Phytochemicals in Cranberries
By
Thais De Nardo
Maria Fernanda Polit
Kimberly Steffen
FST 694 – Phytochemicals in Fruits and Vegetables
November 8th, 2007
Introduction
Cranberries are dwarf shrubs of the family Ericaceae,
genus Vaccinium and subgenus Oxycoccus.
There are four species of cranberry:
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Vaccinium Oxycoccus or Oxycoccus palustris
Vaccinium microcarpum or Oxycoccus microcarpus
Vaccinium macrocarpon or Oxycoccus macrocarus
Vaccinium erythrocarpum or Orxycoccus erythrocarpus
Introduction
• Cranberries are shrubs of
approximately 5 to 20 cm height and
2 m long. With wiry stems, not
thickly woody and small evergreen
leaves. The berry is initially white and
turns in to a deep red when it is ripe.
• Cranberries are harvested in
the fall from late September
into October.
Phytochemicals in Cranberries
Cranberries contain many phenolic compounds:
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Anthocyanins
Flavonoids
Proanthocyanidins
Condensed tannins
Low molecular weight phenolic acids
Phytochemicals Cranberries
• Chen et al found that the major phenolic acid
detected in Cranberries is Benzoic acid.
• The study also found the presence of
(+)-Catechin, p-anisic acid and myricetrin.
Chen, 2001
Phytochemicals in Cranberries
Chen, 2001
Phytochemicals in Cranberries
• Vinson et al showed that cranberries have the
highest content of total phenolics per serving by
weight among 20 analyzed fruits (373mg of total
phenols/55grams of cranberries).
Vinson, 2001
Phytochemicals in Cranberries
• Cranberries were ranked in the same study #6 in
overall antioxidant quality.
Vinson, 2001
Phytochemicals in Cranberries
• Cranberries have a wide protective activity:
• Prevention of adhesion of certain bacteria in urinary
tract infections
• May help against heart disease, cancer and other
diseases.
Phytochemicals in Cranberries
These health benefits are
probably the result of
synergistic effects of all
phytochemicals present in
Cranberries.
Cranberry’s health effects on
cancer prevention
Cranberry’s health effects on cancer
prevention
• Cancer is a generic name for more than 100 diseases
that can affect all body parts.
• Cancer occurs when cells become abnormal and start
dividing rapidly, leading to the formation of more
cells without control or order.
• Cancer is the second leading cause of death in the
United States
Cranberry’s health effects on cancer
prevention
• Several epidemiological studies have proved that an
increase in the consumption of fruits and vegetables
are associated with a decrease in the risk of cancer.
• Recent studies show that not only antioxidant
activity of cranberries contributes to the
observed antitumor activities but also suggests
that this anticancer activity may involve a variety
of mechanisms
Cranberry’s health effects on cancer
prevention
• In 2004 a UCLA (Neto, 2007) study showed that water
soluble cranberry phenolic extracts inhibit
proliferation of several human tumor lines:
– 2 oral cancer cell lines (CAL27 and KB)
– 4 colon cancer cell lines (HT-29, HCT-116, SW480, and
SW620)
– 3 prostate cancer cell lines (RWPE-1, RWPE-2, and 22Rv1)
Quercetin in cranberries
• Inhibits the growth of MCF human breast
adenocarcinoma
• HT-29 human colon adenocarcinoma
• K562 human chronic myelogenous leukemia cell lines.
• Mammary MCF-7 cells
Cranberry’s health effects on cancer
prevention
• The studies shown that quercetin chemopreventive
action includes:
– induction of apoptosis
– inhibition of epidermal growth factor receptor expression
and associated tyrosine kinase activity
– reduced expression of Ras protein in colon cancer cells and
primary colorectal tumors
– increased expression of endogenous inhibitors of matrix
metalloproteinases
– phytoestrogenic activity involving interaction with the
estrogen a- and b-receptors of human
Proanthocyaninds
• Cranberry proanthocyanidins have been proved to
inhibit:
– ODC (ornithine decarboxylase) in epithelial cells
– To selectively inhibit the growth of H460 human large cell
lung carcinoma, HT-29 colon adenocarcinoma, and K562
chronic myelogenous leukemia cells
Cranberry peel
• The peel of cranberry fruit contains pentacyclic
triterpenoid ursoli acid which has shown to inhibit
growth of:
– Several leukemia cell lines
– A-549 human lung carcinoma
– Tumor colony formation of HT-29 and HCT116
models of colon cancer.
– Induces a high rate of apoptosis in MFC-7 breast
tumor cell line, HepG2 human hepatoblastoma cells
and HT-29 colon cells
Mechanisms for tumor inhibition:
(in vitro studies)
• Induction of apoptosis in cancer cells
• Decreased invasion and metastasis as a result of the
inhibition of MMPs
• Inhibition of ornithine decarboxylase expression
• Activity and inhibition of inflammatory processes
including cyclooxygenase (COX) activity
Cranberry’s health effects on
cardio vascular diseases
Cranberries and CVD
• Cardiovascular diseases are the leading cause of
death in both men and women in most developed
countries, including the United States (Chu, 2005)
Causes of CVD
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Increasing age
Gender
Heredity
Physical inactivity
Obesity
High blood pressure
High cholesterol
Stress
Tobacco
Alcohol
Diet
Cardiovascular Health
• According to recent studies, dietary modifications are
suggested to be an effective strategy to prevent CVD.
• The increase in intake of one daily serving of fruits
and vegetables translates to a 4% reduced risk of
CVD (Chu, 2005).
Cranberry Flavanoids
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Cranberries contain many flavonoids and phenolic
acids which studies have shown to have potent
antioxidant capacity.
1. Anthocyanins
2. Flavonols
3. Proanthocyanidins
Antioxidant mechanisms of Flavonoids
1. Direct radical scavenging
2. Down-regulation of radical production
3. Elimination of radical precursors, such as hydrogen
peroxide.
4. Metal chelation
5. Inhibition of xanthine oxidase
6. Elevation of endogenous antioxidants
Cranberries and CVD
• Cranberries have shown to have potent antioxidant
activity in preventing low density lipoprotein (LDL)
oxidation.
Low Density Lipoproteins
• Increased rate of LDL in intima initiates an
inflammatory response causing oxidation.
• Oxidation leads to leasions on the arteries, known as
fatty streaks.
• Oxidation of human LDL is involved with
development of atherosclerotic plaques in arteries,
leading to heart attacks and strokes.
How can cranberries help?
• Proanthocyanidins have shown the highest inhibitory
effect on copper-induced oxidation of LDL (Reed, 2002).
• Quercetin, a flavonol, is able to be rapidly absorbed
into the bloodstream of humans, and has shown
antioxidant effects in vitro. (Reed, 2002).
How can cranberries help?
• A study done by Chu et al (2005) showed that a single serving
of cranberry juice was found to significantly increase plasma
antioxidant levels up to 7 hours.
• The study measured the inhibition of LDL oxidation by
different concentrations of cranberry (Chu, 2005):
• 1mg cranberry/ml → 50.7% inhibition
• 2.5mg cranberry/ml → 71.41% inhibtion
• 5mg cranberry/ml → 94.7% inhibition
• 10mg cranberry/ml → 100% inhibition
LDL oxidation by Cranberries
Chu, 2005
How can cranberries help?
• A study done by Porter et al (2001), looked at the
actions of proanthocyanidins with inhibition of
copper induced LDL oxidation in vitro.
• Study looked at 6 different fractions:
• Fraction 2 → hydroxycinnamic acid and anthocyanins
• Fraction 3 → flavonols
• Fraction 4 → flavonols and few low molecular weight
proanthocyanidins
• Fraction 5 and 6 → proanthocyanidins
Effect of cranberry flavonoids on lag time
of copper induced LDL oxidation
proanthocyanidins
proanthocyanidins
Porter, 2001
How can cranberries help?
• A study done by Ruel et al (2005) looked at the
health benefits of drinking cranberry juice (Ocean
Spray’s Light Cranberry Juice Cocktail) at a daily dose
of 7ml/kg of body weight for 14 consecutive days.
How can cranberries help?
Plasma antioxidant capacity before
(white) and after (black) 14 day cranberry
juice supplementation
Oxidized LDL before (white) and
after (black) 14 day cranberry
juice supplementation
Ruel, 2005
In summary
• LDL oxidation is responsible for heart attacks and
strokes.
• Flavonoids in cranberries have shown to have potent
antioxidant activity.
• Cranberries are not a required compound in human
diet, however, a diet rich in cranberries could
possibly help prevent CVD.
Cranberries to prevent urinary
tract infections
Prevention as opposed to treatment.
Urinary Tract
• System responsible for
making urine and
carrying it out of the
body
• Includes:
– Bladder
– Kidneys
– Connecting tubes
How common are UTIs?
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How common are UTIs?
• One quarter of women
will experience what is
known as a UTI during
their lifetime
– Of these, another
quarter will suffer
recurrent infections.
Treatment
• Direct costs of treatments last year exceeded $1.6
billion.
• Antibiotic therapy is typical:
– Pathogens such as Escherichia coli, Proteus and
Pseudomonas are fimbriated gram-negative rods,
and the fimbriae attach the bacteria to epithelial
cells. These pathogens account for nearly all UTIs;
requiring antibiotic therapy.
• With treatment options hindered and expensive,
cranberries, particularly in the form of cranberry
juice, have been widely used for the prevention of
UTIs. Cranberry has been associated with preventing
UTIs for the last century. In recent years, physicians
have begun to recommend daily intake of cranberry
as a safe alternative to prevent UTIs. Cranberry juice,
especially in the form of a juice cocktail drink with
27% cranberry, is the usual choice for UTI prevention.
100% cranberry juice is highly acidic and thereby
diluted into palatable cocktail drinks.
• Cranberry juice is effective at preventing bacterial
adherence instead of displacing the bacteria already
attached to epithelial walls.
• Cranberry juice causes loss of fimbriae and
elongation of the bacterial cell wall.
• Evidence for the prevention of UTIs rather than
treatment, exists in studies done over a 12-month
period in women, citing two controlled, randomized,
double-blind, placebo-controlled experiments.
• Yet, no evidence exists that cranberries will treat UTI
once an infection is present.
For infection (UTIs) to develop, bacteria wants
to adhere to cells.
Since the adherence of many bacteria species to
cells is mediated by lectin-sugar interactions,
foods high in lectins or carbohydrates may
affect the infection process – cranberries.
Problems
• Potential problems arise
when considering any
phytochemical for
prevention and/or
treatment purposes.
• We are unable to tell who is most likely to benefit
from long-term treatment with cranberries.
• Nearly all studies done on cranberries have used
different preparations and amounts of cranberry or
cranberry extract. The optimal preparation and dose
have yet to be determined.
• Cranberry juice has a high oxalate content; there is a
risk for precipitate urinary stone formation with
regular use.
• The success of cranberries as a preventive agent
depends on the consumer. At present, cranberry is
not available as a prescription.
Conclusion:
• Cranberries have shown a wide variety of health
effects due to synergistic effects of its phytochemical
compounds.
• In vitro research has shown health benefits including
chemopreventive action, cardiovascular protection
and urinary tract infection prevention.
• Future steps include in vivo research to support in
vitro findings.
Questions?
References:
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Edition. Marcel Dekker, Inc: New York, NY. 165-203p.
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Chu Y. and R.H. Liu. 2005. Cranberries inhibit LDL oxidation and induce LDL receptor expression in
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