CMAJ • SEPT. 19, 2000; 163 (6) 739
© 2000 Canadian Medical Association or its licensors
Drs. Agarwal and Rao are
with the Department of
Nutritional Sciences, Faculty
of Medicine, University of
Toronto, Toronto, Ont.
This article has been peer reviewed.
LYCOPENE IS A CAROTENOID THAT IS PRESENT IN TOMATOES
, processed tomato products
and other fruits. It is one of the most potent antioxidants among dietary
carotenoids. Dietary intake of tomatoes and tomato products containing lycopene
has been shown to be associated with a decreased risk of chronic diseases, such as
cancer and cardiovascular disease. Serum and tissue lycopene levels have been
found to be inversely related to the incidence of several types of cancer, including
breast cancer and prostate cancer. Although the antioxidant properties of lycopene
are thought to be primarily responsible for its beneficial effects, evidence is accu-
mulating to suggest that other mechanisms may also be involved. In this article we
outline the possible mechanisms of action of lycopene and review the current un-
derstanding of its role in human health and disease prevention.
hronic diseases, including cancer and cardiovascular disease, are the main
causes of death in the Western world. Along with genetic factors and age,
lifestyle and diet are also considered important risk factors.
About 50% of
all cancers have been attributed to diet.
Oxidative stress induced by reactive oxygen species is one of the main foci of re-
cent research related to cancer and cardiovascular disease. Reactive oxygen species
are highly reactive oxidant molecules that are generated endogenously through reg-
ular metabolic activity, lifestyle activity and diet. They react with cellular compo-
nents, causing oxidative damage to such critical cellular biomolecules as lipids, pro-
teins and DNA. There is strong evidence that this damage may play a significant
role in the causation of several chronic diseases.
Antioxidants are protective agents that inactivate reactive oxygen species and
therefore significantly delay or prevent oxidative damage. Antioxidants such as su-
peroxide dismutase, catalase and glutathione peroxidase are naturally present within
human cells. In addition, antioxidants such as vitamin E, vitamin C, polyphenols
and carotenoids are available from food. Current dietary guidelines to combat
chronic diseases, including cancer and coronary artery disease, recommend in-
creased intake of plant foods, including fruits and vegetables, which are rich sources
The role of dietary antioxidants, including vitamin C, vitamin E,
carotenoids and polyphenols, in disease prevention has received much attention in
These antioxidants appear to have a wide range of anticancer and
These observations may explain the epidemiological
data indicating that diets rich in fruits and vegetables are associated with a reduced
risk of numerous chronic diseases.
Another dietary antioxidant thought to be important in the defence against oxida-
tion is lycopene, of which tomatoes are an important dietary source.
a natural pigment synthesized by plants and microorganisms but not by animals. It is
a carotenoid, an acyclic isomer of β-carotene. Lycopene is a highly unsaturated hy-
drocarbon containing 11 conjugated and 2 unconjugated double bonds. As a polyene
it undergoes cis-trans isomerization induced by light, thermal energy and chemical
reactions (Fig. 1).
Lycopene from natural plant sources exists predominantly in an
all-trans configuration, the most thermodynamically stable form.
plasma, lycopene is present as an isomeric mixture, with 50% as cis isomers.
Lycopene is one of the most potent antioxidants,
with a singlet-oxygen-
Tomato lycopene and its role
in human health and chronic diseases
Sanjiv Agarwal, Akkinappally Venketeshwer Rao
Table of Contents
Return to September 19, 2000
quenching ability twice as high as that of β-carotene and
10 times higher than that of α-tocopherol.
It is the most
predominant carotenoid in human plasma. Its level is af-
fected by several biological and lifestyle factors.
to their lipophilic nature, lycopene and other carotenoids
are found to concentrate in low-density and very-low-den-
sity lipoprotein fractions of the serum.
Lycopene is also
found to concentrate in the adrenal gland, testes, liver and
prostate gland, where it is the most prominent caro-
Table 1 shows the lycopene levels in various hu-
man and rat tissues.
Tissue-specific lycopene distribu-
tion may be important in the role of this antioxidant.
However, unlike other carotenoids, lycopene levels in
serum or tissues do not correlate well with overall intake
of fruits and vegetables.
Mechanisms of action
The biological activities of carotenoids such as β-
carotene are related in general to their ability to form vita-
min A within the body.
Since lycopene lacks the β-ionone
ring structure, it cannot form vitamin A.
Its biological ef-
fects in humans have therefore been attributed to mecha-
nisms other than vitamin A. Two major hypotheses have
been proposed to explain the anticarcinogenic and an-
tiatherogenic activities of lycopene: nonoxidative and ox-
idative mechanisms. The proposed mechanisms for the role
of lycopene in the prevention of chronic diseases are sum-
marized in Fig. 2.
Among the nonoxidative mechanisms, the anticarcino-
genic effects of lycopene have been suggested to be due to
regulation of gap-junction communication in mouse em-
bryo fibroblast cells.
Lycopene is hypothesized to sup-
press carcinogen-induced phosphorylation of regulatory
proteins such as p53 and Rb antioncogenes and stop cell
division at the G
cell cycle phase.
Astorg and col-
proposed that lycopene-induced modulation of
the liver metabolizing enzyme, cytochrome P450 2E1, was
the underlying mechanism of protection against carcino-
gen-induced preneoplastic lesions in the rat liver. Prelimi-
nary in vitro evidence also indicates that lycopene reduces
cellular proliferation induced by insulin-like growth fac-
tors, which are potent mitogens, in various cancer cell
Regulation of intrathymic T-cell differentiation (im-
munomodulation) was suggested to be the mechanism for
suppression of mammary tumour growth by lycopene
treatments in SHN retired mice.
Lycopene also has
been shown to act as a hypocholesterolemic agent by
inhibiting HMG–CoA (3-hydroxy-3-methylglutaryl–
coenzyme A) reductase.
Lycopene has been hypothesized to prevent carcinogen-
esis and atherogenesis by protecting critical cellular bio-
molecules, including lipids, lipoproteins, proteins and
In healthy human subjects, lycopene- or tomato-
free diets resulted in loss of lycopene and increased lipid
whereas dietary supplementation with lycopene
Agarwal and Rao
740 JAMC • 19 SEPT. 2000; 163 (6)
Table 1: Re
orted mean l
ene levels in human
Mean lycopene level (and SD),
nmol/g wet weight
Tissue Humans Rats
Testes 4.34–21.36 NA
Spleen NA 21.21 (2.22)
Adrenal gland 1.90–21.60 NA
Liver 1.28–5.72 20.30 (1.90)
Prostate gland 0.80 0.32 (0.06)
Breast 0.78 NA
Pancreas 0.70 NA
Lung 0.22–0.57 0.115 (0.015)
Heart NA 0.08 (0.03)
Kidney 0.15–0.62 NA
Colon 0.31 0.046 (0.006)
Skin 0.42 NA
Ovary 0.30 NA
Stomach 0.20 NA
Brain ND 0.017 (0.006)
Note: SD = standard deviation, NA = not available, ND = not detectable.
*Fischer 344 male rats were fed the AIN-93M diet supplemented with 10 ppm o
lycopene for 2 months (AIN = American Institute of Nutrition).
Fig. 1: Structures of trans and cis isomers of lycopene.
for 1 week increased serum lycopene levels and reduced en-
dogenous levels of oxidation of lipids, proteins, lipoproteins
Patients with prostate cancer were found to
have low levels of lycopene and high levels of oxidation of
serum lipids and proteins.
Risk of cancer
The Mediterranean diet, which is rich in vegetables and
fruits, including tomatoes, has been suggested to be re-
sponsible for the lower cancer rates in that region.
intake of tomatoes and tomato products has been found to
be associated with a lower risk of a variety of cancers in sev-
eral epidemiological studies.
A high intake of tomatoes
was linked to protective effects against digestive tract can-
cers in a case–control study
and a 50% reduction in rates
of death from cancers at all sites in an elderly US popula-
The most impressive results come from the US
Health Professionals Follow-up Study, which evaluated the
intake of various carotenoids and retinol, from a food-fre-
quency questionnaire, in relation to risk of prostate can-
The estimated intake of lycopene from various
tomato products was inversely related to the risk of prostate
cancer. This result was not observed with any other caro-
tenoid. A reduction in risk of almost 35% was observed for
a consumption frequency of 10 or more servings of tomato
products per week, and the protective effects were even
stronger with more advanced or aggressive prostate cancer.
In recent studies serum and tissue levels of lycopene were
shown to be inversely associated with the risk of breast can-
and prostate cancer;
no significant association with
other important carotenoids, including β-carotene, was ob-
recently reviewed 72 epidemiolog-
ical studies, including ecological, case–control, dietary and
blood-specimen-based investigations of tomatoes, tomato-
based products, lycopene and cancer. In 57 studies there
was an inverse association between tomato intake or circu-
lating lycopene levels and risk of several types of cancer; in
35 cases the association was statistically significant. None of
the studies showed adverse effects of high tomato intake or
high lycopene levels.
Although the epidemiological evidence of the role of
Role of lycopene in human health
CMAJ • SEPT. 19, 2000; 163 (6) 741
Fig. 2: Proposed mechanisms for the role of lycopene in preventing chronic diseases. Dietary lycopene may increase the lyco-
pene status in the body and, acting as an antioxidant, may trap reactive oxygen species, increase the overall antioxidant poten-
tial or reduce the oxidative damage to lipid (lipoproteins, membrane lipids), proteins (important enzymes) and DNA (genetic
material), thereby lowering oxidative stress. This reduced oxidative stress may lead to reduced risk for cancer and cardiovascu-
lar disease. Alternatively, the increased lycopene status in the body may regulate gene functions, improve intercell communica-
tion, modulate hormone and immune response, or regulate metabolism, thus lowering the risk for chronic disease. These mech-
anisms may also be interrelated and may operate simultaneously to provide health benefits.
lycopene in cancer prevention is persuasive, this role re-
mains to be proven. There are few human intervention tri-
als investigating the effectiveness of lycopene in lowering
cancer risk. Most of the workers have investigated the ef-
fects of tomato or tomato product (lycopene) supplementa-
tion on oxidative damage to lipids, proteins and DNA.
preliminary report has indicated that tomato extract sup-
plementation in the form of oleoresin capsules lowers the
levels of prostate-specific antigen in patients with prostate
Risk of cardiovascular disease
Oxidation of low-density lipoproteins, which carry cho-
lesterol into the blood stream, may play an important role in
the causation of atherosclerosis.
Antioxidant nutrients are
believed to slow the progression of atherosclerosis because of
their ability to inhibit damaging oxidative processes.
Several controlled clinical trials and epidemiological studies
have provided evidence for the protective effect of vitamin E,
which has been ascribed to its antioxidant properties.
However, in the recently completed Heart Outcomes Pre-
vention Evaluation (HOPE) Study, supplementation with
400 IU/d of vitamin E for 4.5 years did not result in any ben-
eficial effects on cardiovascular events in patients at high
In contrast, other studies indicated that consuming
tomatoes and tomato products containing lycopene reduced
the risk of cardiovascular disease.
In a multicentre case–control study, the relation between
antioxidant status and acute myocardial infarction was eval-
Subjects were recruited from 10 European countries
to maximize the variability in exposure within the study.
Adipose tissue antioxidant levels, which are better indicators
of long-term exposure than blood antioxidant levels, were
used as markers of antioxidant status. Biopsy specimens of
adipose tissue were taken directly after the infarction and
were analysed for various carotenoids. After adjustment for
a range of dietary variables, only lycopene levels, and not
β-carotene levels, were found to be protective.
A study from Johns Hopkins University, Baltimore,
showed that smokers with low levels of circulating caro-
tenoids were at increased risk for subsequent myocardial
Lower blood lycopene levels were also found
to be associated with increased risk for and death from
coronary artery disease in a population study comparing
Lithuanian and Swedish cohorts with different rates of
death from coronary artery disease.
Food sources and bioavailability
Red fruits and vegetables, including tomatoes, water-
melons, pink grapefruits, apricots and pink guavas, contain
Processed tomato products, such as juice,
ketchup, paste, sauce and soup, all are good dietary sources
of lycopene. In a recent study in our laboratory, the average
daily dietary intake of lycopene, assessed by means of a
food-frequency questionnaire, was estimated to be 25 mg/d
with processed tomato products, accounting for 50% of the
total daily intake
Although comparative bioavailability values for lycopene
from different tomato products are unknown, lycopene
from processed tomato products appears to be more bio-
available than that from raw tomatoes.
The release of ly-
copene from the food matrix due to processing, the pres-
ence of dietary lipids and heat-induced isomerization from
an all-trans to a cis conformation enhance lycopene bioavail-
The bioavailability of lycopene is also affected by
the dosage and the presence of other carotenoids, such as
β-carotene: Johnson and associates
found that the bioavail-
ability of lycopene was significantly higher when it was in-
gested along with β-carotene than when ingested alone.
The current dietary recommendation to increase the
consumption of fruits and vegetables rich in antioxidants
has generated interest in the role of lycopene in disease
prevention. However, the evidence thus far is mainly sug-
gestive, and the underlying mechanisms are not clearly un-
derstood. Further research is critical to elucidate the role of
lycopene and to formulate guidelines for healthy eating and
disease prevention. Areas for further study include epi-
demiological investigations based on serum lycopene levels,
bioavailability and effects of dietary factors, long-term di-
etary intervention studies, metabolism and isomerization of
lycopene and their biological significance, interaction with
other carotenoids and antioxidants, and mechanism of dis-
Agarwal and Rao
742 JAMC • 19 SEPT. 2000; 163 (6)
Competing interests: None declared.
Table 2: Estimates of dail
intake of l
ene from tomatoe
roducts, as determined from a food-fre
% of total
Tomatoes 200 g 12.70 50.5
Tomato purée 60 mL 1.02 4.1
Tomato paste 30 mL 2.29 9.1
Tomato sauce 227 mL 1.52 6.0
Spaghetti sauce 125 mL 2.44 9.7
Pizza sauce 60 mL 0.66 2.6
Chili sauce 30 mL 0.30 1.2
Tomato ketchup 15 mL 0.53 2.1
Barbecue sauce 30 mL 0.06 0.2
Tomato juice 250 mL 2.20 8.7
Tomato soup 227 mL 0.79 3.1
Clam cocktail 250 mL 0.50 2.0
Bloody Mary mix 156 mL 0.15 0.6
1. Food, nutrition and the prevention of cancer: a global perspective. Washington:
World Cancer Research Fund/American Institute for Cancer Research; 1997.
2. Trichopoulos D, Willett WC. Nutrition and cancer. Cancer Causes Control
3. Williams GM, Williams CL, Weisburger JH. Diet and cancer prevention: the
fiber first diet. Toxicol Sci 1999;52(Suppl):72-86.
4. Pincemail J. Free radicals and antioxidants in human disease. In: Favier AE,
Cadet J, Kalyanaraman B, Fontecave M, Pierre JL, editors. Analysis of free radi-
cals in biological systems. Basel: Birkhäuser Verlag; 1995. p. 83-98.
5. Ames BN, Gold LS, Willett WC. Causes and prevention of cancer. Proc Natl
Acad Sci U S A 1995;92:5258-65.
6. Witztum JL. The oxidation hypothesis of atherosclerosis. Lancet 1994;344:793-5.
7. Halliwell B. Free radicals, antioxidants and human disease: Curiosity, cause or
consequence? Lancet 1994;344:721-4.
8. Canada’s food guide to healthy eating. Ottawa: Health Canada; 1992. Cat no
H39-253/1992E. Available: www.hc-sc.gc.ca/hppb/nutrition/pube/foodguid
/foodguide.html (accessed 2000 Aug 3).
9. Dietary guidelines for Americans. 5th ed. Home and Garden Bulletin no 232.
Washington: US Department of Agriculture, US Department of Health and Hu-
man Services; 2000. Available: www.nal.usda.gov/fnic/dga (accessed 2000 Aug 3).
10. Halliwell B, Murcia MA, Chirico S, Aruoma OI. Free radicals and antioxidants
in food and in vivo: what they do and how they work. Crit Rev Food Sci Nutr
11. Sies H, Stahl W. Vitamins E and C, β-carotene, and other carotenoids as an-
tioxidants. Am J Clin Nutr 1995;62:1315S-21S.
12. Feri B. Natural antioxidants in human health and disease. San Diego: Academic
13. Block G. The data support a role for antioxidants in reducing cancer risk. Nutr
14. Rimm EB, Stampfer MJ, Ascherio A, Giovannucci E, Colditz GA, Willett WC.
Vitamin E consumption and the risk of coronary heart disease in men. N Engl J
15. Steinmetz KA, Potter JD. Vegetables, fruits, and cancer prevention: a review. J
Am Diet Assoc 1996;96:1027-39.
16. Block G, Patterson B, Subar A. Fruits, vegetables and cancer prevention: a re-
view of the epidemiological evidence. Nutr Cancer 1992;18:1-29.
17. Gaziano JM, Manson JE, Branch LG, Colditz GA, Willett WC, Buring JE. A
prospective study of consumption of carotenoids in fruits and vegetables and
decreased cardiovascular mortality in the elderly. Ann Epidemiol 1995;5:255-60.
18. Rao AV, Agarwal S. Role of lycopene as antioxidant carotenoid in the preven-
tion of chronic diseases: a review. Nutr Res 1999;19:305-23.
19. Clinton SK. Lycopene: chemistry, biology, and implications for human health
and disease. Nutr Rev 1998;56:35-51.
20. Nguyen ML, Schwartz SJ. Lycopene: chemical and biological properties. Food
21. Zechmeister L, LeRosen AL, Went FW, Pauling L. Prolycopene, a naturally
occurring stereoisomer of lycopene. Proc Natl Acad Sci U S A 1941;21:468-74.
22. Clinton SK, Emenhiser C, Schwartz SJ, Bostwick DG, Williams AW, Moore
BJ, et al. cis-trans Lycopene isomers, carotenoids, and retinol in the human
prostate. Cancer Epidemiol Biomarkers Prev 1996;5:823-33.
23. Miller NJ, Sampson J, Candeias LP, Bramley PM, Rice-Evans CA. Antioxidant
activities of carotenes and xanthophylls. FEBS Lett 1996;384:240-6.
24. Mortensen A, Skibsted LH. Relative stability of carotenoid radical cations and
homologue tocopheroxyl radicals. A real time kinetic study of antioxidant hier-
archy. FEBS Lett 1997;417:261-6.
25. Woodall AA, Lee SWM, Weesie RJ, Jackson MJ, Britton G. Oxidation of
carotenoids by free radicals: relationship between structure and reactivity.
Biochim Biophys Acta 1997;1336:33-42.
26. DiMascio P, Kaiser S, Sies H. Lycopene as the most effective biological
carotenoid singlet oxygen quencher. Arch Biochem Biophys 1989;274:532-8.
27. Erdman JW, Bierer TL, Gugger ET. Absorption and transport of carotenoids.
Ann N Y Acad Sci 1993;691:76-85.
28. Stahl W, Schwarz W, Sundquist AR, Sies H. cis-trans Isomers of lycopene and
beta-carotene in human serum and tissues. Arch Biochem Biophys 1992;294:173-7.
29. Kaplan LA, Lau JM, Stein EA. Carotenoid composition, concentrations and re-
lationships in various human organs. Clin Physiol Biochem 1990;8:1-10.
30. Schmitz HH, Poor CL, Wellman RB, Erdman JW Jr. Concentrations of se-
lected carotenoids and vitamin A in human liver, kidney and lung tissue. J Nutr
31. Nierenberg DW, Nann SL. A method for determining concentrations of
retinol, tocopherol, and five carotenoids in human plasma and tissue samples.
Am J Clin Nutr 1992;56:417-26.
32. Jain CK, Agarwal S, Rao AV. The effect of dietary lycopene on bioavailability,
tissue distribution, in-vivo antioxidant properties and colonic preneoplasia in
rats. Nutr Res 1999;19:1383-91.
33. Michaud DS, Giovannucci EL, Ascherio A, Rimm EB, Forman MR, Sampson
L, et al. Associations of plasma carotenoid concentrations and dietary intake of
specific carotenoids in samples of two prospective cohort studies using a new
carotenoid database. Cancer Epidemiol Biomarkers Prev 1998;7:283-90.
34. Freeman VL, Meydani M, Yong S, Pyle J, Wan Y, Arvizu-Durazo R, et al. Pro-
static levels of tocopherols, carotenoids, and retinol in relation to plasma levels
and self-reported usual dietary intake. Am J Epidemiol 2000;151:109-18.
35. Stahl W, Sies H. Lycopene: A biologically important carotenoid for humans?
Arch Biochem Biophys 1996;336:1-9.
36. Zhang LX, Cooney RV, Bertram JS. Carotenoids enhance gap junctional com-
munication and inhibit lipid peroxidation in C3H/10T1/2 cells: relationship to
their cancer chemopreventive action. Carcinogenesis 1991;12:2109-14.
37. Zhang LX, Cooney RV, Bertram JS. Carotenoids up-regulate connexin43 gene
expression independent of their provitamin A or antioxidant properties. Cancer
38. Matsushima NR, Shidoji Y, Nishiwaki S, Yamada T, Moriwaki H, Muto Y.
Suppression by carotenoids of microcystin-induced morphological changes in
mouse hepatocytes. Lipids 1995;30:1029-34.
39. Astorg P, Gradelet S, Berges R, Suschetet M. Dietary lycopene decreases the
initiation of liver preneoplastic foci by diethylnitrosamine in the rat. Nutr Can-
40. Levy J, Bosin E, Feldmen B, Giat Y, Miinster A, Danilenko M, et al. Lycopene
is a more potent inhibitor of human cancer cell proliferation than either α-
carotene or β-carotene. Nutr Cancer 1995;24:257-66.
41. Nagasawa H, Mitamura T, Sakamoto S, Yamamoto K. Effects of lycopene on
spontaneous mammary tumour development in SHN virgin mice. Anticancer
42. Kobayashi T, Iijima K, Mitamura T, Toriizuka K, Cyong JC, Nagasawa H. Ef-
fects of lycopene, a carotenoid, on intrathymic T cell differentiation and pe-
ripheral CD4/CD8 ratio in a high mammary tumor strain of SHN retired mice.
Anticancer Drugs 1996;7:195-8.
43. Fuhramn B, Elis A, Aviram M. Hypocholesterolemic effect of lycopene and β-
carotene is related to suppression of cholesterol synthesis and augmentation of
LDL receptor activity in macrophage. Biochem Biophys Res Commun 1997;233:
44. Agarwal S, Rao AV. Tomato lycopene and low density lipoprotein oxidation: a
human dietary intervention study. Lipids 1998;33:981-4.
45. Rao AV, Agarwal S. Bioavailability and in vivo antioxidant properties of ly-
copene from tomato products and their possible role in the prevention of can-
cer. Nutr Cancer 1998;31:199-203.
46. Pool-Zobel BL, Bub A, Muller H, Wollowski I, Rechkemmer G. Consumption
of vegetables reduces genetic damage in humans: first result of a human inter-
vention trial with carotenoid-rich foods. Carcinogenesis 1997;18:1847-50.
47. Rao AV, Agarwal S. Effect of diet and smoking on serum lycopene and lipid
peroxidation. Nutr Res 1998;18:713-21.
48. Rao AV, Fleshner N, Agarwal S. Serum and tissue lycopene and biomarkers of
oxidation in prostate cancer patients: a case control study. Nutr Cancer 1999;33:
49. La Vecchia C. Mediterranean epidemiological evidence on tomatoes and the
prevention of digestive tract cancers. Proc Soc Exp Biol Med 1997;218:125-8.
50. Giovannucci E. Tomatoes, tomato-based products, lycopene, and cancer: re-
view of the epidemiologic literature. J Natl Cancer Inst 1999;91:317-31.
51. Franceschi S, Bidoli E, La Vecchia C, Talamini R, D’Avanzo B, Negri E.
Tomatoes and risk of digestive-tract cancers. Int J Cancer 1994;59:181-4.
52. Colditz GA, Branch LG, Lipnick RJ, Willett WC, Rosner B, Posner BM, et al.
Increased green and yellow vegetable intake and lowered cancer deaths in an el-
derly population. Am J Clin Nutr 1985;41:32-6.
53. Giovannucci E, Ascherio A, Rimm EB, Stampfer MJ, Colditz GA, Willett WC.
Intake of carotenoids and retinol in relation to risk of prostate cancer. J Natl
Cancer Inst 1995;87:1767-76.
54. Dorgan JF, Sowell A, Swanson CA, Potischman N, Miller R, Schussler N, et al.
Relationship of serum carotenoids, retinol, α-tocopherol, and selenium with
breast cancer risk: results from a prospective study in Columbia, Missouri
(United States). Cancer Causes Control 1998;9:89-97.
55. Gann P, Ma J, Giovannucci E, Willett W, Sacks FM, Hennekens CH, et al.
Lower prostate cancer risk in men with elevated plasma lycopene levels: results
of a prospective analysis. Cancer Res 1999;59:1225-30.
56. Kucuk O, Sakr FH, Djuric Z, Li YW, Velazquez F, Banerjee M, et al. Ly-
copene supplementation in men with prostate cancer (PCa) reduces grade and
of preneoplasia (PIN) and tumor, decreases serum prostate specific antigen and
modulates biomarkers of growth and differentiation [abstract P1.13]. Interna-
tional Conference on Diet and Prevention of Cancer; 1999 May 28–June 2;
57. Parthasarathy S, Steinberg D, Witztum JL. The role of oxidized low-density
lipoproteins in pathogenesis of atherosclerosis. Annu Rev Med 1992;43:219-25.
58. Heller FR, Descamps O, Hondekijn JC. LDL oxidation: therapeutic perspec-
tives. Atherosclerosis 1998;137(Suppl):S25-31.
59. Parthasarathy S. Mechanism by which dietary antioxidants may prevent cardio-
vascular diseases. J Med Food 1998;1:45-51.
60. Morris DL, Kritchevsky SB, Davis CE. Serum carotenoids and coronary heart
disease: the Lipid Research Clinics Coronary Primary Prevention Trial and
Follow-up Study. JAMA 1994;272:1439-41.
61. Hodis HN, Mack WJ, LaBree L, Cashin-Hemphill L, Sevanian A, Johnson R,
et al. Serial coronary angiographic evidence that antioxidant vitamin intake re-
Role of lycopene in human health
CMAJ • SEPT. 19, 2000; 163 (6) 743
duces progression of coronary artery atherosclerosis. JAMA 1995;273:1849-54.
62. Paolisso G, Gambardella A, Giugliano D, Galzerano D, Amato L, Volpe C, et
al. Chronic intake of pharmacological doses of vitamin E might be useful in the
therapy of elderly patients with coronary heart disease. Am J Clin Nutr 1995;61:
63. Heart Outcomes Prevention Evaluation Study Investigators. Vitamin E supple-
mentation and cardiovascular events in high-risk patients. N Engl J Med 2000;
64. Kohlmeier L, Kark JD, Gomez-Gracia E, Martin BC, Steck SE, Kardinaal AF,
et al. Lycopene and myocardial infarction risk in the EURAMIC Study. Am J
65. Handelman GJ, Parker L, Cross CE. Destruction of tocopherols, carotenoids and
retinol in human plasma by cigarette smoke. Am J Clin Nutr 1996;63:559-65.
66. Kristenson M, Zieden B, Kucinskiene Z, Elinder LS, Bergdahl B, Elwing B, et
al. Antioxidant state and mortality from coronary heart disease in Lithuanian
and Swedish men: concomitant cross sectional study of men aged 50. BMJ
67. Rao AV, Waseem Z, Agarwal S. Lycopene contents of tomatoes and tomato
products and their contribution to dietary lycopene. Food Res Int 1998;31:737-41.
68. Stahl W, Sies H. Uptake of lycopene and its geometrical isomers is greater
from heat-processed than from unprocessed tomato juice in humans. J Nutr
69. Gärtner C, Stahl W, Sies H. Lycopene is more bioavailable from tomato paste
than from fresh tomatoes. Am J Clin Nutr 1997;66:116-22.
70. Johnson EJ, Qin J, Krinsky NI, Russell RM. Ingestion by men of a combined
dose of β-carotene and lycopene does not affect the absorption of β-carotene
but improves that of lycopene. J Nutr 1997;127:1833-7.
Agarwal and Rao
744 JAMC • 19 SEPT. 2000; 163 (6)
Reprint requests to: Dr. Sanjiv Agarwal or Dr. Akkinappally
Venketeshwer Rao, Department of Nutritional Sciences, Faculty
of Medicine, University of Toronto, 150 College St., Toronto ON
How do you find the information you need
to make the best health care choices?
Now updated quarterly,this electronic library is
designed to give you the evidence you need for informed health care
decision-making.The Cochrane Library now contains 4 databases:
■ The Cochrane Database of Systematic Reviews
■ The York Database of Abstracts of Reviews of Effectiveness
■ The Cochrane Controlled Trials Register
■ The Cochrane Review Methodology Database
$299.95/CMA members, $347.95/nonmembers. All orders must be prepaid. Please add 7% GST/HST
(as applicable), 8% PST (Ontario residents only) and $4 shipping/handling. Please contact CMA Member Service
Centre for network prices. Available on CD-ROM.
CMA Member Service Centre
tel 888 855-2555 or 613 731-8610 x2307