Molecular hydrogen therapy

Molecular hydrogen therapy is the hypothesis that hydrogen gas can have a therapeutic effect on animals or humans. Molecular hydrogen (H<sub>2</sub>) has characteristics of a therapeutic drug; it can penetrate membranes, including the blood brain barrier, and rapidly diffuse into the cytosol, mitochondria and nucleus. Its ability to diffuse into the mitochondria and the nucleus are of particular interest because these organelles are difficult to target pharmacologically and are the primary site for generation of reactive oxygen species (ROS).
Molecular hydrogen also exhibits anti-inflammatory, anti-allergic, and anti-apoptotic properties. As an anti-inflammatory agent, molecular hydrogen can down-regulate various pro-inflammatory cytokines in the cells of the injured tissues. As an anti-allergic agent, molecular hydrogen can decrease the activity of the Ca signalling pathway which controls the expression of certain genes involved in immediate allergic reaction.
Available Forms
Inhalation
Hydrogen gas can be administered via inhalation using facemasks, ventilators, gas chambers or nasal cannulas. A 2-4% hydrogen gas mixture is commonly administered since it is below the flammability level at those concentrations.
Injection
Hydrogen gas can also be administered via intravenous injection as hydrogen-rich saline
In Adults
Smoking
Consumption of hydrogen-rich water has been shown to be beneficial for smokers according to an open label pilot study conducted in 2010. The study reported a statistically significant and clinically effective decrease in total cholesterol/HDL (high density lipoproteins) ratio from baseline to week 4 showing that relief from oxidative stress was most significant among smokers.
Type II Diabetes
As per a human study conducted in 2008, hydrogen-rich water also seems to improve lipid and glucose metabolism in individuals with type II diabetes mellitus and impaired glucose tolerance. Therefore hydrogen-rich water may have a beneficial role for diabetes and insulin resistance.
Cancer
Oxidative stress has been regarded as a major contributor to the development of hepatic cancer. A study published in 2011 on the protective role of hydrogen-rich saline proposed the existence of a casual link between reactive oxygen species (ROS) and cancer. Since studies have shown that molecular hydrogen can neutralize free radicals in all types of cells, hydrogen might be a therapeutic gas for cancer by eliminating the toxic ROS that are generated through radiotherapy. Oxidative stress is the result of excessive ROS build-up which can be prevented with the help of antioxidants, as per the findings of a 2014 study on antioxidants as a candidate treatment for depression. Molecular hydrogen has been shown to selectively reduce ROS and therefore serve as a novel anti-oxidant with no known side effects. A 2016 study investigated the effects of hydrogen-rich water on depressive-like behaviour in mice. Many studies on the effects of hydrogen-rich water or hydrogen-rich saline on oxidative stress induced by intense exertion during exercise have been conducted. In a 2012 pilot study, In particular, accumulation of amyloid β-42, a protein of the neuronal cell membrane initiates a cascade of events that results in oxidative stress. Oxidative stress increases with age due to increase in accumulation and decrease in elimination of reactive oxygen species (ROS). It is claimed that when this imbalance occurs in the brain it damages the DNA and proteins of neuronal cells resulting leading to Alzheimer's disease. Parkinson's disease is a progressively chronic condition that results in loss of controlled movement and although medications for symptom relief such as levodopa are available, there is no known cure for Parkinson's disease. it was found that mice that were drinking hydrogen-rich water exhibited a decrease in accumulation of DNA damage and lipid peroxidation due to oxidative stress showcasing that hydrogen-rich water may be able to slow down the progression of Parkinson's disease. The effects of hydrogen-rich water observed in this study among agreed with previous findings observed in animal models. However, the mechanism by which molecular hydrogen reduces oxidative stress in the brain after the consumption of hydrogen-rich water is still unknown. A 2012 study showed that consumption of hydrogen-rich warm water is effective in reducing oxidative stress without side effects. proteins and there are no naturally occurring mechanisms to prevent the effects of the hydroxyl radical.
Pharmacokinetics
The pharmacokinetics of molecular hydrogen gas and hydrogen-rich saline require further research.
Allergic Reactions
In a 2009 mouse study, it was demonstrated that consumption of hydrogen-rich water abolishes an immediate-type allergic reaction (Type-I allergy) by suppressing NADPH oxidase activity and therefore reducing the generation of hydrogen peroxide,<ref name= "Itoh" /> a type of ROS.<ref name= "Dixon" /> Here the benefits of molecular hydrogen therapy are not due to its radical scavenging properties but due to the modulation of a specific signalling pathway<ref name= "Itoh" /> changing the expression of pro-allergic proteins. Yet, this research still needs to be proven in a clinical setting.

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