Glutathione (GSH) is a critical molecule for the maintenance of antioxidative balance and helping protect cells from oxidative stress. GSH also promotes the optimal function of detoxification pathways, helping detoxify and eliminate toxins and other harmful substances from the body.

GSH is produced endogenously, but the body may require increased amounts during the aging process or during times of increased toxic burden and oxidative stress. Deficiencies in GSH have been linked to certain chronic and age-related illnesses and diseases related to cellular and mitochondrial dysfunction. Type 2 diabetes mellitus, hypertension, cognitive impairment, chronic liver disease, cystic fibrosis, and neurodegenerative diseases, such as Alzheimer’s Disease (AD) and Parkinson’s Disease (PD) have all been associated with reductions in GSH levels.

GSH is also a particularly supportive molecule for cognition and the central nervous system (CNS). Approximately 10% to 20% of GSH exists in the mitochondria of neural cells. Age-related changes to cognitive function and neuronal health have been associated with oxidative damage. The tripeptide structure of GSH interacts with glutamate receptors in the nervous system. Decreased levels of GSH have been associated with AD, PD, bipolar disorder, schizophrenia, and multiple sclerosis. Preclinical evidence suggests that GSH supplementation may support cognition and healthy aging by promoting antioxidative status and several other biochemical pathways. GSH has been shown to support DNA synthesis and repair, calcium signaling, myelin maturation, apoptosis, neuronal differentiation, and cellular communication. 

Glutathione may also help support cellular health and normal detoxification. GSH helps support the hepatic conversion and excretion of toxins including persistent organic pollutants (POPs) and heavy metals such as mercury. A laboratory study reported that GSH may act as a polydentate chelator of metals such as lead.

Inorganic mercury damages the kidneys through many pathways, including the induction of oxidative stress and apoptosis. Mercury has a particular affinity for sulfhydryl groups and can be excreted from the body as a glutathione conjugate. Single nucleotide polymorphisms (SNPs) in glutathione-related genes have been shown to help modulate glutathione levels and potentially help regulate mercury-related toxicities in individuals with occupational exposure.

GSH may also support liver health. A multicenter open-label pilot study investigated the efficacy of GSH supplementation in 34 individuals with nonalcoholic fatty liver disease (NAFLD). Participants first engaged in a 3-month-long diet and lifestyle intervention. This was followed by a 4-month period involving daily supplementation with 300 mg of GSH. Biomarkers associated with liver health, such as alanine aminotransferase (ALT) and triglycerides, were evaluated before and after GSH administration. Improvements in non-esterified fatty acids, triglycerides, ferritin levels, and statistically significant improvements in ALT were reported.

Although more studies are needed before clinical conclusions can be made, glutathione may help support antioxidative status and cellular function. It may also help support cognitive function and healthy aging. 

By Colleen Ambrose, ND, MAT