Does Oral Ingestion of GSH Raise GSH Levels? Should Oral NAC Also Be Used?

The oral ingestion of GSH has often been overlooked as an effective route of augmentation of extracellular GSH for a number of reasons. The first centers around the dispute over whether GSH is cleaved or destroyed in the digestive tract, or whether GSH can be taken up intact from the duodenum and jejunum and transported into the bloodstream. Fortunately, the number and sophistication of recent research articles demonstrating that GSH is taken up intact from the small intestine outweigh those denying that such uptake occurs. [3, 4, 5, 6]. Some researchers have asserted that oral GSH must be accompanied by oral ascorbic acid in order to assist in that uptake, and this should be investigated. Furthermore, blood elevation of GSH after such ingestion has been noted to be of 3-4 hours in duration [2]. Remember that blood elevation of GSH does in fact lead to ELF elevation of GSH [1].

The second reason for overlooking oral ingestion of GSH lies in the nature of the disorders for which such augmentation is usually recommended. In other types of diseases involving glutathione depletion, such as AIDS, there is no CFTR problem. Thus, increased production of GSH is favored over rectification of specifically the extracellular deficit of GSH because all cells are physically capable of effluxing GSH as needed. Thus it is easier to simply boost production and allowed that increased production to solve the extracellular deficit in natural fashion. However, in CF, most of the cells of the body cannot efflux GSH well if at all. Boosting production for the MRP-expressing cells is all well and good -- and hence our advocacy of cysteine augmentation as well -- but the MRP-expressing cells by themselves cannot rectify the type of severe extracellular deficit experienced by CF adults. It is necessary to simultaneously overcome that extracellular deficit, else the added cysteine will never result in intracellular redox equilibirum of GSH in the MRP-expressing cells. Thus, not only is oral ingestion of GSH arguably effective, it is also theoretically justifiable. We urge closer examination of this route of delivery of GSH.

Since cysteine is the rate-limiting element for the body's synthesis of glutathione, we believe supplementation with a cysteine donor in addition to GSH is justifiable. There are many such donors, and the least expensive choice (which is arguably just as effective as more expensive options) is NAC, or n-acetyl cysteine, which can be had from any health food store without a prescription. However, it must be noted that cysteine can be toxic in too-high doses. Indeed, the body quickly converts cysteine into GSH in order to store cysteine in a non-toxic form. Therefore, care must be taken to ensure that a proper dose of a cysteine donor is used.

Please remember to make no changes to your medical treatment without prior consultation with your medical professional!

References

[1] Buhl R et al., "Augmentation of the Antioxidant Screen of the Epithelial Surface of the Lower Respiratory Tract by Aerosol Administration of Glutathione," Proc. Natl. Acad. Sci. USA 87:4063-67, 1990 June.

[2] Private communication, Myron Seligmann, Ph.D.

[3] Iantomasi T et al., "Glutathione transport system in human small intestine epithelial cells," Biochim. Biophys. Acta 1330(2): 274-83, 1997 December 4.

[4] Hunjan MK and DF Evered, "Absorption of glutathione from the gastro-intestinal tract," Biochim. Biophys. Acta 815(2): 184-8, 1985 May 14.

[5] Favilli F et al., "Effect of orally administered glutathione on glutathione levels in some organs of rats: role of specific transporters," Br. J. Nutr. 78(2): 293-300, 1997 August.

[6] Hagen TM et al., "Bioavailability of dietary glutathione: effect on plasma concentration," Am. J. Physiol. 259 (4 Pt 1): G524-9, 1990 October.