Glutathione is an important molecule in the body’s response to oxidative stress. It is a tripeptide containing cysteine, glycine, and glutamate. Glutathione can be produced by the human body from its peptide precursors.

A recently published review article by Palaniyappan and colleagues explored the potential connection between intracortical glutathione levels and schizophrenia. The study reported that in cases of schizophrenia, changes related to oxidative stress have been observed in certain biomarkers. Animal studies have noted reductions in glutathione levels between 27% and 52% in established schizophrenia. The causes of these reported reductions are believed to include environmental, genetic, and epigenetic factors. Low intracortical glutathione levels were also associated with a potential delayed response to antipsychotic medication and a higher symptom burden. The authors do note the relationship between glutathione and schizophrenia is still unknown and further studies need to be conducted.

Another recently published systematic review and meta-analysis by Zinellu and colleagues assessed the relationship between glutathione and its related molecules and chronic obstructive pulmonary disease (COPD). COPD is associated with chronic inflammation and oxidative stress. Glutathione peroxidase (GPx), an enzyme critical to the antioxidant pathway, was shown to occur in significantly lower concentrations in the presence of COPD. 

GPx has eight forms, four of which are selenoproteins. Diminished expression of GPx-1 in the presence of selenium deficiency has been shown in both animal and laboratory studies. The authors note that individuals with COPD often have nutritional deficiencies, including those of selenium. They postulate that selenium deficiency may influence GPx activity and glutathione levels. The downstream effects of these changes in GPx-1 activity have been associated with changes to the heart’s ability to respond to oxidative stress and may contribute to poor cell survival.  

Oxidative stress and GPx were also recently studied in relation to epilepsy in a meta-analysis by Wang and colleagues. The occurrence of another enzyme related to the body’s response to oxidative stress, superoxide dismutase (SOD), was also evaluated. The results of the meta-analysis indicate that oxidative stress may be associated with epilepsy and that SOD levels in erythrocytes in individuals with epilepsy were significantly reduced as compared to healthy participants. Although previously reported studies showed lower activity of GPx in animals with epilepsy, this meta-analysis did not show corresponding changes in human blood cells. However, the authors do connect oxidative stress with epilepsy, although further studies need to be conducted. 

Glutathione is a critical participant in the body’s response to oxidative stress. It continues to be of interest to the research community as emerging evidence continues to broaden our understanding of this important molecule. 

By Colleen Ambrose, ND, MAT