Authors:
Tao, G.R.; Zhang, G.J.; Chen, W.; Yang, C.; Xue, Y.Z.; Song, G.H.; Qin, S.C.

Source:
Journal of Cellular and Molecular Medicine, Volume 26, Issue 14 (2022), pp. 4113–4123
DOI: 10.1111/jcmm.17456
Clinical Trial ID: China Clinical Trial Registry #ChiCTR-IIR-16009114

Background

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease globally, with rising incidence linked to obesity, type 2 diabetes, and cardiovascular disease. Currently, no approved medication exists for NAFLD. Molecular hydrogen (H₂) has shown antioxidant and anti-inflammatory effects with potential therapeutic applications in various diseases. This study investigated the impact of hydrogen/oxygen (H₂/O₂) inhalation on NAFLD patients, with a focus on hepatocellular autophagy mechanisms.

Methodology

• Design: Randomized, placebo-controlled clinical trial

• Participants: 43 subjects with NAFLD

• Duration: 13 weeks of daily H₂/O₂ inhalation

• Assessments:

  • Serum lipid profile and liver enzymes

  • Liver fat content via ultrasound and CT scan

  • A mouse model of NASH (non-alcoholic steatohepatitis) using methionine- and choline-deficient (MCD) diet was employed for mechanistic studies

  • Cell-based experiments using AML-12 hepatocytes and palmitic acid (PA) to induce steatosis

Results

• Clinical Improvements:

  • Significant reductions in serum lipids and liver enzymes

  • Liver fat content significantly improved in moderate to severe NAFLD patients

• Preclinical Findings:

  • In mice, H₂/O₂ inhalation reduced systemic inflammation and improved liver histology

  • Promoted autophagy in hepatocytes; blocking autophagy with chloroquine reversed these benefits

  • In vitro, hydrogen inhibited lipid accumulation in hepatocytes

  • Hydrogen enhanced PA-induced autophagy, and its lipid-lowering effect was partially reversed by 3-methyladenine (3-MA), an autophagy inhibitor

Conclusion

Hydrogen/oxygen inhalation therapy significantly alleviated NAFLD, especially in moderate to severe patients, with evidence suggesting that autophagy activation in liver cells may be a key mechanism. These findings support molecular hydrogen as a potential therapeutic tool for managing fatty liver disease.

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
DOI: 10.3748/wjg.v24.i45.5095
PMID: 30568387

Objective

To investigate the effects of hydrogen-rich water (HRW) and electrolyzed alkaline water (EAW) on non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in mice.

Methodology

• 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 composition were measured. After 12 weeks, liver samples were analyzed histologically and with RT-PCR.

• A separate experiment evaluated HRW effects using two concentrations:

  • Low-HRW (L-HRW): 0.3 mg H₂/l

  • High-HRW (H-HRW): 0.8 mg H₂/l

• The response of hepatocytes isolated from HRW- and RW-drinking mice was tested under palmitate-induced lipid overload.

Key Parameters of EAW Used:

• pH: 11

• Oxidation-reduction potential: –495 mV

• Hydrogen concentration: 0.2 mg/l

Results

• EAW alone showed no significant benefits on NAFLD parameters, possibly due to low H₂ concentration.

• High-concentration HRW (H-HRW) resulted in:

  • Reduced fat mass gain (46% vs. 61%)

  • Increased lean mass (42% vs. 28%)

  • Reduced hepatic lipid accumulation (P < 0.01)

• Hepatocytes from H-HRW mice were more resistant to lipid overload, demonstrating protective effects of molecular hydrogen.

Conclusion

Molecular hydrogen (H₂) is the key therapeutic agent in EAW and significantly alleviates NAFLD in mice fed a high-fat diet. Its effectiveness depends on adequate hydrogen concentration, underscoring the need for high-H₂ formulations for therapeutic purposes.

Authors:
Li, S.W.; Takahara, T.; Que, W.T.; Fujino, M.; Guo, W.Z.; Hirano, S.I.; Ye, L.P.; Li, X.K.

Source:
American Journal of Physiology – Gastrointestinal and Liver Physiology, Volume 320, Issue 4 (2021), pp. G450–G463
DOI: 10.1152/ajpgi.00145.2020

Background

Nonalcoholic steatohepatitis (NASH) can progress to liver fibrosis if not effectively managed. This study aimed to investigate the protective effect of high-concentration hydrogen-rich water (HRW) in a mouse model of NASH and to elucidate the underlying mechanism of action of molecular hydrogen.

Methodology

• Mice were fed for 20 weeks with either:

  • Choline-supplemented, L-amino acid-defined (CSAA) diet

  • Choline-deficient, L-amino acid-defined (CDAA) diet

• Groups were treated with 7 ppm HRW for 4, 8, or 20 weeks.

• Primary hepatocytes were stimulated with palmitate to mimic hepatic lipid metabolism and were cultured in a gas mixture including 3.8% H₂ to simulate high hydrogen exposure in vitro.

Results

• ALT and AST levels were significantly lower in the CSAA + HRW group.

• HRW-treated mice exhibited less histological liver damage and lower expression of inflammatory cytokines.

• HRW reversed fatty acid oxidation disorders, lipogenesis, hepatic inflammation, and fibrosis, even in mice with pre-existing liver fibrosis.

• Molecular hydrogen inhibited lipopolysaccharide (LPS)-induced cytokine production by upregulating heme oxygenase-1 (HO-1).

• HRW also enhanced liver steatosis recovery and Sirt1 expression, linked to the HO-1/AMPK/PPAR-α/PPAR-γ pathway.

• HRW suppressed palmitate-induced fat metabolism abnormalities and reduced oxidative stress and inflammation in both CSAA- and CDAA-induced models.

Conclusion

Hydrogen-rich water significantly ameliorates liver steatosis, inflammation, and fibrosis in NASH models. Its effect is mediated via:

• HO-1 and IL-10 signaling

• Sirt1 activation

• Modulation of AMPK/PPAR-α/PPAR-γ pathways
  HRW is a promising therapeutic agent for nonalcoholic steatohepatitis by targeting both inflammatory and metabolic dysfunctions.

Authors:
Koyama, Y.; Taura, K.; Hatano, E.; Tanabe, K.; Yamamoto, G.; Nakamura, K.; Yamanaka, K.; Kitamura, K.; Narita, M.; Nagata, H.; Yanagida, A.; Iida, T.; Iwaisako, K.; Fujinawa, H.; Uemoto, S.

Source:
Hepatology Research, Volume 44, Issue 6 (2014), Pages 663–677
DOI: 10.1111/hepr.12172

Background

Liver fibrosis is a common consequence of chronic liver diseases. Persistent hepatocyte injury triggers an inflammatory response, activating hepatic stellate cells (HSCs), which are the main fibrogenic cells in the liver. Reactive oxygen species (ROS) contribute to liver damage and are considered a therapeutic target in liver fibrosis. Hydrogen water has been proposed as a novel treatment option due to its ability to scavenge ROS.

Objective

To investigate the anti-fibrotic effects of hydrogen-rich water (HRW) and elucidate the underlying mechanisms in mouse models of liver fibrosis.

Methodology

• Animal models: C57BL/6 mice were administered either hydrogen-rich water or control water.

• Liver fibrosis was induced using:

  • Carbon tetrachloride (CCl₄)

  • Thioacetamide (TAA)

  • Bile duct ligation (BDL)

• Isolated hepatocytes and hepatic stellate cells were cultured with or without hydrogen exposure.

• Antimycin A was used to induce hydroxyl radical formation in hepatocytes, simulating oxidative liver injury.

Results

• HRW significantly suppressed liver fibrogenesis in both CCl₄- and TAA-induced models.

• No anti-fibrotic effect was observed in the bile duct ligation model.

• In vitro, hydrogen-enriched media selectively suppressed hydroxyl radical formation and cell death in hepatocytes.

• HRW did not affect activation of hepatic stellate cells.

Conclusion

Hydrogen-rich water protects the liver primarily by:

• Scavenging hydroxyl radicals in hepatocytes,

• Preventing hepatocyte death,
  leading to inhibition of liver fibrogenesis in chemical injury models.
  However, it does not directly affect hepatic stellate cell activation, suggesting the protective mechanism is hepatocyte-centric.

Authors:
Tian, Y.; Guo, S.B.; Zhang, Y.; Xu, Y.; Zhao, P.; Zhao, X.C.

Source:
Molecular Neurobiology, Volume 54, Issue 4 (2017), Pages 2579–2584
DOI: 10.1007/s12035-016-9825-2

Objective

To investigate the protective effects and mechanisms of hydrogen-rich saline (HRS) on postoperative cognitive dysfunction (POCD) in aged mice following partial hepatectomy.

Methodology

• Subjects: 96 aged male Kunming mice, randomly divided into 4 groups (n = 24 per group):

  • C (Control)

  • H (Hydrogen-rich saline only)

  • P (POCD)

  • PH (POCD + Hydrogen-rich saline)

• Assessment tools:

  • Morris Water Maze (MWM) to evaluate learning and memory

  • ELISA for measuring TNF-α, IL-1β, and NF-κB activity

  • H&E staining to observe hippocampal morphology

Results

• Mice in the POCD group (P) had significantly impaired cognitive function on day 10 and 14 post-surgery:

  • Longer escape latency

  • Reduced time spent in the target quadrant

  • Lower platform-crossing frequency

• Inflammatory markers (TNF-α, IL-1β, NF-κB) were elevated in group P after surgery.

• In the PH group (HRS-treated POCD mice):

  • Cognitive performance significantly improved

  • Escape latency decreased

  • Time and frequency in the target quadrant increased

  • Inflammatory markers were reduced compared to the POCD group

  • Hippocampal cell necrosis was alleviated

Conclusion

Hydrogen-rich saline mitigates postoperative cognitive dysfunction in aged mice by:

• Inhibiting NF-κB activity in the hippocampus

• Reducing inflammatory cytokines (TNF-α and IL-1β)

• Protecting hippocampal neurons from necrosis

This suggests potential therapeutic value for HRS in the prevention or treatment of POCD, especially in elderly populations undergoing major surgery.

Original Czech Title:
Voda bohatá na vodík zabraňuje progresi nealkoholické steatohepatitidy a doprovodné hepatokarcinogenezi u myší

Authors:
Kawai, D.; Takaki, A.; Nakatsuka, A.; Wada, J.; Tamaki, N.; Yasunaka, T.; Koike, K.; Tsuzaki, R.; Matsumoto, K.; Miyake, Y.; Shiraha, H.; Morita, M.; Makino, H.; Yamamoto, K.

Source:
Hepatology, Volume 56, Issue 3 (2012), Pages 912–921
DOI: 10.1002/hep.25782

Background

Oxidative stress plays a critical role in the progression of simple fatty liver to nonalcoholic steatohepatitis (NASH). Molecular hydrogen, as a selective antioxidant, has the potential to neutralize cytotoxic reactive oxygen species (ROS).

Objective

To investigate the protective effects of hydrogen-rich water (HRW) and compare them to pioglitazone, a pharmaceutical treatment, on the progression of NASH and associated liver cancer (hepatocarcinogenesis) in mouse models.

Methodology

• A mouse model using a methionine-choline-deficient (MCD) diet was developed.

• Mice were divided into 3 experimental groups for 8 weeks:

  1. MCD diet + Control Water (CW group)

  2. MCD diet + Hydrogen-Rich Water (HW group)

  3. MCD diet + Pioglitazone (PGZ group)

• Parameters assessed:

  • Liver enzymes (ALT)

  • Inflammatory markers (TNF-α, IL-6)

  • Genes related to fatty acid synthesis

  • Oxidative stress biomarker 8-OHdG

  • Apoptosis (TUNEL-positive cells)

• STAM mice, a NASH-related liver cancer model, were used to assess hepatocarcinogenesis:

  • STAM mice were assigned to CW-STAM, HW-STAM, or PGZ-STAM groups

  • Tumor development was evaluated after 8 weeks

Results

• Both HRW and pioglitazone reduced:

  • Liver enzyme levels

  • Inflammatory cytokines

  • Oxidative stress markers

  • Apoptosis in liver tissue

• HW group showed:

  • Stronger antioxidant activity than PGZ

  • Lower expression of PPAR-α

  • Smaller decrease in liver cholesterol

• In the STAM mouse model:

  • HW-STAM and PGZ-STAM groups had significantly fewer tumors

  • HW-STAM group had the smallest maximum tumor size

Conclusion

Hydrogen-rich water may be an effective therapeutic option for NASH by:

• Reducing oxidative stress, apoptosis, and inflammation

• Preventing the progression to hepatocellular carcinoma (HCC)

These findings support the potential of HRW as a non-pharmacologic intervention in chronic liver disease management.

Authors:
Lin, C.P.; Chuang, W.C.; Lu, F.J.; Chen, C.Y.

Source:
World Journal of Gastroenterology, Volume 23, Issue 27 (2017), Page 4920
DOI: 10.3748/wjg.v23.i27.4920

Objective

To evaluate the protective effects of hydrogen-rich water (HRW) on ethanol-induced early-stage fatty liver disease in mice, with focus on antioxidant and anti-inflammatory mechanisms.

Methodology

• In vitro: The ability of HRW to neutralize hydrogen peroxide was measured using a chemiluminescence system.

• In vivo: Female mice were divided into 5 groups:

  1. Control (no ethanol)

  2. Ethanol (EtOH)

  3. EtOH + Silymarin (positive control)

  4. EtOH + Hydrogen-rich water (HRW)

  5. EtOH + Silymarin + HRW

• Mice were fed a Lieber-DeCarli liquid diet with ethanol or isocaloric maltodextrin for 12 weeks.

• HRW was freshly prepared and administered 1.2 ml/mouse, three times daily.

• Blood and liver tissue samples were collected for biochemical and histological analyses.

Results

In vitro

• HRW directly scavenged hydrogen peroxide, confirming its antioxidant potential.

In vivo

• HRW increased acyl-ghrelin expression, associated with food intake regulation.

• HRW significantly reduced EtOH-induced increases in:

  • ALT and AST (liver enzymes)

  • Triglycerides and total cholesterol

  • Liver lipid accumulation

  • Proinflammatory cytokines: TNF-α and IL-6

• HRW also:

  • Decreased malondialdehyde (MDA) levels (marker of lipid peroxidation)

  • Restored glutathione (GSH) levels

  • Increased antioxidant enzyme activities: superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase

• Additionally, HRW:

  • Lowered TNF-α and IL-6

  • Increased IL-10 and IL-22 (anti-inflammatory cytokines)

Conclusion

Hydrogen-rich water provides protective effects against chronic ethanol-induced liver injury by:

• Inducing acyl-ghrelin

• Suppressing pro-inflammatory cytokines (TNF-α, IL-6)

• Enhancing anti-inflammatory cytokines (IL-10, IL-22)

• Activating antioxidant enzymes to mitigate oxidative stress

These findings suggest that HRW is a promising intervention for preventing alcohol-related fatty liver disease through combined antioxidant and anti-inflammatory mechanisms.

Authors:
Zhang, J.Y.; Song, S.D.; Pang, Q.; Zhang, R.Y.; Wan, Y.; Yuan, D.W.; Wu, Q.F.; Liu, C.

Source:
World Journal of Gastroenterology, Volume 21, Issue 14 (2015), Page 4195
DOI: 10.3748/wjg.v21.i14.4195

Objective

To evaluate the hepatoprotective effects and mechanisms of hydrogen-rich water (HRW) against acetaminophen (APAP)-induced liver damage in mice.

Methodology

• Male mice were randomly assigned to four groups:

  1. Control group (NS): Received physiological saline

  2. HRW control group: Received HRW only

  3. APAP + NS group: Received lethal or sublethal APAP and then saline

  4. APAP + HRW group: Received APAP and then treated with HRW (5 ml/kg, twice daily for 3 days)

• Two experiments:

  • Lethal dose of APAP (750 mg/kg) to observe 5-day survival

  • Sublethal dose (500 mg/kg) to assess biochemical markers and liver pathology at 24, 48, and 72 hours post-injection

Results

• Survival rate: HRW significantly increased 5-day survival (60% vs. 26.67%, P < 0.05)

• Liver enzymes (ALT & AST): Significantly lower in HRW-treated mice at all timepoints

• Other liver function markers (alkaline phosphatase, bilirubin, LDH): Improved in HRW group

• Liver pathology:

  • Lower liver index and necrotic area in HRW-treated mice

  • Histological improvements confirmed protective effects

• Oxidative stress:

  • Reduced malondialdehyde (MDA) levels in HRW group

  • Restored SOD activity and significantly increased glutathione (GSH)

• Inflammation:

  • Lower serum TNF-α and IL-6

  • Suppression of 4-HNE, nitrotyrosine, phospho-JNK, connexin-32, and CYP2E1 expression

• Liver regeneration:

  • HRW enhanced hepatocyte mitosis and supported liver recovery

Conclusion

Hydrogen-rich water demonstrates significant therapeutic potential in mitigating acetaminophen-induced liver toxicity in mice. It works by:

• Inhibiting oxidative stress

• Reducing inflammatory responses

• Promoting liver regeneration

These findings support the possible clinical application of HRW as a supportive therapy in cases of drug-induced liver injury.

Authors:
Tao, G.R.; Zhang, G.J.; Chen, W.; Yang, C.; Xue, Y.Z.; Song, G.H.; Qin, S.C.

Source:
Journal of Cellular and Molecular Medicine, Volume 26, Issue 14 (2022), Pages 4113–4123
DOI: 10.1111/jcmm.17456
PMID: 35734974
PMCID: PMC9279585

Background

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease globally, with a rising incidence linked to obesity, type 2 diabetes, and cardiovascular conditions. Currently, no approved pharmacological treatment exists for NAFLD.

Molecular hydrogen (H₂)—a known antioxidant and anti-inflammatory agent—has shown therapeutic and preventive effects across multiple diseases. This study investigated the effect of hydrogen/oxygen (H₂/O₂) inhalation on patients with NAFLD and explored hepatocyte autophagy as a potential mechanism.

Methods

• Design: 13-week randomized, placebo-controlled clinical trial (China Clinical Trial Registry: ChiCTR-IIR-16009114)

• Participants: 43 subjects with NAFLD

• Intervention: Daily inhalation of a hydrogen/oxygen gas mixture

• Outcomes measured:

  • Serum lipids and liver enzymes

  • Liver fat content via ultrasound and CT (in moderate to severe cases)

  • A complementary animal study using a methionine–choline-deficient (MCD) diet mouse model was also conducted to explore underlying mechanisms

Results

• Clinical findings in humans:

  • H₂/O₂ inhalation significantly improved serum lipids and liver enzymes

  • Liver fat content was significantly reduced in moderate-to-severe NAFLD cases, as confirmed by imaging (ultrasound, CT)

• Animal and cellular experiments:

  • H₂/O₂ inhalation reduced systemic inflammation and improved liver histology in MCD diet-induced mice

  • H₂ promoted autophagy activation in hepatocytes

  • The beneficial effects of hydrogen were reversed by autophagy inhibitors like chloroquine and 3-methyladenine (3-MA)

  • Hydrogen also inhibited lipid accumulation in AML-12 liver cells, particularly when induced with palmitic acid (PA)

Conclusion

Hydrogen/oxygen inhalation alleviates NAFLD, especially in moderate-to-severe cases. The protective effect is likely mediated through the activation of hepatic autophagy, offering a promising non-pharmacological approach for managing NAFLD.

Authors:
Yang, Q.; Ji, G.; Pan, R.; Zhao, Y.; Yan, P.

Source:
Molecular and Clinical Oncology, Volume 7, Issue 5 (2017), Pages 891–896
DOI: 10.3892/mco.2017.1409

Objective

This study aimed to evaluate the hepatoprotective effects of hydrogen-rich water (HRW) on liver function in patients with colorectal cancer (CRC) undergoing mFOLFOX6 chemotherapy, which is known to cause liver-related side effects.

Methodology

• Design: Controlled, randomized, single-blind clinical trial

• Setting: Oncology Department, Taishan Hospital, Taian, China (June 2010 – February 2016)

• Participants:

  • Initially enrolled: 152 CRC patients

  • Included: 146 met the inclusion criteria

  • Randomized: 144 patients into two groups

    • HRW group (n = 80)

    • Placebo group (n = 64)

  • Final analysis included:

    • 76 in HRW group

    • 60 in placebo group

• Assessment: Liver function was evaluated using serum markers:

  • ALT (alanine aminotransferase)

  • AST (aspartate aminotransferase)

  • Alkaline phosphatase

  • Indirect bilirubin (IBIL)

  • Direct bilirubin

• The focus was on elevations in ALT, AST, and IBIL, which are indicative of liver damage from chemotherapy.

Results

• HRW group:

  • No significant changes in liver enzyme levels before and after chemotherapy

  • Indicated effective protection of liver function

• Placebo group:

  • Significant elevations in ALT, AST, and IBIL after chemotherapy

  • Indicative of liver injury caused by mFOLFOX6 treatment

Conclusion

The findings suggest that hydrogen-rich water can alleviate liver damage associated with mFOLFOX6 chemotherapy in colorectal cancer patients. HRW presents a promising supportive therapy to reduce chemotherapy-induced hepatotoxicity.

Authors:
Kang, K.M.; Kang, Y.N.; Choi, I.B.; Gu, Y.; Kawamura, T.; Toyoda, Y.; Nakao, A.

Source:
Medical Gas Research, Volume 1, Article 11 (2011)
DOI: 10.1186/2045-9912-1-11

Background

Cancer patients undergoing radiotherapy often experience fatigue and a decline in quality of life (QOL). Many radiation-related side effects are linked to oxidative stress and inflammation caused by the production of reactive oxygen species (ROS) during treatment. Molecular hydrogen (H₂), known for its antioxidant and anti-inflammatory properties, was investigated in this study as a potential method to alleviate such side effects by consuming hydrogen-rich water (HRW).

Methodology

• Design: Randomized, placebo-controlled trial

• Participants: 49 patients receiving radiotherapy for malignant liver tumors

• Intervention:

  • Hydrogen-rich water group: Received drinking water enriched with H₂ (0.55–0.65 mM), produced by inserting a metallic magnesium stick into the water.

  • Placebo group: Received regular water without hydrogen enhancement.

• Duration: 6 weeks

• Assessment Tools:

  • Korean version of the EORTC QLQ-C30 (a standard tool for assessing QOL in cancer patients)

  • Blood tests for reactive oxygen metabolite derivatives (d-ROMs) and biological antioxidant power (BAP)

Results

• Drinking hydrogen-rich water:

  • Reduced oxidative stress markers in the blood

  • Maintained antioxidant capacity in plasma

  • Significantly improved QOL scores compared to placebo during radiotherapy

• Importantly, there was no difference between the HRW and placebo groups in terms of tumor response to radiotherapy, indicating HRW did not compromise anti-tumor efficacy.

Conclusion

Daily consumption of hydrogen-rich water may serve as a novel therapeutic strategy to enhance quality of life in cancer patients during radiotherapy. It effectively reduces radiation-induced oxidative stress without hindering the anti-cancer effects of the treatment.

Authors:
Xia, C.X.; Liu, W.W.; Zeng, D.X.; Zhu, L.Y.; Sun, X.L.; Sun, X.J.

Source:
CTS – Clinical and Translational Science, Volume 6, Issue 5 (2013)
DOI: 10.1111/cts.12076

Objective

To investigate the effects of hydrogen-rich water (HRW) on oxidative stress, liver function, and HBV DNA levels in patients with chronic hepatitis B (CHB).

Methodology

• Participants:

  • 60 patients with chronic hepatitis B

  • Randomized into:

    • Routine treatment group

    • Hydrogen treatment group (routine care + oral HRW at 1200–1800 ml/day, twice daily for 6 weeks)

  • Control group: 30 healthy subjects

• Measurements: Before and after treatment:

  • Serum oxidative stress markers

  • Liver function tests

  • HBV DNA viral load

Results

• Baseline:

  • CHB patients had significantly elevated oxidative stress and impaired liver function compared to healthy controls.

• After treatment:

  • Routine group: No change in oxidative stress

  • Hydrogen group: Significant reduction in oxidative stress levels

  • Liver function and HBV DNA levels improved in both patient groups, but no significant difference between them after treatment

Conclusion

Hydrogen-rich water significantly reduces oxidative stress in patients with chronic hepatitis B.
While both liver function and HBV DNA load showed improvement, the study suggests that longer treatment durations are needed to determine whether HRW has a sustained and significant effect on liver function and viral load.

Authors:
Korovljev, D.; Stajer, V.; Ostojic, J.; LeBaron, T.W.; Ostojic, S.M.

Source:
Clinics and Research in Hepatology and Gastroenterology, Volume 43, Issue 6 (2019)
DOI: 10.1016/j.clinre.2019.05.007

Background

Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disorder worldwide, but effective treatment options remain limited. Given that metabolic dysfunction is central to NAFLD, agents like molecular hydrogen (H₂) that improve lipid and glucose metabolism may offer new therapeutic avenues.

Objective

To evaluate the effects of 28-day intake of hydrogen-rich water (HRW) on liver fat accumulation, body composition, and biochemical markers in overweight patients with mild-to-moderate NAFLD.

Methodology

• Participants:
  12 overweight outpatients with NAFLD (mean age 56.2 ± 10.0 years, BMI 37.7 ± 5.3 kg/m², 7 females, 5 males)

• Design:

  • Double-blind, placebo-controlled, crossover study

  • Participants received either 1L/day of HRW or placebo water for 28 days

  • Registered on ClinicalTrials.gov (ID: NCT03625362)

• Assessments:

  • Dual-echo MRI for liver fat content

  • Serum liver enzyme profiles

  • Body weight and composition

Results

• Liver Fat Reduction:

  • HRW significantly reduced liver fat content compared to placebo

  • Mean liver fat dropped from 284.0 ± 118.1 mM to 256.5 ± 108.3 mM (2.9% relative decrease; 95% CI: 0.5–5.5)

• Liver Enzymes:

  • Aspartate aminotransferase (AST) levels decreased by 10.0% (95% CI: –23.2 to 3.4)

• Body Metrics:

  • No significant changes in body weight or composition were observed between the groups

Conclusion

Preliminary findings suggest that hydrogen-rich water may serve as an adjuvant treatment for mild-to-moderate NAFLD by reducing hepatic fat and improving liver enzyme profiles, without affecting body weight. These results warrant further clinical trials to fully assess the safety and efficacy of molecular hydrogen in treating NAFLD.