On September 9, 2015, the office of New York Attorney General (NY AG) Eric Schneiderman issued cease-and-desist letters to 13 companies* that market, distribute, or sell devil’s claw (Harpagophytum procumbens or H. zeyheri, Pedaliaceae) dietary supplements. In addition, the NY AG asked the companies to identify and reimburse consumers who purchased these products.1
Devil’s claw is an important African medicinal plant found in the Kalahari Desert region. Both H. procumbens and H. zeyheri are known as devil’s claw and used interchangeably, which was pointed out in a press release from the American Botanical Council.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” for relief of minor joint pain and mild digestive disorders, such as bloating and flatulence, and where there is loss of appetite.3 However, the first edition of the American Herbal Products Association’s (AHPA’s) Herbs of Commerce, which was incorporated into federal regulations, lists only H. procumbens as devil’s claw. (Herbs of Commerce is an industry self-regulatory publication that provides accepted labeling guidelines for common names of herbal and vegetable food ingredients in US commerce.4) On this basis, the NY AG established that all devil’s claw products containing H. zeyheri are mislabeled and thus adulterated.
The contents of tested products were identified using a DNA mini-barcode approach, which was performed by scientists from the New York Botanical Garden who specialize in DNA authentication of plant materials. A total of 23 commercial devil’s claw supplements were analyzed, 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 unclear if these two products contained devil’s claw extracts that were processed in a manner that rendered the DNA undetectable by barcoding methods.)
The NY AG gave the companies 10 days to detail current quality control measures for their devil’s claw products and plans to improve or reform these measures. Companies were also required to explain how they would identify and compensate affected consumers.
Nature’s Way, which was not on the list of the 13 companies targeted by the NY AG, has already agreed to implement additional quality control measures, including DNA barcode testing for all its herbal dietary supplements that contain only one or two ingredients. In addition, the company has stated that their devil’s claw products will be made exclusively with H. procumbens.1
The use of devil’s claw for medicinal purposes by the San, Nama, and Khoi peoples of Namibia and South Africa dates back centuries. Investigations by Western nations into the medicinal properties of devil’s claw began in the 1950s, but large-scale exports of the plant did not start until the early 1960s.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),** 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
Older analytical technologies (e.g., the analysis of iridoid glycosides by thin-layer chromatography) were unable to distinguish the two species, so it is unclear which Harpagophytum species were used in clinical trials of devil’s claw. However, high-performance liquid chromatography (HPLC) analyses of old batches indicate that many 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 US Pharmacopeial Convention.9
Since botanical nomenclature and human knowledge of botanicals in commerce are constantly evolving, some of the entries in the second edition of AHPA’s Herbs of Commerce (2000) are likely outdated, which may create some confusion in the US dietary supplement industry.10 The constant revisions to botanical nomenclature were a problem recognized by the editors of the book, as was the fact that the addition of new species would 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 issued 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 compositions, despite the fact that there can be 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 the recent letters from the NY AG, is not supported by the study of Mncwangi et al. which found the compound in both Harpagophytum species.13
Also, according to the paper by Mncwangi et al., the potentially active compound harpagoside occurs in both H. procumbens and H. zeyheri, but less than 50% of tested 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.
Products that contain H. zeyheri but claim on their label to contain only H. procumbens are technically mislabeled under US law. However, for companies to receive cease-and-desist letters when official pharmacopeias (British Pharmacopoeia, European Pharmacopoeia, United States Pharmacopeia, etc.) and EMA monographs recognize the interchangeability of the two species seems to be splitting taxonomic hairs in a manner that does not afford any perceptible benefit to consumers. There are more compelling quality control problems currently occurring in US and international herb markets.
—Stefan Gafner, PhD
* 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 conduct business in the state of New York.
** AAMPS is the publisher of the African Herbal Pharmacopoeia (2010), which Brendler co-edited.
- AG 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: 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.
- 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: cms.herbalgram.org/press/2015/NewYorkAttorneyGeneralsInvestigationonDevilsClawIgnoresExpertEvaluationsandProvidesNoBenefittothePublic.html. Accessed October 5, 2015.
- 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. Available at: www.ema.europa.eu/docs/en_GB/document_library/Herbal_-_Community_herbal_monograph/2010/01/WC500059018.pdf. Accessed October 5, 2015.
- Moley T, Awang D, Hu SY, et al., eds. Herbs of Commerce. 1st ed. Austin, TX and Silver Spring, MD: American Herbal Products Association; 1992.
- 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.
- Nott K. A survey of the harvesting and export of Harpagophytum procumbens and H. zeyheri in SWA/Namibia. Okaukuejo, Namibia: Etosha Ecological Institute; 1986.
- 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.
- The European Directorate for the Quality of Medicines & HealthCare. European Pharmacopoeia (EP 8.7). Harpagophyti radix. Strasbourg, France: Council of Europe; 2015.
- 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.
- McGuffin M, Kartesz JT, Leung AY, Tucker AO. Herbs of Commerce. 2nd ed. Silver Spring, MD: American Herbal Products Association; 2000.
- Schultz H. Complexity of herbal nomenclature becomes point of vulnerability for industry. NutraIngredients-USA website. Available at: www.nutraingredients-usa.com/Regulation/Complexity-of-herbal-nomenclature-becomes-point-of-vulnerability-for-industry. Accessed October 5, 2015.
- 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: www.ahpa.org/Default.aspx?tabid=571. Accessed October 5, 2015.
- Mncwangi NP, Viljoen AM, Zhao J, Vermaak I, Chen W, Khan I. 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.