learn more about the wide-ranging potential benefits of molecular hydrogen

H2

Molecular Hydrogen may have wide-ranging and powerful health benefits, and at trusii, we believe the evidence is STRONG. Over 850 peer-reviewed, scientific articles have shown H2’s remarkable potential for over 170 disease models, and many more high-impact clinical studies are currently underway. In addition, studies have demonstrated H2’s possible benefits for boosting physical and cognitive performance.

At trusii, we've compiled a comprehensive list of the existing scientific research. Our team is constantly scouring the scientific literature for the most cutting-edge and trailblazing studies in the field, and for the first time ever, a comprehensive list of the studies is available here. By clicking on any of the health conditions below, you’ll be taken to a list of corresponding scientific studies.

Health Conditions
 

Selective, clean, and safe. While taking high doses of supplemental antioxidants has negative health effects, it is impossible to take too much H2. Molecular Hydrogen ONLY scavenges and neutralizes the harmful free radicals, leaving the beneficial ones alone. Many antioxidants leave behind toxic byproducts, but the only byproduct of H2 is water. Click below to view the evidence based studies related to molecular hydrogen's safety profile.

Safety Profile

Clinical effects of hydrogen administration: From animal and human diseases to exercise medicine

 

“There are no safety issues with 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.”

 

Nicolson, G. L., Mattos, G. F., Settineri, R., Costa, C., Ellithorpe, R., Rosenblatt, S., . . . Ohta, S. (2016). Clinical effects of hydrogen administration: From animal and human diseases to exercise medicine. International Journal of Clinical Medicine, 7(1), 32-76. doi: 10.4236/ijcm.2016.71005

Experimental verification of protective effect of hydrogen-rich water against cisplatin-induced nephrotoxicity in rats using dynamic contrast-enhanced CT

 

“If too much hydrogen is taken in, the excess would be expired through the lungs. Thus, hydrogen-rich water has great potential for clinical use.”

 

Kitamura, A., Kobayashi, S., Matsushita, T., Fujinawa, H., & Murase, K. (2010). Experimental verification of protective effect of hydrogen-rich water against cisplatin-induced nephrotoxicity in rats using dynamic contrast-enhanced CT. The British Journal of Radiology, 83(990), 509-514. doi: 10.1259/bjr/25604811

 

Hydrogen-rich water exerting a protective effect on ovarian reserve function in a mouse model of immune premature ovarian failure induced by zona pellucida 3

 

“Hydrogen has not been reported to be toxic at high doses, because excess hydrogen is expired via the lungs into the air.”

 

 Ma, Y., He, X., Wang, S., Yin, C., Wang, T., & Jia, C. (2016). Hydrogen-rich water exerting a protective effect on ovarian reserve function in a mouse model of immune premature ovarian failure induced by zona pellucida 3. Chinese Medical Journal, 129(9), 2331-2337. doi: 10.4103/0366-6999.190668

 

Estimation of the hydrogen concentration in rat tissue using an airtight tube following the administration of hydrogen via various routes

 

“Hydrogen has not been reported to be toxic at effective doses, and overdoses are unlikely, as excess hydrogen is expired via the lungs.”

 

Liu, C., Kurokawa, R., Fujino, M., Hirano, S., Sato, B., & Li, X. (2014). Estimation of the hydrogen concentration in rat tissue using an airtight tube following the administration of hydrogen via various routes. Scientific Reports, 4(5485), 1-7. doi: 10.1038/srep05485

Protective effect of hydrogen-rich saline on ischemia/reperfusion injury in rat skin flap

 

“H2 can reach relatively high concentrations quickly, and excessive H2 can be eliminated from the body via breathing, causing no side effects.”

 

Zhao, L., Wang, Y., Qin, S., Ma, X., Sun, X., Wang, M., & Zhong, R. (2013). Protective effect of hydrogen-rich saline on ischemia/reperfusion injury in rat skin flap. Journal of Zhejiang University Science B, 14(5), 382-391. doi: 10.1631/jzus.b1200317 

 

Hydrogen-rich saline attenuates radiation-induced male germ cell loss in mice through reducing hydroxyl radicals

 

“Our recent studies suggest that H2 (hydrogen) has a potential as a novel radioprotector without known toxic side effects. Our results represent the first in vivo evidence in support of a radioprotective role of H2 by neutralizing •OH in irradiated tissue with no side effects.”

 

Chuai, Y., Gao, F., Li, B., Zhao, L., Qian, L., Cao, F., . . . Cai, J. (2012). Hydrogen-rich saline attenuates radiation-induced male germ cell loss in mice through reducing hydroxyl radicals. Biochemical Journal, 442(1), 49-56. doi: 10.1042/bj20111786

 

Hydrogen-rich water improves neurological functional recovery in experimental autoimmune encephalomyelitis mice

 

“Because Hydrogen rich water is non-toxic, inexpensive, easily administered, and can readily cross the blood-brain barrier, our experiments suggest that HRW may have great potential in the treatment of Multiple Sclerosis.”

 

Zhao, M., Liu, M., Pu, Y., Wang, D., Xie, Y., Xue, G., . . . Cao, L. (2016). Hydrogen-rich water improves neurological functional recovery in experimental autoimmune encephalomyelitis mice. Journal of Neuroimmunology, 294, 6-13. doi: 10.1016/j.jneuroim.2016.03.006

 

Hydrogen-rich water affected blood alkalinity in physically active men

 

“No volunteers withdrew before the end of the study, and no participant reported any vexatious side effects of h2 supplementation. These results support the hypothesis that HRW administration is safe and may have an alkalizing effect in young physically active men.”

 

Ostojic, S. M., & Stojanovic, M. D. (2014). Hydrogen-rich water affected blood alkalinity in physically active men. Research in Sports Medicine, 22(1), 49-60. doi: 10.1080/15438627.2013.852092

Hydrogen-rich saline as an innovative therapy for cataract: A hypothesis

 

“Hydrogen as a natural molecule could be a safe and effective antioxidant without known toxic effects.”

 

Qin, L., Tao, Y., Wang, L., Chen, H., Liu, Y., & Huang, Y. F. (2016). Hydrogen-rich saline as an innovative therapy for cataract: A hypothesis. Medical Science Monitor, 22, 3191-3195. doi: 10.12659/msm.899807

Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventative and therapeutic applications

 

“H2 has more advantages from the aspect of toxicity: H2 has no cytotoxicity even at high concentration.”

 

Ohta, S. (2011). Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventative and therapeutic applications. Current Pharmaceutical Design, 17(22), 2241-2252. doi: 10.2174/138161211797052664

Hydrogen therapy attenuates irradiation-induced lung damage by reducing oxidative stress

 

“This study thus demonstrated that H(2) treatment is valuable for protection against irradiation lung damage with no known toxicity.”

 

Terasaki, Y., Ohsawa, I., Terasaki, M., Takahashi, M., Kunugi, S., Dedong, K., . . . Fukuda, Y. (2011). Hydrogen therapy attenuates irradiation-induced lung damage by reducing oxidative stress. American Journal of Physiology: Lung Cellular and Molecular Physiology, 301(4), 415-426. doi: 10.1152/ajplung.00008.2011

Hydrogen-rich saline attenuates steroid-associated femoral head necrosis through inhibition of oxidative stress in a rabbit model

 

“There were no mortalities at any time during the experiment, and no side effects of the hydrogen-rich saline on the overall well-being of the rabbits were observed in either group.”

 

Huang, S., Jiao, J., & Yan, H. (2015). Hydrogen-rich saline attenuates steroid-associated femoral head necrosis through inhibition of oxidative stress in a rabbit model. Experimental and Therapeutic Medicine, 11(1), 177-182. doi: 10.3892/etm.2015.2883

Intrathecal infusion of hydrogen-rich normal saline attenuates neuropathic pain via inhibition of activation of spinal astrocytes and microglia in rats

 

“HRS has the following advantages: easy to use, no side effects and no tolerance develops when given continuously, indicating that therapeutic use of HRS may be promising.”

 

​Ge, Y., Wu, F., Sun, X., Xiang, Z., Yang, L., Huang, S., . . . Yu, W. (2014). Intrathecal infusion of hydrogen-rich normal saline attenuates neuropathic pain via inhibition of activation of spinal astrocytes and microglia in rats. PLOS ONE, 9(5), 1-12. doi: 10.1371/journal.pone.0097436

 

Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome

 

“We did not observe any unwanted side effects of H2, including headache, diarrhea, or vomiting. Our data give us a clue that H2 might have the potential to be used as a novel lipid-regulating agent with the advantage of no toxicity compared with other commonly used lipid-regulating drugs that have side-effects on the liver and kidney.”

 

Song, G., Li, M., Sang, H., Zhang, L., Li, X., Yao, S., . . . Qin, S. (2013). Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome. The Journal of Lipid​ Research, 54(7), 1884-1893. doi: 10.1194/jlr.m036640

 

Effects of hydrogen-rich water on depressive-like behavior in mice        

 

“Identifying effective anti-depressive compounds with little to no side effects may serve as effective alternative or preventative treatments. It is unclear if hydrogen-rich water, which has no known side effects, may have beneficial effects in mitigating depression symptoms.”

 

Zhang, Y., Su, W., Chen, Y., Wu, T., Gong, H., Shen, X., . . . Jiang, C. (2016). Effects of hydrogen-rich water on depressive-like behavior in mice. Scientific Reports, 6, 1-7. doi: 10.1038/srep23742

 

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Aging

 

H2 combats aging with its antioxidant and anti-inflammatory properties. Molecular hydrogen works as a "selective" antioxidant; i.e. it only attacks and neutralizes harmful free radicals, leaving beneficial free radicals alone to do their jobs. The toxic free radicals that H2 neutralizes are the primary source of premature aging.

Hydrogen-saturated saline protects intensive narrow band noise-induced hearing loss in guinea pigs through an antioxidant effect

 

“Our findings suggest that hydrogen-saturated saline is effective in preventing intensive narrow band noise-induced hearing loss through the antioxidant effect.”

 

Chen, L., Yu, N., Lu, Y., Wu, L., Chen, D., Guo, W., . . . Zhai, S. (2014). Hydrogen-saturated saline protects intensive narrow band noise-induced hearing loss in guinea pigs through an antioxidant effect. PLOS ONE, 9(6), 1-5. doi: 10.1371/journal.pone.0100774

 

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

 

“Molecular hydrogen given in drinking water reverses many of the sequelae of controlled cortical impact and suggests that it could be an easily administered, highly effective treatment for traumatic brain injury.”

 

Dohi, K., Kraemer, B. C., Erickson, M. A., Mcmillan, P. J., Kovac, A., Flachbartova, Z., . . . Banks, W. A. (2014). Molecular hydrogen in drinking water protects against neurodegenerative changes induced by traumatic brain injury. PLOS ONE, 9(9), 1-16. doi: 10.1371/journal.pone.0108034 

Protective effect of saturated hydrogen saline against blue light-induced retinal damage in rats

 

“Saturated hydrogen saline could protect the retina from light-induced damage by attenuating oxidative stress.”

 

Feng, M., Wang, X., Yang, X., Xiao, Q., & Jiang, F. (2012). Protective effect of saturated hydrogen saline against blue light-induced retinal damage in rats. International Journal of Ophthalmology, 5(2), 151-157. doi: 10.3980/j.issn.2222-3959.2012.02.07 

Hydrogen as a selective antioxidant: A review of clinical and experimental studies

“H2 is emerging as a novel and safe therapeutic antioxidant. It has selective antioxidant properties, giving it anti-inflammatory properties.”

 

Hong, Y., Chen, S., & Zhang, J. (2010). Hydrogen as a selective antioxidant: A review of clinical and experimental studies. Journal of International Medical Research, 38(6), 1893-1903. doi: 10.1177/147323001003800602  

 

The potential utilizations of hydrogen as a promising therapeutic strategy against ocular diseases

 

“Hydrogen can modulate several biological functions, and exhibits antioxidant and anti-inflammatory effects. The ability of hydrogen to neutralize free radicals, especially the hydroxyl radicals as well as other detrimental ROS, can be utilized to treat or prevent ocular disorders related to oxidative stress.”

 

Huang, Y. F., Tao, Y., Geng, L., Xu, W., Peng, G., & Qin, L. (2016). The potential utilizations of hydrogen as a promising therapeutic strategy against ocular diseases. Therapeutics and Clinical Risk Management, 12, 799-806. doi: 10.2147/tcrm.s102518

 

Hydrogen-rich electrolyzed warm water represses wrinkle formation against UVA ray together with type-I collagen production and oxidative-stress diminishment in fibroblasts and cell-injury prevention in keratinocytes

 

“HW-bathing significantly improved wrinkle in four subjects on the back of neck on 90th day as compared to 0 day. Thus, HW may serve as daily skin care to repress UVA-induced skin damages by ROS-scavenging and promotion of type-I collagen synthesis in dermis.”

 

Kato, S., Saitoh, Y., Iwai, K., & Miwa, N. (2012). Hydrogen-rich electrolyzed warm water represses wrinkle formation against UVA ray together with type-I collagen production and oxidative-stress diminishment in fibroblasts and cell-injury prevention in keratinocytes. Journal of Photochemistry and Photobiology B: Biology, 106, 24-33. doi: 10.1016/j.jphotobiol.2011.09.006

 

Hydrogen protects auditory hair cells from free radicals

 

“Incubation with a hydrogen-saturated medium significantly reduced ROS generation and subsequent lipid peroxidation in the auditory epithelia, leading to increased survival of the hair cells. These findings show the potential of hydrogen to protect auditory hair cells from ROS-induced damage.”

 

Kikkawa, Y. S., Nakagawa, T., Horie, R. T., & Ito, J. (2009). Hydrogen protects auditory hair cells from free radicals. NeuroReport, 20(7), 689-694. doi: 10.1097/wnr.0b013e32832a5c68

 

Inhaled hydrogen gas therapy for prevention of noise-induced hearing loss through reducing reactive oxygen species

 

“H2-treated group showed decreased immunoreactivity for 8-OHdg. the H2-treated group showed decreased immunoreactivity for 8-OHdG. These findings strongly suggest that inhaled hydrogen gas protects against noise induced hearing loss.”

 

Kurioka, T., Matsunobu, T., Satoh, Y., Niwa, K., & Shiotani, A. (2014). Inhaled hydrogen gas therapy for prevention of noise-induced hearing loss through reducing reactive oxygen species. Neuroscience Research, 89, 69-74. doi: 10.1016/j.neures.2014.08.009

 

Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer's disease by reduction of oxidative stress

 

“Hydrogen-rich saline prevented Abeta-induced neuroinflammation and oxidative stress, which may contribute to the improvement of memory dysfunction in this rat model.”

 

Li, J., Wang, C., Zhang, J. H., Cai, J., Cao, Y., & Sun, X. (2010). Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer's disease by reduction of oxidative stress. Brain Research, 1328, 152-161. doi: 10.1016/j.brainres.2010.02.046 

 

 

Hydrogen in drinking water attenuates noise-induced hearing loss in guinea pigs

 

“These findings suggest that hydrogen can facilitate the recovery of hair cell function and attenuate noise-induced temporary hearing loss.”

 

Lin, Y., Kashio, A., Sakamoto, T., Suzukawa, K., Kakigi, A., & Yamasoba, T. (2011). Hydrogen in drinking water attenuates noise-induced hearing loss in guinea pigs. Neuroscience Letters, 487(1), 12-16. doi: 10.1016/j.neulet.2010.09.064

 

Protection of the retina by rapid diffusion of hydrogen: administration of hydrogen-loaded eye drops in retinal ischemia-reperfusion injury

 

“H(2) has no known toxic effects on the human body. Thus, the results suggest that H(2)-loaded eye drops are a highly useful neuroprotective and antioxidative therapeutic treatment for acute retinal I/R injury.”

 

Oharazawa, H., Igarashi, T., Yokota, T., Fujii, H., Suzuki, H., Machide, M., . . . Ohsawa, I. (2010). Protection of the retina by rapid diffusion of hydrogen: Administration of hydrogen-loaded eye drops in retinal ischemia-reperfusion injury.  Investigative Ophthalmology & Visual Science, 51(1), 487-492. doi: 10.1167/iovs.09-4089

 

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

“Hydrogen selectively reduces the hydroxyl radical, the most toxic free radical, and effectively protects cells. It does not react with free radicals that have physiological benefits, making it an incredibly effective therapy to neutralize acute oxidative stress.”

 

Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., . . . Ohta, S. (2007). Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nature Medicine, 13(6), 688-694. doi: 10.1038/nm1577  

Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventative and therapeutic applications

“H2 prevented the decline of the mitochondrial membrane potential. This suggested that H2 protected mitochondria from OH. Along with this protective effect, H2 also prevented a decrease in the cellular level of ATP synthesized in mitochondria. The fact that H2 protected mitochondria and nuclear DNA provided evidence that H2 penetrated most membranes and diffused into organelles.”

 

Ohta, S. (2011). Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventative and therapeutic applications. Current Pharmaceutical Design, 17(22), 2241-2252. doi: 10.2174/138161211797052664

 

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

 

“Erythema of these 4 patients and associated symptoms improved significantly after the H2 treatment and did not recur. Administration of H2 did not change physiological parameters and did not cause deterioration of the blood chemistry.”

 

Ono, H., Nishijima, Y., Adachi, N., Sakamoto, M., Kudo, Y., Nakazawa, J., . . . Nakao, A. (2012). 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. Medical Gas Research, 2(14), 1-9. doi: 10.1186/2045-9912-2-14 

 

Inhalation of hydrogen gas attenuates ouabain-induced auditory neuropathy in gerbils

 

“The results demonstrate that H(2) treatment is beneficial to ouabain-induced auditory neuropathy via reducing apoptosis. Thus, H(2) might be a potential agent for treating hearing impairment in AN patients.”

 

Qu, J., Gan, Y., Xie, K., Liu, W., Wang, Y., Hei, R., . . . Qiu, J. (2012). Inhalation of hydrogen gas attenuates ouabain-induced auditory neuropathy in gerbils. Acta Pharmacologica Sinica, 33(4), 445-451. doi: 10.1038/aps.2011.190

 

Hydrogen-rich saline promotes survival of retinal ganglion cells in a rat model of optic nerve crush

 

“These results demonstrated that H₂ protects retinal ganglion cell and helps preserve the visual function after optic nerve crush and had a neuroprotective effect in a rat model subjected to optic nerve crush.”

 

Sun, J., Xu, T., Zuo, Q., Wang, R., Qi, A., Cao, W., . . . Xu, J. (2014). Hydrogen-rich saline promotes survival of retinal ganglion cells in a rat model of optic nerve crush. PLOS ONE, 9(6), 1-10. doi: 10.1371/journal.pone.0099299

Hydrogen-rich saline ameliorates the retina against light-induced damage in rats

 

“Peritoneal injection of hydrogen-rich saline provides protection and treatment against light-induced retinal degeneration in rats.”

 

Tian, L., Zhang, L., Xia, F., An, J., Sugita, Y., & Zhang, Z. (2013). Hydrogen-rich saline ameliorates the retina against light-induced damage in rats. Medical Gas Research, 3(19), 1-6. doi: 10.1186/2045-9912-3-19

Hydrogen-rich saline protects retina against glutamate-induced excitotoxic injury in guinea pig

 

“The administration of hydrogen-rich saline through the intravitreal or/and intraperitoneal routes could reduce the retinal excitotoxic injury and promote retinal recovery.”

 

Wei, L., Ge, L., Qin, S., Shi, Y., Du, C., Du, H., . . . Sun, X. (2012). Hydrogen-rich saline protects retina against glutamate-induced excitotoxic injury in guinea pig. Experimental Eye Research, 94(1), 117-127. doi: 10.1016/j.exer.2011.11.016

 

 

Protective effect of molecular hydrogen against oxidative stress caused by peroxynitrite derived from nitric oxide in rat retina

 

“H2 reduces cellular peroxynitrite, a highly toxic reactive nitrogen species. Thus, H2 may be an effective and novel clinical tool for treating glaucoma and other oxidative stress-related diseases.”

 

Yokota, T., Kamimura, N., Igarashi, T., Takahashi, H., Ohta, S., & Oharazawa, H. (2015). Protective effect of molecular hydrogen against oxidative stress caused by peroxynitrite derived from nitric oxide in rat retina. Clinical & Experimental Ophthalmology, 43(6), 568-577. doi: 10.1111/ceo.12525

 

Hydrogen-rich saline alleviates experimental noise-induced hearing loss in guinea pigs

 

“Hydrogen-rich saline can alleviate experimental noise-induced hearing loss in guinea pigs, partially by preventing the death of cochlear hair cells after intensive noise exposure.”

 

Zhou, Y., Zheng, H., Ruan, F., Chen, X., Zheng, G., Kang, M., . . . Sun, X. (2012). Hydrogen-rich saline alleviates experimental and noise-induced hearing loss in guinea pigs. Neuroscience, 209, 407-53. doi: 10.1016/j.neuroscience.2012.02.028

 
 

Allergies

Studies show H2 suppresses allergic reactions. Not only does H2 combat inflammation, it also apparently improves and modulates cell signaling, affording it anti-allergy benefits.

​​

Hydrogen as a selective antioxidant: A review of clinical and experimental studies

 

“H2 is emerging as a novel and safe therapeutic antioxidant. It has selective antioxidant properties, giving it anti-inflammatory properties.”

 

Hong, Y., Chen, S., & Zhang, J. (2010). Hydrogen as a selective antioxidant: A review of clinical and experimental studies. Journal of International Medical Research, 38(6), 1893-1903. doi: 10.1177/147323001003800602

​​

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

“H2 prevented the decline of the mitochondrial membrane potential. This suggested that H2 protected mitochondria from OH. Along with this protective effect, H2 also prevented a decrease in the cellular level of ATP synthesized in mitochondria. The fact that H2 protected mitochondria and nuclear DNA provided evidence that H2 penetrated most membranes and diffused into organelles.” 

 

Ohta, S. (2011). Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventive and therapeutic applications. Current Pharmaceutical Design, 17(22), 2241-2252. doi: 10.2174/138161211797052664

 

The drinking effect of hydrogen water on atopic dermatitis induced by dermatophagoides farina allergen in NC/Nga mice

 

“To conclude, drinking HW suppressed the levels of inflammation-related mediators such as Th1, Th2, and pro-inflammatory cytokines which are number one players in the pathogenesis of human AD. In addition, this study provides a new insight of the relevance of certain cytokines in AD. HW represents a potentially alternative therapeutic and preventive treatment of AD.”

 

Ignacio, R. M., Kwak, H., Yun, Y., Sajo, M. E., Yoon, Y., Kim, C., . . . Lee, K. (2013). The drinking effect of hydrogen water on atopic dermatitis induced by dermatophagoides farina allergen in NC/Nga mice. Evidence-Based Complementary and Alternative Medicine,  2013, 1-5. doi: 10.1155/2013/538673

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

 

“Hydrogen is qualified to cross the blood brain barrier, to enter the mitochondria, and even has the ability to translocate to the nucleus under certain conditions. Once in these ideal locations of the cell, previous studies have shown that hydrogen exerts antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective properties that are beneficial to the cell.”

 

Dixon, B. J., Tang, J., & Zhang, J. H. (2013). The evolution of molecular hydrogen: A noteworthy potential therapy with clinical significance. Medical Gas Research, 3(10), 1-12. doi: 10.1186/2045-9912-3-10

 

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

 

“A total of 321 original articles have been published from 2007 to June 2015. Most studies have been conducted in Japan, China, and the USA. The effects have been reported in essentially all organs covering 31 disease categories that can be subdivided into 166 disease models, human diseases, treatment-associated pathologies, and pathophysiological conditions of plants with a predominance of oxidative stress-mediated diseases and inflammatory diseases.”

 

Ichihara, M., Sobue, S., Ito, M., Ito, M., Hirayama, M., & Ohno, K. (2015). Beneficial biological effects and the underlying mechanisms of molecular hydrogen - comprehensive review of 321 original articles. Medical Gas Research, 5(12), 1-21. doi: 10.1186/s13618-015-0035-1

 

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

 

“Effects of molecular hydrogen on various diseases have been documented for 63 disease models and human diseases in the past four and a half years. Six human diseases have been studied to date: diabetes mellitus type 2, metabolic syndrome, hemodialysis, inflammatory and mitochondrial myopathies, brain stem infarction, and radiation-induced adverse effects.”

 

Ohno, K., Ito, M., Ichihara, M., & Ito, M. (2012). Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases. Oxidative Medicine and Cellular Longevity, 2012, 1-11. doi: 10.1155/2012/353152

 

Hydrogen gas presents a promising therapeutic strategy for sepsis 

 

“Sepsis is characterized by a severe inflammatory response to infection. Our studies have found that hydrogen gas can improve the survival and organ damage in mice and rats with cecal ligation and puncture, zymosan, and lipopolysaccharide-induced sepsis.”

 

Xie, K., Liu, L., Yu, Y., & Wang, G. (2014). Hydrogen gas presents a promising therapeutic strategy for sepsis. BioMed Research International, 2014, 1-9. doi: 10.1155/2014/807635

 

Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice

 

“To investigate the hepatoprotective effects and mechanisms of hydrogen-rich water (HRW) in acetaminophen (APAP)-induced liver injury in mice. HRW has significant therapeutic potential in APAP-induced hepatotoxicity by inhibiting oxidative stress and inflammation and promoting liver regeneration.”

 

Zhang, J. (2015). Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice. World Journal of Gastroenterology, 21(14), 4195-4209. doi: 10.3748/wjg.v21.i14.4195

 

Athletic Performance & Recovery

 

H2 has been shown to be beneficial for exercise performance in a variety of ways. First, H2 was able to prevent metabolic acidosis during heavy exercise, which typically would hinder performance. H2's antioxidant and anti-inflammatory properties also seem to improve recovery between workouts.

 

Pilot study: Effects of drinking hydrogen-rich water on muscle fatigue caused by acute exercise in elite athletes

“HW may be suitable hydration for athletes by preventing elevation of blood lactate during heavy exercise. Adequate hydration with hydrogen-rich water pre-exercise reduced blood lactate levels and improved exercise-induced decline of muscle function.”

 

Aoki, K., Nakao, A., Adachi, T., Matsui, Y., & Miyakawa, S. (2012). Pilot study: Effects of drinking hydrogen-rich water on muscle fatigue caused by acute exercise in elite athletes. Medical Gas Research, 2(12), 1-6. doi: 10.1186/2045-9912-2-12 

 

Molecular hydrogen affected post-exercise recovery in judo athletes

 

“Hydrogen-rich water appears to be an appropriate strategy to positively affect post-exercise lactates in judo athletes.”

 

Drid, P., Stojanovic, M. D., Trivic, T., & Ostojic, S. M. (2016). Molecular hydrogen affected post-exercise recovery in judo athletes. Medicine and Science in Sports and Exercise, 48(5), 3820. doi: 10.1249/01.mss.0000488223.41775.bc

 

Hydrogen as a selective antioxidant: A review of clinical and experimental studies

“H2 is emerging as a novel and safe therapeutic antioxidant. It has selective antioxidant properties, giving it anti-inflammatory properties.”

 

Hong, Y., Chen, S., & Zhang, J. (2010). Hydrogen as a selective antioxidant: A review of clinical and experimental studies. Journal of International Medical Research, 38(6), 1893-1903. doi: 10.1177/147323001003800602

 

Hydrogen-supplemented drinking water protects cardiac allografts from inflammation-associated deterioration

“Hydrogen treatment was also associated with increased graft ATP levels and increased activity of the enzymes in mitochondrial respiratory chain.”

 

Noda, K., Tanaka, Y., Shigemura, N., Kawamura, T., Wang, Y., Masutani, K., . . . Nakao, A. (2012). Hydrogen-supplemented drinking water protects cardiac allografts from inflammation-associated deterioration. Transplant International, 25(12), 1213-1222. doi: 10.1111/j.1432-2277.2012.01542.x

 

 

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

“Hydrogen selectively reduces the hydroxyl radical, the most toxic free radical, and effectively protects cells. It does not react with free radicals that have physiological benefits, making it an incredibly effective therapy to neutralize acute oxidative stress.”

 

Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., . . . Ohta, S. (2007). Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nature Medicine, 13(6), 688-694. doi: 10.1038/nm1577

 

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

“H2 prevented the decline of the mitochondrial membrane potential. This suggested that H2 protected mitochondria from OH. Along with this protective effect, H2 also prevented a decrease in the cellular level of ATP synthesized in mitochondria. The fact that H2 protected mitochondria and nuclear DNA provided evidence that H2 penetrated most membranes and diffused into organelles.”

 

Ohta, S. (2011). Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventive and therapeutic applications. Current Pharmaceutical Design, 17(22), 2241-2252. doi: 10.2174/138161211797052664

 

 

Drinks with alkaline negative oxidative reduction potential improve exercise performance in physically active men and women: Double-blind, randomized, placebo-controlled, cross-over trial of efficacy and safety

“Drinks with alkaline negative oxidative reduction potential improve exercise performance in physically active men and women by reducing the rate of blood lactate accumulation during and after exercise, increase time to exhaustion, increase serum buffering capacity and not increase prevalence of adverse effects as compared to the control drink.”

 

Ostojić, S. (2011). Drinks with alkaline negative oxidative reduction potential improve exercise performance in physically active men and women: Double-blind, randomized, placebo-controlled, cross-over trial of efficacy and safety. Serbian Journal of Sports Sciences, 5(3), 83-89. Retrieved from https://www.researchgate.net/publication/225183451_DRINKS_WITH_ALKALINE_NEGATIVE_OXIDATIVE_REDUCTION_POTENTIAL_IMPROVE_EXERCISE_PERFORMANCE_IN_PHYSICALLY_ACTIVE_MEN_AND_WOMEN_DOUBLE-BLIND_RANDOMIZEDPLACEBO-CONTROLLED_CROSS-OVER_TRIAL_OF_EFFICACY_AND_SAFETY

 

 

Hydrogen-rich water affected blood alkalinity in physically active men

“Hydrogen-rich water may be an effective and safe alkalizing agent in the treatment of exercise-induced acidosis.”

 

Ostojic, S. M., & Stojanovic, M. D. (2014). Hydrogen-rich water affected blood alkalinity in physically active men. Research in Sports Medicine, 22(1), 49-60. doi: 10.1080/15438627.2013.852092.

 

 Serum alkalinization and hydrogen-rich water in healthy men ​

 

“Metabolic acidosis during intense exercise results in muscle ache, muscle burning, rapid breathing, nausea and stomach pain. The consumption of hydrogen-rich water by healthy athletes engaging in intense exercise helped to reduce the level of acidosis, suggesting that hydrogen-rich water provides benefits as a neutralizing agent.”

 

Ostojic, S. M. (2012). Serum alkalinization and hydrogen-rich water in healthy men. Mayo Clinic Proceedings, 87(5), 501-502. doi: 10.1016/j.mayocp.2012.02.008 

 

Molecular hydrogen in sports medicine: New therapeutic perspectives

“In the past 2 decades, molecular hydrogen emerged as a novel therapeutic agent, with antioxidant, anti-inflammatory and anti-apoptotic effects demonstrated in plethora of animal disease models and human studies. In particular, hydrogen therapy may be an effective and specific innovative treatment for exercise-induced oxidative stress and sports injury, with potential for the improvement of exercise performance.”

 

Ostojic, S. (2014). Molecular hydrogen in sports medicine: New therapeutic perspectives. International Journal of Sports Medicine, 36(4), 273-279. doi: 10.1055/s-0034-1395509

 

Effect of treadmill exercise and hydrogen-rich water intake on serum oxidative and anti-oxidant metabolites in serum of thoroughbred horses

“The present study aimed to clarify changes of oxidative stress and antioxidative functions in treadmill-exercised Thoroughbred horses using recently developed techniques for measurement of oxidative stress and antioxidative markers. Also, the effect of nasogastric administration of hydrogen-rich water (HW) or placebo water preceding the treadmill exercise on these parameters was examined. The marked elevation of oxidative stress and anitioxidative functions occurred simultaneously in the intensively exercised horses, and suggest a possibility that HW has some antioxidative efficacy.”

 

Tsubone, H., Hanafusa, M., Endo, M., Manabe, N., Hiraga, A., Ohmura, H., & Aida, H. (2013). Effect of treadmill exercise and hydrogen-rich water intake on serum oxidative and anti-oxidant metabolites in serum of thoroughbred horses. Journal of Equine Science, 24(1), 1-8. doi: 10.1294/jes.24.1

 

Chronic hydrogen-rich saline treatment attenuates vascular dysfunction in spontaneous hypertensive rats

 

“Treatment with HRS depressed pro-inflammatory cytokines expression including IL-6 and IL-1β and suppressed NF-κB activation, restored mitochondrial function including ATP formation and membrane integrity.”

 

Zheng, H., & Yu, Y. (2012). Chronic hydrogen-rich saline treatment attenuates vascular dysfunction in spontaneous hypertensive rats. Biochemical Pharmacology, 83(9), 1269-1277. doi: 10.1016/j.bcp.2012.01.031

Autoimmune Disease

 

In addition to the apparent beneficial applications for rheumatoid arthritis, the powerful antioxidant and anti-inflammatory ability of H2 would logically promote a healthy immune balance.

 

Hydrogen as a selective antioxidant: A review of clinical and experimental studies

“H2 is emerging as a novel and safe therapeutic antioxidant. It has selective antioxidant properties, giving it anti-inflammatory properties.”

 

Hong, Y., Chen, S., & Zhang, J. (2010). Hydrogen as a selective antioxidant: A review of clinical and experimental studies. Journal of International Medical Research, 38(6), 1893-1903. doi: 10.1177/147323001003800602

Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventative and therapeutic applications

“H2 prevented the decline of the mitochondrial membrane potential. This suggested that H2 protected mitochondria from OH. Along with this protective effect, H2 also prevented a decrease in the cellular level of ATP synthesized in mitochondria. The fact that H2 protected mitochondria and nuclear DNA provided evidence that H2 penetrated most membranes and diffused into organelles.”

 

Ohta, S. (2011). Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventative and therapeutic applications. Current Pharmaceutical Design, 17(22), 2241-2252. doi: 10.2174/138161211797052664

 

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

“Hydrogen selectively reduces the hydroxyl radical, the most toxic free radical, and effectively protects cells. It does not react with free radicals that have physiological benefits, making it an incredibly effective therapy to neutralize acute oxidative stress.”

 

Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., . . . Ohta, S. (2007). Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nature Medicine, 13(6), 688-694. doi: 10.1038/nm1577

Anti-inflammation effects of hydrogen saline in LPS activated macrophages and carrageenan induced paw oedema

 

“Oxidative stress is thought to play an important role in the pathogenesis of inflammation. Recent studies have found that hydrogen gas has the effect of eliminating free radicals. Hydrogen saline exhibits a protective effect against inflammation and it might provide a novel therapeutic approach for inflammatory diseases.”

 

Xu, Z., Zhou, J., Cai, J., Zhu, Z., Sun, X., & Jiang, C. (2012). Anti-inflammation effects of hydrogen saline in LPS activated macrophages and carrageenan induced paw oedema. Journal of Inflammation, 9(2), 1-8. doi: 10.1186/1476-9255-9-2

 

Protective effect of hydrogen-rich saline against radiation-induced immune dysfunction

 

“Recent studies showed that hydrogen can be used as an effective radioprotective agent through scavenging free radicals. We found that H2 could regulate the polarization of CD4+ T cells and the level of related cytokines. This study suggests H2 as an effective radioprotective agent on immune system by scavenging reactive oxygen species.”

 

Zhao, S., Yang, Y., Liu, W., Xuan, Z., Wu, S., Yu, S., . . . Zhao, Y. (2014). Protective effect of hydrogen-rich saline against radiation-induced immune dysfunction. Journal of Cellular and Molecular Medicine, 18(5), 938-946. doi: 10.1111/jcmm.12245

 

 

Therapeutic effects of hydrogen-rich solution on aplastic anemia in vivo

 

“Our study firstly showed that hydrogen-rich solution accelerated the recovery of either hematological or immunological recovery on aplastic anemia mice. This finding suggests hydrogen-rich solution as a potential clinical therapeutic agent for aplastic anemia.”

 

Zhao, S., Mei, K., Qian, L., Yang, Y., Liu, W., Huang, Y., . . . Ni, J. (2013). Therapeutic effects of hydrogen-rich solution on aplastic anemia in vivo. Cellular Physiology and Biochemistry, 32(3), 549-560. doi: 10.1159/000354459

Hydrogen-rich water improves neurological functional recovery in experimental autoimmune encephalomyelitis mice

 

“Because HRW is non-toxic, inexpensive, easily administered, and can readily cross the blood-brain barrier, our experiments suggest that HRW may have great potential in the treatment of Multiple sclerosis.”

 

Zhao, M., Liu, M., Pu, Y., Wang, D., Xie, Y., Xue, G., . . . Cao, L. (2016). Hydrogen-rich water improves neurological functional recovery in experimental autoimmune encephalomyelitis mice. Journal of Neuroimmunology, 294, 6-13. doi: 10.1016/j.jneuroim.2016.03.006

 

Treatment of hydrogen molecule abates oxidative stress and alleviates bone loss induced by modeled microgravity in rats

 

“Treatment with HW alleviated HLS-induced reduction of bone mineral density, ultimate load, stiffness, and energy in femur and lumbar vertebra. Treatment with HW alleviated HLS-induced augmentation of malondialdehyde content and peroxynitrite content and reduction of total sulfhydryl content in femur and lumbar vertebra. Treatment with molecular hydrogen alleviates microgravity-induced bone loss through abating oxidative stress, restoring osteoblastic differentiation, and suppressing osteoclast differentiation and osteoclastogenesis.”

 

Sun, Y., Shuang, F., Chen, D. M., & Zhou, R. B. (2012). Treatment of hydrogen molecule abates oxidative stress and alleviates bone loss induced by modeled microgravity in rats. Osteoporosis International, 24(3), 969-978. doi: 10.1007/s00198-012-2028-4

 

Treatment with hydrogen molecules prevents RANKL-induced osteoclast differentiation associated with inhibition of ROS formation and inactivation of MAPK, AKT and NF-kappa B pathways in murine RAW264.7 cells

 

“The bone protective effects of the hydrogen molecule (H2) have been demonstrated in several osteoporosis models. Hydrogen molecules prevented RANKL-induced osteoclast differentiation associated with inhibition of reactive oxygen species formation and inactivation of NF-κB, mitogen-activated protein kinase and AKT pathways.”

 

Li, D., Zhang, Q., Dong, X., Li, H., & Ma, X. (2013). Treatment with hydrogen molecules prevents RANKL-induced osteoclast differentiation associated with inhibition of ROS formation and inactivation of MAPK, AKT and NF-kappa B pathways in murine RAW264.7 cells. Journal of Bone and Mineral Metabolism, 32(5), 494-504. doi: 10.1007/s00774-013-0530-1

 

Hydrogen water consumption prevents osteopenia in ovariectomized rats

 

“Accumulating evidence indicates an important role of oxidative stress in the progression of osteoporosis. HW consumption prevents osteopenia in ovariectomized rats possibly through the ablation of oxidative stress induced by oestrogen withdrawal.”

 

Guo, J., Li, L., Shi, Y., Wang, H., & Hou, S. (2013). Hydrogen water consumption prevents osteopenia in ovariectomized rats. British Journal of Pharmacology, 168(6), 1412-1420. doi: 10.1111/bph.12036 

 
 

Colitis

 

In a study on rats with ulcerative colitis, treatment with H2 water alleviated mucosal damage of the colon and reduced diarrhea and weight loss. Additionally, H2 may inhibit vascular endothelial growth factor (VEGF), which is correlated with disease activity.

 

Protective effects of hydrogen-rich saline on ulcerative colitis rat model

 

“Treatment with hydrogen-rich saline reduced the weight loss and diarrhea and alleviated the colonic mucosal damage in the UC rats. In addition, the expression of vascular endothelial growth factor in the UC rats increased and could be inhibited by hydrogen treatment. Antioxidative hydrogen-rich saline effectively protected the rats from UC, which might be, at least in part, because of inhibition of vascular endothelial growth factor.”

 

He, J., Xiong, S., Zhang, J., Wang, J., Sun, A., Mei, X., . . . Wang, Q. (2013). Protective effects of hydrogen-rich saline on ulcerative colitis rat model. Journal of Surgical Research, 185(1), 174-181. doi: 10.1016/j.jss.2013.05.047

​​

Protective effects of hydrogen-rich saline on necrotizing enterocolitis in neonatal rats

 

“HRS treatment maintained the body weight, reduced the incidence of NEC from 85% (17/20) to 54.5% (12/22), increased the survival rate from 25% (5/20) to 68.2% (15/22), and attenuated the severity of NEC. In addition, HRS inhibited the mRNA expression of pro-inflammatory mediators (inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-6), down-regulated lipid peroxidation, enhanced total antioxidant capacity, and prevented the increase of diamine oxidase in serum. HRS showed beneficial effects on neonatal rats with NEC via decreasing oxidative stress, increasing antioxidant capacity, suppressing inflammation, and preserving mucosal integrity.”

 

Sheng, Q., Lv, Z., Cai, W., Song, H., Qian, L., & Wang, X. (2013). Protective effects of hydrogen-rich saline on necrotizing enterocolitis in neonatal rats. Journal of Pediatric Surgery, 48(8), 1697-1706. doi: 10.1016/j.jpedsurg.2012.11.038

 

Hydrogen mediates suppression of colon inflammation induced by dextran sodium sulfate

 

“By its antioxidant effect, molecular hydrogen gas (H2) was reported to protect organs from tissue damage induced by ischemia reperfusion. Histological analysis also revealed that the DSS-mediated colonic tissue destruction accompanied by macrophage infiltration was remarkably suppressed by H2. Therefore, the present study indicated that H2 can prevent the development of DSS-induced colitis in mice.”

 

Kajiya, M., Silva, M. J., Sato, K., Ouhara, K., & Kawai, T. (2009). Hydrogen mediates suppression of colon inflammation induced by dextran sodium sulfate. Biochemical and Biophysical Research Communications, 386(1), 11-15. doi: 10.1016/j.bbrc.2009.05.117

 

Hydrogen-rich saline protects against intestinal ischemia/reperfusion injury in rats

 

“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.”

 

Zheng, X., Zheng, X., Mao, Y., Cai, J., Li, Y., Liu, W., . . . Yuan, H. (2009). Hydrogen-rich saline protects against intestinal ischemia/reperfusion injury in rats. Free Radical Research, 43(5), 478-484. doi: 10.1080/10715760902870603

 

The effects of hydrogen-rich saline on the contractile and structural changes of intestine induced by ischemia-reperfusion in Rats

 

“Hydrogen-rich saline treatment significantly attenuated the severity of intestinal I/R injury, with inhibiting of I/R-induced apoptosis, and promoting enterocytes proliferation. Moreover, Hydrogen-rich saline treatment significantly limited the neutrophil infiltration, lipid oxidation, and ameliorated the decreased contractility response to KCl in the intestine subjected to I/R. These results suggest that hydrogen treatment has a protective effect against intestinal contractile dysfunction and damage induced by intestinal I/R. This protective effect is possibly due to its ability to inhibit I/R-induced oxidative stress, apoptosis, and to promote epithelial cell proliferation.”

 

Chen, H., Sun, Y. P., Hu, P. F., Liu, W. W., Xiang, H. G., Li, Y., . . . Wang, Q. (2011). The effects of hydrogen-rich saline on the contractile and structural changes of intestine induced by ischemia-reperfusion in Rats. Journal of Surgical Research, 167(2), 316-322. doi: 10.1016/j.jss.2009.07.045

 

Diabetes (Type 1)

 

Hydrogen improves glycemic control in type1 diabetic animal model by promoting glucose uptake into skeletal muscle

 

“Our study demonstrates that H(2) exerts metabolic effects similar to those of insulin and may be a novel therapeutic alternative to insulin in type 1 diabetes mellitus that can be administered orally.”

 

Amitani, H., Asakawa, A., Cheng, K., Amitani, M., Kaimoto, K., Nakano, M., . . . Inui, A. (2013). Hydrogen improves glycemic control in type1 diabetic animal model by promoting glucose uptake into skeletal muscle. PLOS ONE, 8(4), 1-14. doi: 10.1371/journal.pone.0053913

Suppressive effects of electrolyzed reduced water on alloxan-induced apoptosis and type 1 diabetes mellitus

 

“These results suggest that electrolyzed reduced water can prevent apoptosis of pancreatic β-cells and the development of symptoms in type 1 diabetes model mice by alleviating the alloxan-derived generation of reactive oxygen species.”

 

Li, Y., Hamasaki, T., Nakamichi, N., Kashiwagi, T., Komatsu, T., Ye, J., . . . Shirahata, S. (2010). Suppressive effects of electrolyzed reduced water on alloxan-induced apoptosis and type 1 diabetes mellitus. Cytotechnology, 63(2), 119-131. doi: 10.1007/s10616-010-9317-6

 

Rheumatoid Arthritis

In addition to showing powerful abilities to combat inflammation throughout the body by scavenging hydroxyl radicals, studies suggest that H2 has tremendous therapeutic potential for rheumatoid arthritis.

 

Molecular hydrogen decelerates rheumatoid arthritis progression through inhibition of oxidative stress

 

“Rheumatoid arthritis (RA) is a chronic inflammatory disease which results in progressive destruction of the joint. Our data suggested that H2 can directly neutralize OH and ONOO- to reduce oxidative stress. Moreover, MAPK and NF-κB pathway also play roles in oxidative damage caused by H2O2in RA-FLSs. H2 can provide protection to cells against inflammation, which may be related to inhibition of the activation of MAPK and NF-κB.”

 

Meng, J., Yu, P., Jiang, H., Yuan, T., Liu, N., Tong, J., . . . Zhao, J. (2016). Molecular hydrogen decelerates rheumatoid arthritis progression through inhibition of oxidative stress. American Journal of Translational Research, 8(10), 4472-4477. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5095341/

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

“Hydrogen selectively reduces the hydroxyl radical, the most toxic free radical, and effectively protects cells. It does not react with free radicals that have physiological benefits, making it an incredibly effective therapy to neutralize acute oxidative stress.”

 

Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., . . . Ohta, S. (2007). Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nature Medicine, 13(6), 688-694. doi: 10.1038/nm1577

 

Hydrogen as a selective antioxidant: A review of clinical and experimental studies

“H2 is emerging as a novel and safe therapeutic antioxidant. It has selective antioxidant properties, giving it anti-inflammatory properties.”

 

Hong, Y., Chen, S., & Zhang, J. (2010). Hydrogen as a selective antioxidant: A review of clinical and experimental studies. Journal of International Medical Research, 38(6), 1893-1903. doi: 10.1177/147323001003800602

 

Treatment with hydrogen molecule alleviates TNFα-induced cell injury in osteoblast

 

“Tumor necrosis factor-alpha (TNFα) plays a crucial role in inflammatory diseases such as rheumatoid arthritis and postmenopausal osteoporosis. Recently, it has been demonstrated that hydrogen gas, known as a novel antioxidant, can exert therapeutic anti-inflammatory effect in many diseases. Treatment with H(2) alleviates TNFα-induced cell injury in osteoblast through abating oxidative stress, preserving mitochondrial function, suppressing inflammation, and enhancing NO bioavailability.”

 

Cai, W., Zhang, M., Yu, Y., & Cai, J. (2012). Treatment with hydrogen molecule alleviates TNFα-induced cell injury in osteoblast. Molecular and Cellular Biochemistry, 373(1-2), 1-9. doi: 10.1007/s11010-012-1450-4

 

Consumption of water containing a high concentration of molecular hydrogen reduces oxidative stress and disease activity in patients with rheumatoid arthritis: An open-label pilot study

 

“Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of bone and cartilage. Although its etiology is unknown, the hydroxyl radical has been suggested to be involved in the pathogenesis of RA. The results suggest that the hydroxyl radical scavenger H2 effectively reduces oxidative stress in patients with this condition. The symptoms of RA were significantly improved with high H2 water.”

 

Ishibashi, T., Sato, B., Rikitake, M., Seo, T., Kurokawa, R., Hara, Y., . . . Nagao, T. (2012). Consumption of water containing a high concentration of molecular hydrogen reduces oxidative stress and disease activity in patients with rheumatoid arthritis: An open-label pilot study. Medical Gas Research, 2(27), 1-8. doi: 10.1186/2045-9912-2-27

 

Therapeutic efficacy of infused molecular hydrogen in saline on rheumatoid arthritis: A randomized, double-blind, placebo-controlled pilot study

 

“The aim of this study was to demonstrate the safety and efficacy of H2-saline infusion for treatment of rheumatoid arthritis (RA). We conducted a randomized, double-blind, placebo-controlled investigation of the infusion of 1 ppm H2-dissolved saline (H2-saline) in 24 RA patients. Drop infusion of H2 safely and effectively reduced RA disease activity.”

 

Ishibashi, T., Sato, B., Shibata, S., Sakai, T., Hara, Y., Naritomi, Y., . . . Nagao, T. (2014). Therapeutic efficacy of infused molecular hydrogen in saline on rheumatoid arthritis: A randomized, double-blind, placebo-controlled pilot study. International Immunopharmacology, 21(2), 468-473. doi: 10.1016/j.intimp.2014.06.001

 

Improvement of psoriasis-associated arthritis and skin lesions by treatment with molecular hydrogen: A report of three cases

 

“Psoriasis, a chronic inflammatory skin disease, is caused by infiltrating lymphocytes and associated cytokines, including tumor necrosis factor (TNF) α, interleukin (IL)-6, and IL-17. IL-6 levels decreased during H2 treatment in Case 1 and 2. IL-17, whose concentration was high in Case 1, was reduced following H2 treatment, and TNFα also decreased in Case 1. The psoriatic skin lesions almost disappeared at the end of the treatment. H2 administration reduced inflammation associated with psoriasis in the three cases examined and it may therefore be considered as a treatment strategy for psoriasis-associated skin lesions and arthritis.”

 

Ishibashi, T., Ichikawa, M., Sato, B., Shibata, S., Hara, Y., Naritomi, Y., . . . Nagao, T. (2015). Improvement of psoriasis-associated arthritis and skin lesions by treatment with molecular hydrogen: A report of three cases. Molecular Medicine Reports, 12, 2757-2764. doi: 10.3892/mmr.2015.3707

 

Molecular hydrogen: New antioxidant and anti-inflammatory therapy for rheumatoid arthritis and related diseases

 

“H2 showed significant therapeutic potential, which also seemed to assist diagnosis and treatment decisions of RA. The possible expectations regarding the potential benefits of H2 by reducing the oxidative stress, resulting from inflammatory factors, are raised and discussed here. They include prevention of RA and related atherosclerosis, as well as therapeutic validity for RA.”

 

Ishibashi, T. (2013). Molecular hydrogen: New antioxidant and anti-inflammatory therapy for rheumatoid arthritis and related diseases. Current Pharmaceutical Design, 19(35), 6375-6381. doi: 10.2174/13816128113199990507

 

Hydrogen water consumption prevents osteopenia in ovariectomized rats

 

“Accumulating evidence indicates an important role of oxidative stress in the progression of osteoporosis. HW consumption prevents osteopenia in ovariectomized rats possibly through the ablation of oxidative stress induced by oestrogen withdrawal.”

 

Guo, J., Li, L., Shi, Y., Wang, H., & Hou, S. (2013). Hydrogen water consumption prevents osteopenia in ovariectomized rats. British Journal of Pharmacology, 168(6), 1412-1420. doi: 10.1111/bph.12036 

 

Treatment with hydrogen molecules prevents RANKL-induced osteoclast differentiation associated with inhibition of ROS formation and inactivation of MAPK, AKT and NF-kappa B pathways in murine RAW264.7 cells

 

“The bone protective effects of the hydrogen molecule (H2) have been demonstrated in several osteoporosis models. Hydrogen molecules prevented RANKL-induced osteoclast differentiation associated with inhibition of reactive oxygen species formation and inactivation of NF-κB, mitogen-activated protein kinase and AKT pathways.”

 

Li, D., Zhang, Q., Dong, X., Li, H., & Ma, X. (2013). Treatment with hydrogen molecules prevents RANKL-induced osteoclast differentiation associated with inhibition of ROS formation and inactivation of MAPK, AKT and NF-kappa B pathways in murine RAW264.7 cells. Journal of Bone and Mineral Metabolism, 32(5), 494-504. doi: 10.1007/s00774-013-0530-1

 

Treatment of hydrogen molecule abates oxidative stress and alleviates bone loss induced by modeled microgravity in rats

 

“Treatment with HW alleviated HLS-induced reduction of bone mineral density, ultimate load, stiffness, and energy in femur and lumbar vertebra. Treatment with HW alleviated HLS-induced augmentation of malondialdehyde content and peroxynitrite content and reduction of total sulfhydryl content in femur and lumbar vertebra. Treatment with molecular hydrogen alleviates microgravity-induced bone loss through abating oxidative stress, restoring osteoblastic differentiation, and suppressing osteoclast differentiation and osteoclastogenesis.”

 

Sun, Y., Shuang, F., Chen, D. M., & Zhou, R. B. (2012). Treatment of hydrogen molecule abates oxidative stress and alleviates bone loss induced by modeled microgravity in rats. Osteoporosis International, 24(3), 969-978. doi: 10.1007/s00198-012-2028-4

Bone Health

 

H2 has been shown to alleviate cell injury induced by tumor necrosis factor-alpha, which plays a crucial role in postmenopausal osteoporosis. In rat studies, H2 water was shown to prevent osteopenia in rats.

 

Treatment with hydrogen molecule alleviates TNFα-induced cell injury in osteoblast

 

“Tumor necrosis factor-alpha (TNFα) plays a crucial role in inflammatory diseases such as rheumatoid arthritis and postmenopausal osteoporosis. Recently, it has been demonstrated that hydrogen gas, known as a novel antioxidant, can exert therapeutic anti-inflammatory effect in many diseases. Treatment with H(2) alleviates TNFα-induced cell injury in osteoblast through abating oxidative stress, preserving mitochondrial function, suppressing inflammation, and enhancing NO bioavailability.”

 

Cai, W., Zhang, M., Yu, Y., & Cai, J. (2012). Treatment with hydrogen molecule alleviates TNFα-induced cell injury in osteoblast. Molecular and Cellular Biochemistry, 373(1-2), 1-9. doi: 10.1007/s11010-012-1450-4

 

Hydrogen water consumption prevents osteopenia in ovariectomized rats

 

“Accumulating evidence indicates an important role of oxidative stress in the progression of osteoporosis. HW consumption prevents osteopenia in ovariectomized rats possibly through the ablation of oxidative stress induced by oestrogen withdrawal.”

 

Guo, J., Li, L., Shi, Y., Wang, H., & Hou, S. (2013). Hydrogen water consumption prevents osteopenia in ovariectomized rats. British Journal of Pharmacology, 168(6), 1412-1420. doi: 10.1111/bph.12036

​​

Hydrogen gas treatment prolongs replicative lifespan of bone marrow multipotential stromal cells in vitro while preserving differentiation and paracrine potentials

 

“Hydrogen molecules have been shown to exert organ protective effects through selective reduction of hydroxyl radicals. As oxidative stress is one of the key insults promoting cell senescence in vivo as well as in vitro, we hypothesized that hydrogen molecules prevent senescent process during MSC expansion. Addition of 3% hydrogen gas enhanced preservation of colony forming early progenitor cells within MSC preparation and prolonged the in vitro replicative lifespan of MSCs without losing differentiation potentials and paracrine capabilities.”

 

Kawasaki, H., Guan, J., & Tamama, K. (2010). Hydrogen gas treatment prolongs replicative lifespan of bone marrow multipotential stromal cells in vitro while preserving differentiation and paracrine potentials. Biochemical and Biophysical Research Communications, 397(3), 608-613. doi: 10.1016/j.bbrc.2010.06.009

 

Treatment with hydrogen molecules prevents RANKL-induced osteoclast differentiation associated with inhibition of ROS formation and inactivation of MAPK, AKT and NF-kappa B pathways in murine RAW264.7 cells

 

“The bone protective effects of the hydrogen molecule (H2) have been demonstrated in several osteoporosis models. Hydrogen molecules prevented RANKL-induced osteoclast differentiation associated with inhibition of reactive oxygen species formation and inactivation of NF-κB, mitogen-activated protein kinase and AKT pathways.”

 

Li, D., Zhang, Q., Dong, X., Li, H., & Ma, X. (2013). Treatment with hydrogen molecules prevents RANKL-induced osteoclast differentiation associated with inhibition of ROS formation and inactivation of MAPK, AKT and NF-kappa B pathways in murine RAW264.7 cells. Journal of Bone and Mineral Metabolism, 32(5), 494-504. doi: 10.1007/s00774-013-0530-1

 

Treatment of hydrogen molecule abates oxidative stress and alleviates bone loss induced by modeled microgravity in rats

 

“Treatment with HW alleviated HLS-induced reduction of bone mineral density, ultimate load, stiffness, and energy in femur and lumbar vertebra. Treatment with HW alleviated HLS-induced augmentation of malondialdehyde content and peroxynitrite content and reduction of total sulfhydryl content in femur and lumbar vertebra. Treatment with molecular hydrogen alleviates microgravity-induced bone loss through abating oxidative stress, restoring osteoblastic differentiation, and suppressing osteoclast differentiation and osteoclastogenesis.”

 

Sun, Y., Shuang, F., Chen, D. M., & Zhou, R. B. (2012). Treatment of hydrogen molecule abates oxidative stress and alleviates bone loss induced by modeled microgravity in rats. Osteoporosis International, 24(3), 969-978. doi: 10.1007/s00198-012-2028-4

 

Improvement of psoriasis-associated arthritis and skin lesions by treatment with molecular hydrogen: A report of three cases

 

“Psoriasis, a chronic inflammatory skin disease, is caused by infiltrating lymphocytes and associated cytokines, including tumor necrosis factor (TNF) α, interleukin (IL)-6, and IL-17. IL-6 levels decreased during H2 treatment in Case 1 and 2. IL-17, whose concentration was high in Case 1, was reduced following H2 treatment, and TNFα also decreased in Case 1. The psoriatic skin lesions almost disappeared at the end of the treatment. H2 administration reduced inflammation associated with psoriasis in the three cases examined and it may therefore be considered as a treatment strategy for psoriasis-associated skin lesions and arthritis.”

 

Ishibashi, T., Ichikawa, M., Sato, B., Shibata, S., Hara, Y., Naritomi, Y., . . . Nagao, T. (2015). Improvement of psoriasis-associated arthritis and skin lesions by treatment with molecular hydrogen: A report of three cases. Molecular Medicine Reports, 12(2), 2757-2764. doi: 10.3892/mmr.2015.3707

 

Hydrogen-rich saline may be an effective and specific novel treatment for osteoradionecrosis of the jaw

 

“It has long been known that most radiation-induced symptoms are caused by free radicals generated by radiolysis of H2O, and the hydroxyl radical is the most reactive of these. Reducing the hydroxyl radical can distinctly improve the protection of cells from radiation damage. We hypothesized that hydrogen-rich saline might be an effective and specific method of managing and preventing osteoradionecrosis of the jaw.”

 

Tian, L., Chen, Y., Guo, Y., & Zong, C. (2015). Hydrogen-rich saline may be an effective and specific novel treatment for osteoradionecrosis of the jaw. Therapeutics and Clinical Risk Management, 2015(11), 1581-1585. doi: 10.2147/tcrm.s90770 

Molecular hydrogen protects chondrocytes from oxidative stress and indirectly alters gene expressions through reducing peroxynitrite derived from nitric oxide

 

“These results imply that one of the functions of H2 exhibits cytoprotective effects and transcriptional alterations through reducing ONOO-. Moreover, novel pharmacological strategies aimed at selective removal of ONOO- may represent a powerful method for preventive and therapeutic use of H2 for joint diseases.”

 

Hanaoka, T., Kamimura, N., Yokota, T., Takai, S., & Ohta, S. (2011). Molecular hydrogen protects chondrocytes from oxidative stress and indirectly alters gene expressions through reducing peroxynitrite derived from nitric oxide. Medical Gas Research, 1(18), 1-9. doi: 10.1186/2045-9912-1-18

 

Consumption of water containing a high concentration of molecular hydrogen reduces oxidative stress and disease activity in patients with rheumatoid arthritis: An open-label pilot study

 

“Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by the destruction of bone and cartilage. Although its etiology is unknown, the hydroxyl radical has been suggested to be involved in the pathogenesis of RA. The results suggest that the hydroxyl radical scavenger H2 effectively reduces oxidative stress in patients with this condition. The symptoms of RA were significantly improved with high H2 water.”

 

Ishibashi, T., Sato, B., Rikitake, M., Seo, T., Kurokawa, R., Hara, Y., . . . Nagao, T. (2012). Consumption of water containing a high concentration of molecular hydrogen reduces oxidative stress and disease activity in patients with rheumatoid arthritis: An open-label pilot study. Medical Gas Research, 2(27), 1-8. doi: 10.1186/2045-9912-2-27

 

Molecular hydrogen: New antioxidant and anti-inflammatory therapy for rheumatoid arthritis and related diseases 

 

“H2 showed significant therapeutic potential, which also seemed to assist diagnosis and treatment decisions of RA. The possible expectations regarding the potential benefits of H2 by reducing the oxidative stress, resulting from inflammatory factors, are raised and discussed here. They include prevention of RA and related atherosclerosis, as well as therapeutic validity for RA.”

 

Ishibashi, T. (2013). Molecular hydrogen: New antioxidant and anti-inflammatory therapy for rheumatoid arthritis and related diseases. Current Pharmaceutical Design, 19(35), 6375-6381. doi: 10.2174/13816128113199990507

 
 

Brain Injury

 

A variety of studies shown strong potential for H2 to be a highly effective and easily administered treatment of traumatic brain injury and concussion, and potentially in cases of CTE.  In one study, a treatment with H2 water reduced the acute changes induced controlled cortical impact (CCI) by about half and completely blocked pathological tau expression.

 

Hydrogen is neuroprotective against surgically induced brain injury

 

“Hydrogen appears to be promising as an effective, yet inexpensive way to reduce cerebral edema caused by surgical procedures. Hydrogen has the potential to improve clinical outcome, decrease hospital stay, and reduce overall cost to patients and the health care system.”

 

Eckermann, J. M., Chen, W., Jadhav, V., Hsu, F. P., Colohan, A. R., Tang, J., & Zhang, J. H. (2011). Hydrogen is neuroprotective against surgically induced brain injury. Medical Gas Research, 1(7), 1-6. doi: 10.1186/2045-9912-1-7

 

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

“Hydrogen selectively reduces the hydroxyl radical, the most toxic free radical, and effectively protects cells. It does not react with free radicals that have physiological benefits, making it an incredibly effective therapy to neutralize acute oxidative stress.”

 

Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., . . . Ohta, S. (2007). Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nature Medicine, 13(6), 688-694. doi: 10.1038/nm1577

 

Hydrogen-rich saline alleviates early brain injury via reducing oxidative stress and brain edema following experimental subarachnoid hemorrhage in rabbits

 

“The results suggest that treatment with hydrogen in experimental SAH rabbits could alleviate brain injury via decreasing the oxidative stress injury and brain edema. Hence, we conclude that hydrogen possesses the potential to be a novel therapeutic agent for EBI after SAH.”

 

Zhuang, Z., Zhou, M., You, W., Zhu, L., Ma, C., Sun, X., & Shi, J. (2012). Hydrogen-rich saline alleviates early brain injury via reducing oxidative stress and brain edema following experimental subarachnoid hemorrhage in rabbits. BioMed Central Neuroscience, 13(47), 1-10. doi: 10.1186/1471-2202-13-47

 

 

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

 

“Hydrogen is qualified to cross the blood brain barrier, to enter the mitochondria, and even has the ability to translocate to the nucleus under certain conditions. Once in these ideal locations of the cell, previous studies have shown that hydrogen exerts antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective properties that are beneficial to the cell.”

 

Dixon, B. J., Tang, J., & Zhang, J. H. (2013). The evolution of molecular hydrogen: A noteworthy potential therapy with clinical significance. Medical Gas Research, 3(10), 1-12. doi: 10.1186/2045-9912-3-10

 

Hydrogen inhalation ameliorated mast cell-mediated brain injury after intracerebral hemorrhage in mice

 

“Activation of mast cells following intracerebral hemorrhage contributed to increase of blood-brain barrier permeability and brain edema. Hydrogen inhalation preserved blood-brain barrier disruption by prevention of mast cell activation after intracerebral hemorrhage.”

 

Manaenko, A., Lekic, T., Ma, Q., Zhang, J. H., & Tang, J. (2013). Hydrogen inhalation ameliorated mast cell–mediated brain injury after intracerebral hemorrhage in mice. Critical Care Medicine, 41(5), 1266-1275. doi: 10.1097/ccm.0b013e31827711c9

 

Hydrogen-rich water protects against ischemic brain injury in rats by regulating calcium buffering proteins

 

“Hydrogen-rich water (HRW) has anti-oxidant activities, and it exerts neuroprotective effects during ischemia-reperfusion brain injury. All these results suggest that HRW could protect against ischemic brain injury and that the maintenance of parvalbumin and hippocalcin levels by HRW during ischemic brain injury might contribute to the neuroprotective effects against neuron damage.”

 

Han, L., Tian, R., Yan, H., Pei, L., Hou, Z., Hao, S., . . . Zhang, Q. (2015). Hydrogen-rich water protects against ischemic brain injury in rats by regulating calcium buffering proteins. Brain Research, 1615, 129-138. doi: 10.1016/j.brainres.2015.04.038

 

Neuroprotective effect of hydrogen-rich saline against neurologic damage and apoptosis in early brain injury following subarachnoid hemorrhage: Possible role of the Akt/GSK3β signaling pathway

 

“HS significantly reduced neuronal apoptosis and improved neurological function at 24 hours after SAH. HS could attenuate neuronal apoptosis in EBI and improve the neurofunctional outcome after SAH, partially via the Akt/GSK3β pathway.”

 

Hong, Y., Shao, A., Wang, J., Chen, S., Wu, H., Mcbride, D. W., . . . Zhang, J. (2014). Neuroprotective effect of hydrogen-rich saline against neurologic damage and apoptosis in early brain injury following subarachnoid hemorrhage: Possible role of the Akt/GSK3β signaling pathway. PLOS ONE, 9(4), 1-10. doi: 10.1371/journal.pone.0096212

 

Inhalation of hydrogen gas attenuates brain injury in mice with cecal ligation and puncture via inhibiting neuroinflammation, oxidative stress and neuronal apoptosis

 

“We found that the beneficial effects of H2 on brain injury in septic mice were linked to the decreased levels of inflammatory cytokines and oxidative products and the increased activities of antioxidant enzymes in serum and hippocampus. In addition, 2% H2 inhalation promoted the expression and transposition of Nrf2 and the expression of HO-1 to mitigate brain injury in sepsis. Thus, the inhalation of hydrogen gas may be a promising therapeutic strategy to relieve brain injury in sepsis.”

 

Liu, L., Xie, K., Chen, H., Dong, X., Li, Y., Yu, Y., . . . Yu, Y. (2014). Inhalation of hydrogen gas attenuates brain injury in mice with cecal ligation and puncture via inhibiting neuroinflammation, oxidative stress and neuronal apoptosis. Brain Research, 1589, 78-92. doi: 10.1016/j.brainres.2014.09.030

 

Protective effects of hydrogen on fetal brain injury during maternal hypoxia

 

“Hydrogen treatment improved the body-righting reflex and negative geotropism (P<0.05 vs. room air group). The above-mentioned functional changes caused by hypoxia were not associated with morphology and cell death of oligodendrocytes. Therefore, the maternal hypoxia-induced body weight loss, and functional abnormalities and hydrogen treatment during hypoxia offered a protective effect and improved functions in neonates.”

 

Liu, W., Chen, O., Chen, C., Wu, B., Tang, J., & Zhang, J. H. (2011). Protective effects of hydrogen on fetal brain injury during maternal hypoxia. Acta Neurochirugica Supplement, 111, 307-311. doi: 10.1007/978-3-7091-0693-8_51

 

Hydrogen rich saline reduces immune-mediated brain injury in rats with acute carbon monoxide poisoning

 

“Expression levels of MIP-1-alpha and ICAM-1 increased in the brains of CO-poisoned rats and H(2) rich saline treatment decreased the levels. The results indicate that H(2) rich saline prevents immune-mediated brain injury after CO poisoning.”

 

Wang, W., Li, Y., Ren, J., Xia, F., Li, J., & Zhang, Z. (2012). Hydrogen rich saline reduces immune-mediated brain injury in rats with acute carbon monoxide poisoning. Neurological Research, 34(10), 1007-1015. doi:10.1179/1743132812y.0000000106

 

Hydrogen gas ameliorates oxidative stress in early brain injury after subarachnoid hemorrhage in rats

 

“Hydrogen gas significantly alleviated brain edema and blood-brain barrier disruption, reduced apoptosis, and improved neurologic function at 24 hrs but not 72 hrs after subarachnoid hemorrhage. These effects were associated with the amelioration of oxidative injury of lipid, protein, and DNA. Hydrogen gas could exert its neuroprotective effect against early brain injury after subarachnoid hemorrhage by its antioxidative activity.”

 

Zhan, Y., Chen, C., Suzuki, H., Hu, Q., Zhi, X., & Zhang, J. H. (2012). Hydrogen gas ameliorates oxidative stress in early brain injury after subarachnoid hemorrhage in rats. Critical Care Medicine, 40(4), 1291-1296. doi: 10.1097/ccm.0b013e31823da96d

 

CTE / Concussion / Traumatic Brain Injury (TBI)

 

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

 

“Molecular hydrogen given in drinking water reverses many of the sequelae of controlled cortical impact and suggests that it could be an easily administered, highly effective treatment for traumatic brain injury.”

 

Dohi, K., Kraemer, B. C., Erickson, M. A., Mcmillan, P. J., Kovac, A., Flachbartova, Z., . . . Banks, W. A. (2014). Molecular hydrogen in drinking water protects against neurodegenerative changes induced by traumatic brain injury. PLOS ONE, 9(9), 1-16. doi: 10.1371/journal.pone.0108034

 

Chronic neurodegeneration after traumatic brain injury: Alzheimer disease, chronic traumatic encephalopathy, or persistent neuroinflammation?

 

“It has long been suggested that prior traumatic brain injury (TBI) increases the subsequent incidence of chronic neurodegenerative disorders, including Alzheimer disease, Parkinson disease, and amyotrophic lateral sclerosis. Among these, the association with Alzheimer disease has the strongest support. There is also a long-recognized association between repeated concussive insults and progressive cognitive decline or other neuropsychiatric abnormalities. The latter was first described in boxers as dementia pugilistica, and has received widespread recent attention in contact sports such as professional American football. The term chronic traumatic encephalopathy was coined to attempt to define a "specific" entity marked by neurobehavioral changes and the extensive deposition of phosphorylated tau protein. Nearly lost in the discussions of post-traumatic neurodegeneration after traumatic brain injury has been the role of sustained neuroinflammation, even though this association has been well established pathologically since the 1950s, and is strongly supported by subsequent preclinical and clinical studies. Manifested by extensive microglial and astroglial activation, such chronic traumatic brain inflammation may be the most important cause of post-traumatic neurodegeneration in terms of prevalence. Critically, emerging preclinical studies indicate that persistent neuroinflammation and associated neurodegeneration may be treatable long after the initiating insult(s).”

 

Faden, A. I., & Loane, D. J. (2014). Chronic neurodegeneration after traumatic brain injury: Alzheimer disease, chronic traumatic encephalopathy, or persistent neuroinflammation? Neurotherapeutics, 12(1), 143-150. doi: 10.1007/s13311-014-0319-5 

 

Hydrogen-rich saline protects against oxidative damage and cognitive deficits after mild traumatic brain injury

 

“Oxidative stress is the principal factor in traumatic brain injury (TBI) that initiates events that result in protracted neuronal dysfunction and remodeling. These results suggest that hydrogen-rich saline can protect the brain against the deleterious effects of mild TBI on synaptic plasticity and cognition and that hydrogen-rich saline could be an effective therapeutic strategy for patients with cognitive deficits after TBI.”

 

Hou, Z., Luo, W., Sun, X., Hao, S., Zhang, Y., Xu, F., . . . Liu, B. (2012). Hydrogen-rich saline protects against oxidative damage and cognitive deficits after mild traumatic brain injury. Brain Research Bulletin, 88(6), 560-565. doi: 10.1016/j.brainresbull.2012.06.006

 

Beneficial effects of hydrogen gas in a rat model of traumatic brain injury via reducing oxidative stress

 

“We found that the decrease of oxidative products and the increase of endogenous antioxidant enzymatic activities in the brain tissue may be associated with the protective effects of H(2) treatment in TBI-challenged rats. The present study supports that H(2) inhalation may be a more effective therapeutic strategy for patients with TBI.”

 

Ji, X., Liu, W., Xie, K., Liu, W., Qu, Y., Chao, X., . . . Fei, Z. (2010). Beneficial effects of hydrogen gas in a rat model of traumatic brain injury via reducing oxidative stress. Brain Research, 1354, 196-205. doi: 10.1016/j.brainres.2010.07.03

 

Protective effects of hydrogen-rich saline in a rat model of traumatic brain injury via reducing oxidative stress

 

“TBI-challenged rats exhibited significant brain injuries characterized by the increase of BBB permeability, brain edema, and lesion volume as well as neurological dysfunction, which were dose-dependently ameliorated by HS treatment. Hydrogen-rich saline can exert a protective effect against TBI via reducing oxidative stress. Molecular hydrogen may be a more effective therapeutic strategy for TBI patients.”

 

Ji, X., Tian, Y., Xie, K., Liu, W., Qu, Y., & Fei, Z. (2012). Protective effects of hydrogen-rich saline in a rat model of traumatic brain injury via reducing oxidative stress. Journal of Surgical Research, 178(1), 9-16. doi: 10.1016/j.jss.2011.12.038

 

Cardiovascular Disease

 

Studies point to the potential for H2 combat and ameliorate all facets of cardiovascular disease, including the abilities to lower serum LDL, combat atherosclerosis, regulate hypertension, and reduce chronic inflammation.  A study on rats has shown potential for improved survival rates and neurological outcome after cardiac arrest, and other studies have demonstrated H2’s ability to attenuate the severity of strokes.

 

Hydrogen as a selective antioxidant: A review of clinical and experimental studies

“H2 is emerging as a novel and safe therapeutic antioxidant. It has selective antioxidant properties, giving it anti-inflammatory properties.”

 

Hong, Y., Chen, S., & Zhang, J. (2010). Hydrogen as a selective antioxidant: A review of clinical and experimental studies. Journal of International Medicine Research, 38(6), 1893-1903. doi: 10.1177/147323001003800602​

 

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

“Hydrogen selectively reduces the hydroxyl radical, the most toxic free radical, and effectively protects cells. It does not react with free radicals that have physiological benefits, making it an incredibly effective therapy to neutralize acute oxidative stress.”

 

Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., . . . Ohta, S. (2007). Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nature Medicine, 13(6), 688-694. doi: 10.1038/nm1577

 

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

 

“Hydrogen is qualified to cross the blood brain barrier, to enter the mitochondria, and even has the ability to translocate to the nucleus under certain conditions. Once in these ideal locations of the cell, previous studies have shown that hydrogen exerts antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective properties that are beneficial to the cell.”

 

Dixon, B. J., Tang, J., & Zhang, J. H. (2013). The evolution of molecular hydrogen: A noteworthy potential therapy with clinical significance. Medical Gas Research, 3(10), 1-12. doi: 10.1186/2045-9912-3-10

 

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

“H2 prevented the decline of the mitochondrial membrane potential. This suggested that H2 protected mitochondria from OH. Along with this protective effect, H2 also prevented a decrease in the cellular level of ATP synthesized in mitochondria. The fact that H2 protected mitochondria and nuclear DNA provided evidence that H2 penetrated most membranes and diffused into organelles.” 

 

Ohta, S. (2011). Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventive and therapeutic applications. Current Pharmaceutical Design, 17(22), 2241-2252. doi: 10.2174/138161211797052664

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

 

“Effects of molecular hydrogen on various diseases have been documented for 63 disease models and human diseases in the past four and a half years. Six human diseases have been studied to date: diabetes mellitus type 2, metabolic syndrome, hemodialysis, inflammatory and mitochondrial myopathies, brain stem infarction, and radiation-induced adverse effects.”

 

​​Ohno, K., Ito, M., Ichihara, M., & Ito, M. (2012). Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases. Oxidative Medicine and Cellular Longevity, 2012, 1-11. doi: 10.1155/2012/353152

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

 

“A total of 321 original articles have been published from 2007 to June 2015. Most studies have been conducted in Japan, China, and the USA. The effects have been reported in essentially all organs covering 31 disease categories that can be subdivided into 166 disease models, human diseases, treatment-associated pathologies, and pathophysiological conditions of plants with a predominance of oxidative stress-mediated diseases and inflammatory diseases.”

 

Ichihara, M., Sobue, S., Ito, M., Ito, M., Hirayama, M., & Ohno, K. (2015). Beneficial biological effects and the underlying mechanisms of molecular hydrogen - comprehensive review of 321 original articles. Medical Gas Research, 5(12), 1-21. doi: 10.1186/s13618-015-0035-1

Atherosclerosis

 

H2 has been shown to stop fatty deposits in the blood vessels of the heart in studies involving rats. H2 also was shown to significantly reduce atherosclerotic lesions and decrease oxidative stress in the hearts of mice.

 

Hydrogen-rich water prevents lipid deposition in the descending aorta in a rat periodontitis model

 

“Hydrogen Water intake may prevent lipid deposition in the rat aorta induced by periodontitis by decreasing serum ox-LDL levels and aortic oxidative stress.”

 

Ekuni, D., Tomofuji, T., Endo, Y., Kasuyama, K., Irie, K., Azuma, T., . . . Morita, M. (2012). Hydrogen-rich water prevents lipid deposition in the descending aorta in a rat periodontitis model. Archives of Oral Biology, 57(12), 1615-1622. doi: 10.1016/j.archoralbio.2012.04.013

 

Hydrogen as a selective antioxidant: A review of clinical and experimental studies

“H2 is emerging as a novel and safe therapeutic antioxidant. It has selective antioxidant properties, giving it anti-inflammatory properties.”

 

Hong, Y., Chen, S., & Zhang, J. (2010). Hydrogen as a selective antioxidant: A review of clinical and experimental studies. Journal of International Medical Research, 38(6), 1893-1903. doi: 10.1177/147323001003800602

 

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

“Hydrogen selectively reduces the hydroxyl radical, the most toxic free radical, and effectively protects cells. It does not react with free radicals that have physiological benefits, making it an incredibly effective therapy to neutralize acute oxidative stress.”

 

Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., . . . Ohta, S. (2007). Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nature Medicine, 13(6), 688-694. doi: 10.1038/nm1577

 

Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice

 

“Atherosclerotic lesions were significantly reduced by ad libitum drinking of H2–water (p = 0.0069) as judged by Oil-Red-O staining series of sections of aorta. The oxidative stress level of aorta was decreased. Accumulation of macrophages in atherosclerotic lesions was confirmed. Thus, consumption of H2-dissolved water has the potential to prevent arteriosclerosis.”

 

Ohsawa, I., Nishimaki, K., Yamagata, K., Ishikawa, M., & Ohta, S. (2008). Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice. Biochemical and Biophysical Research Communications, 377(4), 1195-1198. doi: 10.1016/j.bbrc.2008.10.156

 

Hydrogen-rich water prevents lipid deposition in the descending aorta in a rat periodontitis model

 

“Hydrogen Water intake may prevent lipid deposition in the rat aorta induced by periodontitis by decreasing serum ox-LDL levels and aortic oxidative stress.”

 

Ekuni, D., Tomofuji, T., Endo, Y., Kasuyama, K., Irie, K., Azuma, T., . . . Morita, M. (2012). Hydrogen-rich water prevents lipid deposition in the descending aorta in a rat periodontitis model. Archives of Oral Biology, 57(12), 1615-1622. doi: 10.1016/j.archoralbio.2012.04.013

 

Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome

 

“Supplementation with H2-rich water seems to decrease serum LDL-C and apoB levels, improve dyslipidemia-injured HDL functions, and reduce oxidative stress, and it may have a beneficial role in prevention of potential metabolic syndrome.”

 

Song, G., M. Li, H. Sang, L. Zhang, X. Li, S. Yao, Y. Yu, C. Zong, Y. Xue, and S. Qin. (2013). Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome. The Journal of Lipid Research, 54(7), 1884-1893. doi: 10.1194/jlr.M036640

 

Hydrogen-rich saline attenuates lipopolysaccharide-induced heart dysfunction by restoring fatty acid oxidation in rats by mitigating C-jun N-terminal kinase activation

 

“Inhibition of c-Jun N-terminal kinase by Hydrogen-rich saline showed beneficial effects on lipopolysaccharide-challenged rats, at least in part, by restoring cardiac fatty acid oxidation.”

 

Tao, B., Liu, L., Wang, N., Tong, D., Wang, W., & Zhang, J. (2015). Hydrogen-rich saline attenuates lipopolysaccharide-induced heart dysfunction by restoring fatty acid oxidation in rats by mitigating C-jun N-terminal kinase activation. Shock, 44(6), 593-600. doi: 10.1097/SHK.0000000000000467

 

Molecular hydrogen attenuates fatty acid uptake and lipid accumulation through downregulating CD36 expression in HepG2 cells

 

“Hydrogen inhibits fatty acid uptake and lipid accumulation through the downregulation of CD36 at the protein level in hepatic cultured cells, providing insights into the molecular mechanism underlying the hydrogen effects in vivo on lipid metabolism disorders.”

 

Iio, A., Ito, M., Itoh, T., Terazawa, R., Fujita, Y., Nozawa, Y., . . . Ito, M. (2013). Molecular hydrogen attenuates fatty acid uptake and lipid accumulation through downregulating CD36 expression in HepG2 cells. Medical Gas Research, 3(6), 1-7. doi: 10.1186/2045-9912-3-6

 

Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance

“Supplementation with molecular hydrogen-rich water may have a beneficial role in the prevention of type 2 diabetes and insulin resistence by helping to stabilize blood sugar, which is a critical aspect of long-term weight loss.”

 

Kajiyama, S., Hasegawa, G., Asano, M., Hosoda, H., Fukui, M., Nakamura, N., . . . Yoshikawa, T. (2008). Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutrition Research, 28(3), 137-143. doi: 10.1016/j.nutres.2008.01.008

 

Molecular hydrogen improves obesity and diabetes by inducing hepatic FGF21 and stimulating energy metabolism in db/db mice

 

“Long-term drinking H(2)-water significantly controlled fat and body weights, despite no increase in consumption of diet and water. The present results suggest the potential benefit of H(2) in improving obesity, diabetes, and metabolic syndrome”

 

Kamimura, N., Nishimaki, K., Ohsawa, I., & Ohta, S. (2011). Molecular hydrogen improves obesity and diabetes by inducing hepatic FGF21 and stimulating energy metabolism in db/db mice. Obesity, 19(7), 1396-1403. doi: 10.1038/oby.2011.6

 

Molecular hydrogen stimulates the gene expression of transcriptional coactivator PGC-1α to enhance fatty acid metabolism

 

“In wild-type mice fed the fatty diet, H2-water improved the level of plasma triglycerides and extended their average of lifespan. H2 induces expression of the PGC-1αgene, followed by stimulation of the PPARα pathway that regulates FGF21, and the fatty acid and steroid metabolism.”

 

Kamimura, N. Ichimaya, H. Iuchi, K. & Ohta, S. (2016). Molecular hydrogen stimulates the gene expression of transcriptional coactivator PGC-1a to enhance fatty acid metabolism. NPJ Aging and Mechanisms of Disease, 2, 1-8. doi: 10.1038/npjamd.2016.8

 

Molecular hydrogen: new antioxidant and anti-inflammatory therapy for rheumatoid arthritis and related diseases 

 

“H2 showed significant therapeutic potential, which also seemed to assist diagnosis and treatment decisions of RA. The possible expectations regarding the potential benefits of H2 by reducing the oxidative stress, resulting from inflammatory factors, are raised and discussed here. They include prevention of RA and related atherosclerosis, as well as therapeutic validity for RA.”

 

Ishibashi, T. (2013). Molecular hydrogen: New antioxidant and anti-inflammatory therapy for rheumatoid arthritis and related diseases. Current Pharmaceutical Design, 19(35), 6375-6381. doi: 10.2174/13816128113199990507

 

Molecular hydrogen stabilizes atherosclerotic plaque in low-density lipoprotein receptor-knockout mice

 

“Hydrogen (H(2)) attenuates the development of atherosclerosis in mouse models. The inhibitory effects of H(2) on the apoptosis of macrophage-derived foam cells, which take effect by suppressing the activation of the ERS pathway and by activating the Nrf2 antioxidant pathway, might lead to an improvement in atherosclerotic plaque stability.”

 

Song, G., Zong, C., Zhang, Z., Yu, Y., Yao, S., Jiao, P., . . . Qin, S. (2015). Molecular hydrogen stabilizes atherosclerotic plaque in low-density lipoprotein receptor-knockout mice. Free Radical Biology and Medicine, 87, 58-68. doi: 10.1016/j.freeradbiomed.2015.06.018

 

Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label pilot study

 

“Metabolic syndrome is characterized by cardiometabolic 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.  In conclusion, drinking hydrogen rich water represents a potentially novel therapeutic and preventive strategy for metabolic syndrome.” 

 

Nakao, A., Toyoda, Y., Sharma, P., Evans, M., & Guthrie, N. (2010). Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome—An open label pilot study. Journal of Clinical Biochemistry and Nutrition, 46(2), 140-149. doi: 10.3164/jcbn.09-100

 

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

 

“Hydrogen is qualified to cross the blood brain barrier, to enter the mitochondria, and even has the ability to translocate to the nucleus under certain conditions. Once in these ideal locations of the cell, previous studies have shown that hydrogen exerts antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective properties that are beneficial to the cell.” 

 

Dixon, B. J., Tang, J., & Zhang, J. H. (2013). The evolution of molecular hydrogen: A noteworthy potential therapy with clinical significance. Medical Gas Research, 3(10), 1-12. doi:10.1186/2045-9912-3-10

 

Blood Clots

 

Hydrogen therapy reduces hydroxyl radical and increases endogenous antioxidants caused by oxidative stress

 

“Hydrogen therapy reduces hydroxyl radical and increases endogenous antioxidants caused by oxidative stress. Molecular hydrogen is proposed to be protective by increasing endogenous antioxidants in addition to scavenging the hydroxyl radical after an injury such as oxidative stress. Hydrogen is qualified to cross the blood brain barrier, to enter the mitochondria, and even has the ability to translocate to the nucleus under certain conditions. Once in these ideal locations of the cell, previous studies have shown that hydrogen exerts antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective properties that are beneficial to the cell.”

Dixon, B. J., Tang, J., & Zhang, J. H. (2013). The evolution of molecular hydrogen: A noteworthy potential therapy with clinical significance.  ​Medical Gas Research, 3(10), 1-12. doi: 10.1186/2045-9912-3-10

Hydrogen-rich water prevents lipid deposition in the descending aorta in a rat periodontitis model

 

“Hydrogen Water intake may prevent lipid deposition in the rat aorta induced by periodontitis by decreasing serum ox-LDL levels and aortic oxidative stress.”

 

Ekuni, D., Tomofuji, T., Endo, Y., Kasuyama, K., Irie, K., Azuma, T., . . . Morita, M. (2012). Hydrogen-rich water prevents lipid deposition in the descending aorta in a rat periodontitis model. Archives of Oral Biology, 57(12), 1615-1622. doi: 10.1016/j.archoralbio.2012.04.013

 

Hydrogen as a selective antioxidant: A review of clinical and experimental studies

“H2 is emerging as a novel and safe therapeutic antioxidant. It has selective antioxidant properties, giving it anti-inflammatory properties.”

 

Hong, Y., Chen, S., & Zhang, J. (2010). Hydrogen as a selective antioxidant: A review of clinical and experimental studies. Journal of International Medical Research, 38(6), 1893-1903.  ​doi: 10.1177/147323001003800602 

 

Hydrogen-rich saline improves survival and neurological outcome after cardiac arrest and cardiopulmonary resuscitation in rats

 

“Hydrogen-rich saline treatment improved survival and neurological outcome after cardiac arrest/resuscitation in rats, which was partially mediated by reducing oxidative stress, inflammation, and apoptosis.”

                            

Huo, T., Zeng, Y., Liu, X., Sun, L., Han, H., Chen, H., . . . Xiong, L. (2014). Hydrogen-rich saline improves survival and neurological outcome after cardiac arrest and cardiopulmonary resuscitation in rats. Anesthesia & Analgesia, 119(2), 368-380. doi: 10.1213/ane.0000000000000303 

Hydrogen-supplemented drinking water protects cardiac allografts from inflammation-associated deterioration

 

“Drinking hydrogen water prolongs survival of cardiac allografts and reduces intimal hyperplasia of aortic allografts.”

 

Noda, K., Tanaka, Y., Shigemura, N., Kawamura, T., Wang, Y., Masutani, K., . . . Nakao, A. (2012). Hydrogen-supplemented drinking water protects cardiac allografts from inflammation-associated deterioration. Transplant International, 25(12), 1213-1222. doi: 10.1111/j.1432-2277.2012.01542.x 

 ​

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

“Hydrogen selectively reduces the hydroxyl radical, the most toxic free radical, and effectively protects cells. It does not react with free radicals that have physiological benefits, making it an incredibly effective therapy to neutralize acute oxidative stress.”

Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., . . . Ohta, S. (2007). Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nature Medicine, 13(6), 688-694. doi: 10.1038/nm1577

Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice

 

“Atherosclerotic lesions were significantly reduced by ad libitum drinking of H2–water (p = 0.0069) as judged by Oil-Red-O staining series of sections of aorta. The oxidative stress level of aorta was decreased. Accumulation of macrophages in atherosclerotic lesions was confirmed. Thus, consumption of H2-dissolved water has the potential to prevent arteriosclerosis.”

 

Ohsawa, I., Nishimaki, K., Yamagata, K., Ishikawa, M., & Ohta, S. (2008). Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice. Biochemical and Biophysical Research Communications, 377(4), 1195-1198. doi: 10.1016/j.bbrc.2008.10.156 

 

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

 

“Molecular hydrogen has been observed to have beneficial effects for a variety of disease models, including myocardial infarcation and atherosclerosis.”

 

Ohno, K., Ito, M., Ichihara, M., & Ito, M. (2012). Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases. Oxidative Medicine and Cellular Longevity, 2012, 1-11. doi: 10.1155/2012/353152  

 

 

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

“H2 prevented the decline of the mitochondrial membrane potential. This suggested that H2 protected mitochondria from OH. Along with this protective effect, H2 also prevented a decrease in the cellular level of ATP synthesized in mitochondria. The fact that H2 protected mitochondria and nuclear DNA provided evidence that H2 penetrated most membranes and diffused into organelles.” 

 

Ohta, S. (2011). Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventive and therapeutic applications. Current Pharmaceutical Design, 17(22), 2241-2252. doi: 10.2174/138161211797052664 

Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome

 

“Supplementation with H2-rich water seems to decrease serum LDL-C and apoB levels, improve dyslipidemia-injured HDL functions, and reduce oxidative stress, and it may have a beneficial role in prevention of potential metabolic syndrome.”

 

Song, G., M. Li, H. Sang, L. Zhang, X. Li, S. Yao, Y. Yu, C. Zong, Y. Xue, and S. Qin. (2013). Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome. The Journal of Lipid Research, 54(7), 1884-1893. doi: 10.1194/jlr.M036640

 
 

Cholesterol Balance

 

Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome

 

“Supplementation with H2-rich water seems to decrease serum LDL-C and apoB levels, improve dyslipidemia-injured HDL functions, and reduce oxidative stress, and it may have a beneficial role in prevention of potential metabolic syndrome.”

 

Song, G., M. Li, H. Sang, L. Zhang, X. Li, S. Yao, Y. Yu, C. Zong, Y. Xue, and S. Qin. (2013). Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome. The Journal of Lipid Research, 54(7), 1884-1893. doi: 10.1194/jlr.M036640

​​

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

 

“Hydrogen is qualified to cross the blood brain barrier, to enter the mitochondria, and even has the ability to translocate to the nucleus under certain conditions. Once in these ideal locations of the cell, previous studies have shown that hydrogen exerts antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective properties that are beneficial to the cell.” 

 

Dixon, B. J., Tang, J., & Zhang, J. H. (2013). The evolution of molecular hydrogen: A noteworthy potential therapy with clinical significance. Medical Gas Research, 3(10), 1-12.  doi: 10.1186/2045-9912-3-10 

Hydrogen activates ATP-binding cassette transporter A1-dependent efflux ex vivo and improves high-density lipoprotein function in patients with hypercholesterolemia: A double-blinded, randomised and placebo-controlled trial

 

“H2 activates ATP-binding cassette transporter A1-dependent efflux, enhances HDL antiatherosclerotic functions, and has beneficial lipid-lowering effects. The present findings highlight the potential role of H2 in the regression of hypercholesterolemia and atherosclerosis.”

 

Song, G., Lin, Q., Zhao, H., Liu, M., Ye, F., Sun, Y., . . . Qin, S. (2015). Hydrogen activates ATP-binding cassette transporter A1-dependent efflux ex vivo and improves high-density lipoprotein function in patients with hypercholesterolemia: A double-blinded, randomized, and placebo-controlled trial. The Journal of Clinical Endocrinology & Metabolism, 100(7), 2724-2733. doi: 10.1210/jc.2015-1321

 

Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome-an open label pilot study

 

“Metabolic syndrome is characterized by cardiometabolic 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.  In conclusion, drinking hydrogen rich water represents a potentially novel therapeutic and preventive strategy for metabolic syndrome.” 

 

Nakao, A., Toyoda, Y., Sharma, P., Evans, M., & Guthrie, N. (2010). Effectiveness of hydrogen rich water on antioxidant status of subjects with potential metabolic syndrome—An open label pilot study. Journal of Clinical Biochemistry and Nutrition, 46(2), 140-149. doi: 10.3164/jcbn.09-100

 

Administration of hydrogen-saturated saline decreases plasma low-density lipoprotein cholesterol levels and improves high-density lipoprotein function in high-fat diet-fed hamsters

 

“Administration of hydrogen-saturated saline decreases plasma LDL cholesterol and apo B levels and improves hyperlipidemia-injured HDL functions, including the capacity of enhancing cellular cholesterol efflux and playing antioxidative properties, in high-fat diet-fed hamsters.”

 

Zong, C., Song, G., Yao, S., Li, L., Yu, Y., Feng, L., . . . Qin, S. (2012). Administration of hydrogen-saturated saline decreases plasma low-density lipoprotein cholesterol levels and improves high-density lipoprotein function in high-fat diet–fed hamsters. Metabolism, 61(6), 794-800. doi: 10.1016/j.metabol.2011.10.014

 

Hydrogen-rich water prevents lipid deposition in the descending aorta in a rat periodontitis model

 

“Hydrogen Water intake may prevent lipid deposition in the rat aorta induced by periodontitis by decreasing serum ox-LDL levels and aortic oxidative stress.”

 

Ekuni, D., Tomofuji, T., Endo, Y., Kasuyama, K., Irie, K., Azuma, T., . . . Morita, M. (2012). Hydrogen-rich water prevents lipid deposition in the descending aorta in a rat periodontitis model. Archives of Oral Biology, 57(12), 1615-1622. doi: 10.1016/j.archoralbio.2012.04.013

 

Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance

“Supplementation with molecular hydrogen-rich water may have a beneficial role in the prevention of type 2 diabetes and insulin resistence by helping to stabilize blood sugar, which is a critical aspect of long-term weight loss.”

 

Kajiyama, S., Hasegawa, G., Asano, M., Hosoda, H., Fukui, M., Nakamura, N., . . . Yoshikawa, T. (2008). Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutrition Research, 28(3), 137-143. doi: 10.1016/j.nutres.2008.01.008

 

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

 

“Effects of molecular hydrogen on various diseases have been documented for 63 disease models and human diseases in the past four and a half years. Six human diseases have been studied to date: diabetes mellitus type 2, metabolic syndrome, hemodialysis, inflammatory and mitochondrial myopathies, brain stem infarction, and radiation-induced adverse effects.”

 

Ohno, K., Ito, M., Ichihara, M., & Ito, M. (2012). Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases. Oxidative Medicine and Cellular Longevity, 2012, 1-11. doi: 10.1155/2012/353152

 

H2 inhibits TNF-α-induced lectin-like oxidized LDL receptor-1 expression by inhibiting nuclear factor κB activation in endothelial cells

 

“H(2) is a therapeutic antioxidant that can reduce oxidative stress. Oxidized low-density lipoprotein, which plays roles in atherosclerosis, may promote endothelial dysfunction by binding the cell-surface receptor LOX-1. H(2) inhibited the expression of LOX-1 and the activation of NF-κB in apolipoprotein E knockout mice, an animal model of atherosclerosis. Thus, H(2) probably inhibits cytokine-induced LOX-1 gene expression by suppressing NF-κB activation.”

 

Song, G., Tian, H., Liu, J., Zhang, H., Sun, X., & Qin, S. (2011). H2 inhibits TNF-α-induced lectin-like oxidized LDL receptor-1 expression by inhibiting nuclear factor κB activation in endothelial cells. Biotechnology Letters, 33(9), 1715-1722. doi: 10.1007/s10529-011-0630-8

 

Molecular hydrogen stabilizes atherosclerotic plaque in low-density lipoprotein receptor-knockout mice

 

“Hydrogen (H(2)) attenuates the development of atherosclerosis in mouse models. The inhibitory effects of H(2) on the apoptosis of macrophage-derived foam cells, which take effect by suppressing the activation of the ERS pathway and by activating the Nrf2 antioxidant pathway, might lead to an improvement in atherosclerotic plaque stability.”

 

Song, G., Zong, C., Zhang, Z., Yu, Y., Yao, S., Jiao, P., . . . Qin, S. (2015). Molecular hydrogen stabilizes atherosclerotic plaque in low-density lipoprotein receptor-knockout mice. Free Radical Biology and Medicine, 87, 58-68. doi: 10.1016/j.freeradbiomed.2015.06.018

Hypertension Regulation

 

Concomitant inhibition of oxidative stress and angiogenesis by chronic hydrogen-rich saline and N-acetylcysteine treatments improves systemic, splanchnic and hepatic hemodynamics of cirrhotic rats

 

“Both hydrogen-rich saline and N-acetylcysteine alleviate portal hypertension, the severity of portosystemic collaterals, mesenteric angiogenesis, hepatic endothelial dysfunction and intrahepatic resistance in cirrhotic rats. N-Acetylcysteine and the new antioxidant, hydrogen-rich saline are potential treatments for the complications of cirrhosis.”

 

Lee, P., Yang, Y., Huang, C., Hsieh, S., Lee, K., Hsieh, Y., . . . Lin, H. (2014). Concomitant inhibition of oxidative stress and angiogenesis by chronic hydrogen-rich saline and N-acetylcysteine treatments improves systemic, splanchnic and hepatic hemodynamics of cirrhotic rats. Hepatology Research, 45(5), 578-588. doi: 10.1111/hepr.12379

 

Heart Attack

 

Hydrogen-containing saline attenuates doxorubicin-induced heart failure in rats

 

“Cardiac function was significantly improved and that the plasma levels of oxidative-stress markers and myocardial autophagic activity were decreased in animals treated with hydrogen-containing saline. Therefore, we conclude that hydrogen-containing saline may have beneficial effects for doxorubicin-induced heart failure.”

 

Wu, S., Zhu, L., Yang, J., Fan, Z., Dong, Y., Luan, R., . .  . Fu, L. (2014). Hydrogen-containing saline attenuates doxorubicin-induced heart failure in rats. Pharmazie, 69(8), 633-636. doi: 10.1691/ph.2014.3859

 

Improving outcomes from resuscitation: From hypertension and hemodilution to therapeutic hypothermia to H2

 

“The benefits of H2 gas were documented in their prior work using a similar rat model of cardiac arrest resuscitated with 100% oxygen. Improvement of cardiac function with hydrogen inhalation was highlighted. The salutary impact of H2 gas was at least partially attributed to its radical-scavenging effect.”

 

Drabek, T., & Kochanek, P. M. (2014). Improving outcomes from resuscitation: From hypertension and hemodilution to therapeutic hypothermia to H2. Circulation, 130(24), 2133-2135. doi: 10.1161/circulationaha.114.013566

 

H2 gas improves functional outcome after cardiac arrest to an extent comparable to therapeutic hypothermia in a rat model

 

“H2 gas inhalation, but not TH, prevented a rise in left ventricular end-diastolic pressure and increase in serum IL-6 level after ROSC. The salutary impact of H2 gas was at least partially attributed to the radical-scavenging effects of H2 gas, because both 8-OHdG- and 4-HNE-positive cardiomyocytes were markedly suppressed by H2 gas inhalation after ROSC. Inhalation of H2 gas is a favorable strategy to mitigate mortality and functional outcome of post-CA syndrome in a rat model, either alone or in combination with TH.”

 

Hayashida, K., Sano, M., Kamimura, N., Yokota, T., Suzuki, M., Maekawa, Y., . . . Hori, S. (2012). H2 gas improves functional outcome after cardiac arrest to an extent comparable to therapeutic hypothermia in a rat model. Journal of the American Heart Association, 1(5). doi: 10.1161/jaha.112.003459

 

Hydrogen inhalation during normoxic resuscitation improves neurological outcome in a rat model of cardiac arrest independently of targeted temperature management

 

“H2 inhalation was beneficial when begun after ROSC, even when delivered in the absence of hyperoxia. Combined TTM and H2 inhalation was more effective than TTM alone.”

 

Hayashida, K., Sano, M., Kamimura, N., Yokota, T., Suzuki, M., Ohta, S., . . . Hori, S. (2015). Response to letter regarding article, “Hydrogen inhalation during normoxic resuscitation improves neurological outcome in a rat model of cardiac arrest independently of targeted temperature management.” Circulation, 132(11), 1-2. doi: 10.1161/circulationaha.115.016785

 

Hydrogen-rich saline improves survival and neurological outcome after cardiac arrest and cardiopulmonary resuscitation in rats

 

“Hydrogen-rich saline treatment improved survival and neurological outcome after cardiac arrest/resuscitation in rats, which was partially mediated by reducing oxidative stress, inflammation, and apoptosis.”

 

Huo, T., Zeng, Y., Liu, X., Sun, L., Han, H., Chen, H., . . . Xiong, L. (2014). Hydrogen-rich saline improves survival and neurological outcome after cardiac arrest and cardiopulmonary resuscitation in rats. Anesthesia & Analgesia, 119(2), 368-380. doi: 10.1213/ane.0000000000000303

 

The effect of hydrogen gas on a mouse bilateral common carotid artery occlusion

 

“The reduction of the expression of 8-OHdG, the decrease in the neuronal injury in the hippocampal CA1 sector, and the attenuation in brain water content were observed in hydrogen-treated mice. In conclusion, hydrogen gas might be effective in a mouse BCCAO model.”

 

Nagatani, K., Takeuchi, S., Kobayashi, H., Otani, N., Wada, K., Fujita, M., . . . Shima, K. (2013). The effect of hydrogen gas on a mouse bilateral common carotid artery occlusion. Acta Neurochirurgica Supplement, 118, 61-63. doi: 10.1007/978-3-7091-1434-6_10

 

Breathing nitric oxide plus hydrogen gas reduces ischemia-reperfusion injury and nitrotyrosine production in murine heart

 

“Breathing NO + H₂ during I/R reduced the infarct size and maintained cardiac function, and reduced the generation of myocardial nitrotyrosine associated with NO inhalation. Administration of NO + H₂ gases for inhalation may be useful for planned coronary interventions or for the treatment of I/R injury.”

 

Shinbo, T., Kokubo, K., Sato, Y., Hagiri, S., Hataishi, R., Hirose, M., & Kobayashi, H. (2013). Breathing nitric oxide plus hydrogen gas reduces ischemia-reperfusion injury and nitrotyrosine production in murine heart. American Journal of Physiology and Circulatory Physiology, 305(4), 542-550. doi: 10.1152/ajpheart.00844.2012

 
 
 

Stroke

 

Rats were subjected to a blockage of their left cerebral arteries and then exposed to hydrogen gas. The rats showed significantly smaller infarction (a type of stroke) volumes compared to controls. The study attributed the beneficial effect to H2's scavenging ability of hydroxyl radicals.

 

​​

Hydrogen inhalation ameliorated mast cell-mediated brain injury after intracerebral hemorrhage in mice

 

“Activation of mast cells following intracerebral hemorrhage contributed to increase of blood-brain barrier permeability and brain edema. Hydrogen inhalation preserved blood-brain barrier disruption by prevention of mast cell activation after intracerebral hemorrhage.”

 

Manaenko, A., Lekic, T., Ma, Q., Zhang, J. H., & Tang, J. (2013). Hydrogen inhalation ameliorated mast cell–mediated brain injury after intracerebral hemorrhage in mice. Critical Care Medicine, 41(5), 1266-1275. doi: 10.1097/ccm.0b013e31827711c9

 ​

Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventative and therapeutic applications

“H2 prevented the decline of the mitochondrial membrane potential. This suggested that H2 protected mitochondria from OH. Along with this protective effect, H2 also prevented a decrease in the cellular level of ATP synthesized in mitochondria. The fact that H2 protected mitochondria and nuclear DNA provided evidence that H2 penetrated most membranes and diffused into organelles.” 

 

Ohta, S. (2011). Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventative and therapeutic applications. Current Pharmaceutical Design, 17(22), 2241-2252. doi: 10.2174/138161211797052664 

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

 

“Effects of molecular hydrogen on various diseases have been documented for 63 disease models and human diseases in the past four and a half years. Six human diseases have been studied to date: diabetes mellitus type 2, metabolic syndrome, hemodialysis, inflammatory and mitochondrial myopathies, brain stem infarction, and radiation-induced adverse effects.”

 

​​Ohno, K., Ito, M., Ichihara, M., & Ito, M. (2012). Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases. Oxidative Medicine and Cellular Longevity, 2012, 1-11. doi: 10.1155/2012/353152

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

 

“A total of 321 original articles have been published from 2007 to June 2015. Most studies have been conducted in Japan, China, and the USA. The effects have been reported in essentially all organs covering 31 disease categories that can be subdivided into 166 disease models, human diseases, treatment-associated pathologies, and pathophysiological conditions of plants with a predominance of oxidative stress-mediated diseases and inflammatory diseases.”

 

Ichihara, M., Sobue, S., Ito, M., Ito, M., Hirayama, M., & Ohno, K. (2015). Beneficial biological effects and the underlying mechanisms of molecular hydrogen - comprehensive review of 321 original articles. Medical Gas Research, 5(12), 1-21. doi: 10.1186/s13618-015-0035-1

 

Molecular hydrogen: An overview of its neurobiological effects and therapeutic potential for bipolar disorder and schizophrenia

 

“Hydrogen gas is a bioactive molecule that has a diversity of effects, including anti-apoptotic, anti-inflammatory and anti-oxidative properties. Therefore, it is hypothesized that administration of hydrogen molecule may have potential as a novel therapy for bipolar disorder, schizophrenia, and other concurrent disorders characterized by oxidative, inflammatory and apoptotic dysregulation.”

 

Ghanizadeh, A., & Berk, M. (2013). Molecular hydrogen: An overview of its neurobiological effects and therapeutic potential for bipolar disorder and schizophrenia. Medical Gas Research, 3(11), 1-6. doi: 10.1186/2045-9912-3-11

 

Improved brain MRI indices in the acute brain stem infarct sites treated with hydroxyl radical scavengers, Edaravone and hydrogen, as compared to Edaravone alone. A non-controlled study

 

“Administration of hydroxyl radical scavengers in acute stage of brainstem infarction improved MRI indices against the natural course. The effects were more obvious and significant in the EH group. These findings may imply the need for more frequent daily administration of hydroxyl scavenger, or possible additional hydrogen effects on scavenger mechanisms.”

 

Ono, H., Nishijima, Y., Adachi, N., Tachibana, S., Chitoku, S., Mukaihara, S., . . . Nawashiro, H. (2011). Improved brain MRI indices in the acute brain stem infarct sites treated with hydroxyl radical scavengers, Edaravone and hydrogen, as compared to Edaravone alone. A non-controlled study. Medical Gas Research, 1(12), 1-9. doi: 10.1186/2045-9912-1-12

 

Hydrogen improves neurological function through attenuation of blood–brain barrier disruption in spontaneously hypertensive stroke-prone rats

 

“This study suggests that ingestion of hydrogen-rich water can improve neurological function due to its ability to penetrate the blood-brain barrier and neutralize reactive oxygen species.”

 

Takeuchi, S., Nagatani, K., Otani, N., Nawashiro, H., Sugawara, T., Wada, K., & Mori, K. (2015). Hydrogen improves neurological function through attenuation of blood–brain barrier disruption in spontaneously hypertensive stroke-prone rats. BioMed Central Neuroscience, 16(22), 1-13. doi: 10.1186/s12868-015-0165-3

 

Cancer

 

H2 prevents oxidative stress and regulates gene expression and also alleged symptoms from radiation therapy. H2 has also been shown to halt tumor growth and convert cancer cells back to normal cells due to its selective free radical scavenging ability. Significant benefits have been demonstrated for a number of different cancers, including liver, tongue, and colon cancer cells.

 

Hydrogen as a selective antioxidant: A review of clinical and experimental studies

“H2 is emerging as a novel and safe therapeutic antioxidant. It has selective antioxidant properties, giving it anti-inflammatory properties.”

 

Hong, Y., Chen, S., & Zhang, J. (2010). Hydrogen as a selective antioxidant: A review of clinical and experimental studies. Journal of International Medical Research, 38(6), 1893-1903. doi: 10.1177/147323001003800602

 

Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors

 

“The consumption of 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 hydrogen-rich water compared to patients receiving placebo water. Daily consumption of 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.”

 

Kang, KM., Kang, YM., et al. (2011). Effects of drinking hydrogen-rich water on the quality of life of patients treated with radiotherapy for liver tumors. Medical Gas Research, 1(11), 1-8. doi: 10.1186/2045-9912-1-11

 

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

 

“Effects of molecular hydrogen on various diseases have been documented for 63 disease models and human diseases in the past four and a half years. Six human diseases have been studied to date: diabetes mellitus type 2, metabolic syndrome, hemodialysis, inflammatory and mitochondrial myopathies, brain stem infarction, and radiation-induced adverse effects.”

 

Ohno, K., Ito, M., Ichihara, M., & Ito, M. (2012). Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases. Oxidative Medicine and Cellular Longevity, 2012, 1-11. doi: 10.1155/2012/353152

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

“Hydrogen selectively reduces the hydroxyl radical, the most toxic free radical, and effectively protects cells. It does not react with free radicals that have physiological benefits, making it an incredibly effective therapy to neutralize acute oxidative stress.”

 

Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., . . . Ohta, S. (2007). Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nature Medicine, 13(6), 688-694. doi: 10.1038/nm1577

 

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

“H2 prevented the decline of the mitochondrial membrane potential. This suggested that H2 protected mitochondria from OH. Along with this protective effect, H2 also prevented a decrease in the cellular level of ATP synthesized in mitochondria. The fact that H2 protected mitochondria and nuclear DNA provided evidence that H2 penetrated most membranes and diffused into organelles.” 

 

Ohta, S. (2011). Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventive and therapeutic applications. Current Pharmaceutical Design, 17(22), 2241-2252. doi: 10.2174/138161211797052664

Platinum nanocolloid-supplemented hydrogendissolved water inhibits growth of human tongue carcinoma cells preferentially over normal cells

 

“Anti-cancer activity of Pt-nc-supplemented HD-water was shown by its preferential cell-growth inhibition to human tongue carcinoma cells HSC-4 over normal human tongue cells DOK, and might be partly attributed to HD-water-caused enhancement of Pt-nc-relevant antioxidant ability. Pt-nc-supplemented HD-water is expected as a novel agent against human tongue cancers due to its cancer progression-repressive abilities.”

 

Saitoh, Y., Yoshimura, Y., Nakano, K., Miwa, N. (2009). Platinum nanocolloid-supplemented hydrogen dissolved water inhibits growth of human tongue carcinoma cells preferentially over normal cells. Experimental Oncology, 31(3), 156-162. Retrieved from http://exp-oncology.com.ua/uploads/magazine/772.pdf?upload 

Neutral pH hydrogen-enriched electrolyzed water achieves tumor-preferential clonal growth inhibition over normal cells and tumor invasion inhibition concurrently with intracellular oxidant repression

 

“NHE water diminished hydroxyl radicals as demonstrated by ESR in a cell-free system. NHE water was shown to achieve tumor-preferential growth inhibition and tumor invasion together with scavenging of intracellular oxidants, and is expected as a preventive material against tumor progression and invasion.”

 

Saitoh, Y., Okayasu, H., Xiao, L., Harata, Y., & Miwa, N. (2008). Neutral pH hydrogen-enriched electrolyzed water achieves tumor-preferential clonal growth inhibition over normal cells and tumor invasion inhibition concurrently with intracellular oxidant repression. Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics, 17(6), 247-255. doi: 10.3727/096504008786991620

 

Hydrogen-water enhances 5-fluorouracil-induced inhibition of colon cancer

 

“Oxidative stress is involved in cancer development. Hydrogen (H2) is a potent antioxidant and exhibits anti-inflammatory and potentially anticancer-like activities. High-content hydrogen water can inhibit colon cancer, particularly in combination with 5-fluorouracil.”

 

Runtuwene, J., Amitani, H., Amitani, M., Asakawa, A., Cheng, K., & Inui, A. (2015). Hydrogen–water enhances 5-fluorouracil-induced inhibition of colon cancer. PeerJ, 3, 1-15. doi: 10.7717/peerj.859 

Growth suppression of HL60 and L6 cells by atomic hydrogen

 

“We previously reported electrolyzed reduced water (ERW) which produced near the cathode by electrolysis has a reductive activity. We also revealed that ERW contains both molecular hydrogen and platinum nanoparticles (Pt nps) derived from platinum-coated titanium electrodes. These results suggest that atomic hydrogen catalyzed by Pt nps induced significant cell growth suppression and atomic hydrogen may be one of new signal of cell function.”

 

Nakanishi, K., Hamasaki, T., Nakamura, T., Abe, M., Teruya, K., Katakura, Y., . . . Shirahata, S. (2010). Growth Suppression of HL60 and L6 Cells by Atomic Hydrogen. Animal Cell Technology: Basic and Applied Aspects, 16, 323-325. doi: 10.1007/978-90-481-3892-0_53

 

Consumption of hydrogen-rich water protects against ferric nitrilotriacetate-induced nephrotoxicity and early tumor promotional events in rats

 

“Consumption with HW decreased the incidence of renal cell carcinoma and suppressed tumor growth in Fe-NTA-treated in rats. In conclusion, drinking with HW attenuated Fe-NTA-induced renal injury and inhibited early tumor promotional events in rats.”

 

Li, F., Zhu, S., Wang, Z., Wang, H., Zhao, Y., & Chen, G. (2013). Consumption of hydrogen-rich water protects against ferric nitrilotriacetate-induced nephrotoxicity and early tumor promotional events in rats. Food and Chemical Toxicology, 61, 248-254. doi: 10.1016/j.fct.2013.10.004

 

Hydrogen protects mice from radiation induced thymic lymphoma in BALB/c mice

 

“Ionizing radiation (IR) is a well-known carcinogen, however the mechanism of radiation induced thymic lymphoma is not well known. Hydrogen, or H(2), is seldom regarded as an important agent in medical usage, especially as a therapeutic gas. Here in this study, we found that H(2) protects mice from radiation induced thymic lymphoma in BALB/c mice.”

 

Zhao, L., Zhou, C., Zhang, J., Gao, F., Li, B., Chuai, Y., . . . Cai, J. (2011). Hydrogen protects mice from radiation induced thymic lymphoma in BALB/c mice. International Journal of Biological Sciences, 7(3), 297-300. doi: 10.7150/ijbs.7.297

 

Hyperbaric hydrogen therapy: A possible treatment for cancer

 

“Hairless albino mice with squamous cell carcinoma were exposed to a mixture of 2.5 percent oxygen and 97.5 percent hydrogen 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 hydrogen, would cause a regression of the skin tumors. Marked aggression of the tumors was found, leading to the possibility that hyperbaric hydrogen therapy might also prove to be of significance in the treatment of other types of cancer.”

 

Dole, M., Wilson, F., & Fife, W. (1975). Hyperbaric hydrogen therapy: A possible treatment for cancer. Science, 190(4210), 152-154. doi: 10.1126/science.1166304

 

Hydrogen-rich water improves neurological functional recovery in experimental autoimmune encephalomyelitis mice

 

“Because HRW is non-toxic, inexpensive, easily administered, and can readily cross the blood-brain barrier, our experiments suggest that HRW may have great potential in the treatment of Multiple sclerosis.”

 

Zhao, M., Liu, M., Pu, Y., Wang, D., Xie, Y., Xue, G., . . . Cao, L. (2016). Hydrogen-rich water improves neurological functional recovery in experimental autoimmune encephalomyelitis mice. Journal of Neuroimmunology, 294, 6-13. doi: 10.1016/j.jneuroim.2016.03.006

 

Hydrogen-rich water prevents progression of nonalcoholic steatohepatitis and accompanying hepatocarcinogenesis in mice

 

“Oxidative stress is a strong contributor to the progression from simple fatty liver to nonalcoholic steatohepatitis (NASH). Consumption of hydrogen-rich water may be an effective treatment for NASH by reducing hepatic oxidative stress, apoptosis, inflammation, and hepatocarcinogenesis.”

 

Kawai, D., Takaki, A., Nakatsuka, A., Wada, J., Tamaki, N., Yasunaka, T., . . . Yamamoto, K. (2012). Hydrogen-rich water prevents progression of nonalcoholic steatohepatitis and accompanying hepatocarcinogenesis in mice. Hepatology, 56(3), 912-921. doi: 10.1002/hep.25782

 

Hydrogen-rich saline attenuate chemotherapy-induced ovarian injury via regulation of oxidative stress

 

“Hydrogen has been reported to exert a therapeutic effect in several diseases due to its antioxidative, anti-inflammatory and anti-apoptotic properties. Hydrogen‑rich saline exerts a protective effect against cisplatin-induced ovarian injury by reducing MDA and increasing SOD and CAT activity. Ovarian injury induced by chemotherapy involves the activation of Nrf2.”

 

Meng, X., Chen, H., Wang, G., Yu, Y., & Xie, K. (2015). Hydrogen-rich saline attenuates chemotherapy-induced ovarian injury via regulation of oxidative stress. Experimental and Therapeutic Medicine, 10(6), 2277-2282. doi: 10.3892/etm.2015.2787

Cognitive Performance & Recovery

 

The ability of H2 to increase levels of brain-derived neurotropic factor may increase cognitive function.

Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer's disease by reduction of oxidative stress

 

“Hydrogen-rich saline prevented amyloid beta-induced neuroinflammation and oxidative stress, which may contribute to the improvement of memory dysfunction in this rat model.”

 

Li, J., Wang, C., Zhang, J. H., Cai, J., Cao, Y., & Sun, X. (2010). Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer's disease by reduction of oxidative stress. Brain Research, 1328, 152-161. doi: 10.1016/j.brainres.2010.02.046

 

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

 

“Molecular hydrogen given in drinking water reverses many of the sequelae of controlled cortical impact and suggests that it could be an easily administered, highly effective treatment for traumatic brain injury.”

 

Dohi, K., Kraemer, B. C., Erickson, M. A., Mcmillan, P. J., Kovac, A., Flachbartova, Z., . . . Banks, W. A. (2014). Molecular hydrogen in drinking water protects against neurodegenerative changes induced by traumatic brain injury. PLOS ONE, 9(9), 1-16. doi: 10.1371/journal.pone.0108034

Hydrogen-rich saline protects against spinal cord injury in rats

 

“We observed that administration of hydrogen-rich saline decreased the number of apoptotic cells, suppressed oxidative stress, and improved locomotor functions. In conclusion, hydrogen-rich saline reduced acute spinal cord contusion injury, possibly by reduction of oxidative stress and elevation of BDNF.”

 

Chen, C., Chen, Q., Mao, Y., Xu, S., Xia, C., Shi, X., . . . Sun, X. (2010). Hydrogen-rich saline protects against spinal cord injury in rats. Neurochemical Research, 35(7), 1111-1118. doi: 10.1007/s11064-010-0162-y

 

Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury

 

“Hydrogen can relieve tissue-damaging oxidative stress, inflammation and apoptosis. Injection of hydrogen-rich saline is an effective method for transporting molecular hydrogen. The present study confirms that hydrogen-rich saline injected within 2 weeks of injury effectively contributes to the repair of spinal cord injury in the acute stage.”

 

Zhang, K., Wang, J., Zhang, Q., Zhu, K., Sun, J., Zhang, Z., & Sun, J. (2015). Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury. Neural Regeneration Research, 10(6), 958-964. doi: 10.4103/1673-5374.158361

 

Hydrogen-rich saline protects against oxidative damage and cognitive deficits after mild traumatic brain injury

 

“Oxidative stress is the principal factor in traumatic brain injury (TBI) that initiates events that result in protracted neuronal dysfunction and remodeling. These results suggest that hydrogen-rich saline can protect the brain against the deleterious effects of mild TBI on synaptic plasticity and cognition and that hydrogen-rich saline could be an effective therapeutic strategy for patients with cognitive deficits after TBI.”

 

Hou, Z., Luo, W., Sun, X., Hao, S., Zhang, Y., Xu, F., . . . Liu, B. (2012). Hydrogen-rich saline protects against oxidative damage and cognitive deficits after mild traumatic brain injury. Brain Research Bulletin, 88(6), 560-565. doi: 10.1016/j.brainresbull.2012.06.006

 

Hydrogen-rich saline prevents early neurovascular dysfunction resulting from inhibition of oxidative stress in STZ-diabetic rats

 

“Based on its inhibition of oxidative stress and up-regulation of anti-oxidative enzymes, we conclude that hydrogen-rich saline is a potentially valuable therapeutic modality for the treatment of Diabetic Retinopathy.”

 

Feng, Y., Wang, R., Xu, J., Sun, J., Xu, T., Gu, Q., & Wu, X. (2012). Hydrogen-rich saline prevents early neurovascular dysfunction resulting from inhibition of oxidative stress in STZ-diabetic rats. Current Eye Research, 38(3), 396-404. doi: 10.3109/02713683.2012.748919

Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice

 

“Consumption of hydrogen water ad libitum throughout this study suppressed the increase in the oxidative stress markers and prevented cognitive impairment. Continuous consumption of hydrogen water reduces oxidative stress in the brain, and prevents the stress-induced decline in learning and memory caused by chronic physical restraint. Hydrogen water may be applicable for preventive use in cognitive or other neuronal disorders.”

 

Nagata, K., Nakashima-Kamimura, N., Mikami, T., Ohsawa, I., & Ohta, S. (2008). Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice. Neuropsychopharmacology, 34(2), 501-508. doi: 10.1038/npp.2008.95

 

Hydrogen-rich saline reverses oxidative stress, cognitive impairment, and mortality in rats submitted to sepsis by cecal ligation and puncture

 

“The hippocampal reactive oxygen species and malondialdehyde levels increased significantly, and superoxide dismutase activity decreased significantly. HRS reversed these changes in a dose-dependent manner. These findings indicate that HRS could attenuate the consequences of sepsis induced by cecal ligation and puncture in rats, at least in part, by the inhibition of oxidative stress.”

 

Zhou, J., Chen, Y., Huang, G., Li, J., Wu, G., Liu, L., . . . Wang, J. (2012). Hydrogen-rich saline reverses oxidative stress, cognitive impairment, and mortality in rats submitted to sepsis by cecal ligation and puncture. Journal of Surgical Research, 178(1), 390-400. doi: 10.1016/j.jss.2012.01.041

 

Drinking hydrogen water ameliorated cognitive impairment in senescence-accelerated mice 

 

“In this study, scientists investigated the efficacies of drinking hydrogen water for prevention of spatial memory decline and age-related brain alterations using mice that exhibited early aging syndromes including declining learning ability and memory. However, treatment with hydrogen water for 30 days prevented age-related declines in cognitive ability. In addition, drinking hydrogen water for 18 weeks inhibited neurodegeneration in hippocampus, while marked loss of neurons was noted in control, aged brains of mice receiving regular water. On the basis of these results, hydrogen water merits further investigation for possible therapeutic/preventative use for age-related cognitive disorders.”

 

Gu, Y., Huang, C., Inoue, T., Yamashita, T., Ishida, T., Kang, K., & Nakao, A. (2010). Drinking hydrogen water ameliorated cognitive impairment in senescence-accelerated mice. Journal of Clinical Biochemistry and Nutrition, 46(3), 269-276. doi: 10.3164/jcbn.10-19

 

Inhalation of hydrogen gas attenuates cognitive impairment in transient cerebral ischemia via inhibition of oxidative stress

 

“Inhalation of hydrogen gas could attenuate cognitive impairment in the ischemic rats. This protection is associated with decreased neuronal death in CA1 region and inhibition of oxidative stress.”

 

Ge, P., Zhao, J., Li, S., Ding, Y., Yang, G., & Luo, Y. (2012). Inhalation of hydrogen gas attenuates cognitive impairment in transient cerebral ischemia via inhibition of oxidative stress. Neurological Research, 34(2), 187-194. doi: 10.1179/1743132812y.0000000002

 
 

Diabetes (Type 2)

 

Oxidative stress is widely recognized as being associated with a number of diseases, including type 2 diabetes. In a randomized, double-blind, placebo-controlled study on patients with either type 2 diabetes or impaired glucose tolerance, treatment with H2 rich water was associated with significant improvements in lipid and glucose metabolism, suggesting that hydrogen-rich water may have a beneficial role in the prevention of type 2 diabetes and insulin resistance.

 

Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance

“Supplementation with molecular hydrogen-rich water may have a beneficial role in the prevention of type 2 diabetes and insulin resistence by helping to stabilize blood sugar, which is a critical aspect of long-term weight loss.”

 

Kajiyama, S., Hasegawa, G., Asano, M., Hosoda, H., Fukui, M., Nakamura, N., . . . Yoshikawa, T. (2008). Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutrition Research, 28(3), 137-143. doi: 10.1016/j.nutres.2008.01.008

 

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

“H2 prevented the decline of the mitochondrial membrane potential. This suggested that H2 protected mitochondria from OH. Along with this protective effect, H2 also prevented a decrease in the cellular level of ATP synthesized in mitochondria. The fact that H2 protected mitochondria and nuclear DNA provided evidence that H2 penetrated most membranes and diffused into organelles.” 

 

Ohta, S. (2011). Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventive and therapeutic applications. Current Pharmaceutical Design, 17(22), 2241-2252. doi: 10.2174/138161211797052664

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

“Hydrogen selectively reduces the hydroxyl radical, the most toxic free radical, and effectively protects cells. It does not react with free radicals that have physiological benefits, making it an incredibly effective therapy to neutralize acute oxidative stress.”

 

Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., . . . Ohta, S. (2007). Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nature Medicine, 13(6), 688-694. doi: 10.1038/nm1577

 

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

 

“Effects of molecular hydrogen on various diseases have been documented for 63 disease models and human diseases in the past four and a half years. Six human diseases have been studied to date: diabetes mellitus type 2, metabolic syndrome, hemodialysis, inflammatory and mitochondrial myopathies, brain stem infarction, and radiation-induced adverse effects.”

 

Ohno, K., Ito, M., Ichihara, M., & Ito, M. (2012). Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases. Oxidative Medicine and Cellular Longevity, 2012, 1-11. doi: 10.1155/2012/353152

 

Hydrogen improves glycemic control in type1 diabetic animal model by promoting glucose uptake into skeletal muscle

 

“Our study demonstrates that H(2) exerts metabolic effects similar to those of insulin and may be a novel therapeutic alternative to insulin in type 1 diabetes mellitus that can be administered orally.”

 

Amitani, H., Asakawa, A., Cheng, K., Amitani, M., Kaimoto, K., Nakano, M., . . . Inui, A. (2013). Hydrogen improves glycemic control in type1 diabetic animal model by promoting glucose uptake into skeletal muscle. PLOS ONE, 8(1), 1-14. doi: 10.1371/journal.pone.0053913

 

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

 

“Hydrogen is qualified to cross the blood brain barrier, to enter the mitochondria, and even has the ability to translocate to the nucleus under certain conditions. Once in these ideal locations of the cell, previous studies have shown that hydrogen exerts antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective properties that are beneficial to the cell.” 

 

Dixon, B. J., Tang, J., & Zhang, J. H. (2013). The evolution of molecular hydrogen: A noteworthy potential therapy with clinical significance. Medical Gas Research, 3(10), 1-12. doi: 10.1186/2045-9912-3-10

 

​Hydrogen-rich saline prevents early neurovascular dysfunction resulting from inhibition of oxidative stress in STZ-diabetic rats 

 

“Based on its inhibition of oxidative stress and up-regulation of anti-oxidative enzymes, we conclude that hydrogen-rich saline is a potentially valuable therapeutic modality for the treatment of Diabetic Retinopathy.”

 

Feng, Y., Wang, R., Xu, J., Sun, J., Xu, T., Gu, Q., & Wu, X. (2012). Hydrogen-rich saline prevents early neurovascular dysfunction resulting from inhibition of oxidative stress in STZ-diabetic rats. Current Eye Research, 38(3), 396-404. doi: c10.3109/02713683.2012.748919

 

 

Anti type 2 diabetic effect and anti-oxidation effect in active hydrogen water administration KK-Ay mice

 

“Active hydrogen water is capable of anti-oxidation and it also has a controlling effect on the blood glucose level in type 2 diabetes.”

Gu, Y., Oonishi, K., Fujii, T., Itokawa, Y., Masubuchi, T., Kurono, Y., . . . Ishida, T. (2006). Anti type 2 diabetic effect and anti-oxidation effect in active hydrogen water administration KK-Ay mice. Medicine and Biology, 150(11), 384-392. Retrieved from http://www.suzuka-u.ac.jp/information/bulletin/pdf/07-02-gu2.pdf ​

 

Protective effects of hydrogen-rich saline in a rat model of traumatic brain injury via reducing oxidative stress

 

“TBI-challenged rats exhibited significant brain injuries characterized by the increase of BBB permeability, brain edema, and lesion volume as well as neurological dysfunction, which were dose-dependently ameliorated by HS treatment. Hydrogen-rich saline can exert a protective effect against TBI via reducing oxidative stress. Molecular hydrogen may be a more effective therapeutic strategy for TBI patients.”

 

Ji, X., Tian, Y., Xie, K., Liu, W., Qu, Y., & Fei, Z. (2012). Protective effects of hydrogen-rich saline in a rat model of traumatic brain injury via reducing oxidative stress. Journal of Surgical Research, 178(1), 9-16. doi: 10.1016/j.jss.2011.12.038

 

Molecular hydrogen improves obesity and diabetes by inducing hepatic FGF21 and stimulating energy metabolism in db/db mice

 

“Long-term drinking H(2)-water significantly controlled fat and body weights, despite no increase in consumption of diet and water. The present results suggest the potential benefit of H(2) in improving obesity, diabetes, and metabolic syndrome”

 

Kamimura, N., Nishimaki, K., Ohsawa, I., & Ohta, S. (2011). Molecular hydrogen improves obesity and diabetes by inducing hepatic FGF21 and stimulating energy metabolism in db/db mice. Obesity, 19(7), 1396-1403. doi: 10.1038/oby.2011.6

 

Hydrogen-rich water inhibits glucose and α,β -dicarbonyl compound-induced reactive oxygen species production in the SHR.Cg-Lepr cp /NDmcr rat kidney

 

“Hydrogen rich water inhibited glucose- and α,β-dicarbonyl compound-induced ROS production in kidney homogenates from Wistar rats in vitro. Therefore, it has therapeutic potential for renal dysfunction in patient with type 2 diabetes and metabolic syndrome.”

 

Katakura, M., Hashimoto, M., Tanabe, Y., & Shido, O. (2012). Hydrogen-rich water inhibits glucose and α,β -dicarbonyl compound-induced reactive oxygen species production in the SHR.Cg-Leprcp/NDmcr rat kidney. Medical Gas Research, 2(18), 1-7. doi: 10.1186/2045-9912-2-18

 

Protective effects of hydrogen-rich saline against erectile dysfunction in a streptozotocin induced diabetic rat model

 

“Hydrogen-rich saline effectively improved erectile function in a streptozotocin induced diabetic rat model of erectile dysfunction.”

 

Fan, M., Xu, X., He, X., Chen, L., Qian, L., Liu, J., . . . Sun, X. (2013). Protective effects of hydrogen-rich saline against erectile dysfunction in a streptozotocin induced diabetic rat model. The Journal of Urology, 190(1), 350-356. doi: 10.1016/j.juro.2012.12.001

 

Therapeutic effects of hydrogen saturated saline on rat diabetic model and insulin resistant model via reduction of oxidative stress

 

“Hydrogen saturated saline showed great efficiency in improving the insulin sensitivity and lowering blood glucose and lipids. Hydrogen saturated saline markedly attenuated the malondialdehyde level and elevated the levels of antioxidants superoxide dismutase and glutathione.”

 

Wang, Q. J., Zha, X. J., Kang, Z. M., Xu, M. J., Huang, Q., & Zou, D. J. (2012). Therapeutic effects of hydrogen saturated saline on rat diabetic model and insulin resistant model via reduction of oxidative stress. Chinese Medical Journal, 125(9), 1633-1637. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/22800834/ 

 

Hydrogen-rich medium protects human skin fibroblasts from high glucose or mannitol induced oxidative damage

 

“Hydrogen may have applications in the treatment of skin diseases caused by diabetes.”

 

Yu, P., Wang, Z., Sun, X., Chen, X., Zeng, S., Chen, L., & Li, S. (2011). Hydrogen-rich medium protects human skin fibroblasts from high glucose or mannitol induced oxidative damage. Biochemical and Biophysical Research Communications, 409(2), 350-355. doi: 10.1016/j.bbrc.2011.05.024

 

Hydrogen gas reduced acute hyperglycemia-enhanced hemorrhagic transformation in a focal ischemia rat model

 

“We found that hydrogen inhalation for 2 h reduced infarct and hemorrhagic volumes and improved neurological functions. Hydrogen gas reduced brain infarction, hemorrhagic transformation, and improved neurological function in rats.”

 

Chen, C., Manaenko, A., Zhan, Y., Liu, W., Ostrowki, R., Tang, J., & Zhang, J. (2010). Hydrogen gas reduced acute hyperglycemia-enhanced hemorrhagic transformation in a focal ischemia rat model. Neuroscience, 169(1), 402-414. doi: 10.1016/j.neuroscience.2010.04.043

 

Depression

 

Oxidative stress and major depression

 

“The study concluded that in the absence of known oxidative injury causative agents, the lowered levels of antioxidants and higher levels of MDA implicate the high degree of oxidative stress in unipolar depression.”

 

Bajpai, A., Verma, A. K., Srivastava, M., & Srivastava, R. (2014). Oxidative stress and major depression. Journal Of Clinical And Diagnostic Research, 8(12), 4-7. doi: 10.7860/jcdr/2014/10258.5292

 

Depression and oxidative stress: Results from a meta-analysis of observational studies

 

“This meta-analysis observed an association between depression and oxidative stress and antioxidant status across many different studies. Differences in measures of depression and markers of oxidative stress and antioxidant status markers could account for the observed heterogeneity. These findings suggest that well-established associations between depression and poor health outcomes may be mediated by high oxidative stress.”

 

Palta, P., Samuel, L. J., Miller, E. R., & Szanton, S. L. (2014). Depression and oxidative stress: Results from a meta-analysis of observational studies. Psychosomatic Medicine, 76(1), 12-19. doi: 10.1097/psy.0000000000000009

 

Novel therapeutic targets in depression and anxiety: Antioxidants as a candidate treatment

 

“There is growing evidence that the imbalance between oxidative stress and the antioxidant defense system may be associated with the development neuropsychiatric disorders, such as depression and anxiety. Major depression and anxiety are presently correlated with a lowered total antioxidant state and by an activated oxidative stress (OS) pathway.”

 

Xu, Y., Wang, C., Klabnik, J. J., & O'Donnell, J. M. (2014). Novel therapeutic targets in depression and anxiety: Antioxidants as a candidate treatment. Current Neuropharmacology, 12(2), 108-119. doi: 10.2174/1570159X11666131120231448

 

Review: The role of inflammation in depression

 

“The role of inflammation in major depressive disorder (MDD) has been of growing interest over the past two decades and evidence suggests it plays a role in depression. Cytokines have been found to influence almost every pathway involved in the pathogenesis of depression including alterations to the expression of neurotransmitters, neuroendocrine function, synaptic plasticity and basal ganglia.”

 

Patel, A. (2013). Review: The role of inflammation in depression. Psychiatria Danubina, 25(2), 216-223. Retrieved from http://www.hdbp.org/psychiatria_danubina/pdf/dnb_vol25_sup2/dnb_vol25_sup2_216.pdf

A meta-analysis of oxidative stress markers in depression

 

“Studies have suggested that depression was accompanied by oxidative stress dysregulation, including abnormal total antioxidant capacity (TAC), antioxidants, free radicals, oxidative damage and autoimmune response products. This meta-analysis supports the facts that the serum TAC, paraoxonase and antioxidant levels are lower, and the serum free radical and oxidative damage product levels are higher than controls in depressed patients.”

 

Liu, T., Zhong, S., Liao, X., Chen, J., He, T., Lai, S., & Jia, Y. (2015). A meta-analysis of oxidative stress markers in depression. PLOS ONE, 10(10), 1-17. doi: 10.1371/journal.pone.0138904

​ 

Oxidative stress and antioxidant parameters in patients with major depressive disorder compared to healthy controls before and after antidepressant treatment: Results from a meta-analysis

 

“Results suggest that oxidative stress plays a role in depression and that antidepressant activity may be mediated via improving oxidative stress/antioxidant function.”

 

Jiménez-Fernández, S., Gurpegui, M., Díaz-Atienza, F., Pérez-Costillas, L., Gerstenberg, M., & Correll, C. U. (2015). Oxidative stress and antioxidant parameters in patients with major depressive disorder compared to healthy controls before and after antidepressant treatment: Results from a meta-analysis. The Journal of Clinical Psychiatry, 76(12), 1658-1667. doi: 10.4088/jcp.14r09179

 

From inflammation to sickness and depression: When the immune system subjugates the brain

 

“Inflammation is therefore an important biological event that might increase the risk of major depressive episodes, much like the more traditional psychosocial factors.”

 

Dantzer, R., O'Connor, J., Freund, G., Johnson, R., & Kelley, K. (2008). From inflammation to sickness and depression: When the immune system subjugates the brain. Nature Reviews Neuroscience, 9(1), 45-46. doi: 10.1038/nrn2297

 

A meta-analysis of cytokines in major depression

 

“This meta-analysis reports significantly higher concentrations of the proinflammatory cytokines TNF-alpha and IL-6 in depressed subjects compared with control subjects. While both positive and negative results have been reported in individual studies, this meta-analytic result strengthens evidence that depression is accompanied by activation of the IRS.”

 

Dowlati, Y., Herrmann, N., Swardfager, W., Liu, H., Sham, L., Reim, E., & Lanctot, K. (2010). A meta-analysis of cytokines in major depression. Biological Psychiatry, 67(5), 446-57. doi: 10.1016/j.biopsych.2009.09.033

 

Inflammation in depression: Is adiposity a cause?

 

“Mounting evidence indicates that inflammation may play a significant role in the development of depression. Patients with depression exhibit increased inflammatory markers, and administration of cytokines and other inflammatory stimuli can induce depressive symptoms.”

 

Shelton, R., & Miller, A. (2011). Inflammation in depression: Is adiposity a cause? Dialogues in Clinical Neuroscience, 13(1), 41-53. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181969/

 

Serum brain-derived neurotrophic factor, depression, and antidepressant medications: Meta-analyses and implications

 

“Converging lines of evidence implicate the neurotrophin brain-derived neurotrophic factor (BDNF) in the pathophysiology of major depression. The meta-analysis revealed strong evidence that BDNF levels were lower in depressed subjects than healthy control subjects.”

 

Sen, S., Duman, R., & Sanacora, G. (2008). Serum brain-derived neurotrophic factor, depression, and antidepressant medications: Meta-analyses and implications. Biological Psychiatry, 64(6), 527-532. doi: 10.1016/j.biopsych.2008.05.005

Brain-derived neurotrophic factor in mood disorders and antidepressant treatments

 

“Levels of brain-derived neurotrophic factor (BDNF) are reduced in the brain and serum of depressed patients and at least the reduction in serum levels is reversible upon successful treatment.”

 

Castrén, E., & Kojima, M. (2016). Brain-derived neurotrophic factor in mood disorders and antidepressant treatments. Neurobiology of Disease. Neurobiology of Disease, 97, 119-126. doi: 10.1016/j.nbd.2016.07.010

 

Involvement of brain-derived neurotrophic factor in late-life depression

 

“Evidence suggests that BDNF is involved in major depression, such that the level of BDNF is decreased in depressed patients and that antidepressants reverse this decrease.”

 

Dwivedi, Y. (2013). Involvement of brain-derived neurotrophic factor in late-life depression. The American Journal of Geriatric Psychiatry, 21(5), 433-449. doi: 10.1016/j.jagp.2012.10.026

 

 

Brain-derived neurotrophic factor: Role in depression and suicide

 

“Several lines of evidence suggest that BDNF is involved in depression, such that the expression of BDNF is decreased in depressed patients. Overall, these studies suggest the possibility that BDNF and its mediated signaling may participate in the pathophysiology of depression and suicidal behavior.”

 

Yogesh, D. (2009). Brain-derived neurotrophic factor: Role in depression and suicide. Neuropsychiatric Disease and Treatment, 5, 433-449. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2732010/

 

 

Hydrogen-rich saline protects against spinal cord injury in rats

 

“Administration of hydrogen-rich saline decreased the number of apoptotic cells, suppressed oxidative stress, and improved locomotor functions. Hydrogen-rich saline increased the release of Brain derived neurotrophic factor.”

 

Chen, C., Chen, Q., Mao, Y., Xu, S., Xia, C., Shi, X., . . . Sun, X. (2010). Hydrogen-rich saline protects against spinal cord injury in rats. Neurochemical Research, 35(7), 1111-1118. doi: 10.1007/s11064-010-0162-y

 

Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury

 

“The benefits of hydrogen-rich saline are not limited to the kidney; it also reduces acute spinal cord contusion injury, possibly by decreasing oxidative stress, inflammation and apoptosis while increasing brain-derived neurotrophic factor expression and activation of the mitochondrial adenosine triphosphate-dependent potassium (mitoK ATP) channel.”

 

Zhang, K., Wang, J., Zhang, Q., Zhu, K., Sun, J., Zhang, Z., & Sun, J. (2015). Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury. Neural Regeneration Research, 10(6), 958-964. doi: 10.4103/1673-5374.158361

 

Hydrogen-rich saline protects against oxidative damage and cognitive deficits after mild traumatic brain injury

 

“Treatment with hydrogen-rich saline, which elevated the levels of molecules associated with brain-derived neurotropic factor (BDNF)-mediated synaptic plasticity, improved cognitive performance.”

 

Hou, Z., Luo, W., Sun, X., Hao, S., Zhang, Y., Xu, F., . . . Liu, B. (2012). Hydrogen-rich saline protects against oxidative damage and cognitive deficits after mild traumatic brain injury. Brain Research Bulletin, 88(6), 560-565. doi: 10.1016/j.brainresbull.2012.06.006

 

Hydrogen-rich saline prevents early neurovascular dysfunction resulting from inhibition of oxidative stress in STZ-diabetic rats

 

“Hydrogen-rich saline reduced oxidative stress, increased antioxidant enzyme activities and preserved synaptophysin and brain derived neurotrophic factor levels in the diabetic rat retina.”

 

Feng, Y., Wang, R., Xu, J., Sun, J., Xu, T., Gu, Q., & Wu, X. (2012). Hydrogen-rich saline prevents early neurovascular dysfunction resulting from inhibition of oxidative stress in STZ-diabetic rats. Current Eye Research, 38(3), 396-404. doi: 10.3109/02713683.2012.748919

 

 

Effects of hydrogen-rich water on depressive-like behavior in mice

 

“Emerging evidence suggests that neuroinflammation and oxidative stress may be major contributors to major depressive disorder (MDD). Our data suggest that the beneficial effects of hydrogen-rich water on depressive-like behavior may be mediated by suppression of the inflammasome activation resulting in attenuated protein IL-1β and ROS production.”

 

Zhang, Y., Su, W., Chen, Y., Wu, T., Gong, H., Shen, X., . . . Jiang, C. (2016). Effects of hydrogen-rich water on depressive-like behavior in mice. Scientific Reports, 6(23742), 1-7. doi: 10.1038/srep23742

 

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

 

“Hydrogen is qualified to cross the blood brain barrier, to enter the mitochondria, and even has the ability to translocate to the nucleus under certain conditions. Once in these ideal locations of the cell, previous studies have shown that hydrogen exerts antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective properties that are beneficial to the cell.”

 

Dixon, B. J., Tang, J., & Zhang, J. H. (2013). The evolution of molecular hydrogen: A noteworthy potential therapy with clinical significance. Medical Gas Research, 3(10), 1-12. doi: 10.1186/2045-9912-3-10

 

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

 

“H2 has a number of advantages as a potential antioxidant: H2 rapidly diffuses into tissues and cells, and it is mild enough neither to disturb metabolic redox reactions nor to affect reactive oxygen species (ROS) that function in cell signaling, thereby, there should be little adverse effects of consuming H2. H2 shows not only effects against oxidative stress, but also various anti-inflammatory and anti-allergic effects. H2 regulates various gene expressions and protein-phosphorylations as well.”

 

Ohta, S. (2011). Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventive and therapeutic applications. Current Pharmaceutical Design, 17(22), 2241-2252. doi: 10.2174/138161211797052664

 

Hydrogen as a selective antioxidant: A review of clinical and experimental studies

“H2 is emerging as a novel and safe therapeutic antioxidant. It has selective antioxidant properties, giving it anti-inflammatory properties.”

Hong, Y., Chen, S., & Zhang, J. (2010). Hydrogen as a selective antioxidant: A review of clinical and experimental studies. Journal of International Medical Research, 38(6), 1893-1903. doi: 10.1177/147323001003800602

 

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

“Hydrogen selectively reduces the hydroxyl radical, the most toxic free radical, and effectively protects cells. It does not react with free radicals that have physiological benefits, making it an incredibly effective therapy to neutralize acute oxidative stress.”

 

Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., . . . Ohta, S. (2007). Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nature Medicine, 13(6), 688-694. doi: 10.1038/nm1577  

 

Hydrogen-rich water attenuates brain damage and inflammation after traumatic brain injury in rats

 

“HRW treatment also decreased the levels of pro-inflammatory cytokines (TNF-α, IL-1β and HMGB1), inflammatory cell number (Iba1) and inflammatory metabolites (Cho) and increased the levels of an anti-inflammatory cytokine (IL-10) in the brain tissues of TBI-challenged rats. In conclusion, HRW could exert a neuroprotective effect against TBI and attenuate inflammation, which suggests HRW as an effective therapeutic strategy for TBI patients.”

 

Tian, R., Hou, Z., Hao, S., Wu, W., Mao, X., Tao, X., . . . Liu, B. (2016). Hydrogen-rich water attenuates brain damage and inflammation after traumatic brain injury in rats. Brain Research, 1637, 1-13. doi: 10.1016/j.brainres.2016.01.029

 

Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer's disease by reduction of oxidative stress

 

“Hydrogen-rich saline prevented Abeta-induced neuroinflammation and oxidative stress, which may contribute to the improvement of memory dysfunction in this rat model.”

 

Li, J., Wang, C., Zhang, J. H., Cai, J., Cao, Y., & Sun, X. (2010). Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer's disease by reduction of oxidative stress. Brain Research, 1328, 152-161. doi: 10.1016/j.brainres.2010.02.046

 

Molecular hydrogen reduces LPS-induced neuroinflammation and promotes recovery from sickness behaviour in mice

 

“We found that molecular hydrogen reduces the LPS-induced sickness behaviour and promotes recovery. These effects are associated with a shift towards anti-inflammatory gene expression profile at baseline (downregulation of TNF- α and upregulation of IL-10). In addition, molecular hydrogen increases the amplitude, but shortens the duration and promotes the extinction of neuroinflammation.”

 

Spulber, S., Edoff, K., Hong, L., Morisawa, S., Shirahata, S., & Ceccatelli, S. (2012). Molecular hydrogen reduces LPS-induced neuroinflammation and promotes recovery from sickness behaviour in mice. PLOS ONE, 7(7). doi: 10.1371/journal.pone.0042078

 

 

Hydrogen-rich saline reduces oxidative stress and inflammation by inhibit of JNK and NF-κB activation in a rat model of amyloid-beta-induced Alzheimer's disease

 

“Hydrogen-rich saline prevented amyloid beta-induced neuroinflammation and oxidative stress in this rat model.”

 

Wang, C., Li, J., Liu, Q., Yang, R., Zhang, J. H., Cao, Y., & Sun, X. (2011). Hydrogen-rich saline reduces oxidative stress and inflammation by inhibit of JNK and NF-κB activation in a rat model of amyloid-beta-induced Alzheimer's disease. Neuroscience Letters, 491(2), 127-132. doi: 10.1016/j.neulet.2011.01.022

 

Inhalation of hydrogen gas attenuates brain injury in mice with cecal ligation and puncture via inhibiting neuroinflammation, oxidative stress and neuronal apoptosis

 

“We found that the beneficial effects of H2 on brain injury in septic mice were linked to the decreased levels of inflammatory cytokines and oxidative products and the increased activities of antioxidant enzymes in serum and hippocampus. In addition, 2% H2 inhalation promoted the expression and transposition of Nrf2 and the expression of HO-1 to mitigate brain injury in sepsis.”

 

Liu, L., Xie, K., Chen, H., Dong, X., Li, Y., Yu, Y., . . . Yu, Y. (2014). Inhalation of hydrogen gas attenuates brain injury in mice with cecal ligation and puncture via inhibiting neuroinflammation, oxidative stress and neuronal apoptosis. Brain Research, 1589, 78-92. doi: 10.1016/j.brainres.2014.09.030

 

General Health

 

Molecular Hydrogen has significant therapeutic potential for a wide range of disease models. 

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

“H2 prevented the decline of the mitochondrial membrane potential. This suggested that H2 protected mitochondria from OH. Along with this protective effect, H2 also prevented a decrease in the cellular level of ATP synthesized in mitochondria. The fact that H2 protected mitochondria and nuclear DNA provided evidence that H2 penetrated most membranes and diffused into organelles.”

 

Ohta, S. (2011). Recent progress toward hydrogen medicine: Potential of molecular hydrogen for preventive and therapeutic applications. Current Pharmaceutical Design, 17(22), 2241-2252. doi: 10.2174/138161211797052664

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

 

“Hydrogen is qualified to cross the blood brain barrier, to enter the mitochondria, and even has the ability to translocate to the nucleus under certain conditions. Once in these ideal locations of the cell, previous studies have shown that hydrogen exerts antioxidant, anti-apoptotic, anti-inflammatory, and cytoprotective properties that are beneficial to the cell.” 

 

Dixon, B. J., Tang, J., & Zhang, J. H. (2013). The evolution of molecular hydrogen: A noteworthy potential therapy with clinical significance. Medical Gas Research, 3(10), 1-12. doi: 10.1186/2045-9912-3-10

 

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

 

“A total of 321 original articles have been published from 2007 to June 2015. Most studies have been conducted in Japan, China, and the USA. The effects have been reported in essentially all organs covering 31 disease categories that can be subdivided into 166 disease models, human diseases, treatment-associated pathologies, and pathophysiological conditions of plants with a predominance of oxidative stress-mediated diseases and inflammatory diseases.”

 

Ichihara, M., Sobue, S., Ito, M., Ito, M., Hirayama, M., & Ohno, K. (2015). Beneficial biological effects and the underlying mechanisms of molecular hydrogen - comprehensive review of 321 original articles. Medical Gas Research, 5(12), 1-21. doi: 10.1186/s13618-015-0035-1

 

A review of hydrogen as a new medical therapy

 

“In the past few years many initial and subsequent clinical studies have demonstrated that hydrogen can act as an important physiological regulatory factor to cells and organs on the antioxidant, anti-inflammatory, anti-apoptotic and other protective effects. So far several delivery methods applied in these studies have proved to be available and convenient, including inhalation, drinking hydrogen-dissolved water and injection with hydrogen-saturated saline.”

 

Zhang, J., Liu, C., Zhou, L., Qu, K., Wang, R., Tai, M., . . . Wang, Z. (2012). A Review of hydrogen as a new medical therapy. Hepatogastroenterology, 59(116), 1026-1032. doi: 10.5754/hge11883

 

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

 

“The numerous publications on its biological and medical benefits revealed that H2 reduces oxidative stress not only by direct reactions with strong oxidants, but also indirectly by regulating various gene expressions. Moreover, by regulating the gene expressions, H2 functions as an anti-inflammatory and anti-apoptotic, and stimulates energy metabolism. In addition to growing evidence obtained by model animal experiments, extensive clinical examinations were performed or are under investigation. Since most drugs specifically act to their targets, H2 seems to differ from conventional pharmaceutical drugs. Owing to its great efficacy and lack of adverse effects, H2 has promising potential for clinical use against many diseases.”

 

Ohta, S. (2014). Molecular hydrogen as a preventive and therapeutic medical gas: Initiation, development and potential of hydrogen medicine. Pharmacology & Therapeutics, 144(1), 1-11. doi: 10.1016/j.pharmthera.2014.04.006

 

Kidney Disease

 

H2's antioxidant properties have been shown, in rat studies, to be effective at combatting the severity of contrast-induced acute kidney injury and renal injury.

Inhalation of hydrogen gas is beneficial for preventing contrast-induced acute kidney injury in rats

 

“Mechanistic analyses showed that inhalation of H2 gas significantly reduced renal cell apoptosis, expression of cleaved caspase 3, and expression of an oxidative stress marker, 8-hydroxydeoxyguanosine, in injured kidneys. Results suggest that H2 gas inhalation is effective in ameliorating the severity of CIAKI in rats by reducing renal cell apoptosis and oxidative stress.”

 

Homma, K., Yoshida, T., Yamashita, M., Hayashida, K., Hayashi, M., & Hori, S. (2014). Inhalation of hydrogen gas is beneficial for preventing contrast-induced acute kidney injury in rats. Nephron Experimental Nephrology, 128(3-4), 116-122. doi: 10.1159/000369068

 

Hydrogen-rich saline ameliorates renal injury induced by unilateral ureteral obstruction in rats

 

“HS treatment significantly reduced the fibrosis and infiltration of macrophage in UUO kidneys. Significant increase in the MDA level and decrease in the SOD activity were observed in UUO group and the UUO + saline group. MDA level of UUO + HS group was significantly reduced. In addition, SOD activity of was significantly improved after treatment of HS. The data provide a biochemical and histologic basis for HS acting as a novel therapeutic strategy for preventing the renal injury induced by UUO.”

 

Xu, B., Zhang, Y., Li, Z., Yang, M., Wang, S., & Jiang, D. (2013). Hydrogen-rich saline ameliorates renal injury induced by unilateral ureteral obstruction in rats. International Immunopharmacology, 17(2), 447-452. doi: 10.1016/j.intimp.2013.06.033

 

Amelioration of cardio-renal injury with aging in dahl salt-sensitive rats by H2-enriched electrolyzed water

 

“Long-term ad libitum consumption of H2-enriched electrolyzed water can ameliorate the processes of kidney injury and cardiac remodeling with aging in Dahl SS rats by suppressing, at least partly, elevated inflammation and oxidative stress.”

 

Zhu, W., Nakayama, M., Mori, T., Hao, K., Terawaki, H., Katoh, J., . . . Ito, S. (2013). Amelioration of cardio-renal injury with aging in dahl salt-sensitive rats by H2-enriched electrolyzed water. Medical Gas Research, 3(26), 1-8. Retrieved from http://medicalgasresearch.biomedcentral.com/articles/10.1186/2045-9912-3-26

 

Hydrogen as a selective antioxidant: A review of clinical and experimental studies

“H2 is emerging as a novel and safe therapeutic antioxidant. It has selective antioxidant properties, giving it anti-inflammatory properties.”

 

Hong, Y., Chen, S., & Zhang, J. (2010). Hydrogen as a selective antioxidant: A review of clinical and experimental studies. Journal of International Medical Research, 38(6), 1893-1903. doi: 10.1177/147323001003800602

 

Hydrogen-rich University of Wisconsin solution attenuates renal cold ischemia-reperfusion injury

 

“HRUW solution improved graft function and prolonged graft survival compared with simple cold storage using UW solution by protecting tubular epithelial cells from inflammation and apoptosis. Our new method of organ preservation is a groundbreaking, safe, and simple strategy that may be applied in the clinical setting.”

 

Abe, T., Li, X., Yazawa, K., Hatayama, N., Xie, L., Sato, B., . . . Nonomura, N. (2012). Hydrogen-rich university of Wisconsin solution attenuates renal cold ischemia–reperfusion injury. Transplantation Journal, 94(1), 14-21. doi: 10.1097/tp.0b013e318255f8be

 

Pretreatment with hydrogen-rich saline reduces the damage caused by glycerol-induced rhabdomyolysis and acute kidney injury in rats

 

“All these factors were significantly improved by both doses of HRS, but the mean histologic damage score, urea, Cr, CK, ROS, 8-OH-dG, GSH-PX, IL-6, and TNF-α for the high dose HRS treatment group were even lower. Pretreatment by HRS ameliorated renal dysfunction in glycerol-induced rhabdomyolysis by inhibiting oxidative stress and the inflammatory response.”

 

Gu, H., Yang, M., Zhao, X., Zhao, B., Sun, X., & Gao, X. (2014). Pretreatment with hydrogen-rich saline reduces the damage caused by glycerol-induced rhabdomyolysis and acute kidney injury in rats. Journal of Surgical Research, 188(1), 243-249. doi: 10.1016/j.jss.2013.12.007

 

Hydrogen-rich saline solution attenuates renal ischemia–reperfusion injury

 

“These protective effects were likely due to the antioxidant properties of HRSS. These results suggest that HRSS is a potential therapeutic candidate for treating various I/R diseases.”

 

Shingu, C., Koga, H., Hagiwara, S., Matsumoto, S., Goto, K., Yokoi, I., & Noguchi, T. (2010). Hydrogen-rich saline solution attenuates renal ischemia–reperfusion injury. Journal of Anesthesia, 24(4), 569-574. doi: 10.1007/s00540-010-0942-1

 

Hydrogen-rich water inhibits glucose and α,β -dicarbonyl compound-induced reactive oxygen species production in the SHR.Cg-Lepr cp /NDmcr rat kidney

 

“Hydrogen rich water inhibited glucose- and α,β-dicarbonyl compound-induced ROS production in kidney homogenates from Wistar rats in vitro. Therefore, it has therapeutic potential for renal dysfunction in patient with type 2 diabetes and metabolic syndrome.”

 

Katakura, M., Hashimoto, M., Tanabe, Y., & Shido, O. (2012). Hydrogen-rich water inhibits glucose and α,β -dicarbonyl compound-induced reactive oxygen species production in the SHR.Cg-Leprcp/NDmcr rat kidney. Medical Gas Research, 2(18), 1-7. doi: 10.1186/2045-9912-2-18

 

Hydrogen-rich saline attenuates acute renal injury in sodium taurocholate-induced severe acute pancreatitis by inhibiting ROS and NF-κB pathway

 

“These results proved that hydrogen-rich saline attenuates acute renal injury in sodium taurocholate-induced acute pancreatitis, presumably because of its detoxification activity against excessive ROS, and inhibits the activation of NF-κB by affecting IκB nitration and degradation. Our findings highlight the potential value of hydrogen-rich saline as a new therapeutic method on acute renal injury in severe acute pancreatitis clinically.”

 

Shi, Q., Liao, K., Zhao, K., Wang, W., Zuo, T., Deng, W., . . . Zhao, L. (2015). Hydrogen-rich saline attenuates acute renal injury in sodium taurocholate-induced severe acute pancreatitis by inhibiting ROS and NF-κB pathway. Mediators of Inflammation, 2015, 1-13. doi: 10.1155/2015/685043

 

Intake of water with high levels of dissolved hydrogen (H2) suppresses ischemia-induced cardio-renal injury in Dahl salt-sensitive rats

 

“Consumption of EW by ad libitum drinking has the potential to ameliorate ischemia-induced cardio-renal injury in CKD model rats. This indicates a novel strategy of applying H2 produced by water electrolysis technology for the prevention of CKD cardio-renal syndrome.”

 

Zhu, W., Nakayama, M., Mori, T., Nakayama, K., Katoh, J., Murata, Y., . . . Ito, S. (2010). Intake of water with high levels of dissolved hydrogen (H2) suppresses ischemia-induced cardio-renal injury in Dahl salt-sensitive rats. Nephrology Dialysis Transplantation, 26(7), 2112-2118. doi: 10.1093/ndt/gfq727

 

Liver Disease (Cirrhosis)

 

Multiple studies on mice and rats have shown that H2 can repair liver damage and reduce inflammation associated with liver disease. H2 was shown to suppress liver fibrosis, which is a universal consequence of chronic liver disease. In other studies, H2 relieved liver injury, mostly because of the abilities to activate the body's antioxidant capabilities and to down regulate extracellular signal-regulated protein kinase activation.

 

Effects of oral intake of hydrogen water on liver fibrogenesis in mice

 

“Oral intake of hydrogen water significantly suppressed liver fibrogenesis in the carbon tetrachloride and thioacetamide models, but these effects were not seen in the bile duct ligation model. We conclude that hydrogen water protects hepatocytes from injury by scavenging hydroxyl radicals and thereby suppresses liver fibrogenesis in mice.”

 

Koyama, Y., Taura, K., Hatano, E., Tanabe, K., Yamamoto, G., Nakamura, K., . . . Uemoto, S. (2013). Effects of oral intake of hydrogen water on liver fibrogenesis in mice. Hepatology Research, 44(6), 663-677. doi: 10.1111/hepr.12165

 

Hydrogen-rich saline protects against liver injury in rats with obstructive jaundice

 

“Hydrogen selectively reduces levels of hydroxyl radicals and alleviates acute oxidative stress in many models. Hydrogen-rich saline attenuates BDL-induced liver damage, possibly by the reduction of inflammation and oxidative stress and the inhibition of the ERK1/2 pathway.”

 

Liu, Q., Shen, W., Sun, H., Fan, D., Nakao, A., Cai, J., . . . Sun, X. (2010). Hydrogen-rich saline protects against liver injury in rats with obstructive jaundice. Liver International, 30(7), 958-968. doi: 10.1111/j.1478-3231.2010.02254.x

 

The protective role of hydrogen-rich saline in experimental liver injury in mice

 

“HS significantly increased hydrogen concentration in liver and kidney tissues. As a result, acute liver injury, hepatic cirrhosis, and hepatocyte proliferation were reduced through the quenching of detrimental ROS. Activity of pro-apoptotic players, such as JNK and caspase-3, were also inhibited. HS could protect against liver injury and also inhibit the processes leading to liver cirrhosis and hepatocyte compensatory proliferation.”

 

Sun, H., Chen, L., Zhou, W., Hu, L., Li, L., Tu, Q., . . . Wang, H. (2011). The protective role of hydrogen-rich saline in experimental liver injury in mice. Journal of Hepatology, 54(3), 471-480. doi: 10.1016/j.jhep.2010.08.011

 

Saturated hydrogen saline attenuates endotoxin-induced acute liver dysfunction in rats

 

“Saturated hydrogen saline may attenuate LPS-induced acute liver dysfunction in rats, possibly by reducing inflammation and cell apoptosis. Mitogen-activated protein kinase (MAPK), NF-kappaB, and Smac may contribute to saturated hydrogen saline-mediated liver protection.”

 

Zhang, Y., Liu, Y., & Zhang, J. (2015). Saturated hydrogen saline attenuates endotoxin-induced lung dysfunction. Journal of Surgical Research, 1, 41-49. doi: 10.1016/j.jss.2015.04.055

 

Anti-inflammatory properties of molecular hydrogen: Investigation on parasite-induced liver inflammation

 

“Molecular hydrogen reacts with the hydroxyl radical, a highly cytotoxic species produced in inflamed tissues. It has been suggested therefore to use gaseous hydrogen in a new anti-inflammatory strategy. The treatment had significant protective effects towards liver injury, namely decreased fibrosis, improvement of hemodynamics, increased NOSII activity, increased antioxidant enzyme activity, decreased lipid peroxide levels and decreased circulating TNF-alpha levels.”

 

Gharib, B., Hanna, S., Abdallahi, O. M., Lepidi, H., Gardette, B., & Reggi, M. D. (2001). Anti-inflammatory properties of molecular hydrogen: Investigation on parasite-induced liver inflammation. Comptes Rendus De L'Académie Des Sciences - Series III - Sciences De La Vie, 324(8), 719-724. doi: 10.1016/s0764-4469(01)01350-6

 

Effect of hydrogen-rich water on oxidative stress, liver function, and viral load in patients with chronic hepatitis B

 

“When compared with controls, oxidative stress was obvious in CHB patients, and the liver function also significantly impaired. After treatment, the oxidative stress remained unchanged in routine treatment group, but markedly improved in hydrogen treatment group. HRW significantly attenuates oxidative stress in CHB patients, but further study with long-term treatment is required to confirm the effect of HRW on liver function and HBV DNA level.”
 

Xia, C., Liu, W., Zeng, D., Zhu, L., Sun, X., & Sun, X. (2013). Effect of hydrogen-rich water on oxidative stress, liver function, and viral load in patients with chronic hepatitis B. Clinical and Translational Science, 6(5), 372-375. doi: 10.1111/cts.12076

 

Concomitant inhibition of oxidative stress and angiogenesis by chronic hydrogen-rich saline and N-acetylcysteine treatments improves systemic, splanchnic and hepatic hemodynamics of cirrhotic rats

 

“Both hydrogen-rich saline and N-acetylcysteine alleviate portal hypertension, the severity of portosystemic collaterals, mesenteric angiogenesis, hepatic endothelial dysfunction and intrahepatic resistance in cirrhotic rats. N-Acetylcysteine and the new antioxidant, hydrogen-rich saline are potential treatments for the complications of cirrhosis.”

 

Lee, P., Yang, Y., Huang, C., Hsieh, S., Lee, K., Hsieh, Y., . . . Lin, H. (2014). Concomitant inhibition of oxidative stress and angiogenesis by chronic hydrogen-rich saline and N-acetylcysteine treatments improves systemic, splanchnic and hepatic hemodynamics of cirrhotic rats. Hepatology Research, 45(5), 578-588. doi: 10.1111/hepr.12379

 

Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice

 

“To investigate the hepatoprotective effects and mechanisms of hydrogen-rich water (HRW) in acetaminophen (APAP)-induced liver injury in mice. HRW has significant therapeutic potential in APAP-induced hepatotoxicity by inhibiting oxidative stress and inflammation and promoting liver regeneration.”

 

Zhang, J. (2015). Hydrogen-rich water protects against acetaminophen-induced hepatotoxicity in mice. World Journal of Gastroenterology, 21(14), 4195. doi: 10.3748/wjg.v21.i14.4195

 

Protective effects of hydrogen enriched saline on liver ischemia reperfusion injury by reducing oxidative stress and HMGB1 release

 

“Hydrogen enriched saline treatment significantly attenuated the severity of liver injury induced by ischemia-reperfusion. These results suggest that, in our model, hydrogen enriched saline treatment is protective against liver ischemia-reperfusion injury. This effect may be mediated by both the anti-oxidative and anti-inflammatory effects of the solution.”

 

Liu, Y., Yang, L., Tao, K., Vizcaychipi, M. P., Lloyd, D. M., Sun, X., . . . Yu, W. (2014). Protective effects of hydrogen enriched saline on liver ischemia reperfusion injury by reducing oxidative stress and HMGB1 release. BMC Gastroenterology, 14(12), 1-9. doi: 10.1186/1471-230x-14-12

 

Hydrogen gas inhalation protects against liver ischemia/reperfusion injury by actiiating the NF-kB signaling pathway

 

“Hydrogen has been demonstrated to function as a novel antioxidant and exert therapeutic antioxidant activity in a number of diseases. The results indicate that hydrogen inhalation at 2% concentration for 1 h prior to liver transplantation protected the rats from ischemia/reperfusion injury by activation of the NF-κB signaling pathway.”

 

Zhang, C., Tang, Y., Xu, X., Guo, S., & Wang, H. (2015). Hydrogen gas inhalation protects against liver ischemia/reperfusion injury by activating the NF-κB signaling pathway. Experimental and Therapeutic Medicine, 9(6), 2114-2120. doi: 10.3892/etm.2015.2385

 

Lung Disease

 

Hydrogen rich saline has been shown to be protective of the lungs against oxygen toxicity and other oxidative-stress mediated diseases of the lung.

 

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

 

“Effects of molecular hydrogen on various diseases have been documented for 63 disease models and human diseases in the past four and a half years. Six human diseases have been studied to date: diabetes mellitus type 2, metabolic syndrome, hemodialysis, inflammatory and mitochondrial myopathies, brain stem infarction, and radiation-induced adverse effects.”

 

Ohno, K., Ito, M., Ichihara, M., & Ito, M. (2012). Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases. Oxidative Medicine and Cellular Longevity, 2012, 1-11. doi: 10.1155/2012/353152

 

Hydrogen gas improves survival rate and organ damage in zymosan-induced generalized inflammation model

 

“H2 exerts a therapeutic antioxidant activity by neutralizing cytotoxic free radicals and has been shown to be protective against organ damage in a generalized inflammation model.”

 

Xie, K., Yu, Y., Zhang, Z., Liu, W., Pei, Y., Xiong, L., . . . Wang, G. (2010). Hydrogen gas improves survival rate and organ damage in zymosan-induced generalized inflammation model. Shock, 34(5), 495-501. doi: 10.1097/shk.0b013e3181def9aa

 

Saturated hydrogen saline protects the lung against oxygen toxicity

 

“Saturated hydrogen saline decreased lung edema, reduced LDH activity in BALF and serum, and decreased total cells and protein concentration in BALF. These results demonstrated that saturated hydrogen saline alleviated hyperoxia-induced pulmonary injury, which was partly responsible for the inhibition of oxidative damage.”

 

Zheng, J., Liu, K., Kang, Z., Cai, J., Liu, W., Xu, W., . . . Sun, X. (2010). Saturated hydrogen saline protects the lung against oxygen toxicity. Undersea Hyperbaric Medicine: Journal of the Undersea and Hyperbaric Medical Society, Inc., 37(3), 185-192. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/20568549

 

Hydrogen-rich saline protects against acute lung injury induced by extensive burn in rat model

 

“Administration of hydrogen-rich saline or edaravone dramatically reduced the pulmonary levels of pulmonary inflammation mediators and myeloperoxidase. Intraperitoneal administration of hydrogen-rich saline improves pulmonary function by reducing oxidative stress and inflammatory response in severe burn-induced acute lung injury.”

 

Fang, Y., Fu, X., Gu, C., Xu, P., Wang, Y., Yu, W., . . . Yao, M. (2011). Hydrogen-rich saline protects against acute lung injury induced by extensive burn in rat model. Journal of Burn Care & Research, 32(3), 82-91. doi: 10.1097/bcr.0b013e318217f84f

 

The effects of hydrogen gas inhalation during ex vivo lung perfusion on donor lungs obtained after cardiac death

 

“Hydrogen gas inhalation during EVLP improved the function of donation after cardiac death lungs, which may increase the utilization of donation after cardiac death lungs.”

 

Haam, S., Lee, S., Paik, H. C., Park, M. S., Song, J. H., Lim, B. J., & Nakao, A. (2015). The effects of hydrogen gas inhalation during ex vivo lung perfusion on donor lungs obtained after cardiac death. Eur J Cardiothorac Surg European Journal of Cardio-Thoracic Surgery, 48(4), 542-547. doi:10.1093/ejcts/ezv057

 

Hydrogen inhalation ameliorates ventilator-induced lung injury

 

“In the lungs treated with hydrogen, there was less malondialdehyde compared with lungs treated with nitrogen. Inhaled hydrogen gas effectively reduced VILI-associated inflammatory responses, at both a local and systemic level, via its antioxidant, anti-inflammatory and antiapoptotic effects.”

 

Huang, C., Kawamura, T., Lee, S., Tochigi, N., Shigemura, N., Buchholz, B. M., . . . Nakao, A. (2010). Hydrogen inhalation ameliorates ventilator-induced lung injury. Critical Care, 14(6), 1-15. doi: 10.1186/cc9389

 

Hydrogen inhalation reduced epithelial apoptosis in ventilator-induced lung injury via a mechanism involving nuclear factor-kappa B activation

 

“Hydrogen inhalation increased oxygen tension, decreased lung edema, and decreased the expression of proinflammatory mediators. Chemical inhibition of early NFκB activation using SN50 reversed these protective effects. NFκB activation and an associated increase in the expression of Bcl-2 may contribute, in part, to the cytoprotective effects of hydrogen against apoptotic and inflammatory signaling pathway activation during VILI.”

 

Huang, C., Kawamura, T., Peng, X., Tochigi, N., Shigemura, N., Billiar, T. R., . . . Toyoda, Y. (2011). Hydrogen inhalation reduced epithelial apoptosis in ventilator-induced lung injury via a mechanism involving nuclear factor-kappa B activation. Biochemical and Biophysical Research Communications, 408(2), 253-258. doi: 10.1016/j.bbrc.2011.04.008

 

Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo

 

“These findings indicate that hydrogen gas can ameliorate hyperoxic lung injury through induction of Nrf2-dependent genes, such as HO-1. The findings suggest a potentially novel and applicable solution to hyperoxic lung injury and provide new insight into the molecular mechanisms and actions of hydrogen.”

 

Kawamura, T., Wakabayashi, N., Shigemura, N., Huang, C., Masutani, K., Tanaka, Y., . . . Nakao, A. (2013). Hydrogen gas reduces hyperoxic lung injury via the Nrf2 pathway in vivo. American Journal of Physiology: Lung Cellular and Molecular Physiology, 304(10), 646-656. doi: 10.1152/ajplung.00164.2012

 

Consumption of hydrogen water reduces paraquat-induced acute lung injury in rats

 

“Recent studies have reported that consumption of water with dissolved molecular hydrogen to a saturated level (hydrogen water) prevents oxidative stress-induced diseases. The results showed that hydrogen water ameliorated these alterations, demonstrating that hydrogen water alleviated paraquat-induced acute lung injury possibly by inhibition of oxidative damage.”

 

Liu, S., Liu, K., Sun, Q., Liu, W., Xu, W., Denoble, P., . . . Sun, X. (2011). Consumption of hydrogen water reduces paraquat-induced acute lung injury in rats. Journal of Biomedicine and Biotechnology, 2011, 1-7. doi: 10.1155/2011/305086

 

Lung inflation with hydrogen during the cold ischemia phase decreases lung graft injury in rats

 

“The lung injury score determined by histopathology, the cell apoptotic index, and the caspase-3 protein expression in lung grafts were decreased after hydrogen treatment, and the static pressure-volume curve of lung graft was improved by hydrogen inflation. In conclusion, lung inflation with 3% hydrogen during the cold ischemia phase alleviated lung graft injury and improved graft function.”

 

Liu, R., Fang, X., Meng, C., Xing, J., Liu, J., Yang, W., . . . Zhou, H. (2015). Lung inflation with hydrogen during the cold ischemia phase decreases lung graft injury in rats. Experimental Biology and Medicine, 240(9), 1214-1222. doi: 10.1177/1535370214563895

 

Combination therapy with nitric oxide and molecular hydrogen in a murine model of acute lung injury

 

“Combination therapy with subthreshold concentrations of NO and H2 still had a significantly beneficial effect against lung injury induced by LPS and polymicrobial sepsis. Collectively, these results demonstrate that combination therapy with NO and H2 provides enhanced therapeutic efficacy for ALI.”

 

Liu, H., Liang, X., Wang, D., Zhang, H., Liu, L., Chen, H., . . . Xie, K. (2015). Combination therapy with nitric oxide and molecular hydrogen in a murine model of acute lung injury. Shock, 43(5), 504-511. doi: 10.1097/shk.0000000000000316

 

Combined early fluid resuscitation and hydrogen inhalation attenuates lung and intestine injury

 

“Combined early fluid resuscitation and hydrogen inhalation may protect the lung and intestine of the septic shock rats from the damage induced by oxidative stress and the inflammatory reaction.”

 

Liu, W. (2013). Combined early fluid resuscitation and hydrogen inhalation attenuates lung and intestine injury. World Journal of Gastroenterology, 19(4), 492-502. doi: 10.3748/wjg.v19.i4.492

 

Hydrogen preconditioning during ex vivo lung perfusion improves the quality of lung grafts in rats

 

“Lung grafts on EVLP exhibited prominent proinflammatory changes and compromised metabolic profiles. Preconditioning lung grafts using inhaled hydrogen attenuated these proinflammatory changes, promoted mitochondrial biogenesis in the lungs throughout the procedure, and resulted in better posttransplant graft function.”

 

Noda, K., Shigemura, N., Tanaka, Y., Bhama, J., D’Cunha, J., Kobayashi, H., . . . Bermudez, C. A. (2014). Hydrogen preconditioning during ex vivo lung perfusion improves the quality of lung grafts in rats. Transplantation, 98(5), 499-506. doi: 10.1097/tp.0000000000000254

 

Hydrogen inhalation ameliorates lipopolysaccharide-induced acute lung injury in mice

 

“Hydrogen further attenuated histopathological alterations and mitigated lung cell apoptosis. Importantly, hydrogen inhibited the activation of P-JNK, and also reversed changes in Bax, Bcl-xl and caspase-3. In conclusion, our data demonstrated that hydrogen inhalation ameliorated LPS-induced ALI and it may be exerting its protective role by preventing the activation of ROS-JNK-caspase-3 pathway.”

 

Qiu, X., Li, H., Tang, H., Jin, Y., Li, W., Y., . . . Xia, Z. (2011). Hydrogen inhalation ameliorates lipopolysaccharide-induced acute lung injury in mice. International Immunopharmacology, 11(12), 2130-2137. doi: 10.1016/j.intimp.2011.09.007

 

Hydrogen saline is protective for acute lung ischaemia/reperfusion injuries in rats

 

“Hydrogen saline significantly protected vasoactivity of the pulmonary artery, reduced pulmonary oedema, decreased lung malondialdehyde (MDA), 8-OHdG concentration, alleviated lung epithelial cell apoptosis and lowered the level of such biomarkers as WBC, CRP, ALT and TBiL.”

 

Shi, J., Yao, F., Zhong, C., Pan, X., Yang, Y., & Lin, Q. (2012). Hydrogen saline is protective for acute lung ischaemia/reperfusion injuries in rats. Heart, Lung and Circulation, 21(9), 556-563. doi: 10.1016/j.hlc.2012.05.782

 

Hydrogen-rich saline provides protection against hyperoxic lung injury

 

“Hydrogen-rich saline treatment provides protection against HALI by inhibiting lipid, DNA oxidation, and tissue edema. Moreover, hydrogen-rich saline treatment could inhibit apoptosis and inflammation while no significant reduction was observed in nitrogen-rich saline treated animals. The results of this study demonstrate that hydrogen-rich saline ameliorated hyperoxia-induced acute lung injury by reducing oxidative stress and inflammatory cascades in lung tissue.”

 

Sun, Q., Cai, J., Liu, S., Liu, Y., Xu, W., Tao, H., & Sun, X. (2011). Hydrogen-rich saline provides protection against hyperoxic lung injury. Journal of Surgical Research, 165(1), 43-49. doi: 10.1016/j.jss.2010.09.024

 

Profiling molecular changes induced by hydrogen treatment of lung allografts prior to procurement

 

“Donor ventilation with hydrogen significantly increases expression of surfactant-related molecules, ATP synthases and stress-response molecules in lung grafts. The induction of these molecules may underlie hydrogen's protective effects against I/R injury during transplantation.”

 

Zhang, J. Y., & Liu, C. (2012). Letter to the editor on “Profiling molecular changes induced by hydrogen treatment of lung allografts prior to procurement.” Biochemical and Biophysical Research Communications, 427(1), 227. doi: 10.1016/j.bbrc.2012.09.073

 

Hydrogen therapy attenuates irradiation-induced lung damage by reducing oxidative stress

 

“Molecular hydrogen (H(2)) is an efficient antioxidant that diffuses rapidly across cell membranes, reduces reactive oxygen species (ROS), such as hydroxyl radicals and peroxynitrite, and suppresses oxidative stress-induced injury in several organs. This study thus demonstrated that H(2) treatment is valuable for protection against irradiation lung damage with no known toxicity.”

 

Terasaki, Y., Ohsawa, I., Terasaki, M., Takahashi, M., Kunugi, S., Dedong, K., . . . Fukuda, Y. (2011). Hydrogen therapy attenuates irradiation-induced lung damage by reducing oxidative stress. American Journal of Physiology: Lung Cellular and Molecular Physiology, 301(4), 415-426. doi: 10.1152/ajplung.00008.2011

 

Hydrogen-rich saline ameliorates lung injury associated with cecal ligation and puncture-induced sepsis in rats

 

“This observation indicated that hydrogen-rich saline peritoneal injection improves histological and functional assessment in rat model of CLP-induced ALI. The therapeutic effects of hydrogen-rich saline may be related to antioxidant and anti-inflammatory actions.”

 

Zhai, Y., Zhou, X., Dai, Q., Fan, Y., & Huang, X. (2015). Hydrogen-rich saline ameliorates lung injury associated with cecal ligation and puncture-induced sepsis in rats. Experimental and Molecular Pathology, 98(2), 268-276. doi: 10.1016/j.yexmp.2015.03.005

 

Saturated hydrogen saline protects the lung against oxygen toxicity

 

“Saturated hydrogen saline decreased lung edema, reduced LDH activity in BALF and serum, and decreased total cells and protein concentration in BALF. These results demonstrated that saturated hydrogen saline alleviated hyperoxia-induced pulmonary injury, which was partly responsible for the inhibition of oxidative damage.”

 

Zheng, J., Liu, K., Kang, Z., Cai, J., Liu, W., Xu, W., . . . Sun, X. (2010). Saturated hydrogen saline protects the lung against oxygen toxicity. Undersea Hyperbaric Medicine: Journal of the Undersea and Hyperbaric Society, Inc., 37(3), 185-192. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/20568549

Metabolic Syndrome

Studies that also show potential benefits for patients with type 2 diabetes, high cholesterol, and elevated triglycerides are also promising for metabolic syndrome, since there are often related and share similar features.

 

Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance

“Supplementation with molecular hydrogen-rich water may have a beneficial role in the prevention of type 2 diabetes and insulin resistence by helping to stabilize blood sugar, which is a critical aspect of long-term weight loss.”

 

Kajiyama, S., Hasegawa, G., Asano, M., Hosoda, H., Fukui, M., Nakamura, N., . . . Yoshikawa, T. (2008). Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. Nutrition Research, 28(3), 137-143. doi: 10.1016/j.nutres.2008.01.008

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Hydrogen improves glycemic control in type1 diabetic animal model by promoting glucose uptake into skeletal muscle

 

“Our study demonstrates that H(2) exerts metabolic effects similar to those of insulin and may be a novel therapeutic alternative to insulin in type 1 diabetes mellitus that can be administered orally.”

 

Amitani, H., Asakawa, A., Cheng, K., Amitani, M., Kaimoto, K., Nakano, M., . . . Inui, A. (2013). Hydrogen improves glycemic control in type1 diabetic animal model by promoting glucose uptake into skeletal muscle. PLOS ONE, 8(4), 1-14. doi: 10.1371/journal.pone.0053913

 

Hydrogen gas reduced acute hyperglycemia-enhanced hemorrhagic transformation in a focal ischemia rat model

 

“We found that hydrogen inhalation for 2 h reduced infarct and hemorrhagic volumes and improved neurological functions. Hydrogen gas reduced brain infarction, hemorrhagic transformation, and improved neurological function in rats.”

 

Chen, C., Manaenko, A., Zhan, Y., Liu, W., Ostrowki, R., Tang, J., & Zhang, J. (2010). Hydrogen gas reduced acute hyperglycemia-enhanced hemorrhagic transformation in a focal ischemia rat model. Neuroscience, 169(1), 402-414. doi: 10.1016/j.neuroscience.2010.04.043

 

Hydrogen-rich water prevents lipid deposition in the descending aorta in a rat periodontitis model

 

“Hydrogen Water intake may prevent lipid deposition in the rat aorta induced by periodontitis by decreasing serum ox-LDL levels and aortic oxidative stress.”

 

Ekuni, D., Tomofuji, T., Endo, Y., Kasuyama, K., Irie, K., Azuma, T., . . . Morita, M. (2012). Hydrogen-rich water prevents lipid deposition in the descending aorta in a rat periodontitis model. Archives of Oral Biology, 57(12), 1615-1622. doi: 10.1016/j.archoralbio.2012.04.013

 

Molecular hydrogen improves obesity and diabetes by inducing hepatic FGF21 and stimulating energy metabolism in db/db mice

 

“Long-term drinking H(2)-water significantly controlled fat and body weights, despite no increase in consumption of diet and water. The present results suggest the potential benefit of H(2) in improving obesity, diabetes, and metabolic syndrome.”

 

Kamimura, N., Nishimaki, K., Ohsawa, I., & Ohta, S. (2011). Molecular hydrogen improves obesity and diabetes by inducing hepatic FGF21 and stimulating energy metabolism in db/db mice. Obesity, 19(7), 1396-1403. doi: 10.1038/oby.2011.6

 

Molecular hydrogen stimulates the gene expression of transcriptional coactivator PGC-1α to enhance fatty acid metabolism

 

“In wild-type mice fed the fatty diet, H2-water improved the level of plasma triglycerides and extended their average of lifespan. H2 induces expression of the PGC-1αgene, followed by stimulation of the PPARα pathway that regulates FGF21, and the fatty acid and steroid metabolism.”

 

Kamimura, N. Ichimaya, H. Iuchi, K. & Ohta, S. (2016). Molecular hydrogen stimulates the gene expression of transcriptional coactivator PGC-1a to enhance fatty acid metabolism. Npj Aging and Mechanisms of Disease, 2(16008), 1-8. doi: 10.1038/npjamd.2016.8

 

Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice

 

“Atherosclerotic lesions were significantly reduced by ad libitum drinking of H2–water (p = 0.0069) as judged by Oil-Red-O staining series of sections of aorta. The oxidative stress level of aorta was decreased. Accumulation of macrophages in atherosclerotic lesions was confirmed. Thus, consumption of H2-dissolved water has the potential to prevent arteriosclerosis.”

 

Ohsawa, I., Nishimaki, K., Yamagata, K., Ishikawa, M., & Ohta, S. (2008). Consumption of hydrogen water prevents atherosclerosis in apolipoprotein E knockout mice. Biochemical and Biophysical Research Communications, 377(4), 1195-1198. doi: 10.1016/j.bbrc.2008.10.156 

 

Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome

 

“Supplementation with H2-rich water seems to decrease serum LDL-C and apoB levels, improve dyslipidemia-injured HDL functions, and reduce oxidative stress, and it may have a beneficial role in prevention of potential metabolic syndrome.”

 

Song, G., Li, M., Sang, H., Zhang, L., Li, X., Yao, S., . . . Qin, S. (2013). Hydrogen-rich water decreases serum LDL-cholesterol levels and improves HDL function in patients with potential metabolic syndrome. Journal of Lipid Research, 54(7), 1884-1893. doi: 10.1194/jlr.M036640

 

Hydrogen-rich saline attenuates lipopolysaccharide-induced heart dysfunction by restoring fatty acid oxidation in rats by mitigating C-jun N-terminal kinase activation

 

“Inhibition of c-Jun N-terminal kinase by Hydrogen-rich saline showed beneficial effects on lipopolysaccharide-challenged rats, at least in part, by restoring cardiac fatty acid oxidation.”

 

Tao, B., Liu, L., Wang, N., Tong, D., Wang, W., & Zhang, J. (2015). Hydrogen-rich saline attenuates lipopolysaccharide-induced heart dysfunction by restoring fatty acid oxidation in rats by mitigating C-jun N-terminal kinase activation. Shock, 44(6), 593-600. doi: 10.1097/SHK.0000000000000467

 

 

Hydrogen-rich water prevents lipid deposition in the descending aorta in a rat periodontitis model

 

“Hydrogen Water intake may prevent lipid deposition in the rat aorta induced by periodontitis by decreasing serum ox-LDL levels and aortic oxidative stress.”

 

Ekuni, D., Tomofuji, T., Endo, Y., Kasuyama, K., Irie, K., Azuma, T., . . . Morita, M. (2012). Hydrogen-rich water prevents lipid deposition in the descending aorta in a rat periodontitis model. Archives of Oral Biology, 57(12), 1615-1622. doi: 10.1016/j.archoralbio.2012.04.013

 

Effects of hydrogen-rich water on abnormalities in a SHR.Cg-Leprcp/NDmcr rat - a metabolic syndrome rat model

 

“Hydrogen (H2), a potent free radical scavenger, selectively reduces the hydroxyl radical, which is the most cytotoxic of the reactive oxygen species (ROS). An increase in oxygen free radicals induces oxidative stress, which is known to be involved in the development of metabolic syndrome. The present findings suggest that HRW conferred significant benefits against abnormalities in the metabolic syndrome model rats, at least by preventing and ameliorating glomerulosclerosis and creatinine clearance.”

 

Hashimoto, M., Katakura, M., Nabika, T., Tanabe, Y., Hossain, S., Tsuchikura, S., & Shido, O. (2011). Effects of hydrogen-rich water on abnormalities in a SHR.Cg-Leprcp/NDmcr rat - a metabolic syndrome rat model. Medical Gas Research 1(26), 1-6. doi: 10.1186/2045-9912-1-26

 

Molecular hydrogen attenuates fatty acid uptake and lipid accumulation through downregulating CD36 expression in HepG2 cells

 

“Hydrogen inhibits fatty acid uptake and lipid accumulation through the downregulation of CD36 at the protein level in hepatic cultured cells, providing insights into the molecular mechanism underlying the hydrogen effects in vivo on lipid metabolism disorders.”

 

Iio, A., Ito, M., Itoh, T., Terazawa, R., Fujita, Y., Nozawa, Y., . . . Ito, M. (2013). Molecular hydrogen attenuates fatty acid uptake and lipid accumulation through downregulating CD36 expression in HepG2 cells. Medical Gas Research, 3(6), 1-7. doi: 10.1186/2045-9912-3-6

 

H2 inhibits TNF-α-induced lectin-like oxidized LDL receptor-1 expression by inhibiting nuclear factor κB activation in endothelial cells

 

“H(2) is a therapeutic antioxidant that can reduce oxidative stress. Oxidized low-density lipoprotein, which plays roles in atherosclerosis, may promote endothelial dysfunction by binding the cell-surface receptor LOX-1. H(2) inhibited the expression of LOX-1 and the activation of NF-κB in apolipoprotein E knockout mice, an animal model of atherosclerosis. Thus, H(2) probably inhibits cytokine-induced LOX-1 gene expression by suppressing NF-κB activation.”

 

Song, G., Tian, H., Liu, J., Zhang, H., Sun, X., & Qin, S. (2011). H2 inhibits TNF-α-induced lectin-like oxidized LDL receptor-1 expression by inhibiting nuclear factor κB activation in endothelial cells. Biotechnology Letters, 33(9), 1715-1722. doi: 10.1007/s10529-011-0630-8

 

Hydrogen decreases athero-susceptibility in apolipoprotein B-containing lipoproteins and aorta of apolipoprotein E knockout mice

 

“Hydrogen significantly improved HDL functionality in C57BL/6J mice assessed in two independent ways, namely (i) stimulation of cholesterol efflux from macrophage foam cells by measuring HDL-induced [(3)H]cholesterol efflux, and (ii) protection against LDL oxidation as a measure of Cu(2+)-induced TBARS formation. These results reveal that administration of hydrogen-saturated saline decreases athero-susceptibility in apoB-containing lipoprotein and aortic atherosclerosis in apoE-/- mice and improves HDL functionality in C57BL/6J mice.”

 

Song, G., Tian, H., Qin, S., Sun, X., Yao, S., Zong, C., . . . Wang, X. (2012). Hydrogen decreases athero-susceptibility in apolipoprotein B-containing lipoproteins and aorta of apolipoprotein E knockout mice. Atherosclerosis, 221(1), 55-65. doi: 10.1016/j.atherosclerosis.2011.11.043

 

Therapeutic effects of hydrogen saturated saline on rat diabetic model and insulin resistant model via reduction of oxidative stress

 

“Hydrogen saturated saline showed great efficiency in improving the insulin sensitivity and lowering blood glucose and lipids. Hydrogen saturated saline markedly attenuated the malondialdehyde level and elevated the levels of antioxidants superoxide dismutase and glutathione.”

 

Wang, Q., Zha, X., Kang, Z., Xu, M., Huang, Q., & Zou, D. (2012). Therapeutic effects of hydrogen saturated saline on rat diabetic model and insulin resistant model via reduction of oxidative stress. Chinese Medical Journal, 125(9), 1633-1637. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/22800834

 
 

Mitochondrial Myopathies / Muscular Dystrophy

 

H2 improved mitochondrial dysfunction in patients with mitochondrial myopathies and muscular distrophy.

Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies

 

“Hydrogen-enriched water improves mitochondrial dysfunction in MM and inflammatory processes in PM/DM. Less prominent effects with the double-blind trial compared to the open-label trial were likely due to a lower amount of administered hydrogen and a shorter observation period, which implies a threshold effect or a dose-response effect of hydrogen.”

 

Ito, M., Ibi, T., Sahashi, K., Ichihara, M., Ito, M., & Ohno, K. (2011). Open-label trial and randomized, double-blind, placebo-controlled, crossover trial of hydrogen-enriched water for mitochondrial and inflammatory myopathies. Medical Gas Research, 1(24), 1-8. doi: 10.1186/2045-9912-1-24

 

Hydrogen-supplemented drinking water protects cardiac allografts from inflammation-associated deterioration

 

“Hydrogen treatment was also associated with increased graft ATP levels and increased activity of the enzymes in mitochondrial respiratory chain.”

 

Noda, K., Tanaka, Y., Shigemura, N., Kawamura, T., Wang, Y., Masutani, K., . . . Nakao, A. (2012). Hydrogen-supplemented drinking water protects cardiac allografts from inflammation-associated deterioration. Transplant International, 25(12), 1213-1222. doi: 10.1111/j.1432-2277.2012.01542.x

 

Chronic hydrogen-rich saline treatment attenuates vascular dysfunction in spontaneous hypertensive rats

 

“Treatment with HRS depressed pro-inflammatory cytokines expression including IL-6 and IL-1β and suppressed NF-κB activation, restored mitochondrial function including ATP formation and membrane integrity.”

 

Zheng, H., & Yu, Y. (2012). Chronic hydrogen-rich saline treatment attenuates vascular dysfunction in spontaneous hypertensive rats. Biochemical Pharmacology, 83(9), 1269-1277. doi: 10.1016/j.bcp.2012.01.031

 

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

 

“Mitochondria are the major source of oxidative stress. Acute oxidative stress causes serious damage to tissues, and persistent oxidative stress is one of the causes of many common diseases, cancer and the aging process. Hydrogen has many advantages for therapeutic and preventive applications, and shows not only anti-oxidative stress effects, but also has various anti-inflammatory and anti-allergic effects. Preliminary clinical trials show that drinking hydrogen-dissolved water seems to improve the pathology of mitochondrial disorders.”

 

Ohta, S. (2012). Molecular hydrogen is a novel antioxidant to efficiently reduce oxidative stress with potential for the improvement of mitochondrial diseases. Biochimica Et Biophysica Acta, 1820(5), 586-594. doi: 10.1016/j.bbagen.2011.05.006

 

Pilot study: Effects of drinking hydrogen-rich water on muscle fatigue caused by acute exercise in elite athletes

“HW may be suitable hydration for athletes by preventing elevation of blood lactate during heavy exercise. Adequate hydration with hydrogen-rich water pre-exercise reduced blood lactate levels and improved exercise-induced decline of muscle function.”

 

Aoki, K., Nakao, A., Adachi, T., Matsui, Y., & Miyakawa, S. (2012). Pilot study: Effects of drinking hydrogen-rich water on muscle fatigue caused by acute exercise in elite athletes. Medical Gas Research, 2(12), 1-6. doi: 10.1186/2045-9912-2-12

Neurodegenerative Diseases

 

Alzheimer’s Disease

 

Treatment with H2 appears to elevate brain-derived neurotropic factor, improving brain function. H2 treatment has also been shown to block pathological expression of tau proteins (i.e. neurofibrillary tangles, which are a central feature of Alzheimer's disease). Additionally, H2 appears to combat neuroinflammation and oxidative stress.

 

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

 

“Molecular hydrogen given in drinking water reverses many of the sequelae of controlled cortical impact and suggests that it could be an easily administered, highly effective treatment for traumatic brain injury.”

 

Dohi, K., Kraemer, B. C., Erickson, M. A., Mcmillan, P. J., Kovac, A., Flachbartova, Z., . . . Banks, W. A. (2014). Molecular hydrogen in drinking water protects against neurodegenerative changes induced by traumatic brain injury. PLOS ONE, 9(9), 1-16. doi: 10.1371/journal.pone.0108034

 

Hydrogen as a selective antioxidant: A review of clinical and experimental studies

“H2 is emerging as a novel and safe therapeutic antioxidant. It has selective antioxidant properties, giving it anti-inflammatory properties.”

 

Hong, Y., Chen, S., & Zhang, J. (2010). Hydrogen as a selective antioxidant: A review of clinical and experimental studies. Journal of International Medical Research, 38(6), 1893-1903. doi: 10.1177/147323001003800602

 

Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer's disease by reduction of oxidative stress

 

“Hydrogen-rich saline prevented amyloid beta-induced neuroinflammation and oxidative stress, which may contribute to the improvement of memory dysfunction in this rat model.”

 

Li, J., Wang, C., Zhang, J. H., Cai, J., Cao, Y., & Sun, X. (2010). Hydrogen-rich saline improves memory function in a rat model of amyloid-beta-induced Alzheimer's disease by reduction of oxidative stress. Brain Research, 1328, 152-161. doi: 10.1016/j.brainres.2010.02.046

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

 

“Effects of molecular hydrogen on various diseases have been documented for 63 disease models and human diseases in the past four and a half years. Six human diseases have been studied to date: diabetes mellitus type 2, metabolic syndrome, hemodialysis, inflammatory and mitochondrial myopathies, brain stem infarction, and radiation-induced adverse effects.”

 

Ohno, K., Ito, M., Ichihara, M., & Ito, M. (2012). Molecular hydrogen as an emerging therapeutic medical gas for neurodegenerative and other diseases. Oxidative Medicine and Cellular Longevity, 2012, 1-11. doi: 10.1155/2012/353152

 

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

“Hydrogen selectively reduces the hydroxyl radical, the most toxic free radical, and effectively protects cells. It does not react with free radicals that have physiological benefits, making it an incredibly effective therapy to neutralize acute oxidative stress.”

 

Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., . . . Ohta, S. (2007). Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nature Medicine, 13(6), 688-694. doi: 10.1038/nm1577

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Hydrogen-rich saline reduces oxidative stress and inflammation by inhibit of JNK and NF-κB activation in a rat model of amyloid-beta-induced Alzheimer's disease

 

“Hydrogen-rich saline prevented amyloid beta-induced neuroinflammation and oxidative stress in this rat model.”

 

Wang, C., Li, J., Liu, Q., Yang, R., Zhang, J. H., Cao, Y., & Sun, X. (2011). Hydrogen-rich saline reduces oxidative stress and inflammation by inhibit of JNK and NF-κB activation in a rat model of amyloid-beta-induced Alzheimer's disease. Neuroscience Letters, 491(2), 127-132. doi: 10.1016/j.neulet.2011.01.022

 

Hydrogen-rich water attenuates amyloid β-induced cytotoxicity through upregulation of Sirt1-FoxO3a by stimulation of AMP-activated protein kinase in SK-N-MC cells

 

“Amyloid β (Aβ) peptides are identified in cause of neurodegenerative diseases such as Alzheimer's disease (AD). Our results indicated that HRW directly counteracts oxidative damage by neutralizing excessive ROS, leading to the alleviation of Aβ-induced cell death. Our findings suggest that HRW may have potential therapeutic value to inhibit Aβ-induced neurotoxicity.”

 

Lin, C., Huang, W., Li, H., Huang, C., Hsieh, S., Lai, C., & Lu, F. (2015). Hydrogen-rich water attenuates amyloid β-induced cytotoxicity through upregulation of Sirt1-FoxO3a by stimulation of AMP-activated protein kinase in SK-N-MC cells. Chemico-Biological Interactions, 240, 12-21. doi: 10.1016/j.cbi.2015.07.013

 

Hydrogen-rich saline protects against spinal cord injury in rats

 

“We observed that administration of hydrogen-rich saline decreased the number of apoptotic cells, suppressed oxidative stress, and improved locomotor functions. In conclusion, hydrogen-rich saline reduced acute spinal cord contusion injury, possibly by reduction of oxidative stress and elevation of BDNF.”

 

Chen, C., Chen, Q., Mao, Y., Xu, S., Xia, C., Shi, X., . . . Sun, X. (2010). Hydrogen-rich saline protects against spinal cord injury in rats. Neurochemical Research, 35(7), 1111-1118. doi: 10.1007/s11064-010-0162-y

 

Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury

 

“Hydrogen can relieve tissue-damaging oxidative stress, inflammation and apoptosis. Injection of hydrogen-rich saline is an effective method for transporting molecular hydrogen. The present study confirms that hydrogen-rich saline injected within 2 weeks of injury effectively contributes to the repair of spinal cord injury in the acute stage.”

 

Zhang, K., Wang, J., Zhang, Q., Zhu, K., Sun, J., Zhang, Z., & Sun, J. (2015). Hydrogen-rich saline injection into the subarachnoid cavity within 2 weeks promotes recovery after acute spinal cord injury. Neural Regeneration Research, 10(6), 958-964. doi: 10.4103/1673-5374.158361

 

Hydrogen-rich saline protects against oxidative damage and cognitive deficits after mild traumatic brain injury

 

“Oxidative stress is the principal factor in traumatic brain injury (TBI) that initiates events that result in protracted neuronal dysfunction and remodeling. These results suggest that hydrogen-rich saline can protect the brain against the deleterious effects of mild TBI on synaptic plasticity and cognition and that hydrogen-rich saline could be an effective therapeutic strategy for patients with cognitive deficits after TBI.”

 

Hou, Z., Luo, W., Sun, X., Hao, S., Zhang, Y., Xu, F., . . . Liu, B. (2012). Hydrogen-rich saline protects against oxidative damage and cognitive deficits after mild traumatic brain injury. Brain Research Bulletin, 88(6), 560-565. doi: 10.1016/j.brainresbull.2012.06.006

 

Hydrogen-rich saline prevents early neurovascular dysfunction resulting from inhibition of oxidative stress in STZ-diabetic rats

 

“Based on its inhibition of oxidative stress and up-regulation of anti-oxidative enzymes, we conclude that hydrogen-rich saline is a potentially valuable therapeutic modality for the treatment of Diabetic Retinopathy.”

 

Feng, Y., Wang, R., Xu, J., Sun, J., Xu, T., Gu, Q., & Wu, X. (2012). Hydrogen-rich saline prevents early neurovascular dysfunction resulting from inhibition of oxidative stress in STZ-diabetic rats. Current Eye Research, 38(3), 396-404. doi: 10.3109/02713683.2012.748919

 

Drinking hydrogen water ameliorated cognitive impairment in senescence-accelerated mice

 

“In this study, scientists investigated the efficacies of drinking hydrogen water for prevention of spatial memory decline and age-related brain alterations using mice that exhibited early aging syndromes including declining learning ability and memory. However, treatment with hydrogen water for 30 days prevented age-related declines in cognitive ability. In addition, drinking hydrogen water for 18 weeks inhibited neurodegeneration in hippocampus, while marked loss of neurons was noted in control, aged brains of mice receiving regular water. On the basis of these results, hydrogen water merits further investigation for possible therapeutic/preventative use for age-related cognitive disorders.”

 

Gu, Y., Huang, C., Inoue, T., Yamashita, T., Ishida, T., Kang, K., & Nakao, A. (2010). Drinking hydrogen water ameliorated cognitive impairment in senescence-accelerated mice. Journal of Clinical Biochemistry and Nutrition, 46(3), 269-276. doi: 10.3164/jcbn.10-19

 

Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice

 

“Consumption of hydrogen water ad libitum throughout this study suppressed the increase in the oxidative stress markers and prevented cognitive impairment. Continuous consumption of hydrogen water reduces oxidative stress in the brain, and prevents the stress-induced decline in learning and memory caused by chronic physical restraint. Hydrogen water may be applicable for preventive use in cognitive or other neuronal disorders.”

 

Nagata, K., Nakashima-Kamimura, N., Mikami, T., Ohsawa, I., & Ohta, S. (2008). Consumption of molecular hydrogen prevents the stress-induced impairments in hippocampus-dependent learning tasks during chronic physical restraint in mice. Neuropsychopharmacology, 34(2), 501-508. doi: 10.1038/npp.2008.95

 

Maternal molecular hydrogen administration ameliorates rat fetal hippocampal damage caused by in utero ischemia-reperfusion

 

“Molecular hydrogen (H2) scavenges hydroxyl radicals. Recently, H2 has been reported to prevent a variety of diseases associated with oxidative stress in model systems and in humans. The present results support the idea that maternal H2 intake helps prevent the hippocampal impairment of offspring induced by IR during pregnancy.”

 

Mano, Y., Kotani, T., Ito, M., Nagai, T., Ichinohashi, Y., Yamada, K., . . . Toyokuni, S. (2014). Maternal molecular hydrogen administration ameliorates rat fetal hippocampal damage caused by in utero ischemia–reperfusion. Free Radical Biology and Medicine, 69, 324-330. doi: 10.1016/j.freeradbiomed.2014.01.037

 

Effects of hydrogen-rich saline on hepatectomy-induced postoperative cognitive dysfunction in old mice

 

“The introduction of hydrogen-rich saline (group PH) partially rescued spatial memory and learning as it shortened escape latency and increased time and crossing frequency of original platform compared to group P (p < 0.05). Moreover, such treatment also decreased TNF-α and IL-1β levels and NF-κB activity (p < 0.05). In addition, cell necrosis in the hippocampus induced by hepatectomy was also rescued by hydrogen-rich saline. Hydrogen-rich saline can alleviate POCD via inhibiting NF-κB activity in the hippocampus and reducing inflammatory response.”

 

Tian, Y., Guo, S., Zhang, Y., Xu, Y., Zhao, P., & Zhao, X. (2016). Effects of hydrogen-rich saline on hepatectomy-induced postoperative cognitive dysfunction in old mice. Molecular Neurobiology, 1-6. doi: 10.1007/s12035-016-9825-2

 

Inhalation of hydrogen gas attenuates brain injury in mice with cecal ligation and puncture via inhibiting neuroinflammation, oxidative stress and neuronal apoptosis

 

“We found that the beneficial effects of H2 on brain injury in septic mice were linked to the decreased levels of inflammatory cytokines and oxidative products and the increased activities of antioxidant enzymes in serum and hippocampus. In addition, 2% H2 inhalation promoted the expression and transposition of Nrf2 and the expression of HO-1 to mitigate brain injury in sepsis. Thus, the inhalation of hydrogen gas may be a promising therapeutic strategy to relieve brain injury in sepsis.”

 

Liu, L., Xie, K., Chen, H., Dong, X., Li, Y., Yu, Y., . . . Yu, Y. (2014). Inhalation of hydrogen gas attenuates brain injury in mice with cecal ligation and puncture via inhibiting neuroinflammation, oxidative stress and neuronal apoptosis. Brain Research, 1589, 78-92. doi: 10.1016/j.brainres.2014.09.030

 

Molecular hydrogen reduces LPS-induced neuroinflammation and promotes recovery from sickness behaviour in mice

 

“Consistently, molecular hydrogen modulates the activation and gene expression in a similar fashion in immortalized murine microglia (BV-2 cell line), suggesting that the effects observed in vivo may involve the modulation of microglial activation. Taken together, our data point to the regulation of cytokine expression being an additional critical mechanism underlying the beneficial effects of molecular hydrogen.”

 

Spulber, S., Edoff, K., Hong, L., Morisawa, S., Shirahata, S., & Ceccatelli, S. (2012). Molecular hydrogen reduces LPS-induced neuroinflammation and promotes recovery from sickness behaviour in mice. PLOS ONE, 7(7), 1-12. doi: 10.1371/journal.pone.0042078

 

Effects of hydrogen-rich water on depressive-like behavior in mice

 

“Emerging evidence suggests that neuroinflammation and oxidative stress may be major contributors to major depressive disorder (MDD). Our data suggest that the beneficial effects of hydrogen-rich water on depressive-like behavior may be mediated by suppression of the inflammasome activation resulting in attenuated protein IL-1β and ROS production.”

 

Zhang, Y., Su, W., Chen, Y., Wu, T., Gong, H., Shen, X., . . . Jiang, C. (2016). Effects of hydrogen-rich water on depressive-like behavior in mice. Scientific Reports, 6(23742), 1-7. doi: 10.1038/srep23742

 

Hydrogen improves neurological function through attenuation of blood–brain barrier disruption in spontaneously hypertensive stroke-prone rats

 

“This study suggests that ingestion of hydrogen-rich water can improve neurological function due to its ability to penetrate the blood-brain barrier and neutralize reactive oxygen species.”

 

Takeuchi, S., Nagatani, K., Otani, N., Nawashiro, H., Sugawara, T., Wada, K., & Mori, K. (2015). Hydrogen improves neurological function through attenuation of blood–brain barrier disruption in spontaneously hypertensive stroke-prone rats. BioMed Central Neuroscience, 16(22), 1-13. doi: 10.1186/s12868-015-0165-3

 

Hydrogen-rich saline reverses oxidative stress, cognitive impairment, and mortality in rats submitted to sepsis by cecal ligation and puncture

 

“The hippocampal reactive oxygen species and malondialdehyde levels increased significantly, and superoxide dismutase activity decreased significantly. HRS reversed these changes in a dose-dependent manner. These findings indicate that HRS could attenuate the consequences of sepsis induced by cecal ligation and puncture in rats, at least in part, by the inhibition of oxidative stress.”

 

Zhou, J., Chen, Y., Huang, G., Li, J., Wu, G., Liu, L., . . . Wang, J. (2012). Hydrogen-rich saline reverses oxidative stress, cognitive impairment, and mortality in rats submitted to sepsis by cecal ligation and puncture. Journal of Surgical Research, 178(1), 390-400. doi: 10.1016/j.jss.2012.01.041

 
 

Amyotrophic Lateral Sclerosis (ALS)

 

The role of oxidative stress in degeneration of the neuromuscular junction in amyotrophic lateral sclerosis

 

“Amyotrophic lateral sclerosis (ALS) is characterized by the progressive loss of motoneurons and degradation of the neuromuscular junctions (NMJ). Consistent with the dying-back hypothesis of motoneuron degeneration the decline in synaptic function initiates from the presynaptic terminals in ALS. Oxidative stress is a major contributory factor to ALS pathology and affects the presynaptic transmitter releasing machinery. Indeed, in ALS mouse models nerve terminals are sensitive to reactive oxygen species (ROS) suggesting that oxidative stress, along with compromised mitochondria and increased intracellular Ca(2+) amplifies the presynaptic decline in NMJ. This initial dysfunction is followed by a neurodegeneration induced by inflammatory agents and loss of trophic support. To develop effective therapeutic approaches against ALS, it is important to identify the mechanisms underlying the initial pathological events. Given the role of oxidative stress in ALS, targeted antioxidant treatments could be a promising therapeutic approach. However, the complex nature of ALS and failure of monotherapies suggest that an antioxidant therapy should be accompanied by anti-inflammatory interventions to enhance the restoration of the redox balance.”

 

Pollari, E., Goldsteins, G., Bart, G., Koistinaho, J., & Giniatullin, R. (2014). The role of oxidative stress in degeneration of the neuromuscular junction in amyotrophic lateral sclerosis. Frontiers in Cellular Neuroscience, 8(131), 1-8. doi: 10.3389/fncel.2014.00131

 

Treatment with hydrogen-rich saline delays disease progression in a mouse model of amyotrophic lateral sclerosis

 

“Treatment of mutant SOD1 G93A mice with hydrogen-rich saline (HRS, i.p.) significantly delayed disease onset and prolonged survival, and attenuated loss of motor neurons and suppressed microglial and glial activation. Treatment of mutant SOD1 G93A mice with HRS inhibited the release of mitochondrial apoptogenic factors and the subsequent activation of downstream caspase-3. Furthermore, treatment of mutant SOD1 G93A mice with HRS reduced levels of protein carbonyl and 3-nitrotyrosine, and suppressed formation of reactive oxygen species (ROS), peroxynitrite, and malondialdehyde. Treatment of mutant SOD1 G93A mice with HRS preserved mitochondrial function, marked by restored activities of Complex I and IV, reduced mitochondrial ROS formation and enhanced mitochondrial adenosine triphosphate synthesis. In conclusion, hydrogen molecule may be neuroprotective against ALS, possibly through abating oxidative and nitrosative stress and preserving mitochondrial function.”

 

Zhang, Y., Li, H., Yang, C., Fan, D., Guo, D., Hu, H., . . . Pan, S. (2015). Treatment with hydrogen-rich saline delays disease progression in a mouse model of amyotrophic lateral sclerosis. Neurochemical Research, 41(4), 770-778. doi: 10.1007/s11064-015-1750-7

Parkinson’s Disease

 

Studies suggest that H2 water is likely and able to retard the progression and development of Parkinson’s disease, mainly because of its selective antioxidant abilities.

Hydrogen as a selective antioxidant: A review of clinical and experimental studies

“H2 is emerging as a novel and safe therapeutic antioxidant. It has selective antioxidant properties, giving it anti-inflammatory properties.”

 

Hong, Y., Chen, S., & Zhang, J. (2010). Hydrogen as a selective antioxidant: A review of clinical and experimental studies. Journal of International Medical Research, 38(6), 1893-1903. doi: 10.1177/147323001003800602

 

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

“Hydrogen selectively reduces the hydroxyl radical, the most toxic free radical, and effectively protects cells. It does not react with free radicals that have physiological benefits, making it an incredibly effective therapy to neutralize acute oxidative stress.”

 

Ohsawa, I., Ishikawa, M., Takahashi, K., Watanabe, M., Nishimaki, K., Yamagata, K., . . . Ohta, S. (2007). Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nature Medicine, 13(6), 688-694. doi: 10.1038/nm1577

 

A review of hydrogen as a new medical therapy

 

“In the past few years many initial and subsequent clinical studies have demonstrated that hydrogen can act as an important physiological regulatory factor to cells and organs on the antioxidant, anti-inflammatory, anti-apoptotic and other protective effects. So far several delivery methods applied in these studies have proved to be available and convenient, including inhalation, drinking hydrogen-dissolved water and injection with hydrogen-saturated saline.”

 

Zhang, J., Liu, C., Zhou, L., Qu, K., Wang, R., Tai, M., . . . Wang, Z. (2012). A Review of hydrogen as a new medical therapy. Hepatogastroenterology, 59(116), 1026-1032. doi: 10.5754/hge11883

 

Molecular hydrogen is protective against 6-hydroxydopamine-induced nigrostriatal degeneration in a rat model of Parkinson's disease

 

“Molecular hydrogen serves as an antioxidant that reduces hydroxyl radicals, but not the other reactive oxygen and nitrogen species. This study suggests that hydrogen water is likely able to retard the development and progression of Parkinson's disease.”

 

Yuan, F., Ito, M., Fujita, Y., Ito, M., Ichihara, M., Masuda, A., . . . Ohno, K. (2009). Molecular hydrogen is protective against 6-hydroxydopamine-induced nigrostriatal degeneration in a rat model of Parkinson’s disease. Neuroscience Letters, 453(2), 81-85. doi: 10.1016/j.neulet.2009.02.016

 

Pilot study of H2 therapy in Parkinson's disease: A randomized double-blind placebo-controlled trial

 

“Oxidative stress is involved in the progression of Parkinson's disease (PD). Recent studies have confirmed that molecular hydrogen (H2) functions as a highly effective antioxidant in cultured cells and animal models. The results indicated that drinking H2-water was safe and well tolerated, and a significant improvement in total UPDRS scores for patients in the H2-water group was demonstrated.”

 

Yoritaka, A., Takanashi, M., Hirayama, M., Nakahara, T., Ohta, S., & Hattori, N. (2013). Pilot study of H2 therapy in Parkinson's disease: A randomized double-blind placebo-controlled trial. Movement Disorders, 28(6), 836-839. doi: 10.1002/mds.25375

 

Hydrogen in drinking water reduces dopaminergic neuronal loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease

 

“Chronic oxidative stress causes neurodegenerative diseases such as Parkinson's disease (PD). The results of this study indicated that low concentration of H2 in drinking water can reduce oxidative stress in the brain. Thus, drinking H2-containing water may be useful in daily life to prevent or minimize the risk of life style-related oxidative stress and neurodegeneration.”

 

Fujita, K., Seike, T., Yutsudo, N., Ohno, M., Yamada, H., Yamaguchi, H., . . . Noda, M. (2009). Hydrogen in drinking water reduces dopaminergic neuronal loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease. PLOS ONE, 4(9). 1-10. doi: 10.1371/journal.pone.0007247

 

Drinking hydrogen water and intermittent hydrogen gas exposure, but not lactulose or continuous hydrogen gas exposure, prevent 6-hydorxydopamine-induced Parkinson's disease in rats

 

“Lack of dose responses of hydrogen and the presence of favorable effects with hydrogen water and intermittent hydrogen gas suggest that signal modulating activities of hydrogen are likely to be instrumental in exerting a protective effect against PD.”

 

Ito, M., Hirayama, M., Yamai, K., Goto, S., Ito, M., Ichihara, M., & Ohno, K. (2012). Drinking hydrogen water and intermittent hydrogen gas exposure, but not lactulose or continuous hydrogen gas exposure, prevent 6-hydorxydopamine-induced Parkinson’s disease in rats. Medical Gas Research, 2(15), 1-7. doi: 10.1186/2045-9912-2-15

 

Therapeutic effects of hydrogen in animal models of Parkinson's disease

 

“Hydrogen has an ability to reduce oxidative damage and ameliorate the loss of nigrostriatal dopaminergic neuronal pathway in two experimental animal models. Thus, it is strongly suggested that hydrogen might provide a great advantage to prevent or minimize the onset and progression of PD.”

 

Fujita, K., Nakabeppu, Y., & Noda, M. (2011). Therapeutic effects of hydrogen in animal models of Parkinson's disease. Parkinson's Disease, 2011(307875), 1-9. doi: 10.4061/2011/307875

 

Oral 'hydrogen water' induces neuroprotective ghrelin secretion in mice

 

“H₂ supplementation increases gastric expression of mRNA encoding ghrelin, a growth hormone secretagogue, and ghrelin secretion. Strikingly, the neuroprotective effect of H₂ water was abolished by either administration of the ghrelin receptor-antagonist, D-Lys(3) GHRP-6, or atenolol. Thus, the neuroprotective effect of H₂ in PD is mediated by enhanced production of ghrelin. Our findings point to potential, novel strategies for ameliorating pathophysiology in which a protective effect of H₂ supplementation has been demonstrated.”

 

Matsumoto, A., Yamafuji, M., Tachibana, T., Nakabeppu, Y., Noda, M., & Nakaya, H. (2013). Oral ‘hydrogen water’ induces neuroprotective ghrelin secretion in mice. Scientific Reports, 3(3273), 1-5. doi: 10.1038/srep03273

 

Therapeutic approach to neurodegenerative diseases by medical gases: Focusing on redox signaling and related antioxidant enzymes

 

“Together with the fact that H2, and H2S themselves have the ability to react with ROS directly, we strongly suggest that these gases can buffer the ROS and in addition might prevent and/or protect the neurons from oxidative stress damages in neurodegenerative diseases.”

 

Fujita, K., Yamafuji, M., Nakabeppu, Y., & Noda, M. (2012). Therapeutic approach to neurodegenerative diseases by medical gases: Focusing on redox signaling and related antioxidant enzymes. Oxidative Medicine and Cellular Longevity, 2012, 1-9. doi: 10.1155/2012/324256

 
 

Reproductive Health

 

Studies point to the close ties between reproductive health and oxidative stress, from fertility through pregnancy and beyond. H2 may have a variety of strong therapeutic applications for reproductive health, including increasing female fertility, increasing sperm motility, and reducing the risk of pregnancy complications such as miscarriage, preeclampsia, and improving fetal developmental programming.

 

Fertility

 

Oxidative stress and epididymal sperm transport, motility and morphological defects

 

“Radical oxidative species (ROS) have an important effect on sperm quality and quantity. High levels of CP can be measured in iOAT patients, indicating that OS could underlie the aetipopathogenesis of the syndrome. OS negatively affects flagellar axonemal structure with subsequent impairment of forward progressive sperm motility. This can put an attention for antioxidants as a therapy for iOAT syndrome and further research to find how to decrease ROS production.”

 

El-Taieb, M. A., Herwig, R., Nada, E. A., Greilberger, J., Merberger, M. (2009). Oxidative stress and epididymal sperm transport, motility and morphological defects. European Journal of Obstetrics, Gynecology, and Reproductive Biology, 144(1), 199-203. doi: 10.1016/j.ejogrb.2009.02.018

 

Effect of oxidative stress in male infertility

 

“Oxidative stress is involved with many chronic pathological conditions and the current study was designed to evaluate any association that may exist between male infertility and oxidative stress. Infertile male patients show an elevation of oxidative stress markers both in the erythrocytes and in the seminal plasma. Indicating that male infertility might be associated with increased oxidative stress.”

 

Naher, Z., Ali, M., Biswas, S., Mollah, F., Fatima, P., Hossain, M., & Arslan, M. (2013). Effect of oxidative stress in male infertility. Mymensingh Medical Journal, 22(1), 136-142. Retrieved from http://europepmc.org/abstract/med/23416821

Stimulation of human damaged sperm motility with hydrogen molecule

 

“Sperm motility is a critical factor in male fertility. Low motility can be caused by a variety factors including abnormal spermatogenesis, oxidative damage, or depletion of intracellular ATP. H2 treatment significantly improved the rate of forward motility, whereas treatment with nitrogen gas did not. Our results illustrated that H2 treatment stimulates low sperm motility. H2 is a new promising tool for male infertility treatments.”

 

Nakata, K., Yamashita, N., Noda, Y., & Ohsawa, I. (2015). Stimulation of human damaged sperm motility with hydrogen molecule. Medical Gas Research, 5(2), 1-8. doi: 10.1186/s13618-014-0023-x

 

 

Impact of oxidative stress on female fertility

 

“Exposures associated with oxidative stress and with evidence to influence the timing and maintenance of a viable pregnancy include pregnancy complications (e.g. preeclampsia), extremes of body weight, alcohol, tobacco, and caffeine intake. Identifying modifiable factors to decrease oxidative stress in the gynecologic environment may be an inexpensive and noninvasive therapy for increasing fertility.”

 

Ruder, E. H., Hartman, T. J., & Goldman, M. B. (2009). Impact of oxidative stress on female fertility. Current Opinion in Obstetrics and Gynecology, 21(3), 219-222. doi: 10.1097/gco.0b013e32832924ba

 

Protective effects of hydrogen-rich saline against erectile dysfunction in a streptozotocin induced diabetic rat model

 

“Hydrogen-rich saline improved nitric oxide synthase activity, and malondialdehyde, nitrite and nitrate, and 8-hydroxydeoxyguanosine levels in the diabetic rat corpus cavernosum. Hydrogen-rich saline effectively improved erectile function in a streptozotocin induced diabetic rat model of erectile dysfunction.”

 

Fan, M., Xu, X., He, X., Chen, L., Qian, L., Lio, J., & Sun, X. (2013). Protective effects of hydrogen-rich saline against erectile dysfunction in a streptozotocin induced diabetic rat model. The Journal of Urology, 190(1), 350-356. doi: 10.1016/j.juro.2012.12.001

 

The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy

 

“Oxidative stress in the male germ line is thought to affect male fertility and impact upon normal embryonic development. Adequately powered, placebo-controlled comprehensive clinical trials are now required to establish a clear role for antioxidants in the prevention of oxidative stress in the male germ line, such that the clinical utility of this form of therapy becomes established once and for all.”

 

Niederberger, C. (2012). Re: The role of sperm oxidative stress in male infertility and the significance of oral antioxidant therapy. The Journal of Urology, 187(4), 1377. doi: 10.1016/j.juro.2011.12.130

 

The role of oxidative stress and antioxidants in male fertility

 

“Spermatozoa are particularly vulnerable to the harmful effects of ROS. Oxidative stress affects their activity, damages DNA structure, and accelerates apoptosis, all of which consequently decrease their numbers, hinders motility and development of normal morphology, and impairs function.  In vitro and in vivo that studies demonstrate many antioxidants possess a beneficial effect on fertility and, therefore, their use is recommended as supportive therapy for the treatment of infertility in men.”

 

Walczak–Jedrzejowska, R., Wolski, J. K., & Slowikowska–Hilczer, J. (2013). The role of oxidative stress and antioxidants in male fertility. Central European Journal of Urology, 65, 60-67. doi: 10.5173/ceju.2013.01.art19

 

Pregnancy

 

Oxidative status and serum prolidase activity in tubal ectopic pregnancy

 

“Total antioxidant capacity levels were lower in the ectopic pregnancy group than the healthy group (p < 0.018), whereas total oxidant status, oxidative stress index and prolidase activity were higher (p < 0.05). Ectopic pregnancy may be associated with increased serum prolidase activity and oxidative stress, and this association may help to provide a better understanding about the pathogenesis of ectopic pregnancy.”

 

Hilali, N., Aksoy, N., Vural, M., Camuzcuoglu, H., & Taskin, A. (2013). Oxidative status and serum prolidase activity in tubal ectopic pregnancy. Journal of the Pakistan Medical Association, 63(2), 169-172. Retrieved from http://www.jpma.org.pk/PdfDownload/3990.pdf

 

Oxidative stress damage as a detrimental factor in preterm birth pathology

 

“Normal term and spontaneous preterm births (PTB) are documented to be associated with oxidative stress (OS), and imbalances in the redox system (balance between pro- and antioxidant) have been reported in the maternal-fetal intrauterine compartments. We postulate that fetal cell senescence signals generated by OS damage are likely triggers for labor.”

 

Menon, R. (2014). Oxidative stress damage as a detrimental factor in preterm birth pathology. Frontiers in Immunology, 5(567), 1-14. doi: 10.3389/fimmu.2014.00567

 

The roles of cellular reactive oxygen species, oxidative stress and antioxidants in pregnancy outcomes

 

“Imbalances between ROS production and antioxidant systems induce oxidative stress that negatively impacts reproductive processes. High levels of ROS during embryonic, fetal and placental development are a feature of pregnancy. Consequently, oxidative stress has emerged as a likely promoter of several pregnancy-related disorders, such as spontaneous abortions, embryopathies, preeclampsia, fetal growth restriction, preterm labor and low birth weight.” 

 

Al-Gubory, K. H., Fowler, P. A., & Garrel, C. (2010). The roles of cellular reactive oxygen species, oxidative stress and antioxidants in pregnancy outcomes. The International Journal of Biochemistry & Cell Biology, 42(10), 1634-1650. doi: 10.1016/j.biocel.2010.06.001

 

A quantitative evaluation of total antioxidant status and oxidative stress markers in preeclampsia and gestational diabetic patients in 24-36 weeks of gestation

 

“We concluded that increased oxidative stress and reduction in antioxidant defense mechanisms may contribute to disease processes both in GDM and preeclampsia.”

 

Karacay, Ö., Sepici-Dincel, A., Karcaaltincaba, D., Sahin, D., Yalvaç, S., Akyol, M., . . . Altan, N. (2010). A quantitative evaluation of total antioxidant status and oxidative stress markers in preeclampsia and gestational diabetic patients in 24–36 weeks of gestation. Diabetes Research and Clinical Practice, 89(3), 231-238. doi: 10.1016/j.diabres.2010.04.015

 

Study of oxidative stress and enzymatic antioxidants in normal pregnancy

 

“Pregnancy is a physiological state accompanied by a high-energy demand and an increased oxygen requirement. It was observed that pregnant women were more susceptible to oxidative damage than non-pregnants as indicated by increased thiobarbituric acid reactive substance and decreased antioxidants.”

 

Patil, S. B., Kodliwadmath, M. V., & Kodliwadmath, S. M. (2007). Study of oxidative stress and enzymatic antioxidants in normal pregnancy. Indian Journal of Clinical Biochemistry, 22(1), 135-137. doi: 10.1007/bf02912897

 

 

Role of oxidative stress in the pathogenesis of preeclampsia

 

“Published evidence of altered biomarkers for the endothelial dysfunction suggests that the initiating event in preeclampsia is the reduced placental perfusion, which leads to widespread dysfunction of the maternal vascular endothelium. This review focuses on the role of free radicals in generating the oxidative stress taking antioxidants into consideration which tend to overcome it as well as the role of placenta in preeclamptic pregnancy.”