Nutritional and Supplemental Interventions for Prevention and Treatment of Oral Mucositis in Pediatric Oncology

Background: Oral mucositis (OM) is a frequent complication of anticancer therapy which arises from cytotoxic injury, having significant clinical implications. Nutritional and supplement-based interventions have been proposed as adjunctive strategies to improve outcomes. Objectives: This systematic review aimed to identify and synthesize evidence from randomized controlled trials (RCTs) evaluating nutritional or natural supplement interventions for prevention or management of OM in pediatric oncology. Methods: We conducted a systematic search (17 August 2025) of Scopus, PubMed/MEDLINE, and Google Scholar (1 January 2000–1 June 2025) following PRISMA guidelines and registered in PROSPERO (CRD420251134454). The review included randomized controlled trials in pediatric cancer patients (≤18 years; up to 25 years for follow-up) receiving chemo-/radiotherapy, assessing nutritional, dietary, or natural product interventions for oral mucositis prevention or treatment. Non-randomized, adult, non-English, non-peer-reviewed, or inaccessible studies were excluded. Outcomes included incidence, severity, duration of OM, and mucositis-associated pain. Risk of bias was assessed using the NIH Study Quality Assessment Tools and the Cochrane RoB 2 tool. Results were qualitatively summarized. Results: Of 5870 records identified, 20 RCTs met inclusion criteria resulting in 1430 total included patients. Interventions tested included systemic supplements (e.g., glutamine, zinc, and bovine colostrum), topically applied agents (e.g., honey, vitamin E, Aloe vera, and olive oil), and nutrient-containing rinses (e.g., chamomile, Caphosol, and Traumeel S). Honey-based interventions showed promising outcomes. Discussion: Study designs and sample sizes varied considerably, and outcome measures were heterogeneous. Challenges with blinding, variable compliance, and inconsistent reporting reduce confidence and precision in the findings. Conclusions: Evidence from pediatric RCTs remains limited but highlights nutritional and natural products as promising supportive care options for OM. Findings suggest potential for practical, low-cost adjuncts to established oral care protocols, warranting further high-quality multicenter trials.