Lycopene's Effects on Health and Diseases

A comprehensive review of the literature

By V. Kalai Selvan, MPharm, PhD, A. Vijayakumar, MPharm, PhD, K. Suresh Kumar, MPharm, and Gyanedra Nath Singh, MPharm, PhD


Lycopene is present in many fruits and vegetables, with tomatoes and processed tomato products being among the richest sources. This review highlights the scientific documentation of lycopene as a therapeutic agent. Lycopene may alleviate chronic diseases such as cancer and coronary heart disease. Lycopene has also been found effective in the treatment of eye diseases, male infertility, inflammation, and osteoporosis. Experimental, clinical, and epidemiological studies have also established its role in the management of diabetes and hepatoprotection. Uses of lycopene have been studied extensively through epidemiological and biochemical investigations of its properties and its bioavailability from tomato-based diets. No adverse events have been reported in association with the consumption of lycopene-containing foods. The present review article supports the therapeutic efficacy of lycopene; however, more multicenter clinical trials are warranted to confirm its efficacy.


Lycopene, a carotenoid without provitamin-A activity, is present in many fruits and vegetables. It is a red, fat-soluble pigment found in certain plants and microorganisms, where it serves as an accessory light-gathering pigment and protects them from ultraviolet B radiation. Gac fruit (Momordica cochinchinensis); tomatoes (Lycopersicon esculentum); and tomato products, including ketchup, tomato juice, and pizza sauce, are the more bioavailable sources of lycopene.1 Gac fruit contains 2,227 mcg/g lycopene; tomato contains 31 mcg/g.2 Lycopene is also found in watermelon, papaya, pink grapefruit, and pink guava. Lycopene is more bioavailable in processed and cooked tomato products than in fresh tomatoes.3,4

Lycopene is synthesized by plants and microorganisms, but not by animals. It is a red open-chain unsaturated carotenoid, acyclic isomer of beta-carotene, and longer than any other carotenoid. This highly unsaturated hydrocarbon contains 11 conjugated and 2 unconjugated double bonds, predisposing lycopene to isomerization and degradation upon exposure to light, excessive heat, and air. This results in color loss and renders tomato extract ineffective as a food or pharmaceutical coloring agent.5,6

Lycopene, also known as psi-carotene, is very sensitive to heat and oxidation and is insoluble in water. Because of the abundance of double bonds in its structure, there are potentially 1,056 different isomers of lycopene, but only a fraction are found in nature.4,7 In a study cis-isomers of lycopene were shown to be more stable, having higher antioxidant potential compared to the all-trans lycopene.8

This review summarizes the background information about lycopene and presents the most current knowledge with respect to its role in human health.

Bioavailability and Pharmacokinetics

The mechanism of absorption of lycopene is still being determined. Lycopene ingested in its natural trans form (eg, in raw tomatoes) is poorly absorbed; heat processing tomatoes and tomato products induces isomerization of lycopene from all-trans to cis configuration, in turn increasing its bioavailability.9 Also, because lycopene is a fat-soluble compound, absorption into tissues is improved when it is consumed with oil. Its concentration in body tissues is higher than all other carotenoids.10,11 In one study, serum concentrations of lycopene increased after consumption of heated tomato juice mixed with oil, with a peak at 24–48 h after ingestion.12,13 Heating tomato juice resulted in trans-to-cis isomerization of lycopene, and on ingestion of this juice, the cis isomers of lycopene appeared to predominate in human serum over the all-trans isomers.12 The exact functions and relative activities of these different isomers are yet to be studied.

Lycopene is incorporated into lipid micelles in the small intestine. These micelles are formed from dietary fats and bile acids and help to solubilize the hydrophobic form of lycopene and allow it to permeate the intestinal mucosal cells by a passive transport mechanism. In blood plasma, lycopene is eventually distributed into the very low– and low-density lipoprotein fractions.12 Lycopene is mainly distributed to fatty tissues and organs such as the adrenal glands, liver, and testes. In contrast to other carotenoids, lycopene’s serum values are not regularly reduced by smoking or alcohol consumption, although levels decrease with increasing age.10

Effect of Lycopene on Free Radical– and Nitric Oxide–Scavenging Properties

Oxidative stress is an important contributor to the risk of chronic diseases. Antioxidants scavenge free radicals, otherwise known as reactive oxygen species (ROS), and prevent the damage they can cause. Free radicals have been associated with pathogenesis of various disorders and diseases such as cancer, cardiovascular disease, osteoporosis, diabetes, and cataracts.14 In one study, lycopene significantly restored the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and glutathione reductase (GR); reduced glutathione (GSH); and decreased levels of the lipid peroxide malondialdehyde (MDA) in hypertensive patients.15 In another study, lycopene was found to have a favorable effect in reducing MDA levels and increasing GSH levels in coronary artery disease in postmenopausal women.16

The protective effect of lycopene on ischemic brain injury in rat brain homogenates has also been established. In one study, lycopene (5 µM and 10 µM) inhibited iron-catalyzed lipid peroxidation and nitric oxide production by about 31% and 61% respectively.17

The generation of nitric oxide gives rise to several other reactive species, including peroxynitrite (ONOO–), which is capable of inflicting tissue damage.18 Lycopene at the concentration of 0.31-10 µM prevented the 3-morpholinosydnonimine stress-induced DNA damage in Chinese hamsters; the protective effect is due to the scavenging of intracellular reactive oxygen and/or nitrogen species, reducing the amounts 47.5% and 42.4% respectively.19,20

Effect of Lycopene on the Management of Diabetes

A recent study demonstrated that administration of lycopene (90 mg/kg body weight) to streptozotocin-induced hyperglycemic rats caused a decrease in glucose levels, an increase in insulin concentration, a decrease in H2O2 and thiobarbituric acid reactive substances levels, increased total antioxidant status, and increased antioxidant enzyme activities (ie, catalase, superoxide dismutase, glutathione peroxidase) with improvement in serum lipid profile.21 Kuhad et al reported that lycopene at doses of 1, 2, and 4 mg/kg has significant, dose-dependent antidiabetic action in streptozotocin-induced diabetic rats.22 In a clinical study investigating the role of lycopene in diabetic patients (N=133), lycopene reduced the risk of diabetic retinopathy.23

Role of Lycopene in Atherogenesis

Inflammatory mediators such as tumor necrosis factor (TNF-α), interleukin (IL)-1β, and IL-8 enhance binding of low-density lipoprotein to endothelium and up-regulate expression of leukocyte adhesion molecules on endothelium during the process of atherogenesis.24 A study found that lycopene inhibited TNF-α-induced NF-κB activation, ICAM-1 expression, and monocyte-endothelial interaction in human umbilical endothelial cells. A further analysis revealed that lycopene attenuated TNF-α-induced IκB phosphorylation, NF-κB expression, and NF-κB p65 translocation from cytosol to nucleus.25 In a placebo-controlled, double-blind, crossover study on healthy human volunteers, 5.7 mg of lycopene for 26 days significantly restricted TNF-α production.26 In one rodent study, lycopene significantly inhibited paw edema formation and attenuated liver injury induced by ischaemia-reperfusion at doses of 25 and 50 mg/kg.27 It also exhibited antiatherogenic effects by inhibiting the expression of inflammatory mediators in hyperhomocysteinemic rats.28

Diet is believed to play a major role in the development of cardiovascular diseases.29 Ingestion of oxidizable lipids and iron catalysts for peroxide decomposition can lead to extensive formation of potentially toxic lipid peroxides, which are implicated in the process of atherosclerosis. Research is focused on preventing cardiovascular diseases through dietary changes. Primarily epidemiological studies, as well as some in vitro and limited in vivo experiments, support the hypothesis that carotenoids, including beta-carotene and lycopene, may protect lipoproteins and vascular cells from oxidation. In particular, lycopene is known to be an efficient scavenger of ROS, including singlet oxygen and other excited species.30,31 Lycopene has demonstrated reduction in oxidative DNA damage in cell culture and in rodent models.32,33 In addition, clinical studies demonstrate that a lycopene-rich diet (including tomato sauce-based pasta dishes for 3 weeks) protects against oxidative DNA damage in human leukocytes in vitro and prostate tissue in vivo.34,35 In another rodent study, the efficacy of lycopene on myocardial injury after ischemia and reperfusion was explored. In histopathological examinations, myocardial damage was significantly reduced in the lycopene-treated group. Lycopene treatment resulted in preservation of the myocardial antioxidant status and altered hemodynamic parameters as compared to control.36

Clinical studies demonstrate that a lycopene-rich diet (including tomato sauce-based pasta dishes for 3 weeks) protects against oxidative DNA damage.

A single-blind placebo controlled clinical trial found tomato extract (250 mg per day) for 4 weeks reduced blood pressure in patients with grade-1 hypertension.37 The hypocholesterolemic effect of lycopene was also demonstrated in an in vitro study in which it inhibited the activity of 3-hydroxy-3-methyl-glutaryl-CoA reductase—the rate-limiting enzyme in cholesterol biosynthesis.38

Effect of Lycopene on Hepatoprotection

Liver damage is associated with cellular necrosis, increase in tissue lipid peroxidation, and depletion of tissue GSH levels. In addition, serum levels of many biochemical markers like serum glutamic oxaloacetic transaminase, serum glutamic pyruvic transaminase, triglycerides, cholesterol, bilirubin, and alkaline phosphatase are elevated when liver damage is present.39 The hepatoprotective effect of lycopene was evaluated against galactosamine/lipopolysaccharide (D-GalN/LPS)-induced hepatitis in rats. Lycopene at a dose of 10 mg/kg (intraperitoneal) significantly reduced the levels of cholesterol, triglycerides, and free fatty acids, followed by a decrease in the levels of phospholipids in the serum and the liver.40 Another study demonstrated lycopene significantly restored antioxidant liver enzymes, such as glutathione peroxidase, glutathione-s-transferase, against N-methyl-N′-nitro-N-nitrosoguanidine, and saturated sodium chloride (S-NaCl)-induced gastric carcinogenesis.41

Role of Lycopene in the Treatment of Hepatitis C

Hepatitis C virus infection and hepatocellular carcinoma are growing health problems around the globe. In vitro, animal, and clinical studies suggest that lycopene may attenuate liver injury and possibly prevent the development of hepatocellular carcinoma.42

Role of Lycopene in the Prevention of Cancer

There have been a few experimental studies on the role of lycopene in preventing or treating cancer.43 Some evidence suggests that cancers of the pancreas, colon and rectum, esophagus, oral cavity, breast, and cervix could be reduced with increased lycopene intake.44,45

Lycopene supplementation in mice reduces experimental tumor metastasis in vivo induced by the human hepatoma cell line SK-Hep-1; the same study suggests that such an action is associated with attenuation of tumor invasion, proliferation, and angiogenesis.46 An in vitro cell culture study showed that lycopene inhibited the growth of human colon cancer HT-29 cells even at low concentration. The inhibitory effects of lycopene on cell proliferation of human colon cancer HT-29 cells were, in part, associated with the down-regulation of the PI-3K/Akt/mTOR signaling pathway.47 Lycopene inhibited platelet-derived growth factor-BB–induced signaling and cell migration in human cultured skin fibroblasts through a direct binding to platelet-derived growth factor-BB.48

The antiproliferative and apoptotic effect of lycopene on various cell lines, such as human colon carcinoma (HuCC), B chronic lymphocytic leukemia (EHEB), human erythroleukemia (K562), and Raji, a prototype of Burkitt lymphoma cell line, was evaluated. Lycopene 4 µM/ml reduced the proliferation capacity.49

Prostate cancer is the most common male cancer in developed countries and is increasing in the developing world. One study of 404 patients in China, 130 of whom had prostate cancer, suggested that those who had the highest intakes of green tea or lycopene, independently, had an inverse association with developing prostate cancer. In addition, those ingesting both green tea and lycopene had an even greater inverse association (P<0.01), suggesting there may be synergistic effects.50In vitro studies with lycopene have shown induction of apoptosis and inhibition of cell growth in androgen-sensitive (LNCaP) and androgen-independent (PC3 and VeCaP) prostate cancer cell lines.51 The data also suggest that lycopene and soy isoflavones may delay progression of both hormone-refractory and hormone-sensitive prostate cancer.51 In a clinical investigation of elderly men, lycopene (15 mg/day) inhibited progression of benign prostate hyperplasia.52 At less than 1 μM concentration, lycopene was shown to inhibit human cancer cell growth by interfering with growth factor receptor signaling and cell cycle progression, specifically in prostate cancer cells, without evidence of toxic effects or apoptosis of cells. Studies using human and animal cells have identified a gene, connexin 43, whose expression is up-regulated by lycopene, allowing direct intercellular gap junction communication (GJC). GJC is deficient in many human tumors, and its restoration or up-regulation is associated with decreased proliferation.53 A recent analysis of the evidence to date stated that there is insufficient evidence to conclude lycopene reduces tumor progression or improves overall survival in patients with existing prostate cancer.54

In cell cultures, lycopene has been found to inhibit breast cancer tumors more efficiently when compared to alpha- and beta-carotene.55,56 In one study, samples taken from the Breast Cancer Serum Bank in Columbia, Mo., were analyzed to evaluate the relationship of types of carotenoids, lycopene, selenium, and retinol with breast cancer. Only lycopene was found to be associated with a reduced risk for developing breast cancer.57

Effect on Eye Diseases

Cataracts are a multifactorial disease. Osmotic stress, together with weakened antioxidant defense mechanisms, is attributed to the changes observed in human diabetic cataract (Figure 4). Epidemiological studies provide evidence that nutritional antioxidants slow down the progression of cataracts and age-related macular degeneration.58 An experimental study found lycopene can protect the human retinal pigment epithelium cell line ARPE-19. ARPE-19 protects against H2O2-induced oxidative stress in vitro.59 Lycopene decreases the serum and lipoproteins in age-related macular degeneration patients.60 The potential role of lycopene in the prevention of cataracts is also established. It prevents sugar-induced morphological changes and modulates antioxidant status of human lens epithelial cells in vitro; 200 mg/kg significantly delayed the onset and progression of 30% galactose-induced cataract on rats; the protective effect was found to be due to the antioxidant potential.61,62

Lycopene and Bone Health

Among the many factors involved in bone health, oxidative stress induced by ROS is one that is associated with osteoporosis.63 Lycopene has an effect on proliferation and differentiation of osteoblasts (human osteoblast-like osteosarcoma SaOS-2 cells), the cells responsible for bone formation.64 In a cross-sectional study, 33 postmenopausal women aged 50–60 years were administered lycopene for 7 days. Serum samples were used to measure serum lycopene, lipid peroxidation, protein thiols, bone alkaline phosphatase, and cross-linked N-telopeptides of type-I collagen (NTx). Higher intake of lycopene decreased the level of NTx and also protein oxidation (P<0.05). Similarly, groups with higher serum lycopene had lower protein oxidation (P<0.05).65 Carbonyl levels, which are the product of protein oxidation, lead to oxidative stress and osteoporosis.66 Hence the possible mechanism of action of lycopene for the treatment of osteoporosis may be by reducing carbonyl levels.

Lycopene Therapy in Male Infertility

Excessive ROS-containing free-oxygen radicals have been identified as one of the causes of male infertility.67 Lycopene is a component of the human redox defense mechanism against free radicals. It is found in high concentrations in the testes and seminal plasma (Figure 3), and decreased levels have been demonstrated in men suffering from infertility.67 Oral administration of lycopene (2 mg twice a day for 3 months) to men with infertility significantly improved the sperm concentration in 66% of cases and motility in 73% of cases.67

Table 1. Summary of the pharmacological actions of lycopene at various dose levels

S. No Pharmacological action Experimental study Effective doses
1 Nitric oxide scavenging In vitro5 5 and 10 µM
2 TNF-α inhibition26 Clinical 5.7 mg/kg
3 Anti-inflammatory27 In vivo 25 and 50 mg/kg
4 Anti-diabetic21 Animal 90 mg/kg
5 Hepatoprotection40 In vivo 10 mg/kg
6 Anti-apoptotic49 In vitro 4 µM
7 Anti-cataract62 In vivo 200 mg/kg
8 Treatment of male infertility67 Clinical 2 mg twice/day

Drug and Food Interactions

Cholesterol-lowering drugs like Probucol decrease the absorption of lycopene.68 Food substances such as mineral oil, red palm oil, fat substitutes, and pectin may also decrease the absorption of lycopene, whereas beta-carotene, medium-chain triglycerides, and dietary oils such as olive oil may enhance its absorption.69,70 Antioxidant effects are increased when lycopene is combined with lutein, and the growth of cancer cells is decreased when it is combined with vitamin D or E.

Toxicity Profile

A sub-chronic toxicity study on lycopene was conducted by oral administration at dietary concentrations of 0.25, 0.50, and 1.0% to rats for a period of 90 days. The results from this study do not show any evidence of toxicity of lycopene at dietary levels up to 1.0% as demonstrated by the findings of clinical observations, neurobehavioral observations, motor activity assessment, body weight and food consumption measurements, ophthalmoscopic examinations, hematology, clinical chemistry, urinalysis, organ weights, gross pathology, or histopathology.71 Another study also demonstrated that intake of lycopene (75 mg/day) did not causes any adverse events in humans.72 A phase I clinical trial conducted on healthy adult male subjects found no significant hepatic or renal toxicity attributable to lycopene doses ranging from 10 to 120 mg, though minimal gastrointestinal toxicity was observed.73

Scientific evidence for lycopene use in pregnancy is not available; however, no adverse events have been reported in association with the consumption of lycopene-containing foods during pregnancy.

Recommended Intake Levels of Lycopene

Due to the variation of lycopene content in food sources, it has been difficult to estimate optimal daily intake. Ranges of 3.7 to 16.15 mg have been reported for the United States.74 Reported values for Finland, the United Kingdom, and Germany have been 0.7, 1.1, and 1.3 mg, respectively.75 A survey in Canada showed daily intake of lycopene to be 25.2 mg.76 However, a recent study in which healthy human subjects ingested lycopene from tomato ketchup and supplements at levels of 5, 10 and 20 mg daily for 1 week found that doses of 5–10 mg significantly increased serum lycopene levels (P<0.05) and also significantly reduced lipid and protein oxidation (P<0.05).77 This level of intake can easily be achieved by ingesting several dietary sources of lycopene.

Summary and Conclusions

Lycopene, as an antioxidant, reduces oxidative stress. It may play a significant role in many health concerns, including cardiovascular disease, diabetes, cancer, osteoporosis, liver disease, cataracts, and male infertility. The appropriate dose and duration of lycopene supplementation remains to be determined. Some of the studies on lycopene have included other food supplements, making it difficult to discern lycopene’s individual effects.

About the Authors

V. Kalai Selvan, MPharm, PhD, is senior scientific officer for the Indian Pharmacopoeia Commission, Government of India (Ministry of Health and Family Welfare), in Ghaziabad. He obtained his bachelor's degree and master's degree in pharmacy from the Tamil Nadu Dr M G R Medical University, Chennai, and his doctorate from Delhi Institute of Pharmaceutical Sciences and Research, University of Delhi. Selvan has published 16 research papers in peer-reviewed national and international journals.


1. Arab L, Steck S. Lycopene and cardiovascular disease. Am J Clin Nutr. 2000;71(6):1691S-1695S.

2. Betty K, Charlotta T, Mary CH, McKeon Thomas A. Fatty acid and carotenoid composition of Gac (Momordica cochinchinensis Spreng) fruit. J Agri Food Chem. 2004;52:274-279.

3. Gartner C, Stahl W, Sies H. Lycopene is more bioavailable from tomato paste than from fresh tomatoes. Am J Clin Nutr. 1997;66:116–122.

4. Rao AV, Agarwal S. Role of lycopene as antioxidant carotenoid in the prevention of chronic diseases: a review. Nutr Res. 1999;19(2):305-323.

5. Lee MT, Chen BH. Stability of lycopene during heating and illumination in a model system. Food Chem. 2002;78;425-432.

6. Yang K, Lule U, Xiao-Lin D. Lycopene: Its properties and relationship to human health. Food Rev International. 2006;22:309-333.

7. Woodall AA, Britton G, Jackson MJ. Carotenoids and protection of phospholipids in solution or in liposomes against oxidation by peroxyl radicals: relationship between carotenoid structure and protective ability. Biochim Biophys Acta. 1997;1336(3):575-586.

8. Chasse GA, Mak ML, Deretey E, et al. An ab initio computational study on selected lycopene isomers. J Mol Struct. 2000;571(1-3):27-37.

9. Micozzi MS, Brown ED, Edwards BK, et al. Plasma carotenoid response to chronic intake of selected foods and beta-carotene supplements in men. Am J Clin Nutr. 1992;55(6):1120-1125.

10. Gerster H. The potential role of lycopene for human health. J Am Coll Nutr. 1997;16(2):109-126.

11. Stahl W, Junghans B, De Boer B, Driomina ES, Briviba K, Sies H. Carotenoid mixtures protect multilamellar liposomes against oxidative damage: synergistic effects of lycopene and lutein. FEBS Lett. 1998;427(2):305-308.

12. 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. 1992;122(11):2161-2166.

13. Clinton SK. Lycopene: chemistry, biology, and implications for human health and disease. Nutr Rev. 1998;56(2 pt 1):35-51.

14. Ratnam DV, Ankola DD, Bharadwaj V, Sahana DK, Kumar MN. Role of antioxidants in prophylaxis and therapy: A pharmaceutical perspective. J Control Release. 2006;113(3):189-207.

15. Bose KS, Agrawal BK. Effect of lycopene from cooked tomatoes on serum antioxidant enzymes, lipid peroxidation rate and lipid profile in coronary heart disease. Singapore Med J. 2007;48(5):415-420.

16. Misra R, Mangi S, Joshi S, Mittal S, Gupta SK, Pandey RM. LycoRed as an alternative to hormone replacement therapy in lowering serum lipids and oxidative stress markers: a randomized controlled clinical trial. Obstet Gynecol. 2006;32(3):299-304.

17. Hsiao G, Fong TH, Tzu NH, Lin KH, Chou DS, Sheu JR. A potent antioxidant, lycopene, affords neuroprotection against microglia activation and focal cerebral ischemia in rats. In Vivo. 2004;18(3):351-356.

18. Varma SD, Kavita RH. Susceptibility of the ocular lens to nitric oxide: implications in cataractogenesis. J Ocul pharmacol Th. 2007;23(2):188-195.

19. Muzandu K, Ishizuka M, Sakamoto KQ, et al. Effect of lycopene and beta-carotene on peroxynitrite-mediated cellular modifications. Toxicol Appl Pharmacol. 2006;215(3):330-340.

20. Jamshidzadeh A, Baghban M, Azarpira N, Bardbori AM, Niknahad H. Effects of tomato extract on oxidative stress induced toxicity in different organs of rats. Food Chem Toxicol. 2008;46(12):3612-3615.

21. Ali MM, Agha FC. Amelioration of streptozotocin-induced diabetes mellitus, oxidative stress and dyslipidemia in rats by tomato extract lycopene. Scand J Clin Lab Invest. 2009;69(3):371-379.

22. Kuhad A, Sethi R, Chopra S. Lycopene attenuates diabetes-associated cognitive decline in rats. Life Science. 2008;83(3-4):128-134.

23. Suzuki K, Ito Y, Nakamura S, Ochiai J, Aoki K. Relationship between serum carotenoids and hyperglycemia: a population-based cross-sectional study. J Epidemiol. 2002;12(5):357-366.

24. Wu WB, Chiang HS, Fang JY, Hung CF. Inhibitory effect of lycopene on PDGF-BB-induced signaling and migration in human dermal fibroblasts: a possible target for cancer. Biochemistry Society Transactions. 2007;35(5):1377-1378.

25. Hung CF, Huang TF, Chen BH, Shieh JM, Wu PH, Wu WB. Lycopene inhibits TNF-alpha-induced endothelial ICAM-1 expression and monocyte-endothelial adhesion. Eur J Pharmacol. 2008;586(1-3):275-282.

26. Riso P, Visioli F, Grande S, Guarnieri S, Gardana C. Effect of a tomato-based drink on markers of inflammation, immunomodulation, and oxidative stress. J Agr Food Chem. 2006;54(7):2563-2566.

27. Leticia B, Joao R, Bruno S, et al. Anti-inflammatory effect of lycopene on carrageenan-induced paw oedema and hepatic ischaemia-reperfusion in the rat. Br J Nutr. 2009;102:126-133.

28. Liu X, Qu D, He F, Lu Q, Wang J, Cai D. Effect of lycopene on the vascular endothelial function and expression of inflammatory agents in hyperhomocysteinemic rats. Asia Pacc J Clin Nutr. 2007;16(Suppl 1):244-248.

29. Torres N, Torre-Villalvazo I, Tovar AR. Regulation of lipid metabolism by soy protein and its implication in diseases mediated by lipid disorders. J Nutrition Biochem. 2006;17(6):365-373.

30. Pavia SAR, Russell RM. ß-Carotene and Other Carotenoids as Antioxidants. J Am College of Nutrition. 1999;18(5):426-433.

31. Stahl W, Junghans B, De Boer ES, Driomina ES, Briviba K, Sies H. Carotenoid mixtures protect multilamellar liposomes against oxidative damage: synergistic effects of lycopene and lutein. Fed Eur Biochem Soc Lett. 1998;427(2):305-308.

32. Engelhard YN, Gazer B, Paran E. Natural antioxidants from tomato extract reduce blood pressure in patients with grade-1 hypertension: a double-blind, placebo-controlled pilot study. Amer Heart J. 2006;151(1):100e1-100e6.

33. Blum A, Monir M, Wirsnsky I, Ben-Arzi S. The beneficial effects of tomatoes. Eur J Intern Med. 2005;16(6):402-404.

34. Matos HR, Capelozzi VI, Gomes OF, Mascio PD, Medeiros MH. Lycopene inhibits DNA damage and liver necrosis in rats treated with ferric nitrilotriacetate. Arch Biochem Biophys 2001;396(2):171-177.

35. Matos HR, Mascio PDI, Medeiros MH. Protective effect of lycopene on lipid peroxidation and oxidative DNA damage in cell cultures. Arch Biochem Biophys. 2000;383(1):56-59.

36. Pool-Zobel BL, Bub A, Müller H, Woollowski L, Rechkemmer G. Consumption of vegetables reduces genetic damage in humans: first results of a human intervention trial with carotenoid-rich foods. Carcinogenesis. 1997;18(9):1847-1850.

37. Bowen P, Chen I, Stacewicz-Sapuntzakis M, et al. Tomato sauce supplementation and prostate cancer: Lycopene accumulation and modulation of biomarkers of carcinogenesis. Experiment Biol Med. 2002;227(10):886-893.

38. Bansal P, Gupta SK, Ojha SK, et al. Cardioprotective effect of lycopene in the experimental model of myocardial ischemia-reperfusion injury. Mol Cell Biochem. 2006;289(1-2):1-9.

39. Sharma A, Shing RT, Sehgal V, Handa SS. Antihepatotoxic activity of some plants used in herbal formulations. Fitoterapia. 1991;62:131-138.

40. Shivashangari KS, Ravikumar V, Vinodhkumar R, Sheriff SAA, Devaki T. Hepatoprotective potential of lycopene on D-alactosamine/lipopolysaccharide induced hepatitis in rats. Pharmacology Online. 2006;2:151-170.

41. Velmurugan B, Bhuvaneswaria V, Balasenthila S, Nagini S. Lycopene, an antioxidant carotenoid modulates glutathione-dependent hepatic biotransformation enzymes during experimental gastric carcinogenesis. Nutr Res. 2001;21(8):1117-1124.

42. Seren S, Mutchnick M, Hutchinson D, et al. Potential role of lycopene in the treatment of hepatitis C and prevention of hepatocellular carcinoma. Nutr Cancer. 2008;60(6):729-735.

43. Doyle C, Kushi LH, Byers T, et al. Nutrition and physical activity during and after cancer treatment: an American Cancer Society guide for informed choices. Canc J Clinicians. 2006;56:323-353.

44. Giovannuccci E. Tomatoes, tomato-based products, lycopene, and cancer: review of the epidemiologic literature. J Natl Canc Inst. 1999;91(4):317-331.

45. Vrieling A, Voskuil DW, Bonfrer JM, Korse CM, Van Doorn J, Cats A. Lycopene supplementation elevates circulating insulin-like growth factor binding protein-1 and -2 concentrations in persons at greater risk of colorectal cancer. Am J Clin Nutr. 2007;86(5):1456-1462.

46. Huang CS, Liao JW, Hu ML. Lycopene inhibits experimental metastasis of human hepatoma SK-Hep-1 cells in athymic nude mice. J Nutr. 2008;138(11):538-543.

47. Tang FY, Cho HJ, Pai MH, Chen YH. Concomitant supplementation of lycopene and eicosapentaenoic acid inhibits the proliferation of human colon cancer cells. J Nutr Biochem. 2009;20(6):426-434.

48. Wu WB, Chiang HS, Fang JY, Hung CF. Inhibitory effect of lycopene on PDGF-BB-induced signaling and migration in human dermal fibroblasts: a possible target for cancer. Biochem Soc Trans. 2007;35(Pt 5):1377-1378.

49. Salman H, Bergman M, Djaldetti M, Bessler H. Lycopene affects proliferation and apoptosis of four malignant cell lines. Biomed Pharmacother. 2007;61(6):366-369.

50. Jian L, Lee AH, Binns CW. Tea and Lycopene protect against prostate cancer. Asia Pac J Clin Nutr. 2007;16(Suppl 1):453-457.

51. Vaishampayan U, Hussain M, Banerjee M, et al. Lycopene and soy isoflavones in the treatment of prostate cancer. Nutr Cancer. 2007;59(1):1-7.

52. Schwarz S, Obermuller-Jevic UC, Hellmis E, Koch W, Jacobi G, Biesalski HK. Lycopene inhibits disease progression in patients with benign prostate hyperplasia. J Nutr. 2008;138(1):49-53.

53. Heber D, Lu QY. Overview of mechanisms of action of lycopene. Exp Biol Med. 2002;227(10):920-923.

54. Perabo FG, Von Low EC, Siener R, Ellinger J, Muller SC, Bastian BJ. A critical assessment of phytotherapy for prostate cancer. Urologe A. 2009;48(3):270-283.

55. Zhang S, Tang G, Russell RM, et al. Measurement of retinoids and carotenoids in breast adipose tissue and a comparison of concentrations in breast cancer cases and control subjects. Am J Clin Nutr. 1997;66(3):626-632.

56. Levy J, Bosin E, Feldman B, et al. Lycopene is a more potent inhibitor of human cancer cell proliferation than either alpha-carotene or beta carotene. Nutr Cancer. 1995;24(3):257-266.

57. Dorgan JF, Sowell A, Swanson CA, et al. Relationships of serum carotenoids, retinal, alpha-tocopherol and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States). Cancer Causes Control. 1998;9(1):89-97.

58. Fernandez MM, Afshari NA. Nutrition and the prevention of cataracts. Curr Opin Ophthalmol. 2008;19(1):66-70.

59. Chichili GR, Nohr D, Frank J, et al. Protective effects of tomato extract with elevated beta-carotene levels on oxidative stress in ARPE-19 cells. Br J Nutr. 2006;96(4):643-649.

60. Cardinault N, Abalain JH, Sairafi B, et al. Lycopene but not lutein nor zeaxanthin decreases in serum and lipoproteins in age-related macular degeneration patients. Clin Chim Acta. 2005;357(1):34-42.

61. Mohanty I, Joshi S, Trivedi D, Srivastava S, Gupta SK. Lycopene prevents sugar-induced morphological changes and modulates antioxidant status of human lens epithelial cells. Br J Nutr. 2002;88(4):347-354.

62. Gupta SK, Trivedi D, Srivastava S, Joshi S, Halder N, Varma SD. Lycopene attenuates oxidative stress induced experimental cataract development: an in vitro and in vivo study. Nutrition. 2003;19(9):794-799.

63. Rodriguez MS, Ramos MR, Munoz EC, Munez VM. Oxidative stress as a risk factor for osteosporosis in elderly Mexicans as characterized by antioxidant enzymes. BMC Musculoskeletal Disorders. 2007;8:124.

64. Kim L, Rao AV, Rao LG. Lycopene II—effect on osteoblasts: the carotenoid lycopene stimulates cell proliferation and alkaline phosphatase activity of SaOS-2 cells. J Med Food. 2003;6(2):79-86.

65. Rao LG, Mackinnon ES, Josse RG, Murray TM, Strauss A, Rao AV. Lycopene consumption decreases oxidative stress and bone resorption markers in postmenopausal women. Osteoporosis Int. 2007;18(1):109-115.

66. Korucuoglu U, Ciftci B, Gulbahar O, et al. Assessment of protein oxidation in women using raloxifene. Mol Cell Biochem. 2006;290(1-2):97-101.

67. Gupta NP, Kumar R. Lycopene therapy in idiopathic male infertility—a preliminary report. Int Urol Nephrol. 2002; 34(3):369-372.

68. Elinder LS, Hadell K, Johansson J, et al. Probucol treatment decreases serum concentrations of diet-derived antioxidants. Arterioscler Thromb Vasc Biol. 1995;15(8):1057-1063.

69. Riedl J, Linseisen J, Hoffmann J, Wolfram G. Some dietary fibers reduce the absorption of carotenoids in women. J Nutr. 1999;129(12):2170-2176.

70. Johnson EJ, Qin J, Krinsky NI. Ingestion by men of a combined dose of beta-carotene and lycopene does not affect the absorption of beta-carotene but improves that of lycopene. J Nutr. 1997;127(9):1833-1837.

71. Jonker D, Kuper CF, Fraile N, Estrella A, Rodriguez Otero C. Ninety-day oral toxicity study of lycopene from Blakeslea trispora in rats. Regul Toxicol Pharmacol. 2003;37(3):396-406.

72. Shao A, Hathcock JN. Risk assessment for the carotenoids: lutein and lycopene. Regul Toxicol Pharmacol. 2006;45(3):289-298.

73. Gustin DM, Rodvold KA, Jeffery A, et al. Single-dose pharmacokinetic study of lycopene delivered in a well-defined food-based lycopene delivery system (tomato paste-oil mixture) in healthy adult male subjects. Cancer Epidemiol Biomarkers Prev. 2004;13(5):850-860.

74. Porrini M, Riso P. What are typical lycopene intakes? Nutr. 2005;135:2042S-2045S

75. Rao V, Heber D. Future directions and intake recommendations. Caledonian Science Press, Scotland U.K., 2001;43.

76. 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(2):159-164.

77. Rao AV, Shen HL. Effect of low dose lycopene intake on lycopene bioavailability and oxidative stress. Nutr Res. 2002;22(10):1125-1131.