New York Attorney General Issues Cease-and-Desist Letters to 13 Companies Marketing Devil’s Claw Dietary Supplements Containing Harpagophytum zeyheri

On September 9, 2015, the office of New York Attorney General (NY AG) Eric Schneiderman issued letters to 13 companies* to cease and desist from marketing, distributing, and selling of devil’s claw (Harpagophytum procumbens or H. zeyheri, Pedaliaceae) dietary supplements. In addition, the NY AG asked the companies to identify consumers who purchased such supplements and reimburse them for the costs occurred.¹ Devil’s claw is an important African medicinal plant growing in the Kalahari Desert region. Harpagophytum procumbens and H. zeyheri are both known as devil’s claw and are used interchangeably, which was pointed out in an ABC press release.² The European Medicines Agency’s (EMA’s) Community Herbal Monograph on devil’s claw allows the use of both species in the “traditional use category,” (a) for relief of minor articular pain, and (b) for the relief of mild digestive disorders such as bloating and flatulence and where there is loss of appetite.³ However, the American Herbal Products Association’s (AHPA’s) Herbs of Commerce, 1st Edition,⁴ an industry self-regulatory publication to provide an accepted labelling guideline for common names for herbal and vegetable food ingredients in commerce in the United States, and which was incorporated into federal regulations, lists only H. procumbens as devil’s claw. On this basis, the NY AG established that all devil’s claw products containing H. zeyheri are mislabeled and thus adulterated.

The contents of the products were identified using a DNA mini-barcode approach, which was performed by scientists from the New York Botanical Garden specializing in DNA authentication of plant materials. A total of 23 commercial devil’s claw products were evaluated during the investigation, but only 18 were for sale in the United States. Of these 18 supplements, two were found to contain no DNA from any Harpagophytum species. (It is not clear whether these two products contained devil’s claw extracts possibly processed in a manner that rendered the DNA undetectable by a DNA barcoding method.)

The NY AG gave the companies marketing these products 10 days to detail current quality control measures for their devil’s claw products and plans to implement reforms to improve these measures. The companies are also required to detail plans on how they plan to recall products currently in commerce and how they will identify affected consumers and compensate them. Nature’s Way, which is not on the list of the 13 companies targeted by the NY AG, has already agreed with the NY AG’s office to implement additional quality control measures, part of which is to implement DNA barcode testing for all of its herbal dietary supplements containing only one or two ingredients and that their devil’s claw supplements will be made exclusively with H. procumbens.¹

Comment: The use of devil’s claw for medicinal purposes by the San, Nama, and Khoi people from Namibia and South Africa dates back centuries. Investigations by Western nations into the medicinal properties of devil’s claw started in the 1950s, but large-scale exports began after 1962.⁵ According to Thomas Brendler, CEO of the dietary supplement industry consulting firm Plantaphile, and director of the Association of African Medicinal Plants Standards (AAMPS), the publisher of the African Herbal Pharmacopoeia (2010) of which he is co-editor, large-scale collection of H. zeyheri started only after 1975, when Namibia restricted the harvesting of H. procumbens in the wild. By 1986, about 65% of the wild material intended for export was apparently H. zeyheri.⁶

Since older analytical technologies (e.g., the analysis of iridoid glycosides by thin-layer chromatography) were unable to distinguish the two species, it is not clear which Harpagophytum species were administered in many of the clinical trials that were carried out with devil’s claw. But it is likely that a mixture of both species was used, since results from analysis of old batches, using high-performance liquid chromatography (HPLC), indicate that commercial products were made of a mixture of both species.⁷ The interchangeable use is explicitly stated in the official “Harpagophyti radix” (Harpagophytum root) monograph of the European Pharmacopoeia,⁸ and also in the proposed “Harpagophytum species root” monograph of the Herbal Medicines Compendium published by the United States Pharmacopeial Convention.⁹

Since botanical nomenclature and human knowledge on botanicals in commerce are constantly evolving, some of the contents in the second edition of AHPA’s Herbs of Commerce (2000)¹⁰ are likely outdated, which may create some confusion in the US dietary supplement industry. The constant revisions to botanical nomenclature were a problem that was recognized by the editors of the book, as was the fact that the addition of new species will be an ongoing process.

As stated by Michael McGuffin, president of AHPA, “The one piece that the attorney general seems to have missed is that Herbs of Commerce has a stated intention to have each common name listed there apply to only one individual species, except in cases where more than one species is considered in authoritative pharmacopeial literature to be interchangeable.”¹¹ AHPA clarified the regulatory significance of Herbs of Commerce with regard to devil’s claw labeling requirements in a press release on September 18, 2015.¹²

Results from a scientific paper published in 2014, where over 300 samples of authentic H. procumbens and H. zeyheri materials were analyzed using ultra high-performance liquid chromatography-mass spectrometry (UHPLC-MS) and nuclear magnetic resonance (NMR) spectroscopy, have shown that the two species can be distinguished based on their chemical composition, despite the fact that there can be an important variability even within the same species depending on the harvest location.¹³ The notion that 6-O-acetylacteoside, a phenylpropanoid glycoside, can be used as a marker compound to distinguish the two species, as indicated in cease-and-desist letters from the NY AG, is not supported by the study of Mncwangi et al.,¹³ where the compound was found to be present in both Harpagophytum species.

Also according to the paper by Mncwangi et al, harpagoside, one of the allegedly active compounds, occurs in both H. procumbens and H. zeyheri, but less than 50% of the samples had the 1.2% harpagoside concentration specified by the European Pharmacopoeia.⁸ However, at this time there is no pharmacological or human clinical evidence that H. procumbens and H. zeyheri produce different pharmacological effects and thus should be sold as separate species. Future pharmacological and clinical studies may show that the two species have slightly different biological activity and thus should be separated. Indeed, if and when such recognition occurs, then regulatory agencies will presumably follow suit and modify (possibly separating) currently existing monographs. While products that contain H. zeyheri but specify on their label to contain solely “Harpagophytum procumbens” are mislabeled under US law, for companies to receive cease-and-desist letters while official pharmacopeias (British Pharmacopoeia, European Pharmacopoeia, United States Pharmacopeia), EMA, et al. recognize the interchangeability of the two species seems to be splitting taxonomic hairs in a manner that does not afford any perceptible benefit to devil’s claw consumers, especially when one considers the more compelling quality control problems currently occurring in the US (and global) herb market, as we continue to document in this publication and in the Botanical Adulterants Program.

*Note: Despite the NY AG’s press release and the media’s reporting that cease-and-desist letters were sent to 13 companies, letters were sent to only 12 companies, since one company, Shine Supplements, could not be located by the NY AG and is not registered to do business in the state of New York.

References

1.     A.G. Schneiderman Issues Cease-And-Desist Letters to 13 Makers of Devil’s Claw Supplements Marketed to Arthritis Sufferers [press release]. Albany, NY: New York State Attorney General’s Office; September 10, 2015. Available at: http://www.ag.ny.gov/press-release/ag-schneiderman-issues-cease-and-desist-letters-13-makers-devil%E2%80%99s-claw-supplements. Accessed October 5, 2015.

2.     American Botanical Council: New York Attorney General’s Investigation on Devil’s Claw Ignores Expert Evaluations and Provides No Benefit to the Public [press release]. Austin, TX: American Botanical Council; September 9, 2015. Available at: http://cms.herbalgram.org/press/2015/NewYorkAttorneyGeneralsInvestigationonDevilsClawIgnoresExpertEvaluationsandProvidesNoBenefittothePublic.html. Accessed October 5, 2015.

3.     European Medicines Agency Committee on Herbal Medicinal Products (HMPC). Community herbal monograph on Harpagophytum procumbens DC. and/or Harpagophytum zeyheri Decne, radix. London, UK: European Medicines Agency; 2008. http://www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_Community_herbal_monograph/2010/01/WC500059018.pdf. Accessed October 5, 2015.

4.     Moley T, Awang D, Hu SY, Kartesz J, Tucker AO, Tyler VE. Foster S, ed. Herbs of Commerce. 1st ed. Austin, TX, and Silver Spring, MD: American Herbal Products Association; 1992.

5.     Mncwangi N, Chen W, Vermaak I, Viljoen AM, Gericke N. Devil's claw—a review of the ethnobotany, phytochemistry and biological activity of Harpagophytum procumbens. J Ethnopharmacol. 2012;143(3):755-771.

6.     Nott K. A survey of the harvesting and export of Harpagophytum procumbens and H. zeyheri in SWA/Namibia. Okaukuejo, Namibia: Etosha Ecological Institute; 1986.

7.     Wegener T. Zur klinischen Wirksamkeit der Südafrikanischen Teufelskrallenwurzel (Harpagophyti radix) bei Patienten mit Cox- und Gonarthrose. Ergebnisse und Bewertung einer klinischen Studie der Phase IV. PhD thesis. Osnabrück, Germany: University of Osnabrück, Dissertations in Biology and Health Sciences; 2005. Available at: http://d-nb.info/980109957/34. Accessed October 5, 2015.

8.     The European Directorate for the Quality of Medicines & HealthCare. European Pharmacopoeia (EP 8.7). Harpagophyti radix. Strasbourg, France: Council of Europe; 2015.

9.     United States Pharmacopeia. Herbal Medicines Compendium. Harpagophytum species root. Rockville, MD: United States Pharmacopeial Convention; 2015. Available at: http://hmc.usp.org/monographs/harpagophytum-species-root-0-1. Accessed October 5, 2015.

10. McGuffin M, Kartesz JT, Leung AY, Tucker AO. Herbs of Commerce. 2nd ed. Silver Spring, MD: American Herbal Products Association; 2000.

11. Schultz H. Complexity of herbal nomenclature becomes point of vulnerability for industry. NutraIngredients-USA website. Available at: http://www.nutraingredients-usa.com/Regulation/Complexity-of-herbal-nomenclature-becomes-point-of-vulnerability-for-industry. Published September 14, 2015. Updated September 22, 2015. Accessed October 5, 2015.

12. Regulatory Relevance of Herbs of Commerce for Devil’s Claw Supplement Labels [press release]. Silver Spring, MD: American Herbal Products Association; September 18, 2015. Available at: http://www.ahpa.org/Default.aspx?tabid=571. Accessed October 5, 2015.

13. Mncwangi NP, Viljoen AM, Zhao J, Vermaak I, Chen W, Khan IA. What the devil is in your phytomedicine? Exploring species substitution in Harpagophytum through chemometric modeling of ¹H-NMR and UHPLC-MS datasets. Phytochemistry. 2014;106:104-115.