Glutathione and Fatty Liver Disease

Glutathione: A Promising Therapy for Fatty Liver Disease?

Published March 2025 in Biomedicines, Nguyen et al.’s paper, “A Literature Review of Glutathione Therapy in Ameliorating Hepatic Dysfunction in Non-Alcoholic Fatty Liver Disease,” dives into an emerging question in liver health:

Can glutathione (GSH) help reverse the damage caused by non-alcoholic fatty liver disease (NAFLD)?

Understanding NAFLD: A Growing Global Challenge

Non-alcoholic fatty liver disease affects nearly 38% of the global population, up sharply from about 25% just a decade earlier . It’s closely linked to obesity, type 2 diabetes, and metabolic dysfunction, and can progress to non-alcoholic steatohepatitis (NASH), fibrosis, cirrhosis, and even liver cancer.

The alarming rise in NAFLD reflects global lifestyle trends—poor diets, sedentary habits, and insulin resistance. Yet, there’s no approved pharmacological treatment for the condition. Current management relies mostly on weight loss, diet, and exercise, which aren’t always sustainable or effective long term .

That’s where glutathione enters the picture.

Glutathione: The Liver’s Natural Defender

Glutathione is a powerful antioxidant produced in the liver. It’s made from three amino acids—glutamate, cysteine, and glycine—and is crucial for neutralizing reactive oxygen species (ROS) and detoxifying harmful compounds.

Think of GSH as the liver’s internal cleaning crew: it scavenges free radicals, prevents lipid peroxidation, and helps regenerate other antioxidants like vitamins C and E .

Low levels of GSH are often found in people with chronic liver disease, including NAFLD. The resulting oxidative stress triggers inflammation, mitochondrial dysfunction, and cell death—processes that worsen liver injury. By replenishing GSH, researchers hope to break this vicious cycle.

What the Research Shows

Nguyen and colleagues reviewed studies published between 2014 and 2024 that tested glutathione supplementation in humans with NAFLD. Only three clinical studies met strict inclusion criteria—small in number but revealing in trend .

Study	Country	Dose & Duration	Main Results
Irie et al. (2016)	Japan	300 mg/day for 3 months	Significant reductions in ALT (a liver enzyme) and 8-OHdG (a DNA damage marker) in NASH patients.
Honda et al. (2017)	Japan	300 mg/day for 4 months + lifestyle changes	Significant drop in ALT; non-significant improvement in liver fat (CAP) and stiffness (LSM).
Reddy et al. (2020)	India	300 mg/day for 3 months	Decreased ALT and GGT levels, with higher serum GSH, though statistical significance unclear.

 

Across all studies, ALT levels improved, indicating better liver function. Markers of oxidative stress also dropped, suggesting GSH’s antioxidant role is clinically relevant.

However, the authors caution that small sample sizes and open-label designs limit confidence. None of the studies included a placebo group, and lifestyle changes may have influenced the outcomes.

Why It Matters

The review’s findings point to glutathione’s potential as a simple, low-risk therapy for fatty liver disease. By reducing oxidative stress and improving liver enzyme profiles, GSH may help slow or even reverse early liver damage.

But the evidence isn’t yet strong enough for clinical recommendations. As the authors note, “Further large-scale randomized controlled trials are required to confirm GSH’s efficacy, determine optimal dosing, and assess long-term effects” .

Looking Ahead: From NAFLD to MASLD

Interestingly, the paper also discusses a shift in terminology. Many researchers now prefer the term metabolic dysfunction–associated steatotic liver disease (MASLD) over NAFLD.

This reflects a broader understanding that fatty liver is part of a metabolic disorder, not an isolated liver condition .

Future studies could explore whether glutathione not only protects liver cells but also improves metabolic markers such as insulin resistance and lipid profiles.

The Bottom Line

Glutathione shows promise as a therapeutic tool for NAFLD, especially in reducing oxidative stress and improving liver enzymes. However, we’re still at the beginning of the evidence curve. Larger, well-designed clinical trials will determine whether GSH truly deserves a place in mainstream fatty liver treatment.

Until then, maintaining a balanced diet, regular exercise, and metabolic health remains the most reliable way to protect your liver—while glutathione may soon offer additional help from within.

Reference:

Nguyen, M.T., Lian, A., Guilford, F.T., & Venketaraman, V. (2025). A Literature Review of Glutathione Therapy in Ameliorating Hepatic Dysfunction in Non-Alcoholic Fatty Liver Disease. Biomedicines, 13(3), 644. https://doi.org/10.3390/biomedicines13030644