Oral 'hydrogen water' induces neuroprotective ghrelin secretion in mice.

Abstract

Although hydrogen-rich water (HRW) consumption is known to exert neuroprotective effects in Parkinson's disease (PD) model mice, striatal hydrogen levels remain undetectable after supplementation, implying an indirect mechanism. This study investigated that mechanism in mice and found that HRW intake elevated gastric ghrelin mRNA expression and circulating ghrelin levels. The β1-adrenoceptor antagonist atenolol blocked this ghrelin upregulation. Critically, the neuroprotective benefit of HRW was eliminated when either the ghrelin receptor antagonist D-Lys(3) GHRP-6 or atenolol was co-administered. These findings establish that ghrelin production, stimulated through adrenergic signaling in the stomach, mediates the neuroprotective action of hydrogen water in PD, identifying a previously unrecognized indirect pathway by which H2 supplementation influences neuronal survival.

Mechanism

Hydrogen-rich water intake stimulates gastric ghrelin mRNA expression and secretion via β1-adrenergic receptor signaling; the resulting ghrelin then activates its receptor to mediate neuroprotection, representing an indirect pathway independent of direct striatal H2 elevation.