Alternative Medicine
Ginkgo Biloba

Janet H. Cuccinelli

 [Clinician Reviews 9(8):93-94, 97, 1999. © 1999 Clinicians Publishing Group and Williams & Wilkins.]

Interest in alternative therapies has exploded among Americans during recent decades, and researchers have responded with studies and reports about the efficacy and safety of these treatments. Practitioners need to stay abreast of this emerging information so they can guide their patients in making informed decisions about using such alternative therapies as herbal medicine, acupuncture, homeopathy, and energy healing. To help PAs and NPs sort through the barrage of available information, each month the Alternative Medicine feature will present an up-to-date and scientific view of a specific therapy.

Description

Sometimes described as a "living fossil," the Ginkgo biloba tree is the last remaining species of a botanic family that was once widely distributed.[1] Though native to China, G biloba is found as an ornamental plant in many countries, including the United States. According to herbal researchers, seeds and fruit harvested from the female ginkgo (or maidenhair) tree have been used medicinally in China for thousands of years.[2,3] But flavonoids in the ginkgo's fan-shaped leaves were not identified until the 1930s, and Western scientific investigation did not begin in earnest until the mid 1970s, when an extract of the leaves was developed in Europe.[3]

Pharmacology

Ginkgo biloba preparation is a standardized extract containing 24% flavone glycosides (primarily quercetin, kaempferol, and isorhamnetin) and 6% terpene lactones (approximately equal parts of bilobalide and ginkgolides A, B, and C); numerous other constituents have been identified. Although the therapeutic effects of the extract's individual components are under investigation, some are known to act synergistically.[3,4]

Ginkgo biloba's primary biologic activity appears to be inhibition of platelet activating factor (PAF) -- and thus, of PAF-induced platelet aggregation.[5] Ginkgolide B is considered largely responsible for PAF antagonism.[6] The extract also functions as an antioxidant to neutralize free radicals5 and may affect norepinephrine, serotonin, monoamine oxidase, acetylcholine, and nitric oxide.[7] By inhibiting corticosteroid synthesis, ginkgolides A and B appear to offer antistress and neuroprotective benefits.[6]

Uses

The Chinese have used G biloba seeds to treat asthma, productive chest cough, and urinary incontinence[2]; preparations from the leaf have been used as a brain tonic and asthma remedy.[3] In France and Germany, the leaf extract is often prescribed for intermittent claudication and "cerebral insufficiency" -- a syndrome associated with impaired circulation and early markers of dementia.[5]

In one clinical study, patients with uncomplicated dementia experienced improvements of approximately 25% in cognitive function after 4 to 6 weeks of ginkgo biloba therapy.[8] In another, a modest but statistically significant improvement was reported in cognitive and social function for 6 months to 1 year.[4]

In other trials, the EGb 761 extract was shown to improve walking distances significantly in patients with intermittent claudication,[9] and pretreatment with a topical formulation reduced response to allergens causing contact dermatitis.[10] French researchers have linked ginkgo biloba therapy to improved visual acuity in patients with macular degeneration.[6]

Despite a biologic basis for using ginkgo biloba extract in asthma, inflammatory conditions, acute myocardial or cerebral ischemia, shock, anaphylaxis, graft rejection, and renal disease, clinical trials do not yet confirm its use for these conditions[5]; only in vitro findings support the possible benefits of ginkgo biloba's antioxidant effects in inflammatory conditions like Behçet's syndrome.[11] However, experimental evidence does suggest that ginkgo biloba enhances vascular relaxation,[12] making it potentially useful to treat ischemic conditions, curb cancer cell growth, and inhibit phospholipase C1.[13]

In patients taking antidepressants (particularly selective serotonin reuptake inhibitors) ginkgo biloba extract has been associated with improved sexual function -- but only in isolated, anecdotal reports; the possibility of spontaneous reversal or placebo effect cannot be disproved.[7] However, some herbal authorities consider impotence a treatable condition that may well respond to the extract's vasodilating property.[3,14]

Additional unsubstantiated uses include treatment of cardiac arrhythmia, varicosities, hemorrhoids, and leg ulcers2; phlebitis, diabetic vascular disease, depression, and Raynaud's syndrome.[15]

Contraindications

Hypersensitivity or intolerance to the extract is a contraindication.[6,15] Ginkgo biloba may prolong bleeding time and should not be used in individuals with hemophilia or other bleeding disorders,[15] or in patients taking anticoagulants or antiplatelet agents. Although no data exist regarding use during pregnancy and lactation, some sources consider these to be contraindications.[6,15]

Drug Interactions

No specific drug interaction has been documented.[5] However, as in other drug classes, it is advisable to avoid using ginkgo biloba with substances that act through similar mechanisms, because of the potential additive effect (eg, warfarin, aspirin).[16] Concurrent alcohol intake may prolong bleeding time.[17]

Adverse Effects

Most side effects are mild: gastrointestinal symptoms, headache, allergic skin reactions,[18] irritability and restlessness,[15] and peripheral visual shimmering.[6] In placebo-controlled clinical studies, the incidence of adverse effects with ginkgo biloba was similar to that with placebo.[8] Hypersensitivity reactions may be more common in those who use G biloba seeds, and contact with the fruit pulp causes dermatitis.[2,15]

Long-term use has been linked with rare occurrences of spontaneous subdural hematoma, intracerebral or intraocular hemorrhage, and prolonged bleeding time -- as has concomitant administration of anticoagulant or antiplatelet agents.[16,17,19]

Toxicity

Ginkgo biloba extracts have not been associated with toxicity -- even in above-average doses.[3] No major adverse effects, such as hepatic or renal impairment, have been seen with long-term use.[3] Neither mutagenicity nor potentiation of mutagenic substances has been detected.[6]

Dosage Regimen

The average dose of standardized extract is 40 mg tid. Individuals age 50 years and older may use 60 mg tid for protection against the effects of aging.[3]

Patients with cerebral insufficiency and dementia have reportedly benefited from taking 120 to 160 mg daily in three divided doses.[18] One study reported comparable results in those taking 240 mg daily of ginkgo biloba or 40 mg of tacrine.[20]

Optimal dosing and duration of treatment have not been determined. While some individuals report benefits within 3 weeks of daily use, most require months before significant effects are felt.[3] Some sources advise taking ginkgo indefinitely, as its efficacy increases and lasts longer with time.[14]

Warnings

In some individuals, even small doses of ginkgo biloba may not be tolerated.[15] Children taking ginkgo biloba -- and adults taking medicinal doses -- should only do so under the care of a qualified health care provider.[15]

Ginkgo biloba should probably not be used by those with risk factors for hemorrhagic stroke (anticoagulant therapy, hypertension, and concurrent alcohol intake; possibly thrombolytic therapy; and use of amphetamines or cocaine). Concurrent cigarette smoking and/or use of platelet-aggregation inhibitors may increase the risk of subarachnoid hemorrhage.[17]

Patients with diabetes mellitus should use ginkgo biloba with caution. While diabetes may be a risk factor for hemorrhagic stroke,[17] the vasodilating and neuroprotective qualities of ginkgo biloba may prove beneficial to diabetic patients.[3,6,15,21]

References

1.        Brockman CF. Trees of North America. New York, NY: Golden Press; 1986.

2.        Ody P. The Complete Medicinal Herbal. New York, NY: Dorling Kindersley; 1993.

3.        Mayell M. Natural Energy: A Consumer's Guide to Legal, Mind-Altering, and Mood-Brightening Herbs and Supplements. New York, NY: Three Rivers Press; 1998.

4.        Le Bars PL, Katz MM, Berman N, et al, for the North American EGb Study Group. JAMA. 1997;278:1327-1332.

5.        Myerscough M. Herbal remedies: how much do you know? Aust Fam Physician [serial online]. November 1998. Available at: www.racgp.org.au/newsletter/nov98/clinical.htm. Accessed July 12, 1999.

6.        Ginkgo biloba [monograph online]. Available at: www.thorne.com/altmedrev/ginkgo3-1.html. Accessed July 16, 1999.

7.        Ellison JM, DeLuca P. Fluoxetine-induced genital anesthesia relieved by ginkgo biloba extract [letter]. J Clin Psychiatry. 1998;59(4):199-200.

8.        Soholm B. Clinical improvement of memory and other cognitive functions by ginkgo biloba: review of relevant literature. Adv Ther. 1998:15(1):54-65.

9.        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 multicenter trial. Vasa. 1998;27(2):106-110.

10.     Castelli D, Colin L, Camel E, Ries G. Pretreatment of skin with a Ginkgo biloba extract/sodium carboxymethyl-beta-1,3-glucan formulation appears to inhibit the elicitation of allergic contact dermatitis in man. Contact Dermatitis. 1998;38(3):123-126.

11.     Kose K, Dogan P, Ascioglu M, Ascioglu O. In vitro antioxidant effect of ginkgo biloba extract (EGb 761) on lipoperoxidation induced by hydrogen peroxide in erythrocytes of Behçet's patients. Jpn J Pharmacol. 1997;75(3):253-258.

12.     Chen X, Salwinski S, Lee TJ. Extracts of ginkgo biloba and ginsenosides exert cerebral vasorelaxation via a nitric oxide pathway. Clin Exp Pharmacol Physiol. 1997;24(12):958-959.

13.     Lee JS, Cho YS, Park EJ, et al. Phospholipase C1 inhibitory principles from the sarcotestas of Ginkgo biloba. J Nat Prod. 1998;61(7):867-871.

14.     Murray MT. Natural Alternatives to Over-the-Counter and Prescription Drugs. New York, NY: William Morrow & Co; 1994.

15.     The Alternative Advisor: The Complete Guide to Natural Therapies and Alternative Treatments. Alexandria, Va: Time Life Inc; 1997.

16.     Matthews MK Jr. Association of ginkgo biloba with intracerebral hemorrhage [letter]. Neurology. 1998;50:1933.

17.     Vale S. Subarachnoid haemorrhage associated with ginkgo biloba [letter]. Lancet. 1998;352:36.

18.     Kleijnen J, Knipschild P. Ginkgo biloba. Lancet. 1992;340:1136-1139.

19.     Rowin J, Lewis SL. Spontaneous bilateral subdural haematomas associated with chronic ginkgo biloba ingestion. Neurology. 1996;46:1775-1776.

20.     Itil TM, Eralp E, Ahmed I, et al. The pharmacological effects of ginkgo biloba, a plant extract, on the brain of dementia patients in comparison with tacrine. Psychopharmacol Bull. 1998;34(3):391-397.

21.     Zhu L, Wu J, Liao H, et al. Antagonistic effects of extract from leaves of ginkgo biloba on glutamate neurotoxicity. Chung Kuo Yao Li Hsueh Pao. 1997;18:344-347.