HerbalEGram: Volume 15, Issue 12, December 2018

By Stefan Gafner, PhD

A workshop titled “Adulteration and Fraud of Botanical and Natural Health Ingredients: Issues, Challenges and Prevention Tools for the Industry” was held November 29-30, 2018, in Frankfurt, Germany, as part of the Health Ingredients Europe trade show. It was organized by botanical extract manufacturer Euromed SA (Mollet del Vallès, Spain) in collaboration with the American Botanical Council (ABC; Austin, Texas), Extrasynthèse SA (Lyon, France), Hylobates Consulting (Rome, Italy), Vitafoods Insights of Informa Exhibitions (London, England), Smart Short Courses of Belgium and USA, and Informa and UBM’s “Health & Nutrition Week 2018.”

The goal of the workshop was to educate the European herbal medicine and food supplement industries about adulteration of herbal ingredients, examine the botanical ingredient supply chain and its vulnerabilities, and discuss new quality control tools to improve the accuracy of herbal ingredient authentication. The workshop included presentations from 17 experts from the European Union (EU) and United States.

The workshop was divided into four sessions. The first session assessed the nature and magnitude of the adulteration problem and was kicked off by ABC Founder and Executive Director Mark Blumenthal’s presentation on the ABC-AHP-NCNPR Botanical Adulterants Prevention Program (BAPP). Blumenthal gave an overview of the extent of adulteration in the United States and the 46 peer-reviewed papers that the BAPP has published to date. BAPP’s draft standard operating procedure (SOP) on “Best Practices for the Disposal/Destruction of Irreparably Defective Articles,” which has recently been evaluated by various dietary supplement industry stakeholders, was viewed by industry members and various regulatory agencies as a helpful initiative to curb adulteration.

In the second talk of the session, Anna Rita Bilia, PhD, of the University of Florence, Italy, reviewed analytical methods to authenticate herbal ingredients. Bilia’s presentation focused on methods of chemical analysis, and she explained that the use of appropriate statistical methods and properly authenticated plant materials may be the best way to detect adulterated materials. These chemometric techniques can be applied to all commonly used chemical analysis methods.

The second session featured presentations regarding the industry’s response to adulteration in the EU and worldwide. Speakers included Patrick Coppens (Food Supplements Europe; Brussels, Belgium), Michel Horn (European Federation of Associations of Health Product Manufacturers [EHPM]; Elsenborn, Belgium), and Bauke van der Veen (European Herb Growers Association [EUROPAM]; Biddinghuizen, Netherlands). Coppens reviewed European regulations regarding food supplements and explained how the industry in Europe was looking at the adulteration problem. According to Coppens, most food supplement products in Europe are of good quality, and issues reported in the European Commission’s Rapid Alert System for Food and Feed (RASFF) are mainly regarding novel foods that have no market authorization in Europe, illegal substances (e.g., products containing active pharmaceutical ingredients such as sildenafil or sibutramine), and contamination (e.g., microbial, heavy metal, pesticide). He also suggested that food supplements are adequately regulated but admitted that “you cannot eradicate fraudulent practices by regulation."

Horn presented the EHPM quality model as an example of the production of high-quality botanical ingredients. He recognized that many fraudulent and potentially unsafe products are sold on the European market via the internet. One of the issues is that products sold online are more difficult to control by state authorities, and Horn pointed to the need for more stringent border controls. He also noted that fraudulent companies can enter the European market in EU countries that have weak legal frameworks, and that these companies can use the “entry country” as a base to distribute their products within the entire EU.

Van der Veen’s talk on transparency as a potential solution to adulteration from the perspective of the EUROPAM ended the session’s presentations. The session concluded with a roundtable discussion that was moderated by Heather Granato (Informa Exhibitions; Phoenix, AZ), who also acted as master of ceremonies for the entire workshop. One particularly controversial point was the extent of the problem of adulteration in Europe, and opinions varied widely among the workshop attendees.

Next, a group of six speakers spoke about the tools available to prevent adulteration. This author and Julien Diaz (BotaniCert; Grasse, France) gave a few examples of botanicals for which adulteration has been reported in Europe, and what analytical methods can be used to detect such fraudulent materials. Among others, examples included the addition of flavonols or flavonol-rich extracts to ginkgo (Ginkgo biloba, Ginkgoaceae) leaf extracts, substitution of cranberry (Vaccinium macrocarpon, Ericaceae) fruit extracts with proanthocyanidin-rich extracts from low-cost sources such as peanut (Arachis hypogaea, Fabaceae) or pine (Pinus spp., Pinaceae) bark, and the sale of milk thistle (Silybum marianum, Asteraceae) seed extracts using spent (previously extracted) milk thistle seeds for production, thus providing an extract devoid of the medicinally important flavonolignans. Diaz emphasized the importance of non-targeted chemical analysis methods, since assays that focus on one or two marker compounds are often inadequate. This was exemplified by an ingredient labeled as high mallow (Malva sylvestris, Malvaceae) leaf extract that turned out to contain the isoquinoline alkaloid berberine, which is not found in plants in the Malvaceae family. If only marker compounds had been assessed, this extract may have passed the test.

David Trosin (NSF International; Ann Arbor, MI) provided insight into the results of botanical ingredient testing by NSF and emphasized the importance of a robust auditing system for all parties involved along the food and dietary supplement supply chain. Len Monheit (Trust Transparency Center; Spring, TX) presented about the importance of food and dietary supplement authenticity from a transparency and consumer trust perspective. He noted that a third of turmeric (Curcuma longa, Zingiberaceae) samples analyzed by his organization contained undeclared synthetic curcumin. Such practices, he suggested, put the food and dietary supplement industry at risk of damaging its reputation and eroding consumer trust.

The session continued with a presentation by Joris Geelen (Food Compliance International Pte. Ltd.; Singapore), who, as a member of the Belgian Federal Public Service Health, Food Chain Safety and Environment, was elemental in putting together a list of plants safe for consumption (known as the BELFRIT list). Geelen, who is now a regulatory consultant in Belgium, talked about his experience as a regulator in constructing this list, and explained the impact and current regulatory relevance of the BELFRIT project.

Luca Bucchini, PhD (Hylobates Consulting), evaluated the safety risks that may result from the addition of undeclared botanical ingredients. He noted that most cases of herbal ingredient adulteration do not pose a safety risk, but pointed to a notable exception in the 1990s, when Stephania tetrandra (Menispermaceae) was substituted with the kidney-toxic Aristolochia fangchi (Aristolochiaceae) in a traditional Chinese medicine formula, leading to a number of cases of aristolochic acid nephropathy, including kidney failure, and even fatalities.¹ He also explained that substitution of grape (Vitis vinifera, Vitaceae) seed extract with peanut is problematic due to the potential of an allergic reaction in consumers that have peanut allergies. Using the case of 1,3-dimethylamylamine (DMAA), which was previously sold as natural rose geranium (Pelargonium graveolens, Geraniaceae) extract,² Bucchini explained the difficulties in establishing that DMAA does not occur naturally in geranium, and that despite the occurrence of serious adverse events, the financial, legal, and reputational impact to companies selling fake geranium extract in Europe is low.

The theme of preventing herbal ingredient adulteration was also prominent in the last session on traceability, herbal ingredient analysis, and key tools for quality control. René de Vaumas (Extrasynthèse SA) lamented the inaccuracy in purity assessments of chemical reference standards. He explained that authentication may rely on the quantification of certain marker compounds, and that using a chemical reference standard for which the purity was measured using inappropriate tools (e.g., high-performance liquid chromatography with ultraviolet detection [HPLC-UV] without the use of a primary standard) can lead to inaccurate results. The advantages and drawbacks of genetic testing were then presented by Johannes Novak, PhD (University of Veterinary Medicine; Vienna, Austria). He gave an overview of DNA barcoding, including the different sequencing methods. He noted that — contrary to the belief of many industry members — DNA can be found in most botanical ingredients, even herbal extracts. However, DNA in extracts is often fragmented and of low quality and may not be suitable for a genetic assay. Therefore, Novac explained, it is important to thoroughly validate the genetic makeup of material prior to processing it for authentication of a botanical material.

Anna Mulà and Agustin Villar of Euromed SA explained how supply chain management and quality control are managed from the perspective of an herbal ingredient supplier. Part of their presentation included results from an investigation into the authenticity of saw palmetto (Serenoa repens, Arecaceae) using infrared spectroscopy and subsequent chemometric analysis, which was able to distinguish authentic saw palmetto oil from adulterated materials. While the presenters did not consider adulteration a high risk for companies with a good quality control system in place, they noted that adulteration offers an attractive financial incentive to unscrupulous companies.

The workshop ended with two presentations on actual cases of adulteration. Bilia gave an overview of her investigation into the composition of an Italian food supplement that led to a number of hospitalizations. The patients, who were admitted for low blood pressure, had taken a food supplement labeled to contain extracts of olive (Olea europaea, Oleaceae) leaves and buds; hawthorn (Crataegus laevigata, Rosaceae) leaves, flowers, and fruits; fumitory (Fumaria officinalis, Papaveraceae) herb, and shepherd’s purse (Capsella bursa-pastoris, Brassicaceae) herb. Using a combination of analytical techniques (HPLC-UV with mass spectrometric [MS] detection, HPLC-MS/MS, and nuclear magnetic resonance [NMR]), the researchers were able to determine that the food supplement contained an extract of a species of Indian snakeroot (Rauvolfia spp., Apocynaceae), and that the observed effects could be attributed to the non-declared Rauvolfia alkaloid-containing material.³

Francis Hadji-Minaglou of BotaniCert then gave an overview of essential oil adulteration, where the financial incentive for substituting the labeled ingredients with lower-cost materials is particularly large. He noted that essential oil adulteration is becoming more sophisticated, with adulterated ingredients more closely matching authentic essential oil profiles. Hadji-Minaglou also emphasized the need for new analytical methods and the importance of knowledge and expertise as the basis for success in quality control of essential oils.

In his concluding remarks, Blumenthal praised the workshop’s organizers for creating a forum for the discussion of food supplement adulteration in Europe. He also mentioned that the small group that met in Frankfurt was an excellent representation of the larger EU-based industry for both food supplements and botanical ingredients sold as medicines. Blumenthal expressed his confidence that the event can be the beginning of a larger effort in the EU and internationally to help research and education efforts and combat fraud in the global botanicals marketplace.

Image credits (top to bottom):

All images ©2018 Steven Foster.

Ginkgo leaf
Hawthorn berries
Milk thistle flower
Saw palmetto fruit and leaf

References

1. Debelle FD, Vanherweghem J-L, Nortier JL, Aristolochic acid nephropathy: a worldwide problem. Kidney Int. 2008;74:158-169.
2. Austin KG, Travis J, Pace G, Lieberman HG. Analysis of 1,3 dimethylamylamine concentrations in Geraniaceae, geranium oil and dietary supplements. Drug Test Anal. 2014;6(7-8):797-804.
3. Karioti A, Giocaliere E, Guccione C, et al. Combined HPLC-DAD-MS, HPLC-MSⁿ and NMR spectroscopy for quality control of plant extracts: The case of a commercial blend sold as dietary supplement. J Pharm Biomed Anal. 2014;88:7-15.