Ginkgo – Medicinal Uses, Interactions, Side Effects, Dosage

By | January 5, 2014

Ginkgo biloba is one of the oldest living tree species. Almost extinct following the Ice Age, the ginkgo tree survived only in Asia, and was imported to Europe and America in the 18th century as an ornamental street tree. An extract is prepared from the dried green leaves.

Uses and Benefits:

A standardized Ginkgo biloba extract (GBE) first became popular in Germany in the 1960s when a group of scientists found it to be particularly active while investigating the effects of exotic herbs on circulation. This extract was extensively researched and used for cognitive defects and peripheral vascular disorders in European countries, and is now commonly promoted for similar uses in the U.S, particularly for the treatment of dementia and Ihe enhancement of memory. GBE is used to treat circulatory impairment (cerebrovascular and peripheral arterial insufficiency), vertigo, tinnitus, impotence, asthma, allergies, premenstrual syndrome, depression, and many other disorders.

Pharmacology:

Ginkgo Biloba Tree

More than 40 components of Ginkgo bilobahave been identified. Two of the most important groups of active chemicals are the flavonoids (e.g., quercetin, kaempferol, isorhamnetin) and the terpene lactones or terpenoids, which include bilobalide and several ginkgolides (A, B, C, J, and M) GBE, standardized to 24% flavonoids and 6% terpenoids, and the individual constituents have been studied in hundreds of in vitro,animal, and human pharmacologic experiments.

In summary, GBE improves cerebral and peripheral bloodflow in animal and human experiments, at least in part via nitric oxide-induced vasodilation. The flavonoid components have antioxidant activity that can also prevent cellular damage. One or both 01″ these effects result in protection against neuronal, myocardial, and retinal damage in laboratory experiments and animal models, especially resulting from hypoxia or ischemia. In vitro, the gink. golides (especially ginkgolide B) inhibit binding of platelet-activating factor (PAF), which is normally a potent mediator of inflammatory and allergic responses. Additionally, activation of various cerebral neurotransmitter systems (especially the cholinergic system) may contribute to ginkgo’s cerebral properties. GBE causes behavioral changes in animals that include increased task performance and behavior adaptation, and produces enhanced alpha-wave activity on human EEG profiles that are similar to other cognitive-activator drugs such as tacrine.

While multiple biologic mechanisms have been well characterized, doses and routes of administration used in these experiments do not always correspond with oral doses in humans.

Clinical Trials:

Dementia and Cerebral Insufficiency-GBE has been used and studied in Europe for many years for the treatment of “cerebral insufficiency,” an ill-defined syndrome consisting of dementia or cognitive defects and a group of related physical and affectivesymptoms (e.g., tinnitus, vertigo, fatigue, headache, depression, anxiety). A 1992 critical review evaluated controlled trials of GBE for the treatment of this syndrome. All but one trial reported positive results, but only eight trials were of acceptable quality or were well performed. Recent research has concentrated on defined diagnoses with more stringent inclusion criteria for dementia of the Alzheimer’s type (OAT) and vascular or multi-infarct dementia (MID). In a recent systematic review, nine of double-blind, randomized, controlled trials met inclusion criteria for the treatment of mild-moderate OAT or MID. Statistically significant bene­fits were found in eight of nine trials. While some of these studies had methodological faults, the overall results demonstrated that ginkgo appeared efficacious in delaying the clinical deteriora­tion of patients with dementia or in bringing about symptomatic improvement.

Adverse Effects:

GBE is well tolerated. Less than 2% of patients develop side effects, which include mild gastrointestinal symptoms, headache, and dermal hypersensitivity. In most controlled clinical trials, the incidence of side effects is similar to that of placebo.

To date, seven case reports in the U.S. literature highlight the potential for bleeding complications, believed to be due to ginkgolide’s inhibitory effects on PAF. Two cases were of sponta-neous subdural hematoma, two were of intracerebral hemorrhage ( One in a 78-year-old man who was also taking warfarin), and there was one case each of subarachnoid hemorrhage, spontaneous eye hyphema (in an elderly man also taking aspirin), and postoperative bleeding. The causality of the relationships is not firmly established, and there have been no reports of bleeding from any of the controlled clinical trials or the millions of patients who have been treated in European countries. Thus, any risk of bleeding appears to be extremely small. Similarly, seven cases of seizures associated with ginkgo use have been recently reported to the FDA, and several other anecdotal cases have been noted. Although causality is uncertain, these reports highlight the potential toxicity of an herb with potent pharmacological properties.

Side Effects and Interactions:

Ginkgo extract given with trazodone was associated with acute CNS depression in an 80-year-old woman, which appeared to be reversed with flumazenil. In light of the in vitroaction of ginkgo on PAF and the case reports of bleeding, ginkgo should be used cautiously with other medications that inhibit clotting or enhance the risk of bleeding.

Cautions:

Data from animal studies indicates no teratogenic or embryotoxic effects with ginkgo; however, there is no human data lor use in pregnancy or lactation. Excessive ingestion of qinkgo seeds (not the leaves) can result in an illness known in Japan as gin-nan poisoning, which includes seizures.

Preparations Doses:

The usual dose of GBE demonstrated to be beneficial in the controlled clinical trials is 120-240 mg/day administered in divided doses (i.e., 40-80 mg taken two to three times a day). For chronic conditions, a 6-to 8-week trial of use has been typically recommended to evaluate efficacy. The GBE formulation is a concentrated 35-67:1 (mean 50:1) extract consisting of dried ginkgo leaves, which is standardized to contain 22-27% flavonoid glycosides and 5-7% terpenoids. This extraction technique also removes polyphenolic compounds including the potentially toxic and allergenic ginkgolic acids (to < 5 ppm).

Summary Evaluation

Ginkgo biloba contains many pharmacologically active constituents and is widely used for cognitive impairment, circulatory disorders, and many other indications. The best evidence for ginkgo’s clinical efficacy is for mild-moderate dementia and for intermittent claudication. However, benefits are likely to be small and have not been proven beyond a reasonable doubt. As a general memory-enhancer in the healthy adult, there is some evidence that GBE can improve selected cognitive testing such as speed of information processing. However, the optimal dose is unknown, and many studies failed to demonstrate beneficial effects; thus, the actual clinical and cognitive implications are unclear and inconclusive. Ginkgo’s role as a potential therapy for many other indications is not well established. Standardized ginkgo extracts are generally well tolerated, although there may be a very small increased risk of bleeding.