Transcript Lycopene - Pennington Biomedical Research Center

Lycopene
Pennington Biomedical Research Center
Division of Education
Heli J. Roy, PhD, RD
Shanna Lundy, BS
Phillip Brantley, PhD, Director
2005
Lycopene: Information
• Belongs to a class referred to as carotenoids
• Carotenoids are yellow, orange, and red pigments
synthesized by plants
• In plants, their function is to absorb light in photosynthesis,
protecting plants against photosensitization
• The five principal carotenoids found in human plasma, as the
result of ingesting plants, include alpha and beta-carotene, betacryptoxanthin, lutein, and lycopene, but over 600 have been
identified to date
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Lycopene: Information
• Lycopene is what gives tomatoes, pink grapefruit,
watermelon, and guava their red color
• It has been estimated that 80% of the lycopene in the
US diet comes from tomatoes and tomato products
like tomato sauce, tomato paste, and catsup
• Unlike Alpha-carotene, Beta-carotene, and Betacryptoxanthin, lycopene is not a provitamin A
carotenoid, meaning that the body cannot convert
lycopene into Vitamin A
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Lycopene: Information
• Tomatoes and tomato products are the single best source of
lycopene, with only a short list of other foods containing much
lower amounts
• In tomatoes, lycopene content is affected by specific variety and
ripening stage
• Deep red varieties contain up to 50 mg/kg, while yellow types
may be as low as 5 mg/kg
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Lycopene: Information
• American lycopene intake averages 3.1 to 3.7 mg/d,
closely matching beta-carotene
• In contrast, British intake averages 1.1 mg/d and that for Finns is
even lower at 0.7 mg/d
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Lycopene: Information
• Was largely ignored for decades because of its lack of
provitamin A activity, long thought to be the distinguishing
characteristic among carotenoids
• In the 1960’s, during a case study which first documented
lycopenemia, an accumulation of lycopene in the body tissues,
the following was stated:
– “So far as is known, lycopene is neither toxic nor beneficial, but is
only an adventitious visitor to the body. Its failure to form Vitamin A
may account for its accumulation in the liver”
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Lycopene: Function
• Far from being inert, by virtue of its unique chemical
properties, studies have shown lycopene to possess superior
antioxidant abilities in comparison to other carotenoids
• It has the ability to quench singlet oxygen and prevent
oxidative damage to other molecules and cellular structures
because of its unique structure of: 11 conjugated double
bonds and no cyclic groups
• Because of this role, many researchers now believe that
lycopene may profoundly influence the evolution of several
chronic diseases in a tissue-specific manner
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Lycopene: Information
• Recent studies of lycopene bioavailability have shown that
cooking tomato products significantly increases lycopene
bioavailability compared to raw products, as does the presence
of a small amount of oil or fat
• This is because the absorption of carotenoids depends
on the presence of fat in the intestine
•
As little as 3-5 grams of fat in a meal appears sufficient to
ensure carotenoid absorption
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Lycopene Content of
Selected Foods
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Food
Serving
Lycopene
(micrograms)
Tomato Paste, canned
1c
75,362
Tomato puree, canned
1c
54,385
Marinara sauce
1c
39,975
Tomato soup, canned
1c
25,615
Vegetable juice cocktail,
canned
1c
23,337
Tomato juice, canned
1c
21,960
Watermelon, raw
1 wedge
12,962
Tomatoes, raw
1c
4,631
Ketchup
1 tablespoon
2,551
Pink grapefruit, raw
½ grapefruit
1,745
Baked beans, canned
1c
1,298
Sweet red peppers, raw
1c
459
Absorption
• The absorption of carotenoids is limited to a range of 10-30%
• Of this amount, the majority is excreted in the feces
• The low absorption and high excretion rate is partly due to the
fact that the carotenoids are tightly bound to large molecules,
forming protein complexes in foods
• Separation of carotenoids from protein complexes or dispersion
of carotenoid aggregates occurs upon heating these food items,
which, as previously mentioned, increases their bioavailability
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Factors that Affect Absorption
Rate of Carotenoids
• Level of dietary fat intake
– Studies comparing carotenoid absorption rate with a 40% fat
diet to a 20% showed a significant reduction in absorption
• Level of carotenoids ingested
– Intestinal absorption decreases significantly as carotenoid
intake increases
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Pathway of Carotenoids:
• Absorption pathway is similar to that of dietary fat
• Carotenoids are believed to passively diffuse from the micelles
across the intestinal cell membrane into the mucosal cell
• Once inside the intestinal cell, carotenoids may be converted to vitamin
A, those that are provitamin A carotenoids, or taken up by chylomicrons
which transport them to the bloodstream via the lymphatic system to
the liver
• From the liver, carotenoids reenter circulation carried by lipoproteins, in
similar proportions as cholesterol among the various fractions
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• Lycopene, which is more lipophilic because of its
non-polar chemical structure, appears to be carried
exclusively by LDL, residing deep within the core of the
lipoprotein, lipid layer
• Beta-carotene probably protrudes into the aqueous
interface of the lipoprotein
• The location of the carotenoid within the lipoprotein
molecule may influence tissue uptake
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Tissue Distribution:
Of Lycopene
• Because of its lipophilic nature, lycopene tends to accumulate in
body tissues
• It predominates in prostate, liver, adrenal glands, and testes,
with lycopene accounting for up to 80% of total carotenoid in
these latter two tissues
• Lycopene concentration in the testes and adrenals is up to 9X’s
higher than in the tissue with the second highest amount,
the liver
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Several factors can influence
lycopene tissue concentrations
• Higher carotenoid concentrations tend to occur in tissues with a
large number of LDL-receptors and high uptake of lipoproteins
the liver, adrenals, and testes
• Other factors include body mass index and waist circumference,
with both exhibiting an inverse relationship with lycopene
concentration in adipose tissue
• Gender- this same study reported up to 50% lower carotenoid
adipose levels in men compared to women
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Biological Activity
• The general mechanism by which carotenoids are thought to
influence the development of chronic disease is by preventing
oxidative damage in biological systems, which includes damage
to the cell membrane and other structures, DNA molecules,
lipids, and proteins
• This damage arises from exposure to free radicals
• Free radicals are molecules with an unpaired electron in their
outer atomic orbital, causing the molecule to be extremely
reactive
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Free Radicals
• Environmental sources of free radicals include:
– Environmental toxins and air pollutantssuch as ozone and nitrogen dioxide
– Sunlight
– Ionizing radiation
– Certain drugs
– Cigarette smoke
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Free Radicals
• The body can also produce free radicals during normal aerobic
respiration, the metabolism of fatty acids, and from an acute or
chronic immune responses
• From the usage of superoxide dismutase, glutathione
peroxidase, and dietary intake of the antioxidant nutrients,
Vitamins E and C, selenium, and the carotenoids, the body can
help fight off oxidative damage
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Lycopene and Chronic
Diseases
Research Findings
Overview:
Digestive Tract Cancers
Prostate Cancer
Bladder, Cervical, Breast, Lung Cancers
Cardiovascular Disease
Other Diseases
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Digestive Tract Cancers
Esophageal and Gastric cancers
• As early as 1979, researchers in Iran reported that weekly tomato
consumption was associated with a 40% reduction in risk for
esophageal cancer
• In 1989, a case controlled study of 2,175 participants was conducted
in Italy in high and low risk areas in order to assess the geographic
variation in mortality rates from gastric cancer
• Tomato products showed a significant inverse relationship
with the occurrence of gastric cancer
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Digestive Tract Cancers
Pancreatic cancer
• In one case-controlled study of 44 matched control subjects and
22 diagnosed cases of pancreatic cancer, it was found that the
greatest difference between controls and cancer cases was in
serum lycopene concentrations
• In the second of two studies, researchers found that low serum
lycopene was significantly correlated with pancreatic cancer
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Prostate Cancers
• Strongest known link between lycopene and chronic disease
• From the Health Professionals Follow-Up Study (HPFS)
conducted from 1986 through January 31, 1992, it was
suggested that frequent intake of tomato products or lycopene,
is associated with reduced risk of prostate cancer
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Prostate Cancers:
Giovannucci et al.
• Evaluated additional data from the HPFS to determine if the
association between lycopene and prostate cancer would persist
• They gathered prostate cancer cases from 1986 through
January 31, 1998, among 47,365 HPFS participants who
completed dietary questionnaires in 1986, 1990, and 1994
• From 1986 to 1998, 2,481 men in the study developed
prostate cancer
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Their Findings
Giovannucci et al.
• For the entire period of 1986 through 1998, using the cumulative
average of the three dietary questionnaires used in the study,
lycopene intake was associated with reduced risk of prostate
cancer
• Intake of tomato sauce, the primary source of bioavailable
lycopene, was associated with an even greater reduction in
prostate cancer risk
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Bladder, Cervical, Breast,
Lung Cancers
• Researchers at the John Hopkins University School of Hygiene
and Public Health reported on a study of 25,802 participants
• 35 cases of bladder cancer were diagnosed after the 12-year
study period, with the risk increasing with decreasing serum
levels of both lycopene and selenium
• Most studies show that lung and breast cancer are not related to
serum lycopene levels, although there is a recent study by the
Harvard School of Public Health linking breast cancer with
lycopene
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Bladder, Cervical, Breast,
Lung Cancers
• Study results have been mixed for cervical cancers
• Although, there has been a recent investigation showing a slight
link between lycopene and cervical cancer
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Cardiovascular Disease
• Oxidative damage is believed to be the underlying mechanism in the
etiology of cardiovascular disease (CVD)
• More recently, the multifaceted role of oxidatively modified LDL has
been proposed as being instrumental in atherogenesis
• It is believed that, along with Vitamin E, carotenoids may function as a
network to protect LDL against oxidation
• Its believed that once Vitamin E is depleted, the carotenoids may
become involved as a second barrier, with LDL succumbing to oxidation
only when the carotenoids are destroyed
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Cardiovascular Disease
In Smokers
• Because of reactive oxygen species found in smoke which
increase LDL oxidation, smokers are at higher risk for
development of CVD
• A recent study of smokers indicated that increased plasma
concentrations of lycopene, Vitamin C, and beta-carotene were
significantly inversely associated with several parameters
indicative of oxidative stress, including oxidation of LDL
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Other Diseases
• Animal and laboratory studies have shown that carotenoids
exert immunomodulatory effects by influencing T and B
lymphocytes, natural-killer cells, and macrophages
• In patients with HIV infection, even with adequate dietary
intake, several have specifically identified carotenoid
deficiencies
• Relationships between lycopene and functional capacity in
the elderly exist, indicating that deficiencies may
significantly decrease self-care ability
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References
• http://sun.science.wayne.edu/~nfs/dietetics/lyco.htm
• http://lpi.oregonstate.edu/infocenter/phytochemicals/carotenoids/index.html
•
Giovannucci et al. A Prospective Study of Tomato Products, Lycopene, and Prostate
Cancer Risk. JNCI. 2002. 94:5 391-398
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