Neuroprotective and Preventative Effects of Molecular Hydrogen.

Abstract

This review examines the neuroprotective capacity of molecular hydrogen (H₂) and its potential relevance to neurodegenerative conditions such as Parkinson's and Alzheimer's diseases, for which disease-modifying pharmacological options remain limited. Multiple mechanisms are discussed, including suppression of reactive oxygen species (ROS)—encompassing both hydroxyl radicals and superoxide—anti-inflammatory signaling, and endocrine regulation through the gut-brain axis. In Parkinson's disease model mice, sustained H₂ intake was associated with increased ghrelin secretion from the stomach. In Alzheimer's disease model mice, sex-dependent neuroprotection was observed: female mice showed preservation of estrogen and estrogen receptor-β (ERβ) levels, accompanied by upregulation of brain-derived neurotrophic factor (BDNF) and its receptor TrkB. The precise molecular targets through which H₂ modulates endocrine pathways and exerts these effects remain to be identified, representing a key direction for future research.

Mechanism

H₂ suppresses ROS generation including hydroxyl radicals and superoxide, exerts anti-inflammatory effects, and modulates the gut-brain endocrine axis by promoting ghrelin release and preserving estrogen/ERβ levels, thereby upregulating BDNF and TrkB expression in neural tissue.