N-Acetylcysteine

    Researchedby:
    Bill Willis, Katie Jantz

    Fact-checked

    by:

    Nick Milazzo, Dmitri Barvinok
    Last Updated: June 12, 2024

    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.

    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]

    Does N-acetylcysteine help with lead toxicity?

    Does N-acetylcysteine affect fertility?

    Does N-acetylcysteine affect mental disorders?

    Does N-acetylcysteine affect exercise performance?

    How does N-acetylcysteine work for acetaminophen toxicity?

    What is oxidative stress?

    Does N-acetylcysteine affect hearing loss?

    Does N-acetylcysteine affect Parkinson’s disease?

    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]

    Does N-acetylcysteine increase the risk or progression of cancer?

    What are other names for N-Acetylcysteine

    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.

    Frequently asked questions

    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]

    Does N-acetylcysteine help with lead toxicity?

    NAC seems to have a direct mineral chelating effect, meaning it can bind tightly to certain minerals and aid in their removal from the body. In rodents, decreased tissue accumulation and increased urinary excretion of lead has been observed following NAC supplementation,[21] and in humans, a reduction in serum lead has been found.[22] Standard oral doses of NAC appear to be protective against lead toxicity in humans, possibly related to a reduction in lead accumulation in the body and reducing oxidative stress.

    Lead is a heavy mineral that can be toxic to the human body. Exposure to lead causes oxidative stress in the body, which seems to deplete both cellular and enzymatic antioxidants, including glutathione.[23] NAC is thought to alleviate the toxic effects of lead by aiding in its removal from the body while also acting as a building block for the synthesis of new glutathione.[21][24]

    In animal studies, NAC has shown protective effects (assessed by biomarkers in serum and histopathological examination) against lead toxicity in the kidneys,[21] the brain,[24][25] and liver tissue.[25] In workers with high levels of occupational lead exposure, oral supplementation of 200–800 mg of N-acetylcysteine daily for 12 weeks reduced blood concentrations of lead and improved markers of oxidative stress.[22]

    Does N-acetylcysteine affect fertility?

    NAC has shown positive effects on parameters of both male and female infertility.

    NAC may improve sperm health and quality (e.g., motility, concentration, morphology, volume) in infertile men, likely through reductions in oxidative stress in the testicular tissue and semen. However, NAC hasn’t consistently been found to influence hormones involved in male fertility (testosterone, luteinizing hormone, follicle stimulating hormone (FSH), and prolactin).[26]

    In women with infertility due to polycystic ovarian syndrome (PCOS), NAC may reduce testosterone and increase follicle stimulating hormone levels.[27] Compared to placebo, NAC seems to increase pregnancy and ovulation rates, but not when compared to metformin (a medication commonly used in PCOS).[28]

    Does N-acetylcysteine affect mental disorders?

    Many mental disorders are associated with dysregulation of the neurotransmitters glutamate and/or dopamine, as well as increased levels of oxidative stress in the brain.[29] Aside from its antioxidant effects, research shows that NAC crosses the blood-brain barrier and can directly alter glutamate neurotransmission, with an indirect effect on dopamine as well,[20] making it a potentially helpful supplement for a variety of conditions.

    When used in addition to standard care, NAC has shown small benefits for the management of schizophrenia,[30][31][32] depression symptoms (including bipolar depression),[33][34] autism spectrum disorder (specifically hyperactivity and irritability),[35] and substance use disorder.[36]

    Does N-acetylcysteine affect exercise performance?

    During physical exercise, cells produce a high level of ROS. While this actually serves a biological role that positively affects skeletal muscle adaptations and force production, in vitro and animal studies suggest that excessively high levels of ROS can contribute to impaired muscle function and muscle fatiguing.[37][38][39]

    NAC has been explored as a potential ergogenic due to its antioxidant effects, but research supporting its use is limited. A 2017 meta-analysis was unable to find any evidence of a performance benefit with NAC supplementation, but the analysis included studies using vastly different dosages, exercise regimens, and study populations (e.g., elite athletes, untrained individuals).[40] NAC seems to display the most consistent benefit when exercise is being performed in a fatigued state,[41][42][43] but it may negatively affect muscle adaptations to training.[44] Ultimately, further research is needed to determine if NAC supplementation is beneficial in this context, and if so, in what setting and dosage.

    How does N-acetylcysteine work for acetaminophen toxicity?

    Acetaminophen (paracetamol) is a widely available medication used to treat fever and pain. It is also the leading cause of liver transplantation in the U.S. and the second leading cause worldwide due to liver toxicity that can occur with overdose. When acetaminophen is overdosed, a toxic metabolite (N-acetyl-p-benzoquinone imine (NAPQI)) begins to build up in the liver. Normally, glutathione is responsible for neutralizing NAPQI, but when glutathione levels become depleted, NAPQI begins reacting with molecules within liver cells, leading to irreversible liver cell death. NAC is an effective antidote for acetaminophen (paracetamol) toxicity primarily because it replenishes glutathione levels, but it can also directly bind to and neutralize NAPQI to minimize liver cell damage and convert NAPQI back to acetaminophen temporarily.[45]

    What is oxidative stress?

    Oxidative stress describes a state of imbalance between oxidants and antioxidant defense mechanisms in the body. When oxidants (e.g., ROS, reactive nitrogen species (RNS)) outweigh the body’s natural antioxidant defenses (e.g., antioxidant enzymes, glutathione), cellular damage can occur, including damage to proteins, lipids, and DNA. This is thought to contribute to the development or worsening of a wide range of diseases.[5]

    Does N-acetylcysteine affect hearing loss?

    NAC may have a role in the prevention or early treatment of hearing loss, although research is still in the early stages.

    Hearing loss is complex and can occur for many reasons, but increased levels of oxidative stress within the ear is an important contributing factor. Excessive levels of reactive oxygen species|ROS within the ear canal can damage or kill auditory hair cells — the cells responsible for converting sound vibrations into electrical signals that the brain can understand — leading to hearing loss.[55]

    Research suggests that NAC may reduce the risk of drug-induced hearing loss when used concurrently with potentially ototoxic drugs (i.e., drugs that are toxic to the ear, such as aminoglycoside antibiotics or cisplatin).[56][57] NAC may also have a protective effect against noise-induced shifts in hearing thresholds (i.e., exposure to noises so loud that they temporarily or permanently raise the minimum volume at which a sound can be detected), specifically for higher sound frequencies (4–6 kHz).[55] For sudden hearing loss (an unexplainable, rapid loss of hearing), combining NAC with corticosteroids may be more effective for regaining hearing than corticosteroids alone.[58]

    Does N-acetylcysteine affect Parkinson’s disease?

    Parkinson’s disease is characterized by the progressive loss of dopamine-producing neurons in the brain and is associated with increased levels of oxidative stress and a relative depletion of glutathione in brain tissue.[59] N-acetylcysteine (NAC) reliably increases glutathione levels in the body, and preclinical and preliminary clinical research has pointed to a possible therapeutic effect of NAC in Parkinson’s disease.

    In two small studies, people with Parkinson’s disease who received NAC for 3 months demonstrated increased dopamine functioning in the brain (determined by a brain scan done before and after the intervention which measured dopamine transporter binding) alongside reduced disease symptoms compared to a control group. NAC was given as a weekly intravenous infusion (50 mg per kg of body weight) in addition to daily oral NAC (1,000 to 1,200 mg). The control groups received standard care, but no placebo, which could bias these findings in favor of NAC.[60]

    It’s important to note that while intravenous NAC does appear to increase glutathione levels in the brain, NAC taken orally (6,000 mg daily) has not currently been found to have this effect in humans. Currently, there’s no evidence in humans that oral NAC alone can improve Parkinson’s disease.[61][62]

    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]

    Does N-acetylcysteine increase the risk or progression of cancer?

    On one hand, excessive reactive oxygen species (ROS) can damage molecules in the body, including DNA, and induce biochemical pathways that may increase the risk of cancer. Additionally, some cancers, like triple-negative breast cancer, use increased ROS signaling for their own survival and progression.[47] In these contexts, antioxidants such as NAC may play a beneficial role.

    On the other hand, the generation of ROS is a defense mechanism the body can use to induce cancer cell death and prevent cancer progression. While antioxidants might protect against ROS-induced damage and reduce cancer progression in some instances,[48] in other contexts they might promote cancer cell survival by reducing oxidative stress within the cell.[49] In fact, there’s evidence to suggest that one mechanism by which cancer cells promote their own survival is by increasing the body's antioxidant defense mechanisms within the cell.[50][51]

    There is no evidence from human clinical trials that NAC causes cancer or increases cancer progression. In breast cancer, one uncontrolled pilot study suggested that NAC might actually inhibit cancer cell proliferation.[48] However, research in mice has suggested that NAC supplementation might promote the progression of certain pre-existing cancers, including skin, liver, and lung cancer, and increase the risk of metastatic disease — in both cases, by reducing oxidative stress in the cancer cells.[52][53][54][49] In mice without pre-existing cancer, the effects are less clear. NAC supplementation did not induce liver cancer in otherwise healthy mice in one study,[54] but it did increase the risk of lung cancer in healthy aged mice in another.[49]

    Clearly, the question of how NAC interacts with cancer risk or progression is incredibly nuanced, and more research is needed to understand this relationship.

    Update History

    References

    1. ^Micaely Cristina Dos Santos Tenório, Nayara Gomes Graciliano, Fabiana Andréa Moura, Alane Cabral Menezes de Oliveira, Marília Oliveira Fonseca GoulartN-Acetylcysteine (NAC): Impacts on Human HealthAntioxidants (Basel).(2021 Jun 16)
    2. ^Guerini M, Condrò G, Friuli V, Maggi L, Perugini PN-acetylcysteine (NAC) and Its Role in Clinical Practice Management of Cystic Fibrosis (CF): A Review.Pharmaceuticals (Basel).(2022-Feb-11)
    3. ^Gerry K SchwalfenbergN-Acetylcysteine: A Review of Clinical Usefulness (an Old Drug with New Tricks)J Nutr Metab.(2021 Jun 9)
    4. ^A L SHEFFNERThe reduction in vitro in viscosity of mucoprotein solutions by a new mucolytic agent, N-acetyl-L-cysteineAnn N Y Acad Sci.(1963 Mar 30)
    5. ^Forman HJ, Zhang HTargeting oxidative stress in disease: promise and limitations of antioxidant therapy.Nat Rev Drug Discov.(2021-Sep)
    6. ^S M BIRNBAUM, M WINITZ, J P GREENSTEINQuantitative nutritional studies with water-soluble, chemically defined diets. III. Individual amino acids as sources of non-essential nitrogenArch Biochem Biophys.(1957 Dec)
    7. ^Vered Gazit, Ron Ben-Abraham, Chaim G Pick, Izhar Ben-Shlomo, Yeshayahu KatzLong-term neurobehavioral and histological damage in brain of mice induced by L-cysteinePharmacol Biochem Behav.(2003 Jul)
    8. ^Chad Kerksick, Darryn WilloughbyThe antioxidant role of glutathione and N-acetyl-cysteine supplements and exercise-induced oxidative stressJ Int Soc Sports Nutr.(2005 Dec 9)
    9. ^M Gracey, V Burke, C M AndersonTreatment of abdominal pain in cystic fibrosis by oral administration of n-acetyl cysteineArch Dis Child.(1969 Jun)
    10. ^Kennon J HeardAcetylcysteine for acetaminophen poisoningN Engl J Med.(2008 Jul 17)
    11. ^Jiang C, Zou J, Lv Q, Yang YSystematic review and meta-analysis of the efficacy of N-acetylcysteine in the treatment of acute exacerbation of chronic obstructive pulmonary disease.Ann Palliat Med.(2021-Jun)
    12. ^Cazzola M, Calzetta L, Page C, Jardim J, Chuchalin AG, Rogliani P, Matera MGInfluence of N-acetylcysteine on chronic bronchitis or COPD exacerbations: a meta-analysis.Eur Respir Rev.(2015-Sep)
    13. ^Fowdar K, Chen H, He Z, Zhang J, Zhong X, Zhang J, Li M, Bai JThe effect of N-acetylcysteine on exacerbations of chronic obstructive pulmonary disease: A meta-analysis and systematic review.Heart Lung.(2017)
    14. ^Wei J, Pang CS, Han J, Yan HEffect of Orally Administered N-Acetylcysteine on Chronic Bronchitis: A Meta-analysis.Adv Ther.(2019-Dec)
    15. ^Huang C, Kuo S, Lin L, Yang YThe efficacy of -acetylcysteine in chronic obstructive pulmonary disease patients: a meta-analysis.Ther Adv Respir Dis.(2023)
    16. ^Anatoly ZhitkovichN-Acetylcysteine: Antioxidant, Aldehyde Scavenger, and MoreChem Res Toxicol.(2019 Jul 15)
    17. ^Aldini G, Altomare A, Baron G, Vistoli G, Carini M, Borsani L, Sergio FN-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why.Free Radic Res.(2018-Jul)
    18. ^S Oka, H Kamata, K Kamata, H Yagisawa, H HirataN-acetylcysteine suppresses TNF-induced NF-kappaB activation through inhibition of IkappaB kinasesFEBS Lett.(2000 Apr 28)
    19. ^Faghfouri AH, Zarezadeh M, Tavakoli-Rouzbehani OM, Radkhah N, Faghfuri E, Kord-Varkaneh H, Tan SC, Ostadrahimi AThe effects of N-acetylcysteine on inflammatory and oxidative stress biomarkers: A systematic review and meta-analysis of controlled clinical trials.Eur J Pharmacol.(2020-Oct-05)
    20. ^Smaga I, Frankowska M, Filip MN-acetylcysteine as a new prominent approach for treating psychiatric disorders.Br J Pharmacol.(2021-Jul)
    21. ^Wang L, Wang Z, Liu JProtective effect of N-acetylcysteine on experimental chronic lead nephrotoxicity in immature female rats.Hum Exp Toxicol.(2010-Jul)
    22. ^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)
    23. ^Dobrakowski M, Pawlas N, Hudziec E, Kozłowska A, Mikołajczyk A, Birkner E, Kasperczyk SGlutathione, glutathione-related enzymes, and oxidative stress in individuals with subacute occupational exposure to lead.Environ Toxicol Pharmacol.(2016-Jul)
    24. ^Nehru B, Kanwar SSModulation by N-acetylcysteine of lead-induced alterations in rat brain: reduced glutathione levels and morphology.Toxicol Mech Methods.(2007)
    25. ^Ercal N, Treeratphan P, Hammond TC, Matthews RH, Grannemann NH, Spitz DRIn vivo indices of oxidative stress in lead-exposed C57BL/6 mice are reduced by treatment with meso-2,3-dimercaptosuccinic acid or N-acetylcysteine.Free Radic Biol Med.(1996)
    26. ^Zhou Z, Cui Y, Zhang X, Zhang YThe role of N-acetyl-cysteine (NAC) orally daily on the sperm parameters and serum hormones in idiopathic infertile men: A systematic review and meta-analysis of randomised controlled trials.Andrologia.(2021 Mar)
    27. ^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)
    28. ^Song Y, Wang H, Huang H, Zhu ZComparison of the efficacy between NAC and metformin in treating PCOS patients: a meta-analysis.Gynecol Endocrinol.(2020-Mar)
    29. ^Ganesh Raghu, Michael Berk, Peter A Campochiaro, Hartmut Jaeschke, Giancarlo Marenzi, Luca Richeldi, Fu-Qiang Wen, Ferdinando Nicoletti, Peter M A CalverleyThe Multifaceted Therapeutic Role of N-Acetylcysteine (NAC) in Disorders Characterized by Oxidative StressCurr Neuropharmacol.(2021)
    30. ^Xu X, Shao G, Zhang X, Hu Y, Huang J, Su Y, Zhang M, Cai Y, Zhou HThe efficacy of nutritional supplements for the adjunctive treatment of schizophrenia in adults: A systematic review and network meta-analysis.Psychiatry Res.(2022-May)
    31. ^Kishi T, Sakuma K, Hatano M, Iwata NN-acetylcysteine for schizophrenia: A systematic review and meta-analysis.Psychiatry Clin Neurosci.(2023-Feb)
    32. ^Yolland CO, Hanratty D, Neill E, Rossell SL, Berk M, Dean OM, Castle DJ, Tan EJ, Phillipou A, Harris AW, Barreiros AR, Hansen A, Siskind DMeta-analysis of randomised controlled trials with -acetylcysteine in the treatment of schizophrenia.Aust N Z J Psychiatry.(2020-May)
    33. ^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)
    34. ^Fernandes BS, Dean OM, Dodd S, Malhi GS, Berk MN-Acetylcysteine in depressive symptoms and functionality: a systematic review and meta-analysis.J Clin Psychiatry.(2016-Apr)
    35. ^Lee TM, Lee KM, Lee CY, Lee HC, Tam KW, Loh EWEffectiveness of -acetylcysteine in autism spectrum disorders: A meta-analysis of randomized controlled trials.Aust N Z J Psychiatry.(2021-Feb)
    36. ^Duailibi MS, Cordeiro Q, Brietzke E, Ribeiro M, LaRowe S, Berk M, Trevizol APN-acetylcysteine in the treatment of craving in substance use disorders: Systematic review and meta-analysis.Am J Addict.(2017-Oct)
    37. ^Reid MBFree radicals and muscle fatigue: Of ROS, canaries, and the IOC.Free Radic Biol Med.(2008-Jan-15)
    38. ^Shindoh C, DiMarco A, Thomas A, Manubay P, Supinski GEffect of N-acetylcysteine on diaphragm fatigue.J Appl Physiol (1985).(1990-May)
    39. ^Reid MB, Haack KE, Franchek KM, Valberg PA, Kobzik L, West MSReactive oxygen in skeletal muscle. I. Intracellular oxidant kinetics and fatigue in vitro.J Appl Physiol (1985).(1992-Nov)
    40. ^Rhodes K, Braakhuis APerformance and Side Effects of Supplementation with N-Acetylcysteine: A Systematic Review and Meta-Analysis.Sports Med.(2017-Aug)
    41. ^Cobley JN, McGlory C, Morton JP, Close GLN-Acetylcysteine's attenuation of fatigue after repeated bouts of intermittent exercise: practical implications for tournament situationsInt J Sport Nutr Exerc Metab.(2011 Dec)
    42. ^Slattery KM, Dascombe B, Wallace LK, Bentley DJ, Coutts AJEffect of N-acetylcysteine on cycling performance after intensified training.Med Sci Sports Exerc.(2014-Jun)
    43. ^Medved I, Brown MJ, Bjorksten AR, Murphy KT, Petersen AC, Sostaric S, Gong X, McKenna MJN-acetylcysteine enhances muscle cysteine and glutathione availability and attenuates fatigue during prolonged exercise in endurance-trained individualsJ Appl Physiol (1985).(2004 Oct)
    44. ^Petersen AC, McKenna MJ, Medved I, Murphy KT, Brown MJ, Della Gatta P, Cameron-Smith DInfusion with the antioxidant N-acetylcysteine attenuates early adaptive responses to exercise in human skeletal muscleActa Physiol (Oxf).(2012 Mar)
    45. ^Agrawal S, Khazaeni BAcetaminophen ToxicityStatPearls.(2023-01)
    46. ^Ghafar Ali Mahmoudi, Peyman Astaraki, Azita Zafar Mohtashami, Maryam AhadiN-acetylcysteine overdose after acetaminophen poisoningInt Med Case Rep J.(2015 Feb 27)
    47. ^Kwon YPossible Beneficial Effects of N-Acetylcysteine for Treatment of Triple-Negative Breast Cancer.Antioxidants (Basel).(2021-Jan-24)
    48. ^Monti D, Sotgia F, Whitaker-Menezes D, Tuluc M, Birbe R, Berger A, Lazar M, Cotzia P, Draganova-Tacheva R, Lin Z, Domingo-Vidal M, Newberg A, Lisanti MP, Martinez-Outschoorn UPilot study demonstrating metabolic and anti-proliferative effects of in vivo anti-oxidant supplementation with N-Acetylcysteine in Breast Cancer.Semin Oncol.(2017-Jun)
    49. ^Breau M, Houssaini A, Lipskaia L, Abid S, Born E, Marcos E, Czibik G, Attwe A, Beaulieu D, Palazzo A, Flaman JM, Bourachot B, Collin G, Tran Van Nhieu J, Bernard D, Mechta-Grigoriou F, Adnot SThe antioxidant N-acetylcysteine protects from lung emphysema but induces lung adenocarcinoma in miceJCI Insight.(2019 Oct 3)
    50. ^Hayes JD, McMahon MNRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer.Trends Biochem Sci.(2009-Apr)
    51. ^DeNicola GM, Karreth FA, Humpton TJ, Gopinathan A, Wei C, Frese K, Mangal D, Yu KH, Yeo CJ, Calhoun ES, Scrimieri F, Winter JM, Hruban RH, Iacobuzio-Donahue C, Kern SE, Blair IA, Tuveson DAOncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis.Nature.(2011-Jul-06)
    52. ^Le Gal K, Ibrahim MX, Wiel C, Sayin VI, Akula MK, Karlsson C, Dalin MG, Akyürek LM, Lindahl P, Nilsson J, Bergo MOAntioxidants can increase melanoma metastasis in mice.Sci Transl Med.(2015-Oct-07)
    53. ^Sayin VI, Ibrahim MX, Larsson E, Nilsson JA, Lindahl P, Bergo MOAntioxidants accelerate lung cancer progression in miceSci Transl Med.(2014 Jan 29)
    54. ^Zhang VX, Sze KM, Chan LK, Ho DW, Tsui YM, Chiu YT, Lee E, Husain A, Huang H, Tian L, Wong CC, Ng IOAntioxidant supplements promote tumor formation and growth and confer drug resistance in hepatocellular carcinoma by reducing intracellular ROS and induction of TMBIM1.Cell Biosci.(2021-Dec-19)
    55. ^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)
    56. ^Orgel E, Knight KR, Chi YY, Malvar J, Rushing T, Mena V, Eisenberg LS, Rassekh SR, Ross CJD, Scott EN, Neely M, Neuwelt EA, Muldoon LL, Freyer DRIntravenous N-Acetylcysteine to Prevent Cisplatin-Induced Hearing Loss in Children: A Nonrandomized Controlled Phase I Trial.Clin Cancer Res.(2023-Jul-05)
    57. ^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)
    58. ^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)
    59. ^Zhou ZD, Yi LX, Wang DQ, Lim TM, Tan EKRole of dopamine in the pathophysiology of Parkinson's disease.Transl Neurodegener.(2023 Sep 18)
    60. ^Monti DA, Zabrecky G, Kremens D, Liang TW, Wintering NA, Bazzan AJ, Zhong L, Bowens BK, Chervoneva I, Intenzo C, Newberg ABN-Acetyl Cysteine Is Associated With Dopaminergic Improvement in Parkinson's Disease.Clin Pharmacol Ther.(2019-Oct)
    61. ^Coles LD, Tuite PJ, Öz G, Mishra UR, Kartha RV, Sullivan KM, Cloyd JC, Terpstra MRepeated-Dose Oral N-Acetylcysteine in Parkinson's Disease: Pharmacokinetics and Effect on Brain Glutathione and Oxidative Stress.J Clin Pharmacol.(2018 Feb)
    62. ^Holmay MJ, Terpstra M, Coles LD, Mishra U, Ahlskog M, Öz G, Cloyd JC, Tuite PJN-Acetylcysteine boosts brain and blood glutathione in Gaucher and Parkinson diseases.Clin Neuropharmacol.(2013 Jul-Aug)
    63. ^Sandilands EA, Bateman DNAdverse reactions associated with acetylcysteine.Clin Toxicol (Phila).(2009 Feb)
    64. ^Niemi TT, Munsterhjelm E, Pöyhiä R, Hynninen MS, Salmenperä MTThe effect of N-acetylcysteine on blood coagulation and platelet function in patients undergoing open repair of abdominal aortic aneurysm.Blood Coagul Fibrinolysis.(2006-Jan)
    65. ^Wijeysundera DN, Karkouti K, Rao V, Granton JT, Chan CT, Raban R, Carroll J, Poonawala H, Beattie WSN-acetylcysteine is associated with increased blood loss and blood product utilization during cardiac surgery.Crit Care Med.(2009 Jun)
    66. ^Ardissino D, Merlini PA, Savonitto S, Demicheli G, Zanini P, Bertocchi F, Falcone C, Ghio S, Marinoni G, Montemartini C, Mussini AEffect of transdermal nitroglycerin or N-acetylcysteine, or both, in the long-term treatment of unstable angina pectoris.J Am Coll Cardiol.(1997-Apr)
    67. ^J D Horowitz, C A Henry, M L Syrjanen, W J Louis, R D Fish, E M Antman, T W SmithNitroglycerine/N-acetylcysteine in the management of unstable angina pectorisEur Heart J.(1988 Jan)
    68. ^Sudesh Vasdev, Pawan Singal, Vicki GillThe antihypertensive effect of cysteineInt J Angiol.(2009 Spring)
    69. ^Ruiz FJ, Salom MG, Inglés AC, Quesada T, Vicente E, Carbonell LFN-acetyl-L-cysteine potentiates depressor response to captopril and enalaprilat in SHRs.Am J Physiol.(1994 Sep)
    70. ^Ahmed Y Shahin, Ibrahim M A Hassanin, Alaa M Ismail, Jan S Kruessel, Jens HirchenhainEffect of oral N-acetyl cysteine on recurrent preterm labor following treatment for bacterial vaginosisInt J Gynaecol Obstet.(2009 Jan)
    71. ^Horowitz RS, Dart RC, Jarvie DR, Bearer CF, Gupta UPlacental transfer of N-acetylcysteine following human maternal acetaminophen toxicity.J Toxicol Clin Toxicol.(1997)
    72. ^McElhatton PR, Sullivan FM, Volans GNParacetamol overdose in pregnancy analysis of the outcomes of 300 cases referred to the Teratology Information Service.Reprod Toxicol.(1997 Jan-Feb)
    73. ^Jenkins DD, Wiest DB, Mulvihill DM, Hlavacek AM, Majstoravich SJ, Brown TR, Taylor JJ, Buckley JR, Turner RP, Rollins LG, Bentzley JP, Hope KE, Barbour AB, Lowe DW, Martin RH, Chang EYFetal and Neonatal Effects of N-Acetylcysteine When Used for Neuroprotection in Maternal Chorioamnionitis.J Pediatr.(2016 Jan)
    74. ^Eva Maria Roes, Maarten T Raijmakers, Theo M de Boo, Petra L Zusterzeel, Hans M Merkus, Wilbert H Peters, Eric A SteegersOral N-acetylcysteine administration does not stabilise the process of established severe preeclampsiaEur J Obstet Gynecol Reprod Biol.(2006 Jul)
    75. ^Peter Calverley, Paola Rogliani, Alberto PapiSafety of N-Acetylcysteine at High Doses in Chronic Respiratory Diseases: A ReviewDrug Saf.(2021 Mar)