Glutathione (γ-L-Glutamyl-L-cysteinylglycine) is a small amino acid containing molecule (peptide) comprised of one molecule of L-glutamic acid, L-cysteine, and Glycine each. The molecule is found in the food supply and in the human body where it acts as an antioxidant. The 'glutathione system' comprises the enzymes that synthesize glutathione within a cell as well as dedicated enzymes that use glutathione as the means to exert antioxidant effects. Supplementation of glutathione is thought to support this pool of glutathione in a cell and thus maintain the efficacy of the entire glutathione system. Despite the pervasive role of glutathione in cell biology, it currently has a limited role in nutritional supplementation due to the following pharmacokinetic properties:
There may be some absorption of glutathione intact from the intestines, but it cannot enter cells intact. It must be metabolized to form L-cystine (two molecules of L-cysteine bound together) before being taken up.
Provision of L-cysteine within the cell is all that is needed to increase glutathione synthesis, and N-Acetylcysteine does this efficiently at a lower financial cost than glutathione.
In effect, glutathione is an indirect and expensive way to provide dietary L-cysteine. Dietary protein itself, including L-cysteine rich sources such as Whey Protein, are effective but inefficient ways to increase L-cysteine intake in the diet and N-Acetylcysteine is both more efficient and cheaper than glutathione.
Although oral glutathione supplementation does not efficiently increase intracellular glutathione levels for the above reasons, it can be absorbed intact into the blood stream. Since increased glutathione levels in the blood have been shown to slow the breakdown of nitric oxide, glutathione supplementation may be useful to augment nitric oxide boosters such as L-Citrulline or L-Arginine.