Acetylcysteine

{{Main|Paracetamol poisoning}}

Intravenous and oral formulations of acetylcysteine are available for the treatment of paracetamol (acetaminophen) overdose.{{cite journal | vauthors = Green JL, Heard KJ, Reynolds KM, Albert D | title = Oral and Intravenous Acetylcysteine for Treatment of Acetaminophen Toxicity: A Systematic Review and Meta-analysis | journal = The Western Journal of Emergency Medicine | volume = 14 | issue = 3 | pages = 218–226 | date = May 2013 | pmid = 23687539 | pmc = 3656701 | doi = 10.5811/westjem.2012.4.6885 }} When paracetamol is taken in large quantities, a minor metabolite called N-acetyl-p-benzoquinone imine (NAPQI) accumulates within the body. It is normally conjugated by glutathione, but when taken in excess, the body's glutathione reserves are not sufficient to deactivate the toxic NAPQI. This metabolite is then free to react with key hepatic enzymes, thereby damaging liver cells. This may lead to severe liver damage and even death by acute liver failure.

In the treatment of paracetamol (acetaminophen) overdose, acetylcysteine acts to maintain or replenish depleted glutathione reserves in the liver and enhance non-toxic metabolism of acetaminophen.{{cite web|title=Acetadote Package Insert|url=http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021539s004lbl.pdf|publisher=FDA|access-date=19 April 2014|url-status=live|archive-url=https://web.archive.org/web/20130825114200/http://www.accessdata.fda.gov/drugsatfda_docs/label/2006/021539s004lbl.pdf|archive-date=25 August 2013}} These actions serve to protect liver cells from NAPQI toxicity. It is most effective in preventing or lessening hepatic injury when administered within 8–10 hours after overdose. Research suggests that the rate of liver toxicity is approximately 3% when acetylcysteine is administered within 10 hours of overdose.

Although IV and oral acetylcysteine are equally effective for this indication, oral administration is generally poorly tolerated due to the higher dosing required to overcome its low oral bioavailability,{{cite journal | vauthors = Borgström L, Kågedal B, Paulsen O | title = Pharmacokinetics of N-acetylcysteine in man | journal = European Journal of Clinical Pharmacology | volume = 31 | issue = 2 | pages = 217–222 | date = 1986 | pmid = 3803419 | doi = 10.1007/bf00606662 | s2cid = 41004554 }} its foul taste and odor, and a higher incidence of adverse effects when taken orally, particularly nausea and vomiting. Prior pharmacokinetic studies of acetylcysteine did not consider acetylation as a reason for the low bioavailability of acetylcysteine.{{cite journal | vauthors = Dilger RN, Baker DH | title = Oral N-acetyl-L-cysteine is a safe and effective precursor of cysteine | journal = Journal of Animal Science | volume = 85 | issue = 7 | pages = 1712–1718 | date = July 2007 | pmid = 17371789 | doi = 10.2527/jas.2006-835 }} Oral acetylcysteine is identical in bioavailability to cysteine precursors. However, 3% to 6% of people given intravenous acetylcysteine show a severe, anaphylaxis-like allergic reaction, which may include extreme breathing difficulty (due to bronchospasm), a decrease in blood pressure, rash, angioedema, and sometimes also nausea and vomiting.{{cite journal | vauthors = Kanter MZ | title = Comparison of oral and i.v. acetylcysteine in the treatment of acetaminophen poisoning | journal = American Journal of Health-System Pharmacy | volume = 63 | issue = 19 | pages = 1821–1827 | date = October 2006 | pmid = 16990628 | doi = 10.2146/ajhp060050 | s2cid = 9209528 }} Repeated doses of intravenous acetylcysteine will cause these allergic reactions to progressively worsen in these people.

Several studies have found this anaphylaxis-like reaction to occur more often in people given intravenous acetylcysteine despite serum levels of paracetamol not high enough to be considered toxic.{{cite journal | vauthors = Dawson AH, Henry DA, McEwen J | title = Adverse reactions to N-acetylcysteine during treatment for paracetamol poisoning | journal = The Medical Journal of Australia | volume = 150 | issue = 6 | pages = 329–331 | date = March 1989 | pmid = 2716644 | doi = 10.5694/j.1326-5377.1989.tb136496.x | s2cid = 40296724 }}{{cite journal | vauthors = Bailey B, McGuigan MA | title = Management of anaphylactoid reactions to intravenous N-acetylcysteine | journal = Annals of Emergency Medicine | volume = 31 | issue = 6 | pages = 710–715 | date = June 1998 | pmid = 9624310 | doi = 10.1016/S0196-0644(98)70229-X }}{{cite journal | vauthors = Schmidt LE, Dalhoff K | title = Risk factors in the development of adverse reactions to N-acetylcysteine in patients with paracetamol poisoning | journal = British Journal of Clinical Pharmacology | volume = 51 | issue = 1 | pages = 87–91 | date = January 2001 | pmid = 11167669 | pmc = 2014432 | doi = 10.1046/j.1365-2125.2001.01305.x }}{{cite journal | vauthors = Lynch RM, Robertson R | title = Anaphylactoid reactions to intravenous N-acetylcysteine: a prospective case controlled study | journal = Accident and Emergency Nursing | volume = 12 | issue = 1 | pages = 10–15 | date = January 2004 | pmid = 14700565 | doi = 10.1016/j.aaen.2003.07.001 }}

Acetylcysteine exhibits mucolytic properties, meaning it reduces the viscosity and adhesiveness of mucus. This therapeutic effect is achieved through the cleavage of disulfide bonds{{cite journal | vauthors = Pedre B, Barayeu U, Ezeriņa D, Dick TP | title = The mechanism of action of N-acetylcysteine (NAC): The emerging role of H₂S and sulfane sulfur species | journal = Pharmacology & Therapeutics | volume = 228 | pages = 107916 | date = December 2021 | pmid = 34171332 | doi = 10.1016/j.pharmthera.2021.107916 | doi-access = free }} within mucoproteins (strongly cross-linked mucins),{{cite journal | vauthors = Raghu G, Berk M, Campochiaro PA, Jaeschke H, Marenzi G, Richeldi L, Wen FQ, Nicoletti F, Calverley PM | title = The Multifaceted Therapeutic Role of N-acetylcysteine (NAC) in Disorders Characterized by Oxidative Stress | journal = Current Neuropharmacology | volume = 19 | issue = 8 | pages = 1202–1224 | date = 2021 | pmid = 33380301 | pmc = 8719286 | doi = 10.2174/1570159X19666201230144109 }} thereby decreasing the mucus viscosity and facilitating its clearance from the respiratory tract. This mechanism is particularly beneficial in conditions characterized by excessive or thickened mucus,{{cite journal | vauthors = Schwalfenberg GK | title = N-acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks) | journal = Journal of Nutrition and Metabolism | volume = 2021 | pages = 9949453 | date = 2021 | pmid = 34221501 | pmc = 8211525 | doi = 10.1155/2021/9949453 | doi-access = free }} such as chronic obstructive pulmonary disease (COPD), cystic fibrosis, rhinitis or sinusitis.{{cite journal | vauthors = Saltagi MZ, Comer BT, Hughes S, Ting JY, Higgins TS | title = Management of Recurrent Acute Rhinosinusitis: A Systematic Review | journal = American Journal of Rhinology & Allergy | volume = 35 | issue = 6 | pages = 902–909 | date = November 2021 | pmid = 33622038 | doi = 10.1177/1945892421994999 }} Acetylcysteine can be administered as a part of a complex molecule, Thiamphenicol glycinate acetylcysteine, which also contains thiamphenicol, an antibiotic.{{cite journal | vauthors = Serra A, Schito GC, Nicoletti G, Fadda G | title = A therapeutic approach in the treatment of infections of the upper airways: thiamphenicol glycinate acetylcysteinate in sequential treatment (systemic-inhalatory route) | journal = International Journal of Immunopathology and Pharmacology | volume = 20 | issue = 3 | pages = 607–617 | date = 2007 | pmid = 17880774 | doi = 10.1177/039463200702000319 }}

Inhaled acetylcysteine has been used for mucolytic therapy in addition to other therapies in respiratory conditions with excessive and/or thick mucus production. It is also used post-operatively, as a diagnostic aid, and in tracheotomy care. It may be considered ineffective in cystic fibrosis.{{cite book | veditors = Rossi S | title = Australian Medicines Handbook | date = 2006 | location = Adelaide | publisher = Australian Medicines Handbook }} A 2013 Cochrane review in cystic fibrosis found no evidence of benefit.{{cite journal | vauthors = Tam J, Nash EF, Ratjen F, Tullis E, Stephenson A | title = Nebulized and oral thiol derivatives for pulmonary disease in cystic fibrosis | journal = The Cochrane Database of Systematic Reviews | volume = 2013 | issue = 7 | pages = CD007168 | date = July 2013 | pmid = 23852992 | pmc = 8078644 | doi = 10.1002/14651858.CD007168.pub3 | url = http://www.repository.heartofengland.nhs.uk/157/1/Nebulized%20and%20oral%20thiol%20derivatives%20for%20pulmonary%20disease%20in%20cystic%20fibrosis..pdf | access-date = 16 May 2018 | url-status = dead | archive-url = https://web.archive.org/web/20220327121154/http://www.repository.uhblibrary.co.uk/id/eprint/157/1/Nebulized%20and%20oral%20thiol%20derivatives%20for%20pulmonary%20disease%20in%20cystic%20fibrosis..pdf | archive-date = 27 March 2022 }}

Acetylcysteine is used in the treatment of obstructive lung disease as an adjuvant treatment.{{cite journal | vauthors = Grandjean EM, Berthet P, Ruffmann R, Leuenberger P | title = Efficacy of oral long-term N-acetylcysteine in chronic bronchopulmonary disease: a meta-analysis of published double-blind, placebo-controlled clinical trials | journal = Clinical Therapeutics | volume = 22 | issue = 2 | pages = 209–221 | date = February 2000 | pmid = 10743980 | doi = 10.1016/S0149-2918(00)88479-9 }}{{cite journal | vauthors = Stey C, Steurer J, Bachmann S, Medici TC, Tramèr MR | title = The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review | journal = The European Respiratory Journal | volume = 16 | issue = 2 | pages = 253–262 | date = August 2000 | pmid = 10968500 | doi = 10.1034/j.1399-3003.2000.16b12.x | title-link = doi | doi-access = free | citeseerx = 10.1.1.516.9510 }}{{cite journal | vauthors = Poole PJ, Black PN | title = Oral mucolytic drugs for exacerbations of chronic obstructive pulmonary disease: systematic review | journal = BMJ | volume = 322 | issue = 7297 | pages = 1271–1274 | date = May 2001 | pmid = 11375228 | pmc = 31920 | doi = 10.1136/bmj.322.7297.1271 }}

Acetylcysteine has been used to complex palladium, to help it dissolve in water. This helps to remove palladium from drugs or precursors synthesized by palladium-catalyzed coupling reactions.{{cite journal | vauthors = Garrett CE, Prasad K |title=The Art of Meeting Palladium Specifications in Active Pharmaceutical Ingredients Produced by Pd-Catalyzed Reactions |journal=Advanced Synthesis & Catalysis |volume=346 |pages=889–900 |year=2004 |doi=10.1002/adsc.200404071 |issue=8|s2cid=94929244 }} N-acetylcysteine can be used to protect the liver.{{citation |title=Acetylcysteine |url=https://livertox.nih.gov/Acetylcysteine.htm |website=livertox.nih.gov |date=2012 |pmid=31643176 |access-date=26 April 2019 |archive-date=25 April 2019 |archive-url=https://web.archive.org/web/20190425234436/https://livertox.nih.gov/Acetylcysteine.htm |url-status=live }}

Acetylcysteine can be used in Petroff's method of liquefaction and decontamination of sputum, in preparation for recovery of mycobacterium.{{cite journal | vauthors = Buijtels PC, Petit PL | title = Comparison of NaOH-N-acetyl cysteine and sulfuric acid decontamination methods for recovery of mycobacteria from clinical specimens | journal = Journal of Microbiological Methods | volume = 62 | issue = 1 | pages = 83–88 | date = July 2005 | pmid = 15823396 | doi = 10.1016/j.mimet.2005.01.010 }} It also displays significant antiviral activity against influenza A viruses.{{cite journal | vauthors = Geiler J, Michaelis M, Naczk P, Leutz A, Langer K, Doerr HW, Cinatl J | title = N-acetyl-L-cysteine (NAC) inhibits virus replication and expression of pro-inflammatory molecules in A549 cells infected with highly pathogenic H5N1 influenza A virus | journal = Biochemical Pharmacology | volume = 79 | issue = 3 | pages = 413–420 | date = February 2010 | pmid = 19732754 | doi = 10.1016/j.bcp.2009.08.025 | url = https://hal.archives-ouvertes.fr/hal-00538093/file/PEER_stage2_10.1016%252Fj.bcp.2009.08.025.pdf | access-date = 14 October 2021 | url-status = live | archive-url = https://web.archive.org/web/20240806002728/https://hal.archives-ouvertes.fr/hal-00538093/file/PEER_stage2_10.1016%252Fj.bcp.2009.08.025.pdf | archive-date = 6 August 2024 }}

Acetylcysteine has bactericidal properties and breaks down bacterial biofilms of clinically relevant pathogens including Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus faecalis, Enterobacter cloacae, Staphylococcus epidermidis, and Klebsiella pneumoniae.{{cite journal | vauthors = Aslam S, Darouiche RO | title = Role of antibiofilm-antimicrobial agents in controlling device-related infections | journal = The International Journal of Artificial Organs | volume = 34 | issue = 9 | pages = 752–758 | date = September 2011 | pmid = 22094553 | pmc = 3251652 | doi = 10.5301/ijao.5000024 }}

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The most commonly reported adverse effects for IV formulations of acetylcysteine are rash, urticaria, and itchiness.

Adverse effects for inhalational formulations of acetylcysteine include nausea, vomiting, stomatitis, fever, rhinorrhea, drowsiness, clamminess, chest tightness, and bronchoconstriction. Although infrequent, bronchospasm has been reported to occur unpredictably in some patients.{{cite web|title=Mucomyst Package Insert|url=http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d2dc24f3-3ad7-4c6c-8e9f-7202d9a146f7|access-date=20 April 2014|url-status=live|archive-url=https://web.archive.org/web/20140421050640/http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=d2dc24f3-3ad7-4c6c-8e9f-7202d9a146f7|archive-date=21 April 2014}}

Adverse effects for oral formulations of acetylcysteine have been reported to include nausea, vomiting, rash, and fever.

Large doses in a mouse model showed that acetylcysteine could potentially cause damage to the heart and lungs.{{cite journal | vauthors = Palmer LA, Doctor A, Chhabra P, Sheram ML, Laubach VE, Karlinsey MZ, Forbes MS, Macdonald T, Gaston B | title = S-nitrosothiols signal hypoxia-mimetic vascular pathology | journal = The Journal of Clinical Investigation | volume = 117 | issue = 9 | pages = 2592–2601 | date = September 2007 | pmid = 17786245 | pmc = 1952618 | doi = 10.1172/JCI29444 }} They found that acetylcysteine was metabolized to S-nitroso-N-acetylcysteine ({{vanchor|SNOAC}}), which increased blood pressure in the lungs and right ventricle of the heart (pulmonary artery hypertension) in mice treated with acetylcysteine. The effect was similar to that observed following a 3-week exposure to an oxygen-deprived environment (chronic hypoxia). The authors also found that SNOAC induced a hypoxia-like response in the expression of several important genes both in vitro and in vivo. The implications of these findings for long-term treatment with acetylcysteine have not yet been investigated. The dose used by Palmer and colleagues was dramatically higher than that used in humans, the equivalent of about 20 grams per day. In humans, much lower dosages (600 mg per day) have been observed to counteract some age-related decline in the hypoxic ventilatory response as tested by inducing prolonged hypoxia.{{cite journal | vauthors = Hildebrandt W, Alexander S, Bärtsch P, Dröge W | title = Effect of N-acetyl-cysteine on the hypoxic ventilatory response and erythropoietin production: linkage between plasma thiol redox state and O(2) chemosensitivity | journal = Blood | volume = 99 | issue = 5 | pages = 1552–1555 | date = March 2002 | pmid = 11861267 | doi = 10.1182/blood.V99.5.1552 | s2cid = 24375953 | title-link = doi | doi-access = free }}

Although N-acetylcysteine prevented liver damage in mice when taken before alcohol, when taken four hours after alcohol it made liver damage worse in a dose-dependent fashion.{{cite journal | vauthors = Wang AL, Wang JP, Wang H, Chen YH, Zhao L, Wang LS, Wei W, Xu DX | title = A dual effect of N-acetylcysteine on acute ethanol-induced liver damage in mice | journal = Hepatology Research | volume = 34 | issue = 3 | pages = 199–206 | date = March 2006 | pmid = 16439183 | doi = 10.1016/j.hepres.2005.12.005 }}

Acetylcysteine serves as a prodrug to L-cysteine, a precursor to the biologic antioxidant glutathione. Hence administration of acetylcysteine replenishes glutathione stores.{{cite web|title=Product Information: Aceradote Concentrated Injection|work=TGA eBusiness Services|publisher=Phebra Pty Ltd|url=https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-03960-3|format=PDF|date=16 January 2013|access-date=8 November 2013|url-status=live|archive-url=https://web.archive.org/web/20170908143219/https://www.ebs.tga.gov.au/ebs/picmi/picmirepository.nsf/pdf?OpenAgent&id=CP-2010-PI-03960-3|archive-date=8 September 2017}}

• Glutathione, along with oxidized glutathione (GSSG) and S-nitrosoglutathione (GSNO), have been found to bind to the glutamate recognition site of the NMDA and AMPA receptors (via their γ-glutamyl moieties), and may be endogenous neuromodulators.{{cite journal | vauthors = Steullet P, Neijt HC, Cuénod M, Do KQ | title = Synaptic plasticity impairment and hypofunction of NMDA receptors induced by glutathione deficit: relevance to schizophrenia | journal = Neuroscience | volume = 137 | issue = 3 | pages = 807–819 | date = February 2006 | pmid = 16330153 | doi = 10.1016/j.neuroscience.2005.10.014 | s2cid = 1417873 }}{{cite journal | vauthors = Varga V, Jenei Z, Janáky R, Saransaari P, Oja SS | title = Glutathione is an endogenous ligand of rat brain N-methyl-D-aspartate (NMDA) and 2-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors | journal = Neurochemical Research | volume = 22 | issue = 9 | pages = 1165–1171 | date = September 1997 | pmid = 9251108 | doi = 10.1023/A:1027377605054 | s2cid = 24024090 }} At millimolar concentrations, they may also modulate the redox state of the NMDA receptor complex. In addition, glutathione has been found to bind to and activate ionotropic receptors that are different from any other excitatory amino acid receptor, and which may constitute glutathione receptors, potentially making it a neurotransmitter.{{cite journal | vauthors = Oja SS, Janáky R, Varga V, Saransaari P | title = Modulation of glutamate receptor functions by glutathione | journal = Neurochemistry International | volume = 37 | issue = 2–3 | pages = 299–306 | year = 2000 | pmid = 10812215 | doi = 10.1016/S0197-0186(00)00031-0 | s2cid = 44380765 }} As such, since N-acetylcysteine is a prodrug of glutathione, it may modulate all of the aforementioned receptors as well.
• Glutathione also modulates the NMDA receptor by acting at the redox site.{{cite journal | vauthors = Lavoie S, Murray MM, Deppen P, Knyazeva MG, Berk M, Boulat O, Bovet P, Bush AI, Conus P, Copolov D, Fornari E, Meuli R, Solida A, Vianin P, Cuénod M, Buclin T, Do KQ | title = Glutathione precursor, N-acetyl-cysteine, improves mismatch negativity in schizophrenia patients | journal = Neuropsychopharmacology | volume = 33 | issue = 9 | pages = 2187–2199 | date = August 2008 | pmid = 18004285 | doi = 10.1038/sj.npp.1301624 | hdl-access = free | title-link = doi | doi-access = free | hdl = 10536/DRO/DU:30071388 }}

L-cysteine also serves as a precursor to cystine, which in turn serves as a substrate for the cystine-glutamate antiporter on astrocytes; hence there is increasing glutamate release into the extracellular space. This glutamate in turn acts on mGluR_2/3 receptors, and at higher doses of acetylcysteine, mGluR₅.{{cite journal | vauthors = Dodd S, Dean O, Copolov DL, Malhi GS, Berk M | title = N-acetylcysteine for antioxidant therapy: pharmacology and clinical utility | journal = Expert Opinion on Biological Therapy | volume = 8 | issue = 12 | pages = 1955–1962 | date = December 2008 | pmid = 18990082 | doi = 10.1517/14728220802517901 | s2cid = 74736842 }}{{cite journal | vauthors = Kupchik YM, Moussawi K, Tang XC, Wang X, Kalivas BC, Kolokithas R, Ogburn KB, Kalivas PW | title = The effect of N-acetylcysteine in the nucleus accumbens on neurotransmission and relapse to cocaine | journal = Biological Psychiatry | volume = 71 | issue = 11 | pages = 978–986 | date = June 2012 | pmid = 22137594 | pmc = 3340445 | doi = 10.1016/j.biopsych.2011.10.024 }} Acetylcysteine may have other biological functions in the brain, such as the modulation of dopamine release and the reduction in inflammatory cytokine formation possibly via inhibiting NF-κB and modulating cytokine synthesis. These properties, along with the reduction of oxidative stress and the re-establishment of glutamatergic balance, would lead to an increase in growth factors, such as brain-derived neurotrophic factor (BDNF), and the regulation of neuronal cell death through B-cell lymphoma 2 expression (BLC-2).

The oral bioavailability of acetylcysteine is relatively low due to extensive first-pass metabolism in the gut wall and liver. It ranges between 6% and 10%.

Intravenous administration of acetylcysteine bypasses the first-pass metabolism, resulting in higher bioavailability compared to oral administration. Intravenous administration of acetylcysteine ensures nearly 100% bioavailability as it directly enters the bloodstream.

Acetylcysteine is extensively liver metabolized, CYP450 minimal, urine excretion is 22–30% with a half-life of 5.6 hours in adults and 11 hours in newborns.{{medical citation needed|date=August 2024}}

Acetylcysteine is the N-acetyl derivative of the amino acid L-cysteine, and is a precursor in the formation of the antioxidant glutathione in the body. The thiol (sulfhydryl) group confers antioxidant effects and is able to reduce free radicals.

Pure acetylcysteine is in a solid state at room temperature, appearing as a white crystalline powder or granules.{{cite journal| doi=10.1515/jbcpp-2020-0099 | title=An insight on safety, efficacy, and molecular docking study reports of N-acetylcysteine and its compound formulations | date=2022 | journal=Journal of Basic and Clinical Physiology and Pharmacology | volume=33 | issue=3 | pages=223–233 | pmid=33638319 | vauthors = Rind L, Ahmad M, Khan MI, Badruddeen, Akhtar J, Ahmad U, Yadav C, Owais M }} The solid form of acetylcysteine is stable under normal conditions, but it can undergo oxidation if exposed to air or moisture over time, leading to the formation of its dimeric form, diacetylcysteine, which can have different properties.{{cite book|isbn=978-3-319-28570-2|doi=10.1007/978-3-319-28570-2_4 |chapter=N-Acetylcysteine |title=Utility of Bromelain and N-Acetylcysteine in Treatment of Peritoneal Dissemination of Gastrointestinal Mucin-Producing Malignancies |date=2016 |pages=81–98 | vauthors = Amini A, Masoumi-Moghaddam S, Morris DL }} Acetylcysteine is highly hygroscopic, i.e., it absorbs moisture if exposed to open air.

Acetylcysteine can sometimes appear as a light yellow cast powder instead of pure white due to oxidation. The sulfur-containing amino acids, like cysteine, are more easily oxidized than other amino acids. When exposed to air or moisture, acetylcysteine can oxidize, leading to a slight yellowish tint.

Acetylcysteine in a form of a white or white with light yellow cast powder has a pK_a of 9.5 at 30 °C.{{cite web|title=N-Acetyl-L-cysteine Product Information |url=https://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Sigma-Aldrich/Product_Information_Sheet/a7250pis.pdf |website=Sigma |publisher=Sigma-Aldrich |access-date=9 November 2014 |url-status=dead |archive-url=https://web.archive.org/web/20140611120709/http://www.sigmaaldrich.com/content/dam/sigma-aldrich/docs/Sigma-Aldrich/Product_Information_Sheet/a7250pis.pdf |archive-date=11 June 2014 }}

N-acetyl-L-cysteine is soluble in water and alcohol, and practically insoluble in chloroform and ether.{{cite web|title=N-Acetyl-L-cysteine {{pipe}} C₅H₉NO₃S|work = PubChem |publisher=National Center for Biotechnology Information, U.S. National Library of Medicine |url=https://pubchem.ncbi.nlm.nih.gov/compound/N-acetyl-L-cysteine#section=Chemical-and-Physical-Properties|access-date=22 July 2016|url-status=live|archive-url=https://web.archive.org/web/20160816171151/https://pubchem.ncbi.nlm.nih.gov/compound/N-acetyl-L-cysteine#section=Chemical-and-Physical-Properties|archive-date=16 August 2016}}

Acetylcysteine is highly soluble in water: it dissolves readily in water, forming a clear solution. The pH of a maximum-saturated acetylcysteine solution typically ranges between 6.0 and 7.5,{{cite web | url=http://ftp.uspbpep.com/v29240/usp29nf24s0_m780.html?form=MG0AV3 | title=USP Monographs: Acetylcysteine Solution }} depending on temperature, purity of the compound, presence of other ions (that can affect the pH by interacting with acetylcysteine or altering the overall ionic strength of the solution), thus on the concentration of acetylcysteine itself: higher concentrations of acetylcysteine can lead to a lower pH due to the increased presence of the acetylcysteine molecule itself. This range of pH between 6.0 and 7.5 ensures that the solution is neither too acidic nor too alkaline, making it suitable for various medical applications. Aqueous solutions of acetylcysteine are compatible with 0.9% sodium chloride solution; compatibility with 5% and 10% glucose solutions is also good.

As for the sunlight stability, acetylcysteine in dry powder form is relatively stable and does not degrade quickly when exposed to sunlight, but when dissolved in aqueous solution, acetylcysteine can degrade when exposed to sunlight, especially if the solution is not stored in a dark, cool place. Besides that, acetylcysteine in aqueous solution can undergo hydrolysis, leading to the breakdown of the amide bond in the molecule. Still, aqueous solutions of acetylcysteine are generally stable when stored properly: the solutions should be kept in tightly sealed containers and stored at controlled room temperature to prolong the stability.{{cite journal|doi=10.2146/ajhp100214 |title=Stability of extemporaneously prepared acetylcysteine 1% and 10% solutions for treatment of meconium ileus |date=2011 |journal=American Journal of Health-System Pharmacy |volume=68 |pages=69–72 |pmid=21164069 | vauthors = Fohl AL, Johnson CE, Cober MP |issue=1 }}

File:Acetylcysteine Life Extension.jpg]]

Acetylcysteine was first studied as a drug in 1963. Amazon removed acetylcysteine for sale in the US in 2021, due to claims by the FDA of it being classified as a drug rather than a supplement.{{cite news |vauthors=Long J |date=6 May 2021 |title=Amazon confirms plans on removing NAC supplements |url=https://www.naturalproductsinsider.com/regulatory/amazon-confirms-plans-removing-nac-supplements |access-date=21 September 2023 |archive-date=16 May 2021 |archive-url=https://web.archive.org/web/20210516105959/https://www.naturalproductsinsider.com/regulatory/amazon-confirms-plans-removing-nac-supplements |url-status=live }}{{cite news | vauthors = Long J | date = 22 April 2021 | work = Natural Products Inside | url = https://www.naturalproductsinsider.com/regulatory/amazon-reportedly-removes-nac-containing-dietary-supplements | title = Amazon reportedly removes NAC-containing dietary supplements | access-date = 16 May 2021 | archive-date = 16 May 2021 | archive-url = https://web.archive.org/web/20210516121310/https://www.naturalproductsinsider.com/regulatory/amazon-reportedly-removes-nac-containing-dietary-supplements | url-status = live }}{{cite news |title=Warning Letter |work=benjaminmcevoy.com |url=https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/benjaminmcevoycom-607149-05142020 |publisher=U.S. Food and Drug Administration |access-date=3 May 2022 |archive-date=3 May 2022 |archive-url=https://web.archive.org/web/20220503215137/https://www.fda.gov/inspections-compliance-enforcement-and-criminal-investigations/warning-letters/benjaminmcevoycom-607149-05142020 |url-status=live }}{{cite news |title=FDA Sends Warning Letters to Seven Companies Illegally Selling Hangover Products |url=https://www.fda.gov/food/cfsan-constituent-updates/fda-sends-warning-letters-seven-companies-illegally-selling-hangover-products |access-date=3 May 2022 |archive-date=3 May 2022 |archive-url=https://web.archive.org/web/20220503215141/https://www.fda.gov/food/cfsan-constituent-updates/fda-sends-warning-letters-seven-companies-illegally-selling-hangover-products |url-status=live }} In April 2022, the FDA released draft guidance on FDA's policy regarding products labeled as dietary supplements that contain N-acetyl-L-cysteine.{{cite news|title=FDA Releases Draft Guidance on Enforcement Discretion for Certain NAC Products|url=https://www.fda.gov/food/cfsan-constituent-updates/fda-releases-draft-guidance-enforcement-discretion-certain-nac-products|access-date=3 May 2022|archive-date=3 May 2022|archive-url=https://web.archive.org/web/20220503215145/https://www.fda.gov/food/cfsan-constituent-updates/fda-releases-draft-guidance-enforcement-discretion-certain-nac-products|url-status=live}} Amazon subsequently re-listed NAC products as of August 2022.{{cite web | vauthors = Long J |title=Amazon resumes sales of NAC supplements |url=https://www.naturalproductsinsider.com/regulatory/amazon-resumes-sales-nac-supplements |website=Natural Products Insider |access-date=11 January 2023 |date=25 August 2022}}

While many antioxidants have been researched to treat a large number of diseases by reducing the negative effect of oxidative stress, acetylcysteine is one of the few that has yielded promising results, and is currently already approved for the treatment of paracetamol overdose.{{cite journal | vauthors = Head SI | title = Antioxidant therapy in a mouse model of Duchenne muscular dystrophy: some promising results but with a weighty caveat | journal = The Journal of Physiology | volume = 595 | issue = 23 | pages = 7015 | date = December 2017 | pmid = 29034480 | pmc = 5709324 | doi = 10.1113/jp275232 }}

• In mouse mdx models of Duchenne's muscular dystrophy, treatment with 1–2% acetylcysteine in drinking water significantly reduces muscle damage and improves strength.
• It is being studied in conditions such as autism, where cysteine and related sulfur amino acids may be depleted due to multifactorial dysfunction of methylation pathways involved in methionine catabolism.{{cite journal | vauthors = Gu F, Chauhan V, Chauhan A | title = Glutathione redox imbalance in brain disorders | journal = Current Opinion in Clinical Nutrition and Metabolic Care | volume = 18 | issue = 1 | pages = 89–95 | date = January 2015 | pmid = 25405315 | doi = 10.1097/MCO.0000000000000134 | s2cid = 25333289 }}
• Animal studies have also demonstrated its efficacy in reducing the damage associated with moderate traumatic brain or spinal injury, and also ischaemia-induced brain injury. In particular, it has been demonstrated to reduce neuronal losses and to improve cognitive and neurological outcomes associated with these traumatic events.
• Research on acetylcysteine usage seems to show a positive efficiency in treating androgenetic alopecia (male baldness), with or without adjacent treatments such as the use of topical minoxidil solution.{{cite journal|title= Efficacy and Tolerability of N-Acetyl-Cysteine for Treatment of The Early-onset Androgenetic Alopecia in Men|journal=QJM: An International Journal of Medicine|editor=Oxford University Press|issue=Suppl.1|date=October 2021|volume=114|doi=10.1093/qjmed/hcab093.024|author1=Mahira Hamdy El Sayed|author2=Marwa Yassin Soltan|author3=Ahmed Sadek|author4=Mohamed Abo Shabana Hussein Mohamed}}
• Research on mouse models also shows that acetylcysteine could be "used as an efficient and safe therapeutic option for hair loss induced by chemotherapy".{{cite journal |author=Yomna F Hassan, Dalia A Shabaan|title= Effect of N-acetylcysteine on hair follicle changes in mouse model of cyclophosphamide-induced alopecia: histological and biochemical study|journal= Histochemistry and Cell Biology|volume=161|date=20 April 2024|issue= 6|pages=477–491|pmid= 38641701|pmc=11162382|doi=10.1007/s00418-024-02282-0}}
• It has been suggested that acetylcysteine may help people with aspirin-exacerbated respiratory disease by increasing levels of glutathione allowing faster breakdown of salicylates, although there is no evidence that it is of benefit.{{cite journal | vauthors = Bachert C, Hörmann K, Mösges R, Rasp G, Riechelmann H, Müller R, Luckhaupt H, Stuck BA, Rudack C | title = An update on the diagnosis and treatment of sinusitis and nasal polyposis | journal = Allergy | volume = 58 | issue = 3 | pages = 176–191 | date = March 2003 | pmid = 12653791 | doi = 10.1034/j.1398-9995.2003.02172.x | s2cid = 35319457 | title-link = doi | doi-access = }}
• Small studies have shown acetylcysteine to be of benefit to people with blepharitis.{{cite journal | vauthors = Aitio ML | title = N-acetylcysteine -- passe-partout or much ado about nothing? | journal = British Journal of Clinical Pharmacology | volume = 61 | issue = 1 | pages = 5–15 | date = January 2006 | pmid = 16390346 | pmc = 1884975 | doi = 10.1111/j.1365-2125.2005.02523.x }} It has been shown to reduce ocular soreness caused by Sjögren's syndrome.{{cite journal | vauthors = Williamson J, Doig WM, Forrester JV, Tham MH, Wilson T, Whaley K, Dick WC | title = Management of the dry eye in Sjogren's syndrome | journal = The British Journal of Ophthalmology | volume = 58 | issue = 9 | pages = 798–805 | date = September 1974 | pmid = 4433493 | pmc = 1215027 | doi = 10.1136/bjo.58.9.798 }}
• Research has found that acetylcysteine may have otoprotective properties and could potentially be useful for preventing hearing loss and tinnitus in some cases.{{cite book | vauthors = Schlee W, Langguth B, Ridder DD, Vanneste S, Kleinjung T, Møller AR |title=Textbook of Tinnitus |publisher=Springer |year=2024 |edition=2nd |isbn=978-3-031-35646-9 |page=394, 620}}{{cite journal | vauthors = Chang PH, Liu CW, Hung SH, Kang YN | title = Effect of N-acetyl-cysteine in prevention of noise-induced hearing loss: a systematic review and meta-analysis of randomized controlled trials | journal = Archives of Medical Science | volume = 18 | issue = 6 | pages = 1535–1541 | date = 2022 | pmid = 36457967 | pmc = 9710288 | doi = 10.5114/aoms/109126 }} A 2011 study showed that N-acetylcysteine may protect the human cochlea from subclinical hearing loss caused by loud noises such as impulse noise.{{cite journal | vauthors = Lindblad AC, Rosenhall U, Olofsson A, Hagerman B | title = The efficacy of N-acetylcysteine to protect the human cochlea from subclinical hearing loss caused by impulse noise: a controlled trial | journal = Noise & Health | volume = 13 | issue = 55 | pages = 392–401 | date = November–December 2011 | pmid = 22122955 | doi = 10.4103/1463-1741.90293 | title-link = doi | doi-access = free }} In animal models, it reduced age-related hearing loss.{{citation needed|date=July 2024}}
• It has been shown effective in the treatment of Unverricht-Lundborg disease in an open trial in four patients. A marked decrease in myoclonus and some normalization of somatosensory evoked potentials with acetylcysteine treatment has been documented.{{cite journal | vauthors = Edwards MJ, Hargreaves IP, Heales SJ, Jones SJ, Ramachandran V, Bhatia KP, Sisodiya S | title = N-acetylcysteine and Unverricht-Lundborg disease: variable response and possible side effects | journal = Neurology | volume = 59 | issue = 9 | pages = 1447–1449 | date = November 2002 | pmid = 12427904 | doi = 10.1212/wnl.59.9.1447 }}{{EMedicine|article|1153370|Ataxia with Identified Genetic and Biochemical Defects}}
• Addiction to certain addictive drugs (including cocaine, heroin, alcohol, and nicotine) is correlated with a persistent reduction in the expression of excitatory amino acid transporter 2 (EAAT2) in the nucleus accumbens (NAcc); the reduced expression of EAAT2 in this region is implicated in addictive drug-seeking behavior. In particular, the long-term dysregulation of glutamate neurotransmission in the NAcc of long-term, drug-dependent users is associated with an increase in vulnerability to relapse after re-exposure to the addictive drug or its associated drug cues. Drugs that help to normalize the expression of EAAT2 in this region, such as N-acetylcysteine, have been proposed as an adjunct therapy for the treatment of addiction to cocaine, nicotine, alcohol, and other drugs.
• It has been tested for the reduction of hangover symptoms, though the overall results indicate very limited efficacy.{{ClinicalTrialsGov|NCT02541422|Use of NAC in Alleviation of Hangover Symptoms – Study Results}}{{cite journal | vauthors = Coppersmith V, Hudgins S, Stoltzfus J, Stankewicz H | title = The use of N-acetylcysteine in the prevention of hangover: a randomized trial | journal = Scientific Reports | volume = 11 | issue = 1 | pages = 13397 | date = June 2021 | pmid = 34183702 | pmc = 8238992 | doi = 10.1038/s41598-021-92676-0 | s2cid = 235673455 | bibcode = 2021NatSR..1113397C }}
• A double-blind placebo controlled trial of 262 patients has shown NAC treatment was well-tolerated and resulted in a significant decrease in the frequency of influenza-like episodes, severity, and length of time confined to bed.{{cite journal | vauthors = De Flora S, Grassi C, Carati L | title = Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment | journal = The European Respiratory Journal | volume = 10 | issue = 7 | pages = 1535–1541 | date = July 1997 | pmid = 9230243 | doi = 10.1183/09031936.97.10071535 | title-link = doi | doi-access = free }}

N-acetylcysteine has been widely believed to prevent adverse effects of long term Ketamine use on the bladder and kidneys, and there is growing body of evidence to support this.{{cite journal | vauthors = Ryu CM, Shin JH, Yu HY, Ju H, Kim S, Lim J, Heo J, Lee S, Shin DM, Choo MS | title = N-acetylcysteine prevents bladder tissue fibrosis in a lipopolysaccharide-induced cystitis rat model | journal = Scientific Reports | volume = 9 | issue = 1 | pages = 8134 | date = May 2019 | pmid = 31148586 | pmc = 6544636 | doi = 10.1038/s41598-019-44631-3 | bibcode = 2019NatSR...9.8134R }}

Evidence for the benefit of acetylcysteine to prevent radiocontrast induced kidney disease is mixed.{{cite journal | vauthors = Pistolesi V, Regolisti G, Morabito S, Gandolfini I, Corrado S, Piotti G, Fiaccadori E | title = Contrast medium induced acute kidney injury: a narrative review | journal = Journal of Nephrology | volume = 31 | issue = 6 | pages = 797–812 | date = December 2018 | pmid = 29802583 | doi = 10.1007/s40620-018-0498-y | s2cid = 44128861 }}

Acetylcysteine has been used for cyclophosphamide-induced haemorrhagic cystitis, although mesna is generally preferred due to the ability of acetylcysteine to diminish the effectiveness of cyclophosphamide.{{cite web |title=Hemorrhagic Cystitis Treatment & Management: Approach Considerations, Clot Evacuation, Bladder Irrigation Agents |url=https://emedicine.medscape.com/article/2056130-treatment#d12 |access-date=18 December 2019 |date=5 December 2019 |archive-date=29 October 2020 |archive-url=https://web.archive.org/web/20201029193235/https://emedicine.medscape.com/article/2056130-treatment#d12 |url-status=live }}

Acetylcysteine has been studied for major psychiatric disorders,{{cite journal | vauthors = Bartoli F, Cavaleri D, Bachi B, Moretti F, Riboldi I, Crocamo C, Carrà G | title = Repurposed drugs as adjunctive treatments for mania and bipolar depression: A meta-review and critical appraisal of meta-analyses of randomized placebo-controlled trials | journal = Journal of Psychiatric Research | volume = 143 | pages = 230–238 | date = November 2021 | pmid = 34509090 | doi = 10.1016/j.jpsychires.2021.09.018 | s2cid = 237485915 }}{{cite journal | vauthors = Bavarsad Shahripour R, Harrigan MR, Alexandrov AV | title = N-acetylcysteine (NAC) in neurological disorders: mechanisms of action and therapeutic opportunities | journal = Brain and Behavior | volume = 4 | issue = 2 | pages = 108–122 | date = March 2014 | pmid = 24683506 | pmc = 3967529 | doi = 10.1002/brb3.208 }} including bipolar disorder, major depressive disorder, and schizophrenia.{{cite journal | vauthors = Dean O, Giorlando F, Berk M | title = N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action | journal = Journal of Psychiatry & Neuroscience | volume = 36 | issue = 2 | pages = 78–86 | date = March 2011 | pmid = 21118657 | pmc = 3044191 | doi = 10.1503/jpn.100057 }}{{cite journal | vauthors = Berk M, Malhi GS, Gray LJ, Dean OM | title = The promise of N-acetylcysteine in neuropsychiatry | journal = Trends in Pharmacological Sciences | volume = 34 | issue = 3 | pages = 167–177 | date = March 2013 | pmid = 23369637 | doi = 10.1016/j.tips.2013.01.001 }}

Tentative evidence exists for N-acetylcysteine also in the treatment of Alzheimer's disease, autism, obsessive-compulsive disorder,{{cite journal | vauthors = Carollo M, Carollo N, Montan G | title = The promise of N-acetylcysteine in the treatment of obsessive-compulsive disorder | journal = CNS Neuroscience & Therapeutics | volume = 30 | issue = 2 | pages = e14653 | date = February 2024 | pmid = 38385640 | pmc = 10883097 | doi = 10.1111/cns.14653 }} specific drug addictions (cocaine), drug-induced neuropathy, trichotillomania, excoriation disorder, and a certain form of epilepsy (progressive myoclonic). Preliminary evidence showed efficacy in anxiety disorder, attention deficit hyperactivity disorder and mild traumatic brain injury although confirmatory studies are required.{{cite journal | vauthors = Slattery J, Kumar N, Delhey L, Berk M, Dean O, Spielholz C, Frye R | title = Clinical trials of N-acetylcysteine in psychiatry and neurology: A systematic review | journal = Neuroscience and Biobehavioral Reviews | volume = 55 | pages = 294–321 | date = August 2015 | pmid = 25957927 | doi = 10.1016/j.neubiorev.2015.04.015 | title-link = doi | doi-access = free }}{{cite journal | vauthors = Berk M, Dean OM, Cotton SM, Jeavons S, Tanious M, Kohlmann K, Hewitt K, Moss K, Allwang C, Schapkaitz I, Robbins J, Cobb H, Ng F, Dodd S, Bush AI, Malhi GS | title = The efficacy of adjunctive N-acetylcysteine in major depressive disorder: a double-blind, randomized, placebo-controlled trial | journal = The Journal of Clinical Psychiatry | volume = 75 | issue = 6 | pages = 628–636 | date = June 2014 | pmid = 25004186 | doi = 10.4088/JCP.13m08454 | title-link = doi | doi-access = free }}{{cite journal | vauthors = Oliver G, Dean O, Camfield D, Blair-West S, Ng C, Berk M, Sarris J | title = N-acetyl cysteine in the treatment of obsessive compulsive and related disorders: a systematic review | journal = Clinical Psychopharmacology and Neuroscience | volume = 13 | issue = 1 | pages = 12–24 | date = April 2015 | pmid = 25912534 | pmc = 4423164 | doi = 10.9758/cpn.2015.13.1.12 }}{{cite journal | vauthors = Samuni Y, Goldstein S, Dean OM, Berk M | title = The chemistry and biological activities of N-acetylcysteine | journal = Biochimica et Biophysica Acta (BBA) - General Subjects | volume = 1830 | issue = 8 | pages = 4117–4129 | date = August 2013 | pmid = 23618697 | doi = 10.1016/j.bbagen.2013.04.016 | hdl-access = free | s2cid = 2567773 | hdl = 11343/43874 }} Tentative evidence also supports use in cannabis use disorder.{{cite journal | vauthors = Minarini A, Ferrari S, Galletti M, Giambalvo N, Perrone D, Rioli G, Galeazzi GM | title = N-acetylcysteine in the treatment of psychiatric disorders: current status and future prospects | journal = Expert Opinion on Drug Metabolism & Toxicology | volume = 13 | issue = 3 | pages = 279–292 | date = March 2017 | pmid = 27766914 | doi = 10.1080/17425255.2017.1251580 | hdl-access = free | s2cid = 20873065 | hdl = 11380/1116466 }}

It is also being studied for use as a treatment of body-focused repetitive behavior.{{cite journal | vauthors = Hwang AS, Campbell EH, Sartori-Valinotti JC | title = Evidence of N-acetylcysteine efficacy for skin picking disorder: A retrospective cohort study | journal = Journal of the American Academy of Dermatology | volume = 87 | issue = 1 | pages = 148–150 | date = July 2022 | pmid = 34224772 | doi = 10.1016/j.jaad.2021.06.874 | s2cid = 235746237 | doi-access = free }}{{cite journal | vauthors = Popova L, Mancuso J | title = Dramatic Improvement of Trichotillomania with 6 Months of Treatment With N-acetylcysteine | journal = Global Pediatric Health | volume = 9 | pages = 2333794X221086576 | year = 2022 | pmid = 35647220 | pmc = 9133858 | doi = 10.1177/2333794X221086576 }}

Evidence to date does not support the efficacy for N-acetylcysteine in treating addictions to gambling, methamphetamine, or nicotine. Based upon limited evidence, NAC appears to normalize glutamate neurotransmission in the nucleus accumbens and other brain structures, in part by upregulating the expression of excitatory amino acid transporter 2 (EAAT2), {{aka}} glutamate transporter 1 (GLT1), in individuals with addiction.{{cite journal | vauthors = McClure EA, Gipson CD, Malcolm RJ, Kalivas PW, Gray KM | title = Potential role of N-acetylcysteine in the management of substance use disorders | journal = CNS Drugs | volume = 28 | issue = 2 | pages = 95–106 | date = February 2014 | pmid = 24442756 | pmc = 4009342 | doi = 10.1007/s40263-014-0142-x }} While NAC has been demonstrated to modulate glutamate neurotransmission in adult humans who are addicted to cocaine, NAC does not appear to modulate glutamate neurotransmission in healthy adult humans. NAC has been hypothesized to exert beneficial effects through its modulation of glutamate and dopamine neurotransmission as well as its antioxidant properties.

In bipolar disorder, N-acetylcysteine has been repurposed as an augmentation strategy for depressive episodes in light of the possible role of inflammation in the pathogenesis of mood disorders. Nonetheless, meta-analytic evidence shows that add-on N-acetylcysteine was more effective than placebo only in reducing depression scales scores (low quality evidence), without positive effects on response and remission outcomes, limiting its possible role in clinical practice to date.{{cite journal | vauthors = Nery FG, Li W, DelBello MP, Welge JA | title = N-acetylcysteine as an adjunctive treatment for bipolar depression: A systematic review and meta-analysis of randomized controlled trials | journal = Bipolar Disorders | volume = 23 | issue = 7 | pages = 707–714 | date = November 2021 | pmid = 33354859 | doi = 10.1111/bdi.13039 | s2cid = 229692736 }}

Acetylcysteine has been studied as a possible treatment for COVID-19, but has not improved patient outcomes by common measures.{{cite journal | vauthors = Paraskevas T, Kantanis A, Karalis I, Michailides C, Karamouzos V, Koniari I, Pierrakos C, Velissaris D | title = N-acetylcysteine efficacy in patients hospitalized with COVID-19 pneumonia: a systematic review and meta-analysis | journal = Romanian Journal of Internal Medicine | volume = 61 | issue = 1 | pages = 41–52 | date = March 2023 | pmid = 36627753 | doi = 10.2478/rjim-2023-0001 | doi-access = free }}{{cite journal | vauthors = Liu TH, Wu JY, Huang PY, Tsai YW, Hsu WH, Chuang MH, Tang HJ, Lai CC | title = Clinical efficacy of N-acetylcysteine for COVID-19: A systematic review and meta-analysis of randomized controlled trials | journal = Heliyon | volume = 10 | issue = 3 | pages = e25179 | date = February 2024 | pmid = 38318025 | pmc = 10839595 | doi = 10.1016/j.heliyon.2024.e25179 | doi-access = free | bibcode = 2024Heliy..1025179L }}

A combination of guanfacine and N-acetylcysteine has been found to lift the "brain fog" of eight patients with long COVID, according to researchers, but the results are inconclusive and have not been confirmed by other studies.{{cite journal | vauthors = Fesharaki-Zadeh A, Lowe N, Arnstien A | title = Clinical experience with the α2A-adrenoceptor agonist, guanfacine, and N-acetylcysteine for the treatment of cognitive deficits in "Long-COVID19" | journal = Neuroimmunology Reports | volume= 3 | issue = 3 | date = 2022 | page = 100154 | doi = 10.1016/j.nerep.2022.100154 | doi-access = free | pmc = 9691274 }}

A combination of glycine and N-acetylcysteine is suspected to have potential to safely replenish depleted glutathione levels in COVID-19 patients.{{cite journal | vauthors = Kumar P, Osahon O, Vides DB, Hanania N, Minard CG, Sekhar RV | title = Severe Glutathione Deficiency, Oxidative Stress and Oxidant Damage in Adults Hospitalized with COVID-19: Implications for GlyNAC (Glycine and N-Acetylcysteine) Supplementation | journal = Antioxidants | volume = 11 | issue = 1 | pages = 50 | date = December 2021 | pmid = 35052554 | pmc = 8773164 | doi = 10.3390/antiox11010050 | doi-access = free }}

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