Ginkgo biloba is one of the oldest living tree species, existing even before the Ice Age. Although Chinese herbal medicine has used both the ginkgo leaf and seed for centuries, modern research has focused on the standardized Ginkgo biloba extract (GBE), which is produced from the leaves. This extract is highly concentrated and much more effective than any other use of the leaves. More than 400 published studies have been conducted using GBE, making it one of the most studied of all herbal medicines. In Germany and France it is the most frequently prescribed herbal medicine and is in the top five of all medical prescriptions written in those countries. GBE is a powerful aid to circulatory problems, particularly cerebral insufficiency and peripheral arterial insufficiency seen most often in the elderly. It has strong antioxidant properties as well, and may protect both the central nervous system and the cardiovascular system from damage and the effects of aging.

GBE improves circulation by inhibiting platelet aggregation, reducing the potential for atherosclerosis, which, therefore, may aid in prevention and treatment of cerebrovascular insufficiency, coronary artery disease, peripheral arterial insufficiency, and strokes. Cerebrovascular insufficiency can cause much of the mental deterioration or dementia associated with aging, including memory loss, vertigo, tinnitus, disorientation, and depression. GBE has been shown to increase blood flow to the brain, resulting in marked improvement for many patients. It may be effective in preventing the onset of age-related mental deterioration. In a few small studies, GBE seemed to delay the progression of Alzheimer's disease, particularly in the early stages.

GBE has been shown to improve blood flow to the extremities and increase walking tolerance. In fact, clinical studies have demonstrated that GBE is superior to standard treatment with pentoxifylline for peripheral arterial insufficiency. Other peripheral vascular disorders that seem to respond to GBE include diabetic peripheral vascular disease, Raynaud's phenomenon, acrocyanosis, and postphlebitis syndrome. Because of its ability to improve circulation, GBE is being studied as an aid for impotence caused by impaired blood flow. Recent studies suggest good results, which are probably due to GBE's ability to improve blood flow without changing systemic blood pressure. There is evidence that GBE may also reduce certain PMS symptoms, including fluid retention and breast tenderness.

Ginkgo biloba is a deciduous tree that can live up to 1000 years and grow to a height of 120 feet. It has short branches with shoots that have fan-shaped, bilobed leaves. The fruit has a strong, unpleasant odor and is inedible, with an inner seed. Once common in North America and Europe, the Ice Age destroyed all but remnants that survived in China. Now grown in Asia, Europe, and North America.

• Seeds (please see the section on warnings and precautions) 
• Leaves

Ginkgo flavone glycosides (quercetin, kaempferol, isorhamnetine, proanthocyanidins), several terpene molecules unique to ginkgo (ginkgolides and bilobalide), organic acids

Ginkgo biloba extract (50:1) standardized to contain 24% ginkgo flavone glycosides and 6% terpene lactones. This herb is also available in encapsulated and tincture forms.

Traditional herbal actions: heart disease, respiratory tract illnesses, asthma, memory loss in aging, and chilblain (erythema, itching and burning of digits, heels, and nose from extreme cold associated with high humidity)

Clinical applications: intermittent claudication, allergies, dementia, vertigo (if vascular in nature), vascular fragility, short-term memory loss, headache, depression, stroke, poor circulation, atherosclerosis, cerebrovascular insufficiency, Alzheimer's disease, vascular tinnitus, cochlear deafness, macular degeneration, diabetic retinopathy, peripheral arterial insufficiency, impotence, PMS, Raynaud's phenomenon

GBE stabilizes cell membranes by inhibiting lipid peroxidation, and acts as an antioxidant by reducing free radical damage. It also aids cell use of oxygen and glucose. These properties are particularly important for brain cells, which are particularly vulnerable to free radical damage and oxygen deprivation. Brain cells are also protected by GBE's ability to improve blood flow to the brain, particularly the hippocampus and striatum, areas most affected by micro-embolization. These combined effects may allow GBE to reverse mental deterioration caused by vascular insufficiency. The mental deterioration caused by Alzheimer's seems to be significantly delayed by GBE's ability to enhance brain function, along with normalizing acetylcholine receptors in the hippocampus and increasing the rate of cholinergic transmission.

GBE normalizes circulation through a vasodilatory mechanism. GBE stimulates the release of both endothelium-derived relaxing factor and prostacyclin, thereby acting as a vasodilator. In addition, GBE greatly influences platelet function by inhibiting platelet aggregation, platelet adhesion, and degranulation. Along with its antioxidant effects, this influence seems to come from GBE's ability to inhibit platelet-activating factor (PAF). PAF stimulates platelet aggregation, and causes inflammation and allergic reactions by increasing vascular permeability, activation of neutrophils, smooth-muscle contractions including bronchoconstriction, and reducing coronary blood flow. Higher PAF levels are also associated with aging. Many of GBE's clinical results may come from its ability to inhibit PAF and its effects. The unique terpene lactones in GBE, particularly the ginkgolides, are thought to be the main source of this ability to inhibit PAF.

The terpene lactones in GBE (ginkgolides and bilobalide) also protect nerve cells from damage during periods of ischemia or hypoxia. This hypoxic tolerance is seen particularly in cerebral tissue, making GBE an effective treatment for people who have suffered strokes or transient ischemic attacks.

• Take 120 mg daily in two divided doses of 50:1 extract standardized to 24% flavone glycosides. Doses for intermittent claudication may range from 120 to 160 mg/day. Patients with more serious dementia or Alzheimer's disease may need to take up to 240 mg daily in two to three divided doses. Results often take four to six weeks, but should continue to accumulate. Some dramatic changes may not appear for six months. 
• Tincture (1:5): 2 to 4 ml tid 

GBE is considered to be safe and side effects are rare. In a few cases, gastrointestinal upset, headaches, and dizziness have been reported. GBE has been shown not to alter heart rate and blood pressure or to change cholesterol and triglyceride levels. Because it decreases platelet aggregation, there is some concern that ginkgo may increase risk of intracranial hemorrhage. Use with caution in conjunction with other blood-thinning agents (e.g., warfarin). Please refer to the interactions section below for more information.

The fruit of Ginkgo biloba, including the seed, should not be handled or ingested. Ingesting the seed can cause severe adverse effects. The German Commission E reports the only contraindication for GBE is a hypersensitivity to Ginkgo biloba preparations. There are no known contraindications for pregnancy, but pregnant or lactating women should exercise caution since there is a lack of studies showing GBE's effects during pregnancy.

Concurrent use of ginkgo with warfarin may increase the risk of bleeding (Fugh-Berman 2000). There is a case report of intracerebral hemorrhage in a 78-year-old woman who used ginkgo while on warfarin therapy (Matthews 1998). Another case report concerning a possible interaction between aspirin (325 mg/day) and ginkgo (40 mg) involved a 70-year-old man who developed spontaneous hyphema while taking both substances together (Rosenblatt and Mindel 1997). These interactions may be related to inhibition of PAF. In a rat study, the combination of ticlopidine (50 mg/kg/day) and ginkgo (40 mg/kg/day) administered orally prolonged bleeding times by 150% (Kim et al. 1998). Given these reports, it has been recommended that ginkgo not be used with aspirin, warfarin, dipyridamole, clopidogrel, ticlopidine, and heparin (Cupp 1999; Miller 1998).

A study evaluating the effects of Ginkgo biloba in mice treated with the anticonvulsants sodium valproate and carbamazepine found that intraperitoneal administration of ginkgo (50 mg/kg) decreased the protective effect of these medications on picrotoxin- (2 mg/kg) and strychnine- (0.25 mg/kg) induced convulsions (Manocha et al. 1996). This was thought to be related to antagonism of PAF and possible effects on the GABA-ergic system. High dose Ginkgo biloba could decrease the effectiveness of anticonvulsant therapy in patients with coexisting symptoms of cerebral insufficiency.

In an in vitro study, cyclosporin (CsA) stimulated lipid peroxidation up to 10 times the control value (Barth et al. 1991). Ginkgo biloba extract added to the medium inhibited CsA-induced lipid peroxidation in a concentration-dependent manner. Ginkgo biloba extract may be able to prevent CsA mediated free radical damage to human membranes. More research is necessary to fully evaluate the safety and efficacy of this application of GBE.

It has been reported that ginkgo extract has the ability to potentiate the intracavernosal injection of papaverine for impotence (Sikora et al. 1989). For patients with arterial erectile dysfunction who did not respond to papaverine alone, 50% of patients responded to treatment with ginkgo alone and 20% of patients responded sufficiently to the combination of ginkgo and papaverine.

A 5-year toxicological study on traditional remedies and food supplements reported one case of an interaction between Ginkgo biloba and thiazide diuretics (Shaw et al. 1991). A patient taking thiazide diuretics was reported to have increased blood pressure one week after adding Ginkgo biloba to her treatment regimen. Blood pressure returned to pre-treatment levels when both the diuretic and ginkgo were discontinued. However, Ginkgo biloba has not been reported to increase blood pressure levels in any clinical trials.

According to a recent case report, flavonoids in Ginkgo biloba may increase the sedative effects of the drug trazodone (Galluzzi et al. 2000). The report describes the case of an 80-year-old Alzheimer's patient who, after taking trazodone (20 mg bid) with gingko extract (80 mg bid) for 3 days, went into a coma. The patient was revived and experienced no permanent damage. It is possible that the mechanism for this interaction involves the ability of the ginkgo flavonoids to increase the metabolism of trazodone (leading to active metabolites) and activity at the benzodiazepine binding sites. Further studies are needed to confirm this report.

The German Commission E approves specific GBE extracts for use in treating dementia, intermittent claudication associated with peripheral arterial insufficiency, as well as vertigo and tinnitus of vascular and involutional origin.

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