Download Cancer: Current Research

Health Benefits of
Blueberries
Introduction
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The consumption of blueberries may have some
beneficial effects against chronic diseases including
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Alzheimer’s Disease
Diabetes
Cardiovascular Diseases
Cancer
Health benefits are associated to its polyphenolic
compounds
There are no current reports related to toxicity levels
Introduction
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Chemical composition may vary according to
season, environment, and variety
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Blueberries are rich in:
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Anthocyanins
Proanthocyanidins
Flavan-3-ols
Flavonols
Phenolic acids
Hidroxycinnamic acid
(Atalay and others 2003, Schmidt and others 2004, 2006,)
Alzheimer’s Disease (AD)
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4.5 million Americans have AD. Ten percent of those older than
65, and 1 of 2 people at age 85 will be diagnosed with AD
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Women have a greater incidence than men.
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Alzheimer causes:
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Genetics (Chromosome 21)
Head Trauma
Viral agents
Environmental factors
 Organic solvents, aluminum, coffee, alcohol
consumption, and medication use.
(McCollom 2004)
Alzheimer’s Disease
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AD is a dementia disease, progressive and
degenerative causing the loss of intellectual
functions:
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Thinking
Remembering
Sequencing
Reasoning
Behavior
AD is characterized by the neurofibrillary tangles and
senile plaques (amyloid β peptide) (McCollom 2004, Ramassamy 2006).
Amyloid β peptide toxicity
Toxicity
Mechanisms
Apoptosis
Activation of
Mitochondrial the NF-κB
Dysfunction
Neuronal Death
(Ramassamy 2006)
Consequences
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Toxicity of the amyloid β peptide involves transition
metals, formation of hydrogen peroxide, accumulation of
reactive oxygen species and oxidative stress (Ramassamy 2006).
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The brain is especially susceptible to oxidative stress
since it weighs 2% of the body mass and it utilizes 20%
of the total oxygen consumed by the body.
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Normal brain aging is also associated with elevated
levels of neuroinflammation (activation of NF-κB) which
increases ROS production (Lau and others 2005).
Food intake benefits
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Epidemiological evidence indicates that phytochemicas
may provide neuroprotection against age-related
neurodegenerative disorders (Ramassamy 2006).
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Polyphenols could have therapeutical potential for these
pathologies.
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Blueberries, have been found to be beneficial to brain
function. Blueberries contain high levels of polyphenolic
flavonoids (Dunlap and others 2005, Duffy and others 2007).
AD: Current Research
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Lau and others (2005)
Aged rats supplemented with blueberries extracts
showed:
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Reversed age-related deficits in neuronal and cognitive function
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By increasing the levels of ERK and CKC which are important in
mediating cognitive functions especially in conversion to shortterm to long-term memory
Increase in hippocampal, plasticity and cognitive performance in
mice via concerted mechanisms involving
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Neurogenesis, neurotrophic factor IGF-1 and its receptor, and
MAP kinase signal transduction cascades
Diabetes Statistics
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20.8 million children and adults in the U.S, or 7%
of the population have diabetes (ADA 2007)
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180 million people worldwide
(WHO 2007)
Diabetes mellitus
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Chronic disease
 Deficiency in production of insulin by the pancreas
 Ineffectiveness of the insulin produced
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Increased concentrations of glucose in the blood
damage many of the body's systems, in particular the
blood vessels and nerves (WHO 2007)
Type 1 diabetes
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The pancreas fails to produce the insulin which is
essential for survival
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Most frequently
 Children and adolescents (WHO 2007)
Type 2 diabetes
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The body's inability to respond properly to the action
of insulin produced by the pancreas.
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More common (90% of cases worldwide)
 Adults
 It is being noted increasingly in adolescents (WHO 2007)
Importance of food intake
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Because food intake affects the body's need for insulin
and insulin's ability to lower blood sugar, diet is the basis
of diabetes treatment (FDA 2007)
Studies in healthy subjects and those at risk for type 2
diabetes support the importance of including foods
containing
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Carbohydrate particularly from:
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Whole grains
Fruits, vegetables
Low-fat milk (ADA, 2002)
Diabetes and oxidative stress
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Diabetes may be a state of increased oxidative stress
 There has been interest in prescribing antioxidant
vitamins to people with diabetes (ADA 2002)
Blueberry constituents are likely to act by mechanisms
that:
 Counteract oxidative stress
 Decrease inflammation
 Modulate molecular interactions and expression of
genes associated with disease processes (Neto 2007)
Diabetes: Current Research
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Haddad 2001performed an ethnopharmacological survey
of the most used antidiabetic medicinal in Québec and
Morocco
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Vaccinium spp. (blueberry) received first place
Improves the microvascular and lipid perturbations
associated with diabetes
Diabetes: Current Research
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Shane (2001) investigated blueberry’s leaves
 Traditionally been used to control blood sugar levels
in people with diabetes
 Lowers blood sugar
 Could make the effect of diabetes medication
stronger
Diabetes: Current Research
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Cignarella and others (1996 ) studied the effect of an
hydroalcoholic extract of blueberry leaves orally
administered to diabetic rats.
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Plasma glucose levels were consistently found to drop
by about 26%
Diabetes: Current Research
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Eveleen (2006) tested blood glucose levels in diabetic
and non diabetic subjects
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100 g of fresh berries for one month
14.54 and 9.9 % decrease in blood sugar levels in
diabetic and non diabetic subjects respectively.
Diabetes: Current Research
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Martineau and others (2006) tested ethanol extracts
of root, stem, leaf and fruit using multiple cellbased bioassays
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Tested at 12.5 µg/ml
Blueberries have insuline-like activity
Exhibit anti-diabetic effects in pancreatic  cells
Cardiovascular Disease (CVD)
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A general term for all diseases of the heart and blood
vessels
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Almost 1 million Americans die of CVD every year
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40.6% of all deaths
CVD is nation’s No. 1 killer
CDC 2007
Chronic Endothelial Injury and the
Progression of CVD
Atherosclerosis
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Hardening, loss of elasticity,
and thickening of arterial walls
with narrowing of the lumen of
the artery.
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Principal cause of myocardial
infarction and stroke (heart
and brain attack).
CVD: Current Research
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Heinonen and others (1998) reported the antioxidant
activity of phenolic compounds present in berries by two
coppercatalyzed in vitro oxidation assays:
 LDL
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LDL oxidation was inhibited by 68.4 –89.0 % at 10 M and
20 M GAE respectively
Lecithin liposomes
 By 41.2 and 77.1 % measured by the formation of
hydroperoxides (ROOH) and hexanal respectively at
concentration 20 M GAE
CVD: Current Research
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Prior and Cooke (2004) studied the inhibition of platelet
aggregation
 An inhibition of 38% of platelet aggregation was
observed in individuals who consumed 1 cup of
blueberries in their normal diet for 2 weeks
CVD: Current Research
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Norton and others (2005) studied how a blueberry
enriched diet protected rat arteries from contracting
 Rats fed with an enriched diet generated less force in
response to phenylephrine, a stress hormone, than
did arteries in rats fed the same diet without
blueberries
CVD: Current Research
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Ahmet and others (2007) studied how a blueberryenriched diet protects rat’s heart from Ischemic damage
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The myocardial infarction (MI) in blueberry diet was
24% less than in control diet
Risk Factors You Can Change, Treat or
Modify
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High blood pressure
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High blood cholesterol
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Tobacco smoke
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Overweight and obesity
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Physical inactivity
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Diabetes (AHA 2007)
Make Healthy Lifestyle Changes
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Control high blood pressure
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Don’t smoke. If you smoke, quit.
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Maintain healthy cholesterol levels
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Be physically active
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Control or delay the onset of diabetes
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Reduce excess weight or maintain a healthy weight
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Eat a healthful diet
F&V.
Cancer Statistics
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Cancer is the result of a combination of one or more
factors:
 Genetic mutation
 Environment
 Lifestyle
 Age
 Diet
Cancer Statistics
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According to the WHO, there are every year more
than 10 millions new cancer cases in the world (Surh
2003) and this number may be double in the next 20
years (Pecorino 2006).
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In 2003, 1.3 millions new cases of cancer were
diagnosed in USA and from those 550, 000 died
from cancer (Surh 2003).
Cancer Statistics
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Cancer of the lung and the
large intestin (colon and
rectum) are the most
significant in both genders.
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Specific cancers by gender:
 Women: Breast
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Men: Prostate
(Schulz 2005)
(Cancer Research Institute 2003)
Cancer Statistics
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Diet has been identified as responsible of influencing
the cancer risk.
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Researchers have estimated that about 30 - 40% of
all cancer cases are related to dietary habits.
(Davis and Milner 2007; Surh 2003)
Cancer
“Group of diseases (>200) characterized by
unregulated cell growth and the invasion and
spread of cells from the site of origin to other site
in the body.”
Cancer
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Carcinogenesis:
“Process that involves several steps in which distinct
molecular and cellular alteration occurs”
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Three steps:
 Initiation
 Promotion
 Progression
(D'Ambrosio 2007; Surh 2003)
Cancer and Phytochemicals
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Prevention of initiation process by blueberry
phytochemicals may involve:
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Inactivation of carcinogens
Inhibition of phase I enzymes
Induction of phase II enzymes
Blueberry phytochemicals may also inhibit promotion
or progression by eliminating cancer cells or inhibiting
their growth.
Cancer: Current Research
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Kraft and others (2005) worked with blueberry extracts to
study the chemoprevention effect.
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Chemical composition may protect against the initiation,
promotion and progression of carcinogenesis.
Chemical compounds found were phytosterols, phenolic
acids, flavan-3-ols, anthocyanins, and oligomeric
proanthocyanidins; that may interact synergistically,
concomitantly, or additively to enhance its bioactivity.
Cancer: Current Studies
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Schmidt and others (2004) worked with fractions rich in
proanthocyanidins demonstrated a significance positive
correlation between proanthocyanidins content and
antiproliferation assays.
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Schmidt and others (2006) studied wild and cultivated
blueberry to see bioactivity against the proliferation
prostate cancer cell lines.
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Blueberry (wild and cultivated) fractions rich in
proanthocyanidins have an effect on androgen dependant
growth of cancer cell line.
Cancer: Current Research
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Srivastava and others (2007) identified the presence of
delphinidin, cyanidin, peonidin, petunidin and malvidin as
the major anthocyanins in blueberry extracts.
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Anthocyanins rich fraction might increase apoptosis as
well as the activity of detoxifying enzymes quinone
reductase and glutathione S-Trasnferesase.
Cancer: Current Research
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Smith and others (2000), studied the bioactive activity of
several fractions of blueberry extracts.
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Crude extract made of 70% acetone (proanthocyanidins
and anthocyanins), showed induction of quinone
reductase activity, which indicates a potential for
inhibiting the initiation stage of carcinogenesis.
Cancer: Current Research
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Yi and others (2005) studied the bioactivity of phenolic
compounds in several fractions obtained from rabbiteye
blueberry to assess the potential as an antiproliferative
and apoptosis induction on colon cancer cells.
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Phenolic compounds could inhibit cancer cell proliferation
and induce cell apoptosis.
From the four fractions obtained (phenolic acids, tannins,
flavonols and anthocyanins), the anthocyanins fraction
showed the highest antiproliferation and induction of
apoptosis.