Ginkgoaceae (Plant Family)
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)
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
|Dosage Ranges and Duration of
- 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
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
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
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
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
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
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
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
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.
|Regulatory and Compendial
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
Barth SA, Inselmann G, Engemann R, Heidemann HT. Influences of Ginkgo
biloba on cyclosporin A induced lipid peroxidation in human liver microsomes
in comparison to vitamin E, glutathione and N-Acetylcysteine. Biochem
Bauer U. Six-month double-blind randomized clinical trial of Ginkgo
biloba extract versus placebo in two parallel groups of patients suffering
from peripheral arterial insufficiency. Arzneimittelforschung.
Blumenthal M, ed. The Complete German Commission E Monographs: Therapeutic
Guide to Herbal Medicines. Boston, Mass: Integrative Medicine
Brown D. Herbal Prescriptions for Better Health. Rocklin, Calif: Prima
Carper J. Miracle Cures. New York, NY: HarperCollins; 1997.
Cupp MJ. Herbal remedies: adverse effects and drug interactions. Am Fam
De Smet PAGM, Keller K, Hänsel R, Chandler RF, eds. Adverse Effects of
Herbal Drugs. Berlin: Springer-Verlag; 1997.
Fugh-Berman A. Herb-drug interactions. Lancet.
Galluzzi S, Zanetti O, Binetti G, Trabucchi M, Frisoni GB. Coma in a patient
with Alzheimer's disease taking low dose trazodone and Ginkgo biloba.
J Neurol Neurosurg Psychiatry. 2000;68:679-683.
Kim YS, Pyo MK, Park KM, et al. Antiplatelet and antithrombotic effects of a
combination of ticlopidine and Ginkgo biloba ext (EGb 761). Thromb
Kinghorn A, ed. Human Medicinal Agents from Plants. Washington, DC:
American Chemical Society; 1993.
Le Bars PL, Katz MM, Berman N, Itil TM, Freedman AM, Schatzberg AF. A
placebo-controlled, double-blind, randomized trial of an extract of Ginkgo
biloba for dementia. JAMA. 1997;278:1327-1332.
Manocha A, Pillai KK, Husain SZ. Influence of Ginkgo biloba on the
effect of anticonvulsants. Indian J Pharmacol. 1996;28:84-87.
Matthews MK. Association of Ginkgo biloba with intracerebral
hemorrhage [letter]. Neurol. 1998;50(6):1933-1934.
Miller LC. Herbal medicinals: selected clinical considerations focusing on
known or potential drug-herb interactions. Arch Intern Med.
Murray M. The Healing Power of Herbs: The Enlightened Person's Guide to
the Wonders of Medicinal Plants. 2nd ed. Rocklin, Calif: Prima Publishing;
Newall C, Anderson L, Phillipson J. Herbal Medicines: A Guide for
Health-care Professionals. London: Pharmaceutical Press; 1996.
Peters H, Kieser M, Holscher U. Demonstration of the efficacy of Ginkgo
biloba special extract Egb 761 on intermittent claudication a
placebo-controlled, double-blind trial. Vasa. 1998;27:105-110.
Rosenblatt M, Mindel J. Spontaneous hyphema associated with ingestion of
Ginkgo bilboa extract. N Engl J Med. 1997;336:1108.
Schulz V, Hänsel R, Tyler VE. Rational Phytotherapy: A Physicians' Guide
to Herbal Medicine. 3rd ed. Berlin: Springer-Verlag; 1998.
Shaw D, Leon C, Kolev S, Murray V. Traditional remedies and food supplements.
A 5 year toxicological study (1991-1995). Drug Safety.
Sikora R, Sohn M, Deutz F-J, et al. Ginkgo biloba extract in the
therapy of erectile dysfunction. J Urol.
Copyright © 2000 Integrative Medicine
CommunicationsThis publication contains
information relating to general principles
of medical care that should not in any event be construed as specific
instructions for individual patients. The publisher does not accept any
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