N-acetylcysteine (NAC)

N-acetylcysteine is an acetylated form of the amino acid cysteine, used clinically as a mucolytic and as the standard antidote for paracetamol (acetaminophen) overdose. Its principal mechanism in both clinical and longevity contexts is replenishment of intracellular cysteine, the rate-limiting precursor for glutathione biosynthesis, thereby restoring the capacity of the γ-glutamyl-cysteinyl-glycine (GSH) system to buffer reactive oxygen species, support mitochondrial redox balance, and facilitate phase II detoxification. Oral bioavailability is moderate and variable due to first-pass metabolism; liposomal and sustained-release formulations are under study. Beyond antioxidant support, NAC modulates NF-κB-mediated inflammatory signaling and may attenuate cysteine-related DNA methylation shifts. As a standalone agent, it has been evaluated in chronic obstructive pulmonary disease, psychiatric disorders, and metabolic disease with mixed results. In the longevity context it is most relevant as the cysteine-donating half of the GlyNAC combination.