N-acetylcysteine (NAC) is an acetylated form of the amino acid L-cysteine. It has antioxidant and anti-inflammatory properties and is a mucolytic agent, meaning that it helps break down mucus in the respiratory tract.^[3] NAC is converted to L-cysteine after ingestion, which, in turn, is converted into glutathione (GSH), a powerful antioxidant.

L-cysteine can’t be supplemented on its own because free L-cysteine is highly unstable, becoming readily oxidized in solution which can encourage the formation of insoluble precipitates.^[4] Similarly, glutathione is rapidly broken down in the gastrointestinal tract and blood, limiting its availability in the body when supplemented directly.^[5] In contrast, NAC is more stable and has a much lower toxicity than free L-cysteine,^[6][7] making it safer and more effective for increasing cysteine and glutathione levels in the body.

NAC reduces levels of proinflammatory cytokines and oxidative stress.^[1][8] 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),^[9] acetaminophen (paracetamol) toxicity,^[10] and chronic obstructive pulmonary disease (COPD).

In COPD, NAC may improve lung function and speed the rate of symptom improvement when used during a symptom flare up (an exacerbation).^[11] Long-term use (more than 3–6 months) may improve symptoms of chronic bronchitis and reduce the risk of COPD exacerbations,^[12][13][14] although the latter effect has not been found consistently.^[15] Additionally, NAC does not seem to prevent declining lung function when used over a long period of time.^[15]

NAC has cytoprotective (cell-protecting) 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.^[16] NAC increases glutathione levels by acting as a source of the amino acid cysteine, which is a rate-limiting building block for glutathione production.^[17] The anti-inflammatory effects of NAC are indirect and work through its antioxidant activity, which in turn inhibits the pro-inflammatory transcription factor NFKB-Activity^[18] and reduces pro-inflammatory cytokines like IL-8, IL-6, and TNF-α.^[19]

As a mucolytic agent, NAC decreases the thickness of mucus (sputum) by reducing oxidized sulfur bonds between mucus proteins, breaking them up. In the respiratory tract, this effect allows for better mucociliary clearance (the self-cleaning mechanism within the airways) so mucus can be more effectively expelled from the lungs.^[15]

N-acetylcysteine also appears to modulate glutamate and dopamine neurotransmission in a way that may be beneficial for certain neuropsychiatric disorders such as schizophrenia and substance use disorder. However, further research is needed to support these effects.^[20]

NAC is safe and effective at reasonable doses through oral supplementation. The most common side effects from oral NAC include nausea, vomiting, and diarrhea.^[1][40] Due to the sulfur content of NAC, supplements can have an unpleasant rotten-egg odor.^[1] When inhaled, NAC may cause cough and bronchospasm (constriction of the airways).^[2]

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 breakdown (hemolysis), low blood platelet count (thrombocytopenia), kidney failure, and possibly death.^[46]