Ginkgo biloba (Ginkgoaceae) leaf extract is one of the most popular and well-researched herbal preparations. Worldwide, ginkgo is accepted as a formal medicine for enhancing mental acuity, a use supported by dozens of clinical trials based on a few proprietary extracts manufactured in Europe. It is also sold as a food supplement in Europe, a dietary supplement in the United States and elsewhere, and as a natural health product in Canada. Unfortunately, in the past decade, growing evidence has emerged of the production and sale of sub-standard and adulterated ginkgo extracts in the international supply chain, much of it reportedly coming from China

A comparison of HPLC (high-performance liquid chromatography) fingerprints of ginkgo extracts from 19 different sources published in 2006 suggested that three products were adulterated with added rutin.³ In 2008, the adulteration issue was raised again by Hermann Kurth of the German extract manufacturing company Finzelberg in a conference presentation.⁴ In the presentation, rutin (allegedly sourced from buckwheat [Fagopyrum esculentum, Polygonaceae] or Japanese sophora [Sophora japonica syn. Styphnolobium japonicum, Fabaceae]) and kaempferol were found as adulterants of ginkgo extracts.

In 2010, a report about ginkgo food supplements purchased and analyzed in Germany indicated the existence of adulterated ginkgo extracts. Of the 10 products investigated, seven had high concentrations of quercetin, which is atypical for ginkgo extracts.⁵

The adulteration of ginkgo extracts with pure flavonoids, or flavonoid-rich extracts also was detailed in 2011. In that study, Amitabh Chandra, PhD, of Nutrilite (a division of Amway) and colleagues reported that chromatographic profiles of three commercial bulk materials (out of eight products analyzed) labeled to contain ginkgo extracts closely resembled those of commercial extracts obtained from Japanese sophora.6 A Japanese study published in 2012 detailed the analysis of 22 commercial products (16 ginkgo products from Japan and six from Germany and France). The authors found three products with unusually high amounts of quercetin and suspected that the quercetin was an “artificial additive,” or that the ginkgo was manufactured using a special process.⁷

In May 2013, the California botanical extract supply company Ethical Naturals, Inc. issued a revised report on ginkgo adulteration, titled “Ginkgo Adulteration & Identification w/ Fructus sophorae (Sophora japonica),” which describes an HPLC-UV method using genistein as a marker compound to detect adulteration of ginkgo extracts with extracts from the fruit of Japanese sophora.⁸

Adulteration with rutin of commercial ginkgo products purchased in the Turkish market was reported by Demirezer et al. in 2014.⁹ Also in 2014, Australian researchers led by Hans Wohlmuth of Integria Healthcare in Australia published a relatively simple method to detect adulteration of ginkgo extract in commercial dietary supplement products.¹⁰ By using the HPLC conditions of the United States Pharmacopeia before and after hydrolysis (the breaking of a molecule by adding water), the authors discovered admixtures of the flavonols quercetin and kaempferol in three of the eight commercial samples that were analyzed. The three adulterated samples also contained genistein, an isoflavone that has not been found in ginkgo leaves, but is characteristic of some plants in the pea family (Fabaceae), including in the genus Sophora. The authors noted that current pharmacopeial methods are not sufficient to detect ginkgo adulteration and proposed to analyze the samples not only after hydrolysis, as currently required, but also without hydrolysis, as a way to more readily detect adulterations with pure quercetin, kaempferol, and isorhamnetin.

Similar findings were reported in a 2015 study by Avula et al. (researchers at the University of Mississippi’s Natural Center for Natural Product Research, Roy Upton from the American Herbal Pharmacopoeia, and this author).¹¹ Eight botanically authenticated ginkgo leaf samples were analyzed by high-performance thin-layer chromatography (HPTLC) and ultra high-performance-ultraviolet mass spectrometry (UHPLC-UV/MS). Additionally, samples of authenticated ginkgo fruit (n=3), stem (n=2), seed (n=2), and one National Institute of Standards and Technology (NIST)-certified leaf extract were analyzed. Also included in the study were authenticated Japanese sophora fruit (n=3) and flower (n=2) samples. The HPTLC and UHPLC-UV/MS methods were then used to evaluate the authenticity of three bulk ginkgo leaf raw materials, two bulk ginkgo extracts, and 25 commercial dietary supplements labeled to contain G. biloba extract. The dietary supplements were purchased online from retailers in the United States. Isoflavones were not detected in any of the authentic ginkgo materials, but genistein was present in both Japanese sophora fruit and flower. The fruit of Japanese sophora also contained a number of flavonoids that are not found in ginkgo (e.g., kaempferol-3-O-sophoroside, genistein-4’-O-glucoside, and genistein-4’-O-neohesperidoside [sophorabioside]). Most of the characteristic ginkgo terpene lactones (i.e., ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J, and bilobalide) were present in all of the analyzed ginkgo samples, including the commercial dietary supplements. However, 11 out of the 25 tested supplements contained flavonol glycosides that are typically found in S. japonica fruit. Eight additional supplements contained genistein and had quercetin, kaempferol, and isorhamnetin levels inconsistent with authentic ginkgo leaf material, suggesting adulteration with Japanese sophora flower or an unknown adulterant. In total, 19 out of 25 (76%) commercial ginkgo dietary supplements were found to be adulterated.

The ABC-AHP-NCNPR Botanical Adulterants Program is currently developing a "Botanical Adulterants Bulletin" on ginkgo extract adulteration.

—Stefan Gafner, PhD

References

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