GLYCYRRHIZIN: RESEARCH STILL PROMISING, STILL LIMITED

An extract from the root of Glycyrrhiza, the licorice plant, has been studied for several years by Japanese researchers for anti-viral and immunomodulatory activity against HIV, and for therapeutic effects on liver disease.
The extracted substance, glycyrrhizin sulfate, has been observed in laboratory tests to inhibit HIV replication, interfere with virus-to-cell binding and cell-to-cell infection, suppress the clumping of infected cells and induce interferon activity. Of related interest, glycyrrhizin also inactivated herpes simplex virus and varicella zoster virus, both of which can become serious opportunistic infections. Among existing applications it is used in Europe and China to treat stomach ulcers and in Japan to treat hepatitis. Botanic and medical literature refer to two species of Glycyrrhiza as a source for the component: G. radix and G. glabra. Most of the articles discussing HIV refer to the first species.
Glycyrrhizin is one of several members of a chemical group called sulfated polysaccharides which have demonstrated varying degrees of anti-HIV activity. These include lentinan, Carrisyn, heparin and dextran sulfate. Glycyrrhizin's potential as an HIV therapy is not confirmed to be stronger or weaker than any of its chemical relatives, but anti-inflammatory characteristics and protective action against liver damage may make it useful for many people with HIV or hemophilia who must cope with chronic hepatitis or drug-related liver toxicity.
Over three years ago AIDS TREATMENT NEWS reported at length on glycyrrhizin (issue #17, November 7, 1986). Since then, the other sulfated polysaccharides have captured more media and research attention. However work on glycyrrhizin continued, and within the last year several studies in Japan reported promising results with oral and intravenous formulations given to people with HIV or AIDS. At least two of the studies involved people who also have hemophilia.
One study of twenty asymptomatic seropositives at Osaka National Hospital was reported at the V International Conference on AIDS in Montreal last June. Of ten participants in this study who were given daily oral doses of glycyrrhizin, ranging from 150 to 225 mg, none progressed to symptoms over periods of one to two years. In the control group of ten who were not treated, one developed lymphadenopathy, and two others were diagnosed with AIDS and subsequently have died (Ikegami and others, 1989).
Another study was sponsored by Tohoku University, Fukushima Medical College, and Akita University. Nine patients with hemophilia who were HIV+ but asymptomatic were given 200-800 mg of intravenous glycyrrhizin daily for over eight weeks. Eight patients experienced an average 88.9% increase in T4-helper cells, and six experienced an average 66.7% improvement in their T4/T8 ratio. Liver dysfunction noted in four patients improved, and no serious side effects were observed (Mori and others, 1989).
A study conducted at Kumamoto University Medical School and Tokyo Medical College involved glycyrrhizin administered intravenously to three hemophiliac patients with AIDS. Six different courses of treatment were reported, usin mg daily (adjusted by body weight) for at least one month. p24 antigenemia was detectable at the beginning of five of the six treatment episodes, but undetectable by the end of three of those five; for the other two, the levels decreased. The authors suggest that glycyrrhizin might inhibit HIV replication (Hattori and others, 1989).
Glycyrrhizin appears relatively nontoxic, but is capable of causing some side effects, including hypokalemia (low potassium levels), myopathy (muscle soreness or fatigue), high blood pressure, and sodium and fluid retention. Persons currently experiencing these symptoms are advised against using glycyrrhizin. Even in the absence of these conditions, we advocate supervision by an HIV-knowledgeable health provider for people considering a new treatment.
A friend of AIDS TREATMENT NEWS has been using Glycyron 2, a Japanese pharmaceutical preparation of glycyrrhizin for oral use, since last October. He shared with us these impressions so far: For several years prior, his helper cells had remained very stable, in the 500 range. Then, last summer they began to decline rapidly in a trend apparent over consecutive tests. By October they registered 320, and he began taking glycyrrhizin in daily doses of 500 mg. After a month his helper cell count rose to 420, liver enzymes which had been slightly elevated were decreased, and he noticed an increase in energy.
Of course, helper cells fluctuate notoriously in many people, even without HIV involvement, and no one would claim that T-cell counts alone are predictive of illness or the efficacy of a given treatment. But together with symptom improvement, they are a first step toward more intensive monitoring of a trend. Our friend is always careful to have his bloodwork sent to the same lab. In November he began treatments with Compound Q, and has continued since then with both Q and glycyrrhizin, with good results in his bloodwork. His p24 antigen tests were negative before starting either treatment, but in January his p24 antibodies registered 400, compared to a pre-treatment count of 50. (Do not confuse p24 antibodies with p24 antigen. For the antibodies, a high value is desirable; for antigen, the reverse is true.) Attributing the improvements to one treatment or the other is not possible for certain; he feels that they complement each other.
Glycyrrhizin is available over the counter in Japan, where it costs about 10 cents per one 25 mg tablet. Depending on the desired dose, which varied widely in the above studies, glycyrrhizin could be an inexpensive complement in an HIV treatment program. Licorice root is the natural source and is widely available as a tea in health food stores in the U. S. Apparently, glycyrrhizin components comprise from 8 to 12% of licorice root, and they are available simply by drinking the tea. But obviously, this would be a haphazard and not a methodical way to obtain measured, standard amounts of glycyrrhizin. Chinese medicine often employs licorice root, but usually in small amounts combined with other therapeutic plants. We do not know of any U. S. source of the Japanese tablets at this time, but some buyers' clubs are considering carrying them.

References

Ikegami, N and others. Clinical Evaluation of Glycyrrhizin on HIV-Infected Asymptomatic Hemophiliac Patients in Japan. V International Conference on AIDS. Abstract W. B. P. 298, June, 1989.

Mori, K and others. Effects of Glycyrrhizin (SNMC: Stronger Neo-Minophagen C) in Hemophilia Patients with HIV Infection. Tohoku Journal of Experimental Medicine, volume 158, pages 25-35, 1989.

Hattori, T and others. Preliminary evidence for inhibitory effect of glycyrrhizin on HIV replication in patients with AIDS. Antiviral Research, volume 11, pages 255-262, 1989.

Tochikura, TS and others. Antiviral Agents with Activity Against Human Retroviruses. Journal of Acquired Immune Deficiency Syndromes, volume 2, number 5, pages 442-447, 1989.

Tochikura, TS and others. Human Immunodeficiency Virus (HIV)- Induced Cell Fusion: Quantification and Its Application for the Simple and Rapid Screening of Anti-HIV Substances in Vitro. Virology, volume 164, pages 542-546, June, 1988.

Ito, M and others. Mechanism of inhibitory effect of glycyrrhizin on replication of human immunodeficiency virus (HIV). Antiviral Research, volume 10, number 6, pages 289-298, December 1988.