“INTRODUCTION TO MOLECULAR HYDROGEN”

SCIENTIFIC RECOGNITION OF HYDROGEN

Although the primary targets or exact biochemical mechanisms of hydrogen are still not fully understood, the therapeutic effect in cells, tissues, animals, humans and even plants [64] is becoming widely accepted due to the now over 500 peer-reviewed articles and the 1,600 researchers on the medical effects of hydrogen. The quality of the publications is also improving with an average impact factor (IF) of the journals publishing hydrogen is about 3. The table below shows a few of the studies published in the higher IF journals, which range from six to 27.

HYDROGEN AND IMMEDIATE MEDICAL APPLICATIONS

optimistfig10Hydrogen as a medical gas is also growing because it has immediate medical applications to help with many of the current health crises [65, 66]. Dixon and colleagues of Loma-Linda University reported that hydrogen has potential to help with the top 8/10 disease-causing fatalities as listed by the Centers of Disease Control [67]. Dr. Banks,from the VA/U of Washington, reported that ingestion of hydrogen-rich water was protective against neurodegenerative changes induced by traumatic brain injury in mice [68]. Their results show that hydrogen administration reduced brain edema, blocked pathological tau expression, and maintained ATP levels. This and other studies have profound effects for events where brain injury (e.g. concussion, chronic traumatic encephalopathy, etc.) is a common occurrence [69]. Although many people report dramatic effects of hydrogen therapy, from rapid pain and inflammation relief to normalization of glucose and cholesterol levels, other people may not notice any immediate or observable benefits. Hydrogen is not considered a powerful drug, and as mentioned only helps bring the cell/organ back to homeostasis without causing major perturbations. Perhaps some of the reported dramatic effects can be attributed to the placebo effect or other things, although some researchers have noted that some people are more sensitive to hydrogen and experience greater effects. More human studies are needed to answer these questions.

HUMAN RESEARCH

Although the research on hydrogen looks promising in the cell or animal models, more long-term clinical trials are required to confirm its efficacy in humans [70]. There are only a total of 40 human studies; few are in a double-blinded placebo controlled randomized fashion with sufficient subject numbers. A few of these clinical studies suggest that ingestion of hydrogen-rich water was beneficial for metabolic syndrome [71], diabetes [72], and hyperlipidemia [73, 74]. Another 1-year placebo-control clinical study suggested that hydrogen-rich water is beneficial for Parkinson’s disease [75], while other clinical studies suggest significant benefits for rheumatoid arthritis [24, 76], mitochondrial dysfunction [77], exercise performance [78], athletic recovery time [79], wound healing [80-82], reductions of oxidative stress from chronic hepatitis B [83], improvements to blood flow [84], and periodontitis [85], in dialysis [86, 87], and also the quality of life in patients receiving radiotherapy for tumors [88] and others [5].

There have been an additional 15+ human studies completed with promising results, which are in the process of manuscript preparation and publication through the peer-reviewed process. More human studies are required to determine proper dosage, timing, method of administration, and for which diseases, and potentially genotypes, hydrogen is most effective [7]. Hydrogen is still in its infancy, and more data is required before we can scientifically claim any real benefit, but the preliminary data is intriguing. The research on disease models, mechanisms of action, and clinical studies are particularly relevant because the high safety profile of molecular hydrogen make it a superior choice [89].

SAFETY

Hydrogen is naturally produced by intestinal flora upon digestion of fibers [90]. A study from the University of Florida and the Forsythe Institute of Boston, Massachusetts confirmed that hydrogen produced from bacteria exerted therapeutic effects [91]. They found that reconstitution of intestinal microbiota with H2-producing E. coli, but not H2-deficient mutant E. coli, was protective against Concanvalin A-induced hepatitis. Other studies also show that bacterially produced hydrogen from acarbose administration is therapeutic [92]. Perhaps this helps explain why a large clinical trial from the Journal of American Medical Association (JAMA) found significant reductions in cardiovascular events by those taking the hydrogen-producing acarbose drug [92, 93]. These studies not only suggest the therapeutic action of molecular hydrogen, but also demonstrate its high safety profile. Hydrogen is very natural to our bodies, as we are exposed to it on a daily basis as a result of normal bacterial metabolism [1]. Additionally, hydrogen gas has also been used in deep sea diving since the 1940s to prevent decompression sickness [94, 95]. Hundreds of human studies for deep sea diving have shown inhalation of hydrogen gas, at orders of magnitude greater than what is needed for therapeutic use, is well-tolerated by the body with no chronic toxic effects [96]. In some people, however, it is reported that hydrogen may result in loose stools [97], and in rare cases with diabetics, hypoglycemia [77], which is controlled by reducing the level of insulin administered. The hundreds of studies on hydrogen from bacterial production, deep sea diving, and recent medical applications have not revealed any direct noxious side effects of hydrogen administration at biologically therapeutic levels. Such a high safety profile may be considered paradoxical because chemotherapeutic agents that exert biological effects should have both beneficial and noxious effects depending on dosage, timing, location, duration, etc. However, such noxious effects have yet to be reported for hydrogen. However, perhaps the noxious effects are so transient and mild that they are masked by the beneficial effects, or are even what mediate the beneficial effects via hormetic pathways.

FUTURE DIRECTIONS

The goal of the Molecular Hydrogen Foundation (MHF) is to help advance the research, education, and awareness of hydrogen as a therapeutic medical gas. It is uncommon to find a treatment that has both a high therapeutic potential and a high safety profile; hydrogen appears to fit this combination [23]. Some researchers become interested in hydrogen simply due to its unforeseen ability to have a biological effect; with the realization that hydrogen is both safe and effective, a moral obligation develops to advance the research, education, and awareness of hydrogen as a medical gas. We welcome other biomedical researchers to join us in elucidating the in vitro molecular mechanisms of hydrogen, to perform well-controlled clinical trials on hydrogen in order to understand the best dosage, timing, genotype, and method of hydrogen administration. With only a few hundred peer-reviewed articles and a couple thousand biomedical researchers, hydrogen research is still in its infancy. However, the preliminary studies suggest that molecular hydrogen is something that should be pursued, investigated, and elucidated for the potential benefit of disease prevention and treatment.

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