The H2MEDICAL team presents you a translated small part of an OFFICIAL MEDICAL REPORT on the action of H2 and hydrogen water in active athletes and patients with various diseases, such as Diabetes, Parkinson's, Dementia, Rheumatoid Arthritis, Cancer, Metabolic Syndrome, Myocardial Infarction, Stroke and many more. We have put a link to the published official report at the end of the article. Our team has translated the following parts of the report, keeping the numbering so that you can easily navigate your way around when opening the official document. The translated paragraphs are: the Introduction "Abstract", the whole paragraph "6" about the effects of H2 on the health status of different patient groups and the Conclusion of the report "9. Concluding remarks".
TITLE OF THE REPORT: Molecular hydrogen as a preventive and therapeutic medical gas: The origins, development and potential of hydrogen medicine. Published in October 2014.
Introduction "Abstract"
"Molecular hydrogen (H2) has been accepted as an inert and non-functional molecule in our body. We have reversed this concept by showing that H2 reacts with strong oxidants such as the hydroxyl radical in cells and has potential for preventive and therapeutic applications. H2 has a number of advantages exhibiting extensive effects: H2 diffuses rapidly into tissues and cells, not disrupting metabolic redox reactions, and does not affect signaling of reactive oxygen species; therefore, there are no adverse effects of H2. There are several methods of ingesting or ingesting H2; inhaling H2 gas, drinking hydrogen water (H2-enriched water), injecting H2 saline, taking an H2 bath, or placing H2 saline in the eyes. Numerous publications on its biological and medical benefits reveal that H2 reduces oxidative stress not only by neutralizing strong oxidants, but also indirectly by regulating various gene expressions. Thus, H2 has anti-inflammatory and anti-apoptotic effects, and stimulates energy metabolism. A rapidly growing number of clinical studies and experiments have demonstrated the extensive therapeutic properties of H2. Most drugs act specifically on a physiological problem, whereas H2 differs from conventional pharmaceuticals by affecting every organ as well as all biochemical processes in cells. Because of its great efficacy and lack of adverse effects, H2 has promising potential for clinical use against many diseases.
Many reports confirm that H2 exhibits great efficacy in extensive disease models, regardless of ingestion methods.
6. Effects of molecular hydrogen and clinical studies
6.1. Safety of molecular hydrogen for humans H2 has advantages in terms of toxicity:
H2 has no cytotoxicity even at high concentrations (Abraini et al., 1994, Lillo et al., 1997, Fontanari et al., 2000, Lillo and Parker, 2000). Safety standards have been established for high concentrations of H2 gas for inhalation because high-pressure H2 gas is used in deep diving mixtures to prevent decompression sickness and arterial gas thrombi (Fontanari et al., 2000). Important for clinical use: the safety of H2 for humans has been demonstrated by the application of an extremely high concentration of H2 gas in "Hydreliox" (an exotic inhalation gas mixture) of 49% H2, 50% helium and 1% O2, which is used to prevent decompression sickness and nitrogen narcosis during very deep technical diving (Abraini et al., 1994, Lillo et al., 1997, Fontanari et al., 2000, Lillo and Parker, 2000). Given that H2 is an inert gas and does not function in our body, its lack of toxic effects is easily understood. As mentioned above, inhalation of 1-4% H2 gas has great effectiveness (Ohsawa et al., 2007, Hayashida et al., 2008).
6.2. Protective effects against reperfusion injury
Ischemia/reperfusion induces serious oxidative stress and its injury must be considered in many clinical treatments. Inhalation of H2 gas improves ischemia/reperfusion injury in stroke (Ohsawa et al., 2007) and myocardial infarction (Hayashida et al., 2008, Yoshida et al., 2012). All clinical manifestations associated with post-cardiac infarction (CI) syndrome are attributed to ischemia/reperfusion injury in various organs, including the brain and heart. Inhalation of H2 gas resulted in a significant improvement in survival and neurological deficit score in post-SI syndrome in a mouse model (Hayashida et al., 2012).
H2 also reduced disability during transplantation of various organs. A study with H2 gas (Buchholz et al., 2008) and with hydrogen water (Cardinal et al., 2010), and H2 preservation solution (Noda et al., 2013).
Intravenously administered H2-physiological solution, a clinically approved radical scavenger in 8 patients with acute brainstem infarction. Magnetic resonance imaging (MRI) indices of 26 patients who received Edaravone alone were compared. Relative diffusion-weighted imaging (rDWI), regional apparent diffusion coefficients (rADC), and pseudo-normalization times of rDWI and rADC were improved with the combined infusion of H2 with Edaravone (Ono et al., 2011).
6.3. Protective effects against neurodegeneration
Chronic oxidative stress is widely accepted as one of the causes of neurodegeneration, including dementia and Parkinson's disease (PD) (Andersen, 2004, Federico et al., 2012). Experimental oxidative stress in the brain can be induced by chronic physically restrained stress and can impair learning ability and memory (Liu et al., 1996, Abrous et al., 2005). Furthermore, neuronal proliferation in the dentate gyrus of the hippocampus is suppressed by restraint stress (Abrous et al., 2005). Drinking hydrogen water (H2-enriched water) suppresses the increase in this oxidative stress and prevents this cognitive impairment (Nagata et al., 2009). Moreover, H2-water restores neural proliferation in the dentate gyrus of the hippocampus (Nagata et al., 2009). Since antidepressants increase neurogenesis in the elderly (Becker and Wojtowicz, 2007, Sahay and Hen, 2007), hydrogen water is applicable to improve depression and some psychiatric disorders. In Parkinson's, mitochondrial dysfunction and associated oxidative stress are major causes of dopaminergic cell loss in the nigra (Yoritaka et al, 1996, Schapira, 2008). H2 water is given before or after stereotactic surgery for 6-hydroxydopamine-induced nigrostriatal degeneration in a rat model of Parkinson's. H2-water inhibited both the development and progression of nigrostriatal degeneration in rats (Fu et al., 2009). Furthermore, drinking H2-water also suppresses dopaminergic neuronal loss in another Parkinson's model induced by MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) (Fujita et al., 2009).
In a placebo-controlled, shuffled, double-blind, parallel-group clinical pilot study, the efficacy of H2-water in Parkinson's disease patients treated with levodopa was evaluated (Yoritaka et al., 2013). Participants drank 1 L daily of H2-water or placebo water for 48 weeks. Total Unified Parkinson's Disease Rating Scale (UPDRS) scores in the H2-water drinking group (n = 9) improved, whereas UPDRS scores in the placebo group (n = 8) worsened. Despite the low number of patients and the short duration of the trial, the difference was significant (P < .05).
6.4. Preventive effects against metabolic syndrome
Drinking H2-water stimulates energy metabolism (Kamimura et al., 2011). H2-water significantly alleviated fatty liver in db/db mice, which is a type 2 diabetic obese mouse, as well as diet-induced fatty liver in wild-type mice. Long-term hydrogen water drinking significantly reduced fat and body weight, despite increasing diet and water consumption, in db/db mice. Furthermore, drinking H2-water reduced plasma glucose, insulin and triglyceride levels by stimulating energy metabolism (Kamimura et al., 2011).
The beneficial roles of H2-water in the prevention of potential metabolic syndrome are reported by 3 independent clinical studies as follows:
Kajiyama et al. performed a randomized, double-blind, placebo-controlled, crossover study in 30 patients with type II diabetes mellitus and 6 patients with impaired glucose tolerance. Patients consumed 900 ml of hydrogen water or placebo water for 8 weeks with a 12-week washout period. Statistical significance was observed in the improvement of electronegative charge-modified low-density lipoprotein (LDL)-cholesterol, small dense LDL, and urinary 8-isoprostanes. In four of six patients with impaired glucose tolerance, H2 improved their oral glucose tolerance test indices to normal levels (Kajiyama et al., 2008).
An open-label study was conducted in 20 individuals with potential metabolic syndrome (Nakao et al., 2010b). Participants drank H2-water (1.5-2.0 L/day) for 8 weeks and showed an increase in urinary SOD; a decrease in urinary thiobarbituric acid reactive substances (TBARS), a marker of lipid peroxidation; an increase in high-density lipoprotein (HDL)-cholesterol; and a decrease in total cholesterol.
Song et al. characterized the effects of H2-water (0.9-1.0 L/day) on serum lipoprotein content, composition, and bioactivity in 20 patients with potential metabolic syndrome. Serum analysis showed that drinking hydrogen water for 10 weeks resulted in a reduction in serum total cholesterol (TC) and LDL-cholesterol levels. In addition, H2-water significantly improved 1) protection against LDL oxidation, 2) inhibition of tumor necrosis factor-α (TNF-α)-induced adhesion of monocytes to endothelial cells, 3) stimulation of cholesterol efflux from macrophage foam cells, and 4) protection of endothelial cells from TNF-α-induced apoptosis (Song et al., 2013).
Taken together, these results strongly suggest the benefits of drinking hydrogen water in patients with metabolic syndrome.
6.5. Suppressive effects in inflammation
H2 reduced inflammation in experimental animals induced by concanavalin A (Kajiya et al., 2009), dextran sodium sulfate (Kajiya et al., 2009), lipopolysaccharide (LPS) (Xu et al., 2012, Chen et al, 2013) ), Zymosan, an inducer of generalized inflammation (Xie et al., 2010b), and polymicrobial sepsis (GM Li et al., 2013). H2 gas, H2-physiological solution, and H2-water reduced levels of proinflammatory cytokines and suppressed inflammation.
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by bone and cartilage destruction. Intake of hydrogen water containing 4-5 mg/L H2 (H2-saturated water) (0.5 L/day) for 4 weeks in 20 patients with RA. Urinary 8-hydroxy-deoxyguanine (8-OHdG) was significantly reduced by a mean of 14.3% (P < 0.01). Disease activity (DAS28) using reactive C-protein levels also decreased (P < 0.01) during the same period. After the clearing period, both urinary 8-OHdG and mean DAS28 decreased compared with the end of the drinking period. in the second drinking period, mean DAS28 was reduced (P < 0.01). All 5 patients with early RA (duration <12 months) who did not show antibodies to cyclic citrullinated peptides (ACPAs) achieved remission, and 4 of them became asymptomatic at the end of the study. Thus, RA symptoms were significantly improved by drinking H2-water (Ishibashi et al., 2012, Ishibashi, 2013).
6.6. Reducing side effects in cancer treatment
Inhalation of H2 gas and drinking H2-water reduced the mortality and body weight loss caused by treatment with the anticancer drug, cisplatin, and alleviated nephrotoxicity in mice. Despite its protective effects against cisplatin-induced toxicity, H2 did not affect antitumor activity of cisplatin against cancer cell lines in vitro and tumor-bearing mice in vivo (Nakashima-Kamimura et al., 2009).
Kang et al. conducted a randomized placebo-controlled clinical trial of H2-water (0.55-0.65 mM, 1.5-2.0 L/day) for 6 weeks in 49 patients on radiation therapy for malignant liver tumors. H2 suppressed increases in total hydroperoxide levels, maintained serum antioxidant capacity, and improved quality of life (QOL) scores. In particular, H2-water effectively prevents loss of appetite. There was no difference in tumor response to radiotherapy between the two groups (Kang et al., 2011).
6.7. Effects in dermatomyositis and mitochondrial disease
An open-label study of hydrogen water (1.0 L/day) for 12 weeks was performed in 14 patients with muscle diseases including muscular dystrophies, polymyositis/dermatomyositis and mitochondrial myopathies. In the open-label study, significant improvements were observed in lactate:pyruvate ratio, fasting blood glucose, serum matrix metalloproteinase-3 (MMP3), and triglycerides. In particular, the lactate:pyruvate ratio, which is a sensitive biomarker of a compromised mitochondrial electron transport system, was reduced by 28% in mitochondrial myopathies. In addition, MMP3, which represents the activity of inflammation, was reduced by 27% in dermatomyositis (Ito et al., 2011).
Then performed a shuffled, double-blind, placebo-controlled, crossover study of H2-water or placebo-dehydrogenated water (0.5 L/day) for 8 weeks in 22 patients with dermatomyositis and mitochondrial myopathies. In the double-blind study, there was a statistically significant improvement only in serum lactate in mitochondrial myopathies in patients drinking hydrogen water, but the lactate:pyruvate ratio in mitochondrial myopathies and MMP3 in dermatomyositis also tended to decrease with hydrogen water consumption ( Ito et al., 2011).
6.8. Positive effects of H2 in hemodialysis
Nakayama et al. performed an open-label placebo-controlled crossover trial of 12 hemodialysis sessions in 8 patients (Nakayama et al., 2009, Nakayama et al., 2010) and an open-label trial of 78 hemodialysis sessions in 21 patients (Nakayama et al., 2010). In both studies, prolonged sessions of hemodialysis with H2-dialysis solution reduced systolic blood pressure before and after dialysis. In the short-term study, plasma methylguanidine was significantly reduced. In a long-term study, plasma monocyte chemoattractant 1 and myeloperoxidase were significantly reduced.
6.9. Effects in acute erythematous skin diseases
A study treated 4 patients with acute erythematous skin diseases with fever and/or pain by intravenous administration of 0.5 L H2-liquid over 30 minutes for more than 3 days. The erythema of these 4 patients and associated symptoms improved significantly after H2 treatment. In conclusion, improvement of acute erythematous skin diseases followed H2-water administration without compromising safety (Ono et al., 2012b).
6.10. Effects on exercise in sports
Ten young male soccer players were subjected to exercise testing and blood sampling. Each subject was tested twice in a crossover double-blind fashion; they were given hydrogen water or placebo water for one week intervals. Participants were asked to use a cycle ergometer. At 75% maximal oxygen uptake (VO2) for 30 minutes, followed by measurement of peak torque and muscle activity through 100 repetitions of maximal isokinetic knee extension. Heavy exercise resulted in an increase in blood lactate levels of subjects receiving placebo water, whereas oral H2-water supplementation prevented the increase in blood lactate during heavy exercise. Peak torque in the placebo group significantly decreased during maximal isokinetic knee extension, indicating muscle fatigue.
9.Concluding remarks "Concluding remarks"
This article reviews the progress of hydrogen medicine from its inception to clinical applications. H2 is easily applicable as it has no adverse effects and has great effectiveness on almost all pathogenic conditions involving oxidative stress and inflammation. In fact, the clinical effects of H2 have been positive in patients with more than 10 different diseases simultaneously. Because most pharmacological drugs act for specific purposes, H2 appears to differ from conventional drugs because of its extensive and diverse effects. H2 has great potential for preventive and therapeutic applications in many diseases due to its high potency and novel concept.
The H2MEDICAL team truly strives to educate the sociality, as well as contribute to a better quality of life for everyone. Our devices have medical certification and are distinguished by maximum therapeutic effect as well as the highest safety class. /see the devices/
Link to the official medical report.
Find out what are the HYDROGEN WATER-TOLERANT DISEASES /link/.