Fructooligosaccharide feeding during gestation to pregnant mice provided excessive folic acid decreases maternal and female fetal oxidative stress by increasing intestinal microbe-derived hydrogen gas

Fructooligosaccharide (FOS) is fermented by intestinal microbes to generate intestinal microbe-derived hydrogen gas (IMDH). Oxidative stress increases during gestation, whereas hydrogen gas has antioxidant effects with therapeutic benefits. We have previously reported that the offspring from a pregnant, excessive folic acid mouse model (PEFAM) had abnormal glucose metabolism after growth. We hypothesized that IMDH by FOS feeding during gestation in PEFAM would suppress maternal and fetal oxidative stress. C57BL/6J mice on day 1 of gestation were divided into 3 groups and dissected at gestational day 18. The control (CONT) diet was AIN-93G containing folic acid 2 mg/kg diet; PEFAM was fed with an excessive folic acid (EFA) diet containing folic acid 40 mg/kg diet, and the EFA-FOS diet was replaced half of the sucrose in the EFA diet. Hydrogen gas concentrations in maternal livers and whole fetuses in EFA-FOS were significantly higher than those in CONT and EFA, respectively (P < .05). Maternal and fetal 8-hydroxy-2'-deoxyguanosine in EFA-FOS were not significantly different from those in the CONT group, whereas those in the EFA group were significantly increased compared with CONT and EFA-FOS (P < .05). In EFA-FOS, expression of protein and mRNA of superoxide dismutase and heme oxygenase 1 in mothers and superoxide dismutase in fetuses were not significantly different from those in CONT, whereas those in EFA were significantly increased (P < .05). The protein expression of Nrf2 in mothers and fetuses were not significantly different between EFA-FOS and CONT. Therefore, FOS feeding to PEFAM during gestation decreases maternal and fetal oxidative stress through IMDH.

Can Hydrogen Water Enhance Oxygen Saturation in Patients with Chronic Lung Disease? A Non-Randomized, Observational Pilot Study

Background: Recently, chronic lung diseases have been found to be associated with marked inflammation and oxidative stress, which leads to fibrosis in the lungs and chronic respiratory failure. This study aims to determine if hydrogen-rich water (HRW) can enhance oxygen saturation among patients with chronic lung diseases. Methods: Ten patients with chronic lung diseases due to COPD (n = 7), bronchial asthma (n = 2), and tuberculosis of the lung (n = 1) with oxygen saturation of 90-95% were provided high-concentration (>5 mM) HRW using H2-producing tablets for 4 weeks. Oxygen saturation was measured via oximeter and blood pressure via digital automatic BP recorder. Results: HRW administration was associated with a significant increase in oxygen saturation (SpO2) and decrease in TBARS, MDA, and diene conjugates, with an increase in vitamin E and nitrite levels, compared to baseline levels. Physical training carried out after HRW therapy appeared to increase exercise tolerance and decrease hypoxia, as well as delay the need for oxygen therapy. Conclusion: Treatment with HRW in patients with hypoxia from chronic lung diseases may decrease oxidative stress and improve oxygen saturation in some patients. HRW therapy may also provide increased exercise tolerance in patients with chronic hypoxia, but further research is needed. Keywords: COPD; COVD-19; antioxidant; hydrogen-rich water; hypoxia; inflammation; oxidative stress.

Comprehensive brain tissue metabolomics and biological network technology to decipher the mechanism of hydrogen-rich water on Radiation-induced cognitive impairment in rats

Background: Hydrogen-rich water (HRW) has been shown to prevent cognitive impairment caused by ionizing radiation. This study aimed to investigate the pharmacological effects and mechanisms of HRW on ionizing radiation by coupling the brain metabolomics and biological target network methods. Methods and results: HRW significantly improves the cognitive impairment in rats exposed to ionizing radiation. Based on metabolomics and biological network results, we identified 54 differential metabolites and 93 target genes. The KEGG pathway indicates that glutathione metabolism, ascorbic acid and aldehyde acid metabolism, pentose and glucuronic acid interconversion, and glycerophospholipid metabolism play important roles in ionizing radiation therapy. Conclusion: Our study has systematically elucidated the molecular mechanism of HRW against ionizing radiation, which can be mediated by modulating targets, pathways and metabolite levels. This provides a new perspective for identifying the underlying pharmacological mechanism of HRW. Keywords: Biological network; Brain tissue metabolomics; Hydrogen-rich water; Ionizing radiation.

The clinical research on the effect of hydrogen-rich water on primary retinitis pigmentosa

Objective: To investigate the feasibility and effectiveness of hydrogen in the treatment of retinitis pigmentosa (RP) patients through the drinking of hydrogen-rich water (HRW). Methods: RP patients clinically diagnosed in our hospital were selected and given HRW for drinking at 400-500 ml twice a day for four consecutive weeks. Changes in best corrected visual acuity (BCVA), intraocular pressure, the retinal thickness, and choroidal thickness, as well as the amplitude and peak time of visual electrophysiological examinations before and after HRW drinking were observed. Data were statistically analyzed. Results: In total, 24 eyes of 13 patients with RP (3 males and 10 females aged-27-65 years old, were enrolled in the study. The BCVA after HRW drinking was 0.34 ± 0.25, which was statistically improved compared with that before (P < 0.05). There were no significant differences in intraocular pressure, retinal lhickness, or choroidal thickness before and after HRW drinking (all P > 0.05). The amplitudes of the b-wave in Dark-adaptation 0.01 response, a and b waves in Dark-adaptation 3.0 response, the Dark-adaptation Ops total wave, a and b waves in Light-adaptation 3.0 response, and the Light-adaptation Flicker response of electroretinogram (ERG) were significantly higher than those before HRW drinking (all P < 0.05). The corresponding peak times iwere mproved to some extent compared to those before HRW consumption (all P < 0.05). Six patients with RP (11 eyes) had a BCVAm ore than 20/200. The amplitude and peak time of the P100 -ave from the 1°p attern visual evoked potentials (PVEP) were not significantly different from those before HRW drinking (P > 0.05), while the data from the 15′ PVEP were statistically different (P < 0.05). Seven patients with RP (13 eyes) had a BCVA less than. 20/200 No significant differences were found in the amplitude and peak time of the P2 wave from the 1.0 Hz flash visual evoked potentials (FVEP) and the amplitude from the 12 Hz FVEP compared with those before HRW drinking (all P > 0.05). Conclusion: Short-term HRW drinking slightly improved visual function in patients with primary RP, whereas no significant improvement was found in the thickness of the retina and choroid. Keywords: Choroid; Electrophysiology; Hydrogen-rich water; Retina; Retinitis pigmentosa.

The effect of hydrogen-rich water on letrozole-induced polycystic ovary syndrome in rats

Research question: What is the effect of hydrogen-rich water on rats with polycystic ovary syndrome (PCOS)? Design: Female rats were divided into four groups, each consisting of eight animals. The control group received a carboxymethyl cellulose (CMC) solution, the molecular hydrogen (H2) group was given hydrogen-rich water and a CMC solution, the PCOS group was administered letrozole dissolved in a CMC solution and the PCOS + H2 group was given hydrogen-rich water and letrozole dissolved in a CMC solution. Blood and tissue samples were then collected, and biochemical and histopathological analyses were conducted on the samples. Results: The histopathological analysis showed a reduction in the number of cysts in the PCOS + H2 group compared with the PCOS group (P < 0.0001). Additionally, the malondialdehyde, cortisol and testosterone data revealed a significant decrease in the PCOS + H2 group compared with the PCOS group (P = 0.0458, P = 0.0003, P = 0.0041, respectively). The glutathione also showed a statistically significant increase in the PCOS + H2 group compared with the PCOS group (P = 0.0012). Conclusion: The study findings demonstrate that hydrogen-rich water reduces the number of cysts and oxidative damage in rats with PCOS. Keywords: glutathione; hydrogen rich water; malondialdehyde; polycystic ovary syndrome; rats.

Therapeutic Potential of Hydrogen-Rich Water on Muscle Atrophy Caused by Immobilization in a Mouse Model

Skeletal muscle atrophy is associated with poor quality of life and disability. Thus, finding a new strategy for the prevention and treatment of skeletal muscle atrophy is very crucial. This study aimed to investigate the therapeutic potential of hydrogen-rich water (HRW) on muscle atrophy in a unilateral hind limb immobilization model. Thirty-six male Balb/C mice were divided into control (without immobilization), atrophy, and atrophy + hydrogen-rich water (HRW). Unilateral hind limb immobilization was induced using a splint for 7 days (atrophy) and removed for 10 days (recovery). At the end of each phase, gastrocnemius and soleus muscle weight, limb grip strength, skeletal muscle histopathology, muscle fiber size, cross-section area (CSA), serum troponin I and skeletal muscle IL-6, TNF-α and Malondialdehyde (MDA), and mRNA expression of NF-κB, BAX and Beclin-1 were evaluated. Muscle weight and limb grip strength in the H2-treated group were significantly improved during the atrophy phase, and this improvement continued during the recovery period. Treatment by HRW increased CSA and muscle fiber size and reduced muscle fibrosis, serum troponin I, IL-6, TNF-α and MDA which was more prominent in the atrophy phase. These data suggest that HRW could improve muscle atrophy in an immobilized condition and could be considered a new strategy during rehabilitation.

Evaluation of the safety and potential lipid-lowering effects of oral hydrogen-rich coral calcium (HRCC) capsules in patients with metabolic syndrome: a prospective case series study

Background: Metabolic syndrome is characterized by a cluster-like occurrence of conditions such as hypertension, hyperglycaemia, elevated low-density lipoprotein (LDL) cholesterol or triglycerides (TG) and high visceral fat. Metabolic syndrome is linked to the build-up of plaque within the artery, which leads to disorders of the circulatory, nervous and immune systems. A variety of treatments target the regulation of these conditions; nevertheless, they remain dominant risk factors for the development of type 2 diabetes (T2DM) and cardiovascular disease (CVD), which affect 26.9% of the US population. Management and intervention strategies for improving cholesterol and/or TG are worthwhile, and recent studies on hydrogen treatment are promising, particularly as molecular hydrogen is easily ingested. This study aimed to investigate the lipid-lowering effects and quality of life (QOL) improvement of hydrogen-rich coral calcium (HRCC) in patients with metabolic syndrome. Methods: The patients, all Taiwanese, were randomly assigned to 3 different doses (low, medium, and high) of HRCC capsules. The primary outcome was the adverse effects/symptoms during this 4-week use of HRCC capsules. The secondary outcome was lipid profile changes. Complete blood count, inflammatory biomarkers, and QOL were also measured before and after the course of HRCC. Results: Sixteen patients with metabolic syndrome completed this study (7 males, 9 females; mean age: 62 years; range: 32-80). No obvious adverse effects were recorded. Only changes in blood TG reached significance. The baseline TG value was 193.19 μL (SD = 107.44), which decreased to 151.75 μL (SD = 45.27) after 4 weeks of HRCC (p = 0.04). QOL showed no significant changes. Conclusion: This study is the first human clinical trial evaluating HRCC capsules in patients with metabolic syndrome. Based on the safety and potential TG-lowering effects of short-term HRCC, further long-term investigations of HRCC are warranted. Clinical trial registration: [], identifier [NCT05196295].

Hydrogen-rich water upregulates fecal propionic acid levels in overweight adults

Fecal short-chain fatty acids are responsive to oral hydrogen in overweight adults. Propionic acid significantly increased in participants who consumed hydrogen-rich water for 12 wk compared with those who consumed tap water. This finding holds potential significance in addressing metabolic dysregulation.

The Effect of Adjuvant Therapy with Molecular Hydrogen on Endogenous Coenzyme Q10 Levels and Platelet Mitochondrial Bioenergetics in Patients with Non-Alcoholic Fatty Liver Disease

Molecular hydrogen (H2) has been recognized as a novel medical gas with antioxidant and anti-inflammatory effects. Non-alcoholic fatty liver disease (NAFLD) is a liver pathology with increased fat accumulation in liver tissue caused by factors other than alcohol consumption. Platelet mitochondrial function is considered to reflect systemic mitochondrial health. We studied the effect of adjuvant therapy with hydrogen-rich water (HRW) on coenzyme Q10 (CoQ10) content and platelet mitochondrial bioenergetics in patients with NAFLD. A total of 30 patients with NAFLD and 15 healthy volunteers were included in this clinical trial. A total of 17 patients (H2 group) drank water three × 330 mL/day with tablets producing HRW (>4 mg/L H2) for 8 weeks, and 13 patients (P group) drank water with placebo tablets producing CO2. The concentration of CoQ10-TOTAL was determined by the HPLC method, the parameter of oxidative stress, thiobarbituric acid reactive substances (TBARS), by the spectrophotometric method, and mitochondrial bioenergetics in platelets isolated from whole blood by high-resolution respirometry. The patients with NAFLD had lower concentrations of CoQ10-TOTAL in the blood, plasma, and platelets vs. the control group. Mitochondrial CI-linked LEAK respiration was higher, and CI-linked oxidative phosphorylation (OXPHOS) and CII-linked electron transfer (ET) capacities were lower vs. the control group. Plasma TBARS concentrations were higher in the H2 group. After 8 weeks of adjuvant therapy with HRW, the concentration of CoQ10 in platelets increased, plasma TBARS decreased, and the efficiency of OXPHOS improved, while in the P group, the changes were non-significant. Long-term supplementation with HRW could be a promising strategy for the acceleration of health recovery in patients with NAFLD. The application of H2 appears to be a new treatment strategy for targeted therapy of mitochondrial disorders. Additional and longer-term studies are needed to confirm and elucidate the exact mechanisms of the mitochondria-targeted effects of H2 therapy in patients with NAFLD.

Molecular hydrogen modulates brain glutamate/GABA-glutamine cycle in overweight humans

Introduction: We evaluated whether 12-week intake of molecular hydrogen (H2) in 5 overweight adults (3 women; age: 50.2 ±11.9 years, body mass index: 29.4 ±2.1 kg/m2) affects brain levels of the glutamate-glutamine-GABA cycle, critical amino acid neurotransmitters in the mechanism of neuronal activation during appetite regulation. Methods: A 1.5-T single-voxel proton magnetic resonance spectroscopy was used to assess the tissue concentrations of relevant metabolites. Results: The mean glutamate and glutamate-plus-glutamine levels at the posterior cingulate gyrus decreased significantly during the study; this was accompanied by a significant drop in GABA levels at left prefrontal white matter, and glutathione levels at anterior cingulate gyrus. No changes in the brain metabolites were found in the comparable group of overweight individuals (n = 4, 2 women; age: 41.0 ±13.9, BMI 26.8 ±1.3 kg/m2) followed-up in the past without this treatment. Conclusions: We showed a possible hydrogen-driven upregulation of neurotransmitters involved in appetite stimulation leading to hunger suppression and weight loss. Further studies analyzing appetite-controlling metabolic pathways affected by H2 would require monitoring of additional biomarkers of satiation and satiety during different feeding regimens.