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Ginkgo Meta-analysis Confirms Efficacy in Peripheral Arterial Disease

A recent meta-analysis of controlled clinical trials concluded that ginkgo leaf extract (Ginkgo biloba L., Ginkgoaceae) is significantly more effective than placebo in the treatment of the circulatory disorder known as intermittent claudication (Pittler et al., 2000). The results of this study support those of an earlier German meta-analysis of five studies involving 174 subjects (Schneider, 1992).

Intermittent claudication, caused by a buildup of atherosclerotic deposits in the blood vessels of the limbs, is an early symptom of peripheral arterial disease. Claudication (limping) occurs when narrowing of the arteries restricts the flow of blood and oxygen to the leg muscles, causing calf pain and subsequent difficulty in walking. The condition primarily affects older people, and treatment options are limited. Walking is probably the most effective treatment of all, but many patients have difficulty adhering to the recommended exercise program.

For their meta-analysis, the investigators identified eight randomized, placebo-controlled, double blind studies that involved a total of 415 participants. All of the studies used pain-free walking distance as the primary outcome measure. In five of the eight trials, the investigators used a daily dosage of 120 mg standardized ginkgo extract, and three a daily dosage of 160 mg. Seven of the trials utilized EGb 761, a concentrated ginkgo extract standardized to 24 percent ginkgo flavone glycosides and 6 percent terpene lactones (W. Schwabe, Karlsruhe, Germany). The majority of trials lasted 24 weeks, with the exception of one six-week and one 12-week study.

Statistical pooling of results from the eight trials showed that compared to placebo, ginkgo significantly increased pain-free walking distance. The weighted mean difference in walking distance between the gingko and placebo groups was 34 meters (approximately 100 feet). No adverse effects were reported in three trials, which represented nearly half of the total number of participants studied. In the other five trials, stomach upset (including nausea and indigestion) was the most frequently reported adverse event.

The authors concluded, "...this meta-analysis suggests that oral medication with Ginkgo biloba extract prolongs the pain-free (and maximal) walking distance in patients with intermittent claudication." However, they cautioned, "The overall effect seems modest, and several caveats about the available trials prevent a final judgment on the efficacy of this treatment." On the other hand, they also acknowledged the limitations of currently available drug treatments for the condition. Pentoxifylline, one drug approved in the U.S. for intermittent claudication, has "modest" clinical effects and can cause serious adverse effects, including cardiac arrhythmias and bleeding. The drug also costs significantly more than ginkgo extract. In the U.S., the cost of a 120 mg daily dose of ginkgo ranges from 41 to 84 cents. In comparison, a daily dose of pentoxifylline (1200 mg) costs $1.83 to $1.93.

- Evelyn Leigh, Herb Research Foundation [Pittler MH, Ernst E. Ginkgo biloba extract for the treatment of intermittent claudication: A meta-analysis of randomized trials. The American Journal of Medicine 2000; 108: 276-281. Schneider B. Ginkgo biloba Extrakt bei peripheren arteriellen Verschlusskrankeheiten (German with English summary). Arzneimittelforschung 1992; 42(1): 428-436.]

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