Healthy Aging

Molecular Hydrogen: A Surprising New Nutraceutical

What is it, and how does it work?

Molecular hydrogen (H2) contains two atoms of hydrogen (H), the most abundant and lightest element in the universe. H2 is a colorless, odorless, tasteless gas, which was classically thought to have no effect in the body. This view is quickly changing, however, as various biochemical, physiological, and health-promoting effects of H2 are being discovered.[1]

Recent studies have shown that molecular hydrogen is a highly selective antioxidant that may protect essentially all organs, including the brain, against oxidative stress. The biological effects of H2 translate to numerous health benefits—so many, in fact, that hundreds of scientific publications now exist.[2],[3] In today’s post we’ll answer these questions: what is molecular hydrogen, and how does it work?

History of molecular hydrogen

The earliest recorded use of H2, dating back to the 1940s, was as a breathing gas for deep sea diving. Scientists found that a breathing mixture of 96% hydrogen and 4% oxygen (O2) was stable, and that a diver could be sustained with such a mixture.[4] However, safety measures are essential when using such gases, because there is a risk of explosion with such a combination if O2 levels exceed 4%.

H2 gained additional interest in 1975 when it was shown that mice breathing 97.5% H2 and 2.5% O2 in a hyperbaric chamber experienced significant regression of skin cancer.[5] In 2001, a similar hyperbaric treatment was shown to protect against liver injury in animals with hepatitis due to a liver parasite infection.[6] Clinical studies with molecular H2 did not substantially progress, however, until more practical means of achieving therapeutic levels of H2 were discovered.

A breakthrough occurred in 2007 when a group of scientists studied the cellular effects of dissolved H2 in a nutrient solution.[7] They determined that H2 reacts primarily with highly reactive and toxic oxygen radicals, leaving weaker (and biologically necessary) oxidants, such as nitric oxide, undisturbed. The authors conclude, “We propose that H2, one of the most well-known molecules, could be widely used in medical applications as a safe and effective antioxidant with minimal side effects.” They also note: “For prevention, H2 saturated in water could be administered.” This high-impact publication has been cited more than 1400 times to date.[8]

Hydrogen can be administered by inhalation or oral supplementation

For practical daily use, measurable benefits can be achieved by drinking pure water saturated with hydrogen.

Additional methods for administering H2 gas include inhalation (usually 1 to 4% H2),[9],[10] and/or the injection of H2-rich saline,[11] both of which require medical supervision. However, for practical daily use, measurable benefits can also be achieved by drinking pure water saturated with H2.[12],[13],[14]

At standard temperature and pressure (STP), water has almost no free H2 (a mere 8.7 × 10-7 parts per million [ppm], or .00000087 milligrams per liter [mg/L]).[15] The amount of H2 can be increased by bubbling hydrogen gas into pure water,[16] by the use of an electrolysis device,[17] or by using specially formulated tablets that generate H2 when they dissolve in water.[11] The saturation concentration (or maximum solubility) of H2 in water is 1.6 ppm (1.6 mg/L) at STP.[9]

Various H2-producing devices are available on the market, including alkaline water ionizers and neutral-pH H2 water generators, but the results achieved with these systems are highly variable. The H2 concentration produced by such devices generally ranges from less than 0.01 ppm to 1.5 ppm.[18] With H2-generating tablets, however, water can be supersaturated with H2, achieving a concentration of up to 10 ppm. Clinically significant results have been achieved with H2-rich water containing 5 to 10 ppm H2 as well as other less concentrated H2-rich water products.[19],[20],[21]

After the consumption of H2-rich water, the H2 concentrations in the breath and plasma increase in a dose-dependent manner, peaking between five to 15 minutes and returning to baseline roughly 45 to 90 minutes later, depending on the ingested dose.[22],[23] Safety concerns with flammability do not exist with H2-rich water because the amount of H2 is far below the flammability threshold.

Molecular hydrogen’s antioxidant effects

Studies suggest that molecular hydrogen selectively reduces excessive amounts of tissue oxidants in many different diseases.

A modest amount of oxidative stress is normal, and plays an important role in our very existence. Nitric oxide, for example, is an oxidant that triggers necessary cellular signaling pathways and processes such as vasodilation.[24],[25] However, when the body is put into a highly stressed state, which can exist in acute injury, progressive disease, or treatment for a condition like cancer, the threshold above which these and other oxidants can be beneficial is exceeded.[26] Chronic oxidative stress is one of the major contributors to many lifestyle-related and progressive diseases, as well as the process of aging. Studies suggest that H2 selectively reduces excessive amounts of tissue oxidants in many different diseases.[2],[27],[28],[29],[30]

H2 readily passes through cellular membranes, including the blood–brain barrier, thus helping to protect the brain against oxidative stress.[31],[32] H2 can also enter the mitochondria and nucleus within cells.[33],[34] These are very important properties, since many other antioxidants lack the ability to affect the mitochondria or brain so readily.

In addition to mopping up free radicals, H2 activates the nuclear factor erythroid 2-related factor (Nrf2) cell-signaling pathway, an intrinsic mechanism of defense against oxidative stress.[35],[36],[37] Nrf2 turns on the transcription of antioxidant elements, detoxification enzymes, and proteins required for glutathione synthesis and recycling.[36],[38] The impact of treatment with H2 on Nrf2-related antioxidant protection has been shown to extend up to eight hours after H2 is no longer detectible in the cellular medium.[39]

In addition to its antioxidant effects, H2 helps counteract systemic inflammation.[40],[41],[42] Animal and human studies suggest a potential role for H2 in the treatment of chronic inflammatory conditions.[43],[44],[45] H2 helps reduce the inflammatory cascade triggered by lipopolysaccharide (LPS, also known as endotoxin) which often is attributable to dysbiosis in the gut.

The contribution of gut H2 production

Although H2 is being researched for its therapeutic purposes, in some individuals a considerable amount of H2 also is produced by certain bacteria in the gastrointestinal tract as a result of the fermentation of specific carbohydrates.[46],[47],[48] Much of the H2 produced in the gut is quickly absorbed into the circulation and is partially excreted by the lungs.[49] This gut-sourced H2 gas is what is measured by a hydrogen breath test in individuals who have symptoms of irritable bowel syndrome.[50] However, just because supplemental H2 (provided by water or other means) shows up on this same breath test doesn’t mean it is bad, nor will be it the cause of digestive symptoms as it rapidly absorbs into circulation and the tissues.

Researchers observed that centenarians produced elevated levels of exhaled H₂ gas, suggesting an association of high H₂ production with longevity.

Although many individuals try to eradicate these bacteria due to physical symptomatology associated with their presence,[51] the production of H2 by the microbiota has been shown to have positive therapeutic value.[52],[53],[54] Researchers have observed that centenarians produced elevated levels of exhaled H2 gas, suggesting an association of high H₂ production with longevity.[55] Experiments also show that the transplantation of microbiota derived from animals with high H2 production alleviates oxidative stress in animals with low H2 production.[56] These and other studies suggest that gut bacteria-produced H₂ helps maintain a healthy redox balance, thereby potentially suppressing cellular aging.[57]

Neurodegenerative diseases such as Parkinson’s disease (PD) and Alzheimer’s disease are associated with oxidative stress.[58],[59] Interestingly, researchers found that the production of H2 is abnormally low in individuals with PD compared to controls. These and other results suggest that low H2, along with high oxidative stress, may contribute to the development and progression of PD.[60],[61] For these reasons, H2 is being investigated as a remedy for PD and Alzheimer’s disease.[62],[63],[64]

Summary

Although the study of molecular H2 is at an early stage, the health-promoting effects published to date are intriguing and significant, and are supported by a growing number of clinical studies. The research also suggests that meaningful health effects can be achieved by drinking hydrogen-rich water. In an upcoming post we’ll explore the clinical effects of this unique nutraceutical agent.

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