Nutrition Notes

The Role of NAC in Detoxification Pathways

N-Acetyl-L-Cysteine (NAC), a derivative of the amino acid cysteine, is a critical precursor to glutathione (GSH). NAC helps support antioxidative status in the body by helping to promote GSH levels and inactivate reactive oxygen species. NAC has been shown to help prevent the synthesis of pro-inflammatory cytokines tumor necrosis factor-alpha, interleukin (IL)-1beta, IL-6, and IL-8. NAC helps support normal detoxification pathways, liver health, lung function, and a normal inflammatory response.

A publication by Raghu and colleagues explored the potential efficacy of NAC for oxidative stress and toxicity. In addition to its role as a GSH precursor, NAC may help protect against mitochondrial dysfunction. NAC may also help support increased adenosine triphosphate levels in hepatocytes by converting excess NAC that is not used for glutathione synthesis into Krebs cycle intermediates, which promotes mitochondrial function in liver cells. NAC may also help support the replacement of necrotic hepatocytes and help restore homeostasis after mitochondrial dysfunction in the presence of an acetaminophen-induced liver injury.

Impairments in a glutamate transporter called excitatory amino acid transporter-3 (EAAT3) have been associated with age-associated brain and cognition changes. EAAT3 helps transport cysteine. Animal models lacking EAAT3 have been associated with increased oxidative stress, decreased GSH levels, and premature brain aging. In an animal study, the administration of NAC was shown to help reverse learning and memory impairment associated with heavy metal neurotoxicity by potentially acting on EAAT3 and helping to modulate glutamate homeostasis.

NAC may also support many other systems of the body. It acts as a mucolytic agent helping to thin mucous secretions. The free thiol group depolymerizes and degrades mucin by hydrolyzing the disulfide bonds that link the mucin monomers, thereby decreasing the viscosity of sputum. Its role as an antioxidant can also positively influence sputum production, as oxidative stress and inflammation may increase mucus secretion. NAC may also help support cardiovascular function and brain health in the presence of certain neuropsychiatric conditions. Recent studies indicate that NAC may also help support a normal pain response related to diabetic neuropathy.

More studies are needed before clinical conclusions can be made. However, NAC may support many aspects of health, including antioxidative status, a healthy inflammatory response, and detoxification pathways.

By Colleen Ambrose, ND, MAT