The founding paper of molecular hydrogen medicine: demonstrated in Nature Medicine that H2 selectively neutralizes highly toxic hydroxyl radicals (·OH) and peroxynitrite (ONOO-), preserving physiological ROS.
Systematic review outlining H2 rapid diffuse permeability across cellular membranes, mitochondrial organelles, and blood-brain barrier, comparing pharmacokinetics of drinking water vs gas inhalation.
Revealed that H2 functions beyond radical scavenging by modulating transcription factor signaling (Nrf2, NF-kB, MAPK), suppressing pro-inflammatory cascades.
Sun Xuejun team pioneered high-pressure physical dissolution method for saturated hydrogen-rich saline, standardizing dosing in preclinical experimental pathology.
Demonstrated that H2 inhalation suppresses mPTP opening, preserving mitochondrial respiration chain complexes and reducing myocardial infarction area.
Demonstrated that H2 acts as a mild hormetic adaptive signal triggering Nrf2 nuclear translocation and upregulating endogenous defense enzymes (HO-1, SOD).
First double-blind crossover trial in exercise science: 10 elite soccer athletes drinking HRW before maximal treadmill tests exhibited reduced peak blood lactate and muscle fatigue.
Randomized controlled trial demonstrating that 14-day HRW intake elevated fasting blood pH and post-exercise bicarbonate buffering capacity in athletes.
Evaluated eccentric exercise DOMS: athletes receiving hydrogen water showed significantly reduced serum creatine kinase (CK) and muscle soreness at 24-48h.
Double-blind randomized trial showing trained endurance runners drinking HRW improved ventilatory efficiency (lower VE/VO2) and submaximal running economy.
Registered protocol investigating acute H2 gas inhalation and HRW intake on autonomic recovery, heart rate variability, and lactate clearance during repeated sprints.
UMIN trial protocol utilizing Near-Infrared Spectroscopy (NIRS) to quantify muscle re-oxygenation dynamics following maximal resistance exercise under HRW intervention.
Randomized double-blind crossover trial in 30 T2D and 6 IGT patients: 8 weeks of HRW intake significantly lowered modified LDL and urinary 8-isoprostane, normalizing OGTT in 4 of 6 IGT subjects.
10-week clinical pilot in 20 metabolic syndrome subjects: HRW consumption increased urine SOD activity by 39%, lowered TBARS by 43%, and improved the HDL/total cholesterol ratio.
Randomized placebo-controlled trial demonstrating that HRW decreased serum LDL-C, protected apolipoprotein A-I from oxidation, and restored HDL-mediated cholesterol efflux capacity.
Clinical trial utilizing flow-mediated dilation (FMD) demonstrating that HRW intake significantly rescued endothelial dysfunction and reduced endothelial cell microparticle release.
Randomized clinical study in NAFLD patients showing 8-week HRW intervention significantly reduced ultrasound-graded hepatic steatosis and attenuated elevated serum transaminases.
ChiCTR trial evaluating the efficacy of daily hydrogen-rich water consumption on serum urate clearance kinetics, xanthine oxidase modulation, and flare frequency.
Demonstrated that chronic ad libitum HRW consumption prevented stress-induced suppression of neural proliferation in the dentate gyrus, preserving spatial memory in water maze.
Randomized, double-blind, crossover clinical trial demonstrating that supplementary H2 gas inhalation improved total UPDRS motor scores in levodopa-medicated Parkinson patients.
Confirmed that chronic HRW drinking suppressed microglial over-activation and lipid peroxidation in APP-transgenic mice, attenuating progressive spatial memory decline.
Japanese national multicenter randomized Phase II trial assessing 2% H2 inhalation combined with targeted temperature management for 90-day cerebral performance category (CPC) recovery.
RIKEN double-blind crossover study in 26 healthy subjects: 4 weeks of HRW intake significantly attenuated anxiety-depression mood states and elevated parasympathetic tone.
ChiCTR registry investigating resting-state fMRI brain structural network connectivity changes in amnestic mild cognitive impairment subjects under structured H2 inhalation.
Dual cellular and human trial: HRW warm bathing stimulated type-I collagen synthesis by 1.85-fold in dermal fibroblasts and clinically reduced UV-induced neck wrinkle depth.
Demonstrated that topical dissolved H2 penetrates the stratum corneum to downregulate MMP-1 and IL-6, preventing solar elastosis and basement membrane destruction.
Randomized clinical study showing topical immersion and saline infusion of H2 markedly decreased DAS28 scores and urinary 8-OHdG in refractory rheumatoid arthritis.
Demonstrated that topical hydrogen damp dressings accelerated neovascularization and re-epithelialization in deep burn wounds by shifting M1 to M2 macrophage phenotypes.
Proved that topical HRW bathing suppressed dermatitis lesions, serum IgE, and Th2 cytokine expression (IL-4, IL-13) in dust-mite sensitized NC/Nga mice.
Human trial using laser Doppler imaging showing twice-daily topical hydrogen facial mist reduced transepidermal water loss (TEWL) and facial erythema redness over 2 weeks.
Engineered solid-state hydrogen-releasing composite hydrogel dressings maintaining sustained H2 diffusion for over 24h, dramatically accelerating diabetic ulcer closure.