Industry Refutes Study Reporting Ginkgo Biloba Dangerous

ROCHESTER, Mich.--The industry is up in arms about a new study reporting that ginkgo biloba may be dangerous, especially for pregnant women and their fetuses. In the September Chemical Research in Toxicology (14, 9:2001) (http://pubs.acs.org/journals/crtoec/index.html; the September issue is not yet posted online), scientists reported finding colchicine, a substance that might cause birth malformations, in ginkgo biloba supplements. However, the industry stated that this study is flawed and the researchers are jumping to conclusions while making unfounded accusations.

Colchicine, an alkaloid that belongs to the lily family (Colchicum autumnale), among others, is used as a prescription drug to treat rare health conditions that include gout and Familial Mediterranean Fever and is toxic when taken in large amounts. According to the study's authors, mammals do not synthesize colchicine and any accumulation of this substance in a human being is likely due to ingestion of plant materials.

The original purpose of this study was for researchers to see if there was a link between anti-inflammatory agents (i.e., ibuprofen, aspirin) and birth defects. The researchers, led by Howard Petty, Ph.D., from Wayne State University, pooled 3 L of placenta blood from 30 women in two hospitals during four separate occasions. Tests showed that the blood contained 700 micrograms of colchicine.

Because this test was based on a collection of samples, the researchers then looked at placenta blood from 24 women in order to establish the amount of colchicine an individual may carry. Five women were found to have from 49 to 760 micrograms of colchicine in their placental blood; all five women were also found to be herbal supplement users. As a side note, women who reported not using herbal supplements had little to non-detectable levels of colchicine. This led researchers to conduct tests on ginkgo and echinacea products; the researchers did not explain why those two herbs alone were tested.

When testing ginkgo biloba and echinacea samples (the study did not report how many brands were used nor the number of bottles sampled), researchers found "significant" levels of colchicine at 26 micrograms per ginkgo biloba tablet, and 2 micrograms per echinacea tablet. Researchers then inferred that ginkgo may create fetal malformations and that "the potential detrimental roles of natural plant products in reproductive health merit further analysis."

Three Reasons Industry is Questioning Study's Validity

The industry is having problems with this study on many levels. First, ginkgo biloba does not contain colchicine. "Something else in the products, and not ginkgo, may have contained colchicine," reported Joseph Betz, Ph.D., vice president for scientific and technical affairs at the American Herbal Products Association (AHPA). "Over the past 50 years of studying ginkgo, it is unimaginable that experts in this field never once found this alkaloid, and yet scientists not trained in herbs have just found it in ginkgo."

He added that AHPA and the National Nutritional Foods Association (NNFA) have organized an independent analysis of the top-selling ginkgo products. Although analyses will not be finished until next week, preliminary results show that there are no colchicine alkaloids in the products.

Second, there is a compound--possibly an isoflavone--in ginkgo that looks analytically like colchicine but would not have been distinguishable through HPLC methods alone. "The study's researchers could have taken the extra step and used a photo diode array detector that uses all UV wavelengths instead of HPLC's one that may not have picked up the differences between the two similar constituents," Betz explained. "If the researchers had practiced due diligence, these questionable results may not have happened."

Finally, the blood levels of colchicine found in the five expectant mothers were at very high levels--seemingly too high to have been induced through ingestion. "If the reported placental levels were accurate, the mothers and the babies would likely have been poisoned," said Phillip Harvey, Ph.D., R.D., director of science and quality assurance at NNFA. "It seems that there is some sort of analytical interference that gave them artificially high levels."

Betz hypothesized that these false-positive results may be due to either a machine used in the lab analysis being tainted with colchicine (since these scientists have tested for colchicine in previous studies) or tests mistaking the analytically similar gingko compound with colchicine.

In addition, the Council for Responsible Nutrition (CRN) conducted third-party tests on five different ginkgo sources, analyzed by three different methods, and reported that no trace of colchicine has been found. Also, the American Botanical Council (ABC) stated in its press release that University of Illinois professor of pharmacology, Norman Farnsworth, Ph.D., emphatically declared that colchicine was not a constituent in ginkgo biloba. "Anyone who thinks that colchicine can be found naturally in ginkgo is not qualified to be a peer reviewer of this study," he stated, 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.