Shows the lycopene content of tomatoes, some commonly consumed tomato products and other lycopene containing fruits and vegetables.
1. Introduction
Cardiovascular diseases (CVD) are one of the leading causes of death in world. Many epidemiological studies have concluded that a diet rich in fruits and vegetables reduces the incidence of heart disease in humans (Khachik et al., 2002). Carotenoids are important photochemical those are considered to be responsible for the health protective effects of fruits and vegetables (Omoni & Aluko, 2005). The carotenoids are a group of over 600 fat soluble pigments that are responsible for the natural yellow, orange, and red colors of fruits and vegetables (Giovannucci, 2002). Lycopene is one of such carotenoids, and is the pigment principally responsible for the distinctive red color of ripe tomato (
2. Sources and function of lycopene
Animals and humans do to not synthesize lycopene, and thus depend on dietary sources. Tomatoes and tomato products are the major dietary sources of lycopene. Other sources include watermelon, pink grapefruit, apricots, pink guava and papaya (Willis & Wians, 2003). Lycopene is the most abundant carotenoid in ripe tomatoes, comprising approximately 80-90% of the pigments present. The amount of lycopene in fresh tomatoes depends on the variety, maturity, and environmental conditions in which the fruit matures (Shi, 2000).
Source | Lycopene content (mg/100g wet basis) |
Tomatoes fresh | 0.72 – 20 |
Tomato juice | 5.00 – 11.60 |
Tomato sauce | 6.20 |
Tomato paste | 5.40 – 15.00 |
Tomato soup | 7.99 |
Ketchup | 9.90 – 13.44 |
Pizza sauce | 12.71 |
Watermelon | 2.30 – 7.20 |
Pink guava | 5.23 – 5.50 |
Pink grapefruit | 0.35 – 3.36 |
Papaya | 0.11 – 5.30 |
Carrot | 0.65 – 0.78 |
Pumpkin | 0.38 – 0.46 |
Sweet potato | 0.02 – 0.11 |
Apricot | 0.01- 0..05 |
Lycopene is also widely distributed in the human body. It is one of the major carotenoids found in the human serum (between 21 and 43% of total carotenoids) with plasma levels ranging from 0.22 to 1.06 nmol/ml (Cohen, 2002). It is also found in various tissues throughout the body such as the liver, kidney, adrenal glands, tests, ovaries and the prostate gland (Basu & Imrhan, 2006). Unlike other carotenoids like α-and β-carotene, lycopene lacks the β.:onone rang structure common to other carotenooids (Agarwal & Rao, 2000). Although it lacks provitamine an activity, lycopene is known to be a potent antioxidant (Livny et al., 2002). Reactive oxygen (ROS) species have been implicated in playing a major role in the causation and progression of several chronic diseases. These ROS are highly reactive oxidant molecules that are generated endogenously through regular metabolic activity. They react with cellular components, causing oxidative damage to such critical cellular biomolecules as lipids, proteins and DNA. Antioxidants are protective agents that inactive ROS and therefore, significantly delay or prevent oxidative damage associated with chronic disease risk. Lycopene is one of the most potent antioxidants among the dietary carotenoids and may help lower the risk of chronic diseases including cancer and heart disease.
3. Chemical composition of lycopene
Lycopene is a lipophelic, 40-carbon atom highly unsaturated, straight chain hydrocarbon containing 11 conjugated and 2 non-conjugated double bonds. The all-trans isomer of lycopene is the most predominant isomer in fresh tomatoes and is the most thermodynamically stable from (figure 1). The many conjugated double bonds of lycopene make it a potentially powerful antioxidant, a characteristic believed to be responsible for its beneficial effects. The antioxidant activity of lycopene is high light by its singlet oxygen-quenching property and its ability to trap peroxy1 radicals. This singlet quenching ability of lycopene is twice as high as that of β-carotene and 10 times higher than that of α-tocopherol and butylated hydroxyl toluene.
As a result of the 11 conjugated carbon-carbon double bonds in its backbone, lycopene can theoretically assume 211 or 2048 geometrical configurations (Omani & Aluko, 2005).
However, it is now known that the biosynthesis in plants leads to the all-
All-
4. Mechanisms action of lycopene
A cellular and molecular study have shown lycopene to be one of the most potent antioxidants and has been suggested to prevent atherogenesis by protecting critical bimolecules such as DNA, proteins, lipids and low density lipoproteins (Pool-zobel et al., 1997). Lycopene, because of its high number of conjugated double bonds, exhibits higher singlet oxygen quenching ability compared to β-carotene or α-tocopherol (Di-Mascio
5. Lycopene stability
Being acyclic, lycopene possesses symmetrical planarity and has no vitamin A activity, and as a highly conjugated polyene, it is particularly susceptible to oxidative degradation. Physical and chemical factors known to degrade other carotenoids, including elevated temperature, exposure to light, oxygen, extremes in pH, and molecules with active surfaces that can destabilize the double bonds, apply to lycopene as well (Rao et al., 2003).
In a study to determine the photoprotective potential of dietary antioxidants including lycopene carried out by Handley
Badimon
The stability of crystalline lycopene was determined under various temperature conditions (5, 25, and 35°C) while stored in airtight containers, sealed under inert gas, and protected from light. After 30 months of storage, crystalline lycopene remained stable when stored under the recommended conditions (Barros et al., 2011).
Lycopene (synthetically prepared by the Wittig reaction) 5% TG (Tablet Grade) and lycopene 10% WS (Water Soluble) beadlet formulations tested for over 24 months of storage, and Lycopene 10% FS (Fluid Suspension) liquid formulation tested for over 12 months of storage under various temperature conditions (5 and 25°C), were all found to be stable.(25) For the 10% WS lycopene beadlet formulations, an important market application form, stability with respect to oxidation under ambient light conditions and room temperature for 12 months in beverages was found to be 93% of the initial content of the beverage lycopene (Pool-zobel et al., 1997).
6. Dietary intake of lycopene
The human body is unable to synthesize carotenoids, which qualifies diet as the only source of these components in blood and tissues. At least 85% of our dietary lycopene comes from tomato fruit and tomato-based products, the remainder being obtained from other fruits such as watermelon, pink grapefruit, guava, and papaya, Tomatoes are an integral part of the human diet and are commonly consumed in fresh form or in processed form such as tomato juice, paste, puree, ketchup, soup, and sauce. Kim et al., (2012) used a tomato products consumption frequency questionnaire to estimate the average daily consumption of different tomato products in the Canadian population.
Di-Mascio
A study presenting data on dietary intake of specific carotenoids in The Netherlands, based on a food composition database for carotenoids, was done by Furhman
6.1. Bioavailability of lycopene
Although 90% of the lycopene in dietary sources is found in the linear, all-trans conformation, human tissues (Particularly liver, adrenal, adipose tissue, testes and prostate) contain mainly cis-isomers. Hollowy
The process of cooking which releases lycopene from the matrix into the lipid phase of the meal increases its bioavailability, and tomato paste and tomato puree are more bioavailable sources of lycopene than raw tomatoes (Gartner et al., 1997 & Porrini et al., 1998). Factors such as certain fibers, fat substituents, plant sterols and cholesterol-lowering drugs can interfere with the incorporation of lycopene into micelles, thus lowering its absorption (Boileau
6.2. The anti-atherogenic effects of lycopene
In a previous study (Basuny
Scientific evidence indicates that oxidation of low density lipoprotein (LDL), which carry cholesterol in the blood stream plays an important role in the development of atherosclerosis, the underlying disorder leading to heart attacks and ischemic strokes (Rao, 2002). Several studies indicate that consuming the antioxidant lycopene that is contained in tomatoes and tomato lycopene products can reduce the risk of cardiovascular diseases (CVD). Available evidence from the Kuopio Ischaemic Heart Disease Risk Factor (KIHD) study suggests that the thickness of the innermost wall of blood vessels and the risk of myocardial infarction reduced in persons with higher serum and adipose tissue concentrations of lycopene (Rissanen et al., 2003). This finding suggests that the serum lycopene concentration may play a role in the early stages of atherosclerosis. A thick artery wall is a sign of early atherosclerosis, and increased thickness of the intima media has been shown to predict coronary events. Similarly, the relationship between plasma lycopene concentration and intima-media thickness of the common carotid artery wall (CCA-IMT) was investigation in 520 middle-aged men and women 45-69 years as parts of the Antioxidant Supplementation in Atherosclerosis Prevention (ASAP) study (Rissanen et al., 2000). Low levels of plasma lycopene were associated with a 17.80% increment in CCA-IMT in men, while there was no significant difference among women. These findings also suggest that low plasma lycopene concentrations are associated with early atherosclerosis, evidenced by increased CCA-IMT in middle-aged men.
Findings from the Rotterdam Study (Klipstein-Grobusch et al., 2000) showed modest inverse associations between levels of serum lycopene and atherosclerosis, assessed by the presence of calcified plaques in the abdominal aorta. Study population comprised of 108 cases of aortic atherosclerosis and 109 controls aged 55 years and over. The association between serum lycopene levels and atherosclerosis was most pronounced among subjects who were current and former smokers. No association with risk of aortic calcification for the serum carotenoids α-carotene, β-carotene, lutein and zeaxanthin was observed. These results suggest that lycopene may play a protective role in the development of atherosclerosis. Results from the European Study of Antioxidant, Myocardial Infarction, and Cancer of the breast (the EURAMIC study) also show that men with the highest concentration of lycopene in their adipose tissue biopsy had a 48% reduction in risk of myocardial information compared with men with the lowest adipose lycopene concentrations (Kohlmeir et al., 1997). An increase in LDL oxidation is known to be associated with an increased risk of atherosclerosis and coronary heart disease (Parthasarathy, 1998). Agarwal and Rao (1998) investigated the effect of dietary supplementation of lycopene on LDL oxidation in 19 healthy human subjects. Dietary lycopene was provided using tomato juice, spaghetti sauce and tomato oleoresin for a period of 1 week each. Blood samples were collected at the end of each treatment, and TBARS and conjugated dienes were measured to estimate LDL oxidation. In addition to significantly increasing serum lycopene levels by a least twofold, lycopene supplementation significantly reduced serum lipid peroxidation and LDL oxidation. The average decrease of LDL –TBARS and LDL-conjugated diene for the tomato products treatment over placebo was 25 and 13%, respectively. These results suggest significance for lycopene in decreasing risk for coronary heart disease. Results from the ongoing Women’s Health Study (WHS) showed that women with the highest intake of tomato-based foods rich in lycopene had a reduced risk for CVD compared to women with a low intake of those foods (Sesso
Lycopene has also been shown to have a hypercholesterolemic effect both in vivo and in vitro. In a small dietary supplementation study, six healthy male subjects were fed 60 mg/day lycopene for 3 months. At the end of the treatment period, a significant 14% reduction in plasma LDL cholesterol levels was observed in vivo with no effect on HDL cholesterol concentration (Fuhrman et al., 1997) & Lorenz et al., 2012).
6.3. Safety of lycopene
The safety issue for carotenoids attracted much attention after the publication of the β-carotene supplementation trials, which yielded negative results. It is interesting that in thus studies an increased risk for lung cancer was related to a 12- and 16 fold increase in β-carotene plasma levels due to supplementation. β-carotene plasma levels increased from 0.32μml before supplementation up to 3.90 and 5.90 μm, respectively. Rao et al., (2003), which showed no effect for β-carotene supplementation, only a 5-fold increase in the carotenoid serum level was achieved. Interestingly, the only study with positive results after supplementation with β-carotene was achieved in linxian, a chinese community with very low carotenoid levels (0.11μm) before the intervention (Jonker et al., 2003). Although supplementation caused an 11-fold increase in β-carotene level, the final concentration of β-carotene reached was a relatively low 1.5μm. Interestingly, reviewing many studies which measured serum levels of β-carotene and lycopene after supplementation suggests that β-carotene serum levels are significantly higher than those found for lycopene. Serum levels reached for β-carotene are around 3μm and may exceed 5μm after supplementation; on the other hand lycopene levels above 1.2μm are rarely seen even after long-term application. Moreover, the serum level achieved for lycopene was not directly correlated to the amount of the supplementation carotenoid (Nahum
6.4. Lycopene relationship with other micronutrients
When reviewing data related to the chemoprevention of various diseases, it become evident that the use of a single carotenoid, or any other micronutrient which has been successful in vitro and animal models, does not prove as favorable in human intervention studies. That is, there is no magic bullet. In fact, accumulating evidence suggests that a concerted, synergistic action of various micronutrients is, more likely to be the basis of the disease-prevention activity of a diet rich in vegetables and fruits. Indeed, the sources of lycopene used in most of the human studies reviewed there were either prepared tomato products or tomato extracts containing lycopene and other tomato micronutrients and carotenoids in various proportions. Pure lycopene has not been tested as a single in human prevention studies. On the other hand, many studies showing the beneficial effect of lycopene in alleviating chronic conditions have been conducted in which the subjects were provided with tomato-based foods, or tomato extracts, but not with the pure compound. For example, the oleoresin preparation used in many of these studies also contained other tomato carotenoids such as phytoene, phytofluene and β-carotene (Amir et al., 1999; Pastori
6.5. Epidemiologic studies: lycopene and cardiovascular diseases
Epidemiological observations also report an inverse association between plasma of tissue lycopene levels and the incidence of cardiovascular diseases. In the Kuopio Ischemic Heart Disease Risk Factor Study, lower levels of plasma lycopene were seen in men who had a coronary event compared with men who did not. In addition, a higher concentration of serum lycopene was inversely correlated with a decrease in the mean and maximal intima-mediated thickness of the common carotid artery (CCA-IMT) with lo lycopene, resulting in an 18% increase in CCA-IMT (Rissanen et al., 2003). The European Multiccnter Case-Control Study on antioxidants, Myocardial Infarction and Breast Cancer Study (EURAMIC Study) reported that a higher lycopene concentration was independently protective against cardiovascular diseases (Basu & Imrhan 2006). The Women’s Health Study further revealed that a decreased risk for developing cardiovascular diseases was more strongly associated with higher tomato intake than with lycopene intake (Sesso
7. Conclusion
Thus, it can be concluded that moderate amounts of whole food-based supplementation (2–4 servings) of tomato soup, tomato puree, tomato paste, tomato juice or other tomato beverages, consumed with dietary fats, such as olive oil or avocados, leads to increases in plasma carotenoids, particu- larly lycopene. The recommended daily intake of lycopene has been set at 35 mg that can be obtained by consuming two glasses of tomato juice or through a combination of tomato products (Rao and Agarwal, 2000). These foods may have both chemopreventive as well as chemotherapeutic values as outlined in Figure 3. In the light of recent clinical trials, a combination of naturally occurring carotenoids, including lycopene, in food sources and supplements, is a better approach to disease prevention and therapy, versus a single nutrient. Lycopene has shown distinct antioxidant and anticarcinogenic effects at cellular levels, and definitely contributes to the health benefits of consumption of tomato products. However, until further research establishes sig- nificant health benefits of lycopene supplementation per se, in humans, the conclusion may be drawn that consumption of naturally occurring carotenoid-rich fruits and vegetables, particularly processed tomato products containing lycopene, should be encouraged, with positive implications in health and disease.
Type and duration of lycopene supplementation | Effects on biomarkers of oxidative stress/carcinogenesis | |||
Agarwal and Rao (1998) | 19 healthy subjects (mean age 29 years, BMI 2472.8 kg/m2) | 0 mg lycopene (placebo), 39 mg lycopene (spaghetti sauce), 50 mg lycopene (tomato juice), or 75 mg lycopene (tomato oleoresin) per day for 1 week | 25% decrease in LDL-TBARS 13% decrease in LDL-CD for all groups versus | Increase at 7 days in all groups versus placebo (P<0.05) |
placebo (P<0.05) | ||||
Riso et al. (1999) | 10 healthy subjects (mean age 23.171.1 years, BMI 20.571.5 kg/m2) | 16.5 mg lycopene (60 g tomato puree), per day for 21 days | 38% decrease in DNA damage in lymphocytes (P<0.05) | Increase at 21 days versus baseline (P<0.001) |
Bub et al. (2000) | 23 healthy volunteers (mean age 3474 years, BMI 2372 kg/m2) | 40 mg lycopene (330 ml tomato juice) for 2 weeks | 12% decrease in plasma TBARS 18% increase in LDL lag time (P<0.05) no effects on water-soluble antioxidants, FRAP, glutathione peroxidase and reductase activities (P<0.05) | Increase at 2 weeks versus baseline (P<0.05) |
Chopra et al. (2000) | 34 healthy females (mean age 37.578.5 years, BMI 2473.5 kg/m2) | 440 mg lycopene (200 g tomato puree þ 100 g watermelon) per day for 7 days | Significant decrease in LDL oxidizability in nonsmokers (P<0.05); no effects in smokers (P<0.05) | Increase at 7 days versus baseline (P<0.05) |
Porrini and Riso (2000) | 9 healthy subjects (mean age 25.472.2years, BMI 20.371.5 kg/m2) | 7 mg lycopene (25 g tomato puree), per day for 14 days | 50% decrease in DNA damage in lymphocytes (P<0.05) | Increase at 14 days versus baseline (P<0.001) |
Upritchard et al. | 15 well-controlled type II diabetics | Tomato juice (500 ml) per day or placebo | Decreased LDL oxidizability versus | Increase at 4 weeks versus baseline |
(2000) | (mean age 6378years, BMI30.977 kg/m2) | for 4 weeks | baseline (P<0.001) | (P<0.001) |
Hininger et al. (2001) | 175 healthy volunteers (mean age 33.571 years, BMI- 24.370.5 kg/m2) | 15 mg lycopene (natural tomato extract) or placebo per day for 12 weeks | No effects on LDL oxidation, reduced glutathione, protein SH groups and antioxidant metalloenzyme activities (P<0.05) | Increase at 12 weeks versus baseline (P<0.05) |
Chen et al. (2001) | 32 patients with localized prostate | 30 mg lycopene (200 g spaghetti sauce) per day for 3 weeks before surgery or a reference group with no supplementation | Decreased leukocyte and prostate tissue | Increase at 3 weeks versus baseline |
adenocarcinoma (mean age 63.776.1 years, BMI 28.074.9 kg/m2) | oxidative DNA damage; decreased serum PSA levels (P<0.05) | (P<0.001) | ||
Kucuk et al. (2001) | 26 patients with newly diagnosed, clinically localized prostate cancer (mean age 62.1571.85 years, BMI not reported) | 15 mg lycopene (Lyc-O-Mato capsules) twice daily or no supplementation for 3 weeks before surgery | Decreased tumor growth in the intervention group versus control(P<0.05); decreased plasma PSA levels and increased expression of connexin43 in prostate tissue in the intervention group versus control (P<0.05);decreased plasma IGF-1 levels in intervention and control groups(P<0.05) | No effects at 3 weeks versus baseline (P<0.05) |
Porrini et al. (2002) | 9 healthy subjects (mean age 25.272.2 years, BMI 20.271.6 kg/m2) | 7 mg lycopene (25 g tomato puree) with 150 g of spinach and 10 g of olive oil per day for 3 weeks | Decreased DNA oxidative damage (P<0.05) | Not reported |
References
- 1.
Agarwal A. Rao A. 1998 Tomato lycopene and low density lipoprotein oxidation: a human dietary intervention study 33 981 984 - 2.
Agrawal S. Rao V. 2000 Tomato lycopene and its role in human health and chronic diseases. Canadian Medical Association Journal,163 739 744 - 3.
Amir H. Karas M. Giat J. 1999 Lycopene 1, 25 di-hydroxy vitamin-D3 cooperate in the inhibition of cell cycle progression and induction of differentiation in Hl-60 leukemic cells. Nutrition Cancer,33 105 112 - 4.
Badiman L. Vilahur G. Padro T. 2010 Nutraceuticals and atherosclerosis: Human trials. Cardiovascular Therabeutics,28 202 215 - 5.
Barros L. Carbrita L. Boas M. Carvaiho A. Ferreira I. 2011 Chemical, biochemical and electrochemical assays to evaluate phytochemicals and antioxidant activity of wild plants. Food Chemistry,127 1600 1608 - 6.
Basu A. Imrhan V. 2006 Tomato versus lycopene in oxidative stress and carcinogenesis: conclusions from clinical trials. European Journal OF Clinical Nurition,1 9 - 7.
Minia Journal of Agricultural Research and Development,Basuny A. M. Mostafat D. M. Azouz A. (2006 Supplementation of. polyunsaturated oils. with lycopene. as natural antioxidant. antipolymerization during. heating process. 26 449 469 - 8.
Basuny A. M. Gaafar A. M. Arafat S. M. 2009 Tomato lycopene is a natural antioxidant and cn alleviate hypercholesterolemia. African Journal of Biotechnology,23 6627 6633 - 9.
Boileau T. W. Liao Z. Kim S. Lemeshow S. Erdman J. Clinton S. 2003 Prostate carcinogensis in N-methyl-N-nitrosourea (NMW-testosterone-treated rats fed tomato powder, lycopene, or energy-restricted diets. J Natl. Cancer Inst.95 1578 1586 - 10.
Boileau A. C. Merchen N. R. Wasson K. CA Atkinson Erdman. J. W. 1999 cis-Lycopene is more bioavailable than trans-lycopene in vitro and in vivo in lymph-cannulated ferrets. J Nutr129 1176 1181 - 11.
Boileau TWM, Boileau AC, Erdman JW 2002 Bioavailability of alltrans and cis-isomers of lycopene. Exp Biol Med227 914 919 - 12.
Britton G. 1995 Structure and properties of carotenoids in relation to function. FASEB J9 1551 1558 - 13.
Briviba K. Schnabele K. Rechkemmer G. Bub A. 2004 Supplementa- tion of a diet low in carotenoids with tomato or carrot juice does not affect lipid peroxidation in plasma and feces of healthy men. J Nutr134 1081 1083 - 14.
Bub A. Watzl B. Abrahamse L. Delincee H. Adam S. Wever J. 2000 Moderate intervention with carotenoid-rich vegetable products reduces lipid peroxidation in men. J Nutr130 2200 2206 - 15.
Bub A. Barth S. W. Watzl B. Briviba K. Rechkemmer G. 2005 Araoxonase 1 Q192R (PON1-192) polymorphism is associated with reduced lipid peroxidation in healthy young men on a low- carotenoid diet supplemented with tomato juice. Br J Nutr93 291 297 - 16.
Chen L. Stacewicz-Sapuntzakis M. Duncan C. Sharifi R. Ghosh L. Van Breemen R. 2001 Oxidative DNA damage in prostate cancer patients consuming tomato sauce-based entrees as a whole-food intervention. J Natl Cancer Inst93 1872 1879 - 17.
Chopra M. O’Neill M. E. Keogh N. Wortley G. Southon S. Thurnham D. I. 2000 Influence of increased fruit and vegetable intake on plasma and lipoprotein carotenoids and LDL oxidation in smokers and nonsmokers. Clin Chem46 1818 1829 - 18.
Clinton S. K. Emenhiser C. Schwartz S. J. Bostwick D. G. Williams A. W. Moore B. J. 1996 Cis-trans lycopene isomers, carotenoids, and retinol in the human prostate. Cancer Epidemiol Biomarkers Prev5 823 833 - 19.
Cohen L. 2002 A review of animal model studies of tomato carotenoids, lycopene and cancer chemoprevention. Experimental Biology and Medicine,277 864 868 - 20.
Di Mascio P. Kaiser S. Sies H. 1989 Lycopene as the most efficient biological carotenoid singlet oxygen quencher. Arch Biochem Biophys274 532 538 - 21.
Diwadkar-Navsariwala V. Novotny J. A. Gustin D. M. Sosman J. A. Rodvold K. A. Crowell J. A. 2003 A physiological pharmacokinetic model describing the disposition of lycopene in healthy men. J Lipid Res44 1927 1939 - 22.
Fuhrman B. Elis A. Aviram M. 1997 Hydpocholesterolemic effect of lycopene and β-carotene is related to suppression of cholesterol synthesis and augmentation of LDL receptor activity in macrophages-Biochemical and Biophysical Research Communications,233 658 662 - 23.
Gartner C. Stahl W. Sies H. 1997 Lycopene is more bioavailable from tomato paste than from fresh tomatoes. Am J Clin Nutr66 116 122 - 24.
Giovannucci E. 2002 A review of epidemiologic studies of tomatoes, lycopene and prostate cancer. Experimental Biology and Medicine,227 852 859 - 25.
Hadley C. W. Clinton S. K. Schwartz S. J. 2003 The consumption of processed tomato products enhances plasma lycopene concentrations in association with reduced lipoprotein sensitivity to oxidative damage. J Nutr133 727 732 - 26.
Hantz H. L. Young L. F. Martin K. R. 2005 Physiologically attainable concentrations of lycopene induce mitochondrial apoptosis in LNCaP human prostate cancer cells Exp Biol Med230 171 179 - 27.
Hininger I. A. Meyer-Wenger A. Moser U. Wright A. Southon S. Thurnham D. 2001 No significant effects of lutein, lycopene or b-carotene supplementation on biological markers of oxidative stress and LDL oxidizability in healthy adult subjects. J Am Coll Nutr20 232 238 - 28.
Holloway D. E. Yang M. Paganga G. Rice-Evans C. A. Bramley P. M. 2000 Isomerization of dietary lycopene during assimilation and transport in plasma. Free Radical Res32 93 102 - 29.
Hoppe P. P. Kramer K. Van den Berg. H. Steenge G. Vliet T. 2003 Synthetic and tomato-based lycopene have identical bioavailability in humans. Eur J Nutr42 272 278 - 30.
Hwang E. S. Bowen P. E. 2005 Effects of lycopene and tomato paste extracts on DNA and lipid oxidation in LNCaP human prostate cancer cells 23 97 105 - 31.
Jonker D. Kuper C. Fraile N. Estrella A. Otero C. 2003 Ninety-day oral toxicity study of lycopene from Blakeslea trispora in rats. Regul Toxicol Pharmacology,37 396 406 - 32.
Kim Y. Park Y. Lee K. Jeon S. Gregor R. Choi S. 2012 Dose dependent effects of lycopene enriched tomato wino on liver and adipose tissue in high fat diet fed rats. Food Chemistry,130 42 48 - 33.
Kiokias S. Gordon M. H. 2003 Dietary supplementation with a natural carotenoid mixture decreases oxidative stress. Eur J Clin. Nutr57 1135 1140 - 34.
Klipstein-Grobusch K. Launer L. Geleijnse J. Boeing H. Hofman A. Wtteman J. 2000 Serum caroteniods and atherosclerosis. The Rotterdam study. Atherosclerosis,148 49 56 - 35.
Khachik F. Carvalho L. Bernstein P. S. Muir G. Zhao D. Katz N. 2002 Chemistry, distribution and metabolism of tomato carotenoids and their impact on human health. Experimental Biology and Medicine,227 845 851 - 36.
Kohlmeir L. Kark J. Gomez-Garcia E. Martin B. Steck S. Kardinaal A. 1997 Lycopene and myocardial infraction risk in the EURAMIC study. American Journal of Epidemiology,146 618 626 - 37.
Kucuk O. Sarkar F. H. Sakr W. Djurie Z. Pollak M. N. Khachik F. 2001 Phase II randomized clinical trial of lycopene supplemen- tation before radical prostatectomy. Cancer Epidemiol Biomarkers Prev10 861 868 - 38.
Lee A. Thurnham D. Chopra M. 2000 Consumption of tomato products with olive oil but not sunflower oil increases the antioxidant activity of plasma. Free Radical Biol Med29 1051 1055 - 39.
Levin G. Yeshurun M. Mokady S. 1997 In vivo antiperoxidative effect of 9-cis b-carotene compared with that of the all-trans isomer. Nutr Cancer27 293 297 - 40.
Libby P. 2006 Inflammation and cardiovascular disease mechanisms. Am J Clin Nutr 83,456S EOF 460S EOF - 41.
Liu C. Russell R. M. Wang X. D. 2006 Lycopene supplementation prevents smoke-induced changes in J Nutr 136, 106-111.53 p53 phosphorylation, cell proliferation, and apoptosis in the gastric mucosa of ferrets. - 42.
Lorenz M. Fechner M. Kalkowski J. Frohlich K. Trautman A. Bohm V. Liebisch G. Lehneis S. Schmitz G. Ludwing A. Baumann G. Stangl K. Stangle V. 2012 Effects of lycopene on the initial state of atherosclerosis in New Zealand white rabbits. PLoS one7 1 8 - 43.
Livny O. Kaplan I. Reifen R. Polak S. Madar Z. Schwartz B. 2002 Lycopene inhibits proliferation and enhances gap-junctional communication of KB-1 human oral tumor cells. Journal of Nutrition,132 3754 3759 - 44.
Nahum A. Hirsch K. Danilenko M. 2000 Lycopene inhibition of cell cycle progression in breast and endometrial cancer cells in associated with reduction in cyclin D levels and retention of27 in the cyclin E- cdk 2 complexes. Oncogene, 26: 3428-3436. - 45.
Omoni O. Aluko R. 2005 The anticarcinogenic and antiatherogenic effects of lycopene: a review. Trends in Food Science & Technology,16 344 350 - 46.
Parthasarathy S. 1998 Mechanisms by which dietary antioxidants may prevent cardiovascular diseases 1 45 51 - 47.
Paster M. Fander H. Boscoboinik D. Azzi A. 1998 Lycopene in association with α-tocopherol inhibits at physiological concentrations proliferation of prostate carcinoma cells. Biochemistry Biophysics Research communication,35 582 585 - 48.
Obermuller-Jevic U. C. Olano-Martin E. Corbacho A. M. Eiserich J. P. Van der Vliet A. Valacchi G. 2003 Lycopene inhibits the growth of normal human prostate epithelial cells in vitro. J Nutr133 3356 3360 - 49.
Pool-Zobel B. L. Bub A. Muller H. Wollowski I. Rechkemmer G. 1997 Consumption of vegetables reduces genetic damage in humans: first result of a human intervention trial with carotenoid-rich foods. 18 1847 1850 - 50.
Porrini M. Riso P. Testolin G. 1998 Absorption of lycopene from single or daily portions of raw and processed tomato. Br J Nutr80 353 361 - 51.
Porrini M. Riso P. 2000 Lymphocyte lycopene concentration and DNA protection from oxidative damage is increased in women after a short period of tomato consumption130 189 192 - 52.
Porrini M. Riso P. Oriani G. 2002 Spinach and tomato consumption increases lymphocyte DNA resistance to oxidative stress but this is not related to cell carotenoid concentrations. Eur J Nutr41 95 100 - 53.
Porrini M. Riso P. Brusamolino A. Berti C. Guarnieri S. Visioli F. 2005 Daily intake of a formulated tomato drink affects carotenoid plasma and lymphocyte concentrations and improves cellular antioxidant protection. Br J Nutr93 93 99 - 54.
Rao A. V. Shen H. 2002 Effect of low dose lycopene intake on lycopene bioavailability and oxidative stress Nutr Res22 1125 1131 - 55.
Rao G. Guns E. Rao A. 2003 Lycopene: Its role in human health and disease. Agro Food Industry In Tech,8 25 30 - 56.
Rao A. V. 2004 Processed tomato products as a source of dietary lycopene: bioavailability and antioxidant properties. Can J Diet Pract Res65 161 165 - 57.
Reboul E. Borel P. Mikail C. Abou L. Charbonnier M. Caris-Veyrat C. 2005 Enrichment of tomato paste with 6% tomato peel increases lycopene and b-carotene bioavailability in men. J Nutr135 790 794 - 58.
Re R. Fraser P. D. Long M. Bramley P. M. Rice-Evans C. 2001 Isomerization of lycopene in the gastric milieu Biochem Biophys Res Commun281 576 581 - 59.
Richelle M. Bortlik K. Liardet S. Hager C. Lambelet P. Baur M. 2002 A food-based formulation provides lycopene with the same bioavailability to humans as that from tomato paste. J Nutr132 404 408 - 60.
Riso P. Pinder A. Santangelo A. Porrini M. 1999 Does tomato consumption effectively increase the resistance of lymphocyte DNA to oxidative damage? Am J Clin Nutr69 712 718 - 61.
Riso P. Visioli F. Erba D. Testolin G. Porrini M. 2004 Lycopene and vitamin C concentrations increased in plasma and lymphocytes after tomato intake. Effects on cellular antioxidant protection Eur J Clin Nutr58 1350 1358 - 62.
Rissanen T. Voutilainen S. Nyyssonen K. Salonen Salonen J. T. 2000 Low plasma lycopene concentrations is associated with increased intima-media thickness of the carotid artery wall Arteisclerosis, Thrombosis and Vascular Biology,20 677 2681 - 63.
Rissanen T. Voutilainen S. Nyyssonen K. Salonon J. Kaplan G. Salonen J. 2003 Serum lycopene concentration and carotid atherosclerosis: the Kuopio Ischemic Heart Disease Risk Factor Study. Am J Clin Nutr77 133 138 - 64.
Sesson H. D. Liu S. Gaziano M. Buring J. 2003 Dietary lycopene, tomato-based food products and cardiovascular disease in women. Journal of Nutrition,133 2336 341 - 65.
Shi J. 2000 Lycopene in tomatoes: Chemical and physical properties affected by food processing 40 1 42 - 66.
Stahl W. Junghans A. Boer B. Driomina E. Briviba K. Sies H. 1998 Carotenoid mixtures protect multilamellar liposomes against oxidative damage: synergistic effects of lycopene and lutein. FEBS Lett.42 305 308 - 67.
Unlu N. Z. Bohn T. Clinton S. K. Schwartz S. J. 2005 Carotenoid absorption from salad and salsa by humans is enhanced by the addition of avocado or avocado oil. J Nutr135 431 436 - 68.
Upritchard J. E. Sutherland W. H. F. Mann J. I. 2000 Effect of supplementation with tomato juice, vitamin E, and vitamin C on LDL oxidation and products of inflammatory activity in Type 2 diabetes. 23 733 738 - 69.
Visioli F. Riso P. Grande S. Gall C. Porrini M. 2003 Protective activity of tomato products on in vivo markers of lipid oxidation. Eur J Nutr42 201 206 - 70.
Willis M. S. Wiams F. H. 2003 The role of nutrition in preventing prostate cancer: a review of the proposed mechanisms of action of various dietary substance s. Clinica Cimica Acta,330 57 83 - 71.
Wu K. Schwaz S. J. Platz A. Clinton S. Erdman J. Ferruzzi M. 2003 Variations in plasma lycopene and specific isomers over time in a cohort of US men. Journal of Nutrition, 133;1930 1936 - 72.
Zhao X. Aldini G. Johnson E. J. Rasmussen H. Kraemer K. Woolf H. 2006 Modification of lymphocyte DNA damage by carotenoid supplementation in postmenopausal women. Am J Clin Nutr83 163 169