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Supplements

glutathione

What Is It?
Health Benefits
Forms
Dosage Information

Guidelines for Use

General Interaction
Possible Side Effects
Cautions

References

Evidence Based Rating Scale

 

What Is It?

Glutathione is an important part of the body's Antioxidant defense system. It is a tripeptide compound composed of three different Amino acids—cysteine, glutamic acid, and glycine—that is primarily produced in the liver.

The antioxidant properties of glutathione neutralize damaging Free radicals and peroxide molecules, and recharge oxidized Vitamin C so that the body may reuse it. Additionally, glutathione is required for a variety of metabolic processes, it bolsters the structure of body proteins, and it assists in the transport of amino acids across cell membranes.

Vitamins B6 and riboflavin are critical for maintaining adequate levels of glutathione within the body. Research suggests that a variety of dietary minerals, including copper and selenium, influence cellular levels of glutathione. In addition, selenium is an essential part of many different forms of glutathione that exist in the body. Other nutrients that help to increase glutathione levels include vitamin A, vitamin E, N-acetylcysteine (NAC), S-adenosylmethionine (SAMe), Alpha Lipoic Acid, and undenatured whey protein. Silymarin, from the herb Blessed Milk Thistle, has also demonstrated an ability to replenish glutathione levels.  (1-5)

Several foods contain naturally occurring glutathione, including: avocado, watermelon, asparagus, grapefruit, potato, acorn squash, strawberries, orange, tomato, cantaloupe, broccoli, okra, peach, zucchini, and spinach. Interestingly, the phytochemical limonene may boost the body's synthesis of a glutathione-containing Enzyme that helps to detoxify certain chemicals and also has antioxidant properties. Limonene is found in citrus fruit peels, cherries, green foods (celery, fennel), soy products, and wheat.

Health Benefits

Glutathione has several health benefits. Optimal amounts of glutathione are necessary for supporting the immune system: in particular, glutathione is required for replication of the lymphocyte immune cells.

Glutathione also helps the liver to detoxify chemicals, such as acetaminophen (Tylenol®), alcohol, and cadmium—a toxic metal that has been associated with a variety of cancers. (6) Scientists speculate that increasing consumption of antioxidants such as glutathione early in life may promote longevity and reduce chronic disease. (7, 8)

Research is currently exploring the potential benefits of glutathione for several conditions including cancer, cataracts, heart disease, memory loss, osteoarthritis, Parkinson's disease, cornea disorders, kidney dysfunction, eczema, liver disorders, poisoning by heavy metals, and immunodepression that occurs in diseases such as AIDS.

Specifically, glutathione may help to:

Reduce the risk of some cancers. Some evidence indicates the antioxidant properties of glutathione may be effective in fighting cancer-causing free radicals, thus helping to reduce the risk of certain types of cancer. (9, 10)

Interestingly, in one study in which a 3-gram dosage of oral glutathione was given, oral supplementation did not increase plasma glutathione levels. (11) Rather, eating foods, especially raw foods that contain glutathione seems to show the most benefit in cancer risk reduction. For example, in a population-based observational study with 1,830 participants, a reduced risk of new oral cancers was associated with higher consumption of glutathione derived from fruits and vegetables that are usually consumed raw compared to glutathione derived from other vegetables and from meat. (12)

Reduce the side-effects of cancer therapies. Glutathione may be useful in conjunction with conventional therapies for treating cancer. Several studies suggest that increasing glutathione levels helps to protect healthy cells while increasing cancer cell destruction during conventional cancer treatments such as chemotherapy. One set of studies observed the effects of a specific whey protein concentrate (Immunocal) that provides cysteine as a precursor to glutathione. Glutathione levels in prostate cancer cells were normalized in the studies. It is unclear whether the same benefit would be seen with other forms of whey supplementation, and small studies in cancer patients have not had a clear impact on cancer survival. (13-15)

Other studies in humans have focused on toxicity during conventional cancer treatment. Several studies have found that administering glutathione by intravenous injection along with chemotherapy seems to help decrease toxicity from chemotherapy, especially when using platinum containing chemotherapeutic agents, thus allowing for more chemotherapy doses. Quality of life was also improved during treatment of cancers of the breast, bone marrow, colon, larynx, lung, ovary, and stomach. (16-27)

Relieve symptoms of Parkinson's disease. Studies have shown that glutathione deficiency is present in Parkinson's disease, a progressive nervous system disorder that causes physical symptoms such as tremors, rigidity, loss of coordination and a slow, shuffling gait. (28-34) Adequate glutathione levels may help to protect the brain from free-radical damage and may also increase the body's sensitivity to dopamine, which relays messages between nerve and muscle cells. A 1999 study found that elevating levels of glutathione through injection of N-acetylcysteine (NAC) protected against a particular form of free radical-induced oxidative stress in rat brains. (35) Studies evaluating glutathione supplementation for Parkinson's disease are limited. A 2006 review of antioxidant use in Parkinson’s disease found only one study involving glutathione. With fewer than 30 subjects, it did show a small but statistically significant improvement in symptoms of Parkinson's disease. (36) However, a 2009 study had conflicting results. In the study, 20 patients with Parkinson's disease received either 1,400 mg of intravenous glutathione or placebo three times a week for twelve weeks. Over the first four weeks, Unified Parkinson's Disease Rating Scale (UPDRS) scores and motor scores improved by a mean of 2.8 units more in the treatment group. However, scores worsened in the treatment group with continued glutathione supplementation in the eight subsequent weeks. (37) Larger studies are needed to establish appropriate doses and timing of glutathione therapy.

Prevent heart disease. The antioxidant properties of glutathione may be beneficial in preventing heart disease, which is characterized by a narrowing of the arteries that supply the heart with blood, oxygen and nutrients. Scientists believe that free radicals are responsible for oxidation of the LDL ("bad") cholesterol that can lead to the clogged arteries in heart disease. By scavenging the free radicals, glutathione may help to prevent the risk factors that lead to heart disease. A preliminary study in 2004 compared plasma glutathione levels in 134 patients with heart disease to those of healthy control subjects. Mean glutathione levels were lower in all heart disease cases than in control subjects, suggesting that low levels of glutathione present a risk factor for heart disease. (38) A similar study in 2009 measured plasma glutathione levels in 76 patients undergoing surgery for various heart conditions (coronary artery disease, aortic stenosis or terminal cardiomyopathy) and in 15 healthy volunteers of comparable age. Compared to healthy controls, blood glutathione was decreased by 21% in New York Heart Association (NYHA) class I patients with heart disease, and by 40% in patients with NYHA class II-IV symptoms of heart disease suggesting an association between glutathione deficiency and abnormal heart function. (39) However, studies are needed to determine whether supplementation is helpful for preventing heart disease.

Improve memory loss. Studies have shown oxidative stress is a key factor in Alzheimer's disease, a degenerative disorder of the brain that severely impairs memory and mental function. Protecting the brain from free radical damage helps to prevent memory loss. The study described above that showed beneficial effects of injecting glutathione into the brains of rats with Parkinson's disease also noted its benefits against oxidative stress in Alzheimer's disease. The study showed that neurodegenerative diseases such as Alzheimer's disease may benefit from the protective effects of increasing levels of glutathione. (35) Human studies are needed.

Reduce inflammation in osteoarthritis. The anti-inflammatory properties of glutathione may be beneficial in treating the joint pain and swelling of osteoarthritis (OA). A 2003 study of joint cartilage from young and old adult human tissue donors found that the increased oxidative stress that accompanies aging impairs the glutathione antioxidant system and makes the cells in joint cartilage more susceptible to inflammation and OA. (40) A 2008 study of joint fluid samples from 28 patients with severe OA showed a significant decrease in glutathione levels compared to fluid from a control group of patients with pain or sub-acute injury in their knee joints but who had macroscopically intact cartilage. (41)

Prevent vision problems. Glutathione plays an important role in protecting the eyes from harmful toxins and maintaining a healthy lens. Studies have shown that glutathione deficiency is associated with age-related macular degeneration (AMD) and cataracts. (42, 43) A 2000 review of studies evaluating diet, environmental and behavioral risk factors for AMD found that therapeutic or nutritional intervention may enhance the glutathione capacity of the cell layer that nourishes retinal visual cells. (44) Glutathione has been shown to be critical in preventing the development of cataracts, a disorder in which the lens of the eye loses its normal transparency and begins to impair vision. Cataracts are generally characterized by extensive oxidation of lens proteins, and some research has shown glutathione is the key defense against oxidation in the lens. (45, 46) Increasing glutathione levels in glutathione-deficient rats was shown to prevent the formation of cataracts. (47) More research in humans is needed.

Improve survival in AIDS. Patients with Acquired Immunodeficiency Syndrome (AIDS) seem to have low levels of reduced glutathione, which may result in increased HIV expression and impaired T cell function. (48) Boosting glutathione, then, may be important in improving immune function in these patients. The glutathione precursor N-acetylcysteine (NAC) boosts glutathione production and supports the proper functioning of immune-system components such as T cells, B cells, and phagocytes, all of which are important for maintaining the body’s defenses and potentially protecting against AIDS-related illnesses. (49-51) One study indicates that a glutathione deficiency in CD4 T cells is associated with decreased survival time: the probability that HIV-infected subjects will die within two to three years is dramatically higher with glutathione-deficient CD4 T cells. Combined with the evidence that NAC is efficacious in replenishing glutathione levels, the researchers suggested glutathione is a key factor for survival in HIV disease and that the prolonged or extensive use of conventional medications known to deplete levels of glutathione  (such as acetaminophen) should be avoided in HIV patients. (49)

Treat respiratory conditions. The free radical scavenging properties of glutathione are important in the respiratory tract to combat oxidative stress during conditions such as strenuous exercise, smoking. and Farmer's lung.  Glutathione deficiency has also been associated with chronic obstructive pulmonary disease. (52) Treatment studies have shown that inhalation is the only effective method of increasing glutathione in the cells lining the lower respiratory tract. (53)

Forms

  • capsule
  • liquid
  • tablet
  • aerosol for inhalation
  • intramuscular
  • intravenous (IV) 

Dosage Information

A Recommended Dietary Allowance (RDA) has not been established for glutathione, and no studies have demonstrated significant absorption from oral supplements. Ingesting raw fruits and vegetables and supplements of glutathione precursors such as vitamin A, vitamin E, N-acetylcysteine (NAC), S-adenosylmethionine (SAMe), and Alpha-lipoic acid have the greatest possibility of raising glutathione levels for general health. For dosage recommendations, please see the WholeHealthMD articles on these supplements.

For integrative treatment of disease conditions, ask your physician about adding glutathione to your regimen via inhalation, intramuscular, or intravenous routes.

Guidelines for Use

Eating ample amounts of raw fruits and vegetables and glutathione precursors is associated with higher glutathione levels. However, oral supplementation of pure glutathione does not seem to improve levels; therefore, it is not recommended.

Glutathione is most effective when administered intravenously, via intramuscular injections, or via aerosol or nebulizer for respiratory conditions. Consult a doctor for recommendations and prescriptions for glutathione.

General Interaction

There are no known interactions of glutathione with food.

Possible Side Effects

There are no known side effects of glutathione.

Cautions

If there is a concern about glutathione levels, avoid drugs that contain acetaminophen (Tylenol®) because it depletes levels of glutathione.

References

1. Numan IT, Hassan MQ, Stohs SJ. Protective effects of antioxidants against Endrin-induced lipid peroxidation, glutathione depletion, and lethality in rats. Arch Environ Contam Toxicol. 1990;19:302-6.
2. Vendemiale G, Altomare E, Trizio T, et al. Effects of oral S-adenosyl-L-methionine on hepatic glutathione in patients with liver disease. Scand J Gastroenterol. May 1989;24(9):407-15.
3. Busse E, Zimmer G, Schopohl B, Kornhuber B. Influence of alpha-lipoic acid on intracellular glutathione in vitro and in vivo. Arzneimittelforschung. 1992;42(6):829-31.
4. Bounous G, Gold P. The biological activity of undenatured dietary whey proteins: role of glutathione. Clin Invest Med. 1991 Aug;14(4):296-309.
5. Valenzuela A, Aspillaga M, Vial S, Guerra R. Selectivity of silymarin on the increase of the glutathione content in different tissues of the rat. Planta Med. 1989;55(5):420-2.
6. 11th Report on Carcinogens. National Toxicology Program. http://ntp.niehs.nih.gov/index.cfm?objectid=32BA9724-F1F6-975E-7FCE50709CB4C932. Accessed December 14, 2009.
7. Lang C, Mills B, Mastropaolo W, Liu M. Blood glutathione decreases in chronic diseases. J Lab Clin Med. 2000;135:402-5.
8. Lang C. The impact of glutathione on health and longevity. J Anti Aging Med. June 2001;4(2):137-44.
9. Chow HH, Hakim IA. Modulation of human glutathione s-transferases by polyphenone intervention. Cancer Epidemiol Bio Prev. Aug 2007;16(8):1662-6.
10. Han YH, Park WH. The effects of N-acetylcysteine, buthionine sulfoximine, diethyldithiocarbamate or 3-amino-1,2,4-triazole on antimycin A-treated Calu-6 lung cells in relation to cell growth, reactive oxygen species and glutathione. Oncol Rep. Aug 2009;22(2):385-91.
11. Witschi A, Reddy S, Stofer B, Lauterburg BH. The systemic availability of oral glutathione. Eur J Clin Pharmacol. 1992;43:667-9.
12. Flagg EW, Coates RJ, Jones DP, et al. Dietary glutathione intake and the risk of oral and pharyngeal cancer. Am J Epidemiol. 1994 Mar 1;139(5):453-65.
13. Kent KD, Harper WJ, Bomser JA. Effect of whey protein isolate on intracellular glutathione and oxidant-induced cell death in human prostate epithelial cells. Toxicol In Vitro. Feb 2003;17(1):27-33.
14. Kennedy RS, Konok GP, Bounous G, et al. The use of a whey protein concentrate in the treatment of patients with metastatic carcinoma: a phase I-II clinical study. Anticancer Res. 1995 Nov-Dec;1(6B):2643-9.
15. Tsai WY, Chang WH, Chen CH, Lu FJ. Enhancing effect of patented whey protein isolate (Immunocal) on cytotoxicity of an anticancer drug. Nutr Cancer. 2000;38(2):200-8.
16. Leone R, Fracasso ME, Soresi E, et al. Influence of glutathione administration on the disposition of free and total platinum in patients after administration of cisplatin. Cancer Chemother Pharmacol 1992;29:385-90.
17. Locatelli MC, D'Antona A, Labianca R, et al. A phase II study of combination chemotherapy in advanced ovarian carcinoma with cisplatin and cyclophosphamide plus reduced glutathione as potential protective agent against cisplatin toxicity. Tumori 1993;79:37-9.
18. Di Re F, Bohm S, Oriana S, et al. High-dose cisplatin and cyclophosphamide with glutathione in the treatment of advanced ovarian cancer. Ann Oncol 1993;4:55-61.
19. Plaxe S, Freddo J, Kim S, et al. Phase I trial of cisplatin in combination with glutathione. Gynecol Oncol 1994;55:82-6.
20. Parnis FX, Coleman RE, Harper PG, et al. A randomised double-blind placebo controlled clinical trial assessing the tolerability and efficacy of glutathione as an adjuvant to escalating doses of cisplatin in the treatment of advanced ovarian cancer. Eur J Cancer 1995;31A:1721.
21. Cascinu S, Cordella L, Del Ferro E, et al. Neuroprotective effect of reduced glutathione on cisplatin-based chemotherapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled trial. J Clin Oncol. 1995;13:26-32.
22. Smyth JF, Bowman A, Perren T, 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. 1997;8:569-73.
23. Cascinu S, Labianca R, Alessandroni P, et al. Intensive weekly chemotherapy for advanced gastric cancer using fluorouracil, cisplatin, epi-doxorubicin, 6S-leucovorin, glutathione, and filgrastim: a report from the Italian Group for the Study of Digestive Tract Cancer. J Clin Oncol 1997;15:3313-9.
24. Graziano F, Cardarelli N, Marcellini M, et al. A pilot clinical trial of postoperative intensive weekly chemotherapy using cisplatin, epi-doxorubicin, 5-fluorouracil, 6S-leucovorin, glutathione and filgrastim in patients with resected gastric cancer. Tumori 1998;84:368-71.
25. Links M, Lewis C. Chemoprotectants: a review of their clinical pharmacology and therapeutic efficacy. Drugs 1999;57:293-308.
26. Cascinu S, Frontini L, Comella G, et al. Intensive weekly chemotherapy is not effective in advanced pancreatic cancer patients: a report from the Italian Group for the Study of Dig. Tract Cancer (GISCAD). Br J Cancer 1999;79(3-4):491-4.
27. Balendiran GK, Dabur R, Fraser D. The role of glutathione in cancer. Cell Biochem Funct. Nov-Dec 2004;22(6):343-52.
28. Sechi G, Deledda MG, Bua G, et al. Reduced intravenous glutathione in the treatment of early Parkinson's disease. Prog Neuropsychopharmacol Biol Psychiatry 1996;20:1159-70.
29. Pearce RK, Owen A, Daniel S, et al. Alterations in the distribution of glutathione in the substantia nigra in Parkinson's disease. J Neural Transm 1997;104:661-77.
30. Bains JS, Shaw CA. Neurodegenerative disorders in humans: the role of glutathione in oxidative stress-mediated neuronal death. Brain Res Brain Res Rev. 1997;25:335-58.
31. Jenner P. Oxidative mechanisms in nigral cell death in Parkinson's disease. Mov Disord 1998;(13 Suppl)1:24-34.
32. Merad-Boudia M, Nicole A, Santiard-Baron D, et al. Mitochondrial impairment as an early event in the process of apoptosis induced by glutathione depletion in neuronal cells: relevance to Parkinson's disease. Biochem Pharmacol 1998;56:645-55.23.
33. Jenner P, Olanow CW. Understanding cell death in Parkinson's disease. Ann Neurol 1998;44(3 Suppl 1):S72-84.
34. Marshall KA, Reist M, Jenner P, el al. The neuronal toxicity of sulfite plus peroxynitrite is enhanced by glutathione depletion: implications for Parkinson's disease. Free Radic Biol Med 1999;27:515-20.
35. Pocernich CB, La Fontaine M, Butterfield DA. In-vivo glutathione elevation protects against hydroxyl free radical-induced protein oxidation in rat brain. Neurochem Int. 2000 Mar;36(3):185-91.
36. Weber CA, Ernst ME. Antioxidants, supplements, and Parkinson's disease. Ann Pharmacother. 2006 May;40(5):935-8.
37. Hauser RA, Lyons KE, McClain T, Carter S, Perlmutter D. Randomized, double-blind, pilot evaluation of intravenous glutathione in Parkinson's disease. Mov Discord. 2009 May 15;24(7):979-83.
38. Haruki S, Yutaka K, Isao K, et al. Relationship between plasma glutathione levels and cardiovascular disease in a defined population. Stroke. 2004;35:2072.
39. Damy T, Kirsch M, Khouzami L, et al. Glutathione deficiency in cardiac patients is related to the functional status and structural cardiac abnormalities. PloS One. 2009;4(3):e4871.
40. Carlo MD Jr, Loeser RF. Increased oxidative stress with aging reduces chondrocyte survival: correlation with intracellular glutathione levels. Arthritis Rheum. 2003 Dec;48(12):3419-30.
41. Regan EA, Bowler RP, Crapo JD. Joint fluid antioxidants are decreased in osteoarthritic joints compared to joints with macroscopically intact cartilage and subacute injury. Osteoarthritis Cartilage. 2008 Apr;16(4):515-21.
42. Samiec PS, Drews-Botsch C, Flagg EW, et al. Glutathione in human plasma: decline in associated with aging, age-related macular degeneration, and diabetes. Free Radic Biol Med. 1998;24:699-704.
43. Harding JJ. Free and protein-bound glutathione in normal and cataractous human lenses. Biochem J. 1970 May;117(5):957-60.
44. Cai J, Nelson KC, Wu M, et al. Oxidative damage and protection of the RPE. Prog Retin Eye Res. 2000 Mar;19(2):205-21.
45. Babizhaev MA, Deev AI. [Free radical oxidation of lipids and thiol groups in the formation of a cataract.] Biofizika. 1986 Jan-Feb;31(1):109-14.
46. Babizhaev MA, Deev AI, Vladimirov IuA, Deeva IB. [Decomposition of H202 by human cataractous lenses.] Biull Eksp Biol Med. 1986 Aug;102(8):158-60.
47. Martensson J, Steinherz R, Jain A, Meister, A. Glutathione ester prevents buthionine sulfoximine-induced cataracts and lens epithelial cell damage. Proc Natl Acad Sci USA. 1989 Nov;86(22):8727-31.
48. Greenspan HC. The role of reactive oxygen species, antioxidants, and phytopharmaceuticals in human immunodeficiency virus activity. Med Hypotheses. 1993;40:86-92.
49. Herzenberg L, De Rosa S, Dubs J, et al. Glutathione deficiency is associated with impaired survival in HIV disease. Proc Natl Acad Sci USA. 1997 March 4;94(5):1967-72.
50. Mialocq P, Oiry J, Puy JY, Rimaniol AC, Imbach JL, Dormont D, Clayette P. Oxidative metabolism of HIV-infected macrophages: the role of glutathione and a pharmacologic approach. Pathol Biol (Paris). 2001 Sep;49(7):567-71.<

Date Published: 04/18/2005
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