Acetyl Glutathione: A Novel Oral Form with Intracellular Penetration


The antioxidant glutathione, known as GSH, is arguably the most important antioxidant the body makes, and most certainly the most powerful intracellular antioxidant. In its reduced form it plays a pivotal role in DNA repair, immunity, flushing of toxins, removal of heavy metals, quenching of free radicals, and recycling of other antioxidants such as vitamins C and E. Glutathione supports detoxification in the lining fluid of the lung and intestines, enhances macrophage function, and slows virus production. Low levels of glutathione are associated with an astonishing range of diseases, from diabetes to Parkinson’s to asthma to kidney problems, and many other conditions.

Unfortunately, oral supplementation of glutathione has proved tricky and sometimes ineffective, since the molecule when taken orally is not able to effectively reach and be absorbed into the intracellular space where it is needed.(1,2) Optimal exposure to the potential benefits linked to GSH have been achieved with IV therapy but it is expensive and inconvenient, and has only short-term benefits, and so needs to be repeated frequently.

“The contribution of GSH deficiency in many pathologies has stimulated a number of researchers to find new potential approaches for maintaining or restoring GSH levels,” write Italian researchers in a review in the journal Molecules in 2010.(3) And as it turns out, those approaches have borne fruit. One novel formulation of the molecule, S-acetylglutathione (S-GSH), has been shown to be surprisingly well absorbed by cells and of great potential benefit.(3) It crosses the cell membrane more easily than GSH itself, and is easily de-acetylated in the cell, becoming active GSH. The fact that S-GSH can be effectively absorbed by cells after an oral dose argues for its great potential in comparison to IV therapy.

S-GSH proved a significant anti-viral agent both in vitro and in animal studies in a 2005 study from Johann Wolfgang Goethe University Hospital in Germany. Remarkably, it was stable in plasma and taken up directly by cells with subsequent conversion to GSH (the active, reduced form). In cell culture, S-GSH efficiently restored intracellular glutathione, and in mice, S-GSH but not plain glutathione, significantly decreased virally induced mortality. This novel form of glutathione was active and stable.(4)

S-GSH has also been shown to cause the death of certain cancer cells. In a study in the International Journal of Oncology, S-GSH induced significant cell death in three human lymphoma cell lines. It did not have the same effect on normal lymphocytes. The researchers concluded that “S-acetyl glutathione specifically activates programmed cell death in lymphoma cells.” In fact, their analysis showed that this form of glutathione depleted intracellular glutathione in the cancer cells, in a selective effect that was the opposite of its action in normal cells.(5)

Finally, in mice infected with a viral complex, S-GSH was able to reduce spleen viral content by 70% and lymph node viral content by 30%–and to do so at half the concentration of GSH.(6) As the Italian researchers note in Molecules, glutathione analogues such as S-GSH “may offer a promising therapeutic alternative for reducing the GSH functional loss related to many human diseases.”(3)

(Source: Nutricology Newsletter In Focus June 2011)


  1. Witschi A, Reddy S, Stofer B, Lauterburg BH. The systemic availability of oral glutathione. Eur J Clin Pharmacol. 1992;43(6):667-9. PMID: 1362956
  2. Hagen TM, Wierzbicka GT, Sillau AH, Bowman BB, Jones DP. Bioavailability of dietary glutathione: effect on plasma concentration. Am J Physiol. 1990 Oct;259(4 Pt 1):G524-9. PMID: 2221062
  3. Cacciatore I, Cornacchia C, Mollica A, Pinnen F, Di Stefano A. Prodrug Approach for Increasing Cellular Glutathione Levels. Molecule. 3 March 2010. PMID: 20335977
  4. Vogel JU, Cinatl J, Dauletbaev N, Buxbaum S, Treusch G, Cinatl J Jr, Gerein V, Doerr HW. Effects of S-acetylglutathione in cell and animal model of herpes simplex virus type 1 infection. Med Microbiol Immunol. 2005 Jan;194(1-2):55-9. PMID: 14624358
  5. Locigno R, Pincemail J, Henno A, Treusch G, Castronovo V. S-acetyl-glutathione selectively induces apoptosis in human lymphoma cells through a GSH-independent mechanism Int J Oncol. 2002 Jan;20(1):69-75. PMID: 11743644
  6. Fraternale A, Paoletti MF, Casabianca A, Orlandi C, Schiavano GF, Chiarantini L, Clayette P, Oiry J, Vogel JU, Cinatl J Jr, Magnani M. Inhibition of murine AIDS by pro-glutathione (GSH) molecules. Antiviral Res. 2008 Feb;77(2):120-7. PMID: 18164447

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