N-Acetylcysteine

N-acetylcysteine (NAC) is an acetylated form of the amino acid L-cysteine. It has antioxidant, anti-inflammatory, and mucolytic properties.^[1] NAC is converted to L-cysteine after ingestion, which, in turn, is converted into glutathione, a powerful antioxidant. Free L-cysteine is readily oxidized in solution, encouraging the formation of insoluble precipitates.^[2] In contrast, NAC is more stable and has a much lower toxicity than free L-cysteine,^[3][4] making it safer and more effective for increasing cysteine levels in the body.

NAC reduces levels of proinflammatory cytokines and oxidative stress.^[5][6] Because NAC increases glutathione levels in the body, which are rapidly depleted by stress, disease, or drug toxicity, it has applications in clinical settings, in addition to general health and wellness. NAC has been used for the treatment of cystic fibrosis (due to its mucolytic properties),^[7] acute acetaminophen toxicity,^[8] and chronic obstructive lung disease.

NAC is safe and effective at reasonable doses through oral supplementation. NAC toxicity mostly occurs in clinical settings, with one case of overdose occurring due to an error in the preparation of an IV solution. An excessive dose of NAC in a short time period can cause red blood cell lysis (hemolysis), low blood platelet count (thrombocytopenia), kidney failure, and possibly death.^[9]

NAC has cytoprotective effects, which work through antioxidant and anti-inflammatory mechanisms. On the antioxidant side, although the NAC molecule itself has the ability to scavenge reactive oxygen species (ROS), the antioxidant effects of NAC in the body mainly occur through increasing glutathione levels and other indirect mechanisms.^[10] The anti-inflammatory effects of NAC are indirect and work through its antioxidant activity, which in turn inhibits the pro-inflammatory transcription factor NFkB.^[11]