ALPHA GUIDE
A | B | C | D | E | F | G | H | I | J | K | L | M | N | O | P | Q | R | S | T | U | V | W | X | Y | Z

N-Acetylcysteine

Common Name: N-Acetylcysteine
Synonyms: NAC, L-cysteine, acetylcysteine, cysteine

Overview:

NAC or N-acetylcysteine is derived from cysteine, an amino acid common in proteins throughout the body. NAC is an antioxidant and a precursor of glutathione. NAC is used in the treatment of acute and chronic bronchitis, as it helps to break down the excessive amounts of thick mucus that is characteristic of these respiratory illnesses. It is also an antioxidant and important in detoxifying substances that are harmful to the body.

Given orally or intravenously, NAC is a hepatoprotectant used prevent the liver and kidney damage associated with overdosing on acetaminophen. NAC works by regenerating glutathione stores. In an acetaminophen overdose (more common in people who consume alcohol) the depletion of the glutathione levels puts enormous oxidative stress on the liver which can ultimately lead to liver failure, hepatic coma and even death.
In the treatment of acute and chronic bronchitis, NAC reduces the sulfide bond in mucoproteins. This causes them to liquefy making them easier to expel. There is also mounting evidence that NAC may have the ability to stop cell death, especially cells in the cells of the pancreas and nerves.

Benefits

Research in to N-acetylcysteine is not only confirming the benefits of this amino acid but uncovering new health benefits to explore. NAC has:

  1. been used as an antidote for Amanita phalloides (a poisonous mushroom with an extremely high mortality rate). In 11 people suffering from Amanita phalloides poisoning treated with a regime that included NAC, 10 people recovered with out the need for a liver transplant.
  2. Saved many people from liver damage and even death because of its ability to neutralize the toxic effects of acetaminophen overdoses. Acetaminophen overdoses are the most frequent reason for of calls to poison control centers in the United States.
  3. Preliminary evidence also suggests that NAC supplements may:
    • Improve symptoms associated with Sjogren's syndrome (an autoimmune disorder characterized by dry mouth and dry eyes)
    • Enhance cognitive functioning in some individuals with Alzheimer's disease
    • Prevent development of cataracts and macular degeneration
    • Slow down motor impairment in amyotrophic lateral sclerosis (ALS, often called Lou Gehrig's disease which is a progressive loss of control of voluntary muscles due to destruction of nerve cells in the brain and spinal cord)
    • Help treat hepatitis C when combined with standard medical treatment
    • Increase HDL cholesterol (the good kind of cholesterol).
  4. Proven helpful in the treatment of acute respiratory distress syndrome (ARDS). While a review of studies confirmed that intravenous solutions of NAC helps dissolve mucus and improve symptoms of chronic bronchitis, asthma, emphysema and cystic fibrosis.
  5. Been studied and found that NAC supplementation may benefit chronic smokers. Studies on large groups of people have found that N-acetylcysteine appears to have cancer prevention properties in those at high risk of developing lung cancer.
  6. Been used in combination with nitroglycerin in people suffering from a heart attack. This combination has proven more effective than when either NAC or nitroglycerin are used alone to reduce subsequent chest pain, heart attack and risk of death. One group of researchers said both long and short term studies have sown that people with unstable angina pectoris and the threat of heart attack when given either oral or intravenous NAC with nitroglycerine was very effective in decreasing the risk of worsening by preventing an acute heart attack.

In animal models, NAC has been shown to inhibit platelet clumping and lower lipoproteins levels to a degree not achieved by drugs or diet. Still other studies have demonstrated that intravenous infusion of NAC during blood cot destruction is associated with a decrease in the size of the infarct and a increase rescue of left ventricular function.

  1. Shown to be useful in strengthening the immune system in people suffering from HIV/AIDS and diminish the damage of HIV/AIDS on the body. In one well designed study, people with HIV were given a daily regimen of N-acetylcysteine (2400mg), glutathione (40gms), vitamin C (800mg), vitamin E (500IU), beta-carotene (27,000IU) and selenium (280mcg) for twelve weeks. At the conclusion of this study, the patients that received the daily supplements showed a significant weight gain compared to those who received the placebo. In a smaller study using just NAC the supplement did increase the glutathione level wile the placebo group did not. Studies such as this support the theory that NAC may be a useful tool to be used in conjunction with conventional medical treatment for HIV patients. There have however been a few studies that have shown a negative effect of NAC supplements in HIV patients. Further studies are needed in order to prove its benefits.
  2. NAC has shown in animal models to be of some benefit in insulin-dependant diabetes. N-acetylcysteine has shown in animal models to keep pancreatic beta cells apoptosis (cell self destruction) without affecting the production of new beta cells. It has also been shown to moderately decrease blood glucose levels while encouraging glucose stimulated insulin secreation.
  3. Early studies are showing that NAC may be helpful in the early stages of some cancers. Some experimental evidence has demonstrated that NAC inhibits mucogenic ( causing a mutation in genetic material) agents, protects DNA and enzymes in the nucleaus of the cell. It was also found to decrease free radical production.
  4. More studies are needed on the role NAC plays in immune system support. In a small study eight patients who showed resistance to the drugs used to suppress organ rejection after a transplant were given NAC. In these patients, six showed an immediate response, four of these responses were complete wile two were partial. More and larger studies are needed in this promising area of NAC supplementation.
  5. Animal studies have shown that NASC can help prevent the death of nerve cells and help protect the synaptic mitochondria against free radical damage. The mice who received NAC supplementation showed a significant improvement in some memory deficits seen in elderly mice. A significant reduction of free radical destruction in the synaptic mitochondria was also seen when compared with the non supplemented mice.

Dietary Sources

The body makes cysteine from the essential amino acid methionine. Nac is also found in most high protein foods such as:

Ricotta cheese
 Ricotta cheese
Cottage cheese
 Cottage cheese
Yogurt
 Yogurt
Wheat germ
 Wheat germ
Oat flakes
 Oat flakes
Granola
 Granola
Poultry
 Poultry
Pork
 Pork
Pork sausage
 Pork sausage
Beef
 Beef

Recommended Dosage:

NAC is used intravenously in a hospital setting to treat acetaminophen overdoses. Acetaminophen overdose is a medical emergency and treatment needs to begin within 8 hours of ingestion to prevent liver damage.

NAC is available by prescription as:

  1. An aerosol spray
  2. Liquid solution

NAC is available over the counter as:

  1. A powder
  2. Capsules in 500mg, 750mg
  3. Tablets of 500mg and 600mg

Recommended adult dosage is condition dependant. For:

  • A respiratory illness

200mg twice a day for chronic bronchitis

ARDS (acute respiratory distress syndrome) is a medical emergency and treated in the emergency room with intravenous NAC.

  • As a nutritional supplement and for antioxidant protection

500mg a day to start. The dosage should be increase only under the guidance of a health care practioner.

Those with HIV/AIDS may be put on a dose as high as 4,000mg per day.

  • A multivitamin should be added to an NAC regime to ensure that the B vitamins needed when taking NAC are supplied.

Some forms of cysteine are toxic. D-cysteine, D-evsume and 3-methy cysteine should be avoided.

There are no recommendations for NAC supplementation in children. If lab tests reveal an amino acid imbalance a health care practioner may recommend supplementation and monitor the situation.

Contra-indications

NAC supplements have been known to cause gastrointestinal problems such as nausea, vomiting or diarrhea.

NAC given intravenously has been known to cause severe allergic reactions and even anaphylaxis (a life threatening allergic reaction).

People who have a kidney condition known as cystinuria (a condition that causes an excessive amount of cysteine to be excreted in the urine) should not take NAC or cysteine supplements.

People who have a tendency to form kidney stones particularly cysteine stones should avoid NAC supplements.

NAC and its metabolites (breakdown products) could produce a false positive test for ketone bodies (using nitropusside) in those with diabetes.

Preterm newborns should not receive NAC supplements as their kidneys are not developed to handle its breakdown.

There are no other contraindications for NAC when used as a nutritional supplement except in women who are pregnant or breastfeeding should not take NAC except under the guidance of their health care provider.

Drug interactions

When taking along with nitrates NAC has been known to cause headaches.

Carbamazepine taken with NAC supplements may reduce the serum levels of carbamazepine.

There have been no interactions with nutritional supplements or herbs reported.

Although there have been no reported overdoses with oral NAC supplementation, there have been rports when it is used intravenously to treat acetaminophen overdoses.

Web References

  1. http://www.pdrhealth.com/drug_info/nmdrugprofiles/nutsupdrugs/ace_0178.shtml
  2. http://www.uspharmacist.com/oldformat.asp?url=newlook/files/Feat/ace.cfm&pub_id=8&article_id=1
  3. http://en.wikipedia.org/wiki/N-Acetylcysteine
  4. http://www.umm.edu/altmed/ConsSupplements/Cysteinecs.html

Printed Reference Material

  1. Adair JC, Knoefel JE, Morgan N. Controlled trial of N-acetylcysteine for patients with probable Alzheimer's disease. Neurology. 2001;57(8):1515-1517.
  2. Ahola T, Fellman V, Laaksonen R, et al. Pharmacokinetics of intravenous N-acetylcysteine in pre-term new-born infants. Eur J Clin Pharmacol. 1999; 55:645-650.
  3. Ames BN. Micronutrient deficiencies: A major cause of DNA damage. Ann NY Acad Sci. 2000;889:87-106.
  4. Andreassen OA, Dedeoglu A, Klivenyi P, Beal MF, Bush AI. N-acetyl-L-cysteine improves survival and preserves motor performance in an animal model of familial amylotrophic lateral sclerosis. Neuroreport. 2000;11(11):2491-2493.
  5. Ardissino D, Melini 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. 1997; 29:941-947.
  6. Ardissino D, Merlini PA, Savonitto S, Demicheli G, et al. Effect of transdermal nitroglycerin or N-Acetylcysteine, or both, in the long-term treatment of unstable angina pectoris. J Am Coll Cardiol. 1997;29(5):941-947.
  7. Arstall MA, Yang J, Stafford I, Betts WH, Horowitz JD. N-acetylcysteine in combination with nitroglycerin and streptokinase for treatment of evolving acute myocardial infarction: safety and biochemical effects. Circulation. 1995;92:2855-2862.
  8. Behr J, Maier K, Degenkolb B, Krombach F, Vogelmeier C. Antioxidative and clinical effects of high-dose N-acetylcysteine in fibrosing alveolitis. Am J Respir Crit Care Med. 1997;156:1897-1901.
  9. Beloqui O, Prieto J, Suarez M, et al. N-acetyl cysteine enhances the response to interferon-alpha in chronic hepatitis C: a pilot study. J Interferon Res. 1993;13:279-282.
  10. Bongers V, de Jong J, Steen I, et al. Antioxidant-related parameters in patients treated for cancer chemoprevention with N-acetylcysteine. Europ J Cancer. 1995; 31A:921-923.
  11. Cai J, Nelson KC, Wu M, Sternberg P Jr, Jones DP. Oxidative damage and protection of the RPE. Prog Retin Eye Res. 2000;19(2):205-221.
  12. Carter EA. Enhanced acetaminophen toxicity associated with prior alcohol consumption in mice; prevention by N-acetylcysteine. Alcohol. Jan-Feb 1987; 4(1): 69-71.
  13. Chevez-Barrios P, Wiseman AL, Rojas E, Ou CN, Lieberman MW. Cataract develoment in gamma-glutamyl transpeptidase deficient mice. Exp Eye Res. 2000;71(6):575-582.
  14. Chirkov YY, Horowitz JD. N-Acetylcysteine potentiates nitroglycerin-induced reversal of platelet aggregation. J Cardiovasc Pharmacol. 1996;28(3):375-380.
  15. Christman BW, Bernard GR. Antilipid mediator and antioxidant therapy in adult respiratory distress syndrome. New Horiz. Nov 1993; 1(4): 623-630.
  16. Colombo AA, Alessandrino EP, Bernasconi P, et al. N-acetylcysteine in the treatment of steroid-resistant acute graft-versus-host-disease: preliminary results. Gruppo Italiano Trapianto di Midollo Osseo (GITMO) Transplantation. 1999; 68:1414-1416.
  17. D'Agostini F, Bagnasco M, Giunciuglio D, Albini A, De Flora S. Inhibition by oral N-acetylcysteine of doxorubicin-induced clastogenicity and alopecia, and prevention of primary tumors and lung micrometastases in mice. Int J Oncol. 1998;13:217-224.
  18. Davreux CJ, Soric I, Nathens AB, et al. N-acetylcysteine attenuates acute lung injury in the rat. Shock. Dec 1997; 8(6): 432-438.
  19. Dawson AH, et al. Adverse reactions to N-acetylcysteine during treatment for paracetamol poisoning. Med J Aust. 1989; 150:329-331.
  20. De Flora S, D'Agostini F, Masiello L, Giunciuglio D, Albini A. Synergism between N-Acetylcysteine and doxorubicin in the prevention of tumorigenicity and metastasis in murine models. Int J Cancer. 1996;67:842-848.
  21. De Flora S, Grassi C, Carati L. Attenuation of influence-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment. Eur RespirJ. 1997; 10:1535-1541.
  22. De Rosa SC, Zaretsky MD, Dubs JG, Roederer M, Anderson M, Green A, et al. N-acetylcysteine replenishes glutathione in HIV infection. Eur J Clin Invest. 2000;30:915-929.
  23. DeVries N, De Flora S. N-acetyl-L-cysteine. J Cell Biochem. 1993; Supp 17F:270-277.
  24. Domenighetti G, Quattropani C, Schaller MD. Therapeutic use of N-acetylcysteine in acute lung diseases. [Review, French]. Rev Mal Respir. 1999;16(1):29-37.
  25. Domenighetti G, Suter PM, Schaller MD, Ritz R, Perret C. Treatment with N-acetylcysteine during acute respiratory distress syndrome: a randomized, double-blind, placebo-controlled clinical study. J Crit Care. 1997;12(4):177-182.
  26. Doroshow JH, Locker GY, Ifrim I, Myers CE. Prevention of doxorubicin cardiac toxicity in the mouse by N-Acetylcysteine. J Clin Invest. 1981;68:1053-1064.
  27. Droge W. Cysteine and glutathione deficiency in AIDS patients: a rationale for the treatment with N-acetyl-cysteine. [Review]. Pharmacology. 1993;46(2):61-65.
  28. Franceschini G, et al. Dose-related increase in HDL-cholesterol levels after N-acetylcysteine in man. Pharmacol Res. Oct-Nov 1993; 28(3): 213-218.
  29. Gavish D, Breslow JL. Lipoprotein (a) reduction by N-acetylcysteine. Lancet. 1991; 337:203-204.
  30. Goodman MT, McDuffie K, Hernandez B, Wilkens LR, Selhub J. Case-control study of plasma folate, homocysteine, vitamin B12, and cysteine as markers of cervical dysplasia. Cancer. 2000;89:376-382.
  31. Harrison PM, Wendon JA, Gimson AES, et al. Improvement by acetylcysteine of hemodynamics and oxygen transport in fulminant hepatic failure. N Engl J Med. 1991; 324:1852-1857.
  32. Hershkovitz E, Shorer Z, Levitas A, Tal A. Status epilepticus following intravenous N-acetylcysteine therapy. Isr J Med Sci. 1996;32(11):1102-1104.
  33. Ho E, Chen G, Bray TM. Supplementation of N-acetylcysteine inhibits NFkappaB activation and protects against alloxan-induced diabetes in CD-1 mice. FASEB J. 1999; 13:1845-1854.
  34. Hogan JC, Lewis MJ, Henderson AH. Chronic administration of N-acetylcysteine fails to prevent nitrate tolerance in patients with stable angina pectoris. Br J Clin Pharmacol. 1990; 30:573-577.
  35. Hogan JC, Lewis MJ, Henderson AH. N-acetylcysteine fails to attenuate haemodynamic tolerance to glyceryl trinitrate in healthy volunteers. Br J Clin Pharmacol. 1989; 28:421-426.
  36. Holdiness MR. Clinical pharmacokinetics of N-acetylcysteine. Clinical Pharmacokinet. 1991; 20:123-134.
  37. Horowitz JD, Henry CA, Syrjanen ML, et al. Nitroglycerine/N-acetylcysteine in the management of unstable angina pectoris. Eur Heart J. 1988; 9 Suppl A:95-100.
  38. Iversen HK. N-acetylcysteine enhances nitroglycerin-induced headache and cranial artery response. Clin Pharmacol Ther. 1992;52:125-133.
  39. Iversen HK. N-acetylcysteine enhances nitroglycerin-induced headache and cranial artieral response. Clin Pharmacol Ther. 1992; 52:125-133.
  40. Jackson IM, et al. Efficacy and tolerability of oral acetylcysteine (Fabrol) in chronic bronchitis: a double-blind placebo controlled study. J Int Med Res. 1984; 12(3): 198-206.
  41. Jones AL, Jarvie DR, Simpson D, et al. Pharmacokinetics of N-acetylcysteine are altered in patients with chronic liver disease. Aliment Pharmacol Ther. 1997; 11:787-791.
  42. Kelebic T, Kinter A, Poli G, et al. Suppression of human immunodeficiency virus expression in chronically infected monocyte cells by glutathione, glutathione ester, and N-acetylcysteine. Proc Natl Accd Sci. 1991; 88:986-990.
  43. Kozer E, Koren G. Management of paracetamol overdose: current controversies. [Review]. Drug Saf. 2001;24(7):503-512.
  44. Lenz AG, Jorens PG, Meyer B, et al. Oxidatively modified proteins in bronchoalveolar lavage fluid of patients with ARDS and patients at-risk for ARDS. Eur Respir J. 1999;13(1):169-174.
  45. Louwerse ES, Weverling GJ, Bossuyt PM, et al. Randomized double-blind controlled trial of acetylcysteine in amyotrophic lateral sclerosis. Arch Neurol. 1995; 52:559-564.
  46. Mani TGK, et al. Adverse reactions to acetylcysteine and effects of overdose. Br Med J. 1984; 289:217-219.
  47. Marchetti G, Lodola E, Licciardello L, Colombo A. Use of N-acetylcysteine in the management of coronary artery diseases. Cardiologia. Jul 1999; 44(7): 633-637.
  48. Martinez M, Hernandez AI, Martinez N. N-acetylcysteine delays age-associated memory impairment in mice: role in synaptic mitochondric. Brain Res. 2000; 855:100-106.
  49. Micke P, Beeh KM, Schlaak JF, Buhl R. Oral supplementation with whey proteins increases plasma glutathione levels of HIV-infected patients. Eur J Clin Invest. 2001;31(2):171-178..
  50. Molnar Z, Schearer E, Lowe D. N-acetylcysteine treatment to prevent the progression of multisystem organ failure: a prospective, randomized placebo-controlled study. Crit Care Med. 1999; 27:1100-1104.
  51. Montanini S, Sinardi D, Pratico C, et al. Use of acetylcysteine as the life-saving antidote in Amanita phalloides (death cap) poisoning. Case report on 11 patients. Arzneimittel-forschung. 1999; 49:1044-1047.
  52. Muller F, Svardal AM, Nordoy I, Berge RK, Aukrust P, Froland SS. Virological and immunological effects of antioxidant treatment in patients with HIV infection. Eur J Clin Invest. 2000;30(10):905-914.
  53. Oikawa S, Yamada K, Yamashita N, et al. N-acetylcysteine, a cancer chemopreventive agent, causes oxidative damage to cellular and isolated DNA. Carcinogenesis. 1999; 20:1485-1490.
  54. Ortolani O, Conti A, De Gaudio AR, et al. Protective effects of N-acetylcysteine and rutin on the lipid peroxidation of the lung epithelium during the adult respiratory distress syndrome. Shock. 2000; 13:14-18.
  55. Patrick L. Hepatitis C: epidemiology and review of complementary/alternative medicine treatments. Alt Med Rev. 1999;4(4):220-238.
  56. Pelle E, et al. Protection against cigarette smoke-induced damage to intact transformed rabbit corneal cells by N-acetyl-L-cysteine. Cell Biol Toxicol. Aug 1998; 14(4): 253-259.
  57. Perry HE, Shannon MW. Efficacy of oral versus intravenous N-acetylcysteine in acetaminophen ovedose:results of an open-label, clinical trial. J Pediatr. Jan 1998;132(1): 149-152.
  58. Pizzorno JE, Murray MT. Textbook of Natural Medicine. Vol 1. 2nd ed. Edinburgh: Churchill Livingstone; 1999:296-297.
  59. Pizzulli, L, Hagendorff A, Zirbes M, Jung W, Lüderitz B. N-Acetylcysteine attenuates nitroglycerin tolerance in patients with angina pectoris and normal left ventricular function. Am J Cardiol. 1997;79:28-33.
  60. Ruiz FJ, et al. N-acetyl-L-cysteine potentiates depressor response to captopril and enalaprilat in SHRs. Am J Physiol. Sep 1994; 267 (3 Pt 2): R767-772.
  61. Shabert JK, Winslow C, Lacey JM, Wilmore DW. Glutamine antioxidant supplementation increases body cell mass in AIDS patients with weight loss: a randomized, double-blind controlled trial. Nutrition. 1999;11:860-864.
  62. Shils, ME, Olson JA, Shike M, Ross AC, eds. Modern Nutrition in Health and Disease. 9th ed. Baltimore, MD: Williams & Wilkins; 1999:543-556.
  63. Smilkstein MJ, Knapp GL, Kulig KW, Rumack BH. Efficacy of oral N-acetylcysteine in the treatment of acetaminophen overdose. Analysis of the national multicenter study (1976 to 1985). N Engl J Med. Dec 15 1988; 319(24): 1557-1562.
  64. Stavem K. Anaphylactic reaction to N-acetylcysteine after poisoning with paracetamol. Tidsskr Nor Laegeforen. May 30 1997; 117(14): 2038-2039.
  65. Stey C, Steurer J, Bachmann S, Medici TC, Tramer MR. The effect of oral N-acetylcysteine in chronic bronchitis: a quantitative systematic review. Eur Respir J. 2000 Aug;16(2):253-262.
  66. Suárez C, Del Arco C, Lahera V, Ruilope LM. N-Acetylcysteine potentiates the antihypertensive effect of angiotensin converting enzyme inhibitors [letter]. Am J Hypertens. 1995;8:859-861.
  67. van Hoogdalem EJ, van den Hoven WE, Terpstra IJ, van Zijtveld J, Verschoor, JSC. Nail penetration of the antifungal agent oxiconazole after repeated topical application in healthy volunteers, and the effect of acetylcysteine. Eur J Pharm Sci. 1997;5:119-127.
  68. van Zandwijk N. N-acetylcysteine for lung cancer prevention. Chest. 1995;107(5):1437-1441.
  69. Walters MT, et al. A double-blind, cross-over, study of oral N-acetylcysteine in Sjogren's syndrome. Scand J Rheumatol Suppl. 1986; 61: 253-258.

Monday, March 31, 2008 10:07:13 AM (US Mountain Standard Time, UTC-07:00)  #    Comments [0]   N  |  Trackback
Home | Wholesale | FAQs | Printable Order Form | Return Policy | Privacy Policy | Contact Us | Site Map