Ginkgo and Colchicine: Curiouser and Curiouser, says Alice - Phytotherapy Review - colchicine in placental blood

Townsend Letter for Doctors and Patients, April, 2002 by Kerry Bone

During my 20 years plus of reviewing the phytotherapy scientific literature I cannot recall coming across a more bizarre episode than the reported occurrence of coichicine in Ginkgo biloba. A group of US scientists, while investigating natural antiinflammatory substances in pooled placental blood, found a compound present which they identified as colchicine. (1) Naturally the scientists were curious as to the origins of this plant chemical, so they decided to examine individual blood samples from 24 pregnant women. Only five of these contained colchicine and the group reported that all of the colchicine-containing blood samples came from women who used herbal supplements. For some reason they next tested Ginkgo and Echinacea products from local retail outlets and found that only Ginkgo contained significant levels of colchicine (26 (g per tablet). The authors concluded that due to its potential harmful effects, it would appear that Ginkgo biloba should be avoided by women who are pregnant or are trying to con ceive.

Commentary

Colchicine is a drug mainly used to treat acute gout which was originally isolated from the autumn crocus (Colchicum autumnale). It is highly toxic and the effective dose is quite close to a toxic dose. Toxic effects include nausea, vomiting and bone marrow suppression. (2) Colchicine inhibits normal cell division (mitosis) and has also been linked to Down's syndrome. Clearly it is contraindicated in pregnancy. (3)

Before critiquing the actual scientific merit of the study, there are some common sense, logical questions which were not answered by the study (and obviously not asked by peer reviewers).

These are:

* Were the five women with the colchicine levels taking Ginkgo?

* If not, what herbs were they taking?

* Why would a pregnant woman wish to take Ginkgo?

* Why choose just Echinacea and Ginkgo for analysis?

* How many Ginkgo products were tested?

* Why were verified Ginkgo leaves not tested as well?

* Do the findings match the known safety record of Ginkgo? Questions about the research from a scientific perspective are:

* Is it known that Ginkgo contains colchicine?

* Can we expect, from a phytochemical perspective, that Ginkgo should contain colchicine?

* How conclusively was colchicine identified in Ginkgo?

* Could the levels of 'colchicine' in Ginkgo account for the levels found in placental blood?

* Are these levels of 'coichicine' toxic? If so, what effects were observed on the mother and child?

In fact colchicine has never before been reported in Ginkgo and a comprehensive literature search by Professor Farnsworth at the University of Chicago found no evidence of coichicine in Ginkgo. (4) According to Professor Farnsworth: "Based on biogenetic considerations, colchicine should never be found outside of the Monocotyledoneae (e.g. Araceae, Liliaceae) and thus the report of its occurrence in Saussurea sacra (Asteraceae) is an anomaly that has not been duplicated by other reports on the chemistry of this species. Thus, coichicine has never been reported as a normal constituent of Ginkgo biloba nor would it be expected or predicted to be present."

Farnsworth also questioned the scientific validity of the study and the editorial process it underwent to be published. "Anyone who thinks that colchicine can be found naturally in Ginkgo is not qualified to be a peer reviewer of this paper," he said, referring to the editorial process for scientific journals in which papers are reviewed by independent experts to determine their scientific merit and the accuracy of their conclusions prior to publication.

Schwabe, the German company which researched and developed Ginkgo extract tested three separate samples of Ginkgo leaf and failed to find colchicine. This finding was backed up by industry testing in the US. (4)

The Australian TGA (equivalent to the FDA) recently tested five Ginkgo biloba products. Coichicine was not found in any (detection limit 1 (g/g). Interestingly, using a method similar to the study in question, a substance was found in the Ginkgo products which had similar analytical properties to colchicine. Although its identity was not determined, further analysis demonstrated conclusively that this was not colchicine. (5)

Could the levels of colchicine in Ginkgo account for those reportedly observed in the pregnant women? The scientists claimed to have found 49 to 763 [micro]g/L of colchicine in the placental blood of the women allegedly taking herbal supplements. (1) They claim to have found 26 [micro]g of colchicine per Ginkgo tablet. In a multiple dose study of the pharmacokinetics of colchicine, 1 mg per day achieves plasma concentrations in human subjects in the range of 0.3 to 2.5 [micro]g/L. (6) Hence to achieve a level of 49 [micro]g/L of coichicine (the lowest value in the reported range) a person would need to consume around 50 mg of colchicine per day. Since each Ginkgo tablet contains only 26 [micro/g, this equates to around 2000 Ginkgo tablets per day. In their defense, the authors claimed that placental tissue is known to concentrate ingredients from the mother's blood. But even assuming a concentration factor of 50, this is still 40 tablets per day to achieve the lowest reported concentration of colchicine, when the normal dose is typically 3 to 4 tablets per day.