By Stefan Gafner, PhD*
*American Botanical Council, P.O. Box
144345, Austin, TX 78723, email
Keywords:
Adulterant,
adulteration, black cohosh, Actaea cimicifuga, Actaea dahurica, Actaea
heracleifolia, Actaea racemosa, Chinese cimicifuga, Cimicifuga
racemosa
Goal: The goal of this bulletin is to
provide timely information and/or updates on issues of adulteration of black
cohosh (Actaea racemosa,
Ranunculaceae) to the international herbal industry and extended natural
products community in general. It is intended to complement the previously
published works with information on black cohosh adulteration, e.g., the
American Herbal Pharmacopeia monograph published by Upton et al.,1
and the review paper by Foster,2 by presenting new data
on the occurrence of adulteration, the market situation, and consequences for
the consumer and the industry.
1 General Information
1.1
Common name: black
cohosh3
1.2
Other common names:
English: Black bugbane, snakeroot, rheumatism
weed, fairy candle, tall bugbane, black bugbane, macrotys, macrotrys,
battleweed, columbine-leaved leontice, cordate rattle top, rattleweed, false
cohosh, papoose root.4
Chinese: Zong zhuang sheng
ma (总状升麻)
French: Actée à grappes noires, cimicaire à grappes,
chasse-punaises, cimifuge, herbe à punaise, serpentaire noire
German:
Traubensilberkerze, Wanzenkraut, Frauenwurzel, langtraubiges Christophskraut,
Nordamerikanische Schlangenwurzel, schwarze Schlangenwurzel
Italian: Cimicifuga, serpentaria nera, actea nera
Spanish: Cohosh negro, raíz de culebra negra
1.3
Accepted Latin binomial: Actaea racemosa5,6
1.4 Synonym: Cimicifuga racemosa
1.5
Botanical family:
Ranunculaceae
1.6 Distribution
range: Black cohosh is native to North America, where it occurs in Eastern
Canada (Ontario, Quebec), and in the Eastern United States from Massachusetts
to Georgia, and west to Illinois and Arkansas.7
1.7
Plant part, form and production method: Whole, chopped, and powdered dry rhizome and root, and
aqueous ethanol or aqueous isopropanol extracts. Extracts are offered as
fluidextracts (plant-solvent ratio 1:1), liquid extracts (hydroalcoholic
extracts, dry extracts dissolved or suspended in glycerin-water mixtures), or
dry extracts in tablet or capsule form. The dry extracts are often standardized
to contain 2.5% triterpene glycosides.1
1.8
General use(s): Currently,
black
cohosh is used to alleviate premenstrual discomfort, dysmenorrhea and symptoms
of menopause (hot flashes, excessive sweating, sleep disorders, irritability).8,9
Traditionally, black cohosh is used for colds, dyspepsia, rheumatoid arthritis,
sciatica, snake bites, tinnitus, and whooping cough, but such use is not
supported by experimental or clinical data.8
2 Market
2.1 Importance in the trade: From 2012-2014, black cohosh has
consistently been one of the 10 top-selling herbs in the mainstream market and
has ranked within the 30 top-selling herbs in the natural foods sector in the
United States (Table 1).
Table 1: Sales data for black cohosh
dietary supplements from 2012-2014.
Channel
|
2012
|
2013
|
2014
|
|
Rank
|
Sales [US$]
|
Rank
|
Sales [US$]
|
Rank
|
Sales [US$]
|
Naturala
|
21
|
3,793,709
|
23
|
3,504,145
|
26
|
3,359,658
|
Mainstream Multi-Outletb
|
4
|
44,646,587
|
4
|
46,007,332
|
5
|
42,463,816
|
aAccording
to SPINS (SPINS
does not track Whole Foods Market sales, which is a major natural products
retailer in the US)
bAccording to SPINS/IRI (the
Mainstream Multi-Outlet channel was formerly known as food, drug and mass
market channel [FDM], possible sales at Walmart and club stores are excluded in
2013 and 2014)
n/a:
not available
Source:
T. Smith (American Botanical Council) e-mails, September 2, 2015 and September
3, 2015
2.2
Supply sources: The
majority of the black cohosh on the market comes from material that is
harvested in the wild. Kentucky and Tennessee are the major areas of collection.
Additional supplies are collected in other states along the Appalachian
Mountains and in the Northeastern United States.1 An evaluation of
the trade in 2010 suggests that habitat loss and
over-collection are threats to the black cohosh supply.10 There
is some cultivated material available. For example, Schaper & Brümmer, the
manufacturer of a leading black cohosh product, Remifemin®, grows
a horticultural variety of black
cohosh in Lower Saxonia and Thuringia, Germany that is registered by the company and protected by the Community Plant
Variety Office (CPVO) of the European Union.
2.3 Raw material forms: Bulk black cohosh crude raw material is sold as whole rhizome and roots, in for of a teabag, cut, or as powdered rhizome and roots.
2.4 Market
dynamics: The annual harvest
of black cohosh has seen some dramatic fluctuations (Table 2).11
Table
2. Estimated Cultivated and Wild Harvest Tonnage for Black Cohosh11
Year
|
Estimated
harvest (metric tons) from cultivation
|
Estimated
material (metric tons) collected in the wild
|
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
2010
|
0
16.07
1.18
0.07
2.96
0.13
0.17
1.50
3.14
0.93
1.01
0.72
0.63
4.47
|
102.97
329.30
65.94
53.45
80.97
76.86
144.31
144.58
61.86
139.48
155.93
129.81
76.51
142.74
|
The reasons
behind the changes in harvest volume are not clear, but excess
inventory built up in the previous years could have led to the sharp drop in
harvest in 2005, and again in 2009.4,12 The large harvest amounts in
2003 and 2004 were possibly a reaction to increased sales of black cohosh
dietary supplements after a large study suggested that hormone treatments of
menopausal women increased their risk of cardiac problems.13 Additionally, Actaea species indigenous to Asia and represented as black cohosh
may also have impacted demand for and, therefore, harvests of authentic A. racemosa. No harvest report data on
black cohosh have been published since 2010.
Sales of branded
black cohosh dietary supplement products have declined over the past several
years, which is in line with the general trend in the market segment for menopause
products. This decline may be due to the lower number of women entering menopause based on the
lower birth rates in the 1960s compared to the 1950s.
In
2011, the price of A. racemosa to manufacturers
reportedly ranged from US $10-17/kg, with the usual cost being US $14.5-16.5/kg.
Material sourced from Asia and sold as “black cohosh” (e.g., Actaea cimicifuga), on the other hand, was
reported to be available at US $6-8/kg, providing an incentive for economically
motivated adulteration (EMA).2 Since 2014, prices of authentic black cohosh have
been steadily increasing.
3 Adulteration
3.1 Known adulterants: Reports of adulteration of black
cohosh have often involved species
in the genus Actaea imported from Asia,
e.g., the following taxa:
- Actaea cimicifuga (syn: Cimicifuga foetida)
- A. dahurica (syn: C. dahurica)
- A. heracleifolia (syn: C. heracleifolia)
- A. simplex (syn: C. simplex)
- A.
brachycarpa (syn: C. brachycarpa).14,15
A paper on frequently misidentified
species on the Hong Kong market lists Serratula chinensis (Asteraceae) as an adulterant of Chinese cimicifuga,16 which may result in uninformed
purchasing agents procuring an adulterant of the adulterant, further confusing
the black cohosh market. Adulterants of A.
racemosa may also include North American species of Actaea growing in the same area as black cohosh, e.g., A.
pachypoda, A. rubra, and
A. podocarpa. The native range of
black cohosh overlaps most with A. pachypoda, followed by A. rubra and then A.
podocarpa. But
overall the
largest plant is A. racemosa, so most wildcrafters will dig black cohosh since
it gets them more money for their effort.4 [E. Fletcher, e-mail communication, April 6,
2015]
3.2
Sources of information confirming adulteration: The most extensive review on
adulteration of black cohosh has been published by Foster.2 Since
its publication in 2012, there have been three new studies that used combinations
of genetic and chemical methods to authenticate commercial black cohosh
products. These studies provided additional evidence of continuing adulteration
of purported A. racemosa products with
Actaea species indigenous to Asia.15,17,18
Two of the studies used genetic authentication techniques (restriction fragment
length polymorphism [RFLP] and amplification refractory mutation system [ARMS]17
or direct sequencing of the ITS1-ITS2, ITS1, and trnL-F regions18) combined with high-performance liquid
chromatography (HPLC-ELSD17 or HPLC-MS18) to establish botanical
identity. In the first study, 16 commercial black cohosh dietary supplements
were analyzed that were purchased through the Internet, originating from the
United States (n = 14), Australia (n = 1) and Canada (n = 1). Of these 16
samples, four were considered to be adulterated.17 Twenty-five
samples from the United States (n = 19) or Europe (n=6) were evaluated in the
second study, where seven out of the 25 samples were found to be adulterated.18
Actaea dahurica was identified as the
primary botanical adulterant in both studies. DNA was obtained from eight out
of 16, and 10 out of 19 dietary supplements products, respectively. The authors
did not attempt to extract DNA from the six herbal medicinal products from
Europe.17,18 Harnly et al. used a combination of DNA barcoding and two
metabolic fingerprinting methods, flow injection mass spectrometry (FIMS) and
proton nuclear magnetic resonance spectrometry (1H-NMR), to
establish the identity of the ingredients in one commercial black cohosh raw
material and 14 finished products.15 The commercial raw material sample
was purchased in China and was identified as A. dahurica.
The MS and NMR fingerprints of the 14 dietary
supplements were different from any of the authentic black cohosh raw material samples
(extracted using 70% aqueous methanol for the 1H-NMR and FIMS
analysis), indicating that variations in the manufacturing process lead to
significantly different phytochemical profiles. Therefore, in the absence of a sufficiently
large number of finished product samples with well-established provenance, the
chemometric methods were considered unsuitable for adequate authentication of
the ingredients in the dietary supplements. However, the techniques are
promising, and could potentially be proven reliable with a properly designed
series of experiments. DNA barcoding was successful for identifying four of the
seven capsule supplements tested as A.
racemosa. One supplement contained A.
brachycarpa, while the two remaining supplements contained either no DNA,
or DNA from an excipient. The remaining seven liquid supplements were not subjected
to DNA barcode analysis since it was expected that DNA would not be present.15
3.3
Accidental or intentional adulteration: The reasons for adulteration of black cohosh are
manifold. Domestic wild harvesting of root and rhizome biomass growing in the
proximity of similar co-habiting species, especially when the berries are
absent, has resulted in unintentional collection of the wrong species by
inexperienced, or irresponsible wildcrafters. The more common adulteration is
substitution of Asian species of Actaea for
A. racemosa by suppliers who either
knowingly or unknowingly apply the common name “black cohosh” inappropriately
to the Asian species of herbal material from the genus Actaea. According to the American
Herbal Products Association’s Herbs of Commerce, 2d edition,3 the standard common name “black cohosh” should
be exclusively applied to A. racemosa,
while the standard common name “Chinese cimicifuga” refers to A. cimicifuga (syn. A. foetida) and A. heracleifolia.
Intentional adulteration of black cohosh with Asian species is mainly due to
economic reasons,19 since the price for Asian Actaea materials is significantly lower (see section 2.4).
3.4
Frequency of occurrence:
There are no large studies on the frequency of black cohosh adulteration. However,
there are five published papers that investigated black cohosh adulteration in
commercial finished products, mainly products sold in North America and Europe.17,18,20-22
In these studies, the adulteration rate overall
(excluding subsets of the sample pool) was between 25% and 36%. Compiling the
data from all five studies, a total of 92 commercial products were analyzed, of
which 65 were determined to contain authentic black cohosh, while 25 samples
(27%) were found to be adulterated. Since the brand names of the analyzed
samples were not identified, it is possible that the same commercial product
was analyzed in more than one study, which might skew the percentage number. It
is also unclear if the products analyzed represent a large part of the sales
volume of black cohosh or if those were samples with a small market share.
Interestingly, the study by Masada-Atsumi et al. found that
all six
herbal medicinal products purchased from pharmacies in Europe contained
authentic black cohosh, while seven out of 19 products (36.8%) purchased
through the Internet from US sellers were adulterated.18
3.5
Possible safety issues:
As noted previously, the consumption of supplements labeled as black cohosh has
been associated with hepatotoxicity. There is speculation that some of these
cases may be due to the presence of an adulterant, specifically a species of Actaea other than A. racemosa. A report in Health Canada’s Adverse Event Newsletter in
2010 concluded that four of six products associated “black cohosh” liver
toxicity were adulterated, while the other two cases included products of
unknown composition that were not authorized for sale in Canada.23 The
phytochemical profiles of several of the products were consistent with those of
Asian Actaea species. There is no
evidence in the English language medical literature suggesting that A. dahurica, A. heracleifolia, or A.
cimicifuga are harmful to the liver. In fact, one study found that methanolic
extracts of A. dahurica have liver-protective
effects in mice.24 High doses of both black cohosh and Chinese
cimicifuga have been reported to cause headaches, tremors, limb contractions,
apathy, vertigo, and abnormal erections. Overdoses may result in nausea,
vomiting, and gastroenteritis.25-27
3.6
Analytical methods to detect adulteration: The roots of
black cohosh are readily distinguished macroscopically from A. dahurica, A. foetida, and A. heracleifolia.
Chinese cimicifuga is almost always sliced, displaying a sinusoid pattern that
is not generally observed in authentic black cohosh. The Chinese cimicifuga
adulterant Serratula chinensis can
be similarly distinguished since it has no morphological resemblance to either
species. (R. Upton e-mail, May 6, 2016)
The phytochemical profiles of authentic black cohosh and the various
adulterating species are similar and therefore identification by these profiles
alone is difficult.14 The European Pharmacopoeia (EP) Monograph Cimicifugae rhizoma includes a high-performance thin layer
chromatography (HPTLC) test to detect possible substitution with A. cimicifuga, A. dahurica, A. heracleifolia,
and A. podocarpa.28 The
high-performance liquid chromatography-evaporative light scattering detector
(HPLC-ELSD) methods in the EP and United States Pharmacopeia (USP) reportedly also provide a
suitable way to distinguish black cohosh from adulterating species.28,29
Genetic methods can be used to differentiate the species in materials where intact
DNA is present, however, it may not appropriate for extracts or processed
material that contain highly fragmented DNA, or where DNA is absent altogether.
The most robust approach for discerning the identity of black cohosh and for
ruling out substitution with non-target Actaea
species is to use multiple methods of identification, preferably a combination
of a genetic approach (if applicable) and a chemical fingerprinting method that
provides data on peak identity (e.g., HPLC-MS). The Black Cohosh Adulteration Laboratory
Guidance Document, a
comprehensive evaluation of published analytical methods with regard to their
ability to authenticate black cohosh and to detect adulteration, was published
by the ABC-AHP-NCNPR Botanical Adulterants Program in November 2015.14
3.7 Perspectives: Of the Actaea species sharing the same habitat, A. podocarpa is
morphologically the most similar to black cohosh with regard to both the aerial
parts and the root. However, with some training, the underground parts can be visually
distinguished from those of A. racemosa just as readily as can the aboveground
parts (E. Fletcher, e-mail communication, April 6, 2015). While misidentification at
collection sites is always possible, adulteration of black cohosh is mainly
associated with products imported from Asia (K. Morel [Naturex], e-mail
communication, February 9, 2015; Michael McGuffin [American Herbal Products
Association], oral communication, March 8, 2015).15,17,18
4 Conclusions: Black
cohosh has been one of the best-selling botanical supplements for many years
and is used primarily for the relief of menopausal symptoms. While black cohosh
has been a staple in North American herbal medicine for hundreds of years,30
the popularity of black cohosh to alleviate symptoms of menopause is largely
due to the introduction of a proprietary product, Remifemin® by the
German company Schaper & Brümmer in the 1950s. Habitat destruction and
over-harvesting in some areas of the United States have decreased the
availability of wild populations of this important medicinal plant.4,10
In addition, the higher price of authentic black cohosh compared to Chinese
cimicifuga has created an incentive for economically-motivated adulteration. While
accidental adulteration of domestically wild-crafted black cohosh with North
American species of Actaea may occur,
it is rarely reported. Most often black cohosh is adulterated with or
substituted by Chinese species of Actaea.
Authentic black cohosh is not native
to Asia, and currently there is no large-scale cultivation of authentic black
cohosh root in Asia. Therefore, any offering of black cohosh from sources
outside of North America, especially if occurring at unexpectedly low prices
relative to market value, should be viewed with suspicion and appropriate
measures should be taken to analytically confirm the identity of such botanical
material. Most of the reports of hepatotoxicity associated with black cohosh
products provide no information about the composition of the product, and
causality has been difficult or impossible to determine. There has been a
single report of a series of cases of hepatotoxicity associated with
adulterated black cohosh products,23 making it imperative to
positively identify black cohosh raw materials and extracts and to assure the
absence of non-target botanical and other adulterants.
5 References
- Upton
R, Graff A, Swisher D. American Herbal Pharmacopoeia and Therapeutic
Compendium: Black cohosh rhizome. Actaea racemosa L. syn. Cimicifuga racemosa (L.) Nutt. Standards of analysis,
quality control and therapeutics. Scotts Valley, CA: American Herbal
Pharmacopoeia; 2002.
- Foster S. Exploring the peripatetic maze of black cohosh
adulteration. HerbalGram 2013;98:32-51.
- McGuffin M, Kartesz JT, Leung AY, Tucker AO. American Herbal Products Association’s Herbs
of Commerce. 2nd
ed. Silver Spring, MD: American Herbal Products Association; 2000.
- Pengelly
A, Bennett K. Appalachian plant monographs. Black cohosh Actaea racemosa L.
2012. Available at: http://www.frostburg.edu/aces/appalachian-plants. Accessed January 22, 2015.
- The Plant List. Version 1.1 (September
2013). Available at: http://www.theplantlist.org. Accessed November 6, 2014.
- Tropicos.org.
Missouri Botanical Garden. Available at: http://www.tropicos.org. Accessed November 6, 2014.
- United States
Department of Agriculture (USDA), Agricultural Research Service (ARS), National
Genetic Resources Program. Germplasm Resources Information Network (GRIN)
Online Database. Beltsville, MD: National Germplasm Resources Laboratory. Available at: https://npgsweb.ars-grin.gov/gringlobal/taxonomydetail.aspx?id=411899. Accessed March 24, 2016.
- Mahady
G, Fong H, Farnsworth N. WHO Monographs
on Selected Medicinal Plant. Vol. 2. Geneva: World Health Organization;
2003.
- Blumenthal M, Goldberg A, Brinkmann J, eds. Herbal Medicine: Expanded Commission E
Monographs. American Botanical Council, Austin Texas 2000.
- Brinkmann
J. Taking a closer look at the US black cohosh rhizome trade. HerbalEGram.
2010;7(12).
- Dentali S, Zimmerman M. American Herbal Products Association
Tonnage Surveys of Select North American Wild-Harvested Plants, 2006-2010.
Silver Spring, MD: American Herbal Products Association; 2012.
- Zimmermann M, Dentali S. AHPA’s 2006-2010 tonnage
survey of select North American wild harvested plants. Presented at: ICNPR Congress;
July-August 2012; New York City, NY.
- Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of
estrogen plus progestin in healthy postmenopausal women: principal results from
the Women's Health Initiative randomized controlled trial. JAMA. 2002;288(3):321-333.
- Gafner S. Black Cohosh Adulteration Laboratory Guidance
Document. American Botanical Council, Austin, TX. 2015.
- Harnly J, Chen P, Sun J, et al. MS,
NMR, and DNA barcoding: complementary methods for identification and
authentication of black cohosh (Actaea
racemosa L.). Planta Med. 2016;82(3):250-262.
- Zhao
Z, Yuen JPS, Wu J, Yu T, Huang W. A systematic study on confused species of
Chinese materia medica in the Hong Kong market. Ann Acad Med Singapore. 2006;35:764-769.
- Masada-Atsumi S, Onuma M, Suenaga E, et al. Genome-based
authentication of black cohosh (Cimicifuga
racemosa; Ranunculaceae) supplements available in the Japanese markets. Jpn J Food Chem Safety.
2013;20(3):178-189.
- Masada-Atsumi S, Kumeta Y, Takahashi Y, Hakamatsuka T, Goda Y. Evaluation of the botanical origin of
black cohosh products by genetic and chemical analyses. Biol Pharm Bull. 2014;37(3):454-60.
- Black
cohosh (Actaea racemosa syn. Cimicifuga
racemosa)
root/rhizome. American Herbal Products
Association website. Available at: http://www.ahpa.org/Resources/TechnicalGuidance/ScientificAffairs/BotanicalAuthenticationProgram/BlackCohoshRoot.aspx. Accessed May 6, 2016.
- Baker DA, Stevenson DW, Little
DP. DNA barcode identification of black cohosh herbal dietary supplements. J AOAC Int. 2012;95(4):1023-1034.
- Jiang B, Kronenberg F, Nuntanakorn
P, Qiu MH, Kennelly EJ. Evaluation of the botanical authenticity and
phytochemical profile of black cohosh products by high-performance liquid
chromatography with selected ion monitoring liquid chromatography-mass spectrometry. J Agric Food
Chem 2006;54(9):3242-3253.
- He K, Pauli GF, Zheng B, et
al.
Cimicifuga species
identification by high performance liquid chromatography–photodiode array/mass
spectrometric/evaporative light scattering detection for quality control of
black cohosh products. J Chromatogr A
2006;1112(1-2):241-254.
- Painter D,
Perwaiz S, Murty M. Black cohosh products and liver toxicity: update. Canadian Adverse Reaction Newsletter. 2010;20(1):12.
- Yamahara J, Kobayashi M, Kimura H. Biologically
active principles of crude drugs. The effect of Cimicifugae Rhizoma and constituents in preventive action on the carbon
tetrachloride-induced liver disorder in mice. Shoyakugaku Zasshi. 1985;39:80-84.
- Gardner Z, McGuffin M,
eds. American
Herbal Products Association’s Botanical Safety Handbook. 2nd ed.
Boca Raton, FL: CRC Press; 2013.
- Felter
HW, Lloyd JU. King’s American
Dispensatory. 18th ed. Volume 1-2. Sandy,
OR: Eclectic Medical Publications; 1983 [Reprint of 1898 original].
- Wood
HC, LaWall C, Youngken HW, Osol A, Griffith I, Gershenfeld L. The Dispensatory of the United
States of America. 22nd
ed. Philadelphia, PA: J. B. Lippincott; 1937.
- The European Directorate for the Quality of
Medicines & HealthCare. European
Pharmacopoeia (EP 8.1).
Cimicifugae rhizoma. Strasbourg,
France: Council of Europe; 2014:3702-3705.
- United
States Pharmacopeial Convention. Black cohosh. In: United States Pharmacopeia and National Formulary (USP 38-NF 33). Rockville, MD: United
States Pharmacopeial Convention. 2015:7787-7789.
- Foster
S. Black cohosh: a literature review. HerbalGram.
1999;45:35-50.
REVISION SUMMARY
Version
# , Author,
|
Date
Revised
|
Section
Revised
|
List
of Changes
|
Version 1,
S. Gafner
new
|
n/a
|
n/a
|
none
|