N-Acetyl Cysteine (NAC)

Overview

N-acetylcysteine is an effective mucolytic agent for treatment of chronic bronchitis and other pulmonary diseases that are complicated by the production of viscous mucous. It is also used as an antidote for acetaminophen poisoning (1) and found to be effective for the prevention of cardiotoxicity by doxorubicin.

N-acetyl cysteine is the acetylated form of the amino acid cysteine. N-acetyl cysteine is a sulfur-containing amino acid that serves as a precursor for the synthesis of glutathione, a detoxifying agent in the body. N-acetyl cysteine is an antioxidant that has been used to combat viruses, (2) and helps the liver detoxify a wide range of pollutants such as cigarette smoke, (3) auto exhaust, (4) certain fungicides, (5) and some toxic metals (6) through improving phase II detoxification mechanisms in the liver.

Dosage Info

Dosage Range

250 to 2,000mg daily. However, doses of 20 grams per day may be used to treat acetaminophen poisoning.

Most Common Dosage

500mg, 2 times daily.

Dosage Forms

Capsules, tablets, powder, and solution.

Adult RDI

None established

Adult ODA

None established

Active Forms

N-acetyl cysteine.

Absorption

N-acetyl cysteine is readily absorbed from the intestinal tract.

Toxicities & Precautions

General

N-acetyl cysteine is generally considered to be quite safe.

When NAC is used at high doses (20 grams/day) to treat acetaminophen poisoning, it may cause excess urinary zinc excretion, in which case it may be wise to monitor both zinc and copper levels. (7)

Side Effects

Although reports of side effects have been rare, the authors of one study reported that 19 percent of patients experienced varying degrees of nausea, vomiting, headache, dry mouth, dizziness, or abdominal pain. (8)

Functions in the Body

Clinical Applications

Aids

AIDS and HIV patients usually have decreased levels of the intracellular antioxidant, glutathione. (9) Providing NAC increases cellular glutathione levels, and it has been proposed that glutathione can inhibit the activation of NF-kB, which results in the inhibition of HIV-1 replication. (10) In HIV-infected patients, therapy with NAC results in enhanced immunological activity, including improved natural killer (NK) cell and T-cell functions. (11)

Asthma

N-acetylcysteine is a potent mucolytic agent. When utilized as a 10% solution with a bronchodilator by pressure machine, clearance of mucous secretions can be achieved in asthmatic subjects without inducing bronchospasm. (12)

Bronchitis

A meta-analysis of ten clinical trials revealed that prolonged treatment with oral N-acetyl cysteine provides substantial benefit in the treatment of chronic bronchitis. Dosages ranged from 400 to 1,200mg daily, and the duration of the studies ranged from three to six months. (13) Chronic bronchitis occurs frequently in smokers, and NAC reportedly reduces the incidence of recurrent infections in these individuals. (14)

Diabetic Retinopathy

Results from animal experiments suggests that n-acetyl-cysteine is an antioxidant that may help inhibit the development of retinopathy in individuals with diabetes. (15)

Heavy Metal Detoxification

N-acetylcysteine acts as a chelating agent in the treatment of acute heavy metal poisoning, both as an agent capable of protecting the liver and kidney from damage and as an intervention to enhance elimination of the metals. For example, NAC helps detoxify and protect against methylmercury (16) , which is a potent neurotoxin and one of the most dangerous environmental pollutants. NAC also detoxifies arsenic (17) , chromium, and boron. (18)

Chemotherapy Support

NAC lessens the cardiotoxicity associated with doxorubicin (Adriamycin), (19) and causes greater than a 50 percent reduction in the incidence of nausea and vomiting in patients receiving cyclophosphamide, epirubicin, and carboplatin. (20)

Chronic Obstructive Pulmonary Disease

At 600mg per day, NAC has proven to be beneficial in the treatment of chronic obstructive pulmonary disease due to its antioxidant, mucolytic, non-enzymatic reaction with free radicals, and due to its ability to reduce hydrogen peroxide induced damage. (21)

Acetaminophen poisoning

Acetaminophen overdose results in more calls to poison control centers in the U.S. than overdose with any other pharmacologic substance. N-acetyl cysteine remains the therapy of choice in the treatment of acetaminophen poisoning. In such cases, it prevents glutathione depletion and is strongly hepatoprotective. (22)

Elevated Lipoprotein (a)

Elevated lipoprotein (a) levels have been associated with an increased risk for atherosclerosis and thrombotic disease. Patients receiving NAC in dosages of 2 gm/day for four weeks, and then 4 gm/day for the next four weeks, experienced nearly a 70 percent reduction in Lp(a) levels. (23)

Hepatitis C

N-acetyl cysteine has reportedly been able to enhance the effectiveness of alpha-interferon therapy in patients with hepatitis C. Glutathione levels increased along with improvements in several other disease parameters that were being measured. (24)

Symptoms and Causes of Deficiency

N-acetyl cysteine is not an essential nutrient for humans and a deficiency condition has not been identified.

Dietary Sources

N-acetyl cysteine does not occur in foods. Its precursor, L-cysteine, occurs in most high-protein foods.

References

  1. View Abstract: Koivusalo AM, Yildirim Y, Vakkuri A, Lindgren L, Hockerstedt K, Isoniemi H. Experience with albumin dialysis in five patients with severe overdoses of paracetamol. Acta Anaesthesiol Scand. Oct2003;47(9):1145-50.
  2. View Abstract: Cavallini L, Alexandre A. Oral N-acetyl-cysteome increases the production of anti HIV chemokines in peripheral blood mononuclear cells. Life Sci. 2000;67(2):147-54.
  3. View Abstract: Banzet N, Francois D, Polla BS. Tobacco smoke induces mitochondrial depolarization along with cell death: effects of antioxidants. Redox Rep. 1999;4(5):229-36.
  4. View Abstract: Kawasaki S, Takizawa H, Takami K, et al. Benzene-extracted components are important for the major activity of diesel exhaust particles: effect on interleukin-8 gene expression in human bronchial epithelial cells. Am J Respir Cell Mol Biol. Apr2001;24(4):419-26.
  5. View Abstract: Cereser C, Boget S, Parvaz P, Revol A. Thiram-induced cytotoxicity is accompanied by a rapid and drastic oxidation of reduced glutathione with consecutive lipid peroxidation and cell death. Toxicology. Jun2001;163(2-3):153-62.
  6. View Abstract: Ballatori N, et al. N-acetylcysteine as an antidote in methylmercury poisoning. Environ Health Perspect. May1998;106(5):267-71.
  7. View Abstract: Brumas V, et al. Can N-acetyl-L-cysteine affect zinc metabolism when used as a paracetamol antidote? Agents Actions. Jul1992;36(3-4):278-88.
  8. View Abstract: Tattersall AB, et al. Acetylcysteine (Fabrol) in chronic bronchitis--a study in general practice. J Int Med Res. 1983;11(5):279-84.
  9. View Abstract: Roberts RL, et al. N-acetylcysteine enhances antibody-dependent cellular cytotoxicity in neutrophils and mononuclear cells from healthy adults and human immunodeficiency virus-infected patients. J Infect Dis. Dec1995;172(6):1492-502.
  10. View Abstract: Kameoka M, et al. Intracellular glutathione as a possible direct blocker of HIV type 1 reverse transcription. AIDS Res Hum Retroviruses. Nov1996;12(17):1635-8.
  11. View Abstract: Breikrutz R, et al. Improvement of immune functions in HIV infection by sulfur supplementation: two randomized trials. J Mol Med. 2000;78(1):55-62.
  12. View Abstract: Millman M, et al. Use of acetylcysteine in bronchial asthma--another look. Ann Allergy. Apr1985;54(4):294-6.
  13. View Abstract: Grandjean EM, 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. Feb2000;22(2):209-21.
  14. View Abstract: Riise GC, et al. The intrabronchial microbial flora in chronic bronchitis patients: a target for N-acetylcysteine therapy? Eur Respir J. Jan1994;7(1):94-101.
  15. Kowluru RA, Tang J, Kern TS. Abnormalities of retinal metabolism in diabetes and experimental galactosemia. VII. Effect of long-term administration of antioxidants on the development of retinopathy. Diabetes. Aug2001;50(8):1938-42.
  16. View Abstract: Ballatori N, et al. N-acetylcysteine as an antidote in methylmercury poisoning. Environ Health Perspect. May1998;106(5):267-71.
  17. View Abstract: Flora SJ, et al. Arsenic-induced oxidative stress and its reversibility following combined administration of N-acetylcysteine and meso 2,3-dimercaptosuccinic acid in rats. Clin Exp Pharmacol Physiol. Nov1999;26(11):865-9.
  18. View Abstract: Flora SJ, et al. Arsenic-induced oxidative stress and its reversibility following combined administration of N-acetylcysteine and meso 2,3-dimercaptosuccinic acid in rats. Clin Exp Pharmacol Physiol. Nov1999;26(11):865-9.
  19. View Abstract: DeFlora S, et al. Synergism between N-acetylcysteine and doxorubicin in the prevention of tumorigenicity and metastasis in murine models. Int J Cancer. Sep1996;67(6):842-8.
  20. de Blasio R, et al. N-acetylcysteine (NAC) in preventing nausea and vomiting induced by chemotherapy in patients suffering from inoperable non-small cell lung cancer (NSCLC). Chest. 1996;110(4,Suppl):103S.
  21. van Herwaarden CL, et al. The Role of N-Acetylcysteine in the Treatment of Chronic Obstructive Pulmonary Disease. The Netherlands Journal of Medicine. 1995;47:45-48.
  22. View Abstract: Zed PJ, Krenzelok EP. Treatment of acetaminophen overdose. Am J Health Syst Pharm. Jun1999;56(11):1081-91.
  23. View Abstract: Gavish D, et al. Lipoprotein (a) Reduction by N-Acetylcysteine. Lancet. Jan1991;337:203-204.
  24. View Abstract: Beloqui O, et al. N-acetyl cysteine enhances the response to interferon-alpha in chronic hepatitis C: a pilot study. J Interferon Res. Aug1993;13(4):279-82.