Tuesday, September 22, 2009

N-Acetyl Cysteine (NAC)

Overview

N-Acetyl Cysteine (NAC) is a derivative of the sulfur-containing amino acid, cysteine. It is produced naturally in the body and is found in many protein-containing foods. NAC is an intermediary, along with glutamic acid and glycine, in the conversion of cysteine into glutathione, the body’s primary cellular antioxidant. Dietary supplements containing NAC are recommended as general antioxidants and specifically to increase cellular glutathione levels, enhance immune system function, and treat bronchitis and other respiratory conditions.


NAC’s proposed benefits in human health are thought to originate from either of its two of its primary actions in the body. First, NAC is rapidly metabolized to intracellular glutathione. Glutathione (GTH) and the enzyme complexes that it forms act as reducing agents and antioxidants in the body. GTH also helps “detoxify” (in the liver) many chemicals into less harmful compounds and accelerates the body’s removal of heavy metals such as mercury and lead. GTH is also known to protect cell membranes, especially those of lymphocytes and phagocytes – two of the major classes of immune cells. While purified glutathione is sold as a dietary supplement, absorption is notoriously low, and NAC is thought to be a better source method of boosting cellular GTH levels. NAC’s second beneficial action in the body is to cleave protein disulfide bonds by converting them to two sulfhydryl groups. In the case of smoker’s cough and bronchitis, this action results in the breakup of mucoproteins in lung mucus, reducing their chain lengths, thinning the mucus and easing breathing.


Comments

Research on NAC has clearly shown value in the treatment of chronic bronchitis and lung ailments as well as for those individuals desiring an increase in generalized antioxidant protection and immune system support.


Scientific Support

Several studies have been performed to confirm that NAC is converted to glutathione in the body (Faintuch et al. 1999). A review of these studies showed that oral NAC supplementation was successful in enhancing the levels of glutathione in the liver, in plasma, and in the bronchioles of the lungs (Walsh and Lee 1999). Lack of glutathione has been shown to contribute to a variety of health conditions such as adult respiratory distress syndrome and idiopathic pulmonary fibrosis (Malorni et al. 1998).


In a double-blind placebo-controlled study of 116 subjects with chronic bronchitis, the therapeutic effects of NAC were investigated over a six-month period (Pela et al. 1999). The group receiving NAC experienced a significant reduction (by almost one-third) in the number of sick days from December to March (173 NAC vs. 456 placebo) as well as a greater reduction (by almost half) in days of coughing (204 NAC vs. 399 placebo). NAC has also been shown to help reduce levels of fatigue and improve ability for muscle contraction during exhaustive exercise, possibly due to reduced levels of oxidative stress (Droge 1999).


A clinical trial of NAC and immune function evaluated the response of the CD4-CD8 lymphocyte system in HIV-positive patients (where falling CD4 counts are an indicator of disease progression). The 15 patients were divided into two groups, one receiving two 400mg doses of NAC parenterally twice daily and the other receiving 600mg orally twice daily (Molnar et al. 1998, Puerto et al. 2002). During the experiment, 8 patients receiving NAC were considered “successful”, including two patients who became serum negative for the illness and 6 patients who experienced no opportunistic infections. The researchers involved concluded that NAC was a useful adjunct to antiviral and immuno-therapy (Malorni et al. 1998.


Safety / Dosage

Toxicological data shows that NAC is safe for consumption in its therapeutic dosage ranges and high intakes of approximately 60-80 grams per day are not associated with significant adverse effects – although extended supplementation with high levels of NAC could lead to minor zinc depletion. Typical dosage recommendations are in the range of 250-1500mg of NAC daily for the majority of therapeutic benefits.


References

1.Droge W. Cysteine and glutathione in catabolic conditions and immunological dysfunction. Curr Opin Clin Nutr Metab Care. 1999 May;2(3):227-33.

2.Faintuch J, Aguilar PB, Nadalin W. Relevance of N-acetylcysteine in clinical practice: fact, myth or consequence? Nutrition. 1999 Feb;15(2):177-9.

3.Malins DC, Hellstrom KE, Anderson KM, Johnson PM, Vinson MA. Antioxidant-induced changes in oxidized DNA. Proc Natl Acad Sci U S A. 2002 Apr 30;99(9):5937-41. Epub 2002 Apr 23.

4.Malorni W, Rivabene R, Lucia BM, Ferrara R, Mazzone AM, Cauda R, Paganelli R. The role of oxidative imbalance in progression to AIDS: effect of the thiol supplier N-acetylcysteine. AIDS Res Hum Retroviruses. 1998 Nov 20;14(17):1589-96.

5.Marchetti G, Lodola E, Licciardello L, Colombo A. Use of N-acetylcysteine in the management of coronary artery diseases. Cardiologia. 1999 Jul;44(7):633-7.

6.Martinez M, Martinez N, Hernandez AI, Ferrandiz ML. Hypothesis: can N-acetylcysteine be beneficial in Parkinson's disease? Life Sci. 1999;64(15):1253-7.

7.Miquel J. Can antioxidant diet supplementation protect against age-related mitochondrial damage? Ann N Y Acad Sci. 2002 Apr;959:508-16.

8.Molnar Z, MacKinnon KL, Shearer E, Lowe D, Watson ID. The effect of N-acetylcysteine on total serum anti-oxidant potential and urinary albumin excretion in critically ill patients. Intensive Care Med. 1998 Mar;24(3):230-5.

9.Pela R, Calcagni AM, Subiaco S, Isidori P, Tubaldi A, Sanguinetti CM. N-acetylcysteine reduces the exacerbation rate in patients with moderate to severe COPD. Respiration. 1999 Nov-Dec;66(6):495-500.

10.Puerto M, Guayerbas N, Victor V, De la Fuente M. Effects of N-acetylcysteine on macrophage and lymphocyte functions in a mouse model of premature ageing. Pharmacol Biochem Behav. 2002 Nov;73(4):797-804.

11.Walsh TS, Lee A. N-acetylcysteine administration in the critically ill. Intensive Care Med. 1999 May;25(5):432-4.


EDITOR'S NOTE: This monograph can be found in The Health Professional's Guide to Dietary Supplements (Lippincott, Williams & Wilkins) by Shawn M. Talbott, PhD and Kerry Hughes, MS.

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