Oral 'hydrogen water' induces neuroprotective ghrelin secretion in mice

Sci Rep. 2013 Nov 20:3:3273. doi: 10.1038/srep03273.


The therapeutic potential of molecular hydrogen (H₂) is emerging in a number of human diseases and in their animal models, including in particular Parkinson's disease (PD). H₂ supplementation of drinking water has been shown to exert disease-modifying effects in PD patients and neuroprotective effects in experimental PD model mice. However, H₂ supplementation does not result in detectable changes in striatal H₂ levels, indicating an indirect effect. Here we show that H₂ supplementation increases gastric expression of mRNA encoding ghrelin, a growth hormone secretagogue, and ghrelin secretion, which are antagonized by the β1-adrenoceptor blocker, atenolol. Strikingly, the neuroprotective effect of H₂ water was abolished by either administration of the ghrelin receptor-antagonist, D-Lys(3) GHRP-6, or atenolol. Thus, the neuroprotective effect of H₂ 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 H₂ supplementation has been demonstrated.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Corpus Striatum / metabolism
  • Disease Models, Animal
  • Gastric Mucosa / metabolism
  • Gene Expression Regulation
  • Ghrelin / genetics
  • Ghrelin / metabolism*
  • Male
  • Mice
  • Neuroprotective Agents / metabolism*
  • Oral Hygiene*
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism
  • Receptors, Adrenergic, beta-1 / metabolism
  • Signal Transduction
  • Water / administration & dosage
  • Water / standards*


  • Ghrelin
  • Neuroprotective Agents
  • Receptors, Adrenergic, beta-1
  • Water