Glutathione (GSH)

    Glutathione (GSH) is a tripeptide composed of three amino acids (cysteine, glycine, and glutamic acid). Glutathione is the most potent intracellular antioxidant in the body. It exists intracellularly in either an oxidized or reduced state.

    GSH acts as an antioxidant and detoxifying agent. Excessive formation of reactive oxygen species (ROS), including hydrogen peroxide (H2O2), is toxic to the cell. Therefore, the metabolism of these free radicals is critical, and they are tightly controlled.

    The availability of the amino acid cysteine ​​is known to be rate-limiting for glutathione synthesis, and it is widely known that cysteine ​​supplementation (in the form of N-acetylcysteine) can increase GSH levels. Alpha-lipoic acid maintains GSH levels by reducing cystine to cysteine, as well as by inducing de novo GSH synthesis.

    Recent literature has also suggested that adequate glycine levels are critical to maintaining glutathione levels, and glycine availability may modulate glutathione production.

    Glutathione’s antioxidant function is largely accomplished by reactions catalyzed by GSH peroxidase. GSH neutralizes hydrogen peroxide and lipid peroxide, resulting in water and alcohol. By accepting a free radical electron, GSH is then oxidized. GSH continues to donate and accept electrons, forming a redox cycle to combat free radicals.

    Glutathione is also involved in phase II detoxification by conjugating hormones, toxins, and xenobiotics to make them water-soluble for excretion. There are many foods that contain significant sources of GSH including, but not limited to, asparagus, avocado, watermelon, ham, and pork.

    There is a transient increase in plasma GSH levels following intravenous supplementation and oral ingestion of GSH, which may be useful under oxidative stress to combat free radical damage.

    Nutritional deficiencies in GSH precursors (cysteine, glycine, glutamine) may result in low GSH. Genetic polymorphisms (SNPs) may also affect GSH production. Without adequate levels of GSH, oxidative stress and free radicals contribute to aging and disease. GSH deficiency and problems with GSH synthesis have been implicated in many diseases, including cancer, neuropsychiatric dysfunction, Parkinson’s disease, HIV, liver disease, and cystic fibrosis.

    The inclusion of GSH in over-the-counter oral supplements may be of limited value, as the reduced state will not be maintained when exposed to normal atmospheric conditions and room temperature. Liposomal GSH has been shown to be an excellent alternative for increasing GSH levels. Additionally, increasing dietary amino acid intake and supplementing with sulfur-containing products (N-acetylcysteine) and foods (cruciferous vegetables such as asparagus, broccoli, cauliflower, Brussels sprouts) will support GSH synthesis. The latter requires a healthy gastrointestinal ecosystem.

LOW GLUTATHIONE (GSH)

•Decreased Hcy

• Decreased GSH precursors (cysteine, glycine, glutamine)

• Increased phase two conjugation in detox pathway

HIGH GLUTATHIONE (GSH)

• Dietary intake of amino cid precursors (cysteine, glycine, glutamine)

• Supplementation

• CBS SNP in the presence of oxidative stress or inflammation

• Inability to convert oxidized to reduced GSH (making excess due to inability to reduce it for use)