2005 Lycopene Pennington Biomedical Research Center Division of Education Heli J. Roy, PhD, RD Shanna Lundy, BS Phillip Brantley, PhD, Director

PBRC 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, beta- cryptoxanthin, lutein, and lycopene, but over 600 have been identified to date

PBRC 2005 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 Beta- cryptoxanthin, lycopene is not a provitamin A carotenoid, meaning that the body cannot convert lycopene into Vitamin A

PBRC 2005 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

PBRC 2005 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

PBRC 2005 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”

PBRC 2005 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

PBRC 2005 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

PBRC 2005 Lycopene Content of Selected Foods

FoodServingLycopene (micrograms) Tomato Paste, canned 1 c75,362 Tomato puree, canned 1 c54,385 Marinara sauce 1 c39,975 Tomato soup, canned 1 c25,615 Vegetable juice cocktail, canned 1 c23,337 Tomato juice, canned 1 c21,960 Watermelon, raw 1 wedge12,962 Tomatoes, raw 1 c4,631 Ketchup 1 tablespoon2,551 Pink grapefruit, raw ½ grapefruit1,745 Baked beans, canned 1 c1,298 Sweet red peppers, raw 1 c459

PBRC 2005 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

PBRC 2005 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

PBRC 2005 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

PBRC 2005 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

PBRC 2005 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

PBRC 2005 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

PBRC 2005 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

PBRC 2005 Free Radicals Environmental sources of free radicals include: –Environmental toxins and air pollutants- such as ozone and nitrogen dioxide –Sunlight –Ionizing radiation –Certain drugs –Cigarette smoke

PBRC 2005 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

PBRC 2005 Lycopene and Chronic Diseases Research Findings Overview: Digestive Tract Cancers Prostate Cancer Bladder, Cervical, Breast, Lung Cancers Cardiovascular Disease Other Diseases

PBRC 2005 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

PBRC 2005 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

PBRC 2005 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

PBRC 2005 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

PBRC 2005 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

PBRC 2005 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

PBRC 2005 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

PBRC 2005 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

PBRC 2005 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

PBRC 2005 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

PBRC 2005 References Giovannucci et al. A Prospective Study of Tomato Products, Lycopene, and Prostate Cancer Risk. JNCI :