Brief History

Electrolyzed reduced water (ERW) and BIOCERAMIC (Natural) process is the most common term in the scientific literature. Both has an alkaline pH (8-10) and contains molecular hydrogen. Water ionizers were invented in the early 1900’s. Research on electrolyzed water started around 1931 in Japan where it gained popularity in the 1950’s. Around this time, the water was touted as having “healing effects” and was called “shin nooru solution” or “synnohl liquid”. In 1962, separate water ionizer companies (one from Nagano Prefecture and the other from Kyoto Prefecture) brought the electrolytic apparatus to the Cabinet Welfare Bureau (equivalent to the Japanese Ministry of Health, Labor, and Welfare [JMHLW]) and applied to manufacture the apparatus as a medical device.

Medical Approval

However, because some tap waters didn’t have sufficient minerals for efficient electrolysis, it was impossible to produce alkaline water with the same characteristics. Adding calcium lactate to the water solved this problem and allowed an alkaline pH to be produced. With addition of calcium lactate as a prerequisite, approval for a “synnohl liquid manufacturing apparatus” was granted in 1965 and recognized as being a “medical substance generator” under the Pharmaceutical Affairs Law as follows: Cathode Water (Alkaline Ionized Water): • o Drinking alkaline ionized water is effective against chronic diarrhea, indigestion, abnormal stomach or intestine fermentation, acid control, and acid indigestion. The JMHLW also approved the mildly and strongly acidic waters as medical substance. In 1978 the Korean FDA also approved these devices for similar reasons. The approval process follow virtually the identical criteria and standards as was developed by Japan. Some of suggested that the approvals are totally different, and that Japanese approvals require extensive testing, even clinical trials and up to 5 years or more of vigorous investigations.

Skepticism And Marketing

Development of water electrolysis apparatuses continued, and in 1979, a continuous-type electrolytic water generator, which could be directly connected to the tap water, was approved. Shortly thereafter, water filters were added to these machines, and the marketing of alkaline ionized water started to be common. In June of 1992, a television news program marketed alkaline ionized water as “Wonder Water”. This was a marketing strategy, which showed the water being used in hospitals and giving beneficial effects against diseases, such as diabetes. The media led people to believe that the water was recognized for ailments beyond what it had been approved for. However, because the original approval required addition of calcium lactate, and calcium was already recognized to help with gastrointestinal issues including chronic diarrhea, antacids, and indigestion, the medical community doubted the efficacy of the water itselfas the benefits could easily be ascribed to the calcium. In December of 1992, product testing by the National Consumer Affairs Center of Japan further cast doubt on the efficacy of the water reporting that it was unrealistic to believe that drinking alkaline water can have similar affects to gastrointestinal drugs, as it would require one to drink more than 10 liters of water to neutralize the stomach acid.

Verification Of Benefits

In 1993, a double-blind clinical study (193 people) conducted by the medical school of Kyoto University reported that there was no statistically significant improvement in the gastrointestinal symptoms of those drinking the alkaline ionized water, but a slight trend of improvement was observed. When the Drugs, Cosmetics, and Medical Instruments Act of Japan was revised in 2005, a device for the ERW production was re-authorized as a home managed medical device for the improvement of gastrointestinal symptoms.

Current Medical Status

Currently, in order to manufacture and/or sell water ionizers, companies must obtain certified approval by the JMHLW according the Pharmaceutical Affairs Law. Actually if a device makes water with a pH of 8.5 or higher then it must obtain the approval. The device is inspected to assure safety and ability to produce alkaline water (e.g. pH ? 9.5) according to the JIS-T 2004 performance test method. ¬This is similar to the American FDA, in requiring products like dental floss, examination gloves, wheel chairs, etc.). After meeting the requirements, an approval number is granted. Commercial products must show this approval number. There are at least eighteen different water ionizer companies that have been approved and certified by the JMHLW. Because all machines must comply with the same requirements for medical approval, the products have the same basic electrolytic cell structure as well as the same basic principles of electrolysis, so there are no significant differences between the various machines in terms of platinum purity design. However, the concentration of dissolved hydrogen and the level of maintenance required (or that is possible) can vary significantly.

Marketing Prohibitions

In Japan the Pharmaceutical Affairs law has also issued strict prohibitions regarding marketing, advertising, and making claims. For example, the names of ERW produced from ionizers must not suggest beneficial effects (e.g. Wonder Water, magical water, etc.). Advertising claims must not exceed or suggest more than those for which it was approved. The fact that these units have been classified as medical devices do not offer any evidence for their potential to treat and or prevent disease. It has also been claimed that the majority of hospitals in Japan use and prescribe ionized water to their patients, but this is also not true. Many medical doctors in Japan have never seen or even heard of a water ionizer being used for hospital patients. There was an early Japanese advertisement that made it appear that this was the case, but it is not.

Recent Advances In Hydrogen Research As A Therapeutic Medical Gas

Recent basic and clinical research has revealed that hydrogen is an important physiological regulatory factor with antioxidant, anti-inflammatory and anti-apoptotic protective effects on cells and organs. Therapeutic hydrogen has been applied by different delivery methods including straightforward inhalation, drinking hydrogen dissolved in water and injection with hydrogen-saturated saline. This review summarizes currently available data regarding the protective role of hydrogen, provides an outline of recent advances in research on the use of hydrogen as a therapeutic medical gas in diverse models of disease and discusses the feasibility of hydrogen as a therapeutic strategy. It is not an overstatement to say that hydrogen’s impact on therapeutic and preventive medicine could be enormous in the future.

Hydrogen-Rich Water Affected Blood Alkalinity In Physically Active Men

Possible appliance of effective and safe alkalizing agent in the treatment of metabolic acidosis could be of particular interest to humans experiencing an increase in plasma acidity, such as exercise-induced acidosis. In the present study we tested the hypothesis that the daily oral intake of 2L of hydrogen-rich water (HRW) for 14 days would increase arterial blood alkalinity at baseline and post-exercise as compared with the placebo. This study was a randomized, double blind, placebo-controlled trial involving 52 presumably healthy physically active male volunteers. Twenty-six participants received HRW and 26 a placebo (tap water) for 14 days. Arterial blood pH, partial pressure for carbon dioxide (pCO2), and bicarbonates were measured at baseline and post exercise at the start (day 0) and at the end of the intervention period (day 14). Intake of HRW significantly increased fasting arterial blood pH by 0.04 (95% confidence interval; 0.01 – 0.08; p< 0.001), and post exercise pH by 0.07 (95% confidence interval; 0.01 – 0.10; p = 0.03) after 14 days of intervention. Fasting bicarbonates were significantly higher in the HRW trial after the administration regimen as compared with the preadministration (30.5 ± 1.9 mEq/L vs. 28.3 ± 2.3 mEq/L; p < 0.0001). No volunteers withdrew before the end of the study, and no participant reported any vexatious side effects of supplementation. These results support the hypothesis that HRW administration is safe and may have an alkalizing effect in young physically active men.

Molecular Hydrogen And Radiation Protection

Molecular hydrogen (hydrogen, H2) acts as a therapeutic antioxidant by selectively reducing hydroxyl radicals (•OH) and peroxynitrite (ONOO–). It has been well-known that ionizing radiation (IR) causes oxidative damage and consequent apoptosis mainly due to the production of •OH that follows radiolysis of H2O. Our department reported the protective effect of H2 in irradiated cells and mice for the first time, and this effect is well repeated by us and another laboratory in different experimental animal models. A randomized, placebo-controlled investigation also showed consumption of H2 can improve the quality of life of patients treated with radiotherapy for liver tumors. These encouraging results suggested that H2 has a potential as a radio protective agent with efficacy and non-toxicity.

Hydrogen-Rich Saline Protects Against Intestinal Ischemia/Reperfusion Injury In Rats

Hydrogen gas was reported to reduce reactive oxygen species and alleviate cerebral, myocardial and hepatic ischemia/reperfusion (I/R) injuries. This paper studied the effect of hydrogen-rich saline, which was easier for clinical application, on the intestinal I/R injury. Model of intestinal I/R injury was induced in male Sprague-Dawley rats. Physiological saline, hydrogen-rich saline or nitrogen-rich saline (5 ml/kg) was administered via intravenous infusion at 10 min before reperfusion, respectively. The intestine damage was detected microscopically and was assessed by Chiu score system after I/R injury. In addition, serum DAO activity, TNF-α, IL-1β and IL-6 levels, tissue MDA, protein carbonyl and MPO activity were all increased significantly by I/R injury. Hydrogen-rich saline reduced these markers and relieved morphological intestinal injury, while no significant reduction was observed in the nitrogen-rich saline-treated animals. In conclusion, hydrogen-rich saline protected the small intestine against I/R injury, possibly by reduction of inflammation and oxidative stress.

Radio Protective Effect Of Hydrogen In Cultured Cells And Mice

It has been demonstrated that hydrogen can selectively reduce hydroxyl and peroxynitrite in vitro. Since most of the ionizing radiation-induced cellular damage is caused by hydroxyl radicals, this study was designed to test the hypothesis that hydrogen may be an effective radio protective agent. This paper demonstrates that treating cells with hydrogen before irradiation could significantly inhibit ionizing irradiation (IR)-induced Human Lymphocyte AHH-1 cells apoptosis and increase cells viability in vitro. This paper also shows that hydrogen can protect gastrointestinal endothelia from radiation-induced injury, decrease plasma malondialdehyde (MDA) intestinal 8-hydroxydeoxyguanosine (8-OHDG) levels and increase plasma endogenous antioxidants in vivo. It is suggested that hydrogen has a potential as an effective and safe radio protective agent.

Hydrogen protects rats from dermatitis caused by local radiation

Background: Radiation therapy produced unwanted side effect on normal tissues, such as radio dermatitis. Hydrogen was previously shown capable of radiation protective in both animals and cell cultures. The effect of hydrogen was now to be investigated on radiation-induced cutaneous. Objective: Development of dermatitis is a frequent side effect of radiotherapy of patients with head-and-neck cancer. Here we analyzed the radio protective efficacy of hydrogen under conditions of local, single-dose or fractionated radiation treatment, and its possible molecular mechanisms. Methods: Rats received either single-dose or fractioned irradiation of the head-and-neck area with or without subcutaneous injection of hydrogen solution before irradiation. In vitro, the effect of hydrogen medium on radiation-induced cell viability, apoptosis, and biochemical assays was measured. Result: Hydrogen significantly reduced the severity of dermatitis, accelerated tissue recovery, and reduced the extent of radiation-induced weight loss in rats after a single dose of 15 or 20 Gy but not 25 Gy of radiation. Hydrogen was also protective from cumulative doses of 30 Gy delivered in three fractions, respectively. Hydrogen also protect HaCaT cells from radiation-induced injury, it could significantly inhibit ionizing injury. Conclusion: These results suggest that hydrogen has a positive effect on acute radio dermatitis.

Mildly acidic water is produced from water ionizers, which use the process of electrolysis. Acidic water is produced at the positive electrode (anode). The Japanese Ministry of Health, Labor, and Welfare (JMHLW) approved this water in 1965, as an astringent for beauty purposes.

The JMHLW also approved the alkaline and strongly acidic waters as medical substance.

Claimed Benefits Of Mildly Acidic Water

The mildly acidic water (pH 4-6), also known as “beauty water” is touted to have benefits as an astringent for beauty and cosmetology. However, no specific article testing electrolyzed mildly acidic water could be located. Nevertheless, because skin surface pH is about 6 ± 0.6 it follows that slightly acidic water would not perturb the pH homeostasis of the skin. Indeed, alkaline water can increase surface pH of the skin leading to irritation by disrupting the physiological protective ‘acid mantle’. It may also alter the cutaneous bacterial flora, alter the activity of enzymes in the upper epidermis and decrease fat from the skin, which may influence hydrating status leading to dry squamous skin. However, no article that directly tests the application of mildly acidic water to skin could be located to substantiate the purported benefits. It appears that there are studies in Japanese, however. Astringencies are generally tannins, organic molecules and chemical salts that cause shrinkage of mucous membranes; all ingredients not contained in mildly acidic water.

chlorine in acidic water

Unfortunately, the mildly acidic water often contains chlorine (produced during electrolysis) and thus becomes a dilute hypochlorous acid solution. Most commercial units filter the chlorine (Cl2) out of the water before it undergoes electrolysis, but the common chloride electrolytes are not removed. These chloride ions (Cl-) are oxidized at the anode to produce chlorine: (2Cl- ? Cl2 +2e-). Chlorine in the acidic water can easily be detected with a simple chlorine test reagent. Some have incorrectly claimed that even though tests for chlorine in the acidic water show positive, the results are invalid as though the indicator measured something else and gave a false positive. This is misleading and false as chlorine production via electrolysis is the preferred method of mass production, and the chlorine indicators are selectively sensitive to chlorine. Thus caution should be exercised regarding the topical application of acidic water to the skin. Indeed chlorinated water negatively effects skin health. One should first test the acidic water for the presence of chlorine before topical administration.

The prominent and therapeutic effects of molecular hydrogen (H2 gas) are emerging to the forefront of scientific research. Humans are continuously fighting the battle against cardiovascular disease, Parkinson’s disease, Alzheimer’s disease, dementia, diabetes, osteoporosis, chronic inflammation, hypertension, hyperlipidemia and many more. The search for a simple method to prevent all such ailments, and in short to halt the aging process and even reverse it to youth, is not a new concept. This idea seems to be prevalent throughout the history of mankind, including the writings of Herodotus about the Fountain of Youth.

The more research that accumulates about molecular hydrogen, the more it appears to have the sought after properties of the Fountain of Youth. A 2010 quality review article on molecular hydrogen.

“IT IS NOT AN OVERSTATEMENT TO SAY THAT HYDROGEN’S IMPACT ON THERAPEUTIC AND PREVENTIVE MEDICINE COULD BE ENORMOUS IN THE FUTURE.”

Since that review article, over 400 additional articles have been published substantiating that declaration. Currently, about 150 different disease models have been studied, in which molecular hydrogen appears to exert a beneficial effect (including the ones listed above)

Hydrogen is #1 on the periodic table because it is tiny. Being tiny allows Hydrogen to get into membranes, joints, brain, gut, organs, lungs, eyes, ears, etc. Molecular or diatomic hydrogen is 2 atoms of hydrogen. It is also referred to as H2.
In the Echo® Hydrogen Enriched Water System™, H2 gas is dissolved in the water. The water is the delivery vehicle for the H2 gas which has benefits. Molecular hydrogen (H2) is why water electrolysis was developed in 1800. H2 is a selective antioxidant only reacting with ROS (reactive oxygen species). ROS damages cells. The most cytotoxic (cell damaging) ROS (free radicals) are Hydroxyl Radicals (HO*). When H2 combines with 2 hydroxyl radicals, 2 water molecule are formed. H2 has therapeutic benefits for every organ in the body. Our bodies were designed to create hydrogen gas in the gut through the normal fermentation and digestion of food. The problem is that many people have issues that prevent their gut from working correctly. 60% of the immune system is based on gut health. If the gut is compromised and the diet does not have beneficial fiber to be converted into hydrogen gas, issues occur.

Some Benefits Of Molecular Hydrogen:

  • Reduction of oxidative stress and Inflammation.
  • Regulation of over 200 Biomolecules in the body.
  • Stimulates gastric ghrelin to increase cognitive function
  • Stimulation of anaerobic microflora in the intestinal tract.
  • Shown to help with Rheumatoid Arthritis and joint issues.
  • 700 studies showing therapeutic effects with 170 human disease models.

Molecular hydrogen has benefits. Peer reviewed articles and studies have shown molecular hydrogen to reduce oxidative stress and inflammation which lead to many diseases. Studies have been conducted on 170+ human diseases and conditions including Rheumatoid Arthritis, Diabetes, Colon Cancer, Autoimmune, Parkinson’s, Alzheimer’s, Autism, Bipolar, Schizophrenia, & IGT. In addition to helping with existing conditions, molecular hydrogen can support the body to avoid susceptibility to diseases and conditions. It is truly one of the best anti-aging tools you can use.

Water Electrolysis: A Hydrogen Generator: How It Works.

In 1800, Anthony Carlisle, a surgeon in London, discovered water electrolysis because he wanted to make a hydrogen generator. Dr. Carlisle wanted a way to produce hydrogen gas easily because he learned in 1798 that hydrogen had antioxidant properties. Traditional electrolysis devises convert water (H2O) to hydrogen gas (H2) and hydroxide ions (OH-) at the negative side (cathode), and oxygen gas (O2) and hydrogen ions (H+) at the positive side (anode). Traditional water electrolysis machines have standard membranes that separates the alkaline OH- ions from the acidic H+ ions if you are separating the water streams. A new method of electrolysis was designed to only produce H2 without changing the pH of the source water. In this method, the water is not separated into alkaline and acid streams. Proton Exchange Membranes (PEM) are used instead of standard membranes. The advantage of the PEM is that it creates its own conductivity in water and can produce H2 gas even in pure water with no minerals as in reverse osmosis or distilled water. The benefits do not come from the pH of the water. The pH change comes if you separate the water streams. It is the H2 gas that can be dissolved in the water that provides the therapeutic benefits. Typically, electrolysis systems that separate the water streams into alkaline and acid water are not able to dissolve H2 gas in the water longer than a few weeks. This is because the positively charged minerals naturally want to bond to the negatively charged cathode (see graphic above). If minerals build up on the cathode, H2 gas will not be dissolved in the water because the hydrogen bubbles will be too large to be dissolved. The H2 gas will go into the atmosphere and the benefits with it. In the Echo® 9 Ultra H2 system, the patented technology changes the polarity of the electrodes every time the machine is used. This makes it impossible for minerals to build up. This is the only system that guarantees H2 gas will always be dissolved in the water. With other electrolysis systems, minerals will build up within 2-3 weeks of use and the benefits will be gone. Other companies tell consumers that they have automatic reverse cleaning systems in their machines to be confusing. They say that their systems change the polarity of the electrodes to further confuse the issue but they don’t do it every time the machine is used. They only change the polarity every 10L or 20L of water and by then the minerals are already bonded and the damage is done. With these inferior systems, the only way to keep the minerals off the cathode is to clean the system every 2 weeks with citric acid or commercial vinegar. Of course, you don’t have to worry about this with any of the Echo® branded systems because it impossible for the minerals to bond to the cathode in the first place.

Benefits Of Echo® Hydrogen Enriched Water™

Everyone is talking about how free radicals are damaging our cells. What most people don’t know is that many free radicals are beneficial to health. It is only the cell damaging (cytotoxic) oxygen radicals that we need to scavenge. H2 converts these cell damaging radicals into water molecules.

Athletic Performance:

Echo® Hydrogen Enriched Water™ has helped many athletes increase performance. It better empowers you to function at optimal efficiency by ridding the cells of Hydroxyl Radicals allowing the mitochondria to produce energy more efficiently. It reduces fatigue by lessening lactate buildup in muscles. Recovery times can be cut in half. When a person is properly hydrated with Echo® hydrogen-enriched water, they perform at peak levels for longer periods of time.

Detoxification And Weight Loss:

Echo® water supports healthy cleansing and weight loss. When the toxins and wastes are flushed, the burden on the body is lessened. Water can also help to clean out the intestines and colon. People feel more hydrated, have more success with their weight loss programs, experience more productive sleep, wake up more alert, have fewer allergy symptoms, and generally feel more energy throughout the day. H2 stimulates gastric Ghrelin that increases cognitive function.

Immune Boost:

The effectiveness of the immune system and the digestive system are directly linked to the level of hydration. Being properly hydrated is one of the best ways to increase your immune system and prevent sickness and disease. 60-75% of your body is water and it should be no surprise that the type of water you drink can directly influences the way you feel. Hydrogen enriched water™ can stimulate anaerobic microflora to naturally restore gut health. The health of your gut is directly related to the strength of your immune system and the susceptibility to disease and sickness.

Intrinsic Energy And Frequencies:

Many people understand that energy and frequencies are all around us. Radio frequencies, cell phone frequencies, Infrared energies, EMF’s, etc. There are good and bad energies and frequencies. Some use energies to benefit individuals in need. The Echo® Water System has hundreds of beneficial energies and frequencies. They can protect you from harmful frequencies and energies. They can also balance chakras and help the body heal. Individuals that are intuitive can feel them. Others say that the water just feels good to them. Professionals in energy medicine, Cranial Sacral Therapists, Reiki Masters, etc. love and recommend Echo® water because of these beneficial energies and frequencies.

Proper Hydration:

Because Echo® Water tastes so great, you will be drinking more water. A study3 conducted by the University of Utah, showed the more water you drink the better. In the study, subjects consumed either 4, 8 or 12 glasses of water daily. On the fifth day before rising, their hydration status was monitored and a computer measured how many calories they had burned in a resting state. The groups who drank 8 and 12 glasses of water daily were sufficiently hydrated, whereas subjects who drank only four glasses showed definite signs of dehydration. The well-hydrated subjects reported better concentration and more
energy. They burned more calories at rest than the group who drank only 4 glasses. These results were in line with previous3 University of Utah findings that the ability to burn calories can decline by about 2% per day when people are dehydrated. Metabolic rate and digestion are increased by being properly hydrated.

Increased Cognitive Function – Ghrelin: Help With Neurological Conditions

Studies show that H2 gas stimulates Ghrelin secretions. Ghrelin is known as the hunger hormone in the body. Ghrelin affects many things in the body including cognitive function, hunger, weight regulation, anti-inflammatory function. This is accomplished in the hippocampus, hypothalamus and the brain stem. Specific studies have shown that water with H2 gas can be helpful with neurologic issues like Parkinson’s, Alzheimer’s, Bipolar, Schizophrenia, and Autism.

Study References:

There are hundreds of studies showing molecular hydrogen to have therapeutic benefits. The studies below are shared for educational purposes only. They are not shared to indicate any expected outcome for anyone with a similar or same disease or pathology. The results achieved in the studies should not be taken as an indicator of results you will experience. The study shows potential outcomes. There are no protocols, drugs, natural methods, or techniques that are 100% effective. Every individual is different and diseases are complex.

Hydrogen–Water Enhances 5-Fluorouracil-Induced Inhibition Of Colon Cancer

Runtuwene et al. (2015), Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer. PeerJ 3:e859; DOI 10.7717/peerj.859. 2015 April 7
Joshua Runtuwene1,2, Haruka Amitani1, Marie Amitani1, Akihiro Asakawa1, Kai-Chun Cheng1 and Akio Inui1
1 Department of Psychosomatic Internal Medicine, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan 2 Faculty of Medicine, Sam Ratulangi University, Manado, Indonesia

ABSTRACT

Oxidative stress is involved in cancer development. Hydrogen (H2) is a potent antioxidant and exhibits anti-inflammatory and potentially anticancer-like activities. This study aimed to investigate the role of H2 in combination with 5-fluorouracil (5-FU) in cancer treatment both in vitro and in vivo using the colon 26 cell line. The survival rate was determined using the Kaplan–Meier survival test, and cell viability was assessed using cell viability imaging kit and the MTT assay, and activation of the cell apoptosis pathway (Phosphorylated adenosine monophosphate activated protein kinase (p-AMPK), Apoptosis-inducing factor (AIF) and Caspase 3) were characterized by western blots. Hydrogen water administration improved the survival of mice with colon 26-induced cancer. Furthermore, hydrogen water enhanced cell apoptosis in cancer cells, resulting in a marked increase in the expression of p-AMPK, AIF and Caspase 3 in colon 26 cells. Hydrogen water also increased the inhibitory effect of 5-FU on colon 26 cells with respect to cell survival rate and anticancer functions. Additionally, high-content hydrogen water exhibited stronger ant oxidative and anticancer activity than did the natural hydrogen water. In conclusion, high-content hydrogen water can inhibit colon cancer, particularly in combination with 5-fluorouracil.

Supplementation Of Hydrogen-Rich Water Improves Lipid And Glucose Metabolism In Patients With Type 2 Diabetes Or Impaired Glucose Tolerance

Nutr Res, 2008 Mar;28(3):137-43. doi:10.1016/j.nutres.2008.01.008.

Kajiyama S, Hasegawa G, Asano M, Hosoda H, Fukui M, Nakamura N, Kitawaki J, Imai S, Nakano K, Ohta M, Adachi T, Obayashi H, Yoshikawa T
Oxidative stress is recognized widely as being associated with various disorders including diabetes, hypertension, and atherosclerosis. It is well established that hydrogen has a reducing action. We therefore investigated the effects of hydrogen-rich water intake on lipid and glucose metabolism in patients with either type 2 diabetes mellitus (T2DM) or impaired glucose tolerance (IGT). We performed a randomized, double-blind, placebo-controlled, crossover study in 30 patients with T2DM controlled by diet and exercise therapy and 6 patients with IGT. The patients consumed either 900 mL/d of hydrogen-rich pure water or 900 mL of placebo pure water for 8 weeks, with a 12-week washout period. Several biomarkers of oxidative stress, insulin resistance, and glucose metabolism, assessed by an oral glucose tolerance test, were evaluated at baseline and at 8 weeks. Intake of hydrogen-rich water was associated with significant decreases in the levels of modified low-density lipoprotein (LDL) cholesterol (ie, modifications that increase the net negative charge of LDL), small dense LDL, and urinary 8-isoprostanes by 15.5% (P b .01), 5.7% (P b .05), and 6.6% (P b .05), respectively. Hydrogen-rich water intake was also associated with a trend of decreased serum concentrations of oxidized LDL and free fatty acids, and increased plasma levels of adiponectin and extracellular-superoxide dismutase. In 4 of 6 patients with IGT, intake of hydrogen-rich water normalized the oral glucose tolerance test. In conclusion, these results suggest that supplementation with hydrogen-rich water may have a beneficial role in prevention of T2DM and insulin resistance.

Selective Stimulation Of The Growth Of Anaerobic Microflora In The Human Intestinal Tract By Electrolyzed Reducing Water.

96-99% of the “friendly” or residential microflora of intestinal tract of humans consists of strict anaerobes and only 1-4% of aerobes. Many diseases of the intestine are due to a disturbance in the balance of the microorganisms inhabiting the gut. The treatment of such diseases involves the restoration of the quantity and/or balance of residential microflora in the intestinal tract. It is known that aerobes and anaerobes grow at different oxidation-reduction potentials (ORP). The former require positive E(h) values up to +400 mV. Anaerobes do not grow unless the E(h) value is negative between -300 and -400 mV. In this work, it is suggested that prerequisite for the recovery and maintenance of obligatory anaerobic microflora in the intestinal tract is a negative
ORP value of the intestinal milieu. Electrolyzed reducing water with E(h) values between 0 and -300 mV produced in electrolysis devices possesses this property. Drinking such water favors the growth of residential microflora in the gut. A sufficient array of data confirms this idea. However, most researchers explain the mechanism of its action by an antioxidant properties destined to detox the oxidants in the gut and other host tissues. Evidence is presented in favor of the hypothesis that the primary target for electrolyzed reducing water is the residential microflora in the gut.

Pilot Study: Effects Of Drinking Hydrogen-Rich Water On Muscle Fatigue Caused By Acute Exercise In Elite Athletes

Kosuke Aoki1, Atsunori Nakao2*, Takako Adachi1, Yasushi Matsui1 and Shumpei Miyakawa1

Abstract
Background: Muscle contraction during short intervals of intense exercise causes oxidative stress, which can play a role in the development of overtraining symptoms, including increased fatigue, resulting in muscle microinjury or inflammation. Recently it has been said that hydrogen can function as antioxidant, so we investigated the effect of hydrogen-rich water (HW) on oxidative stress and muscle fatigue in response to acute exercise. Methods: Ten male soccer players aged 20.9 ± 1.3 years old were subjected to exercise tests and blood sampling. Each subject was examined twice in a crossover double-blind manner; they were given either HW or placebo water (PW) for one week intervals. Subjects were requested to use a cycle ergometer at a 75 % maximal oxygen uptake (VO2) for 30 min, followed by measurement of peak torque and muscle activity throughout 100 repetitions of maximal isokinetic knee extension. Oxidative stress markers and creatine kinase in the peripheral blood were sequentially measured.

Results: Although acute exercise resulted in an increase in blood lactate levels in the subjects given PW, oral intake of HW prevented an elevation of blood lactate during heavy exercise. Peak torque of PW significantly decreased during maximal isokinetic knee extension, suggesting muscle fatigue, but peak torque of HW didn’t decrease at early phase. There was no significant change in blood oxidative injury markers (d-ROMs and BAP) or creatine kinease after exercise.
Conclusion: Adequate hydration with hydrogen-rich water pre-exercise reduced blood lactate levels and improved exercise-induced decline of muscle function. Although further studies to elucidate the exact mechanisms and the benefits are needed to be confirmed in larger series of studies, these preliminary results may suggest that HW may be suitable hydration for athletes.

Effectiveness Of Hydrogen Rich Water On Antioxidant Status Of Subjects With Potential Metabolic Syndrome

Atsunori Nakao1,*, Yoshiya Toyoda1, Prachi Sharma2, Malkanthi Evans2 and Najla Guthrie2
1 Heart, Lung and Esophageal Surgery Institute, Department of Surgery, University of Pittsburgh Medical Center, Pittsburgh, PA, 15213, USA, 2 KGK Synergize, Inc., London, ON, postal code, Canada, N6A 5R8
Published online 24 February, 2010

Summary:
Metabolic syndrome is characterized by cardio metabolic risk factors that include obesity, insulin resistance, hypertension and dyslipidemia. Oxidative stress is known to play a major role in the pathogenesis of metabolic syndrome. The objective of this study was to examine the effectiveness of hydrogen rich water (1.5–2 L/day) in an open label, 8-week study on 20 subjects with potential metabolic syndrome. Hydrogen rich water was produced, by placing a metallic magnesium stick into drinking water (hydrogen concentration; 0.55–0.65 mM), by the following chemical reaction; Mg + 2H2O → Mg (OH)2 + H2. The consumption of hydrogen rich water for 8 weeks resulted in a 39% increase (p<0.05) in antioxidant enzyme superoxide dismutase (SOD) and a 43% decrease (p<0.05) in thiobarbituric acid reactive substances (TBARS) in urine. Further, subjects demonstrated an 8% increase in high density lipoprotein (HDL)-cholesterol and a 13% decrease in total cholesterol/HDL-cholesterol from baseline to week 4. There was no change in fasting glucose levels during the 8 week study. In conclusion, drinking hydrogen rich water represents a potentially novel therapeutic and preventive strategy for metabolic syndrome.

It has also been discovered that the documented “healing” or “curative” waters of Nordau, Germany; Tlacote, Mexico; and Hita Tenryosui, Japan waters contain dissolved hydrogen gas. The existence of molecular hydrogen in these springs could be a result of water reacting with alkali-earth metals, or from molecular hydrogen gas-producing bacteria and algae.

Healing Waters Contain Molecular Hydrogen

Some of the bacteria in our intestinal tract produce hydrogen gas from non-digestible fibers, which is perhaps another reason why a diet rich in fiber reduces inflammation and has cardiovascular and other health benefits.

Hydrogen: From The Beginning

Hydrogen has an intriguing history. It is the father of all elements of the universe, and along with oxygen, it has been intrinsically involved with evolution of life in both prokaryotes and eukaryotes (e.g. hydrogenates, hydrosomes, mitochondria, etc.). It is the extremes of oxygen and hydrogen that provide balance between oxidation and reduction, which is vital to life. Not surprisingly, this intimate relationship of oxygen and hydrogen has remained with higher organisms including plants, animals, and humans. However, until recently, research has only focused on the importance and toxicity of oxygen dismissing the role of hydrogen altogether, which negates the toxicity of oxygen—focusing only on one side of this Yin and Yang type relationship.

We are actively working on discovering the actual molecular mechanisms and primary targets of hydrogen gas. More in vitro data is what is needed to fully demonstrate and understand the therapeutic potential of molecular hydrogen.

Hydrogen gas has been shown to have a therapeutic effect on over 150 human diseases,but what is Hydrogen? Hydrogen is the lightest and simplest element with the symbol H. It consists of only one electron and one proton and, under normal conditions, it exists primarily in its diatomic form as molecular hydrogen (H2 gas). It is what powers the sun by fusion to produce helium. Hydrogen is the center of the prevailing cosmological model that describes the early development of the Universe as well as the origin of life itself.

FEATURES OF Hydrogen Kit

  • Generation of high-concentrated hydrogen water
  • With system control from automatic control program, hydrogen water with more than a certain concentration is always provided by controlling generation of hydrogen, dissolution timing, concentration control of hydrogen water etc. (At present, regular concentration of hydrogen (DH) based on sample device: more than 900 ppb) (Unit to product Hydrogen-reduced water with the function of controlling concentration of dissolved hydrogen: Invention patent)
  • Reduction potential of Hydrogen with strong antioxidant power Antioxidant power of hydrogen is about 150 times of Vitamin C, and 800 times of Coenzyme Q10. The reduction potential of hydrogen water provided in the module of this system is about -450 ~ -580mv with strong reducing power.
  • Provision of neutral (pH) Hydrogen Water Provision of hydrogen water in neutral PH7.2~7.8 with the nature of original water which can wipe out the controversy on pros and cons with strong alkaline in alkaline water.
  • Adoption of Hydrogen Generator in PEM Type PEM type electrolysis cell adopted Proton Exchange Membrane between platinum electrodes generates and provides the hydrogen with 99.9% of purity in rapid response and high efficiency.
  • Installation of high-efficiency Hydrogen Dissolving Unit Hydrogen Dissolving Unit with patent technology is a unique structure applying with an algorism of gaseous/liquid mixture, and ensures high-efficiency safe operation and long life.
  • Installation of ultra-pure reverse osmosis filters for electrolytic Ultra-mini reverse osmosis filter system is equipped for providing ultra-pure water to the hydrogen generating device. Minimum brain filter technology doubles the durability and efficiency of Platinum electrode and Proton exchange membrane.
  • 7Compact Module and Removable Structure Compact Module (Size:(W)93 * (L)76 * (H)134) designed in 3 Part Units can be installed in small products, and easily separated and fixed. 8. Minimization of Maintenance Cost Hydrogen Water Creation

Piping In Installing Hydrogen Water Creation Module

To provide hydrogen water in real-time by using original pressure (Pulmpless) in counter top type hydrogen purifier.

  • To control the operation of the switch by installing Solenoid Valve at the bottom of the filter.
  • If the functional filter is equipped in filter system, it is possible to extract by select functional water, hydrogen water etc. through selection of flow path.
  • The oxygen generated with hydrogen to be released outside or extracted with hydrogen water through the gaseous/liquid separator.
  • The power supply to HYDROGEN GENERATOR to be constructed with SMPS.

Specifications Of Hydrogen Water Creation Module And Guide For Order

Currently underway and optimization work was written based on the results of the prototype test

DivisionDescription
Manufacturing methodsPEM EC + R/O + HDU Combination
Power SupplySMPS Only
SafetySafety unit via the control circuit
Structural FeaturesBulkhead separating structure
Maximum Water supplymore than 720 (Liter/day)
Hydrogen Concentration(DH)more than 900 ppb to 1200 ppb
Oxidation Reduction Potential(ORP)-450~-580 mv
Hydrogen Ion Concentration(pH)7.2~7.8
Hydrogen Supply Pressure2~4.2 kgf/cm2
Dissolved uptimeImmediate and continuous operation
Circulation feeding time (choice)10-30 minutes period (User’s control)
After installation, normal uptimeAvailable immediately

Guide for order of hydrogen water creation module

  • donex Co., Ltd. maintains the technology for hydrogen water creation module and is doing its best to provide the module with patent and the technical support.
  • If you use the hydrogen water creation module, you can constitute hydrogen water system in cold, hot purifier type and direct water system type.
  • We will support the composition of display, control circuit, power circuit according to product design per company.
  • As the hydrogen water creation module is customized specifications, please consult us.

The world-famous miraculous water, including Lourdes (France), Tlacote (Mexico) and Nordenauer (Germany), has one thing in common. The secret is not minerals, but hydrogen!Water comprises 30% of human body, 94.5% of blood, and 74% of brain. It plays a key role of helping the functions of digestion, absorption, circulation and excretion, facilitating metabolism, and discharging toxic waste from the body. So drinking good water is one of the most vital factors to help you stay healthy.The recent standard of excellent water is, besides water quality and taste, the elimination of active oxygen, the main cause of aging and ailments.Doing the very best in R&D of quality water, FINE ALL CROP. Promises to grow with you as a sound company to create a healthy world through healthy lives.We can’t thank you enough.

The medicinal properties of molecular hydrogen appear to be promoted as early as 1798.3 Many years later in 1975, the departments of Biology and Chemistry from the prestigious Baylor University and Texas A&M published a great article on the potential use of molecular hydrogen in medicine in the premier peer-reviewed journal of science. However, it wasn’t until 2007, when an article was published in Nature Medicine, which showed the selective antioxidant properties and ant apoptotic (anti-cell death) activity of molecular hydrogen, that the biomedical field took strong interest in hydrogen’s therapeutic potential. Prior to 2007, only 50 articles were published regarding hydrogen as a medical gas, compared to over 500 articles within the past seven years. Perhaps the main reason why it is only recently that molecular hydrogen is being recognized as a therapeutic molecule is because of scientific skepticism. It is difficult to believe diatomic molecular hydrogen could have any therapeutic effects because it is generally considered to be an inert gas.

How Ii Works

Molecular hydrogen is the smallest element and lightest molecule. There are three main properties that explain hydrogen’s therapeutic effects. 1. Molecular hydrogen can easily diffuse into the subcellular compartments, reducing the levels of cytotoxic oxygen radicals and protecting the DNA, RNA and proteins from oxidative stress. 2. Molecular hydrogen also triggers the activation or up regulation of additional antioxidant enzymes (e.g. glutathione, superoxide dismutase, catalase, etc.) and/or cytoprotective proteins of the body. 3. Molecular hydrogen may be a novel-signaling molecule that can alter cell signaling, cell metabolism and gene expression, and explain the anti-inflammatory, anti-allergic, and anti-apoptotic (or anti-cell death) effects.

Hydroxide (Oh–) Confusion

There appears to be a lot of confusion about the hydroxide ion, i.e. OH–, (also incorrectly called just “hydroxyl”, which ironically is a free radical or even “hydroxyl water”) within the “ionized water community”. This is because numerous websites, marketers, sales pitches, explanations, etc. claim that hydroxides are antioxidants. Recently, however, there are other voices purporting that this hydroxide is not an antioxidant, but the polar opposite: a free radical. The reality of all this confusion is that it is neither.

Notion As An Antioxidant

It seems that most people teach that hydroxide is an antioxidant. This false teaching probably stems from the following four perspectives:

  • The wide held belief in the fallacy that antioxidants are negative whereas free radicals are positive coupled with the fact that hydroxide (OH) has a negative charge.
  • Alkaline ionized water has a high pH and thus contains more hydroxides (OH) ions, which are negatively charged
  • Alkaline ionized water does exhibit a negative oxidation-reduction potential (ORP) and has antioxidant activity.
  • The fact that molecular hydrogen (H2) was not recognized as the reason for the –ORP, the antioxidant activity and the therapeutic effects until about 2007, which means ionized water was marketed decades before the proof of H2 was established.

The belief that hydroxide, or even just water itself, is the antioxidant has been around a long time with comparisons of molecular weight as shown. This of course is considered pseudoscience, as there is no truth to it.

Notion As A Free Radical

It has also been taught that hydroxide (OH) is a free radical. I am not sure how this came to be, but perhaps it was because of the similarity between the terms hydroxide (OH) and hydroxyl OH). The latter is actually one of the the most reactive oxygen radicals there are. Notice the black dot on the upper right side of the H in the symbol (OH.); this is indicative of an unpaired electron, which means it is a free radical.
Those who are not familiar with chemistry often use hydroxyl and hydroxide interchangeably—even though they are entirely different species. The hydroxide ion (far left) is not radically reactive at all, as it contains stable paired electrons.

Hydroxide Is A Base

Hydroxide (OH) or the hydroxyl ion is a component of water.  Water dissociates to form OH ions and H3O+ ions. That is: 2H2O => OH and H3O+
Notice that this reaction is reversible, which means that the hydroxide ion can react with the hydronium ion (H3O+) to form two water molecules. So yes, hydroxides are reactive when discussing Acid/Base chemistry, but not as a biological antioxidant.

Antioxidant In Ionized Water Is Molecular Hydrogen

Another thing to consider is what would happen if hydroxide (OH) acted as an antioxidant and donated an electron? It would turn into the most cytotoxic oxygen radical: the hydroxyl radical (OH.). Thus the reaction produced a radical more reactive than the first one, which isn’t going to happen. Because it is clear that hydroxide is not an antioxidant, much less a free radical, touting it as either one is another reason why many ridicule the concept of ionized water.
The take-home message is that hydroxide (OH) is higher in alkaline water according to the definition of pH, but it is not a biological antioxidant. The therapeutic agent in ionized water is clearly dissolved molecular hydrogen gas (H2).

Mechanism On Fast Removal Of Dirt And Oil

  • Small water molecule clusters of SAW can dissolve the dirt particles
  • Can penetrate into the space between the dirt particles and the object surface resulting in separation of dirt from the object surface
  • Two dirt particles with surfaces being covered by negative OH ions of SAW, causing separation from each other
  • High alkalinity causing emulsification of the oil and fat of the dirt.

Mechanism On Effectiveness In Disinfecting And Sanitising

High alkalinity and negative ORP (Oxygen Reduction Potential) tend to weaken and kill the germs and bacteria by breaking up the cell membrane.

Major Applications

  • Food Industry: — Washing of fruits and vegetables to wash away pesticides and fertilisers — Washing of meat and seafood to clean and take off the bad smell, killing germs and bacteria to preserve the freshness of food. — Cleaning of food processing machines, equipment and utensils in restaurants and kitchens
  • Commercial Buildings, Public Facilities and Home — In Japan, there are hundreds commercial buildings being installed with an SAW machine for use in most types of cleaning with the objective to do away with detergents and chemicals for cleaning of floor, carpets, windows, furniture and toilets etc. Water charge and waste water treatment charges are greatly reduced with less sick leave for cleaning staffs. — For Home use, SAW is very effective and convenient in cleaning air-conditioner, refrigerator, micro-wave oven, barbecue stove etc with simply spray and wipe without rinsing. — In USA and Europe, more and more large commercial end-users, using cleaning chemicals and detergents in the past, are installing SAW making machines for cleaning in hotels, shopping malls, universities and schools, restaurants and food chains.
  • Industrial — In Japan, the car industry is the largest end-user of SAW for cleaning spare parts and new cars with great saving in reducing waste water treatment facilities. — SAW is being used in metal cutting to increase efficiency and reduce cost and in cleaning in the electronic industry. Environmental Control, farming, aquaculture, dairy and poultry — For neutralising the acidity of soil and water due to acid rain. — For cleaning, deodourising and sanitising in farms, aquaculture and dairy industries. — Drinking diluted weak SAW may help to improve the effectiveness of animal food additives to increase productivity of animals in farms with improved health and growth of animals and poultry.

What Is Molecular Hydrogen?

Although the research is early, the 1000+ scientific articles suggest that H2 has therapeutic potential in over 170 different human and animal disease models, and essentially every organ of the human body.

  • Molecular hydrogen (H2) or diatomic hydrogen is a tasteless, odorless, flammable gas
  • H2 reduces oxidative stress and improves redox homeostasis partly mediated via the Nrf2 pathway, which regulates levels of glutathione, superoxide dismutase, catalase, etc.
  • H2, like other gaseous-signaling molecules (e.g. NO*, CO, H2 S), modulates signal transduction, protein phosphorylation, and gene expression, which provides its anti-inflammatory, anti-allergy, and anti-apoptotic protective effects.

Molecular Hydrogen (i.e. H2 gas) is gaining significant attention from academic researchers, medical doctors, and physicians around the world for its recently reported therapeutic potential. One of the earliest publications on hydrogen as a medical gas was in 1975, by Dole and colleagues from Baylor University and Texas A&M. They reported in the journal Science that hyperbaric (8 atm) hydrogen therapy was effective at reducing melanoma tumors in mice. However, the interest in hydrogen therapy only recently began after 2007, when it was demonstrated that administration of hydrogen gas via inhalation (at levels below the flammability limit of 4.6%) or ingestion of an aqueous-solution containing dissolved hydrogen, could also exert therapeutic biological effects. These findings suggest hydrogen has immediate medical and clinical applications.

In 2007, Dr. Ohta’s team reported in Nature Medicine [3] that inhalation of 2-4% hydrogen gas significantly reduced the cerebral infarct volumes in a rat model of ischemia-reperfusion injury induced by middle cerebral artery occlusion. Hydrogen was more effective than edaravone, an approved clinical drug for cerebral infarction, but with no toxic effects (See figure on left). The authors further demonstrated that dissolved hydrogen in the media of cultured cells, at biologically relevant concentrations, reduces the level of toxic hydroxyl radicals (*OH), but does not react with other physiologically important reactive oxygen species (e.g. superoxide, nitric oxide, hydrogen peroxide).

This biomedical research on hydrogen is still in its infancy with only around 500 articles and 1,600 researchers, but these publications and researchers suggest that hydrogen has therapeutic potential in over 170 different human and animal disease modelsand in essentially every organ of the human body. Hydrogen appears to provide these benefits via modulating signal transduction, protein phosphorylation, and gene expressions (See section Pharmacodynamics)

The idea of therapeutic gaseous molecules is not a new concept. For example, carbon monoxide (CO), hydrogen sulfide (H2S), and of course nitric oxide (NO*), which was initially ridiculed by skeptics, but later was subject to a Nobel Prize, are all biologically active gases. However, it may still be difficult to believe that H2 can exert any biological effect, because in contrast to these other gases, hydrogen is a non-radical, non-reactive, non-polar, highly diffusible neutral gas, thus it is unlikely to have specific binding sites, or interact with specificity on a specific receptor.

From an evolutionary perspective it may not be strange that hydrogen exerts a biological effect. In addition to its role in the origins of the universe, hydrogen was also involved in the genesis of life and played an active role in the evolution of eukaryotes. Over the millions of years of evolution, plants and animals have developed a mutualistic relationship with hydrogen-producing bacteria resulting in basal levels of molecular hydrogen in eukaryotic systems. This constant exposure to molecular hydrogen may have conserved the original targets of hydrogen, as can be extrapolated by genetic remnants of hydrogenase enzymes in higher eukaryotes. Alternatively, but not exclusively, eukaryotes may have developed sensitivity to molecular hydrogen over the millions of years of evolution.

METHODS OF ADMINISTRATION

Molecular hydrogen can be administered via inhalation, ingestion of solubilized (dissolved) hydrogen-rich solutions (e.g. water, flavored beverages, etc.), hydrogen-rich hemodialysis solution, intravenous injection of hydrogen-rich saline, topical administration of hydrogen-rich media (e.g. bath, shower, and creams), hyperbaric treatment, ingestion of hydrogen-producing material upon reaction with gastric acid, ingestion of non-digestible carbohydrates as prebiotic to hydrogen-producing intestinal bacteria, rectal insufflation, and other methods.

PHARMACOKINETICS

Hydrogen’s unique physicochemical properties of hydrophobicity, neutrality, size, mass, etc. afford it with superior distribution properties allowing it to rapidly penetrate bio membranes (e.g. cell membranes, blood-brain, placental, and testis barrier) and reach subcellular compartments (e.g. mitochondria, nucleus, etc.) where it can exert its therapeutic effects. Although various medical clinics in Japan use intravenous injection of hydrogen-rich saline, the most common methods are inhalation and drinking hydrogen-rich water. The pharmacokinetics of each method are still under investigation, but are dependent on dosage, route, and timing. An article published in Nature’s Scientific Reports compared inhalation, injection and drinking with different hydrogen concentrations and found helpful insights for clinical use. Based on this and various studies, we briefly summarize the pharmacokinetics of inhalation and drinking.

INHALATION OF HYDROGEN

For inhalation, a 2-4% hydrogen gas mixture is common because it is below the flammability level; however, some studies use 66.7% H2 and 33.3% O2, which is nontoxic and effective, but flammable. Inhalation of hydrogen reaches a peak plasma level (i.e. equilibrium based on Henry’s Law) in about 30 min, and upon cessation of inhalation the return to baseline occurs in about 60 min.

DRINKING DISSOLVED HYDROGEN

The concentration/solubility of hydrogen in water at standard ambient temperature and pressure (SATP) is 0.8 mM or 1.6 ppm (1.6 mg/L). For reference, conventional water (e.g. tap, filtered, bottled, etc.) contains less than 0.0000002 ppm of H2, which is well below the therapeutic level. The concentration of 1.6 ppm is easily achieved by many methods, such as simply bubbling hydrogen gas into water. Because of molecular hydrogen’s low molar mass (i.e. 2.02 g/mol H2 vs. 176.12 g/mol vitamin C), there are more hydrogen molecules in a 1.6-mg dose of H2 than there are vitamin C molecules in a 100-mg dose of pure vitamin C (i.e. 1.6 mg H2 has 0.8 mill moles of H2 vs. 100 mg vitamin C has 0.57 mill moles of vitamin C). The half-life of hydrogen-rich water is shorter than other gaseous drinks (e.g. carbonated or oxygenated water), but therapeutic levels can remain for a sufficiently long enough time for easy consumption. Ingestion of hydrogen-rich water results in a peak rise in plasma and breath concentration in 5-15 min in a dose-dependent manner (see figure). The rise in breath hydrogen is an indication that hydrogen diffuses through the sub mucosa and enters systemic circulation where it is expelled out the lungs. This increase in blood and breath concentration returns to baseline in 45-90 min depending on the ingested dosage.

PHARMACODYNAMICS

Although a significant amount of research in cells, tissues, animals, humans and even plants have confirmed hydrogen’s effect in biological systems, the exact underlying molecular mechanisms and primary targets remain elusive.

ANTIOXIDANT-LIKE EFFECT

It was initially suggested that the beneficial effect of hydrogen was due to an antioxidant as hydrogen selectively neutralized cytotoxic hydroxyl radicals in vitro. However, although H2 reduces *OH radicals, as has been shown in various systems, it may not occur via direct scavenging, and it also cannot fully explain all the benefits of hydrogen. For example, in a double-blinded placebo controlled trial in rheumatoid arthritis, hydrogen had a residual effect that continued improving the disease symptoms for four weeks after hydrogen administration was terminated. Many cell studies also show that pre-treatment with hydrogen has marked beneficial effects even when the assault (e.g. toxin, radiation, injury, etc.) is administered long after all the hydrogen has dissipated out of the system. Additionally, the rate constants of hydrogen against the hydroxyl radical are relatively slow (4.2 x 107 M-1 sec-1), and the concentration of hydrogen at the cellular level is also quite low (micro molar levels), thus making it unlikely that H2 could effectively compete with the numerous other nucleophile targets of the cell. Lastly, if the mechanism were primarily associated with scavenging of hydroxyl radicals, then we should see a greater effect from inhalation compared to drinking, but this is not always the case. In short, we consider it inaccurate or at least incomplete to claim that the benefits of hydrogen are due to its acting directly as a powerful antioxidant. Indeed, hydrogen is selective because it is a very weak antioxidant and thus does not neutralize important ROSor disturb important biological signaling molecules. Nevertheless, a metabolic tracer study using deuterium gas demonstrated that, under physiological conditions, deuterium gas is oxidized, and the oxidation rate of hydrogen increases with an increasing amount of oxidative stress , but the physicochemical mechanism for this may still not be direct radical scavenging. However, not all studies show that hydrogen is oxidized via mammalian tissues and it has also been reported that deuterium gas did not exert a therapeutic effect in the model studied whereas 1H did (unpublished data).

NRF2 PATHWAY Unlike conventional antioxidants hydrogen does have the ability to reduce excessive oxidative stress but only under conditions where the cell is experiencing abnormally high levels of oxidative stress that would be harmful and not hermetic. One mechanism that hydrogen uses to protect against oxidative damage is by the activation of the Nrf2-Keap1 system and subsequent induction of the antioxidant response element (ARE) pathway, which leads to the production of various cytoprotective proteins like glutathione, catalase, superoxide dismutase, glutathione peroxidase, heme-1 oxygenate, etc. In some disease models, the benefits of hydrogen are negated by using Nrf2 gene knockouts Nrf2 genetic silencing using iRNA or pharmacologically blocking the Nrf2 pathway Importantly, hydrogen only activates the Nrf2 pathway when there is an assault (e.g. toxin, injury, etc.) as opposed to constituently acting as a promoter, which could be harmful The method that hydrogen activates the Nrf2 pathway remains unclear.

CELL MODULATION

Besides the potential scavenging of hydroxyl radicals and/or activation of the Nrf2 pathway, hydrogen may ameliorate oxidative stress via a cell modulating effect and reduce the formation of free radicals, such as down regulating the NADPH oxidase system. The various cell modulating effects of hydrogen are responsible for mediating the anti-inflammatory, anti-allergy, and anti-obesity effects of hydrogen. Hydrogen has been shown to down regulate pro-inflammatory cytokines (e.g. IL-1, IL-6, IL-8, etc.), attenuate the activation of TNF-a NF-?B, NFAT, NLRP3, HMGB and other inflammatory mediators. Additionally, hydrogen has beneficial effects on obesity and metabolism by increasing the expression of FGF2, PGC-1a, PPARa, and more. Additional 2nd messenger molecules or transcription factors affected by hydrogen include ghrelin, JNK-1, ERK1/2, PKC, GSK, TXNIP, STAT3, ASK1, MEK, SIRT1, and many more. Over 200 biomolecules are altered by hydrogen administration including over 1000 gene expressions. However, the primary targets and master regulators

responsible for these changes are still elusive. There are many feedback systems and loops to consider, which makes it difficult to determine if we are detecting the cause or the effect of hydrogen administration.

The exact mechanism of how hydrogen modulates signal transduction, gene expression, and protein phosphorylation is still being investigated. A recent publication in Scientific Reports provides good evidence to suggest that one of the mechanisms through which hydrogen accomplishes the various cell-modulating effects is by modifying lipid peroxidation in the cell membrane. In cultured cells, at biologically relevant concentrations, hydrogen suppressed the free radical chain reaction-dependent peroxidation and recovered Ca2+-induced gene expressions, as determined by comprehensive microarray analysis.

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 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

Hydrogen as a medical gas is also growing because it has immediate medical applications to help with many of the current health crises. 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. Dr. Banksfrom the VA/U of Washington, reported that ingestion of hydrogen-rich water was protective against neurodegenerative changes induced by traumatic brain injury in mice. 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. 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. 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, diabetes, and hyperlipidemia.Another 1-year placebo-control clinical study suggested that hydrogen-rich water is beneficial for Parkinson’s disease, while other clinical studies suggest significant benefits for rheumatoid arthritis, mitochondrial dysfunction, exercise performance, athletic recovery time, wound healing, reductions of oxidative stress from chronic hepatitis B, improvements to blood flow, and periodontitis, in dialysis, and also the quality of life in patients receiving radiotherapy for tumors and others. 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. 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.

SAFETY

Hydrogen is naturally produced by intestinal flora upon digestion of fibers. A study from the University of Florida and the Forsythe Institute of Boston, Massachusetts confirmed that hydrogen produced from bacteria exerted therapeutic effects.They found that reconstitution of intestinal micro biota 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. 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. 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. Additionally, hydrogen gas has also been used in deep sea diving since the 1940s to prevent decompression sickness. 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. In some people, however, it is reported that hydrogen may result in loose stools and in rare cases with diabetics, hypoglycemia, 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 hermetic pathways.

FUTURE DIRECTIONS

The goal of the Molecular Hydrogen gas 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. 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.

HISTORY

One of the important parameters of water quality is the pH. A pH measurement reveals whether the solution is acidic, neutral, or alkaline. The chemistry of water has been discussed previously, which will help us understand what pH really is. In the most basic sense, pH refers to the negative logarithmic (log) measurement of the H+ion concentration in solution. The more H+, the more acidic; the less H+, the more alkaline. The term pH was first used in 1920, but the concept was invented by Danish chemist, Soren Peter Sorenson, in 1909 to refer to negative log (inverse of an exponent) of the hydrogen ion concentration. The ‘p’ refers to the German word ‘potenz’ or power (power having reference to it being an exponent). The power referred to is the power of 10 used as the base of the log and not to the strength of the acid in solution.

THE H+ ION

The H+ ion comes from the self-ionization or auto-proteolysis of water, wherein H2O splits to form H+ ion (proton) and OH– ion (hydroxide). That is H2O ? H+ + OH– However, the H+ ion is attracted to the negatively charged oxygen of another water molecule to form H3O+ ion (hydronium ion). Actually H+ ions don’t exist in water and the use of H+ really has reference to the hydronium ion, which is further complexed by additional water molecules.

SELF-IONIZATION OF WATER

The following diagram depicts a more accurate explanation of the self-ionization of water. A water molecule can pull a hydrogen off another water molecule, which results in the two ionic species, hydroxide (OH–) and hydronium (H3O+). Notice that this reaction is reversible. The hydroxide can react with the hydronium ion to form two water molecules. Water is considered to be amphoteric because it can act as an acid (a molecule that produces H3O+) or a base (the produced OH– can neutralize the acid), which is the definition of amphoteric.

THE IONIC PRODUCT OF WATER

If we measure the concentration of H3O+ and OH– in pure water, they would be the same because for every H3O+ ion created, an OH– ion is created. This is why pure water is neutral because the concentration of the two different ions is the same. In pure water (at 25° C), the concentration is 1 X 10-7 moles/liter for both the H3O+ and the OH–. Remember that pH means the –log of the H3O+ concentration, so if you take the – log of 1 X 10-7 you get pH of 7, which we know is neutral. If you multiply the concentration of the H3O+ ion and the OH– ion together (i.e. 1 X 10-7multiplied by 1 X 10-7), you get 1 X 10-14. This is called the ionic product of water; it is a constant with the symbol Kw. Notice that if you take the –log of the Kw you get 14, which as you know is important to the pH scale.

DISSOLVED HYDROGEN AND PH

When talking about hydrogen, some will fail to make the important distinction as to which species of hydrogen is being discussed. The positive hydrogen ion (H+) is often referred to as “hydrogen”. But as we discussed above, this form of hydrogen is responsible for the “acid” level (pH) of water. If one assumes that the hydrogen ion is the species being discussed, they may think that adding hydrogen gas (H2) to water will change the pH of the water. But, molecular hydrogen (H2) is a neutral molecule which, when dissolved in water, has no influence on the water’s pH.Alkaline ionizers raise the pH of the water not as a direct result of adding H2 but because in order to produce H2, they must consume the H+ ions in the water, thus making the water more alkaline. Methods of producing hydrogen water such as bubbling or infusing, which simply add pure hydrogen gas to water, do so without changing the original pH of the water.

MOLECULAR HYDROGEN IN WATER IS GREAT FOR SKIN

The desire to have healthy, elastic, wrinkle-free, and young looking skin dates back to primeval times. One of the ways (which is still used today) to try and accomplish this is the ancient practice of bathing in springs and mineral waters. However, unlike most conventional practices of lotions, creams, oils, powders and other cosmetics that may not help and/or even have negative side effects, bathing in specific waters that have reductive characteristics seems to have great therapeutic application.

One study tested a mineral water with reductive characteristics (most likely due to dissolved molecular hydrogen) and a prepared water containing molecular hydrogen. The results revealed that bathing in both of these waters decreased the oxidation-reduction potential (ORP) of human skin. This is an important observation because healthy skin has reductive characteristics and the ORP of the skin increases by oxidative damage (from sun exposure) and also by aging (as measured by lipid-peroxide levels).This relationship between redox potentials of the skin and aging has been investigated in more detail and shows that reductive waters lower the oxidation of the skin. Bathing in hydrogen water not only reduced the ORP of skin, but also improved its elasticity. Moreover, treating bleached hair with this water gave an improvement in fluency and gloss.

MOLECULAR HYDROGEN & SUNBURNS

One group of researchers gave hairless mice sunburns. They bathed one group in tap water and the other in hydrogen water. The skin of the mice bathed in hydrogen water showed significantly lower indices of skin injury and lower inflammatory cytokine levels. Another group of researchers performed a similar study and found that bathing mice in hydrogen water reduced the level of skin damage, increased activity of the antioxidant glutathione peroxidase, lowered inflammatory cytokines, and prevented ultrastructure changes of the skin, suggesting hydrogen water can protect against UV-induced skin cell damage. This was further validated in another article where hydrogen water was shown to be very beneficial for UV induced skin cell damage. The study showed that Type-1 collagen was synthesized about two-fold more in the cells treated with hydrogen water. It also prevented DNA damage, cell death, and decreased levels of intracellular free radicals. The study also reveals that in human subjects, bathing in hydrogen water for three months significantly improved wrinkles in the skin. The authors concluded that hydrogen water might serve as a daily skin care to repress UVA-induced skin damage by scavenging free radicals and promoting type-1 collagen synthesis. Hydrogen water was also seen to prevent arsenic-impaired calcium signaling (which is involved in skin cancer) in keratinocytes (predominate cell type in skin) through both its antioxidant and non-antioxidant cell signaling effects. In other words, hydrogen not only exerts protection and benefits on the skin because it’s an antioxidant, but also as a cell signaling molecule.

IONIZED WATER: IMPORTANT RECOMMENDATION

Somewhat ironically, proponents of ionized water advocate using the oxidizing acidic water from the anode, as opposed to the reducing water with molecular hydrogen from the cathode. As discussed here, this acidic water is touted as being an astringent for the skin and often referred to as “beauty water”. The idea is that because the skin pH is slightly acidic then the logical choice would be to use slightly acidic water for the skin. There may be some valid research for this concept to some extent simply because high pH water can have negative effects on the skin. The main problem in using this acidic water from an ionizer is that it generally contains hypochlorous acid, which is a strong oxidizer. Obviously, this is not the best choice for youthful, young-looking skin. The problem with using the reducing (alkaline) water is that its high pH is not good for your skin. However, this can easily be overcome by adding a few drops of lemon juice (or other organic acids) to the alkaline water. This gives you the acidic pH and the benefits of molecular hydrogen. The lemon juice itself may also exert beneficial effects.