Glutathione Introduction

Although listed under the classification of an amino acid, glutathione is actually a tripeptide compound. The human body produces glutathione from the synthesis of three key amino acids - cysteine, glycine, and glutamic acid. ‘Glutathione’ is, in fact, a term referring to the reduced and dimeric forms of the tripeptide L-gamma-glutamyl-L-cysteinylglycine. Biochemists often refer to this reduced form as glutathione, and the dimer form as glutathione disulfide.

Glutathione exists as a fundamental compound in all aerobic organisms. In human physiology, glutathione functions as an antioxidant, detoxifier, metabolic enhancer, and component in fatty-acid synthesis. It also acts as a redox buffer, reconstituting antioxidants Vitamin C and E post oxidation. Glutathione is found in varying concentrations in all tissues, with the highest amounts located in the liver, spleen, pancreas, kidneys, and lenses of the eye.

Supplemental glutathione is only available in one active form, GSH. Other oral formulas are often questioned and criticized due to their ineffectiveness and instability when administered. It is often suggested that the increase of glutathione levels within the body directly coincides with the increase of glutathione precursors (raw materials which make glutathione). The N-acetyl form of cysteine (NAC) may conceivably be the most effective amino at increasing overall glutathione levels. [1] This nonessential nutrient (i.e. NAC) may also be derived from the additional supplementation of L-cysteine, L-glutamic acid, and L-glycine.

Food sources with the highest amounts of naturally occurring glutathione include; asparagus, avocado, grapefruit, squash, potato, cantaloupe, peach, zucchini, spinach, broccoli, watermelon, and strawberries. Fish, meat, and foods which yield sulfur containing amino acids (e.g. eggs) are the preferred sources for maintaining and increasing bodily glutathione levels. [2] Due to inconsistencies in data, a food graph has been omitted from this section.

Glutathione is considered by many biochemists to be a key component in the body’s ability to combat free radical damage. Preliminary studies suggest that glutathione exists within that body as a potent antioxidant. [3] It may provide a means for the conversion of various pollutants, and other toxic compounds, into a more tolerable form for bodily excretion. Glutathione may also reduce the side effects of x-rays, chemotherapy, and alcohol poisoning. [4, 5] Furthermore, glutathione assists in the maintenance and integrity of bodily proteins, while being a major element in the transportation of nutrients across cell membranes. Consumption of antioxidants during the early stages in life may promote longevity and a reduced risk for the development of a chronic disease.

Individuals suffering from specific types of cancers may find a dual benefit in regards to glutathione supplementation. Glutathione has been used in various clinical applications as an anti-tumor agent, and (abovementioned) chemoprotectant. [6] Glutathione has also produced significant effects in the regression of liver cancers, and enhanced survival probability in animal studies. This finding is intriguing but merits further research before determining its anti-cancer potential in humans.

Glutathione has also been studied for possible enhancements in immune system response. It has been demonstrated to reverse the age-associated declination of the immune system, while enhancing T-cell response. This may prove to be beneficial for persons suffering from acute and chronic immune disorders.

AIDS-associated cachexia is a disorder in which the epithelial cells of the small and large bowel tissue (enterocytes) are damages by prolonged oxidative stress. Glutathione may assist AIDS patients suffering from this condition by repairing the damage to these cells. In conjunction with AZT, a common treatment for AIDS, glutathione has not only shown promise in the enhancement of immunological function, but equally so in the effectiveness of prescribed medications. [7]

Lung glutathione, the principal antioxidant in deep lung tissue, is often diminished in persons with HIV/AIDS. Clinical study is underway to determine the effectiveness of aerosolized forms of glutathione on the reversal of the oxidant-antioxidant imbalance in this unique area of the body. [8] This may also prove advantageous for acute respiratory illness and for those individuals suffering from pulmonary fibrosis.

Intravenous or intramuscular glutathione has been termed useful for the prevention of platelet aggregation during operations. [9] Supplemental glutathione may also improve other hemostatic factors in certain diseases, especially atherosclerosis. Individuals suffering from impairments of blood glucose tolerance may also derive benefit from supplemental glutathione. [10] This amino acid has been shown to enhance insulin secretion, and may prove beneficial for persons with diabetes.

Glutamine may also prove significant in areas of male fertility, the deactivation of certain viral agents, and reduction of symptoms associated with rhinitis. [11-13] More research into these applications must be done to assess the benefit and tolerance of supplemental glutathione.

A Recommended Dietary Allowance (RDA) has not been established for glutathione; though it is recommended that individuals consume adequate amounts of S-containing amino acids to maintain adequate glutathione levels within the body. [14] Less than 100 milligrams of glutathione is consumed per day in the average adult diet. This may be caused by glutathione’s minimal oral absorption rate.

[15]

The U.S. National Academy of Sciences recommends that healthy people achieve .36 grams of highly bioavailable protein for each pound of bodyweight - equaling 0.8 grams of protein, per kilogram of bodyweight.

Glutathione Deficiencies

Deficiencies of glutathione are marked by increases in tissue oxidative stressors. Oxidative stress is a term used to denote the damage of free radical molecules upon the cellular structures located throughout the body. This is of great importance because oxidative stress is prevalent in many pathological conditions.

Chronic deficiencies of glutathione are linked to certain immune disorders, development of cataracts, and an increased incidence of certain types of malignancies. [16] HIV patients also exhibit signs of a chronic glutathione deficiency, thereby accelerating the pathogenesis of the disease.

Acute deficiencies are usually marked by an intolerable amount of consumed toxins, such as overdose of acetaminophen. This is often paralleled with a reduction of glutathione in hepatocytes (chief functional cells located in the liver), and may lead to liver failure and even death. Liver damage has also been observed in patients with anorexia nervosa, and is suggested that this damage is also the result of acute nutrient deficiencies. [17]

Glutathione Toxicities

Due to the relative scarcity of glutathione in human nutrition, information regarding toxicities of this compound has not been reported. The oral supplementation of glutathione is often speculated as being ineffective in the treatment of certain conditions. This may be due to its minimal absorption rate in the small intestine. The majority of additional glutathione achieved from either diet, or supplementation, is readily used by the body for various physiological processes.

1. Balch, Phyllis A., James F. “Amino Acids.” Prescription for Nutritional Healing. Ed. Amy C Tecklenberg. New York, NY: Penguin Putnam, Inc., 3rd Ed. 2000. 42-53.

2. Jones DP, Coates RJ, Flagg EW, et al. Glutathione in foods listed in the National Cancer Institutes Health Habits and History Food Frequency Questionnaire. Nutr Cancer 1995;17:57-75.

3. Meister A. On the antioxidant effects of ascorbic acid and glutathione. Biochem Pharmacol. 1992;44:1905-1915,

4. Gebbia V, et al. Weekly 5-fluorouracil and Folinic Acid plus Escalating Doses of Cisplatin with Glutathione Protection in Patients with Advanced Head and Neck Cancer. Med Oncol Tumor Pharmacother. 1992;9(4):165-68.

5. Sumiyoshi Y, et al. Glutathione Chemoprotection Therapy against CDDP-induced Neurotoxicity in Patients with Invasive Bladder Cancer. Gan To Kagaku Ryoho. Sep1996;23(11):1506-08.

6. Hercbergs A, Brok-Simoni F, Holtzman F, et al. Erythrocyte glutathione and tumor response to chemotherapy. Lancet. 1992;339:1074-1076.

7. Magnani M, et al. Antiretroviral Effect of Combined Zidovudine and Reduced Glutathione Therapy in Murine AIDS. AIDS Res Hum Retroviruses. Sep1997;13(13):1093-99.

8. Holroyd KJ, Buhl R, Borok Z, et al. Correction of glutathione deficiency in the lower respiratory tract of HIV seropositive individuals by glutathione aerosol treatment. Thorax. 1993;48:985-989.

9. Molly J, Martin JF, Baskerville PA, et al. S-nitrosoglutathione reduces the rate of embolization in humans. Circulation 1998;98:1372-5.

10. Paolisso G, Giugliano D, Pizza G, et al. Glutathione infusion potentiates glucose-induced insulin secretion in aged patients with impaired glucose tolerance. Diabetes Care. 1992;87:438-443.

11. Lenzi A, Culasso F, Gandini L, et al. Placebo-controlled, double-blind, cross-over trial of glutathione therapy in male infertility. Hum Reprod. 1993;8:1657-1662.

12. Palamara AT, Perno C-F, Ciriolo MR, et al. Evidence for antiviral activity of glutathione: in vitro inhibition of herpes simplex virus type I replication. Antiviral Res. 1995;27:237-253.

13. Testa B, Mesolella M, Testa D. Glutathione in the upper respiratory tract. Ann Otol Rhinol Laryngol 1995;104:117-9.

14. Lyons J, Tauh-Pfeiffer A, Yu YM, et al. Blood glutathione synthesis rates in healthy adults receiving a sulfur amino acid-free diet. Proc Natl Acad Sci USA. 2000;97:5071-5076.

15. Zest for life information page. “RDA of amino acids.” (1999-2003) http://www.anyvitamins.com/amino-acids/rda-amino-acids.htm (14 Sept. 2004).

16. Fecondo JV, et al. Superoxide Dismutase, Catalase and Glutathione Peroxidase in the Human Cataractous Lens. Exp Eye Res. Jan1983;36(1):15-23.

17. Zenger F, Russmann S, Junker E, Wuthrich C, Bui MH, Lauterburg BH. Decreased glutathione in patients with anorexia nervosa. Risk factor for toxic liver injury? Eur J Clin Nutr. Feb2004;58(2):238