Glutathione (GSH) is a tripeptide molecule consisting of cysteine, glutamine, and glycine and is the most abundant antioxidant in the body. In scientific literature, oxidative stress has been associated with the accumulation of dysfunctional and damaged mitochondria. Clinical studies have linked deficiencies in GSH to certain chronic and age-related illnesses and diseases that involve cellular and mitochondrial dysfunction.

Approximately 10% to 20% of GSH exists in the mitochondria of neural cells. GSH is a particularly supportive molecule for cognition and central nervous system (CNS) function. Age-related changes to cognitive function and neuronal health have been associated with oxidative damage. GSH may also help promote the optimal function of detoxification pathways, helping bind and eliminate certain harmful substances from the body.

S-acetyl glutathione (SAG) is a derivative of GSH that may help support the replenishment of intracellular GSH levels. Structurally, SAG has an acetyl group attached to the sulfur atom of cysteine in the tripeptide glutathione molecule. This may help protect molecular breakdown in the GI tract, thus helping support the cellular uptake of the intact glutathione molecule. SAG is thought to directly enter cells and undergo conversion to GSH by intracellular thioesterases.

Evidence suggests SAG may be more stable in blood than GSH itself. It may also have a longer plasma half-life compared to GSH. A laboratory study analyzed fibroblasts from individuals with glutathione synthetase deficiency, wherein lowered levels of GSH were originally observed at baseline. After administration of relatively high amounts of SAG for five days, significant increases in intracellular GSH levels were reported.

Laboratory and animal studies have investigated SAG’s potential to support the body’s response to viral load. Human fibroblast cells infected with herpes simplex-1 virus were shown to help support the suppression of virtual replication and helped replenish intracellular GSH levels in the presence of SAG. In murine populations, SAG significantly helped delay virus-induced mortality; in comparison, GSH showed no protective effect, suggesting that SAG may be uniquely suited to support the body’s response to viral challenge.

A laboratory study evaluated SAG’s potential to support cellular health in the presence of carbon tetrachloride, a model for toxin-mediated liver fibrosis due to its ability to induce severe liver cell damage and increase reactive oxygen species levels and the inflammatory response. Administration with SAG was shown to help restore the activity of certain agents that help support antioxidative status, including Nrf2 and heme oxygenase. SAG was also reported to help restore GSH levels and superoxide dismutase activity, and helped reduce levels of proinflammatory cytokines including tumor necrosis factor-α (TNF-α), interleukin (IL)-6, and IL-1β in both serum and liver. 

While more research is needed, particularly in the clinical setting, evidence suggests that SAG may help support antioxidative stress and the inflammatory response. It may also help support optimal cellular health and mitochondrial function.

By Dr. C. Ambrose, ND, MAT