Date Published: October 24, 2017
Publisher: John Wiley and Sons Inc.
Author(s): Motoaki Sano, Masaru Suzuki, Koichiro Homma, Kei Hayashida, Tomoyoshi Tamura, Tadashi Matsuoka, Yoshinori Katsumata, Shuko Onuki, Junichi Sasaki.
It has been reported that hydrogen gas exerts a therapeutic effect in a wide range of disease conditions, from acute illness such as ischemia–reperfusion injury, shock, and damage healing to chronic illness such as metabolic syndrome, rheumatoid arthritis, and neurodegenerative diseases. Antioxidant and anti‐inflammatory properties of hydrogen gas have been proposed, but the molecular target of hydrogen gas has not been identified. We established the Center for Molecular Hydrogen Medicine to promote non‐clinical and clinical research on the medical use of hydrogen gas through industry–university collaboration and to obtain regulatory approval of hydrogen gas and hydrogen medical devices (http://www.karc.keio.ac.jp/center/center-55.html). Studies undertaken by the Center have suggested possible therapeutic effects of hydrogen gas in relation to various aspects of emergency and critical care medicine, including acute myocardial infarction, cardiopulmonary arrest syndrome, contrast‐induced acute kidney injury, and hemorrhagic shock.
The efficacy of molecular hydrogen (hydrogen gas) for the prevention and treatment of various diseases has been reported by numerous non‐clinical and clinical studies, and the multiple effects of hydrogen are attracting attention.
Among various methods for administration of hydrogen gas, we selected inhalation because it allows monitoring of the dose of hydrogen. Hydrogen gas is flammable and is combustible over the range of 4.0–75.0 vol% (hereinafter described as %) in air at room temperature (also known as the explosion limit). The explosion limit of hydrogen in oxygen ranges between 4.0 and 94.0%. Hydrogen gas is less likely to self‐ignite, with the ignition point being higher for it (527°C) than for gasoline (500°C). Hydrogen gas at concentrations of less than 4.0% used for basic and clinical research is not flammable, and there is no risk of combustion or explosion. When hydrogen is released into the air, it undergoes dispersal and there is no risk of combustion provided that the original concentration of gaseous hydrogen is under the explosion limit. Hydrogen has the lowest molecular weight of all molecules and hydrogen gas promptly becomes undetectable due to diffusion in air or even through walls because of its low density.
Efficacy of molecular hydrogen for various diseases has been shown by basic research. When the clinical efficacy of hydrogen gas is confirmed and regulatory approval is obtained, the indications for this treatment will expand over time. In the near future, it is possible that hydrogen gas will be supplied to patients in the ambulance and will be available from standard wall outlets in hospital, as well as being provided for home inhalation after discharge. However, the clinical efficacy of hydrogen gas needs to be verified scientifically. Hydrogen gas has various physiological actions such as an antioxidant effect, anti‐inflammatory effect, and a protective effect against cell death, but the molecular mechanisms involved have not yet been clarified. The suppression of free radicals alone cannot explain the therapeutic effects of hydrogen. In the future, clarification of the target molecule should help to determine the optimum dosage of hydrogen gas and how to administer hydrogen gas for various indications. The particular advantage of using a cylinder to supply hydrogen gas is instant availability of highly pure gas at a stable concentration, but cylinders are disadvantageous for prolonged treatment. If hydrogen becomes widely used as a medical gas, a hydrogen generator that rapidly stabilizes the concentration and provides a sufficient flow rate would also need to be developed to allow prolonged inhalation of hydrogen gas.
All animal experiments were approved by the Keio University Ethics Committee for Animal Experiments.