The Effect of Vitamin D₃ Supplementation on Diarrhea Frequency, Duration, and Neutrophil-to-Lymphocyte Ratio (NLR) in Children with Diarrhea

Trends in Immunotherapy

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The Effect of Vitamin D₃ Supplementation on Diarrhea Frequency, Duration, and Neutrophil-to-Lymphocyte Ratio (NLR) in Children with Diarrhea

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https://doi.org/10.54963/ti.v10i1.1493
Wibowo, S., Wulandari, K. T., & Amalia, N. (2026). The Effect of Vitamin D₃ Supplementation on Diarrhea Frequency, Duration, and Neutrophil-to-Lymphocyte Ratio (NLR) in Children with Diarrhea. Trends in Immunotherapy, 10(1), 130–143. https://doi.org/10.54963/ti.v10i1.1493
Volume 10, Issue 1 (March 2026): In Progress
Copyright (c) 2026 Satrio Wibowo, Kirnia Tri Wulandari, Nurlinah Amalia
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Authors

  • Satrio Wibowo

    Division of Gastroenterohepatology, Department of Pediatrics, Saiful Anwar General Hospital, Faculty of Medicine, Universitas Brawijaya, Malang 65122, Indonesia
  • Kirnia Tri Wulandari

    Division of Gastroenterohepatology, Department of Pediatrics, Saiful Anwar General Hospital, Faculty of Medicine, Universitas Brawijaya, Malang 65122, Indonesia
  • Nurlinah Amalia

    Faculty of Medicine, Universitas Brawijaya, Malang 65145, Indonesia
    Medical Research Center of Indonesia, Surabaya 61257, Indonesia

Received: 4 August 2025; Revised: 29 September 2025; Accepted: 22 October 2025; Published: 4 February 2026

Diarrhea remains a major cause of morbidity in children under five, and although current management is mainly supportive, Vitamin D₃ supplementation has emerged as a potential immunomodulatory approach whose clinical efficacy requires further clarification. This study aimed to evaluate the effect of Vitamin D₃ supplementation on clinical outcomes, specifically diarrhea frequency, duration, and neutrophil-to-lymphocyte ratio (NLR) in children with acute diarrhea. This single-blind, randomized controlled trial employed a pre-post test control group design involving 34 pediatric patients with diarrhea. Participants were allocated into two groups: one receiving standard therapy alone (control) and the other receiving standard therapy plus oral Vitamin D₃ supplementation for 14 days. Outcome measures included diarrhea frequency, duration, and neutrophil-to-lymphocyte ratio (NLR), evaluated pre-post intervention. Post-intervention analysis showed significant improvements in the intervention group compared to controls: shortened diarrhea duration (p = 0.002), reduced diarrhea frequency (p = 0.000), but no significant with NLR reduction (p = 0.124); however, the median delta NLR decreased more in the Vitamin D₃ group (−2.57) than in the control group (−0.13) (p = 0.031). No significant differences in dehydration status were observed between groups (p = 1.000). The intervention group also exhibited a marked increase in serum 25(OH)D levels post-supplementation (p = 0.000). However, after adjusting for baseline NLR using ANCOVA, the reduction was no longer directly attributable to the intervention (p = 0.09), though a strong trend favoring the Vitamin D group persisted. Vitamin D₃ supplementation may serve as an adjunctive immunotherapy, as it demonstrated beneficial effects on clinical outcomes in pediatric diarrhea, suggesting its potential through anti-inflammatory and immunomodulatory properties.

Keywords:

Vitamin D Diarrhea Children Neutrophil-to-Lymphocyte Ratio (NLR)

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