Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development and potential of hydrogen medicine

Molecular hydrogen (H-2) has been accepted to be an inert and nonfunctional molecule in our body. We have turned this concept by demonstrating that H-2 reacts with strong oxidants such as hydroxyl radical in cells, and proposed its potential for preventive and therapeutic applications. H-2 has a number of advantages exhibiting extensive effects: H-2 rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect signaling reactive oxygen species; therefore, there should be no or little adverse effects of H-2. There are several methods to ingest or consume H-2; inhaling H-2 gas, drinking H-2-dissolved water (H(2-)water), injecting H-2-dissolved saline (H-2-saline), taking an H-2 bath, or dropping H-2-saline into the eyes. The numerous publications on its biological and medical benefits revealed that H-2 reduces oxidative stress not only by direct reactions with strong oxidants, but also indirectly by regulating various gene expressions. Moreover, by regulating the gene expressions, H-2 functions as an anti-inflammatory and anti-apoptotic, and stimulates energy metabolism. In addition to growing evidence obtained by model animal experiments, extensive clinical examinations were performed or are under investigation. Since most drugs specifically act to their targets, H-2 seems to differ from conventional pharmaceutical drugs. Owing to its great efficacy and lack of adverse effects, H-2 has promising potential for clinical use against many diseases. (C) 2014 Elsevier Inc. All rights reserved.