Joints / Rheumatology
Around a dozen human studies exist on joints and inflammatory-rheumatic diseases — small controlled trials, pilot projects and several case reports, for example on rheumatoid arthritis — alongside preclinical research in animal and cell models.
The studies tested hydrogen-rich water, H₂ inhalation and hydrogen-rich infusions, often as a complementary measure in addition to standard therapy. They recorded pain and inflammation markers, disease activity as well as tolerability.
Initial works and case reports suggest possible improvements in inflammation and pain parameters but, owing to small case numbers and the absence of large controlled trials, are only preliminary. An established benefit is not proven; H₂ does not replace antirheumatic therapy.
Human studies on molecular hydrogen for Joints / Rheumatology. This page collects the 37 studies catalogued in this area — 3 randomized trials, 8 pilot/observational studies and 5 reviews. Listed newest first.
2026 · Paparella — Medical Gases as Emerging Regulators of Paediatric Endocrine and Neurodevelopmental Pathways: A Mini-Review
Gaseous signalling molecules — including molecular hydrogen (H₂), nitric oxide, carbon monoxide and hydrogen sulphide — are increasingly recognised as modulators of the developing brain and endocrine system in children.
2025 · Bilski — Antioxidant Therapies as Emerging Adjuncts in Rheumatoid Arthritis: Targeting Oxidative Stress to Enhance Treatment Outcomes
Rheumatoid arthritis is driven not only by immune dysregulation but also by oxidative stress — current DMARDs fail to address ROS-mediated joint damage, opening space for antioxidant adjuncts.
2016 · Zheng — Molecular Hydrogen Therapy Ameliorates Organ Damage Induced by Sepsis
This review summarises animal-based evidence suggesting that molecular hydrogen can reduce inflammatory cytokine release, oxidative stress, and organ damage in sepsis models, improving survival rates across brain, lung, liver, kidney, and intestinal tissues.
2015 · Ostojic — Molecular hydrogen in sports medicine: new therapeutic perspectives.
Molecular hydrogen (H₂) may offer a novel approach for addressing exercise-induced oxidative stress and sports injuries, with potential to also improve exercise performance.
2013 · Ishibashi — Molecular hydrogen: new antioxidant and anti-inflammatory therapy for rheumatoid arthritis and related diseases
Reactive oxygen species (ROS) — especially the hydroxyl radical — play a central role in the joint destruction and systemic inflammation of rheumatoid arthritis (RA), and molecular hydrogen (H₂) selectively neutralizes exactly this radical.
2021 · Javorac — Hydrotherapy with hydrogen-rich water compared with RICE protocol following acute ankle sprain in professional athletes: a randomized non-inferiority pilot trial
Hydrogen-rich baths were just as effective as the gold-standard RICE procedure (rest, ice, compression, elevation) for acute ankle sprain in professional athletes.
2014 · Ostojic et al. — Effectiveness of oral and topical hydrogen for sports-related soft tissue injuries.
In male professional athletes with acute soft tissue injuries, adding oral hydrogen tablets (2 g/day) plus topical hydrogen-rich packs accelerated joint range-of-motion recovery and reduced plasma viscosity compared to standard treatment alone.
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 · 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 · Lui et al. — Predicting Therapeutic Response to Molecular Hydrogen in Autoimmune Diseases via Immunophenotyping
Can we predict in advance which autoimmune patients will benefit from H₂ therapy? This prospective study in 25 patients (rheumatoid arthritis, lupus, and others) developed a novel prediction index — the HRPI — based on immune cell profiles.
2025 · Tu et al. — Molecular Hydrogen Therapy in Rheumatoid Arthritis: A Case Report on the Amelioration of Methotrexate-induced Myelosuppression and Immune Modulation
Methotrexate (MTX) is essential for rheumatoid arthritis but can cause dangerous bone marrow suppression.
2024 · Chen — Molecular Hydrogen Therapy in Aneurysmal SAH With RA and Newly-diagnosed SLE, Complicated With Acute Ischemic Infarction: A Case Report of Improved Immune Markers Including Tr1 Cells, Breg Cells and TIM3 Expression on Tc Cells.
A 44-year-old woman with a ruptured brain aneurysm, rheumatoid arthritis, and newly diagnosed lupus remained unconscious despite surgery, immunosuppressants, and plasmapheresis — until daily hydrogen capsules were added.
2022 · Waelti — Radiographic features of magnesium-based bioabsorbable screw resorption in paediatric fractures
When magnesium-based screws dissolve in bone, they release hydrogen gas — and that gas is perfectly normal, not a sign of infection.
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.
2026 · Zhang — Pearl-Like Bioinspired Coating Enables Regulation of Mg Degradation for Osteoporotic Bone Repair
A pearl-inspired multilayer coating for magnesium alloy bone implants was developed to precisely control the rate at which magnesium degrades in osteoporotic bone — specifically preventing premature hydrogen gas release, which can cause local tissue problems.
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 — Spontaneous Hydrogen-releasing Nanoenzyme Alleviates Osteoarthritis via Oxidative Stress Reduction and Mitochondrial Dysfunction Reversal
A newly engineered nanoenzyme that spontaneously releases hydrogen gas alleviated osteoarthritis in animal experiments by reducing oxidative stress, restoring mitochondrial function, promoting the clearance of damaged mitochondria (mitophagy), and slowing cartilage degeneration.
2025 · Maier — Biomechanical Analysis of Biodegradable Magnesium, Zinc, and Polylactide Pins for Fixation of Radial Head Fractures
Biodegradable magnesium and zinc pins outperformed polylactide pins in laboratory biomechanical testing for radial head fracture fixation, with magnesium pins showing the highest stiffness and lowest fracture displacement.
2025 · Lu — Pyroptosis-responsive microspheres modulate the inflammatory microenvironment to retard osteoporosis in female mice.
Bone loss in osteoporosis is partly driven by a destructive inflammation mechanism called pyroptosis — and a newly designed implantable microsphere scaffold that releases hydrogen gas, magnesium ions, and an anti-inflammatory drug simultaneously can interrupt this process.
2025 · Ji — Hydrolysis of 2D Nanosheets Reverses Rheumatoid Arthritis Through Anti-Inflammation and Osteogenesis.
Two-dimensional calcium disilicide nanoparticles (CSN) hydrolyse in joint fluid to release hydrogen gas, calcium hydroxide, and silica simultaneously — tackling three distinct processes that drive rheumatoid arthritis: oxidative stress, joint acidity, and bone erosion.
2025 · An — Hydrogen activates ACOD1-itaconate pathway to ameliorate steroid-associated osteonecrosis
Hydrogen-rich water (HRW) protects bone from cortisone damage: In the mouse model of steroid-induced bone necrosis, H₂ reduced the death of bone cells, improved bone structure and blood perfusion — via activation of the anti-inflammatory ACOD1-itaconate metabolic pathway.
2024 · Lin — Hydrogen-treated CoCrMo alloy: a novel approach to enhance biocompatibility and mitigate inflammation in orthopedic implants.
Treating the surface of a metal alloy used in orthopedic implants with hydrogen reduced free radicals by 85% in cell models, improved cell compatibility, and promoted new bone formation in an initial animal test.
2024 · Chen et al. — Endogenous Melanin and Hydrogen-Based Specific Activated Theranostics Nanoagents: A Novel Multi-Treatment Paradigm for Rheumatoid Arthritis
Researchers developed nanoparticles (MAHI NGs) that release molecular hydrogen, melanin nanoparticles, and a clinical fluorescent dye directly into inflamed joints — guided by the specific chemical environment of rheumatoid arthritis (RA).
2024 · Yano et al. — Charge Neutralization and β-Elimination Cleavage Mechanism of Family 42 L-Rhamnose-α-1,4-D-Glucuronate Lyase Revealed Using Neutron Crystallography
This structural biochemistry study uses neutron and X-ray crystallography to determine, at atomic resolution, exactly how a fungal enzyme cleaves gum arabic — a complex carbohydrate used as an emulsion stabilizer.
2023 · Son — PdO-Nanoparticle-Embedded Carbon Nanotube Yarns for Wearable Hydrogen Gas Sensing Platforms with Fast and Sensitive Responses
Researchers developed a flexible yarn-type sensor that detects explosive hydrogen concentrations within two seconds — opening a path toward wearable H₂ safety monitors.
2022 · Chen et al. — Photocatalytic Glucose Depletion and Hydrogen Generation for Diabetic Wound Healing
Researchers engineered hydrogen-incorporated titanium oxide nanorods that, under visible light, simultaneously deplete glucose and generate molecular hydrogen (H₂) at diabetic wound sites — addressing both the hyperglycaemic microenvironment and chronic inflammation.
2020 · Holweg — A Lean Magnesium-Zinc-Calcium Alloy ZX00 Used for Bone Fracture Stabilization in a Large Growing-Animal Model
This animal study evaluated biodegradable magnesium-zinc-calcium (ZX00) screws for bone fracture fixation in growing sheep, finding no significant difference in screw degradation between fractured and non-fractured bones, and — importantly — no negative effect of incidental hydrogen gas formation on fracture healing.
2020 · Ishihara — Molecular hydrogen suppresses superoxide generation in the mitochondrial complex I and reduced mitochondrial membrane potential.
In isolated mitochondria and cultured cells, molecular hydrogen altered the direction of electron flow at complex I, suppressed superoxide generation by 51 %, and reduced mitochondrial membrane potential by 11 %.
2019 · Wu — Hydrogen gas protects against ovariectomy-induced osteoporosis by inhibiting NF-κB activation.
In mice with surgically induced estrogen deficiency (ovariectomy model of postmenopausal osteoporosis), inhalation of 60 % molecular hydrogen (H₂) markedly reduced bone loss.
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).
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 · Lin — Molecular Hydrogen Suppresses Activated Wnt/β-catenin Signaling
In cell culture and a rat osteoarthritis model, molecular hydrogen (H₂) suppressed abnormally activated Wnt/β-catenin signalling — a pathway implicated in cartilage breakdown — by promoting degradation of β-catenin, and tended to reduce cartilage loss in rats drinking H₂ water.
2015 · Yu et al. — Protective effects of hydrogen-rich medium on lipopolysaccharide-induced monocytic adhesion and vascular endothelial permeability through regulation of vascular endothelial cadherin.
In endothelial cell culture, hydrogen-rich medium reduced the inflammation-triggered adhesion of monocytes to vessel walls and preserved the integrity of the endothelial barrier — effects mediated through the adhesion protein VE-cadherin.
2010 · Wong — A biodegradable polymer-based coating to control the performance of magnesium alloy orthopaedic implants.
This in-vitro and in-vivo study developed a biodegradable polymer coating for magnesium alloy bone implants to control their corrosion rate and reduce the accumulation of hydrogen gas during degradation.
2008 · Hill — Preliminary tribological evaluation of nanostructured diamond coatings against ultra-high molecular weight polyethylene.
This in-vitro materials science study evaluated nanostructured diamond (NSD) coatings on titanium alloy as a potential counterface for polyethylene in joint replacement implants.