Category Archives: [:en]molecular hydrogen water [:ro]apa hidrogenata/apa hidrogenizata/apa cu hidrogen molecular

Molecular hydrogen (water) benefits/effects in disease models, human diseases, treatment-associated pathologies, and pathophysiological conditions of plants

Molecular hydrogen (water) benefits/effects in disease models, human diseases, treatment-associated pathologies, and pathophysiological conditions of plants

Molecular hydrogen (water) is effective in essentially ALL organs, as well as in plants.

We have now classified the organs and diseases into 31 categories and showed the effects of molecular hydrogen in 166 disease models, human diseases, treatment-associated pathologies, and pathophysiological conditions of plants.

 

Table 2 shows the details of organs and diseases for which the effects of molecular hydrogen have been reported.

Table 2 links molecular hydrogen effects and benefits to DISEASES AND CONDITIONS and the corresponding studies:

 

organs and diseases covered

Diseases and conditions & molecular hydrogen benefits

References -plant,animal & human studies &  clinical trials in regards to molecular hydrogen benefits

Brain & molecular hydrogen , Cerebrovascular diseases (CVD)& molecular hydrogen , Cerebral I/R injury & molecular hydrogen,Hypertensive stroke & molecular hydrogen , Brain injury secondary to intracerebral hemorrhage & molecular hydrogen ,  Subarachnoid hemorrhage & molecular hydrogen , Brain injury other than CVD & molecular hydrogen, Traumatic brain injury & molecular hydrogen , Deep hypothermic circulatory arrest-induced brain damage & molecular hydrogen, Neurodegenerative diseases & molecular hydrogen Parkinson’s disease & molecular hydrogen , Alzheimer’s disease & molecular hydrogen, Other brain health conditions & molecular hydrogen, Restraint-induced dementia & molecular hydrogen, ,Senile dementia in senescence-accelerated mice & molecular hydrogen, LPS-induced neuroinflammation & molecular hydrogen , Oxidative stress-induced neuronal cell damage & molecular hydrogen , Spinal Cord and peripheral nerve & molecular hydrogen, Spinal cord I/R injury & molecular hydrogen , Spinal cord injury & molecular hydrogen , Neuropathic pain & molecular hydrogen , Hyperalgesia & molecular hydrogen , Eyes & molecular hydrogen Retinal I/R injury & molecular hydrogen , Diabetic retinopathy & molecular hydrogen , Hyperoxia-induced retinopathy & molecular hydrogen , Light-induced retinopathy & molecular hydrogen , Glutamine-induced retinopathy & molecular hydrogen , S-nitroso-N-acetylpenicillamine-induced retinopathy & molecular hydrogen , Optic nerve crush & molecular hydrogen , Selenite-induced cataract & molecular hydrogen , Corneal alkali-burn & molecular hydrogen , Anti-inflammatory effects on LPS-activated retinal microglia cells & molecular hydrogen, Ears & molecular hydrogen Hearing loss & molecular hydrogen , Cisplatin-induced ototoxicity & molecular hydrogen , Ouabain-induced ototoxicity & molecular hydrogen , Oral Cavity & molecular hydrogen   Periodontitis & molecular hydrogen , Periodontal oxidative damage & molecular hydrogen , Lungs & molecular hydrogen, Lung I/R injury & molecular hydrogen , Oxygen-induced lung injury & molecular hydrogen , Ventilation-induced lung injury & molecular hydrogen , LPS-induced acute lung injury & molecular hydrogen, Intestinal I/R-induced lung injury & molecular hydrogen, Burn-induced lung injury & molecular hydrogen, Paraquat-induced lung injury & molecular hydrogen , cigarette smoking lung injury & molecular hydrogen , Smoke inhalation lung injury & molecular hydrogen, Pulmonary hypertension & molecular hydrogen , Heart & molecular hydrogen Myocardial infarction and I/R injury & molecular hydrogen, Diabetic cardiomyopathy & molecular hydrogen, Sleep apnea-induced left ventricular remodeling & molecular hydrogen , Ventricular hypertrophy & molecular hydrogen , Stomach & molecular hydrogen Stress-induced gastric ulceration & molecular hydrogen , Aspirin-induced gastric ulceration & molecular hydrogen , Intestines & molecular hydrogen Intestinal I/R injury & molecular hydrogen , Ulcerative colitis & molecular hydrogen , Colon inflammation& molecular hydrogen , Sepsis-induced intestinal injury & molecular hydrogen , Necrotizing enterocolitis & molecular hydrogen , Liver & molecular hydrogen   Liver I/R injury & molecular hydrogen, Chronic hepatitis B& molecular hydrogen,Nonalcoholic steatohepatitis & molecular hydrogen, Liver injury induced by massive hepatectomy & molecular hydrogen,Liver injury induced by obstructive jaundice & molecular hydrogen , Liver injury induced by endotoxin & molecular hydrogen , Liver injury induced by acetaminophen & molecular hydrogen , Liver injury induced by carbon tetrachloride & molecular hydrogen ,Liver injury induced by concanavalin A & molecular hydrogen ,Liver cirrhosis & molecular hydrogen , Liver fibrosis & molecular hydrogen , Pancreas & molecular hydrogen Acute pancreatitis & molecular hydrogen , Peritoneum & molecular hydrogen Acute peritonitis & molecular hydrogen ,molecular hydrogen benefits for Kidneys Renal I/R injury & molecular hydrogen ,  Acute renal injury & molecular hydrogen, Hypertensive renal injury & molecular hydrogen,Cisplatin-induced nephropathy & molecular hydrogen , Gentamicin-induced nephrotoxicity & molecular hydrogen, Inhibition of AGEs production & molecular hydrogen ,  Renal calcium deposition & molecular hydrogen ,molecular hydrogen benefits for Bladder Interstitial cystitis & molecular hydrogen , molecular hydrogen benefits for Reproductive organs Testicular I/R injury & molecular hydrogen , Erectile dysfunctions & molecular hydrogen , Nicotine-induced testicular oxidative stress & molecular hydrogen , Cigarette smoke-induced testicular damage, Skin & molecular hydrogen  skin I/R injury & molecular hydrogen, UV-induced skin injury & molecular hydrogen, Acute erythematous skin disease & molecular hydrogen , Atopic dermatitis & molecular hydrogen ,Psoriasis & molecular hydrogen ,   Pressure ulcer & molecular hydrogen ,Burns & molecular hydrogen ,Arsenic toxicity & molecular hydrogen,Bones and Joints & molecular hydrogen   Rheumatoid arthritis & molecular hydrogen , Osteoporosis & molecular hydrogen , Bone loss induced by microgravity & molecular hydrogen , TNFα-induced osteoblast injury & molecular hydrogen , NO-induced cartilage toxicity & molecular hydrogen , molecular hydrogen benefits for Skeletal Muscles sand soft tissues   I/R injury in skeletal muscle & molecular hydrogen , Inflammatory and mitochondrial myopathies & molecular hydrogen , Muscle fatigue & molecular hydrogen ,  Sports-related soft tissue injury & molecular hydrogen , molecular hydrogen benefits for Blood vessel  Atherosclerosis & molecular hydrogen , AGEs-induced blood vessel damage & molecular hydrogen ,Neointimal hyperplasia & molecular hydrogen ,  Hyperplasia in arterialized vein graft& molecular hydrogen ,Vascular dysfunction & molecular hydrogen , Vascular endothelial function& molecular hydrogen , Blood and Bone Marrow & molecular hydrogen Aplastic anemia & molecular hydrogen , Maintenance of multipotential stroma/mesenchymal stem cells & molecular hydrogen ,Neutrophil function & molecular hydrogen, Inhibition of collagen-induced platelet aggregation & molecular hydrogen ,Improvement of blood fluidity & molecular hydrogen ,Metabolism & molecular hydrogen , Diabetes mellitus& molecular hydrogen,Hyperlipidemia & molecular hydrogen ,Metabolic syndrome & molecular hydrogen , Metabolic process-related gene expression & molecular hydrogen , Oxidized low density lipoprotein-induced cell toxicity & molecular hydrogen , Serum alkalinization & molecular hydrogen,Exercise-induced metabolic acidosis & molecular hydrogen,Inflammation/Allergy & molecular hydrogen Sepsis & molecular hydrogen , LPS/IFNγ-induced NO production & molecular hydrogen, LPS-induced inflammatory response & molecular hydrogen , LPS-induced vascular permeability& molecular hydrogen, Zymosan-induced inflammation & molecular hydrogen,Carrageenan-induced paw edema & molecular hydrogen , Inflammatory response of cardiopulmonary bypass & molecular hydrogen,Type I allergy & molecular hydrogen , Asthma & molecular hydrogen , Perinatal Disorders & molecular hydrogen, Neonatal cerebral hypoxia& molecular hydrogen ,LPS-induced fetal lung injury & molecular hydrogen , Preeclampsia & molecular hydrogen, Cancer & molecular hydrogen, Growth of tongue carcinoma cells & molecular hydrogen ,Fe-NTA-induced nephrotoxicity and tumor progression & molecular hydrogen ,Radiation-induced thymic lymphoma & molecular hydrogen , Tumor angiogenesis & molecular hydrogen , Enhancement of 5-FU antitumor efficacy & molecular hydrogen , Radiation & molecular hydrogen Cardiac damage& molecular hydrogen ,  Lung damage & molecular hydrogen , Testicular damage & molecular hydrogen , Skin damage & molecular hydrogen , Germ hematopoietic and other cell damage & molecular hydrogen , Radiation-induced adverse effects & molecular hydrogen,Radiation-induced immune dysfunction & molecular hydrogen , Intoxication & molecular hydrogen Carbon monoxide INTOXICATION & molecular hydrogen , Sevoflurane intoxication & molecular hydrogen ,  Doxorubicin-induced heart failure & molecular hydrogen ,  Melamine-induced urinary stone & molecular hydrogen , Chlorpyrifos-induced neurotoxicity & molecular hydrogen , molecular hydrogen for Transplantation  Heart transplant & molecular hydrogen ,Lung transplant& molecular hydrogen , Kidney transplant & molecular hydrogen ,  Intestine transplant & molecular hydrogen ,Pancreas transplant & molecular hydrogen , Osteochondral grafts & molecular hydrogen ,Acute GVHD & molecular hydrogen ,Resuscitation & molecular hydrogen,   Cardiac arrest & molecular hydrogen , Hemorrhagic shock & molecular hydrogen, Dialysis & molecular hydrogen  Hemodialysis & molecular hydrogen ,  Peritoneal dialysis & molecular hydrogen , Others health conditions & molecular hydrogen , Lifespan extension & molecular hydrogen,  Sperm motility & molecular hydrogen, Decompression sickness & molecular hydrogen,  Genotoxicity and mutagenicity & molecular hydrogen, Plants & molecular hydrogen ,Root organogenesis & molecular hydrogen ,  Salt tolerance & molecular hydrogen ,  Postharvest ripening & molecular hydrogen ,  Stomatal closure & molecular hydrogen , Radish sprout tolerance to UVA & molecular hydrogen ,  High light stress & molecular hydrogen ,  Phytohormone signaling and stress responses & molecular hydrogen ,  Tolerance to paraquat-induced oxidative stress & molecular hydrogen ,  Cadmium toxicity & molecular hydrogen ,  Mercury toxicity & molecular hydrogen

 Brain & molecular hydrogen

 

 Cerebrovascular diseases (CVD)& molecular hydrogen 

 

Cerebral I/R injury & molecular hydrogen 

[11056839499100101102103104105106107108109]

Hypertensive stroke & molecular hydrogen

[110]

Brain injury secondary to intracerebral hemorrhage & molecular hydrogen

[28]

 Subarachnoid hemorrhage & molecular hydrogen

[48616673111112113]

 Brain injury other than CVD & molecular hydrogen 

 

 Traumatic brain injury & molecular hydrogen

[114115116117118]

  Deep hypothermic circulatory arrest-induced brain damage & molecular hydrogen

[57]

Neurodegenerative diseases & molecular hydrogen 

 

 Parkinson’s disease  & molecular hydrogen

[11959697119]

 Alzheimer’s disease & molecular hydrogen

[43120]

 Other brain health conditions & molecular hydrogen 

 

 Restraint-induced dementia & molecular hydrogen

[121]

Senile dementia in senescence-accelerated mice & molecular hydrogen

[122]

 LPS-induced neuroinflammation & molecular hydrogen

[81123]

Oxidative stress-induced neuronal cell damage & molecular hydrogen

[124125]

Spinal Cord and peripheral nerve & molecular hydrogen

 

 Spinal cord I/R injury & molecular hydrogen

[126127]

 Spinal cord injury & molecular hydrogen

[77128]

 Neuropathic pain & molecular hydrogen

[3992129130]

 Hyperalgesia & molecular hydrogen

[79131132]

 Eyes & molecular hydrogen

 

 Retinal I/R injury & molecular hydrogen

[133134]

 Diabetic retinopathy & molecular hydrogen

[135136]

 Hyperoxia-induced retinopathy & molecular hydrogen

[137]

 Light-induced retinopathy & molecular hydrogen

[138139]

 Glutamine-induced retinopathy & molecular hydrogen

[50]

S-nitroso-N-acetylpenicillamine-induced retinopathy & molecular hydrogen

[140]

 Optic nerve crush & molecular hydrogen

[141]

 Selenite-induced cataract & molecular hydrogen

[142]

 Corneal alkali-burn & molecular hydrogen

[55]

 Anti-inflammatory effects on LPS-activated retinal microglia cells & molecular hydrogen

[64]

Ears & molecular hydrogen

 

 Hearing loss & molecular hydrogen

[143144145146147148]

Cisplatin-induced ototoxicity & molecular hydrogen

[149150]

 Ouabain-induced ototoxicity & molecular hydrogen

[151]

Oral Cavity & molecular hydrogen

 

  Periodontitis & molecular hydrogen

[32]

 r Periodontal oxidative damage & molecular hydrogen

[152]

Lungs & molecular hydrogen

 

 Lung I/R injury & molecular hydrogen

[153154]

 Oxygen-induced lung injury & molecular hydrogen

[82155156]

 Ventilation-induced lung injury & molecular hydrogen

[53157]

 LPS-induced acute lung injury & molecular hydrogen

[131416158]

 Intestinal I/R-induced lung injury & molecular hydrogen

[159]

Burn-induced lung injury & molecular hydrogen

[160]

Paraquat-induced lung injury & molecular hydrogen

[161162]

 cigarette smoking lung injury & molecular hydrogen

[163]

 Smoke inhalation lung injury & molecular hydrogen

[74]

 Pulmonary hypertension & molecular hydrogen

[78164]

Heart & molecular hydrogen

 

 Myocardial infarction and I/R injury & molecular hydrogen

[171819202122232484]

Diabetic cardiomyopathy & molecular hydrogen

[40]

 Sleep apnea-induced left ventricular remodeling & molecular hydrogen

[165166]

 Ventricular hypertrophy & molecular hydrogen

[167]

Stomach & molecular hydrogen

 

 Stress-induced gastric ulceration & molecular hydrogen

[38]

 Aspirin-induced gastric ulceration & molecular hydrogen

[168169]

Intestines & molecular hydrogen

 

 Intestinal I/R injury & molecular hydrogen

[170171]

 Ulcerative colitis & molecular hydrogen

[172173]

 Colon inflammation& molecular hydrogen

[174]

Sepsis-induced intestinal injury & molecular hydrogen

[87]

 Necrotizing enterocolitis & molecular hydrogen

[175]

Liver & molecular hydrogen

 

  Liver I/R injury & molecular hydrogen

[7198176177178]

 Chronic hepatitis B& molecular hydrogen

[179]

Nonalcoholic steatohepatitis & molecular hydrogen

[180]

 Liver injury induced by massive hepatectomy & molecular hydrogen

[6793181]

 Liver injury induced by obstructive jaundice & molecular hydrogen

[31]

 Liver injury induced by endotoxin & molecular hydrogen

[35]

 Liver injury induced by acetaminophen & molecular hydrogen

[47]

 Liver injury induced by carbon tetrachloride & molecular hydrogen

[42]

 Liver injury induced by concanavalin A & molecular hydrogen

[182]

 Liver cirrhosis & molecular hydrogen

[183]

 Liver fibrosis & molecular hydrogen

[184]

Pancreas & molecular hydrogen

 

Acute pancreatitis & molecular hydrogen

[76185186187]

Peritoneum & molecular hydrogen

 

Acute peritonitis & molecular hydrogen

[68]

molecular hydrogen benefits for Kidneys

 

 Renal I/R injury & molecular hydrogen

[188189190]

  Acute renal injury & molecular hydrogen

[3772191192193194]

 Hypertensive renal injury & molecular hydrogen

[69]

Cisplatin-induced nephropathy & molecular hydrogen

[195196197]

 Gentamicin-induced nephrotoxicity & molecular hydrogen

[198]

Inhibition of AGEs production & molecular hydrogen

[199]

 Renal calcium deposition & molecular hydrogen

[200]

molecular hydrogen benefits for Bladder

 

Interstitial cystitis & molecular hydrogen

[201]

molecular hydrogen benefits for Reproductive organs

 

 Testicular I/R injury & molecular hydrogen

[202203]

Erectile dysfunctions & molecular hydrogen

[204]

 Nicotine-induced testicular oxidative stress & molecular hydrogen

[205]

 Cigarette smoke-induced testicular damage

[206]

Skin & molecular hydrogen

 

 skin I/R injury & molecular hydrogen

[46207]

 UV-induced skin injury & molecular hydrogen

[45208209210211]

] Acute erythematous skin disease & molecular hydrogen

[212]

 Atopic dermatitis & molecular hydrogen

[213214]

 Psoriasis & molecular hydrogen

[215]

  Pressure ulcer & molecular hydrogen

[216]

  Burns & molecular hydrogen

[4970]

  Arsenic toxicity & molecular hydrogen

[217]

 Bones and Joints & molecular hydrogen

 

  Rheumatoid arthritis & molecular hydrogen

[218219]

  Osteoporosis & molecular hydrogen

[3662]

 Bone loss induced by microgravity & molecular hydrogen

[34]

 TNFα-induced osteoblast injury & molecular hydrogen

[220]

 NO-induced cartilage toxicity & molecular hydrogen

[221]

molecular hydrogen benefits for Skeletal Muscles sand soft tissues

 

  I/R injury in skeletal muscle & molecular hydrogen

[222]

 Inflammatory and mitochondrial myopathies & molecular hydrogen

[223]

 Muscle fatigue & molecular hydrogen

[224]

  Sports-related soft tissue injury & molecular hydrogen

[225]

molecular hydrogen benefits for Blood vessel

 

 Atherosclerosis & molecular hydrogen

[585985226227]

  AGEs-induced blood vessel damage  & molecular hydrogen

[228]

  Neointimal hyperplasia & molecular hydrogen

[29]

  Hyperplasia in arterialized vein graft& molecular hydrogen

[229]

 Vascular dysfunction & molecular hydrogen

[60]

 Vascular endothelial function& molecular hydrogen

[230]

 Blood and Bone Marrow & molecular hydrogen

 

 Aplastic anemia & molecular hydrogen

[231]

 Maintenance of multipotential stroma/mesenchymal stem cells & molecular hydrogen

[232]

 Neutrophil function & molecular hydrogen

[233]

  Inhibition of collagen-induced platelet aggregation & molecular hydrogen

[234]

Improvement of blood fluidity & molecular hydrogen

[235]

Metabolism & molecular hydrogen

 

 Diabetes mellitus& molecular hydrogen

[236237238239240241]

 Hyperlipidemia & molecular hydrogen

[44242243244]

 Metabolic syndrome & molecular hydrogen

[245246247]

Metabolic process-related gene expression & molecular hydrogen

[248]

 Oxidized low density lipoprotein-induced cell toxicity & molecular hydrogen

[54]

 Serum alkalinization & molecular hydrogen

[249]

Exercise-induced metabolic acidosis & molecular hydrogen

[250]

 Inflammation/Allergy & molecular hydrogen

 

 Sepsis & molecular hydrogen

[4186251252253254255]

 LPS/IFNγ-induced NO production & molecular hydrogen

[27]

 LPS-induced inflammatory response & molecular hydrogen

[90]

 LPS-induced vascular permeability& molecular hydrogen

[80256]

 Zymosan-induced inflammation & molecular hydrogen

[257]

Carrageenan-induced paw edema & molecular hydrogen

[258]

Inflammatory response of cardiopulmonary bypass & molecular hydrogen

[259]

Type I allergy & molecular hydrogen

[26]

 Asthma & molecular hydrogen

[63]

Perinatal Disorders & molecular hydrogen

 

Neonatal cerebral hypoxia& molecular hydrogen

[260261262263]

 LPS-induced fetal lung injury & molecular hydrogen

[15]

Preeclampsia & molecular hydrogen

[264265]

Cancer & molecular hydrogen

 

 Growth of tongue carcinoma cells & molecular hydrogen

[266]

 Fe-NTA-induced nephrotoxicity and tumor progression & molecular hydrogen

[65]

  Radiation-induced thymic lymphoma & molecular hydrogen

[267]

 Tumor angiogenesis & molecular hydrogen

[268]

Enhancement of 5-FU antitumor efficacy & molecular hydrogen

[269]

Radiation & molecular hydrogen

 

Cardiac damage& molecular hydrogen

[270]

 Lung damage & molecular hydrogen

[271]

Testicular damage & molecular hydrogen

[272]

 Skin damage & molecular hydrogen

[273274]

 Germ, hematopoietic and other cell damage & molecular hydrogen

[275276277278279280]

Radiation-induced adverse effects & molecular hydrogen

[281]

Radiation-induced immune dysfunction & molecular hydrogen

[282]

 Intoxication & molecular hydrogen

 

 Carbon monoxide INTOXICATION & molecular hydrogen

[283284285286]

Sevoflurane intoxication & molecular hydrogen

[287288]

  Doxorubicin-induced heart failure & molecular hydrogen

[289]

 Melamine-induced urinary stone & molecular hydrogen

[290]

Chlorpyrifos-induced neurotoxicity & molecular hydrogen

[291]

molecular hydrogen for Transplantation

 

 Heart transplant & molecular hydrogen

[52292293294]

 Lung transplant& molecular hydrogen

[3388295296297298299]

 Kidney transplant & molecular hydrogen

[3051]

 Intestine transplant & molecular hydrogen

[89300301]

Pancreas transplant & molecular hydrogen

[302]

Osteochondral grafts & molecular hydrogen

[303]

Acute GVHD & molecular hydrogen

[304305]

Resuscitation & molecular hydrogen

 

  Cardiac arrest & molecular hydrogen

[306307]

 Hemorrhagic shock & molecular hydrogen

[75308309]

Dialysis & molecular hydrogen

 

 Hemodialysis & molecular hydrogen

[310311312313]

 Peritoneal dialysis & molecular hydrogen

[314315]

Others health conditions & molecular hydrogen

 

 Lifespan extension & molecular hydrogen

[316]

 Sperm motility & molecular hydrogen

[317]

 Decompression sickness & molecular hydrogen

[318]

 Genotoxicity and mutagenicity & molecular hydrogen

[319]

Plants & molecular hydrogen

 

 Root organogenesis & molecular hydrogen

[91320]

 Salt tolerance & molecular hydrogen

[321322]

 Postharvest ripening & molecular hydrogen

[323]

 Stomatal closure & molecular hydrogen

[324]

 Radish sprout tolerance to UVA & molecular hydrogen

[325]

 High light stress & molecular hydrogen

[326]

 Phytohormone signaling and stress responses & molecular hydrogen

[327]

 Tolerance to paraquat-induced oxidative stress & molecular hydrogen

[328]

 Cadmium toxicity & molecular hydrogen

[329330]

 Mercury toxicity & molecular hydrogen

[331]

 

 

Once again one can benefit from molecular hydrogen  H2 regardless of the method of administration, including from drinking molecular hydrogen water wich proved to be far superior than inhaling hydrogen gas for example – read more about Modalities of molecular hydrogen administration(in water, gas or saline) to animals, humans, and plantsMolecular hydrogen-rich water is expected to be easily used in place of regular everyday drinking water and will effectively treat chronic maladies such as lifestyle-related diseases.In addition, molecular hydrogen water is both safe and easy to drink at home( we think it’s easier to drink molecular hydrogen water than injecting molecular hydrogen rich saline or inhaling molecular hydrogen gas)
 

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Molecular hydrogen (dissolved in water) alleviates nephrotoxicity induced by an anti-cancer drug cisplatin (chemotherapy)  without compromising anti-tumor activity in mice.

Molecular hydrogen (dissolved in water) alleviates nephrotoxicity induced by an anti-cancer drug cisplatin (chemotherapy)  without compromising anti-tumor activity in mice.

Cisplatin is a widely used anti-cancer drug in the treatment of a wide range of tumors; however, its application is limited by nephrotoxicity, which is affected by oxidative stress ROS. We have reported that molecular hydrogen (H(2)) acts as an efficient selctive antioxidant (Ohsawa et al. in Nat Med 13:688-694, 2007). Here we show that molecular hydrogen efficiently mitigates the side effects of toxic chemotherapeutic cisplatin by reducing oxidative stress.

METHODS:

Mice were administered chemotherapy ( cisplatin)  followed by inhaling molecular hydrogen gas (1% H(2) in air). Furthermore, instead of inhaling molecular hydrogen gas, we examined whether drinking water containing hydrogen (hydrogen water; 0.8 mM H(2) dissolved in water) is applicable by examining oxidative stress, mortality, and body-weight loss. Nephrotoxicity was assessed by morphological changes, serum creatinine and blood urea nitrogen (BUN) levels.

RESULTS:

Inhalation of molecular hydrogen gas improved mortality and body-weight loss caused by chemotherapy/ cisplatin, and alleviated nephrotoxicity. Molecular hydrogen was detected in blood when molecular hydrogen water was placed in the stomach of a rat. Consuming molecular hydrogen water ad libitum also reduced oxidative stress, mortality, and body-weight loss induced by cisplatin in mice. Molecular hydrogen water improved metamorphosis accompanying decreased apoptosis in the kidney, and nephrotoxicity as assessed by serum creatinine and BUN levels.

Despite molecular hydrogen (water)’s protective effects against cisplatin-induced toxicity, molecular hydrogen water did not impair anti-tumor activity of cisplatin against cancer cell lines in vitro and tumor-bearing mice in vivo.

CONCLUSION:

Molecular hydrogen water  has potential for improving the quality of life of patients during chemotherapy by efficiently mitigating the side effects of cisplatin while not compromising antitumor effects.

 

REFERENCES

Nakashima-Kamimura N, Mori T, Ohsawa I, Asoh S, Ohta S. Molecular hydrogen alleviates nephrotoxicity induced by an anti-cancer drug cisplatin without compromising anti-tumor activity in mice. Cancer Chemother Pharmacol. 2009;64(4):753–61. doi: 10.1007/s00280-008-0924-2.[PubMed] [Cross Ref]

Effects of drinking molecular hydrogen water on the quality of life of cancer patients treated with radiation therapy

Effects of drinking molecular hydrogen water on the quality of life of cancer patients treated with radiation therapy

This is the first report demonstrating the benefits of drinking molecular hydrogen water in liver cancer patients receiving radiation therapy for malignant tumors.
– Molecular hydrogen dissolved in water improved the QOL of (liver) cancer patients reciving radiotherapy
– Molecular hydrogen water mitigated oxidative stress marker during radiotherapy
– Molecular hydrogen water did NOT compromise the radiation cancer treatment efficacies
-Molecular hydrogen water treatment did NOT alter liver function or blood composition during radiotherapy

This study examined whether molecular hydrogen (dissolved in water ) treatment, improved QOL in patients receiving radiotherapy.

Cancer patients receiving radiotherapy often experience fatigue and impaired quality of life (QOL).

Most radiation-induced symptoms are believed to be associated with increased oxidative stress and inflammation, due to the generation of reactive oxygen species (ROS) during radiotherapy, and may significantly affect the patient’s quality of life (QOL) [].

Molecular hydrogen (dissolve in water) can be administered as a therapeutic medical gas, has selective ANTIoxidant( molecular hydrogen ( water ) neutralizes only bad free radicals while supporting the beneficial ones)  & ANTIinflammatory (molecular hydrogen( water )reduces inflammation in tisues) properties.

Drinking liquids(i.e. : water) with dissolved molecular hydrogen represents a novel method of molecular hydrogen gas delivery that is easily translatable into clinical practice, with beneficial effects for several medical conditions, including atherosclerosis, type 2 diabetes, metabolic syndrome, and cognitive impairment during aging and in Parkinson’s disease [].

Methods

A randomized, placebo-controlled study was performed to evaluate the effects of drinking molecular hydrogen-rich water on 49 patients receiving radiotherapy for malignant liver tumors.

The subjects were randomly assigned to groups to either drink molecular hydrogen-rich water for 6 weeks (n = 25) or drink water containing a placebo (n = 24).

Subjects were provided with four 500 mL bottles of drinking molecular hydrogen water per day .

Molecular hydrogen rich water had final molecular hydrogen concentration; 0.55~0.65 mM.

The subjects were expected to consume 100-300 mL of molecular hydrogen-rich water more than 10 times per day for a total minimum consumption of 1500 mL (1.5 L) and a maximum consumption of 2000 mL (2.0 L).

Oral intake of molecular hydrogen water or placebo water started on the first day of radiotherapy and continued for 6 weeks.

All participants received 5040-6500 cGy of radiotherapy for 7-8 weeks using a 6 MV system (Cyber Knife, Fanuc, Yamanashi, Japan).

Table 1

Patient Characteristics

All the liver cancer patients survived through the 6 week follow-up period when the QOL questionnaire was administered.

The Korean version of the European Organization for Research and Treatment of Cancer’s QLQ-C30 instrument was used to evaluate global health status and QOL. The concentration of derivatives of reactive oxidative metabolites and biological antioxidant power in the peripheral blood were assessed.

Results & Conclusions

The consumption of molecular hydrogen-rich water for 6 weeks reduced reactive oxygen metabolites in the blood and maintained blood oxidation potential. QOL scores during radiotherapy were SIGNIFICANTLY IMPROVED in patients treated with molecular hydrogen-rich water compared to patients receiving placebo water.

There was no difference in tumor response to radiotherapy between the two groups( meaning drinking molecular hydrogen water did not interfere with the desired antitumor effects of radiation therapy ).

Daily consumption of molecular hydrogen-rich water is a potentially novel, therapeutic strategy for improving QOL after radiation exposure.

Consumption of hydrogen-rich water reduces the biological reaction to radiation-induced oxidative stress without compromising anti-tumor effects.

Molecular hydrogen dissolved in water improved the QOL of (liver) cancer patients receiving radiotherapy

The QOL of the liver cancer patients who were given placebo water deteriorated significantly within the first month of radiotherapy (Figure1A)

Gastrointestinal (GI) symptoms are one of the most common complaints of patients undergoing radiotherapy and are considered to have a high impact on the patient’s QOL after 6 weeks of radiotherapy.

The patients consuming molecular hydrogen water experienced significantly less appetite loss and fewer tasting disorders compared to the patients consuming placebo water.

Liver cancer patients experience GI symptoms and decreased QOL during radiotherapy. These symptoms usually occur as a result of the body repairing damage to healthy cells, are particularly common towards the end of a course of radiation treatment, and can last for some time. The symptoms and their impact on QOL can be worsened by having to travel to the hospital each day.

Drinking molecular hydrogen-rich water improved the QOL of the liver cancer patients receiving radiotherapy and did not require additional hospital visits.

There were no differences between the groups in the QOL subscales for fatigue, depression, or sleep. No significant difference was seen in the mean scores for vomiting or diarrhea (Figure1B).

Figure 1

Placebo water and molecular hydrogen water improved the QOL of patients receiving radiotherapy. A. Weekly assessment of the patients’ QOL. B. Scoring system of GI symptoms after 6 weeks of radiotherapy with or without molecular hydrogen water.

Molecular hydrogen water mitigated oxidative stress marker during radiotherapy

Before treatment, there were no differences in total hydroperoxide levels, representative of total dROM levels, between the treatment groups.

Radiotherapy markedly increased total hydroperoxide levels in the patients consuming placebo water.

However, drinking molecular hydrogen water prevented this increase in total serum hydroperoxide, as determined by the dROM test (Figure2A), indicating DECREASED OXIDATIVE STRESS during radiotherapy in the liver cancer patients who consumed molecular hydrogen water.

Similarly, endogenous serum antioxidant activity significantly deteriorated during radiotherapy in the patients consuming placebo water, and biologic antioxidant activity was MAINTAINED in liver cancer patients who consumed molecular hydrogen-rich water, even after 6 weeks of radiotherapy (Figure2B).

Figure 2

Molecular hydrogen water mitigated oxidative stress marker during radiotherapy. Antioxidative effects in patients with placebo water (n = 24) and molecular hydrogen rich water (n = 25). The dROM level (A) represents the total level of peroxide metabolities, and BAP (B) reflects ...
Previous experimental studies have linked daily consumption of molecular hydrogen-rich water with improvement of a number of conditions in rodent models, including reducing atherosclerosis in apolipoprotein E knockout mice [], alleviating cisplatin(chemotherapy)-induced nephrotoxicity [], reducing vitamin C deficiency-induced brain injury [], preventing chronic allograft nephropathy after renal transplantation [], and ameliorating cognitive defects in senescence-accelerated mice [] and a Parkinson’s disease model []. In human studies, consumption of molecular hydrogen-rich water prevented adult-onset diabetes and insulin resistance [], as well as oxidative stress in potential metabolic syndrome [].

Radiotherapy is associated with an increase in ROS, followed by damage to DNA, lipids, and proteins, and activation of transcription factors and signal transduction pathways. It has been estimated that 60-70% of the ionizing radiation-induced cellular damage is caused by hydroxyl radicals [].

Therefore, a number of trials with the goal of reducing adverse effects due to excess ROS production have been performed with antioxidants delivered during the course of radiotherapy. Supplementation with α-tocopherol improves the salivary flow rate and maintains salivary parameters []. Treatment with the antioxidant enzyme superoxide dismutase prevented radiotherapy-induced cystitis and rectitis in bladder cancer patients receiving radiotherapy []. In addition, the combined use of pentoxifylline and vitamin E reduced radiation-induced lung fibrosis in patients with lung cancer receiving radiotherapy [].

Thus, in general, supplementation with antioxidants is likely to offer overall benefits in the treatment of adverse effects of radiotherapy.

However, not all antioxidants can afford radioprotection [].

Furthermore, of significant concern is the finding that high doses of antioxidants administered as adjuvant therapy might compromise the efficacy of radiation treatment and increase of the risk of local recurrence of cancer [,].

Hence, the relatively lower toxicity associated with the use of these antioxidant agents is appealing, but not at the cost of poor tumor control.

In contrast, in this study, drinking molecular hydrogen-rich water did NOT affect radiotherapy’s anti-tumor effects.

Molecular hydrogen water did NOT compromise the radiation cancer treatment efficacies

Tumor response to radiotherapy was similar between the cancer treatment groups, and 12 of 24 (50.0%)  liver cancer patients in the placebo group and 12 of 25 (48%) patients in molecular hydrogen water group exhibited either a completed response (CR) or a partial response (PR). There were no patients in either group with progressive disease (PD) during the follow-up period (3 months). Thus, drinking molecular hydrogen water did  NOT compromise the anti-tumor effects of radiotherapy.

Our results may suggest that hydrogen water functions not only as an antioxidant, but also plays a protective role by inducing radioprotective hormones or enzymes. 

Molecular hydrogen water treatment did NOT alter liver function or blood composition during radiotherapy

There were no significant differences in aspartate aminotransferase, alanine aminotransferase, gamma-glutamyl transpeptidase (γ-GTP) and total cholesterol levels at week 0 and week 6, regardless of the type of water consumed(Table2), indicating that molecular hydrogen water consumption did NOT alter liver function.

Similarly, there were no significant differences in red blood cell count, white blood cell count, or platelet count between patients consuming molecular hydrogen water and patients consuming placebo water (Table3).

Table 2

Changes in liver function tests

Table 3

Peripheral blood cell counts

 

This finding may provide the foundation for a clinically applicable, effective, and safe strategy for the delivery of molecular hydrogen gas (dissolved in water) to mitigate radiation-induced cellular injury.

Oral intake of daily molecular hydrogen-supplemented water might be a prophylactic strategy to improve QOL of the (liver cancer ) patients receiving radiotherapy.

Although the mechanisms underlying the beneficial effects of molecular hydrogen-rich water during radiotherapy have not been clearly elucidated, drinking molecular hydrogen dissolved in water reduced dROM levels and maintained BAP levels in the serum, suggesting molecular hydrogen-rich water exhibits potent systemic antioxidant activity.

The safety of molecular hydrogen-rich water has also been determined as well as the optimal concentration of molecular hydrogen dissolved in water;

Daily intake of molecular hydrogen-rich water may be a promising approach for counteracting radiation-induced impairments to QOL.

This therapeutic use of molecular hydrogen is also supported by the work of Qian et al., who demonstrated that treating human lymphocyte AHH-1 cells with molecular hydrogen (saline) before irradiation significantly inhibited ionizing irradiation-induced apoptosis and increased cell viability in vitro.

They also showed that injection of molecular hydrogen-rich saline could protect the gastrointestinal endothelia from radiation-induced injury, decrease plasma malondialdehyde and intestinal 8-hydroxydeoxyguanosine levels, and increase plasma endogenous antioxidants in vivo [].

Conclusions

In conclusion, our study demonstrated that drinking molecular hydrogen-rich water improved QOL and reduced oxidative markers in patients receiving radiotherapy for liver tumors.

This novel approach of oral intake of molecular hydrogen-rich water may be applicable to a wide range of radiation-related adverse symptoms.

Drinking solubilized molecular hydrogen (dissolved in water) on a daily basis is beneficial and would be quite easy to administer without complicating or changing a patient’s lifestyle

Background

Radiotherapy is one of the major treatment options for malignant neoplasms. Nearly half of all newly diagnosed cancer patients will receive radiotherapy at some point during treatment and up to 25% may receive radiotherapy a second time []. Radiotherapy adversely affects the surrounding normal cells []. Acute radiation-associated side effects include fatigue, nausea, diarrhea, dry mouth, loss of appetite, hair loss, sore skin, and depression. Radiation increases the long-term risk of cancer, central nervous system disorders, cardiovascular disease, and cataracts. The likelihood of radiation-induced complications is related to the volume of the irradiated organ, the radiation dose delivered, the fractionation of the delivered dose, the delivery of radiation modifiers, and individual radiosensitivity []. Most radiation-induced symptoms are believed to be associated with increased oxidative stress and inflammation, due to the generation of reactive oxygen species (ROS) during radiotherapy, and may significantly affect the patient’s quality of life (QOL) [].

original article:
 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3231938/

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Molecular Hydrogen – ANTItumor effect

Molecular Hydrogen – ANTItumor effect

Hyperbaric medicine is medical treatment in which an ambient pressure greater than sea level atmospheric pressure is a necessary component. The treatment comprises hyperbaric molecular hydrogen therapy (HBMHT), the medical use of molecular hydrogen gas at an ambient pressure higher than atmospheric pressure,

Hairless albino mice with squamous cell carcinoma were exposed to a mixture of 2.5 percent oxygen and 97.5 percent molecular hydrogen gas at a total pressure of 8 atmospheres for periods up to 2 weeks in order to see if a free radical decay catalyzer, such as molecular hydrogen, would cause a regression of the skin tumors.

The 2-week treatment of hyperbaric 97.5% molecular hydrogen gas H 2 gas in the absence of explosion risk caused a significant regression of skin tumor or leukemia in animals (Dole et al., 1975; Roberts et al., 1978)

They found that the skin tumors regressed and proposed that hydrogen might be useful for the treatment of other types of tumors by suppressing free radical production .

Later, Roberts et al. [2] examined the responses of five established transplantable mouse tumors and one mouse leukemia to hyperbaric molecular hydrogen and found that molecular hydrogen H 2 gas could suppress the growth of tumor cells. The actions of molecular hydrogen were established as antioxidant (and therefore anti-oxidative stress), anti-inflammatory, and anti-apoptotic in animal systems [3].

Marked aggression of the tumors was found, leading to the possibility that hyperbaric molecular hydrogen gas therapy might also prove to be of significance in the treatment of other types of cancer.

Molecular hydrogen H2 can be administered as a gas(i.e. hyperbaric), in  saline implants or infusions, as topical solutions or baths or by drinking molecular hydrogen H2enriched water.

 

One can benefit from molecular hydrogen  H2 regardless of the method of administration, including from drinking molecular hydrogen water wich proved to be far superior than inhaling hydrogen gas for example – read more about

Modalities of molecular hydrogen administration(in water, gas or saline) to animals, humans, and plants

Molecular hydrogen-rich water is expected to be easily used in place of regular everyday drinking water and will effectively treat chronic maladies such as lifestyle-related diseases. In addition, molecular hydrogen water is both safe and easy to drink at home( we think it’s easier to drink molecular hydrogen water than injecting molecular hydrogen rich saline or inhaling molecular hydrogen gas)

Drinking molecular hydrogen wate is the easiest and least costly method of administration.

There are no safety issues with molecular  hydrogen; it has been used for years in gas mixtures for deep diving and in numerous clinical  trials without adverse events, and there are no warnings in the literature of its toxicity or long–  term exposure effects of molcular hydrogen.

 

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Molecular hydrogen (water) in the treatment of acute and chronic neurological conditions(Alzheimer’s, Parkinson’s,etc): mechanisms of protection and routes of administration

Molecular hydrogen (water) in the treatment of acute and chronic neurological conditions(i.e Alzheimer’s, Parkinson’s, etc. ): mechanisms of protection and routes of administration

 
 
We review the effects of molecular hydrogen water therapy in acute neuronal conditions and neurodegenerative diseases.
Molecular hydrogen water therapy /drinking water with dissolved molecular hydrogen may be useful for the prevention of neurodegenerative diseases and for reducing the symptoms of acute neuronal conditions.
 
Recently, the neuroprotective effects of treatment with molecular hydrogen (water) have been reported in both basic and clinical settings-as you will see below, we have examined the effects of molecular hydrogen H2  (water) treatment on acute central nervous system diseases and on chronic neurodegenerative diseases. We have also examined the various mechanism by which molecular hydrogen H2 exerts its neuroprotective effects .
Molecular hydrogen  H2 acts as a scavenger for OH and ONOO, affects neuroinflammation, preserves mitochondrial energy production, and possesses neuroprotective properties.
 
Unlike more conventional drugs, molecular hydrogen  H2 treatment, particularly the consumption of  molecular hydrogen  H2-rich water, has no known serious side effects and is effective for preventing the onset of neurodegenerative disease and aggravation of acute neuronal conditions – i.e.:
 

Molecular hydrogen water & Parkinson’s disease (PD)

Parkinson’s disease PD is a disorder that presents with extrapyramidal symptoms caused by the degeneration and loss of dopamine-producing cells in substantia nigra. Oxidative stress is known to be involved in the clinical condition of PD.() Moreover, the involvement of mitochondrial dysfunction in PD has been reported.()

The effects of molecular hydrogen  H2 on Parkinson’s disease PD have been reported in animal models of PD as well as in clinical studies.()

In 2009, Fujita et al.() and Fu et al.() reported that consuming  molecular hydrogen H2-rich water inhibits oxidative stress on the nigrostriatal pathway and prevents the loss of dopamine cells in a PD animal model. With the consumption of molecular hydrogen H2-rich-water-drinking, oxidative stress in the nigrostriatal pathway was inhibited and loss of dopamine cells was decreased. These results suggest that consuming molecular hydrogen H2-rich water could affect the onset of Parkinson’s Disease PD.

In recent years, the results of a clinical trial on the effects of consuming molecular hydrogen H2-rich water for Parkinson’s Disease PD have been reported.() A randomized double-blind study showed that consuming molecular hydrogen H2-rich water (1,000 ml/day) for 48 weeks significantly improved the total Unified Parkinson’s Disease Rating Scale (UPDRS) score of Parkinson’s disease PD patients treated with levodopa. A double-blind multi-center trial of molecular hydrogen H2 water is currently underway (Table 1).()

 

Molecular hydrogen water &  Alzheimer’s disease (AD)

Alzheimer Disease AD, an age-related neurodegenerative disease, is the most common cause of dementia.(,) Pathologically, it is characterized by the deposition of Aβ protein outside nerve cells and the accumulation of phosphorylated tau protein inside nerve cells. There is also a marked loss of nervous cells in the cerebral cortex.() In recent years, oxidative stress and neuroinflammation have been reported to be involved in Alzheimer’s disease AD.(,) To date, reports have centered on the involvement of oxidative stress in brain parenchyma.(,,)The accumulation of Aβ protein is strongly associated with the failure of Aβ clearance that is closely related to the pathogenesis of Alzheimer’s Disease AD.() It is known that low-density lipoprotein receptor-related protein 1 (LRP1) is involved in Aβ protein elimination. LRP dysfunction caused by oxidative stress and neuroinflammation is involved in the onset of Alzheimer’s Disease AD.() The regulation of oxidative stress and neuroinflammation may prevent the onset or progression of Alzheimer’s Disease AD. A number of reports have investigated the effects of molecular hydrogen H2 for the prevention of Alzheimer’s Disease AD onset.(,)

In a rat Alzheimer’s Disease AD model, it has been reported that the administration of molecular H2-rich saline (5 ml/kg, i.p., daily) inhibited oxidative stress, cytokine production, and nuclear factor-κB (NF-κB) production in the hippocampus and cerebral cortex, and improved impaired memory.(,)

It has  been reported that consuming molecular hydrogen H2-rich water inhibits age-related brain alterations and spatial memory decline.()

 

The therapeutic effect of molecular hydrogen H2-rich water following Traumatic brain injury (TBI) and in posttraumatic onset of Alzheimer’s disease (AD) was investigated by Dohi et al. in 2014,() who investigated whether the consumption of molecular hydrogen  H2-rich water 24 h prior to trauma can inhibit neuronal damage in a controlled cortical injury model using mice. The authors found that the expression of the phosphorylated tau proteins AT8 and Alz50 in the hippocampus and cortex was blocked in mice that consumed molecular hydrogen  H2-rich water. Moreover, the activity of astrocytes and microglia were inhibited in mice Traumatic Brain Injury model consuming molecular hydrogen H2-rich water. The expression of genes induced by Traumatic Brain Injury, particularly those that are involved in oxidation/carbohydrate metabolism, cytokine release, leukocyte or cell migration, cytokine transport, and adenosine triphosphate (ATP) and nucleotide binding, was inhibited by consuming molecular hydrogen  H2-rich water.

Dohi et al.() specifically reviewed the role of molecular hydrogen H2-rich water in neuroinflammation following brain trauma. The consumption of molecular hydrogen H2-rich water influenced the production of cytokines and chemokines in the damaged brain and inhibited the production of hypoxia inducible factor-1 (HIF-1), MMP-9, and cyclophilin A. However,molecular hydrogen  H2-rich water did not affect the production of amyloid precursor protein (APP), Aβ-40, or Aβ-42. They also investigated the relationship between molecular hydrogen H2 and ATP production and reported that molecular hydrogen H2 increased basal respiration, reserve capacity, and nonmitochondrial respiration but did not increase aerobic ATP production. It has thus been demonstrated that the inhibitory effects of molecular hydrogen H2 on nerve damage are not solely due to its simple function as a free radical scavenger (Fig. 1 and and22).

 
Molecular hydrogen is well characterized as a selective scavenger of hydroxyl radicals and peroxynitrite.

Oxidative stress caused by reactive oxygen species is considered a major mediator of tissue and cell injuries in various neuronal conditions, including neurological emergencies and neurodegenerative diseases.

 

Oxidative stress caused by reactive oxygen species (ROS) is a major mediator of tissue and cellular injuries in various neuronal conditions, including neurological emergencies and neurodegenerative diseases.()

Control of oxidative stress is a major therapeutic strategy for various neuronal conditions.(,,) There are many methods for controlling oxidative stress with the use of free radical scavengers being the most common approach.(,) Evidence from animal experiments support the notion that free radical scavengers and antioxidants dramatically reduce cerebral damage.() Edaravone (MCI-186), a novel free radical scavenger, was developed to prevent lipid peroxidation in pathological neurological conditions.(,)Edaravone is currently the only antioxidant drug approved for treating cerebral infarction that improves the functional outcome of ischemic stroke.() Brain hypothermia therapy (targeted temperature management) can also effectively control oxidative stress. Brain hypothermia therapy is effective in patients with various acute neuronal diseases.(,,)

In 2007, Ohsawa et al.() reported that molecular hydrogen (H2) can act as an antioxidant to prevent and treat middle cerebral artery occlusion–reperfusion injury in rats. This effect has been supported by additional reports. Recently, the beneficial effect of molecular H2 has been reported in many other organs, including the brain.() The first major therapeutic effect of molecular hydrogen H2 was that of an antioxidant, combining with hydroxyl ions to produce water.() Recently, other biological mechanisms of molecular hydrogen H2 (anti-inflammatory, anti-apoptosis, anti-cytokine, DNA expression, and energy metabolism) have been proposed (Fig. 1 and and22).()Therefore, the biology of molecular hydrogen H2 is not simple. In this review, we discuss the role of molecular H2 in various neuronal conditions.

Fig. 1

Beneficial effects of molecular hydrogen in pathophysiology of various acute neuronal conditions. ATP, adenosine triphosphate; miR-200, microRNA-200; ROS, reactive oxygen species.

Fig. 2

Effect of consumption of molecular hydrogen-rich water as functional water in pathophysiology of neurodegenerative diseases. ATP, adenosine triphosphate; miR-200, microRNA-200; ROS, reactive oxygen species.

Method and Route of Administration in Molecular hydrogen H2 Therapy

As a small (2 Da), uncharged molecule of hydrogen H2, would be expected to readily distribute throughout the body, including being able to easily penetrate cell membranes, However we are unable to determine the distribution of moleclar hydrogen H2 among organs and its concentrations in each organ and serum based on the administration methods and dosage. This problem was investigated in 2014.() A comparative review was conducted on the consumption of molecular hydrogen H2-rich water, i.p. or intravenous administration of molecular hydrogen  H2-rich saline, and inhalation of molecular hydrogen H2 gas. The results showed that the highest concentrations are reached 1 min after intravenous administration and 5 min after oral administration. The highest concentration was reached 30 min after the inhalation of molecular hydrogen H2 gas and was maintained for some time. Although molecular hydrogen H2 concentrations in the brain tend to be high after either intravenous administration or inhalation, no significant differences have been observed in comparison with the concentrations after the consumption of molecular hydrogen  H2-rich water and i.p. administration of molecular hydrogen H2-rich saline. Thus, although there have been variations based on the administration method, all methods have been found to result in the presence of molecular hydrogen H2 in the serum and brain tissue. Liu et al.() measured molecular hydrogen  H2 levels in the arteries, veins, and brain tissues after the inhalation of 2% molecular hydrogen H2 gas. They found that arterial molecular hydrogen H2 peaked at 30 min after administration, whereas venous and brain tissue molecular hydrogen H2 peaked at 45 min after administration. They reported that molecular hydrogen  H2 levels were similar in arteries and brain tissues.

This demonstrated that molecular hydrogen  H2 migrates to the brain tissue regardless of the method of administration(Thus, the studies below might as well have been performed using molecular hydrogen water instead of molecular hydrogen gas or molecular hydrogen saline).

These results suggest that the consumption of molecular hydrogen  H2-rich water prevents neurodegenerative disease and that molecular hydrogen H2-rich drinking water could be used to treat acute brain disorders (Fig. 1 and and22).

 
 
 
 

Molecular Hydrogen & Neurological Diseases

Molecular hydrogen & Ischemic brain injury

It has been reported that molecular hydrogen H2 prevents ischemic brain damage in animal experiments.(,) Ohsawa et al.() reported that inhalation of 2% molecular hydrogen H2 gas strongly suppressed infarct volume after middle cerebral artery ischemia–reperfusion in rats. In an electron spin resonance (ESR) study, they showed that molecular hydrogen  H2 had hydroxyl radical scavenging activity. Hydroxynonenal (HNE) and 8-hydroxy-2′-deoxyguanosine (8-OHdG) immunoreactivity was suppressed in the damaged brain after treatment with 2% molecular hydrogen H2. molecular hydrogen H2 inhalation reduced ischemic damage and hemorrhagic volume after transient middle crebral artery occlusion (MCAO) ischemia.() Free radical generation after ischemia induces matrix metalloproteinase (MMP) expression.(,) MMP-9 promotes hemorrhagic infarction by disrupting cerebral vessels.() molecular hydrogen H2 inhalation has been found to reduce MMP-9 expression in an MCAO rat model. molecular hydrogen H2 also has a neuroprotective effect against global ischemia. Ji et al.() reported that molecular hydrogen H2-rich saline injection [5 ml/kg intra-peritoneal (i.p.) administration] after global ischemia reduced neuronal cell death in hippocampal Cornet d’Ammon 1 (CA1) lesions in rats. Cerebral hypoxia–ischemia and neonatal asphyxia are major causes of brain damage in neonates. molecular hydrogen H2 gas inhalation and molecular hydrogen H2-rich saline injection provide early neuroprotection from neonatal neurological damage.() Nagatani et al.() reported that that an molecular hydrogen H2-enriched intravenous solution is safe for patients with acute cerebral infarction, including patients treated with tissue plasminogen activator (t-PA) therapy.

Metabolic syndrome is a strong risk factor of stroke. It has been reported that molecular hydrogen H2 therapy can improve metabolic syndrome in basic and clinical settings.() molecular hydrogen H2 therapy may reduce stroke in patients with metabolic syndrome involving diabetes mellitus.

Molecular hydrogen & Hemorrhagic stroke

Hemorrhagic stroke involving intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) is a critical neuronal condition, and the mortality rate of hemorrhagic stroke is still high.() Manaenko et al.() reported a neuroprotective effect of molecular hydrogen H2 gas inhalation using an experimental ICH animal model.molecular hydrogen H2 gas inhalation suppresses redox stress and blood brain barrier (BBB) disruption by reducing mast cell activation and degranulation. Brain edema and neurological deficits were also suppressed. In SAH, there are several studies demonstrating the neuroprotective effect of molecular hydrogen  H2 treatment.() A clinical trial has started in patients with SAH (Table 1).()

Table 1

Clinical trials of molecular hydrogen in central nervous system (CNS) diseases

Molecular hydrogen & Traumatic brain injury (TBI)

The efficacy of molecular hydrogen H2 for treating TBI has been investigated in several studies.(,,) Ji et al.() reported that in a rat TBI model,molecular hydrogen H2 gas inhalation has been found to protect BBB permeability and regulate posttraumatic brain edema, thereby inhibiting brain damage. molecular hydrogen H2 gas inhalation also inhibits the decrease in superoxide dismutase (SOD) activity and catalase (CAT) activity. These are antioxidant enzymes in posttraumatic brains that inhibit the production of malondialdehyde (MDA) and 8-iso-prostaglandin F2α (8-iso-PGF2α). Eckermann et al.() reported that in a surgical trauma mouse model involving right frontal lobectomy, molecular hydrogen H2 gas inhalation has been found to inhibit postoperative brain edema and improve the postoperative neurobehavioral score. The same report also showed that lipid peroxidation and the production of oxidative stress substances were not inhibited by molecular hydrogen  H2 gas inhalation.() 

Molecular Hydrogen & Spinal cord injury

Chen et al.() reviewed the effects of molecular hydrogen H2-rich saline administration (i.p.) in a rat traumatic spinal cord injury model. They found that posttraumatic neurological symptoms were improved by molecular hydrogen H2-rich saline treatment. Furthermore, molecular hydrogen H2-rich saline treatment has been found to reduce inflammatory cell infiltration, TdT-mediated dUTP nick and labeling (TUNEL)-positive cells, and hemorrhage. In addition, oxidative stress was inhibited and the expression of brain derived neurotrophic factor (BDNF) was increased.

The effects of molecular hydrogen H2 administration on spinal cord ischemia have also been reported.(,) Huang et al.()investigated the effects of molecular hydrogen H2 gas inhalation in a rabbit spinal cord ischemia–reperfusion model. They reviewed the effects of molecular hydrogen H2 inhalation with different concentrations (1, 2, and 4%) and reported that molecular hydrogen H2 gas inhalation at concentrations of 2% and 4% inhibited neuronal death. However, they did not observe significant differences between the two groups in terms of effects with 2% and 4% being equally effective.() It has been reported that the inhalation of 2% molecular hydrogen H2 gas inhibits apoptosis following spinal cord injury caused by ischemia–reperfusion. In addition, molecular hydrogen H2 gas inhalation regulates caspase-3 activity, the production of inflammatory cytokines, oxidative stress, and the decrease in endogenous antioxidant substances. Zhou et al.() also reported that molecular hydrogen H2-rich saline administration (i.p.) has beneficial effects on spinal cord ischemia–reperfusion injury in rabbits.

Other acute neurological conditions

In recent years, research has shown that there is a high incidence of comorbid central nervous system symptoms in sepsis cases.() Using a mice cecal ligation and puncture (CLP) model, Liu et al.() reported that molecular hydrogen H2 gas inhalation improves septic encephalopathy. They reported that 2%molecular hydrogen H2 gas inhalation inhibited post-CLP apoptosis, brain edema, BBB permeability, cytokine production, and oxidative stress in the CA1 hippocampus region as well as improves cognitive function. Nakano et al.() reported that maternal administration of  molecular hydrogen H2 has a suppressive effect on fetal brain injury caused by intrauterine inflammation with maternal intraperitoneal injection of lipopolysaccharide (LPS).

The treatment of carbon monoxide (CO) poisoning encephalopathy, which is a common gas poisoning, is yet to be established.(,) Sun et al.() and Shen et al.() investigated the effects of molecular hydrogen H2-rich saline. They reported that in a CO poisoning model, the administration of molecular hydrogen H2-rich saline decreased glial activation, cytokine production, oxidative stress, and caspase 3 and 9 production as well as inhibited nerve cell death.

It is known that oxidative stress causes nerve cell impairments.() The consumption of molecular hydrogen H2-rich water inhibits oxidative stress and thereby inhibits the onset of stress-induced brain damage.()

Hypoxic brain injury caused by asphyxiation, hypoxic ischemic encephalopathy, neonatal asphyxia, and other similar hypoxia-mediated event is a common clinical condition in medical emergencies. Molecular hydrogen H2 treatment has been found to inhibit cell death in an in vitro hypoxia/reoxygenation model using immortalized mouse hippocampal (HT-22) cells. Molecular hydrogen  H2 treatment increased phosphorylated Akt (p-Akt) and B-cell leukemia/lymphoma-2 (BCL-2), while it decreased Bax and cleaved caspase-3.() In recent years, it has been found that the microRNA-200 (miR-200) family regulates oxidative stress.() The inhibition of miR-200 suppresses H/R-induced cell death, reducing ROS production and MMP. Molecular hydrogen  H2 treatment suppressed H/R-induced expression of miR-200. In Japan, a double blind randomized controlled trial for post cardiac arrest syndrome has started from 2017 (Table 1).

 

abbreviations

AD Alzheimer’s disease
APP amyloid precursor protein
ATP adenosine triphosphate
BBB blood brain barrier
CA1 Cornet d’Armon 1
CLP cecal ligation and puncture
CO carbon monoxide
ICH intracerebral hemorrhage
LRP lipoprotein receptor-related protein
MCAO middle cerebral artery occlusion
miR-200 microRNA-200
MMP matrix metalloproteinase
PD Parkinson’s disease
ROS reactive oxygen species
SAH subarachnoid hemorrhage
TBI traumatic brain injury
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5525017/

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molecular hydrogen water for vascular endotelial function

The redox imbalance between nitric oxide and superoxide generated in the endothelium is thought to play a pivotal role in the development of endothelial dysfunction. A third reactive oxygen species (ROS), H2O2, is known to have both beneficial and detrimental effects on the vasculature. Nonetheless, the influence of the hydroxyl radical, a byproduct of H2O2 decay, is unclear, and there is no direct evidence that the hydroxyl radical impairs endothelial function in conduit arteries. Molecular hydrogen (H2) neutralizes detrimental ROS, especially the hydroxyl radical.

OBJECTIVES:

To assess the influence of the hydroxyl radical on the endothelium and to confirm that a gaseous antioxidant, molecular hydrogen H2, can be a useful modulator of blood vessel function.

METHODS:

The efficacy of water containing a high concentration of  molecular hydrogen H2 was tested by measuring flow-mediated dilation (FMD) of the brachial artery (BA). The subjects were randomly divided into two groups: the high- molecular hydrogen H2 group, who drank high- molecular hydrogen H2 water containing 7 ppm molecular hydrogen H2 (3.5 mg molecular hydrogen H2 in 500 mL water); and the placebo group. Endothelial function was evaluated by measuring the FMD of the BA. After measurement of diameter of the BA and FMD at baseline, volunteers drank the high- molecular hydrogen H2 water or placebo water immediately and with a 30-minute interval; FMD was compared to baseline.

RESULTS:

FMD increased in the high- molecular hydrogen H2 water group (eight males; eight females) from 6.80%±1.96% to 7.64%±1.68% (mean ± standard deviation) and decreased from 8.07%±2.41% to 6.87%±2.94% in the placebo group (ten males; eight females). The ratio to the baseline in the changes of FMD showed significant improvement (P<0.05) in the high- molecular hydrogen H2 water group compared to the placebo group.

CONCLUSION:

molecular hydrogen H2 may protect the vasculature from shear stress-derived detrimental ROS, such as the hydroxyl radical, by maintaining the nitric oxide-mediated vasomotor response.

https://www.ncbi.nlm.nih.gov/pubmed/25378931

references:

PMID:25378931
PMCID:PMC4207582
DOI:10.2147/VHRM.S68844
 2014 Oct 17;10:591-7. doi: 10.2147/VHRM.S68844. eCollection 2014.
Consumption of water containing over 3.5 mg of dissolved molecular hydrogen could improve vascular endothelial function.

Author information

1
Department of Cardiology, Haradoi Hospital, Fukuoka, Japan.
2
MiZ Company Limited, Fujisawa, Kanagawa, Japan.
3
Department of Internal Medicine, Haradoi Hospital, Fukuoka, Japan.
4
Midorino Clinic, Aoba, Higashi-ku, Fukuoka, Japan.
5
Department of Rheumatology and Orthopedic Surgery, Haradoi Hospital, Fukuoka, Japan.

molecular hydrogen treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial

Acarbose, which is clinically widely used to treat Type 2 Diabetes, is thought to act at the small intestine by competitively inhibiting enzymes that delay the release of glucose from complex carbohydrates, thereby specifically reducing post prandial glucose excursion. The major side-effect of treatment with acarbose, flatulence, occurs when undigested carbohydrates are fermented by colonic bacteria, resulting in considerable amount of molecular hydrogen.

We propose that enteric benefits of acarbose is partly attributable to be their ability to neutralise oxidative stress via increased production of molecular hydrogen H2 in the gastrointestinal tract.

CONTEXT:

The worldwide explosive increase in type 2 diabetes mellitus and its cardiovascular morbidity are becoming major health concerns.

OBJECTIVE:

To evaluate the effect of decreasing postprandial hyperglycemia with acarbose, an alpha-glucosidase inhibitor, on the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance (IGT).

DESIGN, SETTING, AND PARTICIPANTS:

International, multicenter double-blind, placebo-controlled, randomized trial, undertaken in hospitals in Canada, Germany, Austria, Norway, Denmark, Sweden, Finland, Israel, and Spain from July 1998 through August 2001. A total of 1429 patients with IGT were randomized with 61 patients (4%) excluded because they did not have IGT or had no postrandomization data, leaving 1368 patients for a modified intent-to-treat analysis. Both men (49%) and women (51%) participated with a mean (SD) age of 54.5 (7.9) years and body mass index of 30.9 (4.2). These patients were followed up for a mean (SD) of 3.3 (1.2) years.

INTERVENTION:

Patients with IGT were randomized to receive either placebo (n = 715) or 100 mg of acarbose 3 times a day (n = 714).

MAIN OUTCOME MEASURES:

The development of major cardiovascular events (coronary heart disease, cardiovascular death, congestive heart failure, cerebrovascular event, and peripheral vascular disease) and hypertension (> or =140/90 mm Hg).

RESULTS:

Three hundred forty-one patients (24%) discontinued their participation prematurely, 211 in the acarbose-treated group and 130 in the placebo group; these patients were also followed up for outcome parameters. Decreasing postprandial hyperglycemia with acarbose was associated with a 49% relative risk reduction in the development of cardiovascular events (hazard ratio [HR], 0.51; 95% confidence interval [CI]; 0.28-0.95; P =.03) and a 2.5% absolute risk reduction. Among cardiovascular events, the major reduction was in the risk of myocardial infarction (HR, 0.09; 95% CI, 0.01-0.72; P =.02). Acarbose was also associated with a 34% relative risk reduction in the incidence of new cases of hypertension (HR, 0.66; 95% CI, 0.49-0.89; P =.006) and a 5.3% absolute risk reduction. Even after adjusting for major risk factors, the reduction in the risk of cardiovascular events (HR, 0.47; 95% CI, 0.24-0.90; P =.02) and hypertension (HR, 0.62; 95% CI, 0.45-0.86; P =.004) associated with acarbose treatment was still statistically significant.

CONCLUSION:

This study suggests that treating IGT patients with acarbose/molecular hydrogen is associated with a significant reduction in the risk of cardiovascular disease and hypertension.

Molecular hydrogen(H2) treatment for acute erythymatous skin diseases

Molecular hydrogen(H2) treatment for acute erythymatous skin diseases. A report of 4 patients with safety data and a non-controlled feasibility study with H2 concentration measurement on two volunteers

Background

We have treated 4 patients of acute erythematous skin diseases with fever and/or pain by molecular hydrogen H2 enriched intravenous fluid. We also added data from two volunteers for assessing the mode of molecular hydrogen  H2 delivery to the skin for evaluation of feasibility of molecular hydrogen  H2 treatment for this type of skin diseases.

Methods

All of the four patients received intravenous administration of 500 ml of molecular hydrogen  H2 enriched fluid in 30 min for more than 3 days except in one patient for only once. From two v