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Cranberry (Vaccinium macrocarpon) - Botanical Adulterants Bulletin • December 2017 • www.botanicaladulterants.org
Cranberry (Vaccinium macrocarpon) - Botanical Adulterants Bulletin • December 2017 • www.botanicaladulterants.org
1
Adulteration
of Cranberry
(Vaccinium
macrocarpon)
Keywords: Vaccinium macrocarpon, cranberry fruit
extract, adulterant, adulteration
Goal: The goal of this bulletin is to provide timely
information and/or updates on issues of adulteration of
cranberry fruit (Vaccinium macrocarpon) extract to the
international herbal products industry and extended
natural products community in general. It is intended
to present the available data on the occurrence of adul-
teration, the market situation, and consequences for the
consumer and the industry.
1. General Information
1.1 Common name: Cranberry1
1.3 Accepted Latin binomial: Vaccinium macrocarpon
Aiton1
Note: Cranberry products on the dietary supplement,
food and beverage markets are predominantly made
from V. macrocarpon. However, the second edition
of American Herbal Products Association’s Herbs of
Commerce,1 which provides guidance on dietary supple-
ment labeling in the United States, also accepts prod-
ucts derived from V. oxycoccos to be labeled as cranberry.
By Thomas Brendlera* and
Stefan Gafner, PhDb
aPlantaphile, 710 Park Avenue, Collingswood, New
Jersey 08108
bAmerican Botanical Council, 6200 Manor Road,
Austin, TX 78723
*Corresponding author: email
Cranberry
Vaccinium macrocarpon
Photo ©2017 Steven Foster
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Cranberry (Vaccinium macrocarpon) - Botanical Adulterants Bulletin • December 2017 • www.botanicaladulterants.org
1.2 Other common names:
English: American cranberry, large cranberry, North
American cranberry2-5
Chinese: Da guo yue jie (大果越桔)6
French: Canneberge, canneberge d’Amérique, canneberge
à gros fruits, atoca, atoka, ronce d’Amérique2,3
German: Kranbeere, grosse Moosbeere2-4
Italian: Ossicocco americano, mirtillo rosso canadese,
mortella di palude, cranberry7
Spanish: Arándano, arándano americano, arándano trepa-
dor, arándano rojo2-4
1.4 Synonyms: Oxycoca macrocarpa (Aiton) Raf., Oxycoc-
cus macrocarpus (Aiton) Pers., Oxycoccus palustris var. macro-
carpos (Aiton) Pers., Schollera macrocarpa (Aiton) Steud.,
Schollera macrocarpos (Aiton) Britton
1.5 Botanical family: Ericaceae
1.6 Plant part and form: The vast majority of the cran-
berry dietary supplements are made from the fruit. The
ingredients used in dietary supplements are powdered fruit,
dried powdered fruit juice, or extracts made from the whole
fruit, fruit juice or from cranberry press cakes, which is the
material that remains after the juice has been pressed out.
The extraction techniques are often proprietary, and may
include an enzymatic or chemical hydrolysis step to release
proanthocyanidins (PACs) from cell wall polysaccharides.
Further concentration of the phenolic compounds, in
particular the PACs, can be achieved by chromatographic
techniques, e.g., by using specific resins that retain these
phenolic compounds.8,9 While most extracts that give a
defined amount of cranberry compounds are standardized
to PACs, some manufacturers prefer to indicate levels of
organic acids or anthocyanins. Depending on the process-
ing method, the PACs present can be soluble, insoluble,
or both. Dietary supplements made solely from cranberry
seeds or cranberry leaves are not within the scope of this
document.
1.7 General use(s): Investigations in the early 20th
century reported the effect of cranberries on urinary acidity,
i.e., a lowering of the urinary pH after ingestion of cranber-
ries.10,11 Since the late 1950s, the beneficial effect of cran-
berry juice and cranberry juice derivatives in the prevention
and adjuvant treatment of recurrent urinary tract infections
has been demonstrated in a plethora of pre-clinical and clin-
ical investigations. Critical reviews, including meta-analy-
ses, generally support the efficacy of cranberry in the afore-
mentioned indication.12-14 However, a 2012 review indi-
cated that methodological f laws in the design of the clinical
studies and insufficient characterization of the administered
cranberry products impede a reliable assessment.15
Other health benefits and actions of cranberry which
have been investigated include prevention of gastric ulcers
(caused by H. pylori), and activities related to periodon-
tal disease, cancer prevention, glycemic response, antiviral
activities, and a reduction of cardiovascular risk factors.16-20
The PACs with a specific A-type linkage are considered
responsible for the bacterial anti-adhesion activity – the
health benefit which relates to urinary tract infections,
ulcer prevention, and reduction of periodontal disease.
Howell et al. determined that foods containing PACs with
only B-type linkages do not provide as substantial bacte-
rial anti-adhesion activity in urine as the cranberry PACs
with A-type linkages.21 The most common dose used in
early and recent studies demonstrating efficacy was approx-
imately 300 mL of cranberry juice cocktail that, when
calculated, delivers approximately 36 mg of soluble PACs
(as measured with the 4-dimethylaminocinnamaldehyde
[DM AC] color reagent using procyanidin A2 as standard;
see below).19,22,23
Further compounds of note contained in cranberries and
its preparations are PACs with a B-type linkage, anthocya-
nins, f lavonols, organic acids, volatile compounds, sugars,
and vitamins. Ratios of A-type PACs to B-type PACs
Table 1: Sales data for cranberry products in the herbal supplement category in the United States from 2012-2016.
Channel 2012 2013 2014 2015 2016
Rank Sales
[US$]
Rank Sales
[US$]
Rank Sales
[US$]
Rank Sales
[US$]
Rank Sales
[US$]
Naturala10 5,078,657 20 3,855,518 17 4,254,478 13 5,670,347 11 7,513,172
Mainstream
Multi-Outletb
3 66,369,322 4 48,575,307 3 56,366,811 2 65,740,231 2 74,020,175
aAccording to SPINS (SPINS does not track Whole Foods Market sales, which is a major natural products retailer in the United
States.)
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 2013-2016).
Source: Smith et al.24 T. Smith (American Botanical Council) e-mail to S. Gafner, September 2, 2015 and September 3, 2015.
3 2
Cranberry (Vaccinium macrocarpon) - Botanical Adulterants Bulletin • December 2017 • www.botanicaladulterants.org
in cranberry products may be used for authentication.
PACs can be soluble and insoluble (the latter are insoluble
because they are bound to cell wall components such as
polysaccharides or proteins), depending on the prepara-
tion and extraction method (e.g., juice and juice deriva-
tives contain mostly soluble PACs, while whole cranberry
powder, press cake, and press cake derivatives contain
mostly insoluble PACs).19
Apart from the medicinal and supplement use, cranberry
and its derivatives are widely consumed as foods and food
ingredients.
2. Market
2.1 Importance in the trade: Cranberry has seen a
steady growth in sales in the past decade. Cranberry prod-
ucts are among the most popular herbal dietary supple-
ments in the United States with over US $80 million in
sales (Table 1) in 2016, combining both the Natural retail
channel and the Mainstream Multi-Outlet retail chan-
nel (excluding sales data from Walmart and Club stores in
2013-2016, which were not available).
2.2 Supply sources: The majority of fresh cranber-
ries is grown in northern North America (United States
and Canada), followed by Chile and smaller producers in
Europe and China.19
2.3 Market dynamics: The majority of cranberry supple-
ments in the United States are sold in the Mainstream
Multi-Outlet retail channel. A comparison with sales data
from 2000 (US $9,616,326),25 2005 ($15,839,160),26 2010
($35,806,000)27 and 2015 ($65,740,231) in this retail
channel shows the consistent growth of the cranberry
market. This is in line with increases in North American
cranberry production from approximately 300,000 metric
tons in 2000 to 500,000 in 2013.28 According to a report
commissioned by the Cranberry Marketing Committee
USA, Cranberry Institute, and British Columbia Cranberry
Marketing Commission, the most important importers of
cranberry products are the United Kingdom, Germany,
France, Mexico, and Australia.28 However, while the
dietary supplement sales are growing, sales in other cran-
berry categories, in particular cranberry juice concentrates,
have been falling recently, leading to a systemic oversupply
of cranberry in 2014 and to low prices for growers.29
According to an informal inquiry by the authors, market
prices for dried press cake (containing 0.8 to 1.5% PACs)
are around US $50-75/kg; these dominate the bulk cran-
berry ingredient market with over 50% of the market share.
Whole berry extracts, and blends of juice extracts with
berry extracts (3 to 5% PACs) cost around US $150-300/kg,
while prices for pure juice extracts (12 to 24% PACs) range
from US $400-600/kg.
PAC-rich extracts from other plant sources, which are
used to inf late PAC values of lower cost cranberry extracts
or to substitute for cranberry extracts altogether, are avail-
able at much lower cost: For example, the price for peanut
skin extract in 2015 was at US $10-13/kg, while pine bark
extracts were sold for US $20-22/kg.30 In 2017, pricing for
peanut skin extract with a PAC content of 80-90% was
priced between US $30-50.
3. Adulteration
With one notable exception dated around Thanksgiv-
ing 1959†, adulteration of cranberry products is a relatively
recent phenomenon, the first evidence for which appearing
in the mid-1980s when grape anthocyanidins (a mixture
of grape skin pigments collectively called enocyanin) were
detected in cranberry juice.32-34 As the demand for cran-
berry products increased, incidents of admixture of lower
cost and more readily available sources of anthocyanins,
PACs, and f lavanols were more frequently observed. One
primary way of authenticating cranberry preparations is by
determining the presence of A-type linkages in the PACs,
and establish the ratio between A-type and B-type PACs.
This guards against adulteration of cranberry products
with materials from less expensive food sources character-
ized by their B-linked PACs and/or flavanols (epicatechin
or catechin).34
3.1 Known adulterants: Historically, American high-
bush blueberry (V. corymbosum) and alpine blueberry, bog
bilberry or bog blueberry (V. uliginosum) have occasion-
ally been noted as adulterants.19 Grape anthocyanins were
detected in cranberry juice in the 1980s (see above).32-34
More commonly than in juice products, adulteration is
detected in dry concentrates and powdered extracts, likely
due to the absence of standard analytical methods, difficul-
ties in measuring complex PACs, and a lack of readily avail-
able reference standards. Most prevalent adulterants include
grape (Vitis vinifera, Vitaceae) seed and skin extracts, red
peanut (Arachis hypogaea, Fabaceae) skin extracts, but also
maritime pine (Pinus pinaster, Pinaceae) bark extracts, and
extracts of black bean (Phaseolus vulgaris, Fabaceae) skins,
black rice (Oryza sativa, Poaceae), plum (Prunus domestica,
Rosaceae), mulberries (Morus spp., Moraceae), other berries,
and other parts of cranberry.19,3 6-4 3
An interesting case of a scientific investigation inadver-
tently carried out with an adulterated reference material is
provided by Wei and co-workers,44 who isolated delphin-
idin-3-O-sambubioside, cyanidin-3-O-sambubioside, and
p-coumaric acid from a crude “cranberry” extract purchased
from Tiancheng (Shaanxi, China) using high-performance
counter-current chromatography. In fact, those anthocyani-
dins do not occur in V. macrocarpon or V. oxycoccos, but are
known to be the main anthocyanins in hibiscus (Hibiscus
sabdariffa, Malvaceae) calyces.
3.2 Accidental or intentional adulteration: While
historically adulteration of cranberry products may be
considered primarily accidental (see above), more recent
cases are more likely intentional, i.e., for economic reasons.
3.3 Frequency of occurrence: There is no comprehen-
sive published study on the frequency of cranberry adul-
teration.
3.4 Possible safety/therapeutic issues: Adulterants
4
Cranberry (Vaccinium macrocarpon) - Botanical Adulterants Bulletin • December 2017 • www.botanicaladulterants.org
which are commonly detected in cranberry products gener-
ally do not pose a safety risk, although the allergenic
potential of peanut skin extract is a matter of concern.
Efficacy, however, is believed to depend on quantity and
bioavailability specifically of A-type PACs, thus adultera-
tion with other, lower-cost PACs may substantially reduce
efficacy of cranberry products.
While peanut skin contains most of the known peanut
allergens, these are bound and rendered insoluble by the
phenolic compounds (particularly procyanidins, which are
proanthocyanidins formed exclusively from catechin and
epicatechin) present in peanut skin. Furthermore, proteins
extracted from peanut skins do not appear to bind peanut
specific IgE in the presence of phenolic compounds.45 The
allergenicity of spray-dried peanut skin extracts (using 70%
aqueous ethanol as the extraction solvent) was evaluated
by Constanza using a peanut allergen test kit. While no
allergenic proteins were found in the spray-dried materials
containing only the extract, peanut allergens were detected
in a peanut skin extract spray-dried onto maltodextrin.46
Since the manufacturing process for peanut skin extracts
may vary from one supplier to another, elimination of the
allergenic peanut proteins is not guaranteed. Therefore, an
allergic reaction to peanut skin extracts used to adulterate
cranberry extracts cannot be excluded.
3.5 Analytical methods to detect adulteration:
Depending on the level of detail required in terms of
presence, qualification, and quantification of adulterants,
and the analytical endpoint, several analytical methods
of increasing complexity can be utilized in a step-by-step
fashion:
a. Quinic acid and the ratio of quinic to malic acid
can be used to calculate the cranberry juice content;
however, these acids are not unique to cranberry, and
while they may suffice to determine a certain qual-
ity, reliance solely on the assessment of these organic
acids for identification of cranberry will not rule out
adulteration.47, 4 8 The organic acids are predomi-
nantly used as chemical makers for authentication of
cranberry juice and juice-derived products.
b. Anthocyanins: Where identity and purity of the
tested material are known, spectrophotometric anal-
ysis can be used to estimate total anthocyanins.
However, this approach is non-specific and thus
susceptible to adulteration with anthocyanin-rich or
proanthocyanidin-rich materials from other sources.
A more reliable approach to authenticate cranberry
extracts is to use the HPLC-Vis anthocyanin finger-
print. Cranberry has a unique qualitative anthocy-
anin profile.48,49 Comparing HPTLC and HPLC
fingerprints to an authentic reference material are
standard techniques used for the identification of
anthocyanin-containing cranberry extracts. These
methods can also detect the presence of some adul-
terants (e.g., black rice extracts, hibiscus extracts,
and admixture of up to 15% grape skins or grape
seeds).19,50 However, this method is not suitable to
detect admixture of PAC-containing materials that
are devoid of anthocyanins. A validated HPLC-
Vis method was published to quantify five of the
six predominant cranberry anthocyanins (cyanidin-
3-O-galactoside, cyanidin-3-O-arabinoside, cyani-
din-3-O-glucoside, peonidin-3-O-galactoside, and
peonidin-3-O-arabinoside) in commercial cranberry
fruit products.51 Puigventos and co-workers utilized
HPLC-ESI-MS to create “polyphenolic fingerprints”
of cranberry products to elucidate adulteration with
grape. Their results were clearly distributed in rela-
tion to the extent of grape adulteration with overall
quantification errors of <5%.52
c. For (relative) quantitation of soluble PACs,
spectrophotometric DMAC methods using a procy-
anidin A222 standard or using a c-PAC standard53
are employed, whereas the butanol-HCl method can
be used for insoluble PACs (e.g., from press cake).54
The DMAC method was recently modified for
better results with cranberry juice extracts in terms
of intermediate precision (RSD ≤ 5%), repeatability
(RSD ≤ 3%), robustness (≤3%) and linearity (R2 ≥
0.995).19, 23 However, these colorimetric assays are
not suitable for authentication of cranberry.
d. The determination of the compounds obtained after
a reaction of cranberry PACs with benzyl mercaptan
(thiolysis) by HPLC-UV provides information about
the structure and average size (degree of polymer-
ization) of these molecules. While data on the abil-
ity to detect adulteration of cranberries with other
PAC-containing materials are lacking, thiolysis can
provide additional evidence for the authenticity of a
material.
e. Matrix assisted laser desorption ionization-time of
flight mass spectrometry (MALDI-TOF MS) is an
analytic tool that is considered the MS method of
choice for analysis of PACs with structural heteroge-
neity and compliments spectrophotometric methods
to quantify total PACs. MALDI-TOF MS provides
superior mass resolution and allows measuring the
relative ratios of A-type and B-type PAC in cranberry
oligomers, useful when trying to accurately identify
A-type PACs and other PAC compositional differ-
ences.54 -56
f. An assay analyzing DNA by PCR amplification of
the MatK gene was recently presented by Herbst and
co-workers. The assay successfully discriminated
Vaccinium DNA from grape, apple (Malus domestica,
Rosaceae) and pear (Pyrus spp., Rosaceae); however,
the primers developed were unable to discrimi-
nate among Vaccinium spp.57 With the selection of
one/several appropriate genomic region(s), distinc-
tion among Vaccinium species should be possible
by genetic means. Nevertheless, genetic methods
cannot distinguish among plant parts and may be
of limited use in processed materials. Depending on
the nature and extent of the processing, cranberry
extracts may not contain DNA of sufficient quality
5 4
Cranberry (Vaccinium macrocarpon) - Botanical Adulterants Bulletin • December 2017 • www.botanicaladulterants.org
to enable the identification of adulteration by genetic
means.
g. Recently, it has been suggested to utilize anti-adhe-
sion activity of cranberry products in order to detect
adulteration. The approach is based on the distinct
‘A-Type’ linkage proanthocyanidins (PAC’s), which
have been shown to inhibit the adhesion of E. coli
bacteria to the walls of the urinary tract and do
not occur in PACs from many other tannin-rich
substances. However, adulterants containing A-type
PACs, such as peanut skin extracts, may provide false
positive results. In addition, the assay would neither
identify the adulterant nor quantify the PAC concen-
tration.58
3.6 Perspectives: Considering the rapidly-growing
market for cranberry products and the many promising
health benefits of cranberry that still await further elucida-
tion, it can be expected that cases of adulteration will not
disappear anytime soon. Confusion about the exact content
in certain cranberry products due to discrepancies in label-
ing of cranberry ingredients may also lead to instances
where a consumer may not purchase the intended product.
Therefore, a clear indication what the cranberry supplement
is made from, (i.e., dried whole berries, juice, or press cake)
is crucial to meet consumers’ expectations about the prod-
uct. A good source of information on quality control issues
associated with cranberry, cranberry extracts, and the need
for differentiation of the various types of cranberry prod-
ucts is the extensive cranberry monograph of the American
Herbal Pharmacopoeia.19
Emerging new analytical methods, as well as available
methods’ becoming more accessible and widely available,
will contribute to making successful intentional adultera-
tion not only more difficult but also less economically
viable. Recent initiatives by organizations like USP (United
States Pharmacopeia) and AOAC have renewed efforts
to evaluate current analytical methods for cranberry to
produce more widely accepted analytical tests. The efforts
rely on stakeholder, i.e., industry, consensus‡ to choose the
most suitable approaches for qualitative and quantitative
analysis of cranberry and cranberry-derived ingredients.
4. Conclusions
The success and comparatively high cost of cranberry
extracts has provided an incentive for economically-moti-
vated adulteration with anthocyanin- or proanthocyani-
din-rich extracts from other botanical sources, as well as
synthetic colorants. Data on the problem are fragmented,
and mainly based on a small number of published papers
and case reports from industry members. While admix-
ture or substitution with anthocyanin-containing extracts
is readily detected, the inclusion of proanthocyanidins
from, for example, grape seed, peanut skin, or pine species
masquerading as cranberry extract is more difficult to
detect and may require more advanced instrumentation,
Cranberry
Vaccinium macrocarpon
Photo ©2017 Steven Foster
6
Cranberry (Vaccinium macrocarpon) - Botanical Adulterants Bulletin • December 2017 • www.botanicaladulterants.org
and/or a combination of analytical methods. In order
to provide the desired health benefits from a cranberry
supplement, it is imperative to follow an appropriate test
protocol including adequate methods to verify the authen-
ticity of all cranberry-derived ingredients.
†What was initially considered an adulterant turned out
to be a contamination with an herbicide.31
‡For example, a June 2017 USP round-table discus-
sion on cranberry standards with more than 40 partici-
pants from industry concluded to recommend the DMAC
method with the procyanidin A2 standard for USP cran-
berry fruit juice concentrate/powder/dry extract mono-
graphs.
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Cranberry
Vaccinium macrocarpon
Photo ©2017 Steven Foster
8
Cranberry (Vaccinium macrocarpon) - Botanical Adulterants Bulletin • December 2017 • www.botanicaladulterants.org
REVISION SUMMARY
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Official Newsletter of the ABC-AHP-NCNPR
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