NAC (N-Acetyl-L-Cysteine)
N-Acetyl-L-Cysteine, or NAC, is an amino acid that acts as an antioxidant and is a precursor in the body to glutathione (GSH), a critical antioxidant. NAC is a more stable form of the amino acid cysteine (which is very unstable and oxidizes readily) because it has an acetyl group (CH3CO) attached. NAC is also more bioavailable and 6 times as cost-effective as the tripeptide glutathione. Glutathione consists of three amino acids: cysteine, glutamic acid and glycine. The body breaks this tripeptide apart before absorption, but the rate limiting (most valuable) amino acid for the purpose of making glutathione is the cysteine. Therefore, simply taking NAC makes much more sense.
Mechanism of action
Most of the beneficial effects of orally administered NAC are theorized to be a result of increased source of
GSH groups. NAC can stimulate GSH synthesis, enhance glutathione-s-transferase activity, promote detoxification and act as an antioxidant.
Clinical Applications
1. Heart disease. Research has pinpointed a specific lipoprotein called Lp(a) as one of the two most reliable indicators of heart disease. Lp(a) is a much more reliable indicator than blood cholesterol levels, low density lipoprotein (HDL) levels, or the ratio of LDL to HDL.
Diets and drugs designed to lower blood cholesterol levels do not lower Lp(a) levels. Recently, it was reported that NAC is the most effective nutrient known to lower Lp(a) levels. NAC reduced Lp(a) levels by
70%. LP(a) is comprised of an LDL particle attached to the large glycoprotein apo(a) by one or more disulfide bonds. NAC breaks up the disulfide bonds by converting each disulfide group into two sulphydryl groups.
NAC also inhibits heart damage by preventing LDL from being oxidized, by reducing plasma homocysteine levels, and by free-radical quenching effects. NAC also protects against ischaemic and reperfusion damage. NAC also potentiates the coronary dilating and anti-platelet effects of nitroglycerine as well as limiting the development of tolerance to nitroglycerine. Finally, ST-depression, a clinical sign of myocardial ischaemia, was not seen following pretreatment with NAC, suggesting attenuation of impaired tissue oxygenation and preservation of myocardial performance by NAC.
2. Immunity and AIDS. NAC effects immunity via its role in intracellular GSH production. This role becomes clinical when normal GSH production pathways are impaired, as for example, by HIV. Eck has shown that reduced intracellular GSH is the “direct and early consequence of retroviral infection”. Intracellular GSH has a powerful influence on how well T- and B-lymphocyte cells function and the production of phagocytes (macrophages, monocytes and neutrophils). NAC has been shown to block the AIDS virus production in-vitro.
3. Detoxification & Chelator. Sulphydryl groups protect against toxins. SH groups react directly with many poisons, including herbicides, drugs (acetaminophen), environmental pollutants such as carbon tetrachloride, microorganisms including E. coli and aflatoxin, and against heavy metals. Indirectly, NAC helps with detoxification by producing optimal amounts of GSH for conjugation reactions, making harmful compounds less toxic.
NAC is approved as a drug for use to prevent liver damage from acetaminophen overdose.
4. Respiratory effects. NAC has been used for over 30 years as a mucolytic in persons having bronchopulmonary diseases including chronic bronchitis, cystic fibrosis, asthma, sinusitis, and pneumonia. NAC helps reduce the viscosity of mucus so that it may be more easily coughed up. NAC accomplishes this by converting the disulphide bond of the mucoproteins into sulphydryl bonds and cleaving the mucoproteins into smaller molecules. Recently, a number of studies have appeared studying the role of NAC in preventing influenza. In 1991, in an Italian multi-centric double-blind, placebo-controlled study of 262 patients (75% were over 65 years of age), NAC dose of 600mg twice a day resulted in only 29% developing flu-like clinical syndrome, compared to 51% of placebo-treated subjects (p=0.0006).
References
Flanagan, R. (1991). Use of N-Acetyl cysteine in clinical toxicology. AM.J. Med; 91: 131-9.
De Flora S, Grassi C, Carati L. (1997). Attention of influenza symptomatology and improvement of cell-mediated immunity with long-term NAC treatment. Eur. Respir J; 10: 1535-1541.
Lorber A, et al. (1973). Clinical application for heavy metal-complexing potential of N-Acetyl-cystene. J. Clin. Pharmacol; 13: 332-336.
Gavish D, Breslow JL. (1991). Lipoproteins (a) reduction by N-acetylcysteine. The Lancet; 337: 203-4.
