European Journal of Clinical Pharmacology

, Volume 43, Issue 6, pp 667–669 | Cite as

The systemic availability of oral glutathione

  • A. Witschi
  • S. Reddy
  • B. Stofer
  • B. H. Lauterburg
Short Communications


When the plasma glutathione concentration is low, such as in patients with HIV infection, alcoholics, and patients with cirrhosis, increasing the availability of circulating glutathione by oral administration might be of therapeutic benefit.

To assess the feasibility of supplementing oral glutathione we have determined the systemic availability of glutathione in 7 healthy volunteers.

The basal concentrations of glutathione, cysteine, and glutamate in plasma were 6.2, 8.3, and 54 μmol·l−1 respectively. During the 270 min after the administration of glutathione in a dose of 0.15 mmol·kg−1 the concentrations of glutathione, cysteine, and glutamate in plasma did not increase significantly, suggesting that the systemic availability of glutathione is negligible in man.

Because of hydrolysis of glutathione by intestinal and hepatic γ-glutamyltransferase, dietary glutathione is not a major determinant of circulating glutathione, and it is not possible to increase circulating glutathione to a clinically beneficial extent by the oral administration of a single dose of 3 g of glutathione.

Key words

Glutathione systemic availability, cysteine, glutamate 


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  1. 1.
    Aebi S, Assereto R, Lauterburg BH (1991) High dose intravenous glutathione in man. Pharmacokinetics and effects on cyst(e)ine in plasma and urine. Eur J Clin Invest 21: 103–110Google Scholar
  2. 2.
    Beutler HO, Michal G (1974) L-Glutamat. Bestimmung mit Glutamat-Dehydrogenase, Diaphorase und Tetrazoliumsalzen. In: Bergmeyer HU (ed) Methoden der enzymatischen Analyse, 3rd edn. Verlag Chemie, Weinheim, pp 1753–1759Google Scholar
  3. 3.
    Bilzer M, Lauterburg BH (1991) Effect of hypochlorous acid and chloramines on vascular resistance, cell integrity, and biliary glutathione disulfide in the perfused rat liver: modulation by glutathione. J Hepatol 13: 84–89Google Scholar
  4. 4.
    Buhl R, Holroyd KJ, Mastrangeli A, Cantin AM, Jaffe HA, Wells FB, Saltini C, Crystal RG (1989) Systemic glutathione deficiency in symptom-free HIV-seropositive individuals. Lancet II: 1294–1298Google Scholar
  5. 5.
    Burgunder JM, Lauterburg BH (1987) Decreased production of glutathione in patients with cirrhosis. Eur J Clin Invest 17: 408–414Google Scholar
  6. 6.
    Cantin AM, Hubbard RC, Crystal RG (1989) Glutathione deficiency in the epithelial lining fluid of the lower respiratory tract in idiopathic pulmonary fibrosis. Am Rev Respir Dis 139: 370–372Google Scholar
  7. 7.
    Chawla RK, Lewis FW, Kutner MH, Bates DM, Roy RGB, Rudman D (1984) Plasma cysteine, cystine and glutathione in cirrhosis. Gastroenterology 87: 770–776Google Scholar
  8. 8.
    Gmunder H, Roth HS, Eck HP, Gallas H, Mihm S, Droege W (1990) Interleukin-2 messenger RNA expression, lymphokine production and DNA synthesis in glutathione-depleted T-cells. Cellular Immunol 130:520–528Google Scholar
  9. 9.
    Hagen TM, Wierzbicka GT, Sillau AH, Bowman BB, Jones DP (1990) Bioavailability of dietary glutathione — Effect on plasma concentration. Amer J Physiol 259: G524-G529Google Scholar
  10. 10.
    Higashi T, Tateishi N, Naruse A, Sakamoto Y (1977) A novel physiological role of liver glutathione as a reservoir of L-cysteine. J Biochem 82: 117–124Google Scholar
  11. 11.
    Lauterburg BH, Velez ME (1988) Glutathione deficiency in alcoholics: risk factor for paracetamol hepatotoxicity. Gut 29: 1153–1157Google Scholar
  12. 12.
    Newton GL, Dorian R, Fahey RC (1981) Analysis of biological thiols: derivatization with monobromobimane and separation by reverse-phase high-performance liquid chromatography. Anal Biochem 114: 383–387Google Scholar
  13. 13.
    Porta P, Aebi S, Summer K, Lauterburg BH (1991) L-2-oxothiazolidine 4-carboxylic acid (OTC), a cysteine prodrug: pharmacokinetics and effects on thiols in plasma and lymphocytes of man. J Pharmacol Exp Ther 257: 331–334Google Scholar
  14. 14.
    Speisky H, Shackel N, Varghese G, Wade D, Israel Y (1990) Role of hepatic gamma-glutamyltransferase in the degradation of circulating glutathione: studies in the intact guinea pig perfused liver. Hepatology 11: 843–849Google Scholar
  15. 15.
    Wendel A, Cikryt P (1980) The level and half-life of glutathione in human plasma. FEBS Lett 120: 209–211Google Scholar

Copyright information

© Springer-Verlag 1992

Authors and Affiliations

  • A. Witschi
    • 1
  • S. Reddy
    • 1
  • B. Stofer
    • 1
  • B. H. Lauterburg
    • 1
  1. 1.Department of Clinical PharmacologyUniversity of BernBernSwitzerland

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