Glutathione (GSH) is the most abundant and important intracellular antioxidant. GSH in erythrocytes is an indicator of intracellular GSH status, the overall health of cells and of the ability to endure toxic challenges. Low levels of GSH have been reported in cardiovascular disease, cancer, AIDS, autism, alcoholism, and debilitating neurodegenerative diseases such as Alzheimer's and Parkinson's. It has also been associated with chronic retention of many potential toxic elements, chemicals and some drugs. Assessment and support of erythrocyte GSH can contribute to healthy aging and effective detoxification of toxic metals and chemicals.
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Glutathione (GSH) is a tripeptide (λ-glutamyl-cysteinylglycine) synthesized in most cells. The level of GSH in erythrocytes is a sensitive indicator of intracellular GSH status, the overall health of cells and of the ability to endure toxic challenges. GSH is the most abundant non-protein thiol in mammalian cells. It is involved in many biological processes including detoxification of xenobiotics, removal of oxygen-reactive species, regulation of the redox state of cells and the oxidative state of important protein sulfhydryl groups, and regulation of immune function.
GSH levels are thousands of times higher in cells than in plasma. Plasma GSH represents primarily that synthesized and exported from the liver. Reduced GSH (rGSH) is the active form of the tripeptide and the ratio of rGSH: oxidized GSH (GSSH) is normally about 9:1. Once a blood sample is obtained, erythrocyte rGSH is very susceptible to oxidation and the rGSH:GSSH ratio drops rapidly. Specimen handling to prevent the ex vivo oxidation of rGSH is impractical, and direct measurement of rGSH in vivo is not feasible outside of a research setting. However, research clearly indicates that undesirable ratios of rGSH:GSSH are equally associated with abnormally low levels of total cellular GSH. Therefore, it is clinically meaningful to assess the level of total erythrocyte GSH as an indicator of GSH status and metabolism.
Low levels of GSH have been reported in cardiovascular disease, cancer, AIDS, autism, alcoholism and debilitating neurodegenerative diseases such as Alzhiemer's and Parkinson's. It has also been associated with chronic retention of potential toxic elements such as mercury, lead, arsenic, cadmium, manganese and iron, as well as chemicals and some drugs. Intracellular GSH biosynthesis and intracellular levels can be upregulated as a protective mechanism.
Some factors that result in increased biosynthesis and "high normal" erythrocyte GSH levels include, but are not limited to, moderate alcohol consumption, smoking, regular physical exercise and acute exposure to toxic metals. Under such conditions it is essential to provide the body with the key nutrients involved in GSH synthesis in order to sustain functionally appropriate levels of GSH. Magnesium and potassium are required for both energy-dependent enzymatic steps in GSH synthesis, and cysteine is the rate limiting amino acid. Nutritional products that have been documented to increase erythrocyte GSH/GSH biosynthesis include high-quality whey protein preparations, α-lipoic acid, curcumin, oral liposomal GSH, nebulized GSH, and to a lesser extent, N-acetyl-L-cysteine.
Assessing and supporting appropriately high levels of erythrocyte GSH is important for protecting cells and promoting overall health and longevity, and contributes significantly to safe and effective metal detoxification.