AIDS Treatment News No. 017 (San Francisco Sentinel) - November 5,

In the last few weeks, Japanese researchers have found that a component of ordinary licorice can stop the growth of the AIDS virus in test tube cultures of human lymphocytes.

Many substances can stop the AIDS virus in the laboratory. But this discovery, by a joint project of researchers at Fukushima Medical College and Yamaguchi University Medical School, is particularly important for the following reasons: * The licorice ingredient, glycyrrhizin, is already clinically used in Japan as an antiviral, especially for treatment of hepatitis B. Good results have been reported.

* Side effects are mild to moderate.

* Concentrations of 50 ml per liter almost completely protected human blood cells from the AIDS virus. We don't know the concentrations reached during normal medical use of glycyrrhizin, but the usual daily doses are 40 to 200 mg, and much larger doses have been used.

* While many Japanese physicians use an intravenous glycyrrhizin preparation apparently not available in the U. S., others have given it orally. Researchers believe that oral administration can provide comparable doses (Fujiwara and others, 1983). Apparently, physicians use the intravenous preparation because it avoids other possibly unwanted ingredients in licorice; includes other substances to minimize the side effects of pure glycyrrhizin or of licorice; and helps standardize the treatment by avoiding variability in absorption from the digestive systems of different individuals.

* Licorice root, commonly available in health food stores and in licorice candy, can deliver medically effective doses of glycyrrhizin. These sources may provide a workable alternative, should red tape impede clinical AIDS/ARC tests of glycyrrhizin or U. S. availability of the Japanese pharmaceutical preparation.

The Japanese team announced its results on September 22, 1986, and apparently reported them at a meeting of the Japanese Society of Virologists on October 14. We have not yet seen any report of that meeting, only a story in the JAPAN TIMES WEEKLY (October 11), based on a telephone interview with Masahiko Ito, a professor at Fukushima Medical College.

The team has not yet tested glycyrrhizin on persons with AIDS or ARC.

The U. S. press has not picked up this story, and few physicians have heard of glycyrrhizin or licorice as a potential AIDS/ARC treatment. As far as we know, this SF SENTINEL article is the first mention of it in any U. S. publication.

Licorice and Glycyrrhizin The most interesting ingredient in licorice is the chemical glycyrrhizin (a word derived from the biological name of the licorice plant, glycyrrhiza glabra). Glycyrrhizin, fifty times sweeter than sugar, is responsible for the sweet taste of the infusions, tinctures or other preparations made from the licorice root. (The Chinese name for licorice is "gan cao", meaning "sweet weed".) Licorice also contains a number of other medically relevant components, such as glycyrrhizic acid and glycyrrhetinic acid. In one study, the latter showed a "remarkable" effect on the Epstein-Barr virus, although glycyrrhizin itself had none (Okamoto and others, 1983). Most of the Japanese studies used purified glycyrrhizin instead of licorice for experiments and for medical treatment. (We don't know if pure glycyrrhizin is available in the U. S. Licorice root, and various extracts from it, are available in health food stores or from herbalists.) Medical Experiments and Uses A recent Japanese study found that glycyrrhizin enhanced interferon gamma production by human blood cells treated with hepatitis B antigen or another immune stimulus (Shinada and others, 1985). Glycyrrhizin alone did not cause the cells to produce interferon. But pre-treatment with glycyrrhizin enabled the cells to produce more interferon gamma (by a factor of as much as eight) when they were challenged with an immune stimulus (such as hepatitis B antigen). Collaboration between T cells and macrophages was needed to obtain the greatest effect.

Interferon gamma is one of the experimental AIDS/ARC treatments now being tried. According to one recent report (AmFAR, September 1986), these trials have not produced much clinical improvement. However, injecting interferon gamma may not have the same effect as the use of glycyrrhizin to assist the body in producing more of its own interferon as necessary.

Glycyrrhizin has shown antiviral activity in the laboratory (Pompei and others, 1979), and has been widely used in Japan to treat chronic active hepatitis B (Shinada and others, 1986).

The eminent herbalist, Subhuti Dharmananda, discussed licorice in a paper on immunodeficiency syndromes (Dharmananda, 1986). He reported that it has demonstrated both immune enhancing and immune suppressive effects. Licorice has been used for treating gastric ulcer and arthritis; traditional uses in Chinese medicine have included treatment of laryngitis. But licorice is almost always used in combination with other herbs in Chinese medicine.

To learn more about the traditional uses of the herb, we consulted with Quan Yin Acupuncture and Herb Center of San Francisco. They also recommended an herbalist, Brian K. Weissbuch of KW Botanicals, in Fairfax, CA. Both explained that while licorice is widely used in Chinese herbal formulas, it generally constitutes only a small part of the preparation (usually less than four percent). Our discussion with Mr. Weissbuch largely concerned precautions and reasons for avoiding indiscriminate use.

Cautions and Adverse Effects A New Zealand study examined black licorice candy use among 603 high school students (Simpson and Currie, 1982). While these researchers did not search for nor find ill effects among the students, their paper provides a convenient summary of common adverse effects of licorice reported up to that time.

The most common problems were high blood pressure, edema (swelling, often of the ankles, wrists, or face), and muscle pain, weakness, or paralysis. Most of these people had eaten several hundred grams or more of licorice per week, often for months or years. The effects ceased when they stopped using licorice. Licorice acts as a natural cortisone, and may cause sodium and water retention and potassium depletion. Doctors have occasionally found severe or life-threatening reactions requiring medical treatment.

The authors of the New Zealand study warn that person with heart disease, high blood pressure (or a family history of high blood pressure), or who eat a lot of salt or take certain diuretics, should be especially careful of licorice.

Later studies have shown much greater risks to persons who are taking insulin, or who have alcoholic cirrhosis. Even small amounts of licorice can cause severe reactions.

The authors of the New Zealand study suggested that, for healthy people, eating more than about 200 grams per week (about one ounce a day) of black licorice candy sticks might cause adverse health effects. Some kinds of licorice are believed to have a stronger effect than the sticks. About five percent of the high school students studied ate more than the amount believed potentially harmful.

Miscellaneous * One problem with licorice candy is that it is difficult to determine how much licorice is being consumed. And the candy has other ingredients, including oil from anise seeds, which may cause untoward side effects in some people. It also has sugar, molasses, or other sweeteners, and salt. Licorice candies and liquors have caused a number of cases of medical problems, as stated earlier. It may be safer to use the root, which can be found in herb or health food stores and prepared according to a practitioner's instructions, or according to directions in herb books. * What dose ought to be used? One book (John Lust, THE HERB BOOK) suggests one teaspoon of the root, prepared as an infusion, with one cup of water, and used slowly throughout the day. One should check with a physician, practitioner, or at least a good herb book before using licorice. It is clearly advisable to tell one's physician what one is doing, even though few physicians are familiar with medical uses or dangers of licorice, and no one knows how it might affect persons with AIDS or ARC.

* One particular caution: water retention can cause a sudden weight gain of several pounds. This dangerous side effect which can be caused by too much licorice or glycyrrhizin should not be taken as a sign that the treatment is working.

* For those who want to gather licorice in the wild, Weissbuch cautioned that many people confuse the licorice plant with wild fennel, an entirely different plant.

To summarize, glycyrrhizin or licorice might help in treating AIDS or ARC, although no one has tested it with patients at this time. If one does try it, the advice we have been hearing is to use caution, especially in long-term use, to avoid taking too much, and to be aware of one's particular health problems that may rule out the use of licorice, and of symptoms that might be caused by its use.

This column will publish more information about glycyrrhizin or licorice as treatments for AIDS or ARC, as it becomes available.

References AmFAR. "Experimental drugs for AIDS and ARC: A directory of clinical trials." The American Foundation for AIDS Research, 40 West 57th St., Suite 406, New York, NY 10019 (September 15, 1986).

Dharmananda, Subhuti. "A new herbal combination for the treatment of immunodeficiency syndromes." Institute for Traditional Medicine and Preventive Health Care, 2442 S. E. Sherman, Portland, OR 97214 (1986).

Fujiwara, Y., Kikkawa, R., Nakata, K., Kitamura, E., Takama, T., & Shigeta, Y. "Hypokalemia and sodium retention in patients with diabetes and chronic hepatitis receiving insulin and glycyrrhizin." ENDOCRINOL. JAPON., Vol. 20 (2), pp. 243-249 (1983).

JAPAN TIMES WEEKLY. "Component halts AIDS virus growth" (October 11, 1986).

Okamoto, H., Yoshida, D., & Mizusaki, S. "Inhibition of 12-O- tetradecanoylphorbol-13-acetate-induced induction in Epstein- Barr virus early antigen in Raji cells." CANCER LETTER, Vol. 19 (1), pp. 47-53 (May 1983).

Pompei, R., Flore, O., Marccialis, M. A., Pani, A., & Loddo, B. "Glycyrrhizic acid inhibits virus growth and inactivates virus particles." NATURE, Vol. 281, pp. 689-690 (1979).

Shinada, M., Azuma, M., Kawai, H., Sazaki, K., Yoshida, I., Yoshida, T., Suzutani, T., & Sakuma, T. "Enhancement of interferon gamma production in glycyrrhizin-treated human peripheral lymphocytes in response to concanavalin A and to surface antigen of hepatitis B virus." PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE, Vol. 181, pp. 205-210 (1986).

Simpson, F. O., & Currie, I. J. Licorice consumption among high school students." NEW ZEALAND MEDICAL JOURNAL, Vol. 95, pp. 31- 33 (January 27 1982).