Potential interactions of Ginkgo biloba: a critical review of current evidence.
Subject: Pharmacokinetics (Usage)
Pharmacokinetics (Analysis)
Ginkgo (Health aspects)
Ginkgo (Usage)
Ginkgo (Analysis)
Blood platelets (Aggregation)
Blood platelets (Dosage and administration)
Author: Sarris, Jerome
Pub Date: 06/22/2007
Publication: Name: Australian Journal of Medical Herbalism Publisher: National Herbalists Association of Australia Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2007 National Herbalists Association of Australia ISSN: 1033-8330
Issue: Date: Summer, 2007 Source Volume: 19 Source Issue: 2
Geographic: Geographic Scope: Australia Geographic Code: 8AUST Australia
Accession Number: 174818479
Full Text: Potential interactions of Ginkgo biloba: a critical review of current evidence

Bone K. 2007, Potential interaction of Ginkgo biloba leaf with antiplatelet or anticoagulant drugs: what does the evidence imply? Uni New Engl (in press). (JS)

A review of controlled clinical studies and case reports was undertaken to assess the current evidence concerning Ginkgo biloba and increased bleeding episodes. Concerns regarding Ginkgo potentially causing increased bleeding in isolation and in combination with aspirin and warfarin are based on the assumption that Ginkgo possesses antiplatelet activity. As Bone discusses in the review, such concerns are based on in vitro evidence modelled from the use of isolated ginkgolides. This cannot reflect usage of the whole preparation of Ginkgo in vivo (even if standardised to 4% ginkgolides). An in vitro study which confirmed antiplatelet activity used a dosage of ginkgolides 100 times the normal human serum level and does not account for human pharmacokinetic metabolism of the phytochemicals.

Human clinical trials investigating the hemodynamics of Ginkgo usually involve the use of EGb 761, a standardised Ginkgo preparation created by the herbal firm Schwabe[TM]. Evidence from studies involving EGb 761 and human hemodynamics has demonstrated no significant effect on bleeding time or clotting parameters. These results indicate that even a Ginkgo preparation standardised in ginkgolides does not cause bleeding or effect clotting mechanisms in healthy volunteers.

Considering the millions of doses of Ginkgo administered per year, the 21 cases of purported bleeding episodes occurring from Ginkgo use is extremely low. As Bone highlights, the quality of these case reports is extremely poor with inadequate documentation (dosage, preparation, bleeding time and concomitant drug use) and lack of de-challenge, re-challenge. In only one case the subject was withdrawn from Ginkgo use and then re-challenged, with the results demonstrating that the bleeding episodes were indeed related to Ginkgo ingestion.

Comment: As Bone mentions, reviews and meta-analyses have shown that EGb 761 has a remarkably low incidence of side effects, with only 0.5% of 9772 patients having reported adverse events over 44 clinical trials. Although idiosyncratic bleeding events with Ginkgo do occur (with currently only one confirmed case), the evidence strongly indicates that these incidents are extremely rare, and does not reflect the need for a moratorium on Ginkgo and anticoagulant use. While it can be argued that clinical studies investigating hemodynamic interaction with anticoagulants have used small samples, and may not be statistically powerful enough to rule out any idiosyncratic occurrence of bleeding episodes, they do highlight that no firm evidence currently exists proving Ginkgo causes bleeding episodes with or without concomitant anticoagulant use.

Jerome Sarris

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