Hydrogen gas therapy: From preclinical studies to clinical trials

Background: Mounting evidence indicates that hydrogen gas (H₂) is a versatile therapeutic agent, even at very low, non-combustible concentrations. The Chinese National Health and Medical Commission recently recommended the use of inhaled H₂ in addition to O₂ therapy in the treatment of COVID-19-associated pneumonia, and its effects extend to anti-tumor, anti-inflammatory and antioxidant actions. Summary: In this review, we have highlighted key findings from preclinical research and recent clinical studies demonstrating that H₂ reduces the organ damage caused by ischemia-reperfusion. We have also outlined the critical role this effect plays in a variety of medical emergencies, including myocardial infarction, hemorrhagic shock, and out-of-hospital cardiac arrest, as well as in organ transplantation. H₂ is compared with established treatments such as targeted temperature management, and we have also discussed its possible mechanisms of action, including the recently identified suppression of TNF-α-mediated endothelial glycocalyx degradation by inhaled H₂. In addition, our new method that enables H₂ gas to be easily transported to emergency settings and quickly injected into an organ preservation solution at the site of donor organ procurement have been described. Conclusion: H₂ is an easily administered, inexpensive and well-tolerated agent that is highly effective for a wide range of conditions in emergency medicine, as well as for preserving donated organs.