[advances in food and nutrition research] volume 51 || lycopene

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  • B. Cancer

    C. Cardiovascular Diseases

    D. Osteoporosis and Other Bone DisordersE. Hypertension

    F. Male Infertility

    G. Neurodegenerative Diseases

    H. Other Human Diseases

    IX. Dietary Intake Levels of Lycopene

    X. Conclusions


    Oxidative stress is now recognized as an important etiological factor inVIII.the c


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    Eycopene and Human Diseases

    . Lycopene and the Prevention of Chronic Diseases: The Hypothesisusation of several chronic diseases including cancer, cardio

    es, osteoporosis, and diabetes. Antioxidants play an import

    tigating the damaging eVects of oxidative stress on cells. Lycnoid antioxidant, has received considerable scientific int

    years. Epidemiological, tissue culture, and animal studies


    lsevier Inc. All rights reserved DOI: 10.1016/S1043-45VII. Mechanisms of Action of Lycopeneof LycopeneVI. BStability and Antioxidant Properties of Lycopene and Its Isomers

    ioavailability, Tissue Distribution, Metabolism, and SafetyV.Biological MaterialsIV. AChemistry and Dietary Sources of Lycopene

    nalytical Methods of Measuring Lycopene in Food and OtherII.

    III.Oxidative Stress and Chronic DiseasesI. IntroductionUniversity of Toronto, Toronto, Ontario, Canada{Department of Medicine, Calcium Research Laboratory, St. Michaels Hospital{London Regional Cancer Program, London, Ontario, CanadaUniversity of Toronto, Toronto, Ontario, Canada*Department of Nutritional Sciences, Faculty of MedicineA. V. RAO,* M. R. RAY, AND L. G. RAO{ {LYCOPENEvascular

    ant role

    opene, a

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    N: 1043-4526


  • chronic diseases, recognizing the importance of antioxidants, have recom-

    100 A. V. RAO ET AL.mended an increase in the consumption of fruits and vegetables that are

    good sources of dietary antioxidants. In addition to traditional antioxidant

    vitamins, such as vitamins A, E, and C, fruits and vegetables also contain

    several phytonutrient antioxidants. The two important classes of phytonutrient

    antioxidants include the carotenoids and polyphenols. In vitro cell culture

    studies, laboratory animal studies, case control and cohort studies, and dietary

    intervention studies have all provided evidence in support of the role of anti-

    oxidants in the prevention of cancer and other chronic diseases. The focus of

    this chapter will be on lycopene, a potent carotenoid antioxidant. Since animal

    and human experimental studies on the role of lycopene in cancer prevention

    are beginning to be undertaken, a brief overview of some important molecular

    markers of cancer, which could be used in these studies, is also reviewed.convincing evidence supporting the role of lycopene in the prevention of

    chronic diseases. Human intervention studies are now being conducted to

    validate epidemiological observations and to understand the mechanisms of

    action of lycopene in disease prevention. To obtain a better understanding of

    the role of lycopene in human health, this chapter reviews the most recent

    information pertaining to its chemistry, bioavailability, metabolism, role in

    the prevention of prostate cancer and cancer of other target organs, its role

    in cardiovascular diseases, osteoporosis, hypertension, and male infertility.

    A discussion of the most relevant molecular markers of cancer is also

    included as a guide to future researchers in this area. The chapter concludes

    by reviewing global intake levels of lycopene, suggested levels of intake, and

    future research directions.


    Lycopene, as a dietary source of a carotenoid antioxidant, has attracted con-

    siderable interest in recent years as an important phytochemical with a benefi-

    cial role in human health. Chronic diseases including cancer, cardiovascular

    disease, diabetes, and osteoporosis are the major causes of morbidity and

    mortality in the Western World. Along with genetic factors and age, lifestyle

    factors and diet are also considered important risk factors for these diseases

    (Agarwal and Rao, 2000a). The role of oxidative stress induced by reactive

    oxygen species (ROS) and the oxidative damage of important biomolecules is

    one of the main foci of research related to human diseases. Oxidative stress is

    thought to be involved in the cause and progression of several chronic diseases

    (Rao andRao, 2004). Antioxidants are agents that inactivateROS and provide

    protection from oxidative damage. Dietary guidelines for the prevention of

  • fluid levels of several biomarkers of oxidized lipids, proteins, and DNA have

    LYCOPENE 101been shown during aging and also in patients with cancer and cardiovascular

    diseases (Amesetal., 1996;Halliwelletal., 1995;Pincemail, 1995;Stadtman,1992;The authors consider this to be important information in planning future

    animal and human clinical and intervention studies.


    ROS are highly reactive oxidant molecules that are generated endogenously

    through regular metabolic activity, lifestyle activities, such as smoking and

    exercise, environmental factors, such as pollution and ultra violet radiation,

    and diet. Being highly reactive, they can cause oxidative damage to cellular

    components such as lipids, proteins, and DNA (Agarwal and Rao, 2000a).

    Under normal circumstances, presence of endogenous repairmechanisms, such

    as the antioxidant enzymes including superoxide dismutase (SOD), glutathione

    peroxidase (GPx) and catalase and antioxidant vitamins, minerals, and phyto-

    nutrients, help repair the damaged biomolecules. However, when these defense

    mechanisms are overwhelmed by ROS, it leads to permanent damage of the

    biomolecules resulting in increased risk of chronic diseases. Lipid peroxidation

    products are increased in a variety of oxidative stress conditions (Witztum,

    1994). Premenopausalwomenwith highmammographic tissue densities at high

    risk for breast cancer excrete higher levels of the lipid peroxidation product

    malondialdehyde (Boyd andMcGuire, 1990; Boyd et al., 1995).A 20% increase

    in the levels of lipid peroxides were found in prostate cancer patients compared

    to their matched controls with retinoic acid therapy (Rigas et al., 1994).

    Oxidation of the low-density lipoprotein (LDL) has been associated with

    increased formation of atherosclerotic plaque, leading to coronary heart dis-

    ease (CHD) (Arab and Steck, 2000; Parthasarathy et al., 1992; Rao, 2002b).

    Similarly, DNA oxidation increases the risk of cancers and other pathological

    disorders. Cancer tissues contain increased levels of oxidized DNA adducts

    (Loft and Poulsen, 1996;Musarrat et al., 1996;Wang et al., 1996). Oxidation of

    intercellular proteins results in functional changes of enzymes that modulate

    cellular metabolism (Rao and Agarwal, 2000). Both DNA and protein oxida-

    tion are associated with the aging process (Ames et al., 1993). ROS also induce

    the expression of a wide variety of transcription factors, such as NFkB, AP1,

    and oncogenes, such as c-fos and c-jun. Conformational changes are found in

    p53 protein, whichmimic the mutant phenotype induced byROS (Hainaut and

    Miller, 1993; Toledano and Leonard, 1991; Wasylyk and Wasylyk, 1993; Wei,

    1992). By inducing these alterations, ROS can influence cell cycle mechanisms

    and ultimately lead to human health disorders. Increases in the tissue and body

  • lycopene has lmax of 472 nm and e% 3450 (Rao and Agarwal, 1999). It

    102 A. V. RAO ET AL.is an open chain hydrocarbon containing 11 conjugated and 2 nonconju-

    gated double bonds arranged in a linear array. As with other carotenoids,

    the double bonds in lycopene can undergo isomerization from trans to mono

    or ply-cis isomers by light, thermal energy, and chemical reactions. All-trans,Witztum, 1994). Dietary antioxida nt s, such as lycopene, c an protect lipids,

    proteins, a nd DNA from o xidation and play a role in t he prevention of s uch



    Lyc opene belon gs to the fami ly of carote noid compoun ds fou nd in frui ts,

    vege tables an d green plants . In plants these comp ounds are part of the

    phot osynthet ic machi nery and are responsib le for the yell ow, orange, and

    red co lors of fruits and vegeta bles. They are synthes ized by plants a nd

    micr oorganis ms but not by anima ls and hum ans. They are impor tant dieta ry

    sou rces of vitamin A an d are also excell ent antiox idants (Paiva and Ress ell,

    1999 ). More than 600 caroten oids are found in nature, about 40 of whi ch

    are present in a typical human diet, and abo ut 20 ha ve been identifi ed in blood

    an d tissues (Agarw al and Rao, 2000b). The princip al carote noids present in

    the diet an d huma n body are b-carot ene, a-carot ene, lycopene, a -cryptox-an thine, lutei n, a nd zeaxant hin, accoun ting for ove r 9 0% of all carote noids

    ( Gers ter, 1997 ). All carote noids posses certa in common chemi cal feat ures

    co nsisting of a polyis opreno id structure, a long conjugat ed chain of doubl e

    bonds in the central pos ition of the molec ules, an d a nea r bilateral symme try

    around the central double bond (Britton, 1995). However, modifications in

    the base structure by cyclization of the end groups and by introduction of


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