Shows the lycopene content of tomatoes, some commonly consumed tomato products and other lycopene containing fruits and vegetables.
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 paste||5.40 – 15.00|
|Ketchup||9.90 – 13.44|
|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|
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-
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
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.
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
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|
|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)|
|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|
|Bub et al. (2000)||23 healthy volunteers (mean age|
3474 years, BMI 2372 kg/m2)
|40 mg lycopene (330 ml tomato juice) for|
|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|
|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|
|Porrini and Riso|
|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|
|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|
|Increase at 12 weeks versus baseline|
|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|
|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|