N-Acetylcysteine

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N-Acetylcysteine

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N-Acetylcysteine

Common Names

  • Acetylcysteine
  • NAC

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For Patients & Caregivers

How It Works

N-acetylcysteine is used as a drug for acetaminophen overdose and to help break up mucus. It has not been proven to be an effective treatment for cancer.

N-acetylcysteine (NAC) is a dietary supplement derived from the amino acid L-cysteine. It is used as an antidote for acetaminophen overdose. As an antioxidant, it is thought to reduce DNA damage. NAC is also marketed for its liver-protective properties and to support healthy immune functioning.

In humans, NAC can dissolve and loosen mucus caused by some respiratory disorders. It has also been studied for several psychiatric disorders with limited success. Small trials suggest potential to reduce cancer-treatment toxicities, but it has not been shown to treat cancer. Additional studies are needed to determine safety and efficacy of NAC for various conditions.

Purported Uses
  • To treat drug-induced liver toxicity
    NAC is an effective treatment for acetaminophen poisoning, which can be life-threatening. If liver toxicity is suspected, seek immediate medical attention for proper treatment.
  • To treat chronic lung disease
    Study results are mixed. Some trials suggest it may reduce inflammation, flare-ups, or improve lung function, but benefits were not observed in other trials.
  • To treat HIV and AIDS
    A few trials suggest that NAC can raise cysteine and glutathione levels in HIV+ patients, but whether it improves survival or immune function is not known.
  • To treat depression
    Results with NAC as add-on therapy for depression are mixed. Additional studies are needed.
  • To prevent and treat cancer
    A few clinical trials suggest that this supplement can prevent certain pre-cancerous damage, but there is no proof that it can prevent cancer.
  • To reduce cancer treatment side-effects
    A few initial studies suggest possible benefit to reduce some toxicities and symptoms, but more studies are needed to determine safety and effectiveness.
Patient Warnings
  • NAC is used as an antidote for liver toxicity caused by acetaminophen poisoning, which can be life-threatening. If acetaminophen overdose is suspected, seek immediate medical attention for proper treatment.
Do Not Take If
  • You are taking nitroglycerin:  In humans, NAC can further reduce blood pressure and cause severe headaches.
Side Effects
  • Stomach upset
  • Diarrhea
  • Nausea
  • Vomiting
  • Fatigue
  • Eye irritation
  • Skin rash

Less common: Low blood pressure, anaphylactic shock, asthma attacks, headache

Case reports
Light sensitivity: Occurred in pulmonary fibrosis patients taking NAC in combination with pirfenidone. The reaction could not be explained by other variables such as location, season, or other medications taken at the same time.

Special Point
  • It is controversial whether antioxidants like NAC can lessen or negate cancer treatment effects. Because some cancer therapies work by creating free radicals that kill cancer cells, high levels of antioxidants may neutralize these effects and protect cancer cells from these therapies. So what protects healthy cells may protect cancer cells as well. Patients who are interested in taking antioxidants during therapy should consult with their oncologist.
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For Healthcare Professionals

Scientific Name
N-Acetylcysteine
Clinical Summary

N-acetylcysteine (NAC) is an antioxidant that is used as a prescription drug and as a dietary supplement. As a drug, it is given parenterally or orally to treat acetaminophen overdose. The inhalant and oral solution forms have a mucolytic effect, and are used to relieve obstructions in bronchial diseases and in tracheotomy procedures. The oral capsule is marketed as a dietary supplement for its liver-protective properties and to support healthy immune functioning.

Clinical studies show that NAC can treat drug-induced hepatotoxicity (1) (2). Preliminary data suggest it can also improve antioxidant levels in patients with HIV/AIDS (3) and preserve renal function in hemodialysis patients (40) (41).

Results with NAC for chronic lung disease are mixed. Some studies indicate that it may reduce exacerbations (5) (44), inflammation (45), and help improve or maintain lung function (6) (38), but such benefits were not observed in other trials (7) (8) (37) (39). In addition, a meta-analysis suggests it is not the most effective mucolytic agent for chronic obstructive pulmonary disease (COPD) (46).

There has also been interest in NAC to improve psychiatric conditions, with preliminary benefit shown for addiction, substance abuse, and compulsive disorders (11) (12) (13) (14), but effects of adjunctive NAC on depressive symptoms are mixed (47) (48) (49).

Although small studies suggest that NAC may inhibit cancer biomarker development (15) (16), a large trial found it did not inhibit formation of secondary head and neck or lung tumors (17). Preliminary findings suggest possible benefit with NAC for cancer-treatment toxicities such as reduced liver toxicity (4), neuropathy (18), and mucositis (43) (50), although it did not reduce oxidative stress (42) or cisplatin toxicities (51).

Gastrointestinal side effects have been reported following use of NAC (19). Due to its antioxidant activity, it may also accelerate the progression of some cancers evidenced by accelerated lung cancer growth in an animal model (36). Additional studies are therefore needed to determine safety and efficacy.

Purported Uses
  • Liver toxicity
  • Chronic lung disease
  • HIV/AIDS
  • Depression
  • Cancer
  • Cancer treatment side effects
Mechanism of Action

NAC is a precursor to glutathione (GSH). It is used as both an antidote for acetaminophen-induced hepatotoxicity, and as a mucolytic agent for respiratory diseases. NAC reduces disulphide bonds to sulfhydryl bonds to reduce mucus formation (20). Its hepatoprotective action may occur by cytokine-mediated mechanisms as well as GSH replenishment (21). NAC crosses the blood-brain barrier, increases brain GSH levels, and acts as a glutamine modulator (11).

In vitro, NAC improved ifosfamide benefits by decreasing nephrotoxicity without reducing antitumor effects (26). NAC altered doxorubicin-induced NF-κB activity via concentration-dependent anti- and pro-oxidant mechanisms (27). This biphasic effect was also time-dependent (28). In androgen-independent human prostate cancer PC-3 cells, antiproliferative effects were attributed to upregulated Cyr61 protein expression (28).

NAC amide can increase bioavailability and reduce oxidative stress, but it does not decrease doxorubicin-induced cell death in H9c2 cardiomyocytes (29). In an animal model, NAC increased lung cancer cell proliferation due to its antioxidant activity by reducing ROS, DNA damage, and p53 expression (36).

Adverse Reactions

Common (Oral): Gastrointestinal disturbance, diarrhea, nausea, vomiting, fatigue, conjunctival irritation, skin rash (26) (28)
Other: Hypotension, anaphylaxis, asthma attacks, headache (29)

Case reports
Photosensitivity not attributable to location, season, or concomitant medication: Occurred among pulmonary fibrosis patients more frequently with acetylcysteine than placebo in combination with pirfenidone (39).

Herb-Drug Interactions

Nitroglycerin: In humans, the addition of NAC caused severe headaches due to added vasodilation effect (34).
Antidepressants: In animal models, NAC may increase the effects of imipramine and escitalopram (35). Clinical relevance has yet to be determined.

Dosage (OneMSK Only)
References
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  2. Yarema MC, Johnson DW, Berlin RJ, et al. Comparison of the 20-hour intravenous and 72-hour oral acetylcysteine protocols for the treatment of acute acetaminophen poisoning. Ann Emerg Med. Oct 2009;54(4):606-614.
  3. Borges-Santos MD, Moreto F, Pereira PC, et al. Plasma glutathione of HIV(+) patients responded positively and differently to dietary supplementation with cysteine or glutamine. Nutrition. 2012 Jul;28(7-8):753-6.
  4. Al-Tonbary Y, Al-Haggar M, El-Ashry R, et al. Vitamin e and N-acetylcysteine as antioxidant adjuvant therapy in children with acute lymphoblastic leukemia. Adv Hematol. 2009;2009:689639.
  5. Grandjean EM, Berthet P, Ruffmann R, et al. Efficacy of oral long-term N-acetylcysteine in chronic bronchopulmonary disease: a meta-analysis of published double-blind, placebo-controlled clinical trials. Clin Ther. Feb 2000;22(2):209-221.
  6. Stav D, Raz M. Effect of N-acetylcysteine on air trapping in COPD: a randomized placebo-controlled study. Chest. Aug 2009;136(2):381-386.
  7. Decramer M, Rutten-van Molken M, Dekhuijzen PN, et al. Effects of N-acetylcysteine on outcomes in chronic obstructive pulmonary disease (Bronchitis Randomized on NAC Cost-Utility Study, BRONCUS): a randomised placebo-controlled trial. Lancet. Apr 30-May 6 2005;365(9470):1552-1560.
  8. Schermer T, Chavannes N, Dekhuijzen R, et al. Fluticasone and N-acetylcysteine in primary care patients with COPD or chronic bronchitis. Respir Med. Apr 2009;103(4):542-551.
  9. Duijvestijn YC, Brand PL. Systematic review of N-acetylcysteine in cystic fibrosis. Acta Paediatr. Jan 1999;88(1):38-41.
  10. Louwerse ES, Weverling GJ, Bossuyt PM, et al. Randomized, double-blind, controlled trial of acetylcysteine in amyotrophic lateral sclerosis. Arch Neurol. Jun 1995;52(6):559-564.
  11. Schmaal L, Veltman DJ, Nederveen A, et al. N-acetylcysteine normalizes glutamate levels in cocaine-dependent patients: a randomized crossover magnetic resonance spectroscopy study. Neuropsychopharmacology. Aug 2012;37(9):2143-2152.
  12. Dean O, Giorlando F, Berk M. N-acetylcysteine in psychiatry: current therapeutic evidence and potential mechanisms of action. J Psychiatry Neurosci. Mar 2011;36(2):78-86.
  13. Grant JE, Kim SW, Odlaug BL. N-acetyl cysteine, a glutamate-modulating agent, in the treatment of pathological gambling: a pilot study. Biol Psychiatry. Sep 15 2007;62(6):652-657.
  14. Grant JE, Odlaug BL, Kim SW. N-acetylcysteine, a glutamate modulator, in the treatment of trichotillomania: a double-blind, placebo-controlled study. Arch Gen Psychiatry. Jul 2009;66(7):756-763.
  15. Van Schooten FJ, Besaratinia A, De Flora S, et al. Effects of oral administration of N-acetyl-L-cysteine: a multi-biomarker study in smokers. Cancer Epidemiol Biomarkers Prev. Feb 2002;11(2):167-175.
  16. Estensen RD, Levy M, Klopp SJ, et al. N-acetylcysteine suppression of the proliferative index in the colon of patients with previous adenomatous colonic polyps. Cancer Lett. Dec 1 1999;147(1-2):109-114.
  17. van Zandwijk N, Dalesio O, Pastorino U, et al. EUROSCAN, a randomized trial of vitamin A and N-acetylcysteine in patients with head and neck cancer or lung cancer. For the EUropean Organization for Research and Treatment of Cancer Head and Neck and Lung Cancer Cooperative Groups. J Natl Cancer Inst. Jun 21 2000;92(12):977-986.
  18. Lin PC, Lee MY, Wang WS, et al. N-acetylcysteine has neuroprotective effects against oxaliplatin-based adjuvant chemotherapy in colon cancer patients: preliminary data. Support Care Cancer. May 2006;14(5):484-487.
  19. Mullins ME, Schmidt RU, Jr., Jang TB. What is the rate of adverse events with intravenous versus oral N-acetylcysteine in pediatric patients? Ann Emerg Med. Nov 2004;44(5):547-548; author reply 548-549.
  20. Sadowska AM, Verbraecken J, Darquennes K, et al. Role of N-acetylcysteine in the management of COPD. Int J Chron Obstruct Pulmon Dis. 2006;1(4):425-434.
  21. Masubuchi Y, Nakayama J, Sadakata Y. Protective effects of exogenous glutathione and related thiol compounds against drug-induced liver injury. Biol Pharm Bull. Mar 2011;34(3):366-370.
  22. Balansky R, Ganchev G, Iltcheva M, et al. Prevention of cigarette smoke-induced lung tumors in mice by budesonide, phenethyl isothiocyanate, and N-acetylcysteine. Int J Cancer. Mar 1 2010;126(5):1047-1054.
  23. Shimamoto K, Hayashi H, Taniai E, et al. Antioxidant N-acetyl-L-cysteine (NAC) supplementation reduces reactive oxygen species (ROS)-mediated hepatocellular tumor promotion of indole-3-carbinol (I3C) in rats. J Toxicol Sci. 2011;36(6):775-786.
  24. Hao J, Zhang B, Liu B, et al. Effect of alpha-tocopherol, N-acetylcysteine and omeprazole on esophageal adenocarcinoma formation in a rat surgical model. Int J Cancer. Mar 15 2009;124(6):1270-1275.
  25. Reliene R, Schiestl RH. Antioxidant N-acetyl cysteine reduces incidence and multiplicity of lymphoma in Atm deficient mice. DNA repair. Jul 13 2006;5(7):852-859.
  26. Chen N, Hanly L, Rieder M, et al. The effect of N-acetylcysteine on the antitumor activity of ifosfamide. Can J Physiol Pharmacol. May 2011;89(5):335-343.
  27. Finn NA, Kemp ML. Pro-oxidant and antioxidant effects of N-acetylcysteine regulate doxorubicin-induced NF-kappa B activity in leukemic cells. Mol Biosyst. Feb 2012;8(2):650-662.
  28. Lee YJ, Lee DM, Lee CH, et al. Suppression of human prostate cancer PC-3 cell growth by N-acetylcysteine involves over-expression of Cyr61. Toxicol In Vitro. Feb 2011;25(1):199-205.
  29. Shi R, Huang CC, Aronstam RS, et al. N-acetylcysteine amide decreases oxidative stress but not cell death induced by doxorubicin in H9c2 cardiomyocytes. BMC pharmacology. 2009;9:7.
  30. Holdiness MR. Clinical pharmacokinetics of N-acetylcysteine. Clin Pharmacokinet. Feb 1991;20(2):123-134.
  31. Olsson B, Johansson M, Gabrielsson J, et al. Pharmacokinetics and bioavailability of reduced and oxidized N-acetylcysteine. Eur J Clin Pharmacol. 1988;34(1):77-82.
  32. Pendyala L, Schwartz G, Bolanowska-Higdon W, et al. Phase I/pharmacodynamic study of N-acetylcysteine/oltipraz in smokers: early termination due to excessive toxicity. Cancer Epidemiol Biomarkers Prev. Mar 2001;10(3):269-272.
  33. Herr SM. Herb-Drug Interaction Handbook, 2nd ed. Nassau, NY: Church Street Books; 2002.
  34. Ardissino D, Merlini PA, Savonitto S, et al. Effect of transdermal nitroglycerin or N-acetylcysteine, or both, in the long-term treatment of unstable angina pectoris. J Am Coll Cardiol. Apr 1997;29(5):941-947.
  35. Costa-Campos L, Herrmann AP, Pilz LK, et al. Interactive effects of N-acetylcysteine and antidepressants. Prog Neuropsychopharmacol Biol Psychiatry. Feb 16 2013;44C:125-130.
  36. Sayin V, Ibrahim M, Larsson E, et al. Antioxidants Accelerate Lung Cancer Progression in Mice. Sci Transl Med. Jan 2014; 6:(221):ra15.
  37. Johnson K, McEvoy CE, Naqvi S, et al. High-dose oral N-acetylcysteine fails to improve respiratory health status in patients with chronic obstructive pulmonary disease and chronic bronchitis: a randomized, placebo-controlled trial. Int J Chron Obstruct Pulmon Dis. 2016;11:799-807.
  38. Conrad C, Lymp J, Thompson V, et al. Long-term treatment with oral N-acetylcysteine: affects lung function but not sputum inflammation in cystic fibrosis subjects. A phase II randomized placebo-controlled trial. J Cyst Fibros. Mar 2015;14(2):219-227.
  39. Behr J, Bendstrup E, Crestani B, et al. Safety and tolerability of acetylcysteine and pirfenidone combination therapy in idiopathic pulmonary fibrosis: a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Respir Med. Jun 2016;4(6):445-453.
  40. Shahbazian H, Shayanpour S, Ghorbani A. Evaluation of administration of oral N-acetylcysteine to reduce oxidative stress in chronic hemodialysis patients: A double-blind, randomized, controlled clinical trial. Saudi J Kidney Dis Transpl. Jan 2016;27(1):88-93.
  41. Ahmadi F, Abbaszadeh M, Razeghi E, et al. Effectiveness of N-acetylcysteine for preserving residual renal function in patients undergoing maintenance hemodialysis: multicenter randomized clinical trial. Clin Exp Nephrol. Apr 2017;21(2):342-349.
  42. Cassidy PB, Liu T, Florell SR, et al. A Phase II Randomized Placebo-Controlled Trial of Oral N-acetylcysteine for Protection of Melanocytic Nevi against UV-Induced Oxidative Stress In Vivo. Cancer Prev Res (Phila). Jan 2017;10(1):36-44.
  43. Moslehi A, Taghizadeh-Ghehi M, Gholami K, et al. N-acetyl cysteine for prevention of oral mucositis in hematopoietic SCT: a double-blind, randomized, placebo-controlled trial. Bone Marrow Transplant. Jun 2014;49(6):818-823.
  44. Qi Q, Ailiyaer Y, Liu R, et al. Effect of N-acetylcysteine on exacerbations of bronchiectasis (BENE): a randomized controlled trial. Respir Res. Apr 11 2019;20(1):73.
  45. Zhang Q, Ju Y, Ma Y, et al. N-acetylcysteine improves oxidative stress and inflammatory response in patients with community acquired pneumonia: A randomized controlled trial. Medicine (Baltimore). Nov 2018;97(45):e13087.
  46. Rogliani P, Matera MG, Page C, et al. Efficacy and safety profile of mucolytic/antioxidant agents in chronic obstructive pulmonary disease: a comparative analysis across erdosteine, carbocysteine, and N-acetylcysteine. Respir Res. May 27 2019;20(1):104.
  47. Bauer IE, Green C, Colpo GD, et al. A Double-Blind, Randomized, Placebo-Controlled Study of Aspirin and N-Acetylcysteine as Adjunctive Treatments for Bipolar Depression. J Clin Psychiatry. Dec 4 2018;80(1).
  48. Ellegaard PK, Licht RW, Nielsen RE, et al. The efficacy of adjunctive N-acetylcysteine in acute bipolar depression: A randomized placebo-controlled study. J Affect Disord. Feb 15 2019;245:1043-1051.
  49. Zheng W, Zhang QE, Cai DB, et al. N-acetylcysteine for major mental disorders: a systematic review and meta-analysis of randomized controlled trials. Acta Psychiatr Scand. May 2018;137(5):391-400.
  50. Sio TT, Blanchard MJ, Novotny PJ, et al. N-Acetylcysteine Rinse for Thick Secretion and Mucositis of Head and Neck Chemoradiotherapy (Alliance MC13C2): A Double-Blind Randomized Clinical Trial. Mayo Clin Proc. Sep 2019;94(9):1814-1824.
  51. Visacri MB, Quintanilha JCF, de Sousa VM, et al. Can acetylcysteine ameliorate cisplatin-induced toxicities and oxidative stress without decreasing antitumor efficacy? A randomized, double-blind, placebo-controlled trial involving patients with head and neck cancer. Cancer Med. May 2019;8(5):2020-2030.
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