NAC: Major Laboratory Study Supports AIDS Treatment Theory

by John S. James

A laboratory study by Anthony Fauci, M. D., and other scientists at the U. S. National Institute of Allergy and Infectious Diseases, and at the Cornell University Medical College in New York City, has confirmed and extended earlier work by Dr. Leonard A. Herzenberg and colleagues at Stanford University suggesting that n-acetylcysteine (NAC) can inhibit growth of HIV. NAC is used in many European countries to treat bronchitis; it is not approved for this use in the United States, but has been available for over a year through buyers' clubs.

For background on this drug, see "NAC: Bronchitis Drug May Slow AIDS Virus," AIDS TREATMENT NEWS #88, October 6, 1989; also see issues # 92 and 93. Despite widespread public interest and some scientific interest in the drug, no U. S. controlled trial has yet begun; there are rumors of a trial in Europe, but no results have been published. One monitoring study, in which persons using NAC kept diaries, was organized by the Fight for Life Committee, an AIDS activist group in North Lauderdale, Florida in 1989. Preliminary results, which were positive, were summarized in AIDS TREATMENT NEWS #92, December 1, 1989.

No laboratory study can prove that a drug is helpful for people; only clinical trials can do that. But laboratory studies can suggest which drugs should have priority for trials, and what effects to look for (and therefore how the trials should be designed). The recently published laboratory results will certainly increase interest in NAC -- not as a potential cure or means to control HIV or AIDS entirely, but as a safe and available treatment which may be considerably helpful for some patients.

The New Study

The recent NAC study, by a group headed by Fauci and by Alton Meister, M. D., of Cornell, was published February 1 in Proceedings of the National Academy of Sciences, USA (volume 88, pages 986-990). Here is an overview of how this research was conducted, and what it found.

The experimenters used a line of cells created in the laboratory which have HIV as an inherited part of their DNA. These cells have been used for studies of why HIV is usually latent for many years, and only later becomes active and causes serious disease. The researchers used three chemicals which are known to greatly stimulate HIV activity in these cells: PMA, tumor necrosis factor, and interleukin 6 (IL-6); two of these, tumor necrosis factor and IL-6, are normally found in the body and are known to be markedly increased in persons with AIDS. The researchers tested NAC (and also two related substances) to see if they could prevent this stimulation of viral activity caused by each of the three chemicals. In all three cases, NAC did prevent most of the stimulation of the virus.

NAC is believed to work primarily by increasing the level of glutathione in cells. Glutathione is necessary for life; it helps cells produce energy, and it also helps protect them against oxidation; in addition, it may be an immune modulator, necessary for T-cell activation. A German scientist, Dr. Wulf Droge, at the German Cancer Research Center in Heidelberg, had found that glutathione levels were deficient in cells of persons with AIDS, and that the deficiency worsened as the disease progressed; he was the first to suggest NAC as a potential AIDS treatment, since it is known to raise glutathione levels.

Dr. Droge's work came to the attention of Doctors Leonard Herzenberg and Leonore Herzenberg, who are husband and wife and both members of the Genetics Department at Stanford University. The Herzenbergs brought NAC as a possible AIDS treatment to the attention of the U. S. scientific community. In June 1990 their team published results, in the Proceedings of the National Academy of Sciences, showing that NAC inhibited HIV replication in a variety of laboratory tests.

The new study by Fauci, Meister, and others confirmed the Herzenbergs' results. Also, to make sure that NAC was indeed working by raising glutathione levels, the researchers ran similar experiments, using glutathione itself, and also a glutathione derivative, instead of NAC. All three substances did inhibit HIV infection -- probably by more than one mechanism. NAC was found to have an additional antiviral effect which the other two did not have. These effects, especially the latter, are not well understood. The research with NAC, as well as its immediate importance in supporting the need for clinical trials of this drug, is leading to further insights on how HIV becomes activated in cells -- understanding which could lead to treatments designed to keep the virus permanently inactive.

Comment: Practical Consequences

Anecdotal reports suggest that a minority of people who try NAC feel much better, with benefits such as increased energy and appetite, but that most do not notice any change. We checked with buyers' clubs and found that a number of people have continued to use NAC during the last year, but that the demand has been limited when no new scientific information and resulting media coverage has come out.

The following suggestions have come from our conversations with several people familiar with NAC:

* Persons who try the treatment and feel markedly better during the first two weeks should definitely continue. In these cases, NAC may be correcting an abnormally low level of glutathione within cells.

* If no change is noticed, then it is hard to tell whether or not the treatment is doing any good. In some people, T-helper counts have increased, but it may take months to get this effect. There are suggestions that NAC may help stabilize people with HIV infection, or may speed recovery from opportunistic infections, but it is too early to know if there is any real benefit.

* The best formulations of NAC are generally believed to be those made in Europe for treating bronchitis. Three different kinds are available from the PWA Health Group, 212/532-0280; this buyers' club will fill mail orders. Doses used generally range from 600 to 1800 mg per day, with those who are more seriously ill using the higher doses. While glutathione itself is sold in some health-food stores, one expert we talked to said that it would not be effective.

U. S. researchers have been trying to start a clinical trial of NAC for the last two years, but commercial and bureaucratic obstacles have prevented any such study from starting. Researchers at the U. S. National Institutes of Health are now seeking FDA permission to begin a trial.

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