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N-acetyl cysteine (NAC) is a specially modified form of the dietary amino acid cysteine. When taken orally, NAC is thought to help the body make the important antioxidant enzyme glutathione. It has shown promise for a number of conditions, especially chronic bronchitis.
There is no daily requirement for NAC, and it is not found in food.
Optimal levels of NAC have not been determined. The amount used in studies has varied from 250 to 1,500 mg daily.
It has been suggested that NAC may increase excretion of trace minerals; some evidence, however, suggests that this effect is too minimal to make a real difference. 1 Prudence suggests that individuals taking NAC for an extended period of time should also consider taking a standard multivitamin/multimineral supplement.
What Is the Scientific Evidence for N-Acetyl Cysteine?
Individuals who have smoked cigarettes for many years eventually develop deterioration in their lungs leading to various symptoms, including chronic production of thick mucus. This so-called chronic bronchitis (closely related to chronic obstructive pulmonary disease ) tends to flare up periodically into severe acute attacks possibly requiring hospitalization.
Regular use of NAC may diminish the number of these attacks. A review and meta-analysis selected 8 double-blind, placebo-controlled trials of NAC for chronic bronchitis. 2 3 4 5 6 7 8 9 The results of these studies, involving a total of about 1,400 individuals, suggest that NAC taken daily at a dose of 400 mg to 1,200 mg can reduce the number of acute attacks of severe bronchitis. However, the largest and best of these studies, a 3-year, double-blind, placebo-controlled trial of 523 people, failed to find that use of NAC at a dose of 600 mg daily reduced exacerbations or retarded the typical progressive worsening of lung function. 10 It is not clear how NAC works (if it does); the old concept that it acts by thinning mucus may not be correct.
In a double-blind, placebo-controlled study of 262 seniors, regular use of NAC at dose of 600 mg twice daily helped prevent the development of influenza-like illnesses . 11 Over the 6-month study period, only 25% of participants taking NAC developed flu-like symptoms, as compared to 79% in the placebo group, a statistically significant difference.
Interestingly, blood tests suggested that NAC did not prevent influenza infection—about as many people showed antibodies indicating influenza infection in the NAC group as in the placebo group. Rather, the supplement seemed to reduce the rate at which influenza infection became severe enough to cause noticeable symptoms. Tests of immune function hinted that NAC functioned by increasing the strength of the immune response.
Angina pectoris is a squeezing feeling in the chest caused by inadequate blood supply to the heart. It can be a precursor of heart attacks. People with angina often use the drug nitroglycerin to relieve symptoms. One 4-month, double-blind, placebo-controlled study of 200 people with heart disease found that the combination of nitroglycerin and NAC significantly reduced the incidence of heart attacks and other severe heart problems. 12 NAC alone and nitroglycerin alone were not as effective. The only problem was that the combination of nitroglycerin and NAC caused severe headaches in many participants. This effect has been seen in other studies as well. 13 NAC may also help in cases of nitroglycerin tolerance, a condition in which the drug becomes less effective over time. In a small double-blind study of 32 people with angina, tolerance developed in 15 of 16 individuals who took nitroglycerin only, but in just 5 of 16 individuals who took nitroglycerin plus 2 g of NAC daily. 14 However, other studies have found no benefit. 15
In a double-blind, placebo-controlled study of 150 women suffering from infertility who had not responded to treatment with the fertility drug clomiphene, use of NAC at 1,200 mg daily significantly augmented the effectiveness of clomiphene. 16 Treatment was begun on day 3 of the menstrual cycle and continued for 5 days. About 20% of women in the NAC plus clomiphene group became pregnant, as compared to 0% in the placebo plus clomiphene group.
Acute Respiratory Distress Syndrome
A double-blind, placebo-controlled clinical trial compared the effectiveness of NAC, Procysteine (a synthetic cysteine building-block drug), and placebo in 46 people with acute respiratory distress syndrome. 17 This catastrophic lung condition can occur when an unconscious person inhales a small amount of his or her own vomit. Both NAC and Procysteine reduced the severity of the condition in some people (as compared with placebo). However, overall it did not reduce the number of deaths.
Colon Cancer Prevention
A preliminary double-blind, placebo-controlled study of NAC enrolled 62 individuals, each of whom had had a polyp removed from the colon. 18 The abnormal growth of polyps is closely associated with the development of colon cancer. In this study, the potential anticancer benefits of NAC treatment were evaluated by taking a biopsy of the rectum. Individuals taking NAC at 800 mg daily for 12 weeks showed more normal cells in the biopsied tissue as compared to those in the placebo group.
- Hjortsø E, Fomsgaard JS, Fogh-Andersen N. Does N-acetylcysteine increase the excretion of trace metals (calcium, magnesium, iron, zinc and copper) when given orally? Eur J Clin Pharmacol. 39(1):29-31.
- Grandjean EM, Berthet P, Ruffmann R, Leuenberger P. Efficacy of oral long-term N-acetylcysteine in chronic bronchopulmonary disease: a meta-analysis of published double-blind, placebo-controlled clinical trials. Clin Ther. 22(2):209-21.
- Hansen NCG, Skriver A, Brorsen-Riis L, et al. Orally administered N-acetylcysteine may improve general well-being in patients with mild chronic bronchitis. Respir Med. 1994;88:531-535.
- Grassi C, Casali L, Rossi A, Rampulla C, Zanon P, Cerveri I, Mastroberardino M. A comparison between different methods for detecting bronchial hyperreactivity. Bronchial hyperreactivity: methods of study. Eur J Respir Dis Suppl. 106():19-27.
- Grassi C, Morandini GC. A controlled trial of intermittent oral acetylcysteine in the long-term treatment of chronic bronchitis. Eur J Clin Pharmacol. 09(5-6):393-6.
- Riise GC, Larsson S, Larsson P, Jeansson S, Andersson BA. The intrabronchial microbial flora in chronic bronchitis patients: a target for N-acetylcysteine therapy? Eur Respir J. 7(1):94-101.
- Rasmussen JB, Glennow C. Reduction in days of illness after long-term treatment with N-acetylcysteine controlled-release tablets in patients with chronic bronchitis. Eur Respir J. 1(4):351-5.
- Parr GD, Huitson A. Oral Fabrol (oral N-acetyl-cysteine) in chronic bronchitis. Br J Dis Chest. 81(4):341-8.
- Boman G, Bcker U, Larsson S, et al. Oral acetylcysteine reduces exacerbation rate in chronic bronchitis: report of a trial organized by the Swedish Society for Pulmonary Diseases. Eur J Respir Dis. 1983;64:405-415.
- Decramer M, Rutten-van Mölken M, Dekhuijzen PN, Troosters T, van Herwaarden C, Pellegrino R, van Schayck CP, Olivieri D, Del Donno M, De Backer W, Lankhorst I, Ardia A. 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. 365(9470):1552-60.
- De Flora S, Grassi C, Carati L. Attenuation of influenza-like symptomatology and improvement of cell-mediated immunity with long-term N-acetylcysteine treatment. Eur Respir J. 10(7):1535-41.
- 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. 1997;29:941-947.
- Iversen HK. N-acetylcysteine enhances nitroglycerin-induced headache and cranial arterial responses. Clin Pharmacol Ther. 52(2):125-33.
- 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. 79(1):28-33.
- 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. 30(4):573-7.
- Rizk AY, Bedaiwy MA, Al-Inany HG. N-acetyl-cysteine is a novel adjuvant to clomiphene citrate in clomiphene citrate-resistant patients with polycystic ovary syndrome. Fertil Steril. 83(2):367-70.
- Bernard GR, Wheeler AP, Arons MM, et al. A trial of antioxidants N-acetylcysteine and procysteine in ARDS. The Antioxidant in ARDS Study Group. Chest. 1997;112:164-172.
- Estensen RD, Levy M, Klopp SJ, Galbraith AR, Mandel JS, Blomquist JA, Wattenberg LW. N-acetylcysteine suppression of the proliferative index in the colon of patients with previous adenomatous colonic polyps. Cancer Lett. 147(1-2):109-14.