Authors: Jackson K., Dressler N., Ben-Shushan R.S., Meerson A., LeBaron T.W., Tamir S.
Source: World Journal of Gastroenterology, Volume 24, Issue 45 (2018), pp. 5095–5108
https://doi.org/10.3748/wjg.v24.i45.5095

Objective

To determine the effect of hydrogen-rich water (HRW) and electrolyzed alkaline water (EAW) on high-fat-diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) in mice.

Methods

Mice were divided into four groups:

1. Regular Diet (RD) / Regular Water (RW)

2. High-Fat Diet (HFD) / RW

3. RD / EAW

4. HFD / EAW

Body weight and body composition were monitored. After 12 weeks, the mice were sacrificed, and liver samples were processed for histological evaluation and reverse transcription-polymerase chain reaction (RT-PCR). A follow-up experiment was conducted to assess the specific role of molecular hydrogen (H₂) in EAW by comparing RW to low-H₂ HRW (L-HRW = 0.3 mg/L) and high-H₂ HRW (H-HRW = 0.8 mg/L) in HFD-fed mice. In vitro assays were also performed on hepatocytes isolated from HRW- and RW-consuming mice to assess lipid accumulation under palmitate overload.

Results

EAW used in the study had the following properties:

• pH: 11

• Oxidation-Reduction Potential (ORP): –495 mV

• H₂ Concentration: 0.2 mg/L

Contrary to expectations, no significant differences were observed between EAW and RW groups on either RD or HFD, presumably due to the low H₂ concentration in EAW. However, in the comparison between RW, L-HRW, and H-HRW in HFD-fed mice, H-HRW led to:

• A lower increase in fat mass (46% vs. 61%)

• A higher increase in lean mass (42% vs. 28%)

• A significant reduction in hepatic lipid accumulation (P < 0.01)

Furthermore, hepatocytes isolated from H-HRW mice showed significantly reduced lipid accumulation under palmitate-induced stress compared to RW controls, suggesting a protective effect of H₂.

Conclusion

Molecular hydrogen is the therapeutic component in electrolyzed alkaline water and demonstrates efficacy in ameliorating high-fat-diet-induced nonalcoholic fatty liver disease in mice. Its effectiveness is dose-dependent and linked to hydrogen concentration, rather than alkalinity alone.

Citation

Jackson K, Dressler N, Ben-Shushan RS, Meerson A, LeBaron TW, Tamir S. Effects of alkaline-electrolyzed and hydrogen-rich water in a high-fat-diet nonalcoholic fatty liver disease mouse model. World Journal of Gastroenterology. 2018;24(45):5095–5108.
https://doi.org/10.3748/wjg.v24.i45.5095

Authors: Song L.H., Zhang Y., Zhu C., Ding X.W., Yang L., Yan H.L.
Source: Advances in Medical Sciences, Volume 67, Issue 1 (2021), pp. 29–38

Background

Oxidative damage and intestinal dysbiosis play key roles in the pathogenesis and progression of chronic ulcerative colitis (UC). Molecular hydrogen (H₂) has been recognised for its anti-inflammatory and antioxidant properties, making it a potential therapeutic candidate.

Objective

This study aimed to investigate the therapeutic effect and underlying mechanisms of hydrogen-rich water (HRW) in a mouse model of chronic UC induced by dextran sulphate sodium (DSS).

Methods

Male C57BL/6 mice (7 weeks old, 19.6 ± 0.4 g) were randomly divided into three groups:

1. Normal control group (NC)

2. UC model group (DSS)

3. DSS + HRW treatment group

Chronic UC was induced through three DSS cycles:

• Cycles 1 & 2: 2.5% DSS in drinking water for 5 days, followed by 16 days of normal water.

• Cycle 3: 2% DSS for 4 days, followed by 10 days of normal water.

The DSS + HRW group received HRW (0.8 ppm) orally throughout the entire experimental period.

Results

DSS-treated mice exhibited typical clinical signs of colitis. HRW administration partially alleviated these symptoms, improved histopathological damage, significantly increased glutathione (GSH) levels, and reduced tumour necrosis factor-alpha (TNF-α) concentrations.

Microbiological analysis showed HRW significantly suppressed the growth of Enterococcus faecalis, Clostridium perfringens, and Bacteroides fragilis (P < 0.05 vs. DSS group), restoring microbial balance closer to that of the NC group.

Microarray analysis revealed 252 genes significantly altered in the HRW group compared to DSS-only mice, including 17 inflammation-related genes—of which 9 were interferon-stimulated genes (ISGs), indicating an immune-modulatory effect of HRW.

Conclusion

Hydrogen-rich water partially mitigates inflammation, oxidative stress, and intestinal flora dysbiosis in a murine model of chronic ulcerative colitis induced by DSS. These findings support HRW as a potential adjunctive therapeutic strategy in UC management.

Citation

Song L, Zhang Y, Zhu C, Ding X, Yang L, Yan H. Hydrogen-rich water partially alleviates inflammation, oxidative stress and intestinal flora dysbiosis in DSS-induced chronic ulcerative colitis mice. Advances in Medical Sciences. 2022;67(1):29–38.

Authors: Zhang J.Y., Wu Q.F., Song S.D., Wan Y., Zhang R.Y., Tai M.H., Liu C.
Source: International Immunopharmacology, Volume 21, Issue 1 (2014), pp. 94–101
https://doi.org/10.1016/j.intimp.2014.04.002

Objective

To investigate the effect of hydrogen-rich water (HRW) on acute peritonitis using three different rat models.

Methods

Acute peritonitis was induced in male Sprague-Dawley rats through three distinct methods:

1. Intraperitoneal injection of lipopolysaccharide (LPS)

2. Rat faecal peritonitis

3. Caecal ligation and puncture (CLP)

Rats were assigned to the following groups for each model:

• Control with normal saline

• Control with HRW

• Model + saline

• Model + HRW

HRW or saline (3 mL per rat) was administered orally by gavage for 7 days before and 3 days after model induction. Efficacy was evaluated by measuring:

• White blood cell (WBC) counts

• Plasma endotoxin levels

• Cytokines: Interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α)

• Oxidative stress markers in peritoneal tissue: Malondialdehyde (MDA), Myeloperoxidase (MPO), and Glutathione (GSH)

• Histopathological changes using haematoxylin and eosin staining

• NF-κB expression and localisation in peritoneal tissues via immunohistochemistry

Results

Across all three models, HRW consistently showed protective effects against acute peritonitis. Specifically, HRW:

• Significantly reduced WBC counts, plasma endotoxin, IL-6 and TNF-α

• Increased GSH activity

• Decreased MDA and MPO activities in peritoneal tissue

• Alleviated histopathological damage

• Suppressed NF-κB expression, indicating downregulation of the inflammatory response

Conclusion

Hydrogen-rich water effectively alleviates the severity of acute peritonitis in rat models. Its beneficial effects are likely mediated by anti-inflammatory, antioxidant, and potentially antimicrobial mechanisms, including suppression of NF-κB signalling in peritoneal tissues. These findings suggest a promising adjunctive role for HRW in the management of peritoneal inflammation.

Citation

Zhang JY, Wu QF, Song SD, Wan Y, Zhang RY, Tai MH, Liu C. Effect of hydrogen-rich water on acute peritonitis of rat models. International Immunopharmacology. 2014;21(1):94–101. https://doi.org/10.1016/j.intimp.2014.04.002

Authors: Chen K.D., Wang K.L., Chen C., Zhu Y.J., Tang W.W., Wang Y.J., Chen Z.P., He L.H., Chen Y.G., Zhang W.
Source: World Journal of Gastroenterology, Volume 30, Issue 20 (2024), Article 2709
https://doi.org/10.3748/wjg.v30.i20.2709

Background

Constipation is a highly prevalent functional gastrointestinal disorder that significantly impairs quality of life and contributes to healthcare burdens. Oxidative stress is increasingly recognised as a central pathophysiological mechanism underlying colonic dysmotility and constipation symptoms. Molecular hydrogen (H₂), known for its potent antioxidant properties, presents a promising, safe therapeutic strategy.

Objective

To investigate whether hydrogen-rich water (HRW) alleviates constipation and to elucidate its underlying molecular mechanism.

Methods

Constipation was induced in Sprague-Dawley rats by oral administration of loperamide. Rats were allowed free access to HRW. Outcome measures included:

• 24-hour faecal weight and water content

• Intestinal transit rate (charcoal meal method)

• 16S rDNA sequencing of stool microbiota

• Untargeted serum metabolomics

• Oxidative stress markers: Malondialdehyde (MDA) and superoxide dismutase (SOD)

• Histological assessments: H&E, Alcian blue-PAS, immunohistochemistry and immunofluorescence for ROS, c-kit, PGP9.5, SIRT1, Nrf2 and HO-1

• Gene and protein expression: qPCR and Western blot for SIRT1/Nrf2/HO-1 axis

• SIRT1 inhibition: Intraperitoneal injection of EX527 (SIRT1 inhibitor)

• Cellular model: H₂O₂-induced NCM460 cells treated with β-leucine and traumatic acid to evaluate ROS levels and SIRT1 expression

Results

HRW significantly improved key constipation indicators:

• Increased faecal output and water content

• Enhanced intestinal motility

• Improved mucin layer integrity and enteric neuronal density

• Elevated c-kit expression

HRW also:

• Restored microbial balance

• Normalised serum metabolite profiles

• Reduced oxidative stress in colon tissue

• Upregulated the SIRT1/Nrf2/HO-1 pathway, as confirmed by SIRT1 inhibition experiments

Serum metabolites β-leucine and traumatic acid were found to reduce oxidative stress in NCM460 cells via SIRT1 upregulation.

Conclusion

Hydrogen-rich water alleviates constipation by reducing intestinal oxidative stress through activation of the SIRT1/Nrf2/HO-1 signalling pathway. It also modulates gut microbiota and systemic metabolism. The identified metabolites, β-leucine and traumatic acid, may act as novel regulators of SIRT1, offering future targets for oxidative stress-related bowel dysfunction.

Citation

Chen K.D., Wang K.L., Chen C., Zhu Y.J., Tang W.W., Wang Y.J., et al. Hydrogen-rich water alleviates constipation by attenuating oxidative stress through the sirtuin1/nuclear factor-erythroid-2-related factor 2/heme oxygenase-1 signalling pathway. World Journal of Gastroenterology. 2024;30(20):2709.
https://doi.org/10.3748/wjg.v30.i20.2709

Authors: Xia C.X., Liu W.W., Zeng D.X., Zhu L.Y., Sun X.L., Sun X.J.
Source: Clinical and Translational Science, Volume 6, Issue 5 (2013), pp. 372–375
https://doi.org/10.1111/cts.12076

Background

Chronic hepatitis B (CHB) is characterised by persistent liver inflammation, elevated oxidative stress, and viral replication, which together contribute to hepatic dysfunction and disease progression. Molecular hydrogen (H₂) has been proposed as a therapeutic antioxidant with potential benefits in hepatic diseases.

Objective

To evaluate the effect of orally administered hydrogen-rich water (HRW) on oxidative stress, liver function, and viral load (HBV DNA) in patients with chronic hepatitis B.

Methods

A total of 60 CHB patients were randomly assigned into two groups:

• Conventional treatment group

• Hydrogen intervention group, receiving 1200–1800 mL/day of HRW (in two divided doses) for 6 consecutive weeks

Serum oxidative stress markers, liver function parameters, and HBV DNA levels were measured before and after treatment. An additional 30 healthy individuals were included as a control group.

Results

At baseline, CHB patients showed significantly elevated oxidative stress and impaired liver function compared to healthy controls.

• After 6 weeks:

  • Oxidative stress remained unchanged in the conventionally treated group

  • Significant improvement was observed in the HRW group

  • Liver function and HBV DNA levels improved in both groups post-treatment

  • However, no significant difference in liver function or viral load reduction was observed between the two groups

Conclusion

Hydrogen-rich water significantly reduces oxidative stress in patients with chronic hepatitis B. While liver function and viral load also improved, the results suggest these effects may not be specific to HRW, and longer-term studies are required to determine its sustained impact on liver function and HBV suppression.

Citation

Xia C, Liu W, Zeng D, Zhu L, Sun X, Sun X. Effect of hydrogen-rich water on oxidative stress, liver function, and viral load in patients with chronic hepatitis B. Clin Transl Sci. 2013;6(5):372–375.
https://doi.org/10.1111/cts.12076

Authors: Sharma S., Kim Y., Bajgai J., Rahman M.H., Jeong Y.J., Goh S.H., Park H.J., Kim C.S., Kim H.I., Lee K.J.
Source: Processes, Volume 11, Issue 7 (2023), Article 2142
https://doi.org/10.3390/pr11072142

Background

Chronic constipation is a common functional gastrointestinal disorder that negatively affects patient quality of life. Electrolyzed hydrogen-rich alkaline reduced water (EHARW) has shown therapeutic promise in gastrointestinal disorders due to its antioxidant and anti-inflammatory properties.

Objective

To evaluate the effects of daily intake of EHARW (pH 9.5; H₂ & Antioxidant Potential: 0.5 mg/L) on symptoms and quality of life in patients with chronic constipation.

Methods

This was a single-arm, open-label clinical trial involving 30 patients diagnosed with chronic constipation. Following initial screening, 28 patients completed the protocol (per-protocol population). Each participant was instructed to consume EHARW daily for four weeks at a dosage of 20 mL/kg body weight/day, generated from a household-grade medical water device.

Primary endpoint:

• Frequency of complete spontaneous bowel movements (CSBM) per week

Secondary endpoints:

• Bristol stool form scale score

• PAC-SYM (Patient Assessment of Constipation Symptoms)

• PAC-QOL (Patient Assessment of Constipation–Quality of Life)

Results

No adverse effects were reported throughout the intervention period.

• CSBM frequency increased significantly by 29.8% (p < 0.05)

• Bristol stool score improved by 24.6% (p < 0.01)

• PAC-SYM scores decreased by 58.0%, and PAC-QOL scores dropped by 54.2% (p < 0.001)

These findings indicate both symptomatic relief and enhanced quality of life following EHARW consumption.

Conclusion

Daily intake of EHARW (pH 9.5; H₂ & AP: 0.5 mg/L) significantly improves bowel movement frequency, stool consistency, constipation-related symptoms, and quality of life in patients with chronic constipation. The intervention is safe, feasible for home use, and may represent a promising non-pharmacological approach.

Citation

Sharma S, Kim Y, Bajgai J, Rahman MH, Jeong YJ, Goh SH, Park HJ, Kim C-S, Kim HI, Lee K-J. The Effect of Electrolyzed Hydrogen-Rich Alkaline Reduced Water on Patients with Chronic Constipation—A Clinical Trial. Processes. 2023;11(7):2142. https://doi.org/10.3390/pr11072142