Glutathione (GSH) is a tripeptide compound composed of glutamic acid, cysteine and glycine. It is the non-protein thiol compound with the highest concentration in cells, and its concentration is particularly abundant in the liver.
The liver, as the “chemical factory” of the human body, undertakes key physiological functions such as metabolism, detoxification, synthesis and immunity.
With the changes in modern lifestyles, drug abuse, viral infections and the global prevalence of metabolic syndrome, the incidence of liver diseases has continued to rise, posing a severe challenge to global public health.
Among various liver-protecting strategies, the strengthening of endogenous protective mechanisms and the application of exogenous supplements have received extensive attention.
Glutathione and its metabolic system are the first line of defense of the body against oxidative stress and endogenous/exogenous toxins.
An in-depth exploration of the specific applications of glutathione in maintaining liver function and preventing liver damage not only holds significant theoretical importance but also contains great clinical value.
The content of glutathione in the human body gradually decreases with age. The level of GSH in newborns is the highest, but it significantly drops in old age.
When the body is under stress, illness or environmental pollution, the consumption rate of glutathione will accelerate and its synthesis ability may also be inhibited.
distribution of glutathione in human body
- The distribution of glutathione in the human body is not uniform, and the concentration varies greatly among different tissues and organs.
- The liver, as the main detoxification organ, has the highest concentration of glutathione within its cells, which is closely related to its detoxification function.
- In addition, the content of glutathione in tissues sensitive to oxidative damage such as the retina, lens and red blood cells is also relatively high to protect these tissues from oxidative damage.
How does glutathione protect liver?
1. Antioxidation: Resist free radical attacks
During the metabolic process, the liver generates a large amount of reactive oxygen species (ROS) and free radicals. These substances attack cell membranes, proteins and DNA, leading to liver cell damage or even death.
Glutathione directly binds to these harmful substances through the sulfhydryl group (-SH) in its structure, converting them into harmless water or alcohol, thereby protecting the integrity of liver cell structure.
Glutathione is also involved in an efficient “antioxidant cycle” :
Under the catalysis of glutathione peroxidase (GPx), it can reduce peroxides such as hydrogen peroxide, and is oxidized to GSSG itself. Then, under the action of glutathione reductase (GR), it is restored to GSH, which is recycled and continuously exerts antioxidant effects.
2. Detoxification: Resolving “poison crisis” of liver
The liver is the most important detoxification organ in the human body.
Many drugs (such as acetaminophen), alcohol metabolites and environmental toxins all need to processed by the liver.
Glutathione plays the role of a “binder” in these processes.
Under the catalysis of glutathione S-transferase (GSTs), it combines with toxins to form water-soluble substances, which excreted from the body through bile or urine, significantly reducing the direct damage of toxins to the liver.
3. Anti-inflammatory and anti-fibrotic: Blocking progression of liver diseases
Long-term liver damage can cause inflammation and fibrosis (hardening of liver tissue), and eventually may lead to liver cirrhosis or even liver cancer.
Glutathione can indirectly inhibit the release of inflammatory factors by reducing oxidative stress and may also suppress the activation of hepatic stellate cells, thereby delaying or even reversing the process of liver fibrosis.
4. Signal regulation: Activate cell’s self-protection mechanism
Recent studies have found that glutathione is not only a “cleaner” but also a “signalman”.
It can comprehensively enhance the liver’s defense capabilities by regulating the Nrf2 pathway – the “master switch” of cellular antioxidant responses, initiating the expression of a series of protective genes,
including enzymes that synthesize more glutathione and detoxification enzymes.
How is glutathione applied in treatment of liver diseases?
Injection: Commonly used in clinical practice, with definite effects
At present, intravenous injection of reduced glutathione is the mainstream method for the adjuvant treatment of liver diseases, especially suitable for:
- Viral hepatitis
- Drug-induced liver injury
- Alcoholic liver disease
- Chemical liver injury
The common dosage is 1.2 to 1.8 grams per day, and the course of treatment is generally 4 weeks.
Doctors will adjust the dosage based on the specific condition of the patient to achieve individualized treatment.
The therapeutic effect is mainly evaluated through the decline of liver function indicators (such as ALT, AST, and bilirubin), improvement of symptoms (such as fatigue and reduction of abdominal distension), and changes in imaging (such as reduction of fatty liver).
Glutathione injection has good safety, and adverse reactions are rare and mild.
Oral preparations: Convenient but absorption remains a challenge
Although oral glutathione is more convenient, its bioavailability has always controversial because its easily degraded by enzymes in the intestine. However, the latest research shows that:
- Some glutathione can fully absorbed.
- Long-term use can significantly increase the levels of glutathione in the blood and tissues.
- Even if its decomposed, its products (such as cysteine) can used as raw materials to promote synthesis in the body.
Oral preparations still have potential in maintenance treatment and prevention, especially suitable for long-term use by patients with chronic liver diseases.
new role of glutathione in treatment of fatty liver
Non-alcoholic fatty liver disease (NAFLD) and its inflammatory stage Non-alcoholic steatohepatitis (NASH) have become the most common chronic liver disease worldwide, closely related to insulin resistance and oxidative stress.
Research shows:
- Oral administration of glutathione can significantly improve liver function indicators and oxidative stress markers in patients with NAFLD.
- The combination of glutathione with metformin, ursodeoxycholic acid (UDCA), polyene phosphatidylcholine and other drugs has a better effect than monotherapy.
Collaborative mechanism: AMPK/Nrf2 pathway dialogue
It is particularly worth noting that the combination of glutathione and metformin may exert a synergistic effect through the AMPK/Nrf2 pathway:
- Metformin activates AMPK and improves glycolipid metabolism.
- AMPK phosphorylation activates Nrf2, initiating the expression of antioxidant genes.
- Exogenous glutathione provides direct protection and works in synergy with the endogenous defense system.
Future outlook: More precise and efficient applications
Although glutathione has widely used in the treatment of liver diseases, it still faces some challenges:
- Low oral bioavailability: New formulations (such as liposomes, nanoparticles, prodrugs, etc.) need to developed;
- Insufficient high-level clinical evidence: particularly, there is a lack of large-scale Phase III clinical trials for NASH.
- Significant individual differences: Precise supplementation can achieved by testing blood GSH levels or genetic polymorphisms.
Future research should focus on:
- By using isotope labeling and mass spectrometry imaging technology, the distribution of glutathione in human tissues can visually tracked.
- Carry out more high-quality clinical trials to clarify its efficacy in different liver diseases;
- Explore the optimal combination and dosage in combination therapy.
