Molecular hydrogen as a novel antioxidant: overview of the advantages of hydrogen for medical applications

Methods Enzymol. 2015:555:289-317. doi: 10.1016/bs.mie.2014.11.038. Epub 2015 Jan 21.


Molecular hydrogen (H2) was believed to be inert and nonfunctional in mammalian cells. We overturned this concept by demonstrating that H2 reacts with highly reactive oxidants such as hydroxyl radical ((•)OH) and peroxynitrite (ONOO(-)) inside cells. H2 has several advantages exhibiting marked effects for medical applications: it is mild enough neither to disturb metabolic redox reactions nor to affect signaling by reactive oxygen species. Therefore, it should have no or little adverse effects. H2 can be monitored with an H2-specific electrode or by gas chromatography. H2 rapidly diffuses into tissues and cells to exhibit efficient effects. Thus, we proposed the potential of H2 for preventive and therapeutic applications. There are several methods to ingest or consume H2: inhaling H2 gas, drinking H2-dissolved water (H2-water), injecting H2-dissolved saline (H2-saline), taking an H2 bath, or dropping H2-saline onto the eyes. Recent publications revealed that, in addition to the direct neutralization of highly reactive oxidants, H2 indirectly reduces oxidative stress by regulating the expression of various genes. Moreover, by regulating gene expression, H2 functions as an anti-inflammatory, antiallergic, and antiapoptotic molecule, and stimulates energy metabolism. In addition to growing evidence obtained by model animal experiments, extensive clinical examinations were performed or are under way. Since most drugs specifically act on their specific targets, H2 seems to differ from conventional pharmaceutical drugs. Owing to its great efficacy and lack of adverse effects, H2 has potential for clinical applications for many diseases.

Keywords: Clinical examination; Hydroxyl radical; Inert gas; No adverse effect; Peroxynitrite; Rapid diffusion; Selective reduction.

Publication types

  • Review

MeSH terms

  • Administration, Inhalation
  • Administration, Oral
  • Administration, Topical
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Antioxidants / pharmacology*
  • Clinical Trials as Topic
  • Energy Metabolism / drug effects
  • Gene Expression Regulation / drug effects
  • Humans
  • Hydrogen / pharmacology*
  • Hydroxyl Radical / antagonists & inhibitors*
  • Hydroxyl Radical / chemical synthesis
  • Hydroxyl Radical / metabolism
  • Injections, Intravenous
  • Oxidative Stress / drug effects*
  • Peroxynitrous Acid / antagonists & inhibitors*
  • Peroxynitrous Acid / metabolism


  • Anti-Inflammatory Agents, Non-Steroidal
  • Antioxidants
  • Peroxynitrous Acid
  • Hydroxyl Radical
  • Hydrogen