Oral ‘hydrogen water' induces neuroprotective ghrelin secretion in mice

The therapeutic potential of molecular hydrogen (H(2)) is emerging in a number of human diseases and in their animal models, including in particular Parkinson's disease (PD). H(2) supplementation of drinking water has been shown to exert disease-modifying effects in PD patients and neuroprotective effects in experimental PD model mice. However, H(2) supplementation does not result in detectable changes in striatal H(2) levels, indicating an indirect effect. Here we show that H(2) supplementation increases gastric expression of mRNA encoding ghrelin, a growth hormone secretagogue, and ghrelin secretion, which are antagonized by the β(1)-adrenoceptor blocker, atenolol. Strikingly, the neuroprotective effect of H(2) water was abolished by either administration of the ghrelin receptor-antagonist, D-Lys(3) GHRP-6, or atenolol. Thus, the neuroprotective effect of H(2) in PD is mediated by enhanced production of ghrelin. Our findings point to potential, novel strategies for ameliorating pathophysiology in which a protective effect of H(2) supplementation has been demonstrated.