N-Acetylcysteine (NAC): What the Science Actually Supports
N-acetylcysteine (NAC) is a well-established medical drug, listed by the World Health Organization as an essential medicine, with decades of clinical use. Its primary approved indications are the treatment of acetaminophen (paracetamol) overdose and use as a mucolytic agent in respiratory disease. Beyond these settings, NAC is often discussed for its antioxidant and anti-inflammatory potential, but the clinical evidence is nuanced.
How NAC works at a cellular level
NAC is an acetylated precursor of the amino acid L-cysteine. Its most important biological role is indirect antioxidant support. By increasing intracellular cysteine availability, NAC supports the synthesis of glutathione (GSH), the most abundant non-protein thiol in human cells and a central regulator of cellular redox balance.
Glutathione is critical for neutralizing reactive oxygen and nitrogen species and for supporting multiple antioxidant enzymes. Because intracellular cysteine is rate-limiting for glutathione synthesis, NAC functions as an effective pharmacological strategy to restore depleted GSH levels in states of oxidative stress.
NAC also demonstrates anti-inflammatory activity, largely through inhibition of the transcription factor NF-κB. This mechanism has been associated with reduced production of inflammatory cytokines such as TNF-α, IL-6, and IL-1β in experimental and clinical models.
In respiratory disease, NAC has an additional mucolytic effect. It breaks disulfide bonds in mucus proteins, reducing mucus viscosity and improving clearance.
