Tuesday, March 07, 2006

Hypericin and AIDS

Many people infected with the human immunodeficiency virus (HIV) have incorporated St. John’s wort (Hypericum perforatum L., Clusiaceae) into their self-care regimens, based on laboratory evidence that hypericin and pseudohypericin are active against retroviruses such as HIV (Meruelo et al., 1988; Lavie et al., 1990). According to reports about earlier clinical research, St. John’s wort helped to improve outlook, reduce fatigue, and enhance well-being for people with HIV, but it was unclear whether the improvements were related to antidepressant effects or to direct antiviral activity (Bergner, 1990).

To investigate the safety and antiretroviral activity of hypericin in a clinical setting, a group of American researchers conducted a phase I study of 30 HIV-infected people with CD4 counts lower than 350 cells/mm3 (Gulick et al., 1999). Phase I studies are primarily concerned with assessing the safety of a substance and evaluating side effects that occur as dosage is increased.

This small study, which employed oral and injectable treatment with synthetic hypericin, yielded disappointing results. Not only did the pharmaceutical hypericin demonstrate no antiretroviral activity, it caused severe phototoxicity in 48 percent of the participants. Sixteen of the 30 subjects (53 percent) dropped out of the study early because of side effects. Almost all of the participants taking either oral or injectable hypericin experienced some degree of phototoxicity, which caused a painful red rash in areas exposed to light.

The investigators speculated that the lack of anti-retroviral activity could be attributed to the fact that the high incidence of side effects made it impossible for them to achieve sustained blood levels of hypericin sufficient to inactivate the virus. It is important to note that since this study utilized a synthetic hypericin preparation, its results cannot necessarily be extrapolated to St. John’s wort standardized extract or whole plant preparations.

For the study, the participants were divided into four groups. Three of the groups were treated with intravenous hypericin (0.25 or 0.5 mg/kg twice weekly or 0.25 mg/kg three times weekly) and one received oral hypericin (0.5 mg/kg daily). The antiretroviral activity of the synthetic hypericin was assessed by measuring changes in CD4 cell counts, HIV p24 antigen level, virus titer, and HIV RNA copies. There were no detectable changes in any of these parameters. Adverse effects were evaluated weekly and graded according to a four-point scale, with grade 1 representing the mildest adverse reaction and grade 4 representing the most severe reaction. Grade 3 phototoxicity, which was observed in 48 percent of the study subjects, was defined as "intolerable erythema or numbness (or both), temperature sensitivity, and pain despite long-term analgesic therapy." No grade 4 phototoxicity was reported.

The investigators suggested that even though the synthetic hypericin proved too toxic to allow assessment of its clinical value in this study, other applications might hold more promise. "The potent antiviral activity of hypericin in vitro has led to its use in the ex vivo treatment of blood components," they noted. "This approach avoids phototoxicity and uses the well-described enhancement of the antiviral effect of hypericin by light." – Evelyn Leigh

Ginkgo effective in intermittent claudication

In this randomized, controlled, double-blind German study, Ginkgo biloba L. (Ginkgoaceae) was significantly superior to placebo in improving symptoms of intermittent claudication, a type of peripheral arterial disease which causes pain in the legs due to obstructed blood flow [Peters, 1998]. The severity of intermittent claudication is evaluated by measuring pain-free walking distance, an indication of how long patients can walk before experiencing symptoms. After six months of treatment, pain-free walking distance in the ginkgo group improved by almost 50 percent, compared to baseline measurements.

Results of the study lend further support to the positive results of earlier studies on the use of ginkgo in peripheral arterial disease, a number of which were reported in a meta-analysis of five placebo-controlled studies involving a total of 174 patients [Schneider, 1992]. Most of these studies have utilized EGb 761 (W. Schwabe, Karlsruhe, Germany), a concentrated ginkgo extract standardized to 24 percent ginkgo flavone glycosides and 6 percent terpene lactones.

For this 26-week study, 111 patients with confirmed peripheral occlusive arterial disease were randomized into two treatment groups. After a two-week run in placebo phase, subjects received treatment with either one tablet of standardized ginkgo extract three times a day, a total daily dose of 120 mg, or placebo. Results were assessed by comparing pain-free walking distance at the beginning of the trial with changes after eight, 16, and 24 weeks of treatment. The superior efficacy of ginkgo was statistically significant at all three evaluation points. Both treatment groups had increases in pain-free walking distance during the study, but after six months of treatment, the increase in pain-free walking distance in the ginkgo group was almost twice that of the placebo group. Increases in maximum walking distance were also significantly greater with ginkgo treatment. No side effects were reported in the ginkgo group; one patient in the placebo group complained of heartburn and gastric pain.

Green tea and turmeric

(Camellia sinensis and Curcuma longa)

Herbal combination therapy packs a potential one-two punch against oral cancer A major constituent in green tea (epigallocatechin-3-gallate, or EGCG) and one from turmeric (curcumin) were examined for their ability to prevent the development of oral cancer in this in vitro study. Both compounds, particularly the green tea constituent, have been shown to have anticarcinogenic properties, along with antioxidant and anti-inflammatory activities in some studies. Cultures of normal, premalignant and malignant oral epithelial cells were treated with EGCG and curcumin, both of which demonstrated the ability to inhibit cancer cell growth in all cell lines tested. Degree of growth inhibition depended on the particular cell line and the inhibitory agent used, and each agent appeared to block growth at different stages of the cell cycle (EGCG blocked cells in the G1 phase, while curcumin blocked cells in the S/G2M phases). Synergistic activities were noted when both agents were used, resulting in a dose-dependent cell growth inhibition. Using the two agents in combination permitted the dosage of each to be reduced.

Harvard warns of high calcium-prostate cancer link

According to an 11-year study recently completed by researchers from Harvard University Medical School, too much dietary calcium can increase men's risk of developing prostate cancer. The study found a correlation between the incidence of prostate cancer and dairy intake, with participants facing a 34% greater risk of developing the disease if they were among the top 20% of dairy products consumers. The researchers concluded, "These findings may serve to interject a note of caution into the current enthusiastic promotion of a higher intake of calcium in the US." However, Dr. June Chanl, lead author of the report, told HealthWorld, "This is a 'head's up' rather than the sounding of an alarm.