Hydrogen Water Protects Against Liver Damage from Acetaminophen Overdose
- Authors
- Naomi Kamimura, Katsuya Iuchi, Tsutomu Igarashi, Ikuroh Ohsawa, Chikako Nito, Jitsuo Usuda, Shigeo Ohta
- Journal
- Journal of Nutritional Biochemistry
- Year
- 2025
- DOI
- 10.1016/j.jnutbio.2025.110176
- Study Type
- Mouse
- Outcome
- Positive
- Peer Reviewed
- Yes
- Country
- Japan
- Health Condition
- Diabetes
- Body System
- Hepatic
TL;DR
In diabetic mice, hydrogen-rich water significantly reduced acetaminophen-induced liver injury by suppressing mitochondrial oxidative stress and enhancing FGF21 expression, showing superior and synergistic effects with NAC.
Key Finding
Hydrogen-infused water reduced acetaminophen-induced liver damage in diabetic mice and enhanced the protective effects of the standard antidote N-acetylcysteine when used together.
Summary
This study tested whether hydrogen-infused water could protect the livers of diabetic mice from damage caused by acetaminophen (a common pain reliever) overdose. Mice that drank hydrogen water before receiving acetaminophen showed less liver damage, lower levels of liver injury markers in their blood, and reduced harmful oxidative stress (cellular damage from unstable molecules) compared to untreated mice. When hydrogen water was combined with N-acetylcysteine (the standard medical treatment for acetaminophen overdose), the protection was even stronger than either treatment alone.
Practical Takeaway
While this mouse study suggests hydrogen water may help protect against acetaminophen-related liver injury, especially in people with diabetes, these results cannot yet be applied to humans. The study was conducted only in animals, so human clinical trials would be needed to determine if hydrogen water offers similar benefits and is safe for this purpose. Anyone concerned about acetaminophen safety should consult their doctor rather than rely on hydrogen water as a treatment.
Abstract
Acetaminophen (APAP) overdose induces severe liver injury, especially in diabetic patients. N-acetylcysteine (NAC) is commonly used as an approved antidote for APAP toxicity; however, its narrow therapeutic window limits its clinical utility. This study investigated the protective effects of molecular hydrogen (H₂) against APAP-induced hepatotoxicity in diabetic mice. Diabetic db/db mice were provided with hydrogen-dissolved water (H₂-water) for two weeks prior to APAP administration. Consumption of H₂-water significantly attenuated APAP-induced liver injury, as evidenced by improved histological findings and decreased plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Using transgenic mice expressing redox-sensitive green fluorescent protein, H₂ was shown to reduce both cytosolic and mitochondrial oxidative stress caused by APAP overdose. We observed that H₂ modulated c-Jun N-terminal kinase (JNK) activation, inhibited mitochondrial translocation of Bax, and suppressed the release of mitochondrial endonucleases. Additionally, H₂ enhanced the expression of the hepatoprotective hormone fibroblast growth factor 21 (FGF21). These findings suggest that H₂ protects against APAP-induced liver injury in diabetic mice by attenuating oxidative stress and upregulating FGF21 expression. Although NAC acts as an antioxidant, H₂ was more effective in reducing mitochondrial oxidative stress. Importantly, co-treatment with H₂ and NAC provided greater protection against APAP-induced hepatotoxicity than NAC alone. This synergistic effect may result from differences in the mechanisms by which NAC and H₂ influence FGF21 expression and mitochondrial oxidative stress. The combination of H₂ and NAC may offer an improved therapeutic strategy for treating APAP-induced liver injury in diabetic patients.