Ginkgo Biloba

Overview

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 done on GBE, making it one of the best researched 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, protecting both the central nervous system and the cardiovascular system from damage and the effects of aging.

GBE improves circulation by strengthening the vascular system and inhibiting platelet aggregation, preventing atherosclerosis, which leads to cerebral insufficiency, coronary artery disease, peripheral arterial insufficiency, and strokes. Cerebral 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 a marked improvement for many patients. It is also used effectively to prevent the onset of mental deterioration for those approaching old age. In a few small studies, GBE seemed to slow and even stop the progress of Alzheimer's disease, particularly in the early stages.

Peripheral arterial insufficiency is caused by arterial narrowing or obstruction and its most common symptom is intermittent claudication, particularly in the calves. GBE has been shown to improve blood flow in the limbs and increase walking tolerance at levels much higher than standard medical treatments. Other peripheral vascular disorders that 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 have shown good results, which are probably due to GBE's ability to increase blood flow without changing systemic blood pressure. There is evidence that GBE may also reduce certain PMS symptoms, including fluid retention, vascular congestion, and breast tenderness.

Macro Description

Ginkgo biloba is a deciduous tree that can live up to 1,000 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 edible 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.

Part Used/Pharmaceutical Designations

• Seeds
• Leaves

Constituents/Composition

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

Commercial Preparations

Ginkgo biloba extract standardized to contain 24% ginkgo flavone glycosides (50:1 extract) and 6% terpene lactones. (There are several different brands of GBE available in the United States, but almost all of the scientific and clinical studies have been performed on the original German formula.) Encapsulated herb and tincture are also available.

Medicinal Uses/Indications

Traditional herbal actions: circulatory stimulant, antidepressant, antithrombotic

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

Pharmacology

GBE strengthens tissue by stabilizing cell membranes, acting as an antioxidant, and inhibiting free radical damage. It also aids cell use of oxygen and glucose. These properties are particularly important for brain cell tissue, which is most vulnerable to free radical damage and oxygen deprivation. Brain cells are also protected by GBE's ability to improve blood circulation to the brain, particularly the hippocampus and striatum, areas most affected by micro-embolization. GBE has also been shown to increase the rate of transmission of information to the nerve cell level, enhancing memory ability. These combined effects 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 the acetylcholine receptors in the hippocampus and increasing cholinergic transmission.

GBE strengthens the vascular system by focusing on two areas: vascular endothelium and the system that regulates blood vessel tone. As a vasodilator, it stimulates the release of endothelium-derived relaxing factor and prostacyclin. GBE also restricts an enzyme that causes blood vessels to relax and stimulates greater tone throughout the vessels.

GBE greatly influences platelet function by inhibiting platelet aggregation, platelet adhesion, and degranulation. Along with its powers as an antioxidant, this influence seems to come from GBE's ability to inhibit a substance known as platelet-activating factor (PAF). PAF stimulates platelet aggregation, and causes inflammation and allergic reactions by increasing vascular permeability, activation of neutrophil, 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.

Dosage Ranges and Duration of Administration

• Take 120 mg daily in two divided doses of 50:1 extract standardized to 24% flavone glycosides. Patients with more serious dementia or Alzheimer's disease may need to work 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.
• Capsules of dried herb with 10 mg standardized extract (1 to 3 capsules tid)
• Tincture (1:5): 2 to 4 ml tid
• Fluid extract (1:1): 1 to 3 ml tid

Side Effects/Toxicology

GBE is very safe and side effects are rare. In a few cases, gastrointestinal upset, headaches, and dizziness were 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., Coumadin).

Warnings/Contraindications/Precautions

The fruit of Ginkgo biloba 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.

Interactions

Aspirin; Dipyridamole; Heparin; Warfarin

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 platelet-activating factor. 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). It has been recommended that ginkgo not be used with aspirin, warfarin, dipyridamole, clopidogrel, ticlopidine, and heparin (Cupp 1999; Miller 1998).

Carbamazepine; Sodium Valproate

A study evaluated the effects of ginkgo biloba, a platelet activating factor (PAF) antagonist, on mice treated with the anticonvulsants valproate and carbamazepine (Manocha et al. 1996). Ginkgo biloba (50 mg/kg ip) decreased the protective effect of sodium valproate and carbamazepine on picrotoxin- (2 mg/kg ip) and strychnine- (0.25 mg/kg) induced convulsions. High dose ginkgo biloba could decrease the effectiveness of anticonvulsant therapy in patients with coexisting symptoms of cerebral insufficiency.

Cyclosporine

In an in vitro study, cyclosporin (CsA) stimulated lipid peroxidation up to 10 times the control value (Barth et al. 1991). Ginkgo biloba extract (EGb) 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.

Papaverine

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 who did not respond to papaverine alone, those who had arterial erectile dysfunction (50%) did not require the addition of papaverine to ginkgo, while 20% of patients responded sufficiently only to the combination of ginkgo extract and papaverine.

Thiazide Diuretics

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.

Trazodone

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 site. Further studies are needed to confirm this report.

Regulatory and Compendial Status

The German Commission E approves specific GBE extracts for use in treating dementia, peripheral arterial insufficiency, vertigo, and tinnitus.

References

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