Ergothioneine and Liver Health: How a Natural Antioxidant Protects and Repairs the Liver

Educational summary by Dr. Srinivasa, Medical Advisor, and team. Based on Mao Y. et al. (2025), Journal of Applied Toxicology, DOI doi.org/10.1002/jat.4728. Educational only, no product endorsement.

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The liver is a multi-functioning powerhouse. It filters toxins, processes nutrients, and helps regulate metabolism. But chronic injury from alcohol, fat buildup, viruses, or drugs can trigger liver fibrosis, a slow scarring process that can lead to cirrhosis (fatty liver).

Fibrosis develops when liver cells are injured repeatedly, releasing stress signals that activate the liver's repair cells. These cells overproduce collagen, forming stiff scar tissue that replaces healthy liver.

L-Ergothioneine (EGT) is a rare, diet-derived amino acid found in trace amounts in some foods. Known for its antioxidant and anti-inflammatory properties, it is absorbed into cells through a dedicated "transporter" (OCTN1) and accumulates especially in the liver. Scientists are excited to understand the purpose of OCTN1 in the liver as it uniquely draws EGT into liver cells rather than other antioxidants. Here we review a study examining EGT's potential role in repairing or preventing liver damage.

Short Summary of Findings

If you just want the TL;DR on L-Ergothioneine (EGT):

1. Improved Liver Function: EGT lowered signature blood markers of liver injury and reduced visible liver inflammation and fibrosis.

   
   

2. Blocked Fibrosis Signaling: EGT suppressed the biological process that drives scar formation in the liver.

   
   

3. Reset Liver Metabolism: EGT normalized key metabolic pathways, reducing harmful fat derived by-products and supporting cell repair.

   
   

Together these effects suggest EGT acts like a “cellular shield” for the liver by calming inflammation, clearing damaged molecules, and preventing fibrotic scarring.

Improved Liver Function and Reduced Fibrosis

Researchers performed an in vivo "Mus musculus"  study of chronic liver injury. Injured liver models exposed to a six-week daily EGT dose were significantly healthier than liver models without EGT treatment.

Tests comparing the two types of liver model found the EGT group had less biological damage signature markers, indicating less cell breakdown. The study also found less fibrosis signature markers, suggesting less liver scarring.

Microscopic examination of the liver models confirmed these findings. The exams found EGT exposed liver had clearer structure, less scar forming collagen, and a smoother texture.

In plain language: EGT helped restore normal liver function and structure, with less inflammation, fewer scars, and healthier cells.

Blocked Fibrosis Signaling

A major culprit behind fibrosis is a molecular chain reaction that tells liver cells to produce collagen. In the liver this process is called the "TGF-β" signaling pathway, a system that regulates tissue repair. In the study’s injured liver models, this pathway was highly active, switching on proteins that drive scar formation. During chronic injury, the pathway can enter a vicious cycle. Scar-forming proteins and inflammation feed back to keep TGF-β activity high.

EGT treatment broke this cycle. It significantly reduced TGF-β levels and deactivated scar forming proteins. With these switches turned off, scar buildup slowed.

This effect is especially notable because other dietary antioxidants simply neutralize free radicals. EGT seems to intervene directly in cellular signaling, acting upstream of the fibrosis formation pathway.

In plain language: EGT helped “turn off” the liver’s scar-making machinery, giving cells a chance to heal instead of harden.

Reset Liver Metabolism and Cell Defense

Beyond reducing inflammation, EGT had deep effects on cell metabolism. Using "metabolomics", the researchers identified hundreds of molecules whose levels changed during liver injury and recovery.

Key findings included restoration of the "purine" metabolism pathway, which is responsible for producing energy molecules that power cells. In injured livers, purine pathway products were depleted. EGT brought them back to normal, helping cells regain energy and repair capacity.

EGT also normalized GPL metabolism, a pathway that can generate toxic lipid by-products when the liver is inflamed. By reducing these harmful by-products, EGT helped protect cells from damage and preserve intact cell membranes.

In plain language: EGT helped reset cell control mechanisms when they were under strain from injury. This reset restored energy balance and stopped harmful signals before they cause damage.

Final Thoughts

This 2025 study adds to the growing evidence that L-Ergothioneine is a potent cellular protector. By combining antioxidant, anti-inflammatory, and metabolic actions, EGT helped livers recover from fibrotic damage in an in vivo model.

The findings are particularly interesting because EGT acted on multiple levels, reducing oxidative stress, calming inflammation, and interrupting the vicious metabolic cycle that causes scar formation.

These results suggest that EGT may have potential in future nutritional or therapeutic approaches aimed at protecting the liver from chronic injury and supporting balanced metabolic function.