Tyler LeBaron, Founder and Director of the Molecular Hydrogen Institute in Utah, USA, describes the growing research supporting the use of hydrogen in medicine
Molecular hydrogen (ie. H2 gas) is gaining significant attention from academic researchers, medical doctors, and physicians around the world for its recently reported therapeutic potential. One of the earliest publications on hydrogen as a medical gas was in 1975 by Dole and colleagues from Baylor University and Texas A&M. They reported that hyperbaric (8-atom) hydrogen therapy was effective at reducing melanoma tumours in mice.
However, the interest in hydrogen therapy only recently began after 2007, when it was demonstrated that administration of hydrogen gas via inhalation (at levels below the flammability limit of 4.6%) or ingestion of an aqueous solution containing dissolved hydrogen could also exert therapeutic biological effects. These findings suggest hydrogen has immediate medical and clinical applications.
In 2007 Dr Shigeo Ohta’s team reported that inhalation of 2-4% hydrogen gas significantly reduced the cerebral infarct volumes in a rat model of ischemia-reperfusion injury induced by middle cerebral artery occlusion. Hydrogen was more effective than edaravone, an approved clinical drug for cerebral infarction, but with no toxic effects. The authors further demonstrated that dissolved hydrogen in the media of cultured cells, at biologically relevant concentrations, reduces the level of toxic hydroxyl radicals (*OH), but does not react with other physiologically important reactive oxygen species (ROS) (eg. superoxide, nitric oxide, hydrogen peroxide).
This biomedical research on hydrogen is still in its infancy with only around 1,000 articles and 1,600 researchers, but these publications and researchers suggest that hydrogen has therapeutic potential in over 170 different human and animal disease models, and in essentially every organ of the human body. Hydrogen appears to provide these benefits via modulating signal transduction, protein phosphorylation and gene expressions (see below, Pharmacodynamics).
The idea of therapeutic gaseous molecules is not a new concept. For example, carbon monoxide (CO), hydrogen sulfide (H2S) and, of course, nitric oxide (NO*), which was initially ridiculed by sceptics, but later was subject to a Nobel Prize, are all biologically active gases. However, it may still be difficult to believe that H2 can exert any biological effect because, in contrast to these other gases, hydrogen is a non-radical, non-reactive, non-polar, highly diffusible, neutral gas; thus it is unlikely to have specific binding sites or interact with specificity on a specific receptor.
From an evolutionary perspective it may not be strange that hydrogen exerts a biological effect. In addition to its role in the origins of the universe, hydrogen was also involved in the genesis of life and played an active role in the evolution of eukaryotes (organisms whose cells have a nucleus enclosed within a nuclear envelope). Over the millions of years of evolution, plants and animals have developed a mutualistic relationship with hydrogen-producing bacteria, resulting in basal levels of molecular hydrogen in eukaryotic systems. This constant exposure to molecular hydrogen may have conserved the original targets of hydrogen, as can be extrapolated by genetic remnants of hydrogenase enzymes in higher eukaryotes. Alternatively, but not exclusively, eukaryotes may have developed sensitivity to molecular hydrogen over the millions of years of evolution.
Methods of administration
Molecular hydrogen can be administered via inhalation, ingestion of solubilised (dissolved), hydrogen-rich solutions (eg. water, flavoured beverages), hydrogen-rich, hemodialysis solution, intravenous injection of hydrogen-rich saline, topical administration of hydrogen-rich media (eg. bath, shower and creams), hyperbaric treatment, ingestion of hydrogen-producing material upon reaction with gastric acid, ingestion of non-digestible carbohydrates as prebiotic to hydrogen-producing intestinal bacteria, rectal insufflation and other methods.
Read the complete article in issue 106.