Authors: Liang B., Shi L., Du D.Y., Li H., Yi N., Xi Y., Cui J.J., Li P., Kang H.B., Noda M., Sun X.J., Liu J.K., Qin S.C., Long J.A.
Source: Antioxidants, Volume 12, Issue 6 (2023), Article 1245
https://doi.org/10.3390/antiox12061245

Background

Molecular hydrogen (H₂) has demonstrated antioxidant, anti-inflammatory, and anti-apoptotic effects, and has shown promise in modulating glucose and lipid metabolism in several animal models of metabolic disorders. However, its potential benefit in humans with impaired fasting glucose (IFG) remains underexplored.

Objective

This randomised controlled trial (RCT) aimed to evaluate the effects of hydrogen-rich water (HRW) on individuals with IFG and to investigate the underlying mechanisms, particularly in relation to gut microbiota.

Methods

Seventy-three patients with IFG were enrolled in a double-blind, placebo-controlled RCT. Participants were randomly assigned to receive either 1000 mL/day of HRW or placebo (pure water without H₂ infusion) for eight weeks. Metabolic parameters and faecal gut microbiota profiles were evaluated at baseline (week 0) and post-intervention (week 8). A combined metabolomic and microbiome analysis was performed to examine correlations between H₂-related metabolic changes and gut microbial composition.

Results

Both placebo and HRW groups exhibited significant reductions in fasting blood glucose levels. However, the HRW group showed a significantly greater reduction after eight weeks. Among IFG participants with baseline non-alcoholic fatty liver indicators, remission was observed in 62.5% (10/16) of the HRW group compared to 31.6% (6/19) in the placebo group.

16S rRNA sequencing revealed that HRW modified gut microbiota composition, reducing dysbiosis in IFG patients. Pearson correlation analysis demonstrated that several differentially abundant microbial taxa were strongly associated with nine key metabolites involved in metabolic regulation.

Conclusion

Hydrogen-rich water mildly improved metabolic abnormalities and intestinal dysbiosis in patients with impaired fasting glucose. These findings suggest a novel therapeutic approach and theoretical framework for glycaemic control and early metabolic intervention through microbiome modulation.

Citation

Liang B, Shi L, Du D, Li H, Yi N, Xi Y, Cui J, Li P, Kang H, Noda M, Sun X, Liu J, Qin S, Long J. Hydrogen-Rich Water Ameliorates Metabolic Disorder via Modifying Gut Microbiota in Impaired Fasting Glucose Patients: A Randomised Controlled Study. Antioxidants. 2023;12(6):1245. https://doi.org/10.3390/antiox12061245

Authors: Asada R., Tazawa K., Sato S., Miwa N.
Source: Medical Gas Research, Volume 10, Issue 3 (2020), pp. 114–121

Background

Hydrogen-rich water (HRW) is commonly produced via direct-current (DC) electrolysis; however, its generation via alternating-current (AC) electrolysis has been less explored. HRW produced from tap water using AC electrolysis for 20–30 minutes achieved a dissolved hydrogen concentration of 1.55 mg/L — close to the theoretical maximum of 1.6 mg/L — with an oxidation-reduction potential (ORP) of –270 mV (compared to +576 mV in untreated tap water) and a pH of 7.7–7.8, more physiologically aligned than conventional DC-electrolysed HRW.

Objective

The study investigated whether AC-electrolysed HRW retains high hydrogen levels post-boiling, exhibits potent antioxidant properties, and demonstrates clinical efficacy in improving diabetic markers and reducing systemic oxidative DNA damage.

Methods

Nine subjects with out-of-range serum markers related to diabetes consumed 1500 mL of AC-electrolysed HRW daily for eight weeks.

Antioxidant activity was assessed using 5,5-dimethyl-1-pyrroline-N-oxide spin trapping and electron spin resonance (ESR) to measure hydroxyl radical scavenging capacity. Nanoparticle tracking analysis (NTA) was used to evaluate nanobubble stability pre- and post-boiling (10 minutes).

Results

HRW generated by AC electrolysis demonstrated strong hydroxyl radical-scavenging activity. Nanoparticle suspensions containing up to 5.4 × 10⁷ particles/mL were retained at 3.5 × 10⁷ particles/mL even after boiling — thermodynamically challenging Henry’s Law and indicating the presence of boiling-resistant nanobubbles.

Participants showed favourable trends in glycaemic control, including reductions in fasting glucose and fructosamine levels, and increased 1,5-anhydro-D-glucitol. Additionally, urinary levels and formation rates of the oxidative DNA damage marker 8-hydroxy-2-deoxyguanosine (8-OHdG) were significantly decreased.

Conclusion

Hydrogen-rich water generated via alternating-current electrolysis may be effective in improving diabetes-related biomarkers and mitigating systemic oxidative DNA damage. Its benefits may be attributed to high hydrogen concentrations and the formation of thermally stable nanobubbles with sustained antioxidant properties.

Citation

Asada R, Tazawa K, Sato S, Miwa N. Effects of hydrogen-rich water prepared by alternating-current-electrolysis on antioxidant activity, DNA oxidative injuries, and diabetes-related markers. Medical Gas Research. 2020;10(3):114–121. https://doi.org/10.4103/2045-9912.296041

Authors: Retnaningtyas E., Susatia B., Arifah SN., Lestari SR.
Source: Veterinary World, Volume 15, Issue 1 (2022), pp. 182–187

Background

Water plays a vital role in physiological processes. Disruption of fluid balance can lead to metabolic disorders and the development of diseases such as diabetes mellitus (DM). Hydrogen-rich water (HW) has been recognised as a novel antioxidant with therapeutic potential.

Objective

This study aimed to investigate the role of HW in modulating insulin levels, insulin receptor (IR) expression, and superoxide dismutase (SOD) activity in streptozotocin (STZ)-induced diabetic rats.

Methods

A total of 30 male Wistar rats were randomly assigned to five groups:

• Normal (N) group

• DM (diabetic control) group

• DM + Metformin (DM+Met, 45 mg/kg body weight)

• DM + Metformin + HW

• DM + HW

Diabetes was induced by feeding a high-fat diet for 30 days, followed by repeated low-dose intraperitoneal STZ injections (35 mg/kg body weight). Fresh HW was administered orally ad libitum for 14 days. Insulin, IR, and SOD levels were measured in all groups in serum and liver samples.

Results

HW therapy increased insulin levels and IR expression. Additionally, HW treatment enhanced SOD activity in both serum and liver tissue. No statistically significant differences were found between the effects of HW and metformin therapy.

Conclusion

Hydrogen-rich water exhibits antioxidant activity in STZ-induced diabetic rats and improves levels of insulin, insulin receptor expression, and antioxidant enzyme SOD. These findings support HW as a potential complementary approach in diabetes management.

Citation

Retnaningtyas E, Susatia B, Arifah SN, Lestari SR. The improvement of insulin level after hydrogen-rich water therapy in streptozotocin-induced diabetic rats. Veterinary World. 2022;15(1):182–187.
https://doi.org/10.14202/vetworld.2022.182-187

Authors: Hadi L., Hutapea AM., Florenly F.
Source: The Indonesian Biomedical Journal, Volume 15, Issue 6 (2023), pp. 420–428

Background

Orthodontic tooth movement (OTM) in patients with diabetes mellitus (DM) may pose an increased risk of treatment-related complications due to systemic inflammation and altered bone metabolism. Hydrogen-rich water (HRW) has been shown in numerous studies to reduce oxidative stress and cellular damage.

Objective

This study aimed to evaluate the effects of HRW on interleukin-1β (IL-1β) levels, blood glucose, body weight, tooth movement distance, and the populations of osteoclasts and osteoblasts in STZ-induced diabetic rats undergoing OTM.

Methods

Thirty Rattus norvegicus rats were randomly assigned to six groups:

1. OTM,

2. HRW,

3. DM,

4. DM + OTM,

5. DM + HRW,

6. DM + OTM + HRW.

Diabetes was induced in relevant groups using an 8-week high-fat diet (HFD) followed by streptozotocin (STZ) injection and continued HFD feeding for 4 more weeks. OTM groups underwent orthodontic intervention with mechanical force application. HRW groups received oral administration of hydrogen-rich water three times daily for 4 weeks.

At the end of the experiment, rats were sacrificed for analysis. Blood samples were collected for IL-1β measurement via enzyme-linked immunosorbent assay (ELISA), while the maxillae were extracted for tooth movement measurements and histological analysis of osteoclast and osteoblast counts.

Results

The highest IL-1β level was recorded in the DM + OTM group (140.07 ± 5.14 pg/mL), whereas the lowest was in the HRW group (92.80 ± 2.89 pg/mL). Osteoblast counts were higher in tension sites, whereas osteoclast numbers increased in compression areas.

Conclusion

Oral administration of hydrogen-rich water in STZ-induced diabetic rats undergoing orthodontic tooth movement significantly reduced IL-1β levels, limited excessive tooth mobility, and supported balanced bone remodelling by modulating osteoblast and osteoclast activity.

Citation

Hadi L, Hutapea AM, Florenly F. Effects of Hydrogen-Rich Water on Interleukin-1β, Number of Osteoclasts and Osteoblasts in Streptozotocin-Induced Diabetic Rats with Orthodontic Tooth Movement. The Indonesian Biomedical Journal. 2023;15(6):420–428.

Authors: Zhao C., Guo YS., Wang RX., Cheng C., Chen XM.
Source: Korean Journal of Physiology & Pharmacology, Volume 25, Issue 6 (2021), pp. 517–523
https://doi.org/10.4196/kjpp.2021.25.6.517

Objective

This study aimed to investigate the effect of hydrogen-rich water (HRW) on lactic acid levels in diabetic rats treated with metformin under hypoxic conditions.

Methods

Thirty Sprague-Dawley rats were randomly divided into five groups:

1. Normal diet (Control)

2. Diabetic model (DM)

3. DM + Metformin (DMM)

4. DMM + Hypoxia (DMMH)

5. DMMH + Hydrogen-Rich Water (DMMHR)

Lactic acid, pyruvate, and lactate dehydrogenase levels were measured in blood. Antioxidant markers including superoxide dismutase (SOD) and reduced glutathione (GSH) in liver and heart tissues were assessed, along with malondialdehyde (MDA) and oxidised glutathione (GSSG). Gene expression of pro-apoptotic markers Bax and Caspase-3 was analysed via qPCR. Histopathological examination of myocardial tissue was performed using haematoxylin–eosin (HE) staining.

Results

The DMMHR group exhibited significantly lower levels of lactic acid, pyruvate, and lactate dehydrogenase compared to the DMMH group. Levels of SOD and GSH in the liver and heart were significantly increased following HRW treatment, while MDA and GSSG levels were reduced, indicating attenuated oxidative stress.

qPCR analysis revealed upregulation of Bax and Caspase-3 in the DM group, which was suppressed by metformin (DMM group). However, hypoxia reversed this suppression, and HRW had limited effect on apoptosis-related gene expression under hypoxic conditions. Notably, HE staining demonstrated that HRW helped prevent myocardial fibre damage induced by hypoxia.

Conclusion

Hydrogen-rich water may help reduce lactate accumulation and oxidative stress in metformin-treated diabetic rats exposed to hypoxia, thereby offering protective effects against hypoxia-induced myocardial injury. HRW may thus serve as a potential adjunct to metformin therapy in diabetic patients at risk of lactic acidosis and cardiac complications under low-oxygen conditions.

Citation

Zhao C, Guo Y, Wang R, Cheng C, Chen X. Effect of hydrogen-rich water on the lactic acid level in metformin-treated diabetic rats under hypoxia. Korean J Physiol Pharmacol. 2021;25(6):517–523. https://doi.org/10.4196/kjpp.2021.25.6.517