Hydrogen peroxide pathway in ulcerative colitis: Promises and challenges in translating novel pathogenesis to clinical practice

Abstract

This letter addresses Pravda's innovative review, which proposes hydrogen peroxide as the primary pathogenic factor in ulcerative colitis (UC). Although the author presents intriguing mechanistic insights and reports encouraging clinical outcomes with reducing agents, several methodological and clinical considerations require discussion. We examine three key aspects: The selective evidence synthesis approach; the need for rigorous clinical validation of proposed therapies; and the integration of this novel hypothesis with established inflammatory bowel disease pathogenesis. Given the complexity of UC, future therapeutic advances may require collaborative approaches that integrate redox-based mechanisms into existing evidence-based frameworks rather than replacing current paradigms.

Keywords: Ulcerative colitis; Hydrogen peroxide; Pathogenesis; Reducing agents; Therapeutic targets

Core Tip: Pravda's hydrogen peroxide (H₂O₂) hypothesis provides mechanistic insights for ulcerative colitis but faces several clinical translation challenges. These include difficulties in H₂O₂ measurement, limited safety data for reducing agents, and the risk of patients abandoning proven therapies. We recommend conducting phase 2 trials, comprehensive safety assessments, and research approaches that integrate redox mechanisms with established frameworks. Collaborative strategies that balance scientific exploration with patient safety may ensure appropriate validation before clinical adoption.