Dietary gamma-Glutamylcysteine: Its Impact on Glutathione Status and Potential Health Outcomes

Glutathione (GSH) is a tripeptide that is readily synthesized intracellularly in humans and other mammals. More than a century of research suggests that GSH has numerous biological functions, including protection from the potential adverse events associated with reactive oxygen species (ROS) and related redox reactions that may induce oxidative stress, and that may be linked to innate detoxification processes. Normal tissue and plasma levels of GSH decline through the aging process and decrease during various disease states. While the health value of dietary GSH remains controversial, there is evidence that some metabolic intermediates, such as gamma-glutamylcysteine (GGC) may function to preserve adequate GSH levels when the synthetic pathways decline in activity, and the innate antioxidant system is challenged. It is also important to recognize that among the thousands of protein-coding human genes and their respective polymorphisms, at least two genes (Gclc and Gclm) are directly involved with GSH synthesis via glutamate-cysteine ligase. This commentary examines the classic biochemistry, toxicology, safety, and clinical value of GSH and its intermediates that may be modulated by dietary supplementation.