What is Glutathione? High and low values | Lab results explained

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

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

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-acteylcysteine) can increase GSH levels. Recent literature has also suggested that adequate glycine levels are critical in maintaining glutathione levels, and glycine availability may modulate the production of glutathione. [L]

Glutathione’s antioxidant function is accomplished largely by GSH peroxidase-catalyzed reactions. 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 counter free radicals. [L]

Glutathione is also involved in phase II detoxification by conjugating hormones, toxins, and xenobiotics to make them water soluble for excretion. [L]

There is a transient increase in GSH plasma levels after intravenous supplementation and oral GSH ingestion, which may be useful under oxidative stress to counter free radical damage. [L]

There are many foods which contain significant GSH sources including, but not limited to, asparagus, avocado, watermelon, ham, and pork. [L]

GSH inclusion in oral over-the-counter supplements may be of limited value, since 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 to raise GSH levels. [L], [L]

Additionally, increasing amino acid dietary intake and supplementation with sulfur-containing products (N-acetyl cysteine) and foods (cruciferous vegetables, such as asparagus, broccoli, cauliflower, Brussels sprouts) will support GSH synthesis. [L]

The latter requires a healthy gastrointestinal ecosystem.

References:

Townsend DM, Tew KD, Tapiero H. The importance of glutathione in human disease. Biomed Pharmacother. 2003;57(3-4):145-155. [L]

Lu SC. GLUTATHIONE SYNTHESIS. Biochim Biophys Acta. 2013;1830(5):3143-3153. [L]

Wu G, Fang Y-Z, Yang S, Lupton JR, Turner ND. Glutathione Metabolism and Its Implications for Health. J Nutr. 2004;134(3):489-492. [L]

Hagen TM, Wierzbicka GT, Sillau A, Bowman BB, Jones DP. Bioavailability of dietary glutathione: effect on plasma concentration. Am J Physiol-Gastroint Liver Physiol. 1990;259(4):G524-G529. [L]

Jones DP, Coates RJ, Flagg EW, et al. Glutathione in foods listed in the National Cancer Institute’s health habits and history food frequency questionnaire. 1992. [L]

Sinha R, Sinha I, Calcagnotto A, et al. Oral supplementation with liposomal glutathione elevates body stores of glutathione and markers of immune function. Eur J Clin Nutr. 2018;72(1):105-111. [L]

Richie JP, Jr., Nichenametla S, Neidig W, et al. Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Eur J Nutr. 2015;54(2):251-263. [L]

McCarty MF, O’Keefe JH, DiNicolantonio JJ. Dietary Glycine Is Rate-Limiting for Glutathione Synthesis and May Have Broad Potential for Health Protection. Ochsner J. 2018;18(1):81-87. [L] 101

Stabler S, et al. Elevation of serum cystathionine levels in patients with cobalamin and folate deficiency. Blood. 1993;81(12):3404-3413 [L]

DeStefano Vea. Linkage disequilibrium at the cystathionine beta-synthase (CBS) locus and the association between genetic variation at the CBS locus and plasma levels of homocysteine. Ann Human Genet. 1998;62(6):481-490. [L]

WHAT DOES IT MEAN IF YOUR GLUTATHIONE RESULT IS TOO LOW?

– Decreased Hcy

– Decreased GSH precursors (cysteine, glycine, glutamine) [L]

– Increased phase two conjugation in detox pathway [L]

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

WHAT DOES IT MEAN IF YOUR GLUTATHIONE RESULT IS TOO HIGH?

– Dietary intake of amino acid precursors (cysteine, glycine, glutamine)

– Supplementation

– CBS SNP in the presence of oxidative stress or inflammation [L]

– Inability to convert oxidized to reduced GSH (making excess due to inability to reduce it for use) [L]

Disclaimer:

Test results may vary depending on your age, gender, health history, the method used for the test, and other things. Your test results may not mean you have a problem. Ask your healthcare provider what your test results mean for you. 

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