Studies Referencing Hydrogen and Diabetes (Type I and II)

Database:

Primary Topic: Any

Secondary Topic: Diabetes/Diabetes (Type I)/Diabetes (Type II)

Tertiary Topic: Diabetic Nephropathy/Diabetic Retinopathy/Foot Ulcer/Glucose Metabolism/Peripheral Neuropathy, Diabetic (DPN) (or Any)

● Hydrogen improves Diabetes-related markers including

• decreasing fasting glucose (47: Asada et al 2020; 806: Wang et al 2012; 970: Jin et al 2006; 972: Kim and Kim 2006; 1046: Shirahata et al 2011; 850: Li et al 2011; 851: Li et al 2011; 40: Zheng et al 2021; 107: Ming et al 2020; 387: Guo et al 2017; 428: Siswantoro, Purwanto, and Sutomo 2017; 463: Zhang et al 2017; 843: Kamimura et al 2011; 912: Osada et al 2010; 953: Gadek, Hamasaki, and Shirahata al 2008; 956: Kajiyama et al 2008; 963: Kim et al 2007; 966: Shirahata et al 2007; 967: Gadek, Li, and Shirahata 2006; 992: Gadek and Shirahata 2002; 1139: Ogawa et al 2021; 1164: Zou et al 2022),
• decreasing serum fructosamine (47: Asada et al 2020) and cholesterol/triglycerides (806: Wang et al 2012; 970: Jin et al 2006; 40: Zheng et al 2021; 463: Zhang et al 2017; 843: Kamimura et al 2011; 912: Osada et al 2010; 953: Gadek, Hamasaki, and Shirahata al 2008; 956: Kajiyama et al 2008),
• increasing glucose sensitivity/uptake (972: Kim and Kim 2006; 994: Li et al 2002; 1046: Shirahata et al 2011; 689: Amitani et al 2013; 993: Li et al 2002; 107: Ming et al 2020; 463: Zhang et al 2017; 912: Osada et al 2010; 963: Kim et al 2007; 966: Shirahata et al 2007; 1000: Shirahata et al 2001; 1010: Oda et al 1999)
• and reducing insulin resistance (806: Wang et al 2012; 107: Ming et al 2020; 463: Zhang et al 2017; 956: Kajiyama et al 2008; 1139: Ogawa et al 2021; 1158: Retnaningtyas et al 2022), and increasing serum 1,5-Anhydroglucitol (47: Asada et al 2020).

● Hydrogen protects against Diabetes-induced tissue damage including

• Pancreatic β-Cell damage (972: Kim and Kim 2006; ; 850: Li et al 2011; 851: Li et al 2011; 978: Li et al 2005; 993: Li et al 2002; 107: Ming et al 2020; 963: Kim et al 2007),
• Diabetic Nephropathy (11: Indrajani et al 2021; 40: Zheng et al 2021; 463: Zhang et al 2017; 776: Katakura et al 2012),
• Diabetic Peripheral Neuropathy (65: Yu et al 2016; 79: Jiao et al 2020; 309: Li et al 2018; 607: Yu et al 2015),
• Diabetic Cardiomyopathy (599: Wu et al 2015; 1115: Zhao et al 2021),
• Diabetic Retinopathy (697: Feng et al 2013; 715: Liu et al 2013; 810: Xiao et al 2012; 1164: Zou et al 2022),
• Non-Alcoholic Fatty Liver Disease (40: Zheng et al 2021; 843: Kamimura et al 2011),
• Osteoporosis (387: Guo et al 2017),
• Diabetic Skin/Foot Ulcer (126: Supardi et al 2020; 884: Yu et al 2011),
• and Erectile Dysfunction (696: Fan et al 2013).

● Hydrogen can protect the body from toxicity due to the antidiabetic medication Metformin (1115: Zhao et al 2021).

● Hydrogen leads to a reduction of bodily cellular oxidation products, indicators of Diabetes-induced oxidative stress, including

• 8-hydroxy-2-deoxyguanosine (47: Asada et al 2020; 65: Yu et al 2016; 309: Li et al 2018; 607: Yu et al 2015; 697: Feng et al 2013; 696: Fan et al 2013),
• malondialdehyde (806: Wang et al 2012; 107: Ming et al 2020; 696: Fan et al 2013),
• 3-nitrotyrosine (884: Yu et al 2011),
• and 4-hydroxynonenal (697: Feng et al 2013).

● Hydrogen shows multiple modes of action of improving Diabetes, including

• quenching cellular ROS (47: Asada et al 2020; 65: Yu et al 2016; 607: Yu et al 2015; 706: Jiang et al 2013; 884: Yu et al 2011; ; 1046: Shirahata et al 2011; 850: Li et al 2011; 851: Li et al 2011; 978: Li et al 2005; 993: Li et al 2002; 776: Katakura et al 2012; 953: Gadek, Hamasaki, and Shirahata al 2008; 966: Shirahata et al 2007; 967: Gadek, Li, and Shirahata 2006; 1010: Oda et al 1999; 309: Li et al 2018),
• increasing the activity of endogenous antioxidant enzymes (697: Feng et al 2013; 706: Jiang et al 2013; 806: Wang et al 2012; 884: Yu et al 2011; 1046: Shirahata et al 2011; 851: Li et al 2011; 107: Ming et al 2020; 956: Kajiyama et al 2008; 1158: Retnaningtyas et al 2022),
• counteracting inflammation and apoptosis (65: Yu et al 2016; 79: Jiao et al 2020; 599: Wu et al 2015; 607: Yu et al 2015; 706:Jiang et al 2013; 850: Li et al 2011; 851: Li et al 2011; 978: Li et al 2005; 40: Zheng et al 2021; 107: Ming et al 2020; 590: Tamasawa et al 2015; ; 696: Fan et al 2013; 309: Li et al 2018; 1115: Zhao et al 2021; 1164: Zou et al 2022),
• restoring mitochondrial (79: Jiao et al 2020; ; 993: Li et al 2002; 843: Kamimura et al 2011)
• and endoplasmic reticulum (599: Wu et al 2015) function,
• and preventing microvascular damage (11: Indrajani et al 2021).

Literature Cited (numbered as per database):

• (11) Indrajani, Olly; Retnaningtyas, Ekowati; Santoso, Hendry; Setyabudhi, Veronica Verina. Hydrogen water therapy in histopathological improvement of diabetic nephropathy on streptozotocin-induced diabetic rats. 2021. AIP Conference Proceedings. 10.1063/5.0053002

• (40) Zheng, Mengna; Yu, Han; Xue, Yong; Yang, Tong; Tu, Qiufen; Xiong, Kaiqing; Deng, Daihua; Lu, Lei; Huang, Nan. The protective effect of hydrogen-rich water on rats with type 2 diabetes mellitus. 2021. Molecular and Cellular Biochemistry. 10.1007/s11010-021-04145-x

• (47) Asada, Ryoko; Tazawa, Kenji; Sato, Shinkichi; Miwa, Nobuhiko. Effects of hydrogen-rich water prepared by alternating-current-electrolysis on antioxidant activity, DNA oxidative injuries, and diabetes-related markers. 2020. Medical Gas Research. 10.4103/2045-9912.296041

• (65) Yu, Yang; Xie, K.L.; Bian, Y.X.; Wang, G.L.; Yu, Yong-Hao. Abstract: Protective effects of hydrogen-rich medium on high-glucose-induced oxidative stress and poly(ADP-ribose)polymerase-1-dependent cell death (parthanatos) in rat Schwann cells in vitro. 2016. British Journal of Anaesthesia. https://academic.oup.com/bja/article/116/6/e912/2566337#44482609

• (79) Jiao, Yang; Yu, Yang; Li, Bo; Gu, Xiyan; Xie, Keliang; Wang, Guolin; Yu, Yong-Hao. Protective effects of hydrogen‑rich saline against experimental diabetic peripheral neuropathy via activation of the mitochondrial ATP‑sensitive potassium channel channels in rats. 2020. Molecular Medicine Reports. 10.3892/mmr.2019.10795

• (107) Ming, Yi; Ma, Qi-Hang; Han, Xin-Li; Li, Hong-Yan. Molecular hydrogen improves type 2 diabetes through inhibiting oxidative stress. 2020. Experimental and Therapeutic Medicine. 10.3892/etm.2020.8708

• (126) Supardi, Edy; Yusuf, Saldy; Massi, Muh Nasrum; Haeruddin, Hasniati. Evaluation of different type of electrolyzed water against bacterial colonization of diabetic foot ulcers: Study in vitro. 2020. Medicina Clinica Practica. 10.1016/j.mcpsp.2020.100090

• (309) Li, Qing; Jiao, Yang; Yu, Yang; Wang, Guolin; Yu, Yong-Hao. Hydrogen‑rich medium alleviates high glucose‑induced oxidative stress and parthanatos in rat Schwann cells in vitro. 2018. Molecular Medicine. Reports. 10.3892/mmr.2018.9631

• (387) Guo, Jialiang; Dong, Weichong; Jin, Lin; Wang, Pengcheng; Hou, Zhiyong; Zhang, Yingze. Hydrogen-rich saline prevents bone loss in diabetic rats induced by streptozotocin. 2017. International Orthopaedics. 10.1007/s00264-017-3581-4

• (428) Siswantoro, Edy; Purwanto, Nasrul Hadi; Sutomo. Effectiveness of Alkali Water Consumption to Reduce Blood Sugar Levels in Diabetes Mellitus Type 2. 2017. Journal of Diabetes Mellitus. 10.4236/jdm.2017.74020

• (463) Zhang, Xiaolong; Liu, Jiaming; Jin, Keke; Xu, Haifeng; Wang, Chuang; Zhang, Zhuang; Kong, Mimi; Zhang, Zhengzheng; Wang, Qingyi; Wang, Fangyan. Subcutaneous injection of H2 is a novel effective treatment for type 2 diabetes. 2017. Journal of Diabetes Investigation. 10.1111/jdi.12674

• (590) Tamasawa, Atsuko; Mochizuki, Kazuki; Hariya, Natsuyo; Saito, Miyoko; Ishida, Hidenori; Doguchi, Satako; Yanagiya, Syoko; Osonoi, Takeshi. Hydrogen gas production is associated with reduced interleukin-1β mRNA in peripheral blood after a single dose of acarbose in Japanese type 2 diabetic patients. 2015. European Journal of Pharmacology. 10.1016/j.ejphar.2015.04.051

• (599) Wu, Feng; Qiu, Yihua; Ye, Guangming; Luo, Hede; Jiang, Junsong; Yu, Feng; Zhou, Wei; Zhang, Shuai; Feng, Junzhong. Treatment with hydrogen molecule attenuates cardiac dysfunction in streptozotocin-induced diabetic mice. 2015. Cardiovascular Pathology. 10.1016/j.carpath.2015.04.008

• (607) Yu, Yang; Ma, Xiaoye; Yang, Tao; Li, Bo; Xie, Keliang; Liu, Danquan; Wang, Guolin; Yu, Yong-Hao. Protective effect of hydrogen‑rich medium against high glucose‑induced apoptosis of Schwann cells in vitro. 2015. Molecular Medicine Reports. 10.3892/mmr.2015.3874

• (689) Amitani, Haruka; Asakawa, Akihiro; Cheng, Kaichun; Amitani, Marie; Kaimoto, Kaori; Nakano, Masako; Ushikai, Miharu; Li, Yingxiao; Tsai, Minglun; Li, Jiang-Bo; Terashi, Mutsumi; Chaolu, Huhe; Kamimura, Ryozo; Inui, Akio. Hydrogen Improves Glycemic Control in Type1 Diabetic Animal Model by Promoting Glucose Uptake into Skeletal Muscle. 2013. PLoS One. 10.1371/journal.pone.0053913

• (696) Fan, Min; Xu, Xianlin; He, Xiaozhou; Chen, Lujun; Qian, Liren; Liu, Jipu; Qing, Jiandi; Chao, Zhifu; Sun, Xue-Jun. Protective Effects of Hydrogen-Rich Saline Against Erectile Dysfunction in a Streptozotocin Induced Diabetic Rat Model. 2013. Journal of Urology. 10.1016/j.juro.2012.12.001

• (697) Feng, Yanqing; Wang, Ruobing; Xu, Jiajun; Sun, Jingchuan; Xu, Tao; Gu, Qing; Wu, Xingwei. Hydrogen-Rich Saline Prevents Early Neurovascular Dysfunction Resulting from Inhibition of Oxidative Stress in STZ-Diabetic Rats. 2013. Current Eye Research. 10.3109/02713683.2012.748919

• (706) Jiang, Hong; Yu, Pan; Qian, De-Hui; Qin, Zhe-Xue; Sun, Xue-Jun; Yu, Jie; Huang, Lan. Hydrogen-rich medium suppresses the generation of reactive oxygen species, elevates the Bcl-2/Bax ratio and inhibits advanced glycation end product-induced-apoptosis. 2013. International Journal of Molecular Medicine. 10.3892/ijmm.2013.1334

• (715) Liu, Guo-Dan; Zhang, Hong; Wang, Lin; Han, Qing; Zhou, Shi-Feng; Liu, Ping. Molecular hydrogen regulates the expression of miR-9, miR-21 and miR-199 in LPS-activated retinal microglia cells. 2013. International Journal of Ophthalmology. 10.3980/j.issn.2222-3959.2013.03.05

• (776) Katakura, Masanori; Hashimoto, Michio; Tanabe, Yoko; Shido, Osamu. Hydrogen-rich water inhibits glucose and α,β -dicarbonyl compound-induced reactive oxygen species production in the SHR.Cg-Leprcp/NDmcr rat kidney. 2012. Medical Gas Research. 10.1186/2045-9912-2-18

• (806) Wang, Qi-Jin; Zha, Xiao-Juan; Kang, Zhi-Min; Xu, Mao-Jin; Huang, Qin; Zou, Da-Jin. Therapeutic effects of hydrogen saturated saline on rat diabetic model and insulin resistant model via reduction of oxidative stress. 2012. Chinese Medical Journal. 10.3760/cma.j.issn.0366-6999.2012.09.020

• (810) Xiao, Xiang; Cai, Jiping; Xu, Jiajun; Wang, Ruobing; Cai, Jianmei; Liu, Yun; Xu, Weigang; Sun, Xuejun; Li, Runping. Protective Effects of Hydrogen Saline on Diabetic Retinopathy in a Streptozotocin-Induced Diabetic Rat Model. 2012. Journal of Ocular Pharmacology and Therapeutics. 10.1089/jop.2010.0129

• (843) Kamimura, Naomi; Nishimaki, Kiyomi; Ohsawa, Ikuroh; Ohta, Shigeo. Molecular hydrogen improves obesity and diabetes by inducing hepatic FGF21 and stimulating energy metabolism in db/db mice. 2011. Obesity. 10.1038/oby.2011.6

• (850) Li, Yuping; Hamasaki, Takeki; Nakamichi, Noboru; Kashiwagi, Taichi; Komatsu, Takaaki; Ye, Jun; Teruya, Kiichiro; Abe, Masumi; Yan, Hanxu; Kinjo, Tomoya; Kabayama, Shigeru; Kawamura, Munenori; Shirahata, Sanetaka. Suppressive effects of electrolyzed reduced water on alloxan-induced apoptosis and type 1 diabetes mellitus. 2011. Cytotechnology. 10.1007/s10616-010-9317-6

• (851) Li, Yuping; Hamasaki, Takeki; Teruya, Kiichiro; Nakamichi, Noboru; Gadek, Zbigniew; Kashiwagi, Taichi; Yan, Hanxu; Kinjo, Tomoya; Komatsu, Takaaki; Ishii, Yoshitoki; Shirahata, Sanetaka. Suppressive effects of natural reduced waters on alloxan-induced apoptosis and type 1 diabetes mellitus. 2011. Cytotechnology. 10.1007/s10616-011-9414-1

• (884) Yu, Pan; Wang, Zhenxiang; Sun, Xuejun; Chen, Xiaohua; Zeng, Suyun; Chen, Liang; Li, Shirong. Hydrogen-rich medium protects human skin fibroblasts from high glucose or mannitol induced oxidative damage. 2011. Biochemical and Biophysical Research Communications. 10.1016/j.bbrc.2011.05.024

• (912) Osada, Kazuhiro; Li, Yuping; Hamasaki, Takeki; Abe, Masumi; Nakamichi, Noboru; Teruya, Kiichiro; Ishii, Yoshitoki; Wang, Ying; Katakura, Yoshinori; Shirahata, Sanetaka. Anti-Diabetes Effects of Hita Tenryou-Sui Water®, a Natural Reduced Water. 2010. Animal Cell Technology: Basic and Applied Aspects. 10.1007/978-90-481-3892-0_51

• (953) Gadek, Zbigniew; Hamasaki, Takeki; Shirahata, Sanetaka. “Nordenau Phenomenon” – Application of Natural Reduced Water to Therapy. 2008. Animal Cell Technology: Basic and Applied Aspects. 10.1007/978-1-4020-9646-4_41

• (956) Kajiyama, Sizuo; Hasegawa, Goji; Asano, Mai; Hosoda, Hiroko; Fukui, Michiaki; Nakamura, Naoto; Kitawaki, Jo; Imai, Saeko; Nakano, Koji; Ohta, Mitsuhiro; Adachi, Tetsuo; Obayashi, Hiroshi; Yoshikawa, Toshikazu. Supplementation of hydrogen-rich water improves lipid and glucose metabolism in patients with type 2 diabetes or impaired glucose tolerance. 2008. Nutrition Research. 10.1016/j.nutres.2008.01.008

• (963) Kim, Mi-Ja; Jung, Kyung Hee; Uhm, Yoon Kyung; Leem, Kang-Hyun; Kim, Hye Kyung. Preservative effect of electrolyzed reduced water on pancreatic beta-cell mass in diabetic db/db mice. 2007. Biological and Pharmaceutical Bulletin. 10.1248/bpb.30.234

• (966) Shirahata, Sanetaka; Li, Y.; Hamasaki, T.; Gadek, Z.; Teruya, K.; Kabayama, S.; Otsubo, K.; Morisawa, S.; Ishii, Y.; Katakura, Yoshinori. Redox Regulation by Reduced Waters as Active Hydrogen Donors and Intracellular ROS Scavengers for Prevention of type 2 Diabetes. 2007. Cell Technology for Cell Products. 10.1007/978-1-4020-5476-1_15

• (967) Gadek, Zbigniew; Li, Yuping; Shirahata, Sanetaka. Influence of natural reduced water on relevant tests parameters and reactive oxygen species concentration in blood of 320 diabetes patients in the prospective observation procedure. 2006. Animal Cell Technology: Basic and Applied Aspects. 10.1007/1-4020-4457-7_51

• (970) Jin, Dan; Ryu, Sung Hoon; Kim, Hyun Won; Yang, Eun Ju; Lim, Soo Jung; Ryang, Yong Suk; Chung, Choon Hee; Park, Seung Kyu; Lee, Kyu-Jae. Anti-diabetic effect of alkaline-reduced water on OLETF rats. 2006. Bioscience, Biotechnology, and Biochemistry. 10.1271/bbb.70.31

• (972) Kim, Mi-Ja; Kim, Hye Kyung; Anti-diabetic effects of electrolyzed reduced water in streptozotocin-induced and genetic diabetic mice. 2006. Life Sciences. 10.1016/j.lfs.2006.07.027

• (978) Li, Yuping; Teruya, K.; Katakura, Y.; Kabayama, S.; Otsubo, K.; Morisawa, S.; Ishii, Y.; Gadek, Z.; Shirahata, Sanetaka. Effect of Reduced Water on the Apoptotic Cell Death Triggered by Oxidative Stress in Pancreatic β HIT-T15 Cell. 2005. Animal Cell Technology Meets Genomics. 10.1007/1-4020-3103-3_21

• (992) Gadek, Zbigniew; Shirahata, Sanetaka. Changes in the Relevant Test Parameters of 101 Diabetes Patients under the Influence of the So-Called “Nordenau-Phenomenon”. 2002. Animal Cell Technology: Basic and Applied Aspects. 10.1007/978-94-017-0728-2_74

• (993) Li, Yuping; Nishimura, Tomohiro; Teruya, Kiichiro; Maki, Tei; Komatsu, Takaaki; Hamasaki, Takeki; Kashiwagi, Taichi; Kabayama, Shigeru; Shim, Sun-Yup; Katakura, Yoshinori; Osada, Kazuhiro; Kawahara, Takeshi; Otsubo, Kazumichi; Morisawa, Shinkatsu; Ishii, Yoshitoki; Gadek, Zbigniew; Shirahata, Sanetaka. Protective mechanism of reduced water against alloxan-induced pancreatic beta-cell damage: Scavenging effect against reactive oxygen species. 2002. Cytotechnology. 10.1023/A:1023936421448

• (994) Li, Yuping; Nishimura, Tomohiro; Teruya, Kiichiro; Maki, Tei; Komatsu, Takaaki; Hamasaki, Takeki; Kashiwagi, Taichi; Kabayama, Shigeru; Shim, Sun-Yup; Katakura, Yoshinori; Osada, Kazuhiro; Kawahara, Takeshi; Otsubo, Kazumichi; Morisawa, Shinkatsu; Ishii, Yoshitoki; Gadek, Zbigniew; Shirahata, Sanetaka. Protective mechanism of reduced water against alloxan-induced pancreatic β-cell damage: Scavenging effect against reactive oxygen species. 2002. Cytotechnology. 10.1023/A:1023936421448

• (1000) Shirahata, Sanetaka; Nishimura, T.; Kabayama, S.; Aki, D.; Teruya, K.; Otsubo, K.; Morisawa, S.; Ishii, Y.; Gadek, Z.; Katakura, Yoshinori. Anti-Oxidative Water Improves Diabetes. 2001. Animal Cell Technology: From Target to Market. 10.1007/978-94-010-0369-8_137

• (1010) Oda, M.; Kusumoto, K.; Teruya, K.; Hara, T.; Maki, T.; Kabayama, S.; Katakura, Y.; Otsubo, K.; Morisawa, S.; Hayashi, H.; Ishii, Y.; Shirahata, Sanetaka. Electrolyzed and Natural Reduced Water Exhibit Insulin-Like Activity on Glucose Uptake into Muscle Cells and Adipocytes. 1999. Animal Cell Technology: Products from Cells, Cells as Products. 10.1007/0-306-46875-1_90

• (1046) Shirahata, Sanetaka; Hamasaki, Takeki; Haramaki, Keisuke; Nakamura, Takuro; Abe, Masumi; Yan, Hanxu; Kinjo, Tomoya; Nakamichi, Noboru; Kabayama, Shigeru; Teruya, Kiichiro. Abstract: Anti-diabetes

effect of water containing hydrogen molecule and Pt nanoparticles. 2011. BMC Proceedings. 10.1186/1753-6561-5-S8-P18

• (1115) Zhao, Chuan; Guo, Yushu; Wang, Ruoxi; Cheng, Cheng; Chen, Xiangmei. Effect of hydrogen-rich water on the lactic acid level in metformin-treated diabetic rats under hypoxia. 2021. Korean Journal of Physiology & Pharmacology. 10.4196/kjpp.2021.25.6.517

• (1139) Ogawa, Susumu; Ohsaki, Yusuke; Shimizu, Manami; Nako, Kazuhiro; Okamura, Masashi; Kabayama, Shigeru; Tabata, Kiyoshi; Tanaka, Yasuhisa; Ito, Sadoyoshi. Electrolyzed hydrogen-rich water for oxidative stress suppression and improvement of insulin resistance: a multicenter prospective double-blind randomized control trial. 2021. Diabetology International. 10.1007/s13340-021-00524-3

• (1158) Retnaningtyas, Ekowati; Susatia, Budi; Arifah, Siti Nur; Lestari, Sri Rahayu. The improvement of insulin level after hydrogen-rich water therapy in streptozotocin-induced diabetic rats. 2022. Veterinary World. 10.14202/vetworld.2022.182-187

• (1164) Zou, Rentong; Nie, Chaoqun; Pan, Shuang; Wang, Bin; Hong, Xiaojian; Xi, Shuiqing; Bai, Juncai; Yu, Mengshu; Liu, Jiaren; Yang, Wei. Co-administration of hydrogen and metformin exerts cardioprotective effects by inhibiting pyroptosis and fibrosis in diabetic cardiomyopathy. 2022. Free Radical Biology and Medicine. 10.1016/j.freeradbiomed.2022.03.010