WONDERS OF MOLECULAR HYDROGEN

I drink hydrogen-infused water. You should, too. Why? Because the age of hydrogen is here. Molecular hydrogen, that is. We now know that molecular hydrogen has therapeutic potential for nearly every organ in the human body, as well as for 150 different human disease models! And it’s extremely safe.

MOLECULAR HYDROGEN: BACKGROUND

Molecular hydrogen, also known as “diatomic hydrogen,” is a colorless, tasteless, and odorless gas.

Elemental hydrogen (H) is the most abundant element in the universe constituting 75% of its mass. Yet, it is absent on earth in its monoatomic form, being present in water, and inorganic and organic compounds. Molecular hydrogen is found in the earth’s atmosphere at less than one part per million.

The science regarding benefits to health of molecular hydrogen (H₂₎ has advanced rapidly in recent years thanks to the pioneering efforts of research scientists around the globe.

Now hydrogen science is moving quickly beyond theory to practical applications. Moreover, new products exist allowing medical professionals and consumers to leverage the health benefits of hydrogen.

For decades, diatomic molecular hydrogen was generally considered an “inert” gas. That is perhaps the primary reason that molecular hydrogen has been recognized as a therapeutic molecule only recently.

Indeed, science has known about the health benefits of molecular hydrogen as early as 1798. Yet, as noted, for most of modern history the belief persisted that hydrogen was inert in the body. It was only in the late 20th century (ca. 1975) that it gained the attention of medical researchers, and only in the past 10 years has evidence for the health effects of molecular hydrogen gained critical mass in the scientific literature.

There are now more than 500 peer-reviewed articles demonstrating the therapeutic potential of hydrogen for nearly every organ in the human body, as well as in 150 different human disease models, according to the Molecular Hydrogen Foundation.

HEALTH BENEFITS OF MOLECULAR HYDROGEN (H₂)

• Molecular hydrogen reduces oxidative stress as a selective antioxidant and by maintaining homeostatic levels of glutathione, superoxide dismutase, catalase,  and other free-radical scavenging nutrients.

• The antioxidant capacities of molecular hydrogen are such that it is beneficial for persistent and acute oxidative stress.

• Acute oxidative stress arises from a multitude of causes, including inflammation, cardiac or cerebral infarction, organ transplantation, heavy exercise, cessation of operative bleeding, and many other causes.

• Persistent oxidative stress relates to reactive oxygen species (ROS) generated in the body throughout life. For example, during exercise, exposure to pollutants and toxins or UV light, as well as physical and psychological stresses, and the aging process itself. As aerobic organisms, we generate ROS when breathing consumes oxygen.

• Molecular hydrogen is effective against hydroxyl radicals (OH). The hydroxyl radical is the radical species that causes much of the oxidative damage in the body. While vitamin C, glutathione, and certain plant-based antioxidants are somewhat effective against this radical, there is no Nrf2-induced enzyme that effectively quenches the hydroxl radical.

• This positions molecular hydrogen as a uniquely effective antioxidant against the hydroxyl radical. Notably, when molecular hydrogen quenches the hydroxyl radical, it produces water, which is non-toxic in the body.

• Beyond this, molecular hydrogen, like other gaseous signaling molecules such as NO, CO, H₂S, appears to exhibit cell signal-modulating activity that confers it with anti-inflammatory, anti-obesity, anti-allergy, and many other benefits.

MOLECULAR HYDROGEN MEDICINE

The scientific literature discusses the use of molecular hydrogen for many clinical applications, including the following:

• METABOLIC SYNDROME including diabetes, hyperlipidemia, arteriosclerosis, hypertension, and obesity

• ISCHEMIA / REPERFUSION injuries including cerebral and myocardial infarctions, organ transplants, post-cardiac arrest

• NEUROPROTECTION including applications for dementia, Parkinson’s disease, depression, and anesthesia

• INFLAMMATION including applications for polymicrobial sepsis, rheumatoid arthritis, wound healing, and bowel diseases

• MITOCHONDRIAL DISEASES

• HEMODIALYSIS / VENTILATION

• AGING including cognitive decline

• EXERCISE including applications for fatigue, lactic acid, recovery, and oxidative stress related to heavy exercise

• SIDE EFFECTS OF CANCER THERAPIES including radiotherapy and chemotherapy

• MANY OTHER BENEFITS

HOW MOLECULAR HYDROGEN WORKS

According to the Molecular Hydrogen Foundation, there are three ways molecular hydrogen exerts positive health effects.

1.  Molecular hydrogen easily diffuses into subcellular compartments where it scavenges cytotoxic oxygen radicals, thereby protecting DNA, RNA, and proteins against oxidative stress.

2.  Molecular hydrogen triggers activation or upregulation of additional antioxidant enzymes (e.g., glutathione, superoxide dismutase, catalase, and others) and/or cytoprotective proteins of the body.

3.  Molecular hydrogen may be a novel signaling molecule that alters cell signaling, cell metabolism, and gene expression. This may explain its apparent anti-inflammatory, anti-allergic, and anti-apoptotic (or anti-cell death) effects.

MOLECULAR HYDROGEN IS SAFE

Molecular hydrogen exhibits great safety, and it is regarded as safe for use in the body. It is shown no toxicity even in high concentrations.

Safety standards are already established for high concentrations of molecular hydrogen for inhalation because high-pressure H2 gas is used in deep-water diving gas mixtures to prevent decompression sickness.

Notably, H₂ gas combusts only at temperatures higher than 527 °C, and it explodes by chain reaction with oxygen (O₂) only in the range of H₂ concentration (4–75%, vol/vol).

Molecular hydrogen can be used for medical applications safely by several ingestion methods including inhalation of 1–4% hydrogen gas, which exhibits great effectiveness.

All these factors mean that molecular hydrogen is safe, easy-to-use, and effective for therapeutic purposes.

USING MOLECULAR HYDROGEN

Methods for consuming molecular hydrogen include inhalation, oral ingestion of hydrogen-infused water, injection of hydrogen saline, and direct diffusion (eye drops, baths, cosmetics, etc.).

An advantage of inhaled H₂ gas is that is acts rapidly. In this respect, may be suitable for defense against acute oxidative stress.

It has been shown that inhalation of 3–4% hydrogen (H2) gas reaches a plateau at approximately 10–20 μM in the arterial and venous blood in about 20 minutes. This is shown not to affect any physiological parameters (e.g., blood pressure), suggesting no adverse effects.

According to the Molecular Hydrogen Foundation, the consensus is that drinking H2-rich water is the easiest, and often the most effective, method for obtaining molecular hydrogen although it does not provide as many hydrogen molecules to the body as other methods.

Some studies show consuming H2-infused water to be more effective than inhalation or increasing intestinal H2 production via lactulose administration.

Another advantage of drinking hydrogen infused water is that it allows gastric induction of ghrelin, which is mediated via activation of beta 1 adrenergic receptors.

Above all, drinking hydrogen-infused water is easy to do, and convenient as you can drink it at home or while traveling.

HYDROGEN-INFUSED WATER

Inhalation of molecular hydrogen gas may be impractical for continuous H₂ consumption in daily life. In contrast, solubilized H₂ (hydrogen-infused water) is a portable, easily administered, and safe means to ingest H₂.

H₂ can be dissolved in water up to 0.8 mM (1.6 mg/L) under atmospheric pressure at room temperature without changing pH.

H₂ water can be made by several methods: infusing H₂ gas into water under pressure, electrolyzing water to producing H₂, and reacting magnesium metal or its hydride with water.

Notably, H₂ penetrates glass or plastic walls of vessels in a short time, yet aluminum containers retain hydrogen gas for a long time.

Water ionizers produce hydrogen gas via electrolysis. This method produces hydrogen concentrations from less than 0.05 ppm to more than 2.5 ppm. Typically 0.1 to 0.7 ppm hydrogen is produced, yet most companies manufacturing water ionizers neither know the concentration produced nor understand the significance of hydrogen for health.

In this regard, depending upon the production method much of the water containing molecular hydrogen exhibits a negative oxygen reduction potential (ORP). Yet, ORP is only a general indication of hydrogen production and is not a measurement of its concentration.

A second method of producing hydrogen-rich water by electrolysis is by infusion. In this method, hydrogen is directly infused into filtered water within a machine.

Another convenient method to generate molecular hydrogen is to add alkali-earth metals to water. Magnesium metal in commonly used for this purpose. This method allows for the production of high concentrations of molecular hydrogen that are generally near saturation (1.6 ppm), and therefore less water needs to be consumed by individuals drinking it.

Magnesium sticks and tablets/capsules are available (some of which are placed in water and others that can be consumed directly) that rapidly produce 2–4 ppm molecular hydrogen concentration. Like electrolysis, adding metals to water also increased the pH of water because they reduce the concentration of H+ ions.

Other methods exist that can produce supersaturated concentrations of molecular hydrogen with or without alteration of water pH. Advantages of these methods include having to drink a fraction of the amount of water in order to obtain an equal amount of molecular hydrogen.

Drinking water containing molecular hydrogen is probably the easiest and most cost-effective means for most persons to obtain hydrogen.

MOLECULAR HYDROGEN FROM YOUR MICROBIOME

Certain types bacteria in the intestinal tract produce hydrogen gas from non-digestible fibers, which may explain how fiber-rich diets reduce inflammation, and exert cardiovascular and other health benefits.

Diets low in dietary fiber from fruits and vegetables, or a decrease in microbiome diversity could potentially reduce production of molecular hydrogen. This could exert adverse effects on health.

The presence (or absence) of a diverse and robust microbiome may be one of the most significant factors in terms of how much hydrogen can be generated in the body. Most people today do not create the levels of molecular hydrogen in their digestive tracts that humans in earlier time periods generated largely because due to modern diets and less than optimal microbiome health.

Factors that influence or reduce microbiome health and diversity include antibiotic use, imbalanced diet, lack of certain fiber-rich vegetables in the diet, and consumption of herbicides, pesticides, and GMOs (that include glyphosate) that harm microbial populations and cause “leaky gut”.

As knowledge increases regarding ways we can support a healthy microbiome, the biological significance of hydrogen historically produced in our digestive tracts will be better understood.

BENEFIT TODAY FROM MOLECULAR HYDROGEN

The clinical applications of molecular hydrogen are impressive. One of the great advantages of molecular hydrogen infused water is that  it is easy to consume it, or make it in your own home or wherever you happen to be.

HPDI now sells a tablet hydrogen product from Purative known as Active H2.

Active H2 is a unique, patent-pending combination of all-natural minerals used to generate molecular hydrogen and electron-rich potential (-ORP). This distinguishes it from existing hydrogen formulas and electrolysis (water ionizers).

Active H2 is easy to use.  Simply place one tablet of in a 1/2 liter (16 oz) container of pure water (filled to the top) and close tightly. Wait at least 5–10 minutes for it to completely disintegrate (fizz), and then drink.

A one pint glass mason jar works well as a container for this purpose. However, you can use up to one liter (about 32 ounces) of water in a container, so a quart mason jar also works well. Consume the hydrogen-infused water ideally at least 30 minutes before food.

Active H2 formula consists of a proprietary blend of pure magnesium, malic acid, fumaric acid, and maltose that synergistically act to generate molecular hydrogen and electron-rich potential (-ORP).

Active H2 is the only all-natural add-in tablet providing molecular hydrogen in the amount of greater than 1.8 ppm, That is, one tablet typically generates molecular hydrogen in the concentration of about 2 ppm.

There are other molecular hydrogen products, including tablets, sticks, and pre-infused bottled products like H2Bev. H2Bev provides about 1.2–1.5 ppm of molecular hydrogen and comes in a 12 oz coated aluminum container for excellent H2 retention.

MOLECULAR HYDROGEN SUMMARY

Molecular hydrogen sits in the unique position of providing significant, wide-ranging benefits for health with an unmatched ease-of-use, and at relatively low cost for what it delivers.

We highly recommend the use of molecular hydrogen for its health benefits and for therapeutic applications. This includes the consumption of hydrogen-infused water whether from prepared H2 beverages, water ionizers, or highly effective Active H2 tablets.

Below we include important scientific abstracts you may find helpful in understanding the benefits and applications of molecular hydrogen.

SCIENTIFIC STUDIES ON MOLECULAR HYDROGEN

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

From: http://www.ncbi.nlm.nih.gov/pubmed/26483953

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.

Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development and potential of hydrogen medicine

From: http://www.ncbi.nlm.nih.gov/pubmed/24769081

Abstract
Molecular hydrogen (H2) has been accepted to be an inert and nonfunctional molecule in our body. We have turned this concept by demonstrating that H2 reacts with strong oxidants such as hydroxyl radical in cells, and proposed its potential for preventive and therapeutic applications. H2 has a number of advantages exhibiting extensive effects: H2 rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect signaling reactive oxygen species; therefore, there should be no or little adverse effects of H2. There are several methods to ingest or consume H2; inhaling H2 gas, drinking H2-dissolved water (H2-water), injecting H2-dissolved saline (H2-saline), taking an H2 bath, or dropping H2-saline into the eyes. The numerous publications on its biological and medical benefits revealed that H2 reduces oxidative stress not only by direct reactions with strong oxidants, but also indirectly by regulating various gene expressions. Moreover, by regulating the gene expressions, H2 functions as an anti-inflammatory and anti-apoptotic, and stimulates energy metabolism. In addition to growing evidence obtained by model animal experiments, extensive clinical examinations were performed or are under investigation. Since most drugs specifically act to their targets, H2 seems to differ from conventional pharmaceutical drugs. Owing to its great efficacy and lack of adverse effects, H2 has promising potential for clinical use against many diseases.

Molecular hydrogen in drinking water protects against neurodegenerative changes induced by traumatic brain injury.

From: http://www.ncbi.nlm.nih.gov/pubmed/25251220

Abstract
Traumatic brain injury (TBI) in its various forms has emerged as a major problem for modern society. Acute TBI can transform into a chronic condition and be a risk factor for neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases, probably through induction of oxidative stress and neuroinflammation. Here, we examined the ability of the antioxidant molecular hydrogen given in drinking water (molecular hydrogen water; mHW) to alter the acute changes induced by controlled cortical impact (CCI), a commonly used experimental model of TBI. We found that mHW reversed CCI-induced edema by about half, completely blocked pathological tau expression, accentuated an early increase seen in several cytokines but attenuated that increase by day 7, reversed changes seen in the protein levels of aquaporin-4, HIF-1, MMP-2, and MMP-9, but not for amyloid beta peptide 1-40 or 1-42. Treatment with mHW also reversed the increase seen 4 h after CCI in gene expression related to oxidation/carbohydrate metabolism, cytokine release, leukocyte or cell migration, cytokine transport, ATP and nucleotide binding. Finally, we found that mHW preserved or increased ATP levels and propose a new mechanism for mHW, that of ATP production through the Jagendorf reaction. These results show that molecular hydrogen given in drinking water reverses many of the sequelae of CCI and suggests that it could be an easily administered, highly effective treatment for TBI.

The evolution of molecular hydrogen: a noteworthy potential therapy with clinical significance

From: http://www.ncbi.nlm.nih.gov/pubmed/23680032

Abstract
Studies on molecular hydrogen have evolved tremendously from its humble beginnings and have continued to change throughout the years. Hydrogen is extremely unique since it has the capability to act at the cellular level. Hydrogen is qualified to cross the blood brain barrier, to enter the mitochondria, and even has the ability to translocate to the nucleus under certain conditions. Once in these ideal locations of the cell, previous studies have shown that hydrogen exerts antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective properties that are beneficial to the cell. Hydrogen is most commonly applied as a gas, water, saline, and can be applied in a variety of other mediums. There are also few side effects involving hydrogen, thus making hydrogen a perfect medical gas candidate for the convention of novel therapeutic strategies against cardiovascular, cerebrovascular, cancer, metabolic, and respiratory diseases and disorders. Although hydrogen appears to be faultless at times, there still are several deficiencies or snares that need to be investigated by future studies. This review article seeks to delve and comprehensively analyze the research and experiments that alludes to molecular hydrogen being a novel therapeutic treatment that medicine desperately needs.

Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases

From: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3377272/

Abstract
Effects of molecular hydrogen on various diseases have been documented for 63 disease models and human diseases in the past four and a half years. Most studies have been performed on rodents including two models of Parkinson’s disease and three models of Alzheimer’s disease. Prominent effects are observed especially in oxidative stress-mediated diseases including neonatal cerebral hypoxia; Parkinson’s disease; ischemia/reperfusion of spinal cord, heart, lung, liver, kidney, and intestine; transplantation of lung, heart, kidney, and intestine. Six human diseases have been studied to date: diabetes mellitus type 2, metabolic syndrome, hemodialysis, inflammatory and mitochondrial myopathies, brain stem infarction, and radiation-induced adverse effects. Two enigmas, however, remain to be solved. First, no dose-response effect is observed. Rodents and humans are able to take a small amount of hydrogen by drinking hydrogen-rich water, but marked effects are observed. Second, intestinal bacteria in humans and rodents produce a large amount of hydrogen, but an addition of a small amount of hydrogen exhibits marked effects. Further studies are required to elucidate molecular bases of prominent hydrogen effects and to determine the optimal frequency, amount, and method of hydrogen administration for each human disease.

Molecular hydrogen is a novel antioxidant to efficiently reduce oxidative stress with potential for the improvement of mitochondrial diseases

From: http://www.ncbi.nlm.nih.gov/pubmed/21621588

Abstract

BACKGROUND:
Mitochondria are the major source of oxidative stress. Acute oxidative stress causes serious damage to tissues, and persistent oxidative stress is one of the causes of many common diseases, cancer and the aging process; however, there has been little success in developing an effective antioxidant with no side effect. We have reported that molecular hydrogen has potential as an effective antioxidant for medical applications [Ohsawa et al., Nat. Med. 13 (2007) 688-694].

SCOPE OF REVIEW:
We review the recent progress toward therapeutic and preventive applications of hydrogen. Since we published the first paper in Nature Medicine, effects of hydrogen have been reported in more than 38 diseases, physiological states and clinical tests in leading biological/medical journals. Based on this cumulative knowledge, the beneficial biological effects of hydrogen have been confirmed. There are several ways to intake or consume hydrogen, including inhaling hydrogen gas, drinking hydrogen-dissolved water, taking a hydrogen bath, injecting hydrogen-dissolved saline, dropping hydrogen-dissolved saline into the eyes, and increasing the production of intestinal hydrogen by bacteria. Hydrogen has many advantages for therapeutic and preventive applications, and shows not only anti-oxidative stress effects, but also has various anti-inflammatory and anti-allergic effects. Preliminary clinical trials show that drinking hydrogen-dissolved water seems to improve the pathology of mitochondrial disorders.

MAJOR CONCLUSIONS:
Hydrogen has biological benefits toward preventive and therapeutic applications; however, the molecular mechanisms underlying the marked effects of small amounts of hydrogen remain elusive.

GENERAL SIGNIFICANCE:
Hydrogen is a novel antioxidant with great potential for actual medical applications. This article is part of a Special Issue entitled Biochemistry of Mitochondria.

Recent progress toward hydrogen medicine: potential of molecular hydrogen for preventive and therapeutic applications

From: http://www.ncbi.nlm.nih.gov/pubmed/21736547

Abstract
Persistent oxidative stress is one of the major causes of most lifestyle-related diseases, cancer and the aging process. Acute oxidative stress directly causes serious damage to tissues. Despite the clinical importance of oxidative damage, antioxidants have been of limited therapeutic success. We have proposed that molecular hydrogen (H(2)) has potential as a “novel” antioxidant in preventive and therapeutic applications [Ohsawa et al., Nat Med. 2007: 13; 688-94]. H(2) has a number of advantages as a potential antioxidant: H(2) rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect reactive oxygen species (ROS) that function in cell signaling, thereby, there should be little adverse effects of consuming H(2). There are several methods to ingest or consume H(2), including inhaling hydrogen gas, drinking H(2)-dissolved water (hydrogen water), taking a hydrogen bath, injecting H(2)- dissolved saline (hydrogen saline), dropping hydrogen saline onto the eye, and increasing the production of intestinal H(2) by bacteria. Since the publication of the first H(2) paper in Nature Medicine in 2007, the biological effects of H(2) have been confirmed by the publication of more than 38 diseases, physiological states and clinical tests in leading biological/medical journals, and several groups have started clinical examinations. Moreover, H(2) shows not only effects against oxidative stress, but also various anti-inflammatory and antiallergic effects. H(2) regulates various gene expressions and protein-phosphorylations, though the molecular mechanisms underlying the marked effects of very small amounts of H(2) remain elusive.

Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals

From: http://www.ncbi.nlm.nih.gov/pubmed/17486089

Abstract
Acute oxidative stress induced by ischemia-reperfusion or inflammation causes serious damage to tissues, and persistent oxidative stress is accepted as one of the causes of many common diseases including cancer. We show here that hydrogen (H(2)) has potential as an antioxidant in preventive and therapeutic applications. We induced acute oxidative stress in cultured cells by three independent methods. H(2) selectively reduced the hydroxyl radical, the most cytotoxic of reactive oxygen species (ROS), and effectively protected cells; however, H(2) did not react with other ROS, which possess physiological roles. We used an acute rat model in which oxidative stress damage was induced in the brain by focal ischemia and reperfusion. The inhalation of H(2) gas markedly suppressed brain injury by buffering the effects of oxidative stress. Thus H(2) can be used as an effective antioxidant therapy; owing to its ability to rapidly diffuse across membranes, it can reach and react with cytotoxic ROS and thus protect against oxidative damage.

ADDITIONAL RESOURCES

MOLECULAR HYDROGEN (H2) AT FOREFRONT OF HEALTH RESEARCH
by Hank Liers, PhD (from the HPDI blog)

ACTIVE H2 (tablet product)

Molecular Hydrogen Foundation (MHF)

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