Beneficial biological effects and the underlying mechanisms of molecular hydrogen - comprehensive review of 321 original articles

Abstract

Therapeutic effects of molecular hydrogen for a wide range of disease models and human diseases have been investigated since 2007. A total of 321 original articles have been published from 2007 to June 2015. Most studies have been conducted in Japan, China, and the USA. About three-quarters of the articles show the effects in mice and rats. The number of clinical trials is increasing every year. In most diseases, the effect of hydrogen has been reported with hydrogen water or hydrogen gas, which was followed by confirmation of the effect with hydrogen-rich saline. Hydrogen water is mostly given ad libitum. Hydrogen gas of less than 4 % is given by inhalation. The effects have been reported in essentially all organs covering 31 disease categories that can be subdivided into 166 disease models, human diseases, treatment-associated pathologies, and pathophysiological conditions of plants with a predominance of oxidative stress-mediated diseases and inflammatory diseases. Specific extinctions of hydroxyl radical and peroxynitrite were initially presented, but the radical-scavenging effect of hydrogen cannot be held solely accountable for its drastic effects. We and others have shown that the effects can be mediated by modulating activities and expressions of various molecules such as Lyn, ERK, p38, JNK, ASK1, Akt, GTP-Rac1, iNOS, Nox1, NF-κB p65, IκBα, STAT3, NFATc1, c-Fos, and ghrelin. Master regulator(s) that drive these modifications, however, remain to be elucidated and are currently being extensively investigated.

Study details

Article type

Review

Disease / injury model

Multiple disease models including ischemia-reperfusion injury, inflammatory diseases, metabolic syndrome, neurodegenerative diseases, cardiovascular diseases, and more.

Dose comparison

Dose–response effects are observed for both drinking hydrogen-rich water and inhaled hydrogen gas, but not when comparing hydrogen concentrations between water and gas. Hydrogen-rich water often shows more prominent effects than hydrogen gas, despite lower hydrogen intake.

Dose-dependent effect

Yes

Outcome

Positive

Findings

Molecular hydrogen demonstrates beneficial biological effects across a wide range of disease models and human diseases, particularly those involving oxidative stress and inflammation. The review summarizes 321 original articles, showing efficacy in essentially all organs and in plants, with effects mediated by both direct radical scavenging and modulation of signaling pathways.