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Literature Review

Electrolyzed–Reduced Water: Review I. Molecular Hydrogen Is the Exclusive Agent Responsible for the Therapeutic Effects

MHID-7890987PMID: 364990792022International Journal of Molecular Sciences

Tyler W. LeBaron, Randy Sharpe, Kinji Ohno

Numerous benefits have been attributed to alkaline-electrolyzed–reduced water (ERW). Sometimes these claims are associated with easily debunked concepts. The observed benefits have been conjectured to be due to the intrinsic properties of ERW (e.g., negative oxidation–reduction potential (ORP), alkaline pH, H2 gas), as well enigmatic characteristics (e.g., altered water structure, microclusters, fre

Literature ReviewHighlighted

Electrolyzed–Reduced Water: Review II: Safety Concerns and Effectiveness as a Source of Hydrogen Water

MHID-2004094PMID: 364988382022International Journal of Molecular Sciences

Tyler W. LeBaron, Randy Sharpe, Kinji Ohno

Many studies demonstrate the safety of alkaline-electrolyzed–reduced water (ERW); however, several animal studies have reported significant tissue damage and hyperkalemia after drinking ERW. The mechanism responsible for these results remains unknown but may be due to electrode degradation associated with the production of higher pH, in which platinum nanoparticles and other metals that have harmf

In SilicoHighlighted

Antioxidation activity of molecular hydrogen via protoheme catalysis in vivo: an insight from ab initio calculations

MHID-4619667PMID: 360570012022Journal of Molecular Modeling

Song‑Ae Kim, Yu‑Chol Jong, Myong‑Su Kang, Chol‑Jun Yu

Recently, molecular hydrogen has been found to exhibit antioxidation activity through many clinical experiments, but the mechanism has not been fully understandable at atomic level. In this work, we perform systematic ab initio calculations of protoheme-hydrogen complexes to clarify the antioxidation mechanism of molecular hydrogen. We make molecular modeling of iron–protoporphyrin coordinated by

HypothesisOpinion PieceOtherHighlighted

Hydrogen-Rich Water as a Dietary Activator of Brown Adipose Tissue and UCP1?

MHID-0628712PMID: 356757612022Annals of Nutrition and Metabolism

Sergej M Ostojic

Molecular hydrogen (dihydrogen or hydrogen gas) is a small bioactive molecule involved in various metabolic pathways, from redox-sensitive reactions and cell signaling to bioenergetics and gut microbiota biology. Drinking hydrogen-rich water (HRW) has been suggested as a safe, novel, and promising nutritional strategy to attenuate metabolic disorders and burdensome and highly prevalent conditions

Literature ReviewOpinion PieceHighlighted

Commentary: Hydrogen: Lightweight molecule takes on a heavyweight problem

MHID-7464677PMID: 340520182022The Journal of Thoracic and Cardiovascular Surgery

John N. Kheir, MD, James A. DiNardo, MD

Diatomic hydrogen (H2) is the lightest and most abundant molecule in the universe. Hydrogen's reactivity with oxygen is well recognized as a thermodynamically favorable redox reaction that forms water. H2's small size results in unsurpassed diffusivity (even diffusing through steel), enabling it to reach therapeutic targets effectively even in low-flow states. In vivo, inhaled H2 undergoes solubil

In VitroHighlighted

Molecular Hydrogen Enhances Proliferation of Cancer Cells That Exhibit Potent Mitochondrial Unfolded Protein Response

MHID-6868466PMID: 352700302022International Journal of Molecular Sciences

Tomoya Hasegawa, Mikako Ito, Satoru Hasegawa, Masaki Teranishi, Koki Takeda, Shuto Negishi, et al.

Molecular hydrogen ameliorates pathological states in a variety of human diseases, animal models, and cell models, but the effects of hydrogen on cancer have been rarely reported. In addition, the molecular mechanisms underlying the effects of hydrogen remain mostly unelucidated. We found that hydrogen enhances proliferation of four out of seven human cancer cell lines (the responders). The prolif

Animal StudyHighlighted

Long‑term and daily use of molecular hydrogen induces reprogramming of liver metabolism in rats by modulating NADP/NADPH redox pathways

MHID-2655528PMID: 352732492022Scientific Reports

Yao Mawulikplimi Adzavon, Fei Xie, Yang Yi, Xue Jiang, Xiaokang Zhang, Jin He, et al.

Molecular hydrogen (H2) has emerged as a new therapeutic option in several diseases and is widely adopted by healthy people. However, molecular data to support therapeutic functions attributed to the biological activities of H2 remain elusive. Here, using transcriptomic and metabolomic approaches coupled with biochemistry and micro-CT technics, we evaluated the effect of long-term (6 months) and d

Animal StudyHighlighted

Hydrogen‑rich saline alleviates early brain injury through inhibition of necroptosis and neuroinflammation via the ROS/HO‑1 signaling pathway after traumatic brain injury

MHID-9667503PMID: 349703492022Experimental and Therapeutic Medicine

Yun Hu, Xiaoyan Feng, Junhui Chen, Yan Wu, Liuyan Shen

Traumatic brain injury (TBI) has been recognized as a serious public health issue and a key contributor to disability and death, with a huge economic burden worldwide. Hydrogen, which is a slight and specific cytotoxic oxygen radical scav‑enger, has been demonstrated to ameliorate early brain injury (EBI) through reactive oxygen species (ROS), oxidative stress injury, apoptosis and necroptosis. Ne

Animal StudyIn VitroHighlighted

Local Treatment of Hydrogen-Rich Saline Promotes Wound Healing In Vivo by Inhibiting Oxidative Stress via Nrf-2/HO-1 Pathway

MHID-5758484PMID: 353001732022Oxidative Medicine and Cellular Longevity

Yujie Li, Chengcheng Shen, Xin Zhou, Jianghe Zhang, Xiaoyue Lai, Yiming Zhang

Wound healing is a complex dynamic process involving a large number of biological events. Excessive oxidative stress is a key factor delaying wound healing. Hydrogen is an antioxidant, anti-inflammatory, and antiapoptotic medical gas with safety, effectiveness, and penetrability. However, the effects of local treatment of hydrogen on wound healing and its potential mechanisms remain unclear. In this

In VitroHighlighted

Quantification of dissolved H2 and continuous monitoring of hydrogen-rich water for haemodialysis applications: An experimental study

MHID-1024639PMID: 350759432022The International Journal of Artificial Organs

Foivos Leonidas Mouzakis, Lal Babu Khadka, Miguel Pereira da Silva, Khosrow Mottaghy

The prevalence of oxidative and inflammatory stress in end-stage renal disease (ESRD) patients has often been associated with chronic haemodialysis therapies. Over the past decades, several reports have shown the potential of hydrogen molecule as an antioxidant in the treatment of various medical conditions in animal models, as well as in pilot studies with human patients. Recently, a hydrogen-enr

In VitroHighlighted

Antioxidant Properties of Hydrogen Gas Attenuates Oxidative Stress in Airway Epithelial Cells

MHID-0634713PMID: 347707842021Molecules

In-Soo You, Subham Sharma, Ailyn Fadriquela, Johny Bajgai, Thuy Trinh Thi, Md. Habibur Rahman, et al.

Oxidative stress plays a crucial role in the development of airway diseases. Recently, hydrogen (H2) gas has been explored for its antioxidant properties. This study investigated the role of H2 gas in oxidative stress-induced alveolar and bronchial airway injury, where A549 and NCI-H292 cells were stimulated with hydrogen peroxide (H2O2) and lipopolysaccharide (LPS) in vitro. Results show that tim

In VitroOtherHighlighted

Hydrogen Evolution and Absorption Phenomena in the Plasma Membrane of Vigna radiata and Capsicum annuum

MHID-32438852021Journal of Plant Growth Regulation

Xin Zhang, Fei Xie, Zhao Zhang, Yao Mawulikplimi Adzavon, Zehua Su, Qinghui Zhao, et al.

Molecular hydrogen has been shown to exert beneficial effects on plant growth and abiotic stress tolerance, however, the exact mechanism has not yet been fully elucidated. H2 is able to diffuse directly across the plasma membrane, which is the first barrier between H2 and cells. It is possible that H2 may exert its biological effects on plant cells by interacting with PM. Hydrogenases can catalyze

Clinical TrialHighlighted

Hydrogen-rich water and caffeine for alertness and brain metabolism in sleep-deprived habitual coffee drinkers

MHID-9740359PMID: 345320232021Food Science & Nutrition

Nikola Todorovic, Dragana Zanini, Valdemar Stajer, Darinka Korovljev, Jelena Ostojic, Sergej M Ostojic

The main aim of this randomized-controlled cross-over interventional trial was to assess the acute effects of taking a single dose of hydrogen-rich water (HRW), and compare it with caffeine, HRW plus caffeine, and control water, for alertness, brain metabolism, brain and oxygen saturation, and self-reported adverse events in healthy men and women who were habitual coffee drinkers and were sleep-de

In VitroHighlighted

Response of Escherichia coli to hydrogen nanobubbles: an in vitro evaluation using synchrotron infrared spectroscopy

MHID-0456102PMID: 347832272021Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology)

Jinfang LU, Jin ZHENG, Yadi WANG, Jie CHENG, Xueling LI, Jun HU, et al.

Hydrogen (H2)-rich water, an apparent source of molecular H2, is an emerging functional drink with many purported benefits for human health (Yang et al., 2020; Ostojic, 2021). The preventive and therapeutic effects of H2 on various pathological processes have been intensively investigated in numerous clinical trials; it is commonly believed that the beneficial effects are mainly attributed to its

Clinical TrialHighlighted

Safety of Prolonged Inhalation of Hydrogen Gas in Air in Healthy Adults

MHID-1947207PMID: 346511332021Critical Care Explorations

Alexis R. Cole, BS, Francesca Sperotto, MD, James A. DiNardo, MD, Stephanie Carlisle, Michael J. Rivkin, MD, Lynn A. Sleeper, ScD, et al.

BACKGROUND: Ischemia-reperfusion injury is common in critically ill patients, and directed therapies are lacking. Inhaled hydrogen gas diminishes ischemia-reperfusion injury in models of shock, stroke, and cardiac arrest. The purpose of this study was to investigate the safety of inhaled hydrogen gas at doses required for a clinical efficacy study. DESIGN: Prospective, single-arm study. SETTING: T

Animal StudyIn VitroHighlighted

Hydrogen-rich water protects against liver injury in nonalcoholic steatohepatitis through HO-1 enhancement via IL-10 and Sirt 1 signaling

MHID-2423362PMID: 334391022021American Journal of Physiology - Gastrointestinal and Liver Physiology

Shao-Wei Li, Terumi Takahara, Weitao Que, Masayuki Fujino, Wen-Zhi Guo, Shin-ichi Hirano, et al.

Nonalcoholic steatohepatitis (NASH) could progress to hepatic fibrosis in the absence of effective control. The purpose of our experiment was to investigate the protective effect of drinking water with a high concentration of hydrogen, namely, hydrogen-rich water (HRW), on mice with nonalcoholic fatty liver disease to elucidate the mechanism underlying the therapeutic action of molecular hydrogen.

In VitroHighlighted

Molecular hydrogen protects against oxidative stress‑induced RAW 264.7 macrophage cells through the activation of Nrf2 and inhibition of MAPK signaling pathway

MHID-35801392020Molecular & Cellular Toxicology

Rahima Begum, Cheol‑Su Kim, Ailyn Fadriquela, Johny Bajgai, Xingyu Jing, Dong‑Heui Kim, et al.

Background: Oxidative stress is involved in the development of many inflammatory, metabolic and aging diseases. Objective: In this study we investigated, the protective effects of H2 on RAW 264.7 macrophage cell against LPS-and H2O2-induced oxidative stress by the inhibition of MAPK pathway and also activate the Nrf2 pathway. Results: Our results showed H2 increased the macrophage cell prolifera

In VitroEx VivoHighlighted

Hydrogen evolution and absorption phenomena in plasma membrane of higher plants

MHID-98806872020bioRxiv

Xin Zhang, Zhao Zhang, Zehua Su, Qinghui Zhao, Tyler W. LeBaron, Qinjian Li, et al.

Molecular hydrogen (H2) exhibits a wide breadth of botanical effects especially in improving the resistance to abiotic stress. However, the primary target is not clear. Bidirectional hydrogenases have been well studied in microbes and alga, but there is a paucity of research in higher plants. Here, we used real-time spectrophotometry, gas chromatography and H2 sensor to detect the H2-evolving and

Mechanisms ReviewHighlighted

Molecular and Cellular Mechanisms Associated with Effects of Molecular Hydrogen in Cardiovascular and Central Nervous Systems

MHID-2592715PMID: 351026012020Antioxidants

Miroslav Barancik, Branislav Kura, Tyler W. LeBaron, Roberto Bolli, Jozef Buday, Jan Slezak

The increased production of reactive oxygen species and oxidative stress are important factors contributing to the development of diseases of the cardiovascular and central nervous systems. Molecular hydrogen is recognized as an emerging therapeutic, and its positive effects in the treatment of pathologies have been documented in both experimental and clinical studies. The therapeutic potential of

In VitroHighlighted

Molecular Hydrogen Protects Human Melanocytes from Oxidative Stress by Activating Nrf2 Signaling

MHID-7135279PMID: 345586532020Journal of Investigative Dermatology

Wei Fang, Luyan Tang, Guizhen Wang, Jinran Lin, Wanqing Liao, Weihua Pan, et al.

Oxidative stress is proven to be critical for the initiation and progression of vitiligo. Molecular hydrogen (H2) possesses potent antioxidant activity and has been shown to protect against various oxidative stresserelated diseases. In this study, we first investigated the effects and mechanisms of H2 in human melanocytes damaged by hydrogen peroxide. We initially found that H2 reduced intracellula