Glutathione, a tripeptide composed of glutamic acid, cysteine, and glycine, is a potent natural antioxidant vital for protecting our cells from oxidative stress. Whether used in dietary supplements, cosmetics, or advanced medical treatments, glutathione is redefining health and wellness, one molecule at a time. Discover how this tiny but mighty compound is transforming lives!、
Structure and Physiological Functions of Glutathione
1.1 Structure of Glutathione
Glutathione (GSH), chemically known as γ-L-glutamyl-L-cysteinylglycine, is a tripeptide composed of L-glutamic acid, L-cysteine, and glycine. It is a biologically active non-protein thiol compound widely present in living organisms. In both animal and plant cells, glutathione mainly exists in two forms: reduced glutathione (GSH) and oxidized glutathione (GSSG). About 90% of glutathione exists in the active GSH form, while GSSG can be reduced back to GSH by glutathione reductase (GR), consuming NADPH. Apart from GSSG, GSH can also form other mixed disulfide thiol compounds, such as GS-S-CoA and GS-S-Cys.
Figure: Molecular structure of glutathione (GSH)
The chemical structure of glutathione determines its structural stability. The glycine residue protects glutathione from γ-glutamyl cyclotransferase (γ-GCT), and the γ-peptide bond between glutamic acid and cysteine prevents hydrolysis by many peptidases.
Figure: Schematic diagram of glutathione redox cycle
Note: Reduced glutathione GSH is oxidized to glutathione disulfide (GSSG), which is reduced to GSH by glutathione reductase in the presence of NADPH. Glutathione peroxidase converts hydrogen peroxide (H2O2) into water (H2O).
1.2 Metabolism of Glutathione in the Body
The metabolism of glutathione in animals and plants is carried out through the γ-glutamyl cycle.
Figure: Overview of gamma-glutamyl cycle in animals and plants
Applications of Glutathione
The main features of the glutathione molecular structure are its free thiol group and strong ability to donate electrons or protons, which allow it to act as an antioxidant in aqueous solutions and as a cofactor for antioxidant enzymes. It protects DNA, proteins, and other biomolecules from oxidative damage. The structural characteristics of glutathione play an essential role in its physiological functions in the body, and it is widely applied in the pharmaceutical, food, and cosmetics industries.
Figure: Four major application areas of glutathione and its functions
2.1 Applications of Glutathione in Food
Glutathione is widely used in various food processing fields. It is primarily used to inhibit browning, extend shelf life, and enhance food flavor.
- Application in Meat and Seafood: Adding an appropriate amount of glutathione to meat and seafood can effectively inhibit nucleic acid degradation, enhance flavor, and extend the shelf life of the food.
- Application in Alcoholic Beverages: Glutathione protects the aroma components of alcohol, helping extend the storage life of beverages like kiwi wine. In wine production and aging, glutathione plays an important role, such as reducing browning due to its antioxidant properties and optimizing flavor.
- Application in Seasonings: When glutathione is mixed with monosodium glutamate (L-glutamic acid), cysteine, and xylose and heated, it produces a unique beef flavor. It also enhances the flavor of meat when combined with taste nucleotides like inosinate, guanylate, and monosodium glutamate, making it an effective flavor enhancer in food processing.
- Application in Fruits and Vegetables: When added to fruit and vegetable processing, glutathione can effectively prevent browning, preserving the original appealing color, flavor, and nutritional value.
- Application in Pasta Products: During pasta production, adding appropriate glutathione can improve the rheological properties of the dough, control its strength and viscosity, and shorten kneading and drying times. In noodle production, glutathione also acts as an inhibitor of cysteine hydrolase, preventing undesirable color changes.
- Application in Dairy Products and Fermented Foods: Adding glutathione to dairy products can enhance their pleasant flavor and improve quality. In yogurt production, it helps stabilize product quality.
2.2 Applications of Glutathione in Skin Whitening
The color of skin depends on the proportion of two types of melanin: eumelanin (brown-black) and pheomelanin (yellow-red). Glutathione acts as a skin whitener by inhibiting tyrosinase, an enzyme that aids in the formation of melanin. It also converts eumelanin into pheomelanin, leading to lighter skin. Glutathione has thus become a popular skin-whitening agent and is even used by dermatologists to treat melasma and other facial hyperpigmentation disorders.
Glutathione for whitening purposes can be applied in various forms, including topical formulations, oral intake, and injections. After prolonged use, topical treatments show significant improvements in skin tone. Oral formulations are available in tablet and solution forms. The FDA considers sublingual administration safe because it is easier to administer with lower doses, typically 20-40 mg/kg (1g to 2g, administered twice), showing notable effects within just three months. Glutathione can be used alone or combined with other ingredients like ascorbic acid, vitamin E, tranexamic acid, and others.
Figure: Synthesis mechanism of pheomelanin in skin
2.3 Applications of Glutathione in Medicine
Given glutathione's multiple roles in cellular physiology, clinical research focused on modifying glutathione homeostasis has gained attention. A growing list of conditions associated with disrupted glutathione homeostasis reflects its importance and diversity in cell functions. Notable examples include neurodegenerative diseases (particularly Parkinson’s and Alzheimer’s), lung diseases (chronic obstructive pulmonary disease, asthma, acute respiratory distress syndrome), cystic fibrosis, immune disorders (HIV, autoimmune diseases), cardiovascular diseases (hypertension, myocardial infarction, cholesterol oxidation), age-related oxidative diseases (such as cataracts, macular degeneration, hearing loss, and glaucoma), and the aging process itself.
Although sufficient glutathione is a critical defense against various carcinogens, several cancer types have been shown to exhibit elevated GSH levels, making them more resistant to apoptosis and chemotherapy/radiotherapy. Therefore, while therapies aimed at enhancing glutathione synthesis (such as N-acetylcysteine) can prevent chemotherapy-related toxicity, limiting its intake may be required when treating specific cancer cell lines.
Figure: The key role of glutathione in healthy and tumor cells
In the liver, glutathione (GSH) plays a particularly important role as an antioxidant. In the treatment of viral liver diseases, reduced glutathione can enhance the liver’s detoxifying function through methylation and transamination reactions, promoting bile metabolism and protecting liver cells. In the treatment of drug-induced liver disease, glutathione effectively mitigates drug side effects, providing liver protection. In alcoholic liver disease, glutathione accelerates the excretion of free radicals, reduces liver cell damage, restores liver detoxification functions, and promotes recovery of liver function. Oxidative stress is a hallmark of metabolic liver diseases, and like other types of liver diseases, GSH is also used in the treatment of non-alcoholic fatty liver disease (NAFLD).
2.4 Dietary Supplements and Anti-Aging
According to the U.S. Food and Drug Administration (US-FDA) Federal Food, Drug, and Cosmetic Act Section 201(s), oral dietary supplements based on glutathione are generally not restricted in the United States. Given the role of free radicals in the development of age-related diseases, GSH is considered an effective anti-aging agent due to its prominent antioxidant properties. Maintaining optimal GSH levels in various tissues is regarded as an essential strategy for preventing oxidative stress-related diseases. GSH produces metabolites that enter the Krebs cycle to generate energy, and it is also a key component of the glutathione-ascorbic acid cycle. GSH supplements and their alternatives can be obtained through various routes, including transdermal, intramuscular, sublingual, oral, or inhalation.