translation agency

AIDS Treatment News
AIDS/ARC Treatment: A Role for Lecithin?
John S. James
April 25, 1986
AIDS TREATMENT NEWS No. 002 - April 25, 1986

Two separate bodies of medical research suggest that lecithin may be helpful in the treatment of AIDS or ARC.

The first information comes from the development of AL 721, now being tested as an experimental treatment against AIDS in drug trials. AL 721 has been shown to reduce AIDS virus infection of human T-cells in the laboratory (Sarin and others, New England Journal of Medicine, November 14, 1985). It works by changing the cell membrane so that the virus cannot attach itself to receptor sites, and therefore cannot infect the cell.

The active ingredient of AL 721 is lecithin; the rest of the mixture apparently makes the delivery of the lecithin more effective. Much evidence suggests that ordinary lecithin can produce the same "membrane fluidization" effect, which is believed to be the basis of the antiviral action of AL 721, though probably to a lesser degree.

Unfortunately, AL 721 is tied up in the corporate and regu- latory red tape of new-drug approval. Doctors and patients cannot get it, and they may not be able to get it for years. Lecithin could be tried now, at least as a stopgap until AL 721 becomes available.

Meanwhile, different research teams have found purified lec- ithin useful in the treatment of viral hepatitis. A computer literature search turned up four clinical papers; three of them are not readily accessible, and therefore easily overlooked. All four papers reported controlled studies which found strong evidence of effectiveness, and definitely recommended the treatment. Since the antiviral effect of AL 721 is not believed to be specific to AIDS, the hepatitis results may demonstrate a practical clinical use of the same effect shown to prevent AIDS infection of cells in the laboratory.

No published work so far has discussed lecithin and AIDS. A Medline computer search found over 3800 papers concerning AIDS, and over 4100 concerning phosphatidylcholines (lecithin and related substances), but only a single item which discussed both - the AL 721 letter cited above.

While the information collected here cannot prove whether or not lecithin could be useful in the treatment of AIDS or ARC, it certainly suggests that lecithin be tried - especially since it is safe, inexpensive, and readily available.

AL 721 BACKGROUND AL 721 is an experimental AIDS treatment derived from lec- ithin. It was developed from several years' research on "mem- brane fluidity" by dozens of scientists, work spearheaded by Meir Shinitzky, an immunologist doing cancer research at The Weizmann Institute of Science in Israel. AL 721 is known to be safe for human use, and is known to reduce AIDS infection in laboratory cultures, as mentioned above. Unfortunately, clini- cal tests have barely begun and no results are yet available, so we have no direct evidence one way or the other on whether AL 721 will prove useful in the treatment of AIDS or ARC.

AL 721 is a mixture of three lipids (fats), in a 7: 2: 1 ratio; hence the name (the 'AL' stands for "active lipid"). The three ingredients are phosphatidylcholine (purified lecithin - called 'PC' in this article -- which makes up 20 percent of AL 721), phosphatidylethanolamine (PE -- 10 percent -- a related substance also contained in commercial lecithin preparations), and neutral lipids which apparently serve as a carrier to present the active ingredients to the cell membrane more effectively. The particular 7: 2: 1 ratio proved to be the most effective proportion.

All of the ingredients of AL 721 are extracted from ordinary egg yolks.

AL 721 increases the "fluidity" of cell membranes -- the degree to which proteins can move around. It does this by removing cholesterol and increasing the ratio of phospholipids (lec- ithin and related compounds) to cholesterol in the membrane. Increasing the fluidity apparently makes it harder for viruses to attach to receptor sites, which are proteins in the membrane. Unless it can attach to a receptor site, the virus cannot enter and infect the cell.

Incidentally, membrane fluidity decreases with age; and AL 721 has been found to restore certain functions lost with aging. Since increased fluidity should make it harder for the AIDS virus to infect the cell, this theory would predict that susceptibility to AIDS might increase with age.

AL 721 does cross the blood-brain barrier.

For more background on AL 721, see my summary "AL 721: Experimental AIDS Treatment", AIDS Treatment News #1; or check the references at the end of this article.

AL 721 AND LECITHIN A number of published articles outline the science behind AL 721. These papers contain fragmentary but extensive indications that lecithin has the same membrane fluidization effect as AL 721, although to a smaller degree.

No one has collected and organized this evidence; the scien- tists working with AL 721 have, not surprisingly, sought to highlight how that preparation is special. Instead of marshaling the information here, which would turn this short section into a separate paper, we refer the reader to papers by Shinitzky, Lyte, Heron, and the co-authors who appear with them in the References section, below. Also see Physiology of Membrane Fluidity, edited by Shinitzky, for a thorough presentation of the scientific background behind the membrane fluidity theory and the development of AL 721.

The prospectus of Praxis Pharmaceuticals, Inc., of Beverly Hills, CA (the licensee and commercial developer of AL 721), provides other information about this preparation and its relationship to lecithin. In human trials, AL 721 has been shown to restore immune function (lymphocyte proliferative capacity) lost due to the aging process; the restored immune functions were comparable to those of young adults. Animal studies have shown that AL 721 may also be useful for treating alcohol and morphine withdrawal, and to prevent relapses in the treatment of dependency on these drugs. Both these effects are believed due to membrane fluidization. AL 721 also shows promise for treating cystic fibrosis in children, but through a different mode of action.

The prospectus also suggests AL 721 as "a more efficient source of lecithin" for treating bipolar affective disorder, compared to soybean-derived lecithin, which earlier studies had shown might be effective for this condition.

And aside from these therapeutic uses, "AL is a relatively pure form of lecithin derived from egg yolk and may be used as a nutritional supplement".

PREVIOUS LECITHIN THERAPY We have examined dozens of abstracts from nearly 200 studies of lecithin administration or therapy published in medical jour- nals during the last ten years. Most of these studies were based on very different theories of lecithin's mode of action. They used the substance either to increase the amount of choline in the brain, or to reduce fat deposits in blood vessels. For a review of these studies, see Wood and Allison, 1982.

Conspicuously absent from almost all work so far have been studies of lecithin to help the body fight viral diseases. Until the AL 721 study published last November (cited above), there was little or no reason to look for an antiviral effect.

LECITHIN AND VIRAL HEPATITIS Our literature search found four papers on use of lecithin or related substances to treat hepatitis.

Jenkins and others, 1982, reported a double-blind trial on 30 patients with non-A non-B hepatitis. This study compared 15 patients given three grams per day of polyunsaturated phospha- tidylcholine ("Essential Phospholipid", Nattermann & Cie, Ger- many) for one year with those given a placebo; all patients simultaneously received other hepatitis therapy. The study concluded that the phosphatidylcholine definitely helped in the treatment of this condition. In addition, two of the controls but none of the treatment group suffered relapses during the study.

This paper did not consider the possibility of an antiviral effect, but suggested prevention of autoimmune damage as a possible mode of action. It did mention the membrane fluidity work, but no antiviral effects of increased membrane fluidity were expected at that time.

Atoba and others, 1985, in a study in Nigeria, used matched treatment and control groups, each with 30 patients with acute hepatitis B. The treatment group used 1.8 grams of "essential phospholipid choline", and the control group used vitamin-B complex. The treatment group showed faster improvement on almost all measurements. For example, the initial bilirubin and transaminases were comparable for both groups, but after four weeks, 77 percent of the treatment but only 37 percent of the control patients showed normal serum transaminase levels. After six weeks, 93 percent of the treated patients but only 53 percent of the controls had normal levels of both bilirubin and transaminase.

This study was not double blind, as the patients had to buy their own drugs. Cost was a problem, and may have contributed to the decision to use the smaller dose; Jenkins and others, who used three grams, mentioned that they had done a pilot study in which 1.8 grams had proved effective.

(Incidentally, it is difficult to find the Atoba paper, as it was published in an Indian journal received by only four medical libraries in the United States. Copies can be obtained through a commercial research service.) Kosina and others,1981, found improvements in clinical signs, laboratory tests, and number of relapses in 80 patients with hepatitis A or B, compared to controls. This study used "essential cholinephospholipids (Essentiale forte)"; we don't know the dose. The paper is in Czech and we have read only an English abstract; we would appreciate any help with translation.

We have read only the English summary of Visco, 1985. This Italian study reported successful treatment of viral hepatitis with phosphatidylcholine, in a controlled trial.

How is the potential usefulness of lecithin against viral hepatitis relevant to AIDS? The membrane fluidity theory is not specific to the AIDS virus -- the theory just happened to be tried first against it in the laboratory. It is quite possible that membrane fluidization is the mechanism of action of lecithin in these hepatitis trials. If so, it would show that oral lecithin can produce in the body an effect already found to prevent infection by the AIDS virus in the laboratory -- an effect clinically useful against another virus disease.

Even if the effect of lecithin against hepatitis is not due to any antiviral action but rather to the prevention of auto- immune damage, as some of the authors of the papers suggested, there might still be a use against AIDS. A number of researchers suspect that AIDS has an autoimmune component.

DOSAGE AND SIDE EFFECTS As lecithin has yet to be studied as a treatment for AIDS or ARC, we can only review dosage levels used to treat other conditions. Fortunately, the doses used in the hepatitis studies turn out to be within the range which has long been recommended by the manufacturers of the lecithin granules which have been sold in health-food stores for years.

Jenkins and others, 1982, used three grams of phosphati- dylcholine per day. Most commercial lecithin granules contain about 22 percent PC, so three grams is equivalent in PC content to about 14 grams of the granules. This amount happens to be about the same as the two tablespoon maximum daily dose tradi- tionally recommended by commercial vendors of lecithin granules.

Some studies have used higher doses, as much as 100 grams per day of commercial lecithin. These high doses produced unwanted side effects, such as nausea, diarrhea, depression, and loss of appetite, but apparently no lasting ill effects. Therapists giving high doses of lecithin should monitor the patients, particularly for depression (Wood and Allison, 1982).

Most patients could tolerate up to 25 grams of commercial lecithin per day without side effects. Also, most patients could tolerate up to 40 grams of purified (85 percent) PC, meaning that several times as much PC can be administered in the purified form.

On the other hand, a very small dose would probably be inef- fective, because many foods already supply lecithin; adding only a little more would not change much. The amount of lecithin supplied by food varies with diet, but is in the range of one to five grams per day (Wood and Allison, 1982).

Ultimately the only way to determine a dose might be by trial. If T-cell counts are being monitored, they might be the first place to look for an effect, since membrane fluidization (with AL 721) was found to prevent the infection of human T-cells in the laboratory. For those who don't wait for a scien-tific trial, which might or might not take place, the obvious approaches would be to try the maximum dose recommended for the product (equivalent to the dose used in the Jenkins hepatitis study), or to try larger doses to see what seemed to work.

Lecithin is classified as GRAS (generally recognized as safe). In the Medline database since 1980, out of over 4000 references concerning phosphatidylcholines, only five concerned adverse effects. Still, we should note possible problems. Long-term feeding of large doses to pregnant animals has interfered with the development of the fetus (Bell and Lundberg, 1985). And one study of commercial lecithin preparations found that all of the ones tested were contaminated with potentially dangerous methylamines, probably from spoilage (Zeisel and oth- ers, 1983). It would seem reasonable to store lecithin properly, refrigerated in small bottles, to keep it away from moisture, light, and air, and to discard any with a rancid taste or smell.

An alternative source of lecithin is egg yolk. Egg yolk contains all the ingredients of AL 721. It also contains much cholesterol, which might counteract the effect of AL 721; we don't know whether or not this would be a practical problem, and would appreciate advice from nutritionists.

There are slight chemical differences between the PC in egg yolk, and the PC in soy lecithin (the kind sold in health-food stores). We don't know whether or not this difference has any practical effect. The scientific work which developed AL 721 used egg lecithin, while most other studies of lecithin therapy used the soybean variety.

SUMMARY The published information collected here suggests that lec- ithin might be useful in the treatment of AIDS or ARC. This possibility seems to have been overlooked; a computer literature search turned up no papers which discussed it.

We hope that researchers will examine this information, and run clinical tests if justified. There is little danger of harm, and some chance of benefit.

REFERENCES Atoba MA, Ayoola EA, Ogunseyinde O. Effect of essential phospholipid choline on the course of acute hepatitis-B infection. Tropical Gastroenterology, April-June 1985; 6(2), pages 96-99.

Bell, JM, Lundberg PK. Effects of commercial soy lecithin preparation of development of sensorimotor behavior and brain biochemistry in the rat. Developmental Psychobiology 1985; 18(1), pages 59-66.

Heron D, Shinitzky M, Samuel D. Alleviation of drug withdrawal symptoms by treatment with a potent mixture of natural lipids. European Journal of Pharmacology 1982; 83, pages 253-261.

Jenkins PJ, Portmann BP, ddleston ALWF, Williams R. Use of polyunsaturated phosphatidyl choline in HBsAg negative chronic active hepatitis: results of prospective double-blind controlled trial. Liver, 1982(2), pages 77-81.

Kosina F, Budka K, Kolouch Z, Lazarova D, Truksova D. Essential cholinephospholipids in the treatment of virus hepatitis. (English translation of title.) Casopis Lekaru Ceskych August 13, 1981; 120 (31-32) pages 957-960.

Lyte M, Shinitzky M. A special lipid mixture for membrane fluidization. Biochimica Et Biophysica Acta 1985; 812, pages 133-138.

Praxis Pharmaceuticals, Inc. Prospectus, January 17, 1985.

Sarin PS, Gallo RC, Scheer DI, Crews F, Lippa AS. Effects of a novel compound (AL 721) on HTLV-III infectivity in vitro. New England Journal of Medicine, November 14, 1985; 313 (20), pages 1289-1290.

Shinitzky, M. (ed) Physiology of Membrane Fluidity, Vols. 1 and 2, CRC Press, Boca Raton, FL 1984.

Shinitzky M, Samuel D, Antonian L, Lippa AS. AL 721, a novel membrane fluidizer. Drug Development Research (in press).

Visco, G Polyunsaturated phosphatidylcholine in association with vitamin B complex in the treatment of acute viral hepatitis B. Results of a randomized double-blind study. (English translation of title). Clinica Terapeutica August 15, 1985; 114(3), pages 183-188.

Wire-service reports on AL 721: UPI September 2 and November 14, 1985; AP November 13 and 14, 1985.

Wood JL and Allison RG. Effects of consumption of choline and lecithin on neurological and cardiovascular systems. Federation Proceedings 1982; 41, pages 3015-3021.

Zeisel SH, Wishnok, JS, and Blusztajn JK. Formation of methylamines from ingested choline and lecithin. The Journal of Pharmacology and Experimental Therapeutics, 1983; 225(2) pages 320-324.