The dried leaf of the ginkgo tree has been used medicinally for thousands of years. More than 400 studies over the past 30 years have investigated ginkgo's ability to improve blood flow in a variety of conditions, including memory impairment, dementia, peripheral vascular disease, vertigo, tinnitus, asthma, SSRI-induced sexual dysfunction, anxiety and acute mountain sickness. The German Commission E has approved a standardized form of ginkgo leaf extract (EGb 761) for the treatment of cognitive impairment and intermittent claudication. Multiple pharmacologically active compounds have been isolated from ginkgo. Flavonoids have antioxidant and free radical scavenging ability and terpene lactones have platelet-activating factor antagonist activity. In addition, ginkgo extracts increase the production of nitric oxide and activate certain central neurotransmitters, including the cholinergic system, which may contribute to their beneficial effects on memory and cognition. EGb 761—the formulation that has been studied most extensively—is standardized to contain 24% flavonoid glycosides and 6% terpene lactones.
Early studies that assessed ginkgo's efficacy on cognitive function in the elderly showed a modest improvement when compared with placebo. The longest of these studies (1 year) showed stabilization of cognitive and functional abilities in 309 demented patients treated with EGb 761 compared with placebo, with no differences in adverse outcomes. A 2007 systematic review, however, concluded that ginkgo did not have predictable and clinically significant benefits in patients with dementia. There is conflicting evidence about ginkgo's ability to enhance memory in healthy individuals. The NIH has funded investigators at the University of Pittsburgh to determine whether ginkgo taken over 5 years can prevent or delay the development of dementia in 3000 patients 75 years of age or older.
In general, ginkgo is well tolerated in healthy adults at recommended doses for up to 6 months. Allergic skin reactions, gastrointestinal disturbances, and headache occur in less than 2% of patients. There are theoretical concerns about a risk of increased bleeding because antiplatelet activating factor activity has been demonstrated in vitro. Nearly 20 cases of increased bleeding in patients taking ginkgo have been reported, but establishing a causal relationship is challenging because many of these patients had other risk factors including age and use of medications, such as warfarin, aspirin, or NSAIDs. Of note, no excess bleeding complications have been reported in clinical trials and no differences in coagulation, platelet function, or pharmacokinetics of warfarin have been reported in healthy volunteers. Caution should still be exercised in patients with bleeding disorders or who are taking anticoagulants, aspirin, or other herbs that may increase the risk of bleeding. In one study, ginkgo (90 mg/d) did not show any adverse effects on the pharmacokinetics of donepezil (5 mg/d) when administered together, but potential interactions with other medications used to treat dementia are not known.
Ginkgo has also been evaluated for its effect on intermittent claudication. A meta-analysis of nine randomized, placebo-controlled, double-blinded trials of patients treated with EGb 761 showed a modest treatment effect in the increase of pain-free walking distance in favor of ginkgo over placebo. There is insufficient evidence to support ginkgo's efficacy in treating tinnitus, acute mountain sickness, vertigo, or SSRI-associated sexual dysfunction.
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