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.
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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.
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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.
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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
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