The Antioxidant, Antimucus Compound N-Acetylcysteine

Amino acid derivative makes chronic bronchitis easier to bear

It's bad enough to contract an illness - acute bronchitis, for example - that lays you low for a few days or weeks, making your life miserable. But pretty soon, you get better and get back to work or play or whatever it is you do. What's much worse is a chronic illness - one that just won't go away.

The dictionary defines chronic as "lasting for a long period of time or marked by frequent recurrence." An example is chronic bronchitis. For the victim, this disease is an ongoing albatross that makes breathing increasingly difficult. Eventually, when breathing simply becomes too difficult, it stops. Not the disease - the breathing.

So anything that can help with chronic bronchitis (CB) is good news, and the latest news on this front has the catchy name N-acetylcysteine. Let's call it NAC. Researchers in Switzerland have reported that prolonged use of NAC as a dietary supplement prevents acute exacerbations (we'll explain that term shortly) of CB, thus possibly reducing the overall toll taken by the disease in terms of both health and health-care costs.1

This finding was reported in the form of a meta-analysis. In a meta-analysis, experts in the field survey all the literature on a given topic, using tough criteria designed to weed out the poor studies and allow only the really good ones to make the grade. They then crunch the data from all the good studies to arrive at the best estimate of what the truth is.

What Is N-Acetylcysteine?
The N-acetylcysteine molecule is a derivative of the sulfur-containing amino acid cysteine. It is better absorbed by the gut than cysteine, and it is a source of cysteine - which, by the way, is one of three amino acids that constitute a molecule of glutathione, the body's master antioxidant.

In case you're wondering what that N-prefix means, it denotes a nitrogen atom - in this case, in a molecule of cysteine, HSCH2CH(NH2)COOH. In the N-acetylcysteinemolecule, a group of atoms called an acetyl group, -COCH3, is attached to that nitrogen atom, where it replaces one of the two hydrogen atoms that are normally attached there. The formula then becomes HSCH2CH(NHCOCH3)COOH.

Such substitutions of a particular small group of atoms - a methyl group or an acetyl group, for example - for a hydrogen atom on a larger molecule are very common in biochemistry.

They're very important too, because the transfer of such groups from one molecule to another - called methylation or acetylation reactions, in these two examples - plays a vital role in many physiological processes upon which life depends. The presence or absence of such substituent groups can have a profound effect on the molecule's biological activity.

Thus a molecule such as N-acetylcysteine, which can donate its acetyl group, is a key biochemical agent.


To appreciate what NAC can do for chronic bronchitis, we need to be clear on what this disease actually is. Unlike the short-lived acute bronchitis, which is an infection (usually viral) of the bronchial tubes, the chronic condition is not caused by infection. It is defined by doctors as a persistent inflammation of the bronchial tubes that is characterized by production of sputum* on most days of the month for at least three months out of the year and lasting for at least two consecutive years. The condition varies throughout the year and is usually worse in the winter.

*Sputum isn't saliva. It's mainly phlegm coughed up from the respiratory tract. And what is phlegm, exactly? It's a sticky mixture of mucus and puslike material containing white blood cells. It's so disgusting that we put it in this footnote, which we hope you won't read.

Smoking always makes CB worse. In fact, smoking is the principal cause of CB. If you don't smoke, you probably won't get it. If you're a long-term smoker, however, you have a good chance of getting it. The great majority of those who die from it are smokers, and they are ten times more likely to die from it than nonsmokers. Please don't smoke.

The main symptoms of CB are coughing up sputum, wheezing, and shortness of breath. That's the routine stuff. Acute exacerbations of this condition include increased cough (beyond what's normal for you); a change in the quantity or color of your sputum (a yellow-green color usually means that a bacterial infection has set in), and increased breathlessness (again, beyond the norm). A major goal of CB therapy is to reduce the frequency of acute exacerbations. This would lessen the socioeconomic burden imposed by this widespread disease, which afflicts millions of Americans.

For several decades, mucolytic (mucus-reducing) drugs have been advocated for preventing acute exacerbations of CB, but the efficacy of such drugs remains controversial.2 That has prompted interest in the use of the dietary supplement NAC, which has been shown in the laboratory to attack mucus and make it more fluid. NAC is also a potent antioxidant, whose particular mechanism of action is believed to lend itself well to the treatment of bronchopulmonary diseases.3,4 In some studies, but not all, NAC has been shown to prevent acute exacerbations of CB and to provide symptomatic relief as well.

NAC is notable not just as an antioxidant but also as a precursor to the body's "master antioxidant," glutathione, the most important antioxidant in our cells. Glutathione itself cannot be taken as a supplement, by the way, because it breaks down in the digestive tract. Our bodies produce it in great abundance, however. It can become depleted by the frequent use of acetaminophen (Tylenol), and in cases of acetaminophen overdose (the most common reason for calls to poison control centers in the United States), the standard treatment is with NAC, which protects the liver from the damage that would otherwise be done. NAC is also used to treat poisoning by the death cap mushroom, Amanita phalloides.

An excessive intake of NAC can itself have an undesired side effect, however: if glutathione levels are boosted too much through nutritional supplements, the body may decrease its own natural production of glutathione - not a good situation, considering the overwhelming importance of this molecule for life itself.5 It is also worth noting that NAC, if taken in too large an amount, can do a turnaround and become a pro-oxidant rather than anantioxidant.6,7 This underscores the important lesson that no supplement should ever be taken in more than the recommended amount, lest its benefits turn to liabilities.

The Swiss researchers evaluated eight studies from five different countries, conducted between 1976 and 1994 on a total of 1408 patients with chronic bronchitis. Five of the studies had found a positive benefit from NAC, whereas three had not. Their duration ranged from two to six months, and the dosages used varied from 600 mg three times per week (equivalent to 257 mg per day, on average) to 600 mg per day. Several studies used 400 mg per day, which is now considered to be the lower limit of the recommended dose, according to the authors. The NAC was well tolerated: side effects were mostly mild gastrointestinal upset.

When all the statistical smoke cleared, the authors concluded:

. . . the results of the present meta-analysis suggest that 3 to 6 months of therapy with NAC results in a definite, although not extreme, reduction in the expected number of acute exacerbations of CB and may thus decrease morbidity and health care costs.


  1. Grandjean EM, Berthet P, Ruffmann R, Leuenberger P. Efficacy of oral long-term N-acetylcysteine in chronic bronchopulmonary disease: a meta-analysis of double-blind, placebo-controlled clinical trials. Clin Therapeut 2000;22(2):209-21.
  2. Kobayushi K, Wanner A. "Mucociliary clearance and ciliary activity," in Chung KF, Barnes PJ, eds. Pharmacology of the Respiratory Tract: Experimental and Clinical Research. Marcel Dekker, New York, 1993.
  3. Repine JE, Bast A, Lunkhorst J, and the Oxidative Stress Study Group. Oxidative stress in chronic obstructive pulmonary disease. Am J Respir Crit Care Med 1997;156:341-57.
  4. Barnes PJ. New therapies for chronic obstructive pulmonary disease. Thorax 1998;53:137-47.
  5. Sahelian R. Mind Boosters: A Guide to Natural Supplements That Enhance Your Mind, Memory, and Mood. St. Martin's Press, New York, 2000.
  6. Kleinveld HA, Demacker PNM, Stalenhoef AFH. Failure of N-acetylcysteine to reduce low-density lipoprotein oxidizability in healthy subjects. Eur J Clin Pharmacol 1992;43:639-42.
  7. Sprong RC et al. Low-dose N-acetylcysteine protects rats against endotoxin-mediated oxidative stress, but high dose increases mortality. Am J Respir Crit Care Med 1998;157 (4 Pt 1):1283-93.