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Tinnitus - Ginkgo Biloba - A Word of Hope and A Word of Caution

Ginkgo Biloba - A Word of Hope and A Word of Caution

The vast majority of individuals significantly affected by tinnitus encounter the maidenhair tree along the inevitable odyssey in search of relief from incessant ringing. Some walk quickly by, some stop and ponder, and some remain to partake of the fruits (actually extracts from dried leaves) of this tree, which is the oldest living species of tree on earth, having been present since the days of the dinosaur. Ginkgo biloba, the maidenhair tree, was believed at one time to have magical powers. Today Ginkgo is felt by many to have a legitimate medicinal role. The extracts, which can be taken in pill form, as a liquid, or intravenously, are administered- among many reasons- in the hopes of impacting cerebral insufficiency by increasing blood flow to the brain, by improving neurotransmission, and by being free-radical scavengers. Symptoms of cerebral insufficiency, an imprecise term for a condition which demands much greater study, can include difficulties of cognitive skills, decreased energy and physical performance, depression, anxiety, dizziness, headache, and... tinnitus.1

Although some members of the tinnitus population "swear by" Ginkgo biloba, others feel that it is totally ineffective. The question of the true value of this agent should be answered conclusively within the next year, however, when the results of the first large-scale double-blind randomized prospective study (1000 volunteers at Birmingham University in the U.K.) on the efficacy of Ginkgo biloba in tinnitus treatment, will be published. Regardless of the outcome of the study, the many affected by tinnitus who believe that Ginkgo has improved their symptomatology will undoubtedly continue to use it; indeed, if the study does clearly demonstrate efficacy, millions with tinnitus will use it on a regular basis worldwide.

One of the appealing aspects of Ginkgo biloba when considered for tinnitus treatment has been the fact that whether or not it is effective, it is relatively inexpensive, and it supposedly has negligible side effects. The purpose of this article is to explore one particular side effect of Ginkgo, which has recently begun to appear in the medical literature, and which may be grossly under-reported.

For the numerous patients who have taken Ginkgo in search of relief, the main reason for some discontinuing this agent has been failure for tinnitus to improve in their particular cases. Infrequently (but not insignificantly), however, Ginkgo is discontinued because of an apparent increased propensity for epistaxis- nosebleeds.2 The vast majority of individuals on Ginkgo have no problems with nosebleeds... or any other side effects.

In terms of mechanism of action, the most important components of Ginkgo are flavenoids and terpenoids. Ginkgolide B, a terpenoid which is not known to exist in any other living species, has been shown in vitro (in the laboratory) to inhibit the action of platelet Activating Factor (pAF).3 pAF is a crucial element in initiation of platelet aggregation, an early essential step in the coagulation cascade, the blood clotting mechanism. The potential exists, therefore, that in vivo (in real life) Ginkgo biloba might adversely affect blood clotting. Herein lies a potential explanation for the (anecdotal) increased incidence of nosebleeds among individuals taking Ginkgo. The obvious question then arises: if we assume that Ginkgo does, indeed, cause nosebleeds in some cases, then what might it be doing inside the body

In the June 1996 issue of the journal Neurology a case report appeared of a lady in her thirties, who had been taking 120 mg of Ginkgo biloba daily for two years and who presented with large bilateral subdural hematomas- bleeding deep to the covering of the brain, compressing the brain matter itself.4 There was no antecedent history of head trauma, and the patient's only other medications were acetaminophen and a very brief trial of ergotamine/caffeine tablets. Specifically, the patient had taken no anticoagulants. She had taken neither aspirin nor any non-steroidal anti-inflammatory medications. Her bleeding time (see below) was prolonged, but returned to normal when it was re-checked a month after cessation of the Ginkgo. (She underwent emergency surgical evacuation of the subdural hematomas and fortunately made a complete recovery.)

Ordinarily an isolated anecdotal report such as the one just described would arouse little interest. This report, however, was somewhat bothersome for three reasons:

  • Most individuals, when asked by a physician to list "current medications," would tend not to list Ginkgo.
  • Most physicians tend not to explore a "current medication" list further to see if agents such as Ginkgo, not typically considered by Western tradition to be medications at all, might have been inadvertently left off the list.
  • Most physicians do not appreciate the anticoagulant properties of Ginkgo.

These three factors might potentially contribute to under-reporting of a problem of some significance. In fact, just nine months after the subdural hematoma case was reported, a case of (rare) spontaneous hyphema, bleeding into the anterior chamber of the eye, in a gentleman on Ginkgo, appeared in the literature.5

What, then, would be a prudent position to take if one were considering initiating a course of Ginkgo or if one were already taking this agent6 It seems reasonable to assume a "worst case scenario"- to assume that regardless of its efficacy with respect to tinnitus treatment, Ginkgo biloba does in certain cases predispose to bleeding, bleeding not necessarily limited to nosebleeds. Fortunately there is a laboratory test, the "bleeding time," which is a fairly sensitive measure of platelet function (e.g., the bleeding time would be expected to be prolonged if platelet aggregation were inhibited enough to adversely impact coagulation in vivo.) Most often a bleeding time is performed painlessly as a technologist "fires" a device which makes a short and very superficial incision (1 mm deep) on the forearm with a blood pressure cuff inflated to a pressure of 40 mmHg.7

  • There is general agreement that if Ginkgo has not been effective within three months, it will not become effective thereafter. Thus, Ginkgo should be discontinued after three months if ineffective.
  • If Ginkgo is to be continued for longer than three months, the bleeding time should be monitored at six-month intervals. If the bleeding time is significantly prolonged, a decision should be made about whether or not to continue the Ginkgo in consultation with the physician, who should be informed that Ginkgo can interfere with platelet aggregation.
  • If bleeding gums, nosebleeds, bruising, etc. are noticed while on Ginkgo, a bleeding time should be obtained, and a decision should be made whether or not to continue the Ginkgo in consultation with the physician, who should be informed that Ginkgo can interfere with platelet aggregation.
  • If an individual already taking anti-coagulants (blood thinners) is considering starting Ginkgo, the decision whether or not to start the Ginkgo should be made in consultation with the physician, who should be informed that Ginkgo can interfere with platelet aggregation.

Ginkgo biloba is a commonly used agent, which may be helpful in tinnitus therapy. The Birmingham study will hopefully shed light on its true efficacy, and the guidelines above will hopefully increase the margin of safety.

Stephen M. Nagler, MD, FACS

References

  1. KleijnenJ and Knipschildp: Ginkgo biloba. The Lancet 340: 1136-1139, 1992.
  2. personal communications; numerous non-published anecdotal reports
  3. CampbellB and HalushkapV: Lipid-Derived Autacoids. Goodman & Gilman's The pharmacological Basis of Therapeutics, 9th ed., McGraw-Hill, New York, 1996, pp. 601-616.
  4. RowinJ and LewisSL: Spontaneous Bilateral Subdural Hematomas Associated with Chronic Ginkgo Biloba Ingestion. Neurology 46(6): 1775-1776, 1996.
  5. RosenblattM and MindelJ: Spontaneous Hyphema Associated with Ingestion of Ginkgo Biloba Extract. The New England Journal of Medicine 336(15): 1108, 1997.
  6. These are the recommendations of the author, based on medical "common sense" rather than upon any firmly established protocol.
  7. SacherRA and McphersonRA: Widmann's Clinical Interpretation of Laboratory Tests, 10th ed., F.A. Davis, philadelphia, 1991, p. 190.
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