Therapeutic potential of hydrogen-rich water (HRW) in oxidative stress-related diseases.

Oxidative stress is a central mechanism in metabolic, cardiovascular, and neurodegenerative diseases, contributing to inflammation, mitochondrial dysfunction, and apoptosis. Consequently, redox-modulating therapies are increasingly explored as potential therapeutic strategies. This review evaluates the mechanistic basis, experimental evidence, and clinical applicability of hydrogen-rich water (HRW) in oxidative stress-related diseases. A structured literature search identified mechanistic, preclinical, and clinical studies investigating HRW or molecular hydrogen (H2) on oxidative stress, inflammation, mitochondrial regulation, and disease-related outcomes. Due to substantial methodological heterogeneity, findings were synthesized qualitatively. HRW has been proposed to selectively neutralize highly reactive species such as hydroxyl radicals (•OH) and peroxynitrite (ONOO-) while preserving physiological reactive oxygen species signalling. Mechanistic studies demonstrate activation of nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE) pathways, suppression of nuclear factor kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) inflammatory cascades, modulation of JAK/STAT signalling, preservation of mitochondrial bioenergetics, and enhancement of autophagic regulation. Preclinical and clinical studies report improvements in glycaemic control, endothelial function, cardiometabolic health, neuroprotection, exercise performance, and treatment-related fatigue. Despite an excellent safety profile, standardization of HRW preparation and large multicentre randomized controlled trials (RCTs) remain necessary to establish clinical efficacy and translational potential.