Research progress in clinical utilization of H2 as a pleiotropic agent.

H2 is a fundamental environmental factor for the origin of life, providing an energetic basis for the emergence of primitive life. Through its selective antioxidant, anti-inflammatory, and anti-apoptotic activities, as well as its regulatory effects on cell signaling pathways and gene expression, H2 exerts broad biological effects and has emerged as a favorable pleiotropic therapeutic agent. To date, hydrogen medicine research has covered almost all types of diseases across organ systems, with more than 170 disease models under investigation. Amid the growing demand for translational applications of hydrogen medicine, clinical research has gradually become a research hotspot. Here, we extensively reviewed the latest mechanistic understanding of H2 and comprehensively summarized the progress of clinical studies on H2 in diseases of different systems, with the goal of informing future large-scale, multi-center clinical trials and supporting the multidisciplinary development of H2 medicine.