N-Acetylcysteine

Last Updated: November 30, 2023

N-acetylcysteine (NAC) is a precursor for the amino acid L-cysteine. It has antioxidant, anti-inflammatory, and mucus thinning properties. NAC can act as a direct antioxidant, but more importantly, it provides the cysteine required for the production of glutathione, a powerful antioxidant produced in the body. NAC is commonly taken as a supplement for health and wellness and is used in clinical settings to treat drug overdose, cystic fibrosis, and chronic obstructive pulmonary disease.

N-Acetylcysteine is most often used for

What is N-acetylcysteine?

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.

What are N-acetylcysteine’s main benefits?

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]

How does N-acetylcysteine work?

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]

What are N-acetylcysteine’s main drawbacks?

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]

What else is N-Acetylcysteine known as?
Note that N-Acetylcysteine is also known as:
  • N-Acetyl Cysteine
  • NAC
  • N-Ac
Dosage information

N-acetylcysteine can be given orally, intravenously, topically, or through inhalation.[1] Research suggests that in order to achieve the mucolytic effects in the respiratory tract, NAC needs to be administered through inhalation. Alternatively, oral or intravenous administration is the best way to benefit from NAC’s antioxidant effects.[2]

The suggested dosage of NAC depends on what it’s being used for and the route through which it’s being administered. Orally, NAC is most often given in the dosage range of 600–1,800 mg daily (often divided into two or three daily doses), although higher doses are sometimes used in clinical research. Further research is needed to determine the optimal therapeutic dosages for other uses and methods.

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Update History
2023-08-21 00:30:03

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We added some extra studies related to liver enzymes to this database

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References
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Examine Database References
  1. Cocaine Addiction Symptoms - LaRowe SD, Mardikian P, Malcolm R, Myrick H, Kalivas P, McFarland K, Saladin M, McRae A, Brady KSafety and tolerability of N-acetylcysteine in cocaine-dependent individualsAm J Addict.(2006 Jan-Feb)
  2. Mineral Bioaccumulation - Kasperczyk S, Dobrakowski M, Kasperczyk A, Ostałowska A, Birkner EThe administration of N-acetylcysteine reduces oxidative stress and regulates glutathione metabolism in the blood cells of workers exposed to leadClin Toxicol (Phila).(2013 Jul)
  3. Anaerobic Capacity - Cobley JN, McGlory C, Morton JP, Close GLN-Acetylcysteine Attenuates Fatigue Following Repeated-Bouts of Intermittent Exercise: Practical Implications for Tournament SituationsInt J Sport Nutr Exerc Metab.(2011 Aug 29)
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  17. Urinary NOx - Dimitrios Tsikas, Jonas Niemann, Markus Flentje, Alexandra Schwarz, Paschalis TossiosN-Acetylcysteine (NAC) inhibits renal nitrite and nitrate reabsorption in healthy subjects and in patients undergoing cardiac surgery: risk of nitric oxide (NO) bioavailability loss by NAC?Int J Cardiol.(2014 Nov 15)
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  27. Liver Enzymes - Jia D, Guo S, Jia Z, Gao Z, You K, Gong J, Li SN-acetylcysteine in the Donor, Recipient, or Both Donor and Recipient in Liver Transplantation: A Systematic Review With Meta-analysis and Trial Sequential Analysis.Transplantation.(2023-May-08)
  28. Length of hospitalization - Pereira JEG, El Dib R, Braz LG, Escudero J, Hayes J, Johnston BCN-acetylcysteine use among patients undergoing cardiac surgery: A systematic review and meta-analysis of randomized trials.PLoS One.(2019)
  29. Cycling Performance - Rhodes K, Braakhuis APerformance and Side Effects of Supplementation with N-Acetylcysteine: A Systematic Review and Meta-Analysis.Sports Med.(2017-Aug)
  30. Depression Symptoms - Nery FG, Li W, DelBello MP, Welge JAN-acetylcysteine as an adjunctive treatment for bipolar depression: A systematic review and meta-analysis of randomized controlled trials.Bipolar Disord.(2021-11)
  31. Rate Of Pregnancy - Devi N, Boya C, Chhabra M, Bansal D-acetyl-cysteine as adjuvant therapy in female infertility: a systematic review and meta-analysis.J Basic Clin Physiol Pharmacol.(2020-Nov-19)
  32. Testosterone - Zahra Shahveghar Asl, Karim Parastouei, Eslam EskandariThe effects of N-acetylcysteine on ovulation and sex hormones profile in women with polycystic ovary syndrome: a systematic review and meta-analysisBr J Nutr.(2023 Jan 4)
  33. Neuropathic Pain Symptoms - Mohiuddin M, Pivetta B, Gilron I, Khan JSEfficacy and Safety of N-Acetylcysteine for the Management of Chronic Pain in Adults: A Systematic Review and Meta-Analysis.Pain Med.(2021-Dec-11)
  34. Forced Vital Capacity - Rogliani P, Calzetta L, Cavalli F, Matera MG, Cazzola MPirfenidone, nintedanib and N-acetylcysteine for the treatment of idiopathic pulmonary fibrosis: A systematic review and meta-analysis.Pulm Pharmacol Ther.(2016-Oct)
  35. Hearing Loss - Kranzer K, Elamin WF, Cox H, Seddon JA, Ford N, Drobniewski FA systematic review and meta-analysis of the efficacy and safety of N-acetylcysteine in preventing aminoglycoside-induced ototoxicity: implications for the treatment of multidrug-resistant TB.Thorax.(2015-Nov)
  36. Hearing Loss - Chang PH, Liu CW, Hung SH, Kang YNEffect of N-acetyl-cysteine in prevention of noise-induced hearing loss: a systematic review and meta-analysis of randomized controlled trials.Arch Med Sci.(2022)
  37. Hearing Loss - Bai X, Wang M, Niu X, Yu H, Yue JX, Sun YEffect of N-acetyl-cysteine treatment on sensorineural hearing loss: a meta-analysis.World J Otorhinolaryngol Head Neck Surg.(2022-Sep)