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Glutathione

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Principal Proposed UsesOther Proposed Uses


Glutathione

Uses

Principal Proposed Uses

  • None

Other Proposed Uses

  • Antioxidant
In the body, dangerous naturally occurring substances called free radicals pose a risk of harm to many tissues. The body deploys an “antioxidant defense system” to hold them in check. Glutathione, a protein made from the amino acids cysteine, glutamic acid, and glycine, is one of the most important elements of this system.
Glutathione does much of its work in the liver, although it is also found elsewhere in the body. Besides fighting free radicals, it helps keep various essential biological molecules in a chemical state called “reduced” (as opposed to “oxidized”). In addition, glutathione can act on toxins such as pesticides, lead, and dry cleaning solvents, transforming them in such a way that the body can excrete them more easily.
Nutrients such as vitamin C and vitamin E also help neutralize free radicals. In the 1990s, such antioxidant supplements were widely promoted for preventing a variety of diseases, including cancer and heart disease. (Unfortunately, this hope has largely floundered as the results of large, reliable studies have come in.) During this period, oral glutathione became popular as an additional antioxidant supplement. Unfortunately, glutathione is not absorbed when taken by mouth, so such supplements are almost certainly useless. It may be possible, however, to raise glutathione levels in the body by taking other supplements, such as vitamin C , cysteine, lipoic acid , and N-acetylcysteine . Whether doing so would offer any health benefits remains unclear.

Requirements/Sources

There is no dietary requirement for glutathione. The body makes it from scratch, utilizing vitamins and common amino acids found in food.
Glutathione levels in the body are reduced by cigarette smoking. Various diseases are associated with reduced levels of glutathione, including cancer, cataracts , diabetes , and HIV infection . 1

Therapeutic Dosages

A typical recommended dose of oral glutathione is 50 mg twice daily. However, as noted above, when glutathione is taken by mouth it is destroyed. 2 Therefore, no matter what the dose, it won’t make any difference.
It is possible that some glutathione may be absorbed if it is held in the mouth and allowed to dissolve, but this has not been well studied. 3
A more promising method for raising glutathione levels in the body involves taking supplemental cysteine or antioxidant supplements. Evidence suggests that cysteine (often supplied in the form of whey protein, which is high in cysteine) can raise glutathione levels in people with cancer , hepatitis , or HIV . 4-7
In addition, because vitamin C has overlapping functions with glutathione, vitamin C supplements may spare some of the body’s glutathione from being used up, thereby increasing its levels in the body. 8,9 The antioxidant supplement lipoic acid appears to raise glutathione levels as well. 10-15
Other supplements that might raise glutathione levels include N-acetylcysteine , 16-19glutamine , 20methionine , 21 and S-adenosyl methionine (SAMe). 22

Therapeutic Uses

Various websites promote glutathione for a wide variety of health problems, from preventing aging to enhancing sports performance. However, oral glutathione supplements are almost certainly useless for any condition since they are not absorbed.
There is a bit of evidence that injected glutathione might offer a few heath benefits, such as preventing blood clots during surgery, 23 reducing the side effects and increasing the effectiveness of cancer chemotherapy drugs such as cisplatin, 24-26 treating male infertility , 27-31 and alleviating symptoms of early Parkinson’s disease . 32,33 Although oral glutathione is not likely to provide the same benefits, it is at least theoretically possible that taking the nutrients described in the previous section (and thereby raising glutathione levels indirectly) could offer similar benefits. However, there is no direct evidence to indicate that this hypothesis is true.

Safety Issues

Oral glutathione should be entirely safe, since it is not absorbed.

References

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

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

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

4 Bounous G. Whey protein concentrate (WPC) and glutathione modulation in cancer treatment. Anticancer Res . 2000;20:4785-92.

5 Bounous G, Gervais F, Amer V, Batist G, Gold P. The influence of dietary whey protein on tissue glutathione and the diseases of aging. Clin Invest Med . 1989;12:343–9.

6 Micke P, Beeh KM, Schlaak JF, Buhl R. Oral supplementation with whey proteins increases plasma glutathione levels of HIV-infected patients. Eur J Clin Invest . 2001;31:171–8.

7 Watanabe A, Okada K, Shimizu Y, et al. Nutritional therapy of chronic hepatitis by whey protein (non-heated). J Med . 2000;31:283–302.

8 Henning SM, Zhang JZ, McKee RW, Swendseid ME, Jacob RA. Glutathione blood levels and other oxidant defense indices in men fed diets low in vitamin C. J Nutr . 1991;121:1969–75.

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

10 Arivazhagan P, Ramanathan K, Panneerselvam C. Effect of DL-alpha-lipoic acid on glutathione metabolic enzymes in aged rats. Exp Gerontol . 2001;37:81–7.

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.

12 Han D, Handelman G, Marcocci L, et al. Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. Biofactors . 1997;6:321–38.

13 Hultberg B, Andersson A, Isaksson A. Lipoic acid increases glutathione production and enhances the effect of mercury in human cell lines. Toxicology . 2002;175:103–10.

14 Packer L, Kraemer K, Rimbach G. Molecular aspects of lipoic acid in the prevention of diabetes complications. Nutrition . 2001;17:888–95.

15 Sen CK, Roy S, Han D, Packer L. Regulation of cellular thiols in human lymphocytes by alpha-lipoic acid: a flow cytometric analysis. Free Radic Biol Med . 1997;22:1241–57.

16 Droge W, Breitkreutz R. Glutathione and immune function. Proc Nutr Soc . 2000;59:595–600.

17 De Rosa SC, Zaretsky MD, Dubs JG, et al. N-acetylcysteine replenishes glutathione in HIV infection. Eur J Clin Invest . 2000;30:915–29.

18 Witschi A, Junker E, Schranz C, Speck RF, Lauterburg BH. Supplementation of N-acetylcysteine fails to increase glutathione in lymphocytes and plasma of patients with AIDS. AIDS Res Hum Retroviruses . 1995;11:141–3.

19 Droge W, Breitkreutz R. N-acetyl-cysteine in the therapy of HIV-positive patients. Curr Opin Clin Nutr MetabCare . 1999;2:493–8.

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

21 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.

22 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.

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

24 Campbell KC, Larsen DL, Meech RP, Rybak LP, Hughes LF. Glutathione ester but not glutathione protects against cisplatin-induced ototoxicity in a rat model. J Am Acad Audiol . 2003;14:124–33.

25 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.

26 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.

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

28 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.

29 Lenzi A, Gandini L, Picardo M, Tramer F, Sandri G, Panfili E. Lipoperoxidation damage of spermatozoa polyunsaturated fatty acids (PUFA): scavenger mechanisms and possible scavenger therapies. Front Biosci . 2000 Jan 1;5:E1-E15.

30 Lenzi A, Gandini L, Picardo M. A rationale for glutathione therapy. Hum Reprod . 1998;13:1419–22.

31 Lenzi A, Picardo M, Gandini L, Dondero F. Lipids of the sperm plasma membrane: from polyunsaturated fatty acids considered as markers of sperm function to possible scavenger therapy. Hum ReprodUpdate . 1996;2:246–56.

32 Bharath S, Hsu M, Kaur D, Rajagopalan S, Andersen JK. Glutathione, iron and Parkinson's disease. BiochemPharmacol . 2002;64:1037–48.

33 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.

Revision Information

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