Glutathione

Also indexed as: GSH

What is it?

Glutathione is a small protein composed of three amino acids: cysteine, glutamic acid, and glycine.

Glutathione is involved in detoxification—it binds to toxins, such as heavy metals, solvents, and pesticides, and transforms them into a form that can be excreted in urine or bile. Glutathione is also an important antioxidant. In preliminary research, dietary glutathione intake from fruit and raw vegetableshas been associated with protection against some forms of cancer.¹ ² Glutathione has also inhibited cancer in test tube³ and animal studies.⁴ In preliminary research, higher glutathione levels have also been associated with good health in older adults.⁵

Glutathione supplements appear to be efficiently absorbed in rats.⁶ ⁷ However, the same may not be true for glutathione supplements in humans. For example, when seven healthy people were given a single application of up to 3,000 mg of glutathione, there was no increase in blood glutathione levels.⁸ The authors of the study concluded "it is not feasible to increase circulating glutathione to a clinically beneficial extent by the oral administrating of a single application of 3,000 mg of glutathione." Absorption of glutathione may be better in rats because unlike the gastrointestinal tract of rats, the human gastrointestinal tract contains significant amounts of an enzyme (gamma-glutamyltranspeptidase) that breaks down glutathione. Preliminary evidence has suggested that absorption of glutathione can occur in the mouth when glutathione tablets are placed between the teeth and the inner cheek.⁹

Some researchers believe that supplements other than oral glutathione may be more effective in raising blood levels of glutathione. For example, in one trial, blood glutathione levels rose nearly 50% in healthy people taking 500 mg of vitamin C per day for only two weeks.¹⁰ Vitamin C raises glutathione by helping the body manufacture it. In addition to vitamin C, other nutritional compounds that may, according to preliminary research, help increase glutathione levels include alpha lipoic acid,¹¹ glutamine,¹² methionine,¹³ S-adenosyl methionine (SAMe),¹⁴ and whey protein.¹⁵ Vitamin B6, riboflavin, and selenium are required in the manufacture of glutathione. The extent to which any of these nutrients effectively increases glutathione levels in humans remains unclear.

Studies using intravenous or intramuscular glutathione have found it to be useful for preventing clot formation during operations;¹⁶ reducing the side effects and increasing the efficacy of chemotherapy drugs (particularly cisplatin in women with ovarian cancer);¹⁷ ¹⁸ treating Parkinson’s disease;¹⁹ reducing blood pressure in people with diabetes who had high blood pressure;²⁰ and increasing sperm counts in men with low sperm counts.²¹ ²² A glutathione nasal spray has also reduced symptoms in people with chronic rhinitis.²³ Whether oral preparations are also effective is unknown at this time. A small study in eight patients with liver cancer using oral glutathione showed modest benefits in women, but not in men, when given in a daily amount of 5,000 mg.²⁴

An unpublished preliminary study of eight colon cancer patients also found that oral glutathione appeared to have anticancer activity.²⁵ Nonetheless, because questions exist about the extent to which oral glutathione can be absorbed, some doctors are concerned that oral preparations may be either less effective than other forms or not effective at all.

Where is it found?

Dietary glutathione is found in fresh and frozen fruits and vegetables, fish, and meat.²⁶ Asparagus, avocado, and walnuts are particularly rich dietary sources of glutathione.

Glutathione has been used in connection with the following conditions (refer to the individual health concern for complete information):

Science Ratings	Health Concerns
	Colon cancer
Reliable and relatively consistent scientific data showing a substantial health benefit. Contradictory, insufficient, or preliminary studies suggesting a health benefit or minimal health benefit. For a herb, supported by traditional use but minimal or no scientific evidence. For a supplement, little scientific support and/or minimal health benefit.

Who is likely to be deficient?

A deficiency can be the result of diseases that increase the need for glutathione, deficiencies of the amino acids needed for synthesis, or diseases that inhibit glutathione formation.²⁷ Examples of some health conditions that are associated with glutathione deficiency include diabetes, low sperm counts, liver disease, cataracts, and HIV infection, respiratory distress syndrome, cancer, and idiopathic pulmonary fibrosis. Cigarette smoking is also associated with low glutathione levels because it increases the rate of utilization of glutathione.

How much is usually taken?

There is very little evidence that taking glutathione supplements provides any benefit, despite promising evidence about the effects of aerosol, intravenous, and intramuscular glutathione, for people with a wide variety of conditions. People who have a proven glutathione deficiency, which may require administration of glutathione intravenously, intramuscularly, or by aerosol, should be treated by a healthcare professional. All ovarian cancer patients currently taking cisplatin (Platinol®) should discuss using intravenous glutathione with a healthcare professional.

Are there any side effects or interactions?

No side effects or interactions are known with oral administration of glutathione.

Are there any drug interactions?
Certain medicines may interact with glutathione. Refer to drug interactions for a list of those medicines.

References
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1. Sen CK. Nutritional biochemistry of cellular glutathione. Nutr Biochem 1997;8:660-72.

2. Flagg EW, Coates RJ, Jones DP, et al. Dietary glutathione intake and the risk of oral and pharyngeal cancer. Am J Epidemiol 1994;139:453-65.

3. Donnerstag B, Ohlenschläger, Cinatl J, et al. Reduced glutathione and S-acetylglutathione as selective apoptosis-inducing agents in cancer therapy. Cancer Lett 1996;110:63-70.

4. Trickler D, Shklar G, Schwartz J. Inhibition of oral carcinogenesis by glutathione. Nutr Cancer 1993;20:139-44.

5. Julius M, Lang C, Gleiberman L, et al. Glutathione and morbidity in a community-based sample of elderly. J Clin Epidemiol 1994;47:1021-6.

6. Hagen TM, Wierzbicka GT, Sillau AH, et al. Fate of dietary glutathione: disposition in the gastrointestinal tract. Am J Physiol 1990;259(4Pt1):G530-5.

7. Favilli F, Marraccini P, Iantomasis T, Vincenzini MT. Effect of orally administered glutathione on glutathione levels in some organs of rats: role of specific transporters. Br J Nutr 1997;78:293-300.

8. Witschi A, Reddy S, Stofer B, Lauterburg BH. The systemic availability of oral glutathione. Eur J Clin Pharmacol 1992;43:667-9.

9. Hunjan MK, Evered DF. Absorption of glutathione from the gastro-intestinal tract. Biochim Biophys Acta 1985;815:184-8.

10. Johnston CS, Meyer CG, Srilakshmi JC. Vitamin C elevates red blood cell glutathione in healthy adults. Am J Clin Nutr 1993;58:103-5.

11. Bunin AIa, Filina AA, Erchev VP. A glutathione deficiency in open-angle glaucoma and the approaches to its correction. Vestn Oftalmol 1992;108:13-5 [in Russian].

12. Amores-Sanchez MI, Medina MA. Glutamine, as a precursor of glutathione, and oxidative stress. Mol Genet Metab 1999;67:100-5.

13. Wang ST, Chen HW, Sheen LY, Lii CK. Methionine and cysteine affect glutathione level, glutathione-related enzyme activities and the expression of glutathione S-transferase isozymes in rat hepatocytes. J Nutr 1997;127:2135-41.

14. 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 1989;24:407-15.

15. Bounous G, Gervais F, Amer V, et al. The influence of dietary whey protein on tissue glutathione and the diseases of aging. Clin Invest Med 1989;12:343-9.

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

17. 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.

18. 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.

19. 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.

20. Ceriello A, Giugliano D, Quatraro A, Lefebvre PJ. Anti-oxidants show an anti-hypertensive effect in diabetic and hypertensive subjects. Clin Sci 1991;81:739-42.

21. Lenzi A, Picardo M, Gandini L, et al. Glutathione treatment of dyspermia: effect on the lipoperoxidation process. Hum Reprod 1994;9:2044-50.

22. Lenzi A, Culasso F, Gandini L, et al. Placebo-controlled, double-blind, cross-over trial of glutathione therapy in male infertility. Hum Reprod 1993;8:1657-62.

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

24. Dalhoff K, Ranek L, Mantoni M, Poulsen HE. Glutathione treatment of hepatocellular carcinoma. Liver 1992;12:341-3.

25. Garcia-Giralt E, Perdereau B, Brixy F, et al. Preliminary study of glutathione, L-cysteine and anthocyans (Recancostat Compositum™) in metastatic colorectal carcinoma with malnutrition. Seventh International Congress on Anti-Cancer Treatment, February 3-6, 1996, Paris, France.

26. 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.

27. White AC, Thannickal VJ, Fanburg BL. Glutathione deficiency in human disease. J Nutr Biochem 1994;5:218–26.

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The information presented in Healthnotes is for informational purposes only. It is based on scientific studies (human, animal, or in vitro), clinical experience, or traditional usage as cited in each article. The results reported may not necessarily occur in all individuals. For many of the conditions discussed, treatment with prescription or over the counter medication is also available. Consult your doctor, practitioner, and/or chemist for any health problem and before using any supplements or before making any changes in prescribed medications. Information expires March 2007.

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