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Chapter: Basic & Clinical Pharmacology : Dietary Supplements & Herbal Medications

Botanical Substances: Ginkgo (Ginkgo Biloba)

Ginkgo biloba extract is prepared from the leaves of the ginkgotree.




Ginkgo biloba extract is prepared from the leaves of the ginkgotree. The most common formulation is prepared by concentrating 50 parts of the crude leaf to prepare one part of extract. The active constituents in ginkgo are flavone glycosides and terpenoids (ie, ginkgolides A, B, C, J, and bilobalide).

Pharmacologic Effects


A. Cardiovascular Effects


In animal models and some human studies, ginkgo has been shown to increase blood flow, reduce blood viscosity, and promote vasodilation, thus enhancing tissue perfusion. Enhancement of endogenous nitric oxide  and antagonism of platelet-activating factor have been observed in animal models.


Ginkgo biloba has been studied for its effects on mild to mod-erate occlusive peripheral arterial disease. Among 11 randomized, placebo-controlled studies involving 477 participants using stan-dardized ginkgo leaf extract (EGb761) for up to 6 months, a nonsignificant trend toward improvements in pain-free walking distance (increase of 64.5 meters) was observed (p = .06).


The Ginkgo Evaluation of Memory (GEM) study evaluated cardiovascular outcomes associated with the long-term use of ginkgo for 6 years in 3069 patients over 75 years of age. Daily use of 240 mg/d EGb761 did not affect the incidence of hypertension or reduce blood pressure among persons with hypertension or prehypertension. No significant effects in cardiovascular disease

mortality or events or hemorrhagic stroke were observed. There was, however, a significant reduction in peripheral vascular disease events in the ginkgo arm versus the placebo arm.


B. Metabolic Effects


Antioxidant and radical-scavenging properties have been observed for the flavonoid fraction of ginkgo as well as some of the terpene constituents. In vitro, ginkgo has been reported to have superoxide dismutase-like activity and superoxide anion- and hydroxyl radical-scavenging properties. The flavonoid fraction has also been observed to have anti-apoptotic properties. In some studies, it has also dem-onstrated a protective effect in limiting free radical formation in animal models of ischemic injury and in reducing markers of oxida-tive stress in patients undergoing coronary artery bypass surgery.


C. Central Nervous System Effects


In aged animal models, chronic administration of ginkgo for 3–4 weeks led to modifications in central nervous system recep-tors and neurotransmitters. Receptor densities increased for mus-carinic, α2, and 5-HT1a receptors and decreased for β adrenoceptors. Increased serum levels of acetylcholine and norepinephrine and enhanced synaptosomal reuptake of serotonin have also been reported. Additional effects include reduced corticosterone syn-thesis and inhibition of amyloid-beta fibril formation.


Ginkgo has been used to treat cerebral insufficiency and demen-tia of the Alzheimer type. The term cerebral insufficiency, however, includes a variety of manifestations ranging from poor concentra-tion and confusion to anxiety and depression as well as physical complaints such as hearing loss and headache. For this reason, studies evaluating cerebral insufficiency tend to be more inclusive and difficult to assess than trials evaluating dementia. An updated meta-analysis of ginkgo for cognitive impairment or dementia was performed by the Cochrane Collaboration. They reviewed 36 ran-domized, double-blind, placebo-controlled trials ranging in length from 3 to 52 weeks. Significant improvements in cognition and activities of daily living were observed at 12 but not 24 weeks. Significant improvements in clinical global improvement, however, were observed at 24 but not 12 weeks. The authors concluded that the effects of ginkgo in the treatment of cognitive impairment and dementia were unpredictable and unlikely to be clinically relevant. In the GEM study, the effects of gingko as a prophylactic agent to prevent progression to dementia were assessed. No benefit was observed with 6 years of ginkgo treatment. To date, there is no known therapy that prevents progression to dementia.


D. Miscellaneous Effects


Ginkgo has been studied for its effects in allergic and asthmatic bronchoconstriction, short-term memory in healthy, non-demented adults, erectile dysfunction, tinnitus and hearing loss, and macular degeneration. For each of these conditions, there is insufficient evidence to warrant clinical use.


Adverse Effects


Adverse effects have been reported with a frequency comparable to that of placebo. These include nausea, headache, stomach upset,diarrhea, allergy, anxiety, and insomnia. A few case reports noted bleeding complications in patients using ginkgo. In a few of these cases, the patients were also using either aspirin or warfarin.


Drug Interactions & Precautions


Ginkgo may have antiplatelet properties and should not be used in combination with antiplatelet or anticoagulant medications. One case of an enhanced sedative effect was reported when ginkgo was combined with trazodone. Seizures have been reported as a toxic effect of ginkgo, most likely related to seed contamination in the leaf formulations. Uncooked ginkgo seeds are epileptogenic due to the presence of ginkgotoxin. Ginkgo formulations should be avoided in individuals with preexisting seizure disorders.




Ginkgo biloba dried leaf extract is usually standardized to contain24% flavone glycosides and 6% terpene lactones. The daily dose ranges from 120 to 240 mg of the dried extract in two or three divided doses.

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