Hydrogen-Rich Saline (IV): Human Studies
Hydrogen-rich saline: H₂ dissolved in saline and given by infusion or injection. Allows defined doses, but appears almost only in clinical settings and animal models.
Human studies on molecular hydrogen given by Saline / IV. This page collects the 69 studies using this route — 6 randomized trials, 11 pilot/observational studies and 18 reviews. Listed newest first.
Human studies (17)
2021 · Takeuchi — Intravenous Hydrogen Therapy With Intracisternal Magnesium Sulfate Infusion in Severe Aneurysmal Subarachnoid Hemorrhage
In a three-arm randomised trial of 37 patients with life-threatening subarachnoid haemorrhage, adding intravenous hydrogen therapy to intracisternal magnesium sulphate infusion reduced brain injury biomarkers and delayed cerebral ischaemia compared to controls.
2020 · Jin — Changes of nasal nitric oxide in the treatment of allergic rhinitis with hydrogen-rich saline lavage of nasal cavity
A nasal lavage with hydrogen-rich saline significantly changed the nitric-oxide value in the nose and could thus offer a starting point for treating allergic rhinitis (hay fever).
2018 · Jin — Clinical Study of Hydrogen-Rich Saline in the Treatment of Moderate to Severe Allergic Rhinitis
Nasal lavage with hydrogen-rich saline significantly improved symptoms, signs, and quality of life in patients with moderate-to-severe allergic rhinitis — with no relevant adverse effects.
2017 · Ono et al. — Hydrogen Gas Inhalation Treatment in Acute Cerebral Infarction: A Randomized Controlled Clinical Study on Safety and Neuroprotection.
In this randomized controlled trial with 50 stroke patients, inhaling 3% H₂ gas twice daily for 7 days was safe and led to measurable improvements in MRI lesion intensity, stroke severity scores (NIHSS), and functional independence (Barthel Index).
2014 · Takeuchi et al. — Effects of intravenous hydrogen-rich fluid combined with intra-cisternal magnesium sulfate in severe aneurysmal subarachnoid hemorrhage: study protocol for a randomized controlled trial.
This paper describes the registered protocol for a 450-patient RCT testing whether intravenous H₂-rich fluid combined with intra-cisternal magnesium sulfate can prevent cerebral vasospasm and delayed cerebral ischemia after severe subarachnoid hemorrhage.
2014 · Ishibashi et al. — Therapeutic efficacy of infused molecular hydrogen in saline on rheumatoid arthritis: a randomized, double-blind, placebo-controlled pilot study.
In 24 patients with rheumatoid arthritis (RA), intravenous infusion of H₂-enriched saline (500 mL/day, 5 days) significantly reduced disease activity scores (DAS28), lowered IL-6 and the oxidative damage marker 8-OHdG, and reduced MMP-3 — a marker of joint destruction — after 4 weeks.
2026 · Xu et al. — Hydrogen-Enriched Hyaluronic Acid Dressing Ameliorates Diabetic Foot Ulcer via Promoting Mitophagy
A hyaluronic acid dressing enriched with molecular hydrogen accelerated wound healing in diabetic foot ulcer patients and, in parallel laboratory experiments, activated the cellular „self-cleaning“ programme for damaged mitochondria (mitophagy).
2026 · Lin et al. — Adjunctive Molecular Hydrogen Therapy Modulates T Cell Markers and Reduces Anti-Ro Antibody in Refractory Oral Ulcers of Behçet's Disease and Sjögren's Syndrome: A Case Report
A 67-year-old woman with both Behçet's disease and primary Sjögren's syndrome — whose recurrent painful oral ulcers had not responded to years of standard therapy — showed marked clinical improvement and falling anti-Ro antibody levels after adding oral molecular hydrogen capsules to her regimen.
2025 · Kuang et al. — Hydrogen-Rich Saline Combined With Vacuum Sealing Drainage Promotes Wound Healing by Altering Biotin Metabolism
Impaired wound healing is a significant clinical burden — particularly in post-surgical or chronic wound settings.
2025 · Lin et al. — Precision Assessment of Anti-NMDA Receptor Encephalitis: A Case Report on Integrating Clinical Course, Immunophenotyping, and Comprehensive Symptomatology in a Pediatric Patient With Adjunctive Hydrogen Therapy
Anti-NMDA receptor encephalitis is the most common form of autoimmune encephalitis — and it is notoriously difficult to treat when first-line therapies fail.
2025 · Nakazawa et al. — Fatigue Disappearance in Hemodialysis Patients by Dual Approach with Hydrogen Gas Inhalation and Hydrogen-Enriched Dialysate: Two Case Reports
In two men on long-term hemodialysis, adding inhaled 2.5% hydrogen during dialysis sessions for 3 months to dialysis with hydrogen-containing dialysate was followed by a fall in the median fatigue score from 3 to 0 on a scale from 0 to 9.
2024 · Mu — Hydrogen regulated pyroptosis through NLRP3-GSDMD pathway to improve airway mucosal oxidative stress injury induced by endotracheal tube cuff compression.
Endotracheal tube cuffs compress airway tissue during anaesthesia, triggering oxidative stress and a form of inflammatory cell death (pyroptosis) — and hydrogen inhalation or hydrogen-rich saline in the cuff significantly reduced this damage.
2022 · Benjamin — A potential clinical application of hydrogen-rich saline in patients with traumatic brain injury.
This paper from the Journal of Pediatric Surgery explores the potential use of hydrogen-rich saline as a treatment for traumatic brain injury (TBI) — one of the most devastating and difficult-to-treat neurological emergencies, especially in pediatric patients.
2017 · Qian et al. — Therapeutic effects of hydrogen on chronic graft-versus-host disease.
This study combined a mouse model of chronic graft-versus-host disease (cGVHD) with a clinical human component, finding that hydrogen-rich saline increased survival rates and reduced skin lesions in mice — and suggesting human therapeutic relevance in post-transplant patients.
2015 · Ishibashi et al. — Improvement of psoriasis-associated arthritis and skin lesions by treatment with molecular hydrogen: A report of three cases.
In three patients with psoriasis-associated arthritis and skin lesions, H₂ treatment (via saline infusion, inhalation, and/or high-concentration drinking water) reduced DAS28 and PASI scores, caused near-complete clearing of skin lesions, and lowered inflammatory cytokines (IL-6, IL-17, TNFα) in at least one patient.
2014 · Terawaki et al. — Effect of a Hydrogen (H2)-Enriched Solution on the Albumin Redox of Hemodialysis Patients
In eight hemodialysis patients who each had one session with standard and one with hydrogen-enriched dialysis solution, the share of reversibly oxidized albumin fell significantly between dialyzer inlet and outlet only in the hydrogen session.
2013 · Terawaki et al. — Transperitoneal Administration of Dissolved Hydrogen for Peritoneal Dialysis Patients: A Novel Approach to Suppress Oxidative Stress in the Peritoneal Cavity
In six peritoneal dialysis patients, a single test dwell with hydrogen-enriched dialysate left a higher share of reduced albumin, a marker of lower oxidative stress, in the drained fluid than standard dialysate (62.31% compared with 54.70%).
Reviews (18)
2026 · Nguyen — Advances in hydrogen delivery strategies for therapeutic applications
Molecular hydrogen (H₂) has selective antioxidant, anti-inflammatory and anticancer properties — but getting it reliably to target tissues remains the central challenge limiting clinical use.
2023 · Kuo — Molecular Hydrogen: Emerging Treatment for Stroke Management
Molecular hydrogen (H₂) is an emerging therapeutic approach in ischemic stroke — antioxidative, anti-inflammatory and anti-apoptotic.
2023 · Saengsin et al. — Hydrogen Therapy as a Potential Therapeutic Intervention in Heart Disease: From the Past Evidence to Future Application
This comprehensive review in Cellular and Molecular Life Sciences synthesises in-vitro, animal, and clinical evidence for molecular hydrogen's protective effects in cardiovascular disease, covering its antioxidant, anti-inflammatory, and anti-apoptotic mechanisms.
2023 · Wong — A potential clinical application of hydrogen-rich saline in postoperative care
This review article discusses potential clinical uses of hydrogen-rich saline in postoperative care, but no abstract text is publicly available for this record.
2021 · Quan — Protective effects of molecular hydrogen on lung injury from lung transplantation.
This review synthesizes the experimental evidence showing that H₂ — administered via inhalation, drinking, injection, or topical bath — can reduce the oxidative stress and inflammation responsible for primary graft dysfunction after lung transplantation.
2021 · Sano et al. — Hydrogen Gas Therapy: From Preclinical Studies to Clinical Trials.
Hydrogen gas (H₂) has demonstrated broad therapeutic potential in preclinical and early clinical studies — from ischaemia-reperfusion injury to organ transplantation and emergency medicine — and appears safe, inexpensive, and easy to administer.
2021 · Ostojic — Hydrogen Gas as an Exotic Performance-Enhancing Agent: Challenges and Opportunities
This review maps approximately two dozen studies on hydrogen (H₂) and exercise performance, finding promising ergogenic signals — but also highlighting the absence of a gold-standard protocol.
2019 · LeBaron et al. — A New Approach for the Prevention and Treatment of Cardiovascular Disorders. Molecular Hydrogen Significantly Reduces the Effects of Oxidative Stress.
Molecular hydrogen (H₂) has been studied in preclinical and clinical settings for a wide range of cardiovascular conditions linked to oxidative stress and inflammation.
2019 · Wang et al. — Neonatal hypoxic-ischemic encephalopathy: emerging therapeutic strategies based on pathophysiologic phases of the injury.
This 2019 review proposes a phase-based treatment framework for neonatal hypoxic-ischemic encephalopathy (HIE), a major cause of infant death and disability.
2018 · Chen — Research progress of hydrogen-rich saline for eye diseases.
This Chinese-language review summarizes the published research on hydrogen-rich saline (and hydrogen-rich water) for the treatment of eye diseases, including glaucoma, retinal ischemia, and other ocular conditions.
2017 · Iketani — Molecular Hydrogen as a Neuroprotective Agent
Molecular hydrogen (H₂) acts as an antioxidant and anti-inflammatory agent and shows potential in neurological disorders — from stroke through neurodegenerative diseases to brain damage in newborns.
2016 · Iida — The Clinical Application of Hydrogen as a Medical Treatment
This Japanese review surveys research on hydrogen-rich water and hydrogen gas as potential medical treatments, covering disease models such as ischaemia-reperfusion injury, and explores routes of H₂ administration (oral, intravenous, local) and the possible role of H₂ as an antioxidant signalling molecule.
2015 · Ohta — Molecular hydrogen as a novel antioxidant: overview of the advantages of hydrogen for medical applications.
Molecular hydrogen (H₂) is a mild, selective antioxidant that neutralizes the most damaging reactive oxygen species without disrupting normal cellular redox signaling — a key advantage over broad-spectrum antioxidants.
2014 · Ohta — Molecular hydrogen as a preventive and therapeutic medical gas: initiation, development and potential of hydrogen medicine.
One of the founding papers of hydrogen medicine, authored by Shigeo Ohta, summarises how H₂ was discovered to react with harmful hydroxyl radicals in cells — and why this makes it a candidate for preventing and treating a wide range of diseases.
2014 · Fernández-Gajardo et al. — Novel therapeutic strategies for traumatic brain injury: acute antioxidant reinforcement.
This review examines antioxidant-based strategies for treating traumatic brain injury (TBI), including hydrogen-rich saline, arguing that oxidative stress is a central driver of secondary brain damage after trauma.
2013 · Qian — Hydrogen as a new class of radioprotective agent
Molecular hydrogen (H₂) reduces radiation-induced oxidative damage by selectively neutralizing hydroxyl radicals — the main cause of ionizing radiation injury.
2012 · Ohta — Molecular hydrogen is a novel antioxidant to efficiently reduce oxidative stress with potential for the improvement of mitochondrial diseases.
This review by Shigeo Ohta — one of the founders of modern H₂ medicine — surveys the biological effects of molecular hydrogen across more than 38 diseases, physiological states, and clinical tests documented in the years following the 2007 Nature Medicine paper.
2011 · Ohta — Recent progress toward hydrogen medicine: potential of molecular hydrogen for preventive and therapeutic applications.
Since the landmark 2007 Nature Medicine paper demonstrating that molecular hydrogen (H₂) selectively neutralizes toxic hydroxyl radicals, the field of hydrogen medicine has grown rapidly.
Preclinical (34)
2025 · Jingxuan — Four-dimensional Data Independent Acquisition Proteomics and Metabolomics Reveal Mechanisms of Hydrogen-rich Water at Zusanli (ST36) Point against Triple-negative Breast Cancer in Mice
Injecting hydrogen-rich water into the Zusanli acupuncture point (ST36) significantly inhibited tumour growth and enhanced cancer-cell apoptosis in a mouse model of triple-negative breast cancer, according to this animal study combining proteomics and metabolomics.
2025 · Wang — Effect of hydrogen-rich saline on melanopsin after acute blue light-induced retinal damage in rats
Hydrogen protects the retina from blue light: In rats with blue-light-induced retinal damage, hydrogen-rich saline (HRS) accelerated recovery — with markedly more melanopsin and more functional light-sensitive ganglion cells within two weeks.
2024 · Chen — Hydrogen-rich water alleviates constipation by attenuating oxidative stress through the sirtuin1/nuclear factor-erythroid-2-related factor 2/heme oxygenase-1 signaling pathway.
In constipated rats, hydrogen-rich water (HRW) improved stool output, intestinal motility, and gut microbiota composition by reducing oxidative stress through a specific protective signalling pathway.
2024 · Cui et al. — Molecular Hydrogen Attenuates Sepsis-Induced Cardiomyopathy in Mice by Promoting Autophagy
In a mouse model of sepsis-induced cardiomyopathy (SIC), molecular hydrogen inhalation significantly improved 7-day survival, reduced cardiac tissue inflammation, and lowered troponin I levels — effects that operated through promotion of autophagy and mitophagy.
2023 · Aokage — Attenuation of pulmonary damage in aged lipopolysaccharide-induced inflammation mice through continuous 2 % hydrogen gas inhalation: A potential therapeutic strategy for geriatric inflammation and survival
In aged mice (21–23 months) with LPS-induced systemic inflammation, continuous inhalation of 2 % hydrogen gas for 24 hours reduced lung inflammation, lowered senescence-related markers, and improved survival — while having no measurable effect on LPS-induced liver injury.
2023 · Dumbuya — Hydrogen-rich saline regulates NLRP3 inflammasome activation in sepsis-associated encephalopathy rat model
In a juvenile rat model of sepsis-associated encephalopathy (SAE), hydrogen-rich saline (HRS) reduced brain inflammation, suppressed NLRP3 inflammasome activation, decreased neuronal apoptosis, and lowered oxidative stress markers.
2023 · Guo — Hydrogen suppresses oxidative stress by inhibiting the p38 MAPK signaling pathway in preeclampsia
In a rat model of preeclampsia, hydrogen-rich saline significantly reduced inflammation markers, oxidative stress, and blood pressure-related damage — and the protective effect appears to work via inhibiting the p38 MAPK signaling pathway.
2022 · Li — Local Treatment of Hydrogen-Rich Saline Promotes Wound Healing In Vivo by Inhibiting Oxidative Stress via Nrf-2/HO-1 Pathway
Applying hydrogen-rich saline directly to skin wounds in mice accelerated wound closure and reduced inflammation compared to regular saline, with the Nrf-2/HO-1 antioxidant pathway identified as the key mechanism.
2022 · Ge — Microbial hydrogen economy alleviates colitis by reprogramming colonocyte metabolism and reinforcing intestinal barrier
In mice with experimentally induced acute colitis, hydrogen-rich saline administration reduced intestinal inflammation, increased beneficial short-chain fatty acid (SCFA)-producing bacteria, and strengthened the gut barrier.
2020 · Lu — Molecular hydrogen regulates PTEN-AKT-mTOR signaling via ROS to alleviate peritoneal dialysis-related peritoneal fibrosis.
In mice treated with high-glucose dialysate to induce peritoneal fibrosis, and in MeT-5A mesothelial cells in culture, hydrogen-rich peritoneal dialysate inhibited fibrosis by eliminating intracellular reactive oxygen species (ROS) and suppressing the PTEN/AKT/mTOR signalling pathway.
2020 · Jiao — Protective effects of hydrogen-rich saline against experimental diabetic peripheral neuropathy via activation of the mitochondrial ATP-sensitive potassium channel in rats.
In streptozotocin-induced diabetic rats, hydrogen-rich saline injected intraperitoneally for four weeks reduced behavioural, biochemical, and molecular markers of diabetic peripheral neuropathy (DPN), with effects partially mediated through mitochondrial ATP-sensitive potassium (Mito-K-ATP) channels.
2019 · Kou et al. — Acid-responsive H₂-releasing Fe nanoparticles for safe and effective cancer therapy.
This preclinical study describes an ingenious drug-delivery strategy: iron nanoparticles coated with carboxymethyl cellulose that release molecular hydrogen (H₂) selectively inside the acidic tumour microenvironment, enabling targeted, imaging-guided cancer therapy in mice.
2019 · Fan — Acid-Responsive H₂-Releasing 2D MgB₂ Nanosheet for Therapeutic Synergy and Side Effect Attenuation of Gastric Cancer Chemotherapy.
Researchers engineered a magnesium boride (MgB₂) nanosheet that releases molecular hydrogen in acidic environments (such as the stomach) and combined it with the chemotherapy drug doxorubicin in a gastric-tumor mouse model.
2019 · Yan — Hydrogen gas inhalation attenuates sepsis-induced liver injury in a FUNDC1-dependent manner.
In septic mice (cecal ligation and puncture model), 2 % hydrogen (H₂) gas inhalation for 3 hours improved the 7-day survival rate and reduced markers of liver damage.
2018 · Nakayama — Translational Research of Peritoneal Dialysis Solution with Dissolved Molecular Hydrogen
Adding molecular hydrogen to peritoneal dialysis solution (PDS) protected the peritoneal membrane in a chronic kidney disease rat model, and a small 2-week human pilot (n=6 dialysis patients) found it safe and feasible.
2018 · Wan — An In Situ Depot for Continuous Evolution of Gaseous H₂ Mediated by a Magnesium Passivation/Activation Cycle for Treating Osteoarthritis
This mouse study tested intra-muscular injection of magnesium-containing microparticles (Mg@PLGA) as a local H₂ delivery system for osteoarthritis (OA).
2018 · Jiang — Therapeutic efficacy of hydrogen-rich saline alone and in combination with PI3K inhibitor in non-small cell lung cancer
In cultured human lung cancer cells (A549 line), hydrogen-rich saline reduced proliferation and promoted apoptosis; combining it with the PI3K inhibitor LY294002 enhanced these effects further by suppressing the PI3K/Akt signalling pathway.
2017 · Watanabe — Protective Effect of Hydrogen Gas Inhalation on Muscular Damage Using a Mouse Hindlimb Ischaemia-Reperfusion Injury Model
In a mouse hindlimb ischaemia-reperfusion model, inhalation of hydrogen gas — administered before and during reperfusion — significantly reduced muscle infarct zone, dampened inflammation, and improved walking function recovery.
2017 · Zhao — Changes in IL-4 and IL-13 Expression in Allergic Rhinitis Treated with Hydrogen-Rich Saline in a Guinea-Pig Model
Hydrogen-rich saline significantly reduced sneezing, scratching, IgE levels, and key allergy-driving cytokines (IL-4, IL-13) in guinea pigs with experimentally induced allergic rhinitis.
2017 · Li — Protective Effects of Molecular Hydrogen on Steroid-Induced Osteonecrosis in Rabbits via Reducing Oxidative Stress and Apoptosis
In rabbits given high-dose steroids, treatment with molecular hydrogen (injected intraperitoneally) reduced the incidence of bone death (osteonecrosis) from 68% to 29% by suppressing oxidative damage, vascular injury, and cell death (apoptosis).
2016 · Qin — Hydrogen-Rich Saline as an Innovative Therapy for Cataract: A Hypothesis
This paper proposes a theoretical rationale for using molecular hydrogen as an antioxidant to protect against cataract formation — based on H₂'s known ability to selectively neutralise damaging reactive oxygen species (ROS).
2016 · Yang — Effects of hydrogen-rich medium on lipopolysaccharide-induced intestinal epithelial barrier dysfunction of human colon carcinoma cells
In a cell culture model of the intestinal epithelial barrier, hydrogen-rich medium protected Caco2 cells from lipopolysaccharide (LPS)-induced barrier disruption by improving cell viability, reducing cell injury, and partially restoring the expression and structure of tight-junction proteins claudin-1 and occludin.
2016 · Du — Hydrogen-Rich Saline Attenuates Acute Kidney Injury After Liver Transplantation via Activating p53-Mediated Autophagy
In rats undergoing liver transplantation, hydrogen-rich saline (HRS) protected the kidneys from acute injury by reducing oxidative damage and cell death, with p53-mediated autophagy as a key mechanism.
2016 · Zhang — Treatment with Hydrogen-Rich Saline Delays Disease Progression in a Mouse Model of Amyotrophic Lateral Sclerosis
In a transgenic mouse model of ALS, hydrogen-rich saline (HRS) significantly delayed disease onset, prolonged survival, and protected motor neurons from oxidative damage and mitochondrial dysfunction.
2015 · Hattori et al. — Maternal molecular hydrogen treatment attenuates lipopolysaccharide-induced rat fetal lung injury.
Drinking hydrogen-rich water (HRW) before lipopolysaccharide (LPS) injection significantly reduced inflammation, oxidative damage, and cell death in fetal rat lungs — suggesting that maternal H₂ intake could protect premature infants from inflammation-driven lung disease.
2014 · Zhang et al. — Effect of hydrogen-rich water on acute peritonitis of rat models.
This animal study tested hydrogen-rich water (HRW) in three different rat models of acute peritonitis and found consistent protective effects: lower inflammatory markers, reduced oxidative damage, and decreased NF-κB expression in peritoneal tissue.
2013 · Xu et al. — Hydrogen-rich saline ameliorates renal injury induced by unilateral ureteral obstruction in rats.
In a rat model of obstructive kidney disease, hydrogen-rich saline (H₂ dissolved in salt solution) significantly reduced kidney tissue damage, cell death, fibrosis, and oxidative stress markers compared with untreated obstructed animals.
2012 · Takeuchi et al. — Hydrogen may inhibit collagen-induced platelet aggregation: an ex vivo and in vivo study.
In this mixed-design study — combining human ex vivo blood tests and rat in vivo experiments — molecular hydrogen (via H₂ saline or H₂ inhalation) significantly inhibited collagen-induced platelet aggregation.
2012 · Yang et al. — Hydrogen-rich saline protects immunocytes from radiation-induced apoptosis.
Ionizing radiation depletes the immune system by triggering apoptosis (programmed cell death) in immune cells — a major problem in radiation therapy and radiological accidents.
2011 · Chuai — A Possible Prevention Strategy of Radiation Pneumonitis: Combine Radiotherapy with Aerosol Inhalation of Hydrogen-Rich Solution
This theoretical paper proposes that combining radiotherapy with aerosol inhalation of hydrogen-rich physiological saline could reduce radiation pneumonitis — a serious complication of lung cancer radiotherapy — by exploiting H₂'s ability to scavenge the hydroxyl radicals that cause most radiation-induced cell damage.
2010 · Qian — The hypothesis of an effective safe and novel radioprotective agent: hydrogen-rich solution.
This theory paper proposes that hydrogen-rich saline could serve as a safe radioprotective agent — protecting cells from ionising radiation damage by selectively scavenging hydroxyl radicals.
2010 · Liu — Oral administration of mannitol may be an effective treatment for ischemia-reperfusion injury.
This hypothesis paper proposes that oral mannitol — a sugar alcohol that promotes bacterial hydrogen gas production in the colon — could protect organs from ischaemia-reperfusion injury by raising endogenous H₂ levels.
1999 · Ishikawa — A preventive effect of a selective endothelin-A receptor antagonist, S-0139, on the erythropoietin-induced reduction of the renal cortical blood flow.
This animal study in Wistar rats shows that erythropoietin (EPO) reduces renal cortical blood flow (RCBF) by triggering endothelin-1 release, and that the selective ET-A receptor antagonist S-0139 can prevent this reduction.
1999 · Tamori — Role of calcitonin gene-related peptide and capsaicin-sensitive afferents in central thyrotropin-releasing hormone-induced hepatic hyperemia.
This animal study in anesthetized rats demonstrates that central (intracisternal) injection of a TRH analogue increases hepatic blood flow via capsaicin-sensitive afferent neurons and CGRP — and that blocking either pathway completely abolishes this effect.