Herbal Preparations: Ginkgo Biloba Leaf Extract

Ginkgo Biloba Leaf Extract

Ginkgo, or maidenhair tree (Ginkgo biloba), is thought to be the most ancient of living tree species, and it is now also one of the top selling herbs in Europe and the United States because of its reputed ability to improve cognitive function. Ginkgo leaf extract is prepared from ginkgo leaf by a complex process that removes toxic ginkgolic acid. This reduces the risk of allergic reactions to the leaves if they are consumed directly. Ginkgo leaf extract contains 24% flavone glycosides (including the antioxidant rutin, which improves capillary fragility) and 6% terpene lactones.

Mechanism of Action

Ginkgo leaf extract appears to act primarily as a mild cerebral vasodilator that increases cerebral blood flow and reduces blood viscosity. Ginkgolides inhibit platelet activating factor, and this may improve microcircula-tory blood flow in atherosclerotic disease with slightly increased risk of bleeding. There appears to be an an-tioxidant effect that may be neuroprotective. Although some studies suggested a monoamine oxidase inhibitor (MAOI) effect, this is considered to have questionable clinical relevance.

Indications

Ginkgo leaf extract is most popular for cognitive disor-ders, including memory loss, dementia, and cerebrovas-cular insufficiency. A number of well-designed clinical trials have shown modest benefit in Alzheimer’s dis-ease, with ginkgo extract appearing as effective as sec-ond-generation cholinesterase inhibitors. At least one large (214 patient) study, however, failed to show a memory improvement in dementia patients. Studies are now under way to see whether ginkgo use will protect against development of Alzheimer’s disease.

Intermittent claudication appears to benefit from ginkgo therapy: many studies demonstrate improved walking distance and decreased pain. One meta-analysis of eight studies documented statistically significant im-provement but questioned its clinical relevance. In some studies, the high doses (240 mg) appeared more effective.

Vertigo and tinnitus are difficult to treat conditions for which ginkgo is frequently recommended. At least two trials support the use of gingko extract for vertigo, but the evidence for tinnitus remains inconclusive.

Other suggested uses include sexual dysfunction secondary to selective serotonin reuptake inhibitors (SSRIs), macular degeneration, premenstrual syn-drome, and the prevention of acute mountain sickness at high altitude. Some of these uses are supported only by a single study.

Adverse reactions, Contraindications, and Interactions

Allergic reactions are a significant concern with un-processed ginkgo leaf (ginkgolic acid) but are much less likely to occur with the leaf extract. The malodorous ginkgo fruit cross-reacts with poison ivy (urushiol) and may cause an identical contact dermatitis.

Children eating large numbers (>50) of the un-cooked ginkgo kernels have had seizures, and conse-quently there is some concern about using high doses of ginkgo in seizure patients. However, most patients tol-erate gingko extract very well, with only occasional GI upset or headache being reported, and the product is considered safe for healthy nonpregnant adults.

Bleeding complications are an infrequent but seri-ous concern, with subdural hematomas, subarachnoid hemorrhages, hyphema (bleeding of the iris), and surgi-cal bleeding occasionally reported. Stopping ginkgo ad-ministration prior to surgery and the avoidance of its use with anticoagulant drugs and perhaps with aspirin is recommended. Use of ginkgo extract should be avoided in pregnant women and children, since at least one study showed in a ginkgo preparation small amounts of colchicine, a compound that can block cellular division and cause abortion; however, it is unclear whether this is a problem in all ginkgo preparations.

Ginkgo may reduce the effectiveness of thiazide di-uretics for blood pressure control and at least theoreti-cally should be avoided with MAOIs. There is also a suggestion that ginkgo may decrease male and female fertility, and it should be avoided in those trying to con-ceive.

Dose

For cognitive function, total daily doses of 120 to 240 mg divided into 2 or 3 doses of ginkgo leaf extract are rec-ommended. For intermittent claudication, 240 mg a day would be preferable.

Conclusion

The preponderance of evidence indicates that ginkgo is an effective mild cerebral and perhaps general va-sodilator that may mitigate cognitive decline in the eld-erly. Its effect on memory in younger adults is less clear; although some studies show a benefit, others do not. Ginkgo should be avoided with anticoagulants and used with caution with antiplatelet medication. Although ginkgo’s effectiveness in intermittent claudication, ver-tigo, SSRI-induced sexual dysfunction, acute mountain sickness, and other indications may not yet be well enough established for widespread clinical use, this an-cient herb may still play a role in 21st-century medicine.