Therapeutic Potential of Molecular Hydrogen in Metabolic Diseases from Bench to Bedside.

Abstract

Oxidative stress and persistent low-grade inflammation are central to the pathophysiology of metabolic disorders such as diabetes mellitus, metabolic syndrome, fatty liver disease, atherosclerosis, and obesity. This review consolidates pre-clinical and clinical findings on molecular hydrogen (H2), which was historically regarded as a biologically inert gas but has emerged over the past two decades as a candidate antioxidant agent. The authors systematically examine evidence for H2 effects across these conditions and explore multiple proposed mechanisms: canonical antioxidant and anti-inflammatory actions, suppression of endoplasmic reticulum stress, induction of autophagy, restoration of mitochondrial function, modulation of gut microbiota composition, and anti-apoptotic signaling. Putative molecular targets of H2 are also discussed. The review concludes that expanded high-quality clinical trials combined with deeper mechanistic investigation will be necessary before H2 can be routinely applied in clinical settings for metabolic disease management.

Mechanism

H2 is proposed to act through selective scavenging of reactive oxygen species, suppression of NF-κB-mediated inflammatory signaling, attenuation of endoplasmic reticulum stress, induction of autophagy, restoration of mitochondrial function, and modulation of gut microbiota composition.