Molecular hydrogen (dihydrogen; H2) has traditionally been described as a biologically inactive gas, with low capacity to react with most biomolecules. However, in the past two decades hydrogen emerged as a potent therapeutic agent, with antioxidant, anti-inflammatory and anti-apoptotic effects demonstrated in a plethora of animal disease models and human studies. Prominent effects of supplemental H2 in clinical environment are observed especially in oxidative stress-mediated disorders, including neurodegenerative, metabolic, inflammatory and skin diseases. Hydrogen can reach and react with cytotoxic reactive oxygen species (ROS) at the site of cellular damage, and protect tissues against acute and chronic oxidative injuries. In addition, treatment with H2 affected signal transduction and blood buffering capacity, suggesting that scavenging ROS might not be a unique mechanism of its action in vivo. Supplemental hydrogen has been involved in very promising results so far, yet several enigmas remain to be resolved regarding its role in health and disease. In particular, no answer has been provided why large quantities of gut-derived endogenous hydrogen have no systemic effects, while supplemental H2 demonstrates a prominent effect in much less amounts than that produced by intestinal bacteria. In this paper the authors discuss an alternative sites for endogenous H2 production in the human body that might be responsible for systemic effects of hydrogen, and its possible role in the pathogenesis of oxidative stress-related disorders.
Ostojic SM, Vojvodic-Ostojic A. Is melanin a source of bioactive molecular hydrogen? Pharmacol Res. 2016;103:177-9.