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Hydrogen Era

Hydrogen Therapy

History of hydrogen therapy

A Brief History of H2 as a Medical Gas

Although hydrogen therapy may seem as a new phenomenon in the medical field, animal trials evaluating hydrogen as a therapeutic agent since 1789, when Antoine Laurent Lavoisier exposed a type of pigs to hydrogen while investigating the properties of air. As such a newly discovered element, a century passed until further medical experiments with hydrogen were again documented. In 1888, a flurry of reports reported that insufflation, an application where hydrogen is delivered directly into body cavities, could assist with the diagnosis of visceral injury. However, researchers did not expand on these reports, and it would be another 150 years before hydrogen gas was considered as a therapeutic agent, when it was demonstrated that H2 inhalation could be used as a physiological recovery aide for the deep-sea divers.

In 1944, Arne Zetterstrom was credited with creating Hydrox gas, a combination of hydrogen and oxygen (96% and 4%, respectively) that allowed deep-sea divers to traverse depths of up to 500m by preventing decompression sickness. The hydrogen–oxygen mixture can be compressed into cylinders, as the low concentration of oxygen renders the composition nonexplosive, making this method of hydrogen delivery valuable, particularly for exploration, industrial use, and submarine rescue scenarios. Despite the popularity and demonstrated efficacy of hydrogen as an inhalation treatment, further advances in medical research were not put forward until 1975, when Dole and colleagues realized that hyperbaric administration (95% H2/8atm) of H2 for periods of 10–14 days could reduce squamous cell carcinoma in murine models of disease. Even though this discovery was revolutionary, medical hydrogen research again subsided, and it was another thirteen years before another article in this field was published. Shirahata and colleagues describe hydrogen created from the electrolysis of water, could protect DNA from oxidative damage. In 2001, building upon the research conducted by Dole et al., Gharib and associates described a reduction in markers of liver disease resulting from chronic inflammation when utilizing hyperbaric administration of H2 (0.7 MPa for two weeks). Once again, however, research into medical hydrogen lapsed and was not revived until 2007, when Ohsawa’s laboratory in the Department of Biochemistry and Cell Biology, Nippon Medical School, Japan, reported an antioxidant effect of H2 in a rodent model of ischemia-reperfusion injury. Since Ohsawa’s discovery, there has been renewed interest in the effects of H2 as an Aesculapian gas and research into this promising area of medicine is developing rapidly.

Basic Characteristics of H2:

H2 has two different characteristics

Molecular hydrogen is a colorless, odorless, and tasteless gas molecule with poor water solubility. It is considered inert in mammalian cells under physiological conditions. Molecular hydrogen can be broken down by some bacteria via enzymatic catalysis to provide energy and electrons. In addition, bacteria produce molecular hydrogen by anaerobic metabolism. Genes encoding the iron- or nickel-containing enzymes necessary to catalyze these reactions, such as hydrogenase, are lacking in mammals. However, molecular hydrogen is now recognized as a novel medically relevant gas with therapeutic potential. Ohsawa et al. (2007) reported that the inhalation of 2% molecular hydrogen results in the selective scavenging of hydroxyl free radical (·OH) and peroxynitrite anion (ONOO-), significantly improving oxidative stress injury caused by cerebral ischemia/reperfusion (I/R). This study prompted substantial interest in the medical value of molecular hydrogen, and many cellular, animal, and clinical trials and studies have since investigated its preventive and therapeutic effects. Molecular hydrogen can exert biological effects on almost all organs, including the brain, heart, lung, liver, and pancreas. It has a variety of biological functions, including roles in the regulation of oxidative stress and anti-inflammatory and anti-apoptotic effects.

Mechanism of Action of H2:

1. Anti-oxidation

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are by-products of energy metabolism during daily activities. ROS/RNS include superoxide anion (O2 -), ·OH, peroxyl (RO2·), alkoxyl (RO·), and nitric oxide (NO·) radicals. They play critical roles under normal conditions in immune defense, signaling processes, and the extraction of energy from organic molecules. However, if ROS and RNS production exceeds the antioxidant capacity of the body or if the antioxidant capacity of the body is decreased, oxidative stress occurs.

Acute oxidative stress often occurs during inflammation and I/R (e.g., cardiac arrest, myocardial and cerebral infarction, organ transplantation, and intraoperative hemostasis). Chronic ROS injury can occur in a variety of pathological conditions, such as malignant cancer, diabetes, chronic inflammatory diseases, atherosclerosis, and neurodegeneration, as well as in the process of aging. Humans have antioxidant defense systems to protect against free radical toxicity. Antioxidants are divided into enzymatic and non-enzymatic types. Enzymatic types include superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), and non-enzymatic types include bilirubin, α‍-tocopherol (vitamin E), β‍-carotene, and uric acid.

The antioxidant effects of molecular hydrogen are primarily mediated by the following mechanisms:

(1) Molecular hydrogen has a lower molecular weight than other common antioxidants (e.g., SOD, CAT, and α‍-tocopherol). It can selectively react with strong oxidants and can easily penetrate biological membranes, such as nuclear and mitochondrial membranes, without affecting the metabolic redox reaction.

(2) By stimulating nuclear factor erythroid 2-related factor 2 (Nrf2), which regulates the basal and induces expression of many antioxidant enzymes and the proteasome, hydrogen can increase the expression of heme oxygenase-1 (HO-1). It also decreases ·ONOO-related gene expression and production and increases the activity of the antioxidant enzymes SOD, CAT, and myeloperoxidase (MPO).

(3) Molecular hydrogen can block the apoptosis signal-regulating kinase 1 (ASK1) signaling pathway and the downstream signaling molecule p38 mitogen-activated protein kinase (p38MAPK), thereby inhibiting nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity and decreasing free radical production. Through these antioxidant effects, molecular hydrogen protects cells from lipid and fatty acid peroxidation.

2. Anti-inflammatory effects

The major mechanisms underlying the anti-inflammatory effects of molecular hydrogen are as follows:

(1) It inhibits the synthesis and release of the pro-inflammatory factors tumor necrosis factor-‍‍α (TNF-‍α), interleukin (IL)-‍‍‍1β, IL-6, nuclear factor-‍κB (NF-‍κB), and high-mobility group box 1 (HMGB-1); increases the expression of the anti-inflammatory factor IL-‍10; inhibits the release of chemokines, including keratinocyte-derived chemokine, macrophage inflammatory protein (MIP)-‍1α, MIP-2, and monocyte chemoattractant protein 1; and inhibits the release of intercellular cell adhesion molecule-1 (ICAM-1), granulocyte-macrophage colony-stimulating factor (GMCSF), and granulocyte colony-stimulating factor (G-CSF).

(2) It promotes macrophage phagocytosis at lesion sites and inhibits the recruitment of neutrophils and M1 macrophages to lesions.

(3) The anti-inflammatory effects of molecular hydrogen involve multiple signaling pathways. For example, the stimulation of the Nrf2/HO-1/HMGB-1 pathway mitigates endothelial dysfunction and lung injury caused by polymicrobial sepsis. The inhibition of p38MAPK and c-Jun N-terminal kinase (JNK) alleviates lipopolysaccharide (LPS)-induced ALI. The modulation of autophagy-related pathways, such as the mammalian target of rapamycin (mTOR)/transcription factor EB (TFEB) and phosphatase and tensin homolog (PTEN)‍-induced kinase 1 (PINK1)/Parkin pathways, mitigates ALI endothelial dysfunction and myocardial I/R injury.

3. Regulation of autophagy

In eukaryotic cells, catabolism is the degradation of intracellular components by the ubiquitin-proteasome system and lysosomes. Autophagy (particularly macro‍autophagy) is defined as a lysosome-dependent catabolic process for maintaining cellular homeostasis. However, when stress exceeds a critical duration or intensity threshold, it may have maladaptive effects, causing cell damage or even death. Emerging evidence suggests that hydrogen has dual roles in the modulation of autophagy (i.e., roles in both its promotion and inhibition).

4. Regulation of apoptosis

Apoptosis is a canonical form of programmed cell death that does not stimulate inflammatory responses. It is an evolutionarily conserved type of cell death with major effects on biological processes. The molecular mechanism underlying apoptosis involves the sequential activation of cysteine proteases, called caspases, and a series of pro-apoptotic and anti-apoptotic B-cell lymphoma-2 (Bcl-2) family proteins. In various disease models and organs, molecular hydrogen plays a protective role by regulating apoptosis.

It can inhibit apoptosis by regulating apoptosis signaling pathways and apoptosis-related proteins, such as the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK3β), ASK1/JNK, rat sarcoma (Ras)-extracellular signal-related kinase 1/2 (ERK1/2)-mitogen-activated protein kinase 1/2 (MEK1/2), and Akt pathways, and by suppressing the activation of caspase-3, -8, and -9 and the Bcl-2/Bcl-2-associated X (Bax) ratio. Molecular hydrogen also reduces the rate of apoptosis by reducing inflammation and oxidative damage and protects mitochondrial function. The inhibition of autophagy improves cell survival and inhibits apoptosis. For example, in an I/R myocardial injury model, PINK-mediated autophagy alleviates inflammation and apoptosis. Accordingly, there is crosstalk among molecular hydrogen, apoptosis, and autophagy.

5. Regulation of aging

Aging is a progressive loss of physiological function and is an unavoidable process ending in death. It is now considered a major factor underlying the development and progression of various diseases, such as COPD and idiopathic PF. Molecular hydrogen can decrease the expression of the aging-related proteins β‍-galactosidase, p53, and p21, suppress downregulation of sirtuin 3 (Sirt3) expression, and reduce oxidative stress damage, thereby extending cell survival. Research has shown that molecular hydrogen produced by intestinal bacteria in the body suppresses increased hydrogen peroxide (H2O2) by suppressing intracellular ·OH-mediated lipid peroxide formation and cellular senescence, thus contributing to the suppression of aging. Genomic instability is one of the primary hallmarks of the aging process. By reducing oxidative DNA damage, hydrogen can help maintain genomic stability. For example, in cigarette smoke (CS)‍-induced emphysema, hydrogen significantly decreased phosphorylated histone H2AX and 8-hydroxy-2′-deoxyguanosine (8-OHdG), which are markers of oxidative DNA damage. As a “philosophical molecule,” hydrogen may be used for the treatment of intractable diseases and aging.

Routes of H2 Administration:

Hydrogen gas has some special characteristics, such as its nonpolarity, small size, and low solubility (1.6 ppm (part per million, ×10-6)) under physiological conditions. Typical administration routes include the inhalation of hydrogen gas, oral intake of HRW, and injection of HRS. Inhalation is a simple method in which a ventilator circuit, facemask, or nasal cannula is used to administer hydrogen gas. The effects are rapid, and it can be used to treat acute oxidative stress. The oral intake of HRS, which is hydrogen dissolved in water, is a portable, safe, and convenient method for administration. Under normal atmospheric pressure and at room temperature, hydrogen can be dissolved in water up to 0.8 mmol/L (1.6 mg/L). The injection of HRS can provide highly accurate hydrogen doses. Either peritoneal or intravenous injection can be applied to provide a protective effect. In addition, intrathecal injection can produce neuro-protective effects. Its lack of polarity and easy cell penetration make hydrogen promising for the treatment of skin and eye diseases with topical formulations and eye drops.

The Safety of Hydrogen

The safety of hydrogen for humans is demonstrated by its application in Hydreliox, an exotic breathing gas mixture of 49% hydrogen, 50% helium and 1% oxygen, which is used for the prevention of decompression sickness and nitrogen narcosis during very deep technical diving. Also, no adverse effects have been found using drinking hydrogen water in a human study. A study showed that 20 subjects with potential metabolic syndrome consumed 1.5-2.0 l/day of H2–saturated water for 8 weeks, the treated subjects showed significant improvements in liver and kidney function, which showed that H2 had no toxic side effects on liver and kidney and may even protect liver and kidney function. Another study also showed that hemodialysis patients treated with dialysis solution with H2 for 6 months had no adverse clinical signs or symptoms. All these studies are existed in the references section.

Contatc us Now

    Below are some references and researchs that illustrate the extent of the positive therapeutic effect of hydrogen:

    Reference

    Title

    Subject

    Year

    HYDROGEN RESEARCH ON INTESTINES & STOMACH

    Sha, J.B., Zhang, S.S., Lu, Y.M., Gong, W.J., Jiang, X.P., Wang, J.J., Qiao, T.L., Zhang, H.H., Zhao, M.Q., Wang, D.P. and Xia, H., 2018. Effects of the long-term consumption of hydrogen-rich water on the antioxidant activity and the gut flora in female juvenile soccer players from Suzhou, China. Medical gas research, 8(4), p.135.

    Effects of the long-term consumption of hydrogen-rich water on the antioxidant activity and the gut flora in female juvenile soccer players from Suzhou, China

    Gut Flora

    2019

    Zheng, W., Ji, X., Zhang, Q. and Yao, W., 2018. Intestinal microbiota ecological response to oral administrations of hydrogen-rich water and lactulose in female piglets fed a Fusarium toxin-contaminated diet. Toxins, 10(6), p.246.

    Intestinal Microbiota Ecological Response to Oral Administrations of Hydrogen-Rich Water and Lactulose in Female Piglets Fed a Fusarium Toxin Contaminated Diet.

    Protects-Good

    Bacteria

    2018

    Xiao, H.W., Li, Y., Luo, D., Dong, J.L., Zhou, L.X., Zhao, S.Y., Zheng, Q.S., Wang, H.C., Cui, M. and Fan, S.J., 2018. Hydrogen-water ameliorates radiation-induced gastrointestinal toxicity via MyD88’s effects on the gut microbiota. Experimental & Molecular Medicine, 50(1), pp.e433-e433.

    Hydrogen-water ameliorates radiation-induced gastrointestinal toxicity via MyD88’s effects on the gut microbiota.

    GI Toxicity

    2018

    Shen, N.Y., Bi, J.B., Zhang, J.Y., Zhang, S.M., Gu, J.X., Qu, K. and Liu, C., 2017. Hydrogen-rich water protects against inflammatory bowel disease in mice by inhibiting endoplasmic reticulum stress and promoting heme oxygenase-1 expression. World Journal of Gastroenterology, 23(8), p.1375.

    Hydrogen-rich water protects against inflammatory bowel disease in mice by inhibiting endoplasmic reticulum stress and promoting heme oxygenase-1 expression.

     

    Inflammatory

    Bowel Disease

    2017

    HYDROGEN RESEARCH ON SKIN

    Zhao, P., Dang, Z., Liu, M., Guo, D., Luo, R., Zhang, M., Xie, F., Zhang, X., Wang, Y., Pan, S. and Ma, X., 2023. Molecular hydrogen promotes wound healing by inducing early epidermal stem cell proliferation and extracellular matrix deposition. Inflammation and Regeneration, 43(1), pp.1-21.

    Molecular hydrogen promotes wound healing by inducing early epidermal stem cell proliferation and extracellular matrix deposition

    Wound Healing

    2023

    Fang, W., Tang, L., Wang, G., Lin, J., Liao, W., Pan, W. and Xu, J., 2020. Molecular hydrogen protects human melanocytes from oxidative stress by activating Nrf2 signaling. Journal of Investigative Dermatology, 140(11), pp.2230-2241.

    Molecular Hydrogen Protects Human

    Melanocytes from Oxidative Stress by Activating Nrf2 Signaling.

    Melanocytes Oxidative Stress

    2020

    Zhu, Q., Wu, Y., Li, Y., Chen, Z., Wang, L., Xiong, H., Dai, E., Wu, J., Fan, B., Ping, L. and Luo, X., 2018. Positive effects of hydrogen-water bathing in patients of psoriasis and parapsoriasis en plaques. Scientific reports, 8(1), p.8051.

    Positive effects of hydrogen-water bathing in patients of psoriasis and parapsoriasis en plaques.

    Psoriasis

    2018

    Li, Q., Kato, S., Matsuoka, D., Tanaka, H. and Miwa, N., 2013. Hydrogen water intake via tube-feeding for patients with pressure ulcer and its reconstructive effects on normal human skin cells in vitro. Medical gas research, 3, pp.1-17.

    Hydrogen water intake via tube-feeding for patients with pressure ulcer and its reconstructive effects on normal human skin cells in vitro.

    Skin Ulcers

    2013

    Ignacio, R.M.C., Kwak, H.S., Yun, Y.U., Sajo, M.E.J.V., Yoon, Y.S., Kim, C.S., Kim, S.K. and Lee, K.J., 2013. The drinking effect of hydrogen water on atopic dermatitis induced by Dermatophagoides farinae allergen in NC/Nga mice. Evidence-Based Complementary and Alternative Medicine, 2013.

    The Drinking Effect of Hydrogen Water on Atopic Dermatitis Induced by Dermatophagoides farinae Allergen in NC/Nga Mice.

    Dermatitis

    2013

    Ono, H., Nishijima, Y., Adachi, N., Sakamoto, M., Kudo, Y., Nakazawa, J., Kaneko, K. and 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(1), pp.1-9.

    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.

    Skin Diseases

    2012

    Kato, S., Saitoh, Y., Iwai, K. and 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, pp.24-33.

    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.

    Wrinkles

    2012

    HYDROGEN RESEARCH ON ANTIOXIDANT

    Xie, F., Song, Y., Yi, Y., Jiang, X., Ma, S., Ma, C., Li, J., Zhanghuang, Z., Liu, M., Zhao, P. and Ma, X., 2023. Therapeutic Potential of Molecular Hydrogen in Metabolic Diseases from Bench to Bedside. Pharmaceuticals, 16(4), p.541.

    Therapeutic Potential of Molecular Hydrogen in Metabolic Diseases from Bench to Bedside

    Metabolic Disorders

    2023

    Li, J., Ge, Z., Fan, L. and Wang, K., 2017. Protective effects of molecular hydrogen on steroid-induced osteonecrosis in rabbits via reducing oxidative stress and apoptosis. BMC Musculoskeletal Disorders, 18(1), pp.1-9.

    Protective effects of molecular hydrogen on steroid-induced osteonecrosis in rabbits via reducing oxidative stress and

    apoptosis.

    Bone-Health

    2017

    Yoneda, T., Tomofuji, T., Kunitomo, M., Ekuni, D., Irie, K. and Azuma, T., Preventive effects of drinking hydrogen-rich water on gingival oxidative stress and alveolar bone resorption in rats fed a high-fat diet. Nutrients. 2017; 9 (1). pii: E64.

    Preventive Effects of Drinking Hydrogen-Rich Water on Gingival Oxidative Stress and Alveolar Bone Resorption in Rats Fed a High-Fat Diet.

    Obesity

    2017

    Settineri, R., Ji, J., Luo, C., Ellithorpe, R.R., de Mattos, G.F., Rosenblatt, S., LaValle, J., Jinenez, A., Ohta, S. and Nicolson, G.L., 2016. Effects of Hydrogenized Water on Intracellular Biomarkers for Antioxidants, Glucose Uptake, Insulin Signaling and SIRT 1 and Telomerase Activity. American Journal of Food and Nutrition, 4(6), pp.161-168.

    Effects of Hydrogen Water on Intracellular Biomarkers for Antioxidants, Glucose Uptake, Insulin Signaling and SIRT 1 and elomerase Activity.

    Antioxidant

    2016

    Takeuchi, S., Wada, K., Nagatani, K., Osada, H., Otani, N. and Nawashiro, H., 2012. Hydrogen may inhibit collagen-induced platelet aggregation: an ex vivo and in vivo study. Internal Medicine, 51(11), pp.1309-1313.

    Hydrogen may inhibit collagen-induced platelet aggregation: an ex vivo and in vivo study.

    Platelets

    2012

    Kubota, M., Shimmura, S., Kubota, S., Miyashita, H., Kato, N., Noda, K., Ozawa, Y., Usui, T., Ishida, S., Umezawa, K. and Kurihara, T., 2011. Hydrogen and N-acetyl-L-cysteine rescue oxidative stress-induced angiogenesis in a mouse cornealalkali-burn model. Investigative ophthalmology & visual science, 52(1), pp.427-433.

    Hydrogen and N-acetyl-L-cysteine rescue oxidative stress-induced angiogenesis in a mouse corneal alkali-burn model.

    Eyes – Cornea

    2011

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

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

    Obesity &

    Diabetes

    2011

    HYDROGEN RESEARCH ON ANTI-AGING

    Zhang, W., Huang, C., Sun, A., Qiao, L., Zhang, X., Huang, J., Sun, X., Yang, X. and Sun, S., 2018. Hydrogen alleviates cellular senescence via regulation of ROS/p53/p21 pathway in bone marrow-derived mesenchymal stem cells in vivo. Biomedicine & Pharmacotherapy, 106, pp.1126-1134.

    Hydrogen alleviates cellular senescence via regulation of ROS/p53/p21 pathway in bone marrow-derived mesenchymal stem cells in vivo.

    Reduction of

    Senescence-Associated

    Cells

    2018

    Han, A.L., Park, S.H. and Park, M.S., 2017. Hydrogen treatment protects against cell death and senescence induced by oxidative damage. Journal of Microbiology and Biotechnology, 27(2), pp.365-371.

    Hydrogen Treatment Protects against Cell Death and Senescence Induced by Oxidative Damage.

    Anti-Aging & Cell Death

    2017

    Kawasaki, H., Guan, J. and 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), pp.608-613.

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

    Anti-Aging; Bones

    2010

    Park, S.K. and Park, S.K., 2013. Electrolyzed-reduced water increases resistance to oxidative stress, fertility, and lifespan via insulin/IGF-1-like signal in C. elegans. Biological Research, 46(2), pp.147-152.

    Electrolyzed-reduced water increases resistance to oxidative stress, fertility, and lifespan via insulin/IGF-1-like signal in C. elegans.

    Increased Lifespan

    2013

    Shirahata, S., Kabayama, S., Nakano, M., Miura, T., Kusumoto, K., Gotoh, M., Hayashi, H., Otsubo, K., Morisawa, S. and Katakura, Y., 1997. Electrolyzed–reduced water scavenges active oxygen species and protects DNA from oxidative damage. Biochemical and biophysical research communications, 234(1), pp.269-274.

    Electrolyzed-reduced water scavenges active oxygen species and protects DNA from oxidative damage. [Animal study shows hydrogen helps to protect DNA and scavenges harmful radicals.

    Protects DNA

    1997

    HYDROGEN RESEARCH ON ONCOLOGY

    Noor, M.N.Z.M., Alauddin, A.S., Wong, Y.H., Looi, C.Y., Wong, E.H., Madhavan, P. and Yeong, C.H., 2023. A Systematic Review of Molecular Hydrogen Therapy in Cancer Management. Asian Pacific journal of cancer prevention: APJCP, 24(1), p.37.

    A Systematic Review of Molecular Hydrogen Therapy in Cancer Management

    Cancer Management

    2023

    Hirano, S.I., Yamamoto, H., Ichikawa, Y., Sato, B., Takefuji, Y. and Satoh, F., 2021. Molecular Hydrogen as a Novel Antitumor Agent: Possible Mechanisms Underlying Gene Expression. International Journal of Molecular Sciences, 22(16), p.8724.

    Molecular Hydrogen as a Novel Antitumor Agent: Possible Mechanisms Underlying Gene Expression

    Antitumor Agent

    2021

    Hirano, S.I., Aoki, Y., Li, X.K., Ichimaru, N., Takahara, S. and Takefuji, Y., 2021. Protective effects of hydrogen gas inhalation on radiation-induced bone marrow damage in cancer patients: a retrospective observational study. Medical Gas Research, 11(3), p.104.

    Protective effects of hydrogen gas inhalation on radiation-induced bone marrow damage in cancer patients: a retrospective observational study

    Bone Marrow Damage

    2019

    Yang, Q., Ji, G., Pan, R., Zhao, Y. and Yan, P., 2017. Protective effect of hydrogen‑rich water on liver function of colorectal cancer patients treated with mFOLFOX6 chemotherapy. Molecular and Clinical Oncology, 7(5), pp.891-896.

    Protective effect of hydrogen‑rich water on liver function of colorectal cancer patients treated with mFOLFOX6 chemotherapy

    Colorectal Cancer

    2017

    HYDROGEN RESEARCH ON PHYSIOTHERAPY

    Zhou, K., Liu, M., Wang, Y., Liu, H., Manor, B., Bao, D., Zhang, L. and Zhou, J., 2023. Effects of molecular hydrogen supplementation on fatigue and aerobic capacity in healthy adults: A systematic review and meta-analysis. Frontiers in Nutrition, 10, p.1094767.

    Effects of molecular hydrogen supplementation on fatigue and aerobic capacity in healthy adults: A systematic review and meta-analysis

    Fatigue

    2023

    Tanaka, Y., Xiao, L. and Miwa, N., 2022. Hydrogen-rich bath with nano-sized bubbles improves antioxidant capacity based on oxygen radical absorbing and inflammation levels in human serum. Medical Gas Research, 12(3), p.91.

    Hydrogen-rich bath with nano-sized bubbles improves antioxidant capacity based on oxygen radical absorbing and inflammation levels in human serum

    Antioxidant Capacity

    2022

    Kawamura, T., Higashida, K. and Muraoka, I., 2020. Application of molecular hydrogen as a novel antioxidant in sports science. Oxid Med Cell Longev 2020: 2328768.

    Application of Molecular Hydrogen as a Novel Antioxidant in Sports Science

    Sports Science

    2020

    Shibayama, Y., Dobashi, S., Arisawa, T., Fukuoka, T. and Koyama, K., 2020. Impact of hydrogen-rich gas mixture inhalation through nasal cannula during post-exercise recovery period on subsequent oxidative stress, muscle damage, and exercise performances in men. Medical Gas Research, 10(4), p.155.

    Impact of hydrogen-rich gas mixture inhalation through nasal cannula during post-exercise recovery period on subsequent oxidative stress, muscle damage, and exercise performances in men

    Post-exercise Recovery

    2020

    Javorac, D., Stajer, V., Ratgeber, L., Betlehem, J. and Ostojic, S., 2019. Short-term H2 inhalation improves running performance and torso strength in healthy adults. Biology of Sport, 36(4), pp.333-339.

    Short-term H2 inhalation improves running performance and torso strength in healthy adults

    Running Performance

    2019