Glutathione

Glutathione exists in two forms: the antioxidant "reduced glutathione" tripeptide is conventionally called glutathione and abbreviated GSH, the oxidized form is a sulfur-sulfur linked compound, known as glutathione disulfide or GSSG. Glutathione is present inside cells mainly in its reduced (electron-rich, antioxidant) GSH form. Riboflavin, niacinamide, selenium, lipoic acid and glutathione reductase are all essential cofactors for generating reduced glutathione. Glutathione synthesis occurs within cells in two closely linked, enzymatically controlled reactions that utilize ATP and draw on nonessential amino acids as substrates. GSH synthesis is dependant on the availability of substrates (the most critical substrate is cysteine). The activity of the enzyme gamma-glutamylcysteine synthase is controlled by a non-allosteric negative feedback mechanism, inhibited by intracellular GSH. Vitamins B6 and riboflavin are critical for maintaining adequate levels of glutathione within the body.

Glutathione also plays roles in catalysis, metabolism, signal transduction, gene expression and apoptosis. Glutathione is the principal intracellular non protein thiol and plays a major role in the maintenance of the intracellular redox state. It may be thought of as an intracellular redox buffer. Glutathione protects tissues by neutralizing free radicals, and improves the immune system by promoting antigen presentation and stimulating CD8 cells. Glutathione is involved in various liver detoxification processes. Glutathione serves as a reductant, is conjugated to drugs to make them more water soluble, is involved in amino acid transport across cell membranes (the g-glutamyl cycle), is a part of the peptidoleukotrienes, serves as a cofactor for some enzymatic reactions and as an aid in the rearrangement of protein disulfide bonds.

Glutathione functions, uses, and health benefits

The primary biological function of glutathione is to act as a non-enzymatic reducing agent to help keep cysteine thiol side chains in a reduced state on the surface of proteins. The role of glutathione as a reductant is extremely important particularly in the highly oxidizing environment of the erythrocyte. The sulfhydryl of GSH can be used to reduce peroxides formed during oxygen transport. Glutathione’s reducing power is used in conjunction with ascorbate and other antioxidants to protect the entire spectrum of biomolecules, to help regulate their function, and to facilitate the survival and optimal performance of the cell as a living unit.

Glutathione acts as an antioxidant used to prevent oxidative stress in most cells and help to trap free radicals that can damage DNA and RNA. There is a direct correlation with the speed of aging and the reduction of glutathione concentrations in intracellular fluids. Antioxidants are the body's premier resource for protection against the diverse free radical and other oxidative stressors to which it invariably becomes exposed. Glutathione neutralizes damaging free radicals and peroxide molecules, and recharges oxidized vitamin C so that the body may reuse it. Glutathione is required for a variety of metabolic processes. As individuals grow older, glutathione levels drop, and the ability to detoxify free radicals decreases. High levels of glutathione in the blood are associated with longevity, due to the antioxidant performance of glutathione.

Glutathione is a systemic antitoxin. Glutathione is important as a hydrophilic molecule that is added to lipophilic toxins and waste in the liver during biotransformation before they can become part of the bile. Glutathione is needed for the detoxification of methylglyoxal, a toxin produced as a by-product of metabolism. GSH may be especially important for those organs most directly exposed to exogenous toxins, such as the lungs, the intestines, the kidneys, and particularly the liver. Glutathione helps the liver to detoxify chemicals including acetaminophen, copper, and cadmium. Glutathione may significantly enhance quality of life and prevent liver and kidney damage in patients who are receiving chemotherapy. Glutathione plays a crucial role in the elimination of heavy metal toxins. Glutathione helps to counteract the toxic effects of excessive consumption of alcohol and many of the toxic effects of tobacco smoking. Glutathione may be helpful in the treatment of liver disease, along with many toxic and infectious conditions.

Dietary sources of glutathione

Glutathione is widely found in all forms of life. Dietary glutathione is found in fresh and frozen fruits and vegetables, fish, and meat. Plant sources containing glutathione includs avocado, watermelon, asparagus, grapefruit, potato, acorn squash, strawberries, orange, tomato, cantaloupe, broccoli, okra, peach, zucchini, and spinach. Asparagus, avocado, and walnuts are particularly rich dietary sources of glutathione. Cysteine is found in most high-protein foods including ricotta, cottage cheese, yogurt, pork, sausage meat, chicken, turkey, duck, luncheon meat, wheat germ, granola, and oat flakes. Glutamine is found in many foods high in protein, such as fish, meat, beans, and dairy products. Glycine is found in many foods high in protein, such as meat, fish, dairy products, and legumes.

Glutathione dosage, intake

Recommended Dietary Allowance (RDA) has not been established for glutathione. Dosage ranges from 50 to 600 milligrams daily. The amount depends on the purpose of using this supplement. People who have a proven glutathione deficiency may require administration of glutathione. The exact dose should be prescribed by a healthcare professional.

Glutathione deficiency

Glutathione deficiency can be the result of diseases that increase the need for glutathione, deficiencies of the amino acids needed for synthesis, or diseases that inhibit glutathione formation. Glutathione deficiency is an important contributory factor to liver injury, and to enhanced morbidity related to liver hypofunction. GSH deficiencies are related to a number of pulmonary diseases, including acute respiratory distress syndrome (ARDS), asthma, chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, and neonatal lung damage. People with inherited glutathione deficiency often develop neurologic complications early in life. Glutathione levels decline as people age, glutathione levels are extremely low in AIDS and HIV positive patients. Cigarette smoking is also associated with low glutathione levels because it increases the rate of utilization of glutathione.

Toxicity, side effects, interactions, and contraindications

No side effects or interactions are known with oral administration of glutathione. There are no known signs of toxicity from glutathione. GSH and other thiols may be sensitive to redox-active minerals, and care should be taken to omit these from therapeutic preparations.