HerbalEGram: Volume 16, Issue 10, October 2019

BAPP co-sponsors its second workshop in Europe on botanical ingredient adulteration

By Stefan Gafner, PhD

As part of the 67th International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA), the ABC-AHP-NCNPR Botanical Adulterants Prevention Program (BAPP) organized a pre-conference workshop titled “Economic Adulteration of Botanical Ingredients: What Do We Know, and How Can We Solve It?” that occurred on September 1, 2019, in Innsbruck, Austria. Approximately 60 participants from 23 countries registered for the workshop, which was co-organized by botanical extract manufacturer Euromed (Mollet del Vallès, Spain) and botanical industry consulting firm Hylobates Consulting (Rome, Italy). Financial supporters included Euromed, Hylobates Consulting, Extrasynthèse (Lyon, France), and BotaniCert (Grasse, France).

BAPP also sponsored a workshop in November 2018 in Frankfurt, Germany, which occurred during the annual Health ingredients Europe conference and trade show. The goal of this second workshop was to raise awareness about botanical ingredient adulteration at a science-oriented event and provide a forum in which experts from academia and industry, regulators, and members of trade and nonprofit organizations could discuss ways to improve the current situation. The workshop included presentations from 11 experts from the EU and United States and a panel discussion focusing on potential solutions.

The workshop began with a brief introduction by Andrea Zangara, director of scientific marketing at Euromed. Mark Blumenthal, founder and executive director of the American Botanical Council and founder and director of BAPP, then gave an overview of adulteration issues based on almost nine years of BAPP research and publications. Blumenthal reiterated that botanical ingredient adulteration is a global problem since ingredients for food supplements and herbal medicines are sourced around the globe and fraudulent suppliers and manufacturers are located in many countries. He also discussed top-selling botanical ingredients that are intentionally adulterated* and materials that are used as undeclared substitutes. Blumenthal also provided an update on the proposed standard operating procedure (SOP) on “Best Practices for the Disposal/Destruction of Irreparably Defective Articles,” a BAPP initiative for industry use, which is currently under revision based on numerous comments made during a public comment period last year.

Anna-Rita Bilia, PhD, president of the GA and an associate professor of applied pharmaceutical technology at the University of Florence, gave an overview of analytical methods to authenticate herbal ingredients. The focus was on methods of chemical analysis. Using examples from her own investigations and published literature, Bilia provided some insight about methods that are fit-for-purpose for authenticating specific materials. Examples included the chemical analysis of goji berries cultivated in the Tuscany region in Italy, where plants sold as Lycium barbarum (Solanceae) were found to be L. chinense.¹ She also highlighted a high-performance thin-layer chromatography (HPTLC) investigation of materials sold as chamomile (Matricaria recutita, Asteraceae). Using pattern recognition analysis, the researchers were able to distinguish authentic chamomile samples from samples of chamomile-like species in the genera Anthemis, Tanacetum, and Chrysanthemum, which are all in the Asteraceae family.²

Supply chain and quality control management from the perspective of an herbal ingredient supplier was discussed in the talk by Anna Mulà, head of the quality unit of Euromed. Part of the presentation detailed the results from an investigation of the quality of saw palmetto (Serenoa repens, Arecaceae) berry extracts. She stressed the importance of using mature berries, since these have higher fatty acid contents and a different fatty acid composition than extracts made from immature berries. Mulà pointed out that adulteration of saw palmetto extracts with low-cost vegetable oils or fatty acids of animal origin is readily detected if proper quality control systems are in place. As an example, she presented some of the additional test methods developed by Euromed (e.g., the use of ultraviolet [UV]-visible spectrophotometry to assess the color of saw palmetto extracts, or near-infrared [NIR] spectroscopy with subsequent statistical analysis to confirm extract authenticity).

Next, Débora Frommenwiler, scientist at analytical equipment manufacturer Camag AG (Muttenz, Switzerland), gave examples of large-scale investigations of the authenticity of popular herbal ingredients using HPTLC. The work included the analysis of:

• 31 milk thistle (Silybum marianum, Asteraceae)³ and 23 echinacea (Echinacea spp., Asteraceae) products from the United Kingdom,
• 10 bulk cranberry (Vaccinium macrocarpon, Ericaceae) fruit samples from the United States,
• 74 black cohosh (Actaea racemosa, Ranunculaceae) root bulk samples and finished products from the United States and Asia,
• 84 St. John’s wort (Hypericum perforatum, Hypericaceae) herb samples (bulk powdered herb, bulk extracts, and finished products) sourced in the EU and United States,^4,5 and
• 59 ginkgo (Ginkgo biloba, Ginkgoaceae) leaf products from the EU and South America.^6,7

Quality issues were found for all of these botanicals, but samples from products that were registered as herbal medicine or as traditional herbals had fewer quality issues than those categorized as food supplements. The results included previously unpublished data (i.e., on echinacea, black cohosh, and cranberry). For echinacea, 14 of the 22 products were of high quality. Six of the echinacea products did not contain alkylamides, and two contained neither alkylamides nor phenolic compounds and were thus deemed adulterated. Of the 74 black cohosh samples, 35 were of high quality, nine showed a weak or unusual HPTLC fingerprint, and the remaining samples were adulterated with Asian Actaea species or did not contain Actaea at all. In the case of cranberry, two of the 10 bulk ingredients were adulterated with a mixture made from peanut (Arachis hypogaea, Fabaceae) skin and blueberry (Vaccinium spp., Ericaceae) fruit.

Best industry practices to address adulteration were presented by Barry Traband director of research and development for the Europe, India, and Africa regions of Amway GmbH (Puchheim, Germany). He made it clear that many companies offer high-quality supplements but admitted that adulteration is a continuing problem. He made the distinction among three types of adulteration: (1) economically motivated adulteration, (2) accidental adulteration, and (3) the sale of undeclared pharmaceutical drugs masquerading as dietary supplements. Based on his experience, the adulteration of many ingredients is due to the recent market success of these ingredients. Wildcrafting is a traditional means of collecting medicinal plants and is still predominant in Asian countries. However, as wild resources are dwindling, collectors may replace the plants with other species. Sudden price increases when materials are less abundant only add to the incentive to substitute low-cost materials for higher-priced ingredients. Traband also stressed the importance of a robust quality control program, which at Amway includes DNA barcoding of crude drugs, phytochemical fingerprinting, and quantification of appropriate marker compounds such as those listed in national and international pharmacopeias.

A different angle of the adulteration picture was presented by Marinus Henricus “Rien” Van Diesen, seconded national expert at Europol, the EU’s law enforcement agency. While Europol has not investigated food supplement fraud, the organization has supported a number of other agencies’ food and beverage fraud operations. Europol supports law enforcement agencies by co-organizing a yearly operation called OPSON. During the seventh OPSON operation, 16,000 metric tons and 33 million liters of adulterated food and beverages were seized. Besides law enforcement agencies, he strongly suggested involving prosecutors when dealing with food and dietary supplement fraud, as this is a technically complex and fairly new subject for law enforcement and prosecutors. All this should help to ensure the best outcome when cases are investigated and go to court.

Van Diesen suggested bringing up this issue as part of operation OPSON. He also suggested, given the complexity of the subject, to have an area dedicated to the topic of dietary supplement fraud within Europol’s Platform for Experts (EPE). On this collaborative web platform, academics, specialists, and law enforcement agents can share ideas, trends, new developments and data, with support from Europol.

I started my presentation by emphasizing the importance of botanical taxonomy as the basis of species identification. Using the genus Euphrasia (Orobanchaceae), species of which are commonly known in the marketplace as “eyebright,” as an example, I showed that the determination of a species may not always be straightforward and that the interchangeable use of several species may make sense in some cases. I then provided a few examples of how some suppliers and manufacturers take advantage of non-specific analytical methods. Such fraud may include the addition of natural or synthetic pigments to increase absorption at specific wavelengths in the visible range, providing a false sense of herbal ingredient strength. Another frequently encountered type of fraud is the addition of pure compounds or purified fractions containing high concentrations of, for example, rutin, curcumin, or ellagic acid, which are commonly used marker compounds in ginkgo, turmeric (Curcuma longa, Zingiberaceae), and pomegranate (Punica granatum, Lythraceae), respectively. Similarly, extracts with a similar chemical profile may be substituted for the plant extract of interest. An example of the latter is substituting grape (Vitis vinifera, Vitaceae) seed, pine (Pinus spp. Pinaceae) bark, or peanut skin extract for cranberry extract.

Luca Bucchini, PhD, managing director of Hylobates Consulting, focused on the quality of turmeric products that were supposedly associated with at least 21 cases of acute non-viral cholestatic hepatitis in Italy. These cases were reported between May and June 2019.⁸ The issue involved 20 batches of 17 different products labeled to contain turmeric. Based on the analysis of the Italian Ministry of Health, contaminants, reaction byproducts, solvent residues, and substitution with other plants were immediately ruled out as possible causes. Preliminary data suggest that 50% of the products contained synthetic curcumin without presence of any additional curcuminoids indicative of a turmeric extract. Looking at a subset of the products involved, Bucchini noted product label dosage recommendations between 50 and 1,200 mg of “turmeric extract” (standardized to 95% curcuminoids) and 5-160 mg of black pepper (Piper nigrum, Piperaceae) extract containing 95% piperine per day. While the Ministry of Health has requested that manufacturers of turmeric food supplements include a warning that patients with pre-existing liver conditions should avoid turmeric, which is in line with the European Medicine Agency’s assessment report on turmeric,⁹ the ministry also concluded that there was no correlation between turmeric extract consumption and liver injury and that the 21 cases were due to individual patient factors.¹⁰ No regulatory action has been taken so far against manufacturers selling synthetic curcumin as turmeric extract and synthetic piperine as pepper extract.

The next two presentations focused on analytical methods and reference standards to enable the detection of adulteration. Julien Diaz, quality control manager of BotaniCert, made the case for using untargeted analytical methods to detect adulteration. He provided some examples in which unusual adulterants were detected by comparing the high-performance liquid chromatography (HPLC) fingerprint of a sample to those of a number of authenticated reference samples. Occurrence of unexpected peaks that cannot be explained by the chemical variability of the plant suggests the presence of undeclared materials. René de Vaumas, president and CEO of Extrasynthese, pointed to the inaccuracy of purity assessments of chemical reference standards. He explained that authentication may rely on the quantification of specific marker compounds, and that using chemical reference standards in which the purity was measured using inappropriate tools (e.g., by HPLC with UV detection [HPLC-UV] without the use of a primary standard) will lead to inaccurate results.

Rudolf Bauer, PhD, professor of pharmacognosy at the University of Graz, Austria, introduced the topic of adulteration of ingredients used in traditional Chinese medicine (TCM). While he said that large-scale investigations of the authenticity of TCM materials have shown a low percentage of adulteration, there are some issues with specific species. Species that are particularly expensive, such as cordyceps (Ophiocordyceps sinensis, Ophiocordycipitaceae) fruiting body, rou cong rong (Cistanche spp., Orobanchaceae), and older Asian ginseng (Panax ginseng, Araliaceae) roots, have been the targets of economically motivated adulteration.

Bauer further used the case of zi cao to illustrate the problems with using Chinese vernacular names. Roots of the genera Arnebia, Onosma, and Lithospermum (which are all in the Boraginaceae family) traditionally are known as zi cao.¹¹ While the species are sometimes distinguished by prefixes, such as ruan zi cao (Arnebia euchroma), dian zi cao (Onosma paniculata), and ying zi cao (Lithospermum erythrorhizon), such prefix use is not consistent. In addition, species distinction based on genomic or chemical markers is not always possible, as evidenced by analysis of 16 samples sold as A. euchroma (n = 13) or L. erythrorhizon (n = 3). Of these 16 samples, five were A. euchroma, one was L. erythrorhizon, and one was O. paniculata. The remaining samples could not be unambiguously identified by DNA analysis or HPLC.¹¹

The event closed with a panel discussion with Nigel Pollard, chair of Natural Health Science Foundation Inc. in New York, Bilia, Blumenthal, Bucchini, van Diesen, and Traband. Panelists debated why botanical ingredient adulteration is not on the radar of regulatory agencies in Europe and how to improve the quality of food supplement products on the market. The panel agreed that many manufacturers are producing high-quality food supplements. Regarding the lack of regulatory interest in botanical ingredient adulteration, Traband suggested that these agencies had other priorities, and as long as no one gets hurt, enforcement is not likely to happen. There were many ideas on how to solve quality issues. Most panelists agreed that there is a place for both herbal medicines and food supplements and that regulations are unlikely to prevent adulteration if these regulations are not enforced. Increasing quality standards to enter the food supplement category was seen as a possible way to lower the number of adulterated products.

Pollard suggested that the creation of a database listing clinically tested products, which the Natural Health Science Foundation is currently undertaking, will enable consumers to make better choices about which supplements to take, giving credible products an advantage in the marketplace and an incentive for food supplement manufacturers to invest in clinical studies. He also supported harmonization of regulations on a global level as a means to improve product quality. Blumenthal proposed the consideration of a broader implementation of blockchain technology as a means to increase transparency and the ability to determine the source of ingredients, per an article on blockchain that was published in HerbalGram issue 123.¹²

Bilia lamented the lack of funding for proper investigations when quality issues are raised by authorities. Determining the exact composition of a product that has been implicated in a serious adverse event case is not a trivial matter from an analytical point of view, and accordingly, such research needs to be adequately funded. She also noted that many smaller manufacturers do not have the capacity to perform thorough quality control and that they may buy an ingredient and fill it into a capsule without further evaluation. It is not clear how these small enterprises can comply with current food supplement laws.

The workshop was well-received based on the positive feedback from people in the audience. It gave an excellent overview on the main botanical ingredients that are subject to adulteration and provided the attendees with ideas and suitable analytical methods for determining the identity of plant-based ingredients. The event also served as a platform for members of industry, academia, and trade and nonprofit organizations to meet and exchange ideas about how to solve, or at least reduce, adulteration, which may be a growing problem in the herbal medicine and food supplement industries. Several attendees noted the absence of representatives from regulatory agencies and considered it a missed opportunity to inform and engage agents from health authorities, who were unable to attend, despite the efforts of the organizing committee. Hopefully, this can be addressed at a future adulteration workshop.

*Some botanical ingredients can be adulterated accidentally. For example, plant materials can be accidentally substituted and/or mixed in the field, or in processing facilities, usually due to either human error and/or inadequate training of personnel.

Images (top to bottom; all photos ©2019 Steven Foster):

BAPP logo
Goji berries (Lycium barbarum)
Ginkgo leaves (Ginkgo biloba)
Eyebright (Euphrasia roskoviana)
Black cohosh (Actaea racemosa)
Asian ginseng (Panax ginseng)

References

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2. Guzelmeric E, Vovk I, Yesilada E. Development and validation of an HPTLC method for apigenin 7-O-glucoside in chamomile flowers and its application for fingerprint discrimination of chamomile-like materials. J Pharm Biomed Anal. 2015;107:108-118.
3. Trust me – I’m a doctor. Do herbal supplements contain what they say on the label? . British Broadcasting Corporation (BBC) Two; 2015. Available at: http://www.bbc.co.uk/programmes/articles/4hX30rMYkMv9YjMTH38MY6/do-herbal-supplements-contain-what-they-say-on-the-label. Accessed September 23, 2019.
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