whether combining zinc with probiotics is superior to zinc alone in reducing the incidence, severity, and recurrence of diarrhea in children. Methods: A systematic review of 24 studies published in English, including 18 randomized controlled trials (RCTs) and six observational studies, was conducted following PRISMA guidelines. The focus was on children aged 0–12 years with acute diarrhea. Outcomes assessed included fecal and diarrheal frequency, episode duration, and relapse rates within three months. Standardized mean differences (SMDs) and odds ratios (ORs) were calculated for quantitative synthesis. Results: Combination therapy significantly reduced diarrhea duration by 1.25 standard deviations (p < 0.001) and recurrence rates by a factor of 0.65 (p = 0.002) compared to zinc monotherapy. Notably, Saccharomyces boulardii and Lactobacillus rhamnosus GG exhibited the highest efficacy. Sensitivity analysis confirmed the robustness of these findings. Conclusion: Probiotics enhance the effectiveness of zinc in managing acute diarrhea in children. These findings support incorporating combination therapy into pediatric care globally, aligning with public health recommendations to improve outcomes for children

References

Bajoria, S. (2023). In Vitro Stability and in Vivo Performance Considerations to Develop Low-Cost Recombinant Protein Formulations for Passive and Active Immunization (Doctoral dissertation, University of Kansas).

Johnson, K. A. (2018). Prayer: A Helpful Aid in Recovery from Depression. Journal of Religion and Health, 57(6), 2290–2300. https://doi.org/10.1007/s10943-018-0564-8

Barffour, M. A., Hinnouho, G.-M., Wessells, K. R., Kounnavong, S., Ratsavong, K., Sitthideth, D., Bounheuang, B., Sengnam, K., Chanhthavong, B., Arnold, C. D., Brown, K. H., Larson, C. P., & Hess, S. Y. (2020). Effects of therapeutic zinc supplementation for diarrhea and two preventive zinc supplementation regimens on the incidence and duration of diarrhea and acute respiratory tract infections in rural Laotian children: A randomized controlled trial. Journal of Global Health, 10(1). https://doi.org/10.7189/jogh.10.010424

Clemente-Suárez, V. J., Martín-Rodríguez, A., Redondo-Flórez, L., Villanueva-Tobaldo, C. V., Yáñez-Sepúlveda, R., & Tornero-Aguilera, J. F. (2023). Epithelial Transport in Disease: An Overview of Pathophysiology and Treatment. Cells, 12(20), 2455. https://doi.org/10.3390/cells12202455

Guamán, L. P., Carrera-Pacheco, S. E., Zúñiga-Miranda, J., Teran, E., Erazo, C., & Barba-Ostria, C. (2024). The Impact of Bioactive Molecules from Probiotics on Child Health: A Comprehensive Review. Nutrients, 16(21), 3706–3706. https://doi.org/10.3390/nu16213706

Kaźmierczak-Siedlecka, K., Ruszkowski, J., Fic, M., Folwarski, M., & Makarewicz, W. (2020). Saccharomyces boulardii CNCM I-745: A Non-bacterial Microorganism Used as Probiotic Agent in Supporting Treatment of Selected Diseases. Current Microbiology, 77(9), 1987–1996. https://doi.org/10.1007/s00284-020-02053-9

Vassilopoulou, L., Spyromitrou-Xioufi, P., & Ladomenou, F. (2021). Effectiveness of probiotics and synbiotics in reducing duration of acute infectious diarrhea in pediatric patients in developed countries: a systematic review and meta-analysis. European Journal of Pediatrics. https://doi.org/10.1007/s00431-021-04046-7

Rondanelli, M., Lamburghini, S., Faliva, M. A., Peroni, G., Riva, A., Allegrini, P., ... & Miccono, A. (2021). A food pyramid, based on a review of the emerging literature, for subjects with inflammatory bowel disease. Endocrinología, Diabetes y Nutrición (English ed.), 68(1), 17-46. https://doi.org/10.1016/j.endien.2020.01.010

Pendu, J. L., Breiman, A., Rocher, J., Dion, M., & Ruvoën-Clouet, N. (2021). ABO Blood Types and COVID-19: Spurious, Anecdotal, or Truly Important Relationships? A Reasoned Review of Available Data. Viruses, 13(2), 160. https://doi.org/10.3390/v13020160

Chandiwana, N. C., Serenata, C. M., Owen, A., Rannard, S., Pérez Casas, C., Scott, C., Hill, A., Clayden, P., & Flexner, C. (2021). Impact of long-acting therapies on the global HIV epidemic. AIDS, 35(Supplement 2), S137–S143. https://doi.org/10.1097/qad.0000000000003102

Lübbert, C. (2015). Antimicrobial therapy of acute diarrhoea: a clinical review. Expert Review of Anti-Infective Therapy, 14(2), 193–206. https://doi.org/10.1586/14787210.2016.1128824

Lamberti, L. M., Fischer Walker, C. L., & Black, R. E. (2012). Systematic review of diarrhea duration and severity in children and adults in low- and middle-income countries. BMC Public Health, 12(1). https://doi.org/10.1186/1471-2458-12-276

Scarpellini, E., Balsiger, L. M., Maurizi, V., Rinninella, E., Gasbarrini, A., Giostra, N., Santori, P., Abenavoli, L., & Rasetti, C. (2022). Zinc and gut microbiota in health and gastrointestinal disease under the COVID‐19 suggestion. BioFactors, 48(2), 294–306. https://doi.org/10.1002/biof.1829

Srivastav, Y., Prajapati, A., Meera, K., & Madhaw, K. (2023). General overview of the Risk factors, Pathogenesis, and Combined treatments for Hashimoto’s Thyroiditis (HT). World Journal of Current Medical and Pharmaceutical Research, 175–189. https://doi.org/10.37022/wjcmpr.v5i5.290

Mousavi Khaneghah, A., Abhari, K., Eş, I., Soares, M. B., Oliveira, R. B. A., Hosseini, H., Rezaei, M., Balthazar, C. F., Silva, R., Cruz, A. G., Ranadheera, C. S., & Sant’Ana, A. S. (2020). Interactions between probiotics and pathogenic microorganisms in hosts and foods: A review. Trends in Food Science & Technology, 95, 205–218. https://doi.org/10.1016/j.tifs.2019.11.022

Jankiewicz, M., Łukasik, J., Kotowska, M., Kołodziej, M., & Szajewska, H. (2022). Strain-Specificity of Probiotics in Pediatrics: A Rapid Review of the Clinical Evidence. Journal of Pediatric Gastroenterology and Nutrition, 76(2), 227–231. https://doi.org/10.1097/mpg.0000000000003675

Huang, R., Xing, H.-Y., Liu, H.-J., Chen, Z.-F., & Tang, B.-B. (2021). Efficacy of probiotics in the treatment of acute diarrhea in children: a systematic review and meta-analysis of clinical trials. Translational Pediatrics, 10(12), 3248–3260. https://doi.org/10.21037/tp-21-511

Miller, L. E. (2017). Effects of probiotic-containing products on stool frequency and intestinal transit in constipated adults: systematic review and meta-analysis of randomized controlled trials. Annals of Gastroenterology, 30(6). https://doi.org/10.20524/aog.2017.0192