Glutathione

Overview

Glutathione is a sulfur-containing tripeptide that is composed of cysteine, glycine, and glutamic acid. Glutathione is a part of two antioxidant enzymes and it also plays an important role in the removal of toxins from the body. Occasionally glutathione is referred to by the abbreviation GSH. The “SH” refers to a sulfhydryl group attached to the cysteinyl portion of the molecule. (1) The Glutathione must be in its reduced, or GSH form to be active. Some manufacturers list glutathione on their labels without indicating whether it is reduced or not. The unreduced form is cheaper, but it is not metabolically active.

Dosage Info

Dosage Range

50-500mg daily.

Most Common Dosage

250mg daily.

Dosage Forms

Capsules and powder.

Adult RDI

None established

Adult ODA

None established

RDA

Active Forms

L-glutathione, N-(N-L-gamma-Glutamyl-L-cysteinyl)glycine.

Absorption

Several rodent studies have noted that orally ingested glutathione is absorbed unchanged from the gastrointestinal tract, replenishing tissue and plasma levels in depletion scenarios. (2) , (3) With doses as high as 3 grams, human studies have not been able to replicate these findings, noting no significant increase in plasma levels. (4)

Toxicities & Precautions

General

There is no known toxicity associated with glutathione.

Functions in the Body

Antioxidant:

Reduced glutathione can act as an antioxidant, and glutathione is also a part of the antioxidant enzyme glutathione peroxidase. This enzyme neutralizes hydrogen peroxide and organic peroxides in the body, which reduces free radical damage.

Detoxification:

Glutathione is also a part of the enzyme glutathione S-transferase, which helps detoxify many foreign compounds in the liver by chemically transforming them into less harmful substances that can be eliminated through the colon in bile from the liver. Agents detoxified include industrial, agricultural, and environmental pollutants, and insecticides, pesticides, fungicides, herbicides, nitrates, nitrosamines, flavorings, formaldehyde, dyes, detergents, solvents, many of the toxins from cigarette smoke and automobile exhaust, heavy metals such as lead, mercury, cadmium and arsenic, and OTC and prescription drugs.

Glutathione Metabolism:

Facilitates the transport of some amino acids across cellular membranes. One example is L-alanine, which plays a role in the production of lymphocytes, which are a part of the immune system.

Immune Function:

The activity of macrophages, phagocytes, and lymphocytes all depend upon glutathione levels.

Red Blood Cells:

Glutathione plays a role in protecting and maintaining the integrity of red blood cell membranes.

Clinical Applications

Parkinson’s Disease

Autopsy reports indicate that glutathione is virtually absent in the substantia nigra of Parkinson’s disease patients. This finding may hold important implications for the management and prevention of Parkinson’s disease in the future. (5)

Respiratory Tract Infections

10 of 11 children treated with an aerosol providing 600mg of glutathione daily experienced almost complete disappearance of nasal discharge, and significant reduction in ear symptoms and nasal blockage, with no side effects. (6)

Cataracts

In humans and animal models, there is up to a 70 percent reduction of glutathione peroxidase in the lens of the eyes at the onset of nuclear cataracts. (7) Supplements that may be helpful include cysteine, selenium, riboflavin and glutathione.

Circulation

A small placebo controlled trial evaluated the effect of glutathione on the renal function of patients who underwent coronary artery bypass surgery. The treatment group of 10 people received a dose of glutathione before surgery, and then again on the first and second day post-operatively. Patients in the glutathione group had lower mean arterial pressure and systemic vascular resistance and well preserved urine volume, creatine clearance, and renal excretory index. (8)

In a double-blind, placebo controlled, cross-over design, another small study involving 10 atherosclerotic patients noted that intravenous GSH infusion significantly decreased blood viscosity, increased blood filtration, and lengthened partial thromboplastin time. (9)

Liver Disorders

Individuals with both alcoholic and non-alcoholic liver disease have demonstrated reduced hepatic glutathione levels. (10) Lower plasma concentrations of glutathione were found in patients with anorexia nervosa suggesting there might be an increased risk of developing toxic liver injury. (11) Patients with chronic hepatitis C have decreased GSH levels. Significant reductions have been noted in the liver, plasma, lymphocytes, and erythrocytes. Patients with chronic hepatitis C and are HIV positive have systemic depletion and GSH. (12) , (13)

Pulmonary Disease

Below normal concentrations of glutathione in the epithelial lining fluid (ELF) of the lungs has been confirmed in numerous pulmonary diseases. These include idiopathic pulmonary fibrosis, cystic fibrosis, and individuals who are HIV positive and susceptible to numerous opportunistic lung infections. (14) , (15) , (16) Studies evaluating the administration of aerosolized glutathione in both idiopathic pulmonary fibrosis and cystic fibrosis have demonstrated transient repletion of glutathione and oxidized glutathione levels in the ELF of these patients. (17) , (18)

Aids

HIV-infected patients have substantially less glutathione related antioxidant activity, which denotes a weakened immune system. (19) In another study, combining high-dose intramuscular glutathione with zidovudine resulted in improvements that were far greater than the results gained from AZT alone. (20)

Alcoholism

Alcoholics have substantially reduced levels of liver glutathione. (21) Administration of glutathione to alcoholics during recovery produces significant improvements in liver function. (22)

Cancer

Glutathione improves quality of life and successfully protects against liver and kidney damage when administered prior to high dose chemotherapy. (23) , (24) , (25)

Symptoms and Causes of Deficiency

No specific condition has been identified as a result of a glutathione deficiency. However, several disease states and health conditions have been noted to be associated with a glutathione deficiency. They include: AIDS, Parkinson’s Disease, cataracts, alcoholism, diabetes, liver disorders, lung disorders, gastrointestinal conditions. (26) , (27) , (28) , (29) , (30) , (31) , (32)

Dietary Sources

Foods containing glutathione include avocado, watermelon, asparagus, grapefruit, potato, acorn squash, strawberries, orange, tomato, cantaloupe, broccoli, okra, peach, zucchini, and spinach.

References

  1. Glutathione, reduced (GSH), Monograph. Altern Med Rev. Dec2001;6(6):601-7.
  2. View Abstract: Hagen TM, Wierzbicka GT, Sillau AH, Bowman BB, Jones DP. Bioavailability of dietary glutathione: effect on plasma concentration. Am J Physiol. Oct1990;259(4 Pt 1):G524-9.
  3. View Abstract: Aw TY, Wierzbicka G, Jones DP. Oral glutathione increases tissue glutathione in vivo. Chem Biol Interact. 1991;80(1):89-97.
  4. View Abstract: Witschi A, Reddy S, Stofer B, Lauterburg BH. The systemic availability of oral glutathione. Eur J Clin Pharmacol. 1992;43(6):667-9.
  5. View Abstract: Perry TL, et al. Parkinson’s Disease: A Disorder Due to Nigral Glutathione Deficiency? Neurosci Lett. Dec1982;33(3):305-10.
  6. View Abstract: Testa B, et al. Glutathione in the Upper Respiratory Tract. Ann Otol Rhinol Laryngol. Feb1995;104(2):117-19.
  7. View Abstract: Fecondo JV, et al. Superoxide Dismutase, Catalase and Glutathione Peroxidase in the Human Cataractous Lens. Exp Eye Res. Jan1983;36(1):15-23.
  8. View Abstract: Amano J, Suzuki A, Sunamori M. Salutary effect of reduced glutathione on renal function in coronary artery bypass operation. J Am Coll Surg. Dec1994;179(6):714-20.
  9. View Abstract: Coppola L, Grassia A, Giunta R, Verrazzo G, Cava B, Tirelli A, et al. Glutathione (GSH) improved haemostatic and haemorheological parameters in atherosclerotic subjects. Drugs Exp Clin Res. 1992;18(11-12):493-8.
  10. View Abstract: Altomare E, Vendemiale G, Albano O. Hepatic glutathione content in patients with alcoholic and non alcoholic liver diseases. Life Sci. 1988;43(12):991-8.
  11. View Abstract: 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):238-43.
  12. View Abstract: Barbaro G, Di Lorenzo G, Soldini M, Bellomo G, Belloni G, Grisorio B, et al. Vagal system impairment in human immunodeficiency virus-positive patients with chronic hepatitis C: does hepatic glutathione deficiency have a pathogenetic role? Scand J Gastroenterol. Dec1997;32(12):1261-6.
  13. View Abstract: Barbaro G, Di Lorenzo G, Soldini M, Parrotto S, Bellomo G, Belloni G, et al. Hepatic glutathione deficiency in chronic hepatitis C: quantitative evaluation in patients who are HIV positive and HIV negative and correlations with plasmatic and lymphocytic concentrations and with the activity of the liver disease. Am J Gastroenterol. Dec1996;91(12):2569-73.
  14. View Abstract: Borok Z, Buhl R, Grimes GJ, Bokser AD, Hubbard RC, Holroyd KJ, et al. Effect of glutathione aerosol on oxidant-antioxidant imbalance in idiopathic pulmonary fibrosis. Lancet. Jul1991;338(8761):215-6.
  15. View Abstract: Roum JH, Borok Z, McElvaney NG, Grimes GJ, Bokser AD, Buhl R, et al. Glutathione aerosol suppresses lung epithelial surface inflammatory cell-derived oxidants in cystic fibrosis. J Appl Physiol. Jul1999;87(1):438-43.
  16. View Abstract: Holroyd KJ, Buhl R, Borok Z, Roum JH, Bokser AD, Grimes GJ, et al. Correction of glutathione deficiency in the lower respiratory tract of HIV seropositive individuals by glutathione aerosol treatment. Thorax. Oct1993;48(10):985-9.
  17. View Abstract: Borok Z, Buhl R, Grimes GJ, Bokser AD, Hubbard RC, Holroyd KJ, et al. Effect of glutathione aerosol on oxidant-antioxidant imbalance in idiopathic pulmonary fibrosis. Lancet. Jul1991;338(8761):215-6.
  18. View Abstract: Roum JH, Borok Z, McElvaney NG, Grimes GJ, Bokser AD, Buhl R, et al. Glutathione aerosol suppresses lung epithelial surface inflammatory cell-derived oxidants in cystic fibrosis. J Appl Physiol. Jul1999;87(1):438-43.
  19. View Abstract: Look MP, Rockstroh JK, Rao GS, Kreuzer KA, Barton S, Lemoch H, et al. Serum Selenium, Plasma Glutathione (GSH) and Erythrocyte Glutathione Peroxidase (GSH-Px)-levels in Asymptomatic versus Symptomatic Human Immunodeficiency Virus-1 (HIV-1)-Infection. Eur J Clin Nutr. Apr1997;51(4):266-72.
  20. View Abstract: 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.
  21. View Abstract: Jewell SA, et al. Decreased Hepatic Glutathione in Chronic Alcoholic Patients. J Hepatol. 1986;3(1):1-6.
  22. View Abstract: Nardi EA, et al. High-dose Reduced Glutathione in the Therapy of Alcoholic Hepatopathy. Clin Ter. Jan1991;136(1):47-51.
  23. View Abstract: 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.
  24. View Abstract: Smyth JF, et al. Glutathione Reduces the Toxicity and Improves Quality of Life of Women Diagnosed with Ovarian Cancer Treated with Cisplatin: Results of a Double-blind, Randomised Trial. Ann Oncol. Jun1997;8(6):569-73.
  25. View Abstract: 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.
  26. View Abstract: Look MP, Rockstroh JK, Rao GS, Kreuzer KA, Barton S, Lemoch H, et al. Serum Selenium, Plasma Glutathione (GSH) and Erythrocyte Glutathione Peroxidase (GSH-Px)-levels in Asymptomatic versus Symptomatic Human Immunodeficiency Virus-1 (HIV-1)-Infection. Eur J Clin Nutr. Apr1997;51(4):266-72.
  27. View Abstract: Jewell SA, et al. Decreased Hepatic Glutathione in Chronic Alcoholic Patients. J Hepatol. 1986;3(1):1-6.
  28. View Abstract: Fecondo JV, et al. Superoxide Dismutase, Catalase and Glutathione Peroxidase in the Human Cataractous Lens. Exp Eye Res. Jan1983;36(1):15-23.
  29. View Abstract: Perry TL, et al. Parkinson’s Disease: A Disorder Due to Nigral Glutathione Deficiency? Neurosci Lett. Dec1982;33(3):305-10.
  30. View Abstract: Loguercio C, Taranto D, Vitale LM, Beneduce F, Del Vecchio Blanco C. Effect of liver cirrhosis and age on the glutathione concentration in the plasma, erythrocytes, and gastric mucosa of man. Free Radic Biol Med. 1996;20(3):483-8.
  31. View Abstract: Yoshida K, Hirokawa J, Tagami S, Kawakami Y, Urata Y, Kondo T. Weakened cellular scavenging activity against oxidative stress in diabetes mellitus: regulation of glutathione synthesis and efflux. Diabetologia. Feb1995;38(2):201-10.
  32. View Abstract: Iantomasi T, Marraccini P, Favilli F, Vincenzini MT, Ferretti P, Tonelli F. Glutathione metabolism in Crohn’s disease. Biochem Med Metab Biol. Dec1994;53(2):87-91.