2.1. Ochrona DNA, białek i lipidów przed uszkodzeniem oksydacyjnym (ID 1608, 1609, 1611, 1662, 1663, 1664, 1899, 1942, 2081, 2082, 2142, 2374)

The claimed effects are “antioxidant properties”, “antioxidant properties/cell and DNA protection”, “antioxidant properties/protection of DNA”, “oxidative stress control”, “for antioxidant protection system/protection of DNA”, “maintains cardiovascular health”, “prostate health” and “maintains prostate health”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings and clarifications provided by Member States, the Panel assumes that the claimed effects refer to the protection of DNA, proteins and lipids from oxidative damage.
The Panel considers that claims made on the antioxidant capacity/content of lycopene-containing foods based on their capability to scavenge free radicals in vitro refer to a property of the food/food
constituent measured in model systems, and that the information provided does not establish that this exerts a beneficial physiological effect in humans as required by Regulation (EC) No 1924/2006.
Reactive oxygen species (ROS), including several kinds of radicals, are generated in biochemical processes (e.g. respiratory chain) and as a consequence of exposure to exogenous factors (e.g. radiation and pollutants). These reactive intermediates damage molecules such as DNA, proteins and lipids if they are not intercepted by the antioxidant network, which includes free radical scavengers such as antioxidant nutrients.
The Panel considers that protection of DNA, proteins and lipids from oxidative damage may be a beneficial physiological effect.

2.2. Ochrona skóry przed uszkodzeniem promieniami ultrafioletowymi (UV) (ID 1259, 1607, 1665, 2143, 2262, 2373)

The claimed effects are “skin health”, “maintains skin health”, and “for skin health”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings and clarifications provided by Member States, the Panel assumes that the claimed effects refer to the protection of the skin from UV-induced damage, including photo-oxidative damage.
The Panel considers that protection of the skin from UV-induced (including photo-oxidative) damage is a beneficial physiological effect.

2.3. Udział w prawidłowym funkcjonowaniu serca (ID 1610, 2372)

The claimed effects are “heart health” and “cardio-vascular health”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings and clarifications provided by Member States, the Panel assumes that the claimed effects refer to the maintenance of normal cardiac function.
The Panel considers that contribution to normal cardiac function is a beneficial physiological effect.

2.4. Utrzymanie prawidłowego wzroku (ID 1827)

The claimed effect is “eyes”. The Panel assumes that the target population is the general population.
In the context of the proposed wording and from the information provided, the Panel assumes that the claimed effect refers to the maintenance of normal vision.
The Panel considers that maintenance of normal vision is a beneficial physiological effect.

3.1. Ochrona DNA, białek i lipidów przed uszkodzeniem oksydacyjnym (ID 1608, 1609, 1611, 1662, 1663, 1664, 1899, 1942, 2081, 2082, 2142, 2374)

A number of the references provided were narrative reviews or consensus opinions on the health effects of lycopene that did not allow evaluation of original data, reports on intervention studies that assessed the effects of other carotenoids or antioxidant vitamins, either alone or in combination with
lycopene, or human studies assessing the effects of lycopene intake and related products on health outcomes unrelated to the claimed effect (e.g. UV-induced erythema, UV-induced immunomodulation and the risk of chronic disease, such as prostate cancer). The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
Some experimental, and generally small-scale, human studies investigated the effects of lycopene consumption on the total antioxidant activity of plasma measured by various assays (i.e. trolox-equivalent antioxidant capacity (TEAC), total reactive antioxidant potential (TRAP), and a chemiluminescent assay using 2, 2'-azinobis (3-ethylbenzothiazoline-6-sulfonate) (ABTS) as a reagent (Bohm and Bitsch, 1999; Neyestani et al., 2007; Tyssandier et al., 2004)); on GSH concentrations and antioxidant metalloenzyme activities (Hininger et al., 2001); on DNA strand breaks (Briviba et al., 2004a; Pool-Zobel et al., 1997; Porrini et al., 2005; Zhao et al., 2006); on ex vivo DNA oxidation (e.g. to lymphocytes) measured by different modifications of the comet assay (e.g. after challenge with Fe2+ or with hydrogen peroxide before electrophoresis (Riso et al., 1999; 2004; Torbergsen and Collins, 2000; Zhao et al., 2006)); on ex vivo susceptibility of LDL to Cu-ion induced oxidation (Briviba et al., 2004b; Carroll et al., 2000; Fuhrman et al., 2000; Hininger et al., 2001; Maruyama et al., 2001; Silaste et al., 2007; Visioli et al., 2003); on LDL conjugated dienes (Agarwal and Rao, 1998), on the formation of malondialdehyde (MDA) measured as thio-barbituric acid reactive substances (TBARS) (Agarwal and Rao, 1998; Briviba et al., 2004b; Neyestani et al., 2007; Rao and Agarwal, 1998; Rao and Shen, 2002); and on protein thiol concentrations (Hininger et al., 2001; Rao and Agarwal, 1998). The Panel notes that measurements of the total antioxidant activity/potential of plasma, and/or of GSH concentrations, and/or of antioxidant enzyme activities are not considered to be markers of oxidative damage, that the formation of MDA measured as TBARS, as well as the resistance of LDL to oxidation, are not suitable markers to assess lipid peroxidation, that the variants of the comet assay which measure unspecified DNA damage do not reflect DNA oxidative damage but general DNA strand breaks independent of their origin, that the ex vivo DNA resistance to oxidation after oxidative challenge does not reflect in vivo DNA oxidative damage, and that measurement of protein thiol concentrations is not a reliable marker of oxidative damage to proteins (Dalle-Donne et al., 2006; Dragsted, 2008; Griffiths et al., 2002; Knasmuller et al., 2008; Mayne, 2003). In addition, a number of the human studies provided were uncontrolled interventions with lycopene or tomato products (Agarwal and Rao, 1998; Bohm and Bitsch, 1999; Bowen et al., 2002; Hadley et al., 2003; Pool-Zobel et al., 1997; Porrini and Riso, 2000; Rao and Shen, 2002; Riso et al., 2004; Tyssandier et al., 2004; Visioli et al., 2003). The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
Rao and Agarwal (1998) performed a controlled, randomised, cross-over study with five different sources of lycopene in 19 healthy subjects (9 females/10 males), who were non-smokers aged 25- 40 years. The duration of the study was one week with each source providing lycopene at 20.5 mg/day (spaghetti sauce A), 39.2 mg/day (spaghetti sauce B), 50.4 mg/day (tomato juice), 75 mg/day (tomato oleoresin A) and 150 mg/day (tomato oleoresin B). Controls received a placebo which was not further specified. As a marker of DNA damage, 8-oxodG in lymphocytes was measured by HPLC with EC detection. For lipid peroxidation, TBARS were determined in serum, and protein oxidation was estimated by loss of free thiol groups in serum measured with beta dystrobrevin (5,5'-Dithio-bis (2- nitrobenzoic acid), DTNB). There was no statistically significant difference in DNA oxidation between the different verum groups and placebo. The Panel notes that TBARS and loss of free thiol groups in serum measured with DTNB are not reliable markers of oxidative damage to protein and lipids, respectively.
Kucuk et al. (2002) performed a randomised, two-arm clinical intervention study in patients with prostate cancer scheduled for radical prostatectomy. Data were collected from 26 patients and the intervention group took 30 mg of lycopene as tomato oleoresin for three weeks. Levels of 5-OHmdU (5-hydroxy-methyl-desoxy-uridine) in peripheral blood lymphocytes were not significantly different between groups before and after intervention.
In weighing the evidence, the Panel took into account that none of the studies provided reported a significant effect of lycopene consumption on reliable markers of oxidative damage to DNA, lipids or proteins compared to control.
The Panel concludes that a cause and effect relationship has not been established between the consumption of lycopene and protection of DNA, proteins and lipids from oxidative damage.

3.2. Ochrona skóry przed uszkodzeniem promieniami ultrafioletowymi (UV) (ID 1259, 1607, 1665, 2143, 2262, 2373)

A number of the references provided were narrative reviews or consensus opinions on the health effects of lycopene which did not allow evaluation of original data, or reports on intervention studies which assessed the effects of other carotenoids or antioxidant vitamins, either alone or in combination with lycopene, on health outcomes unrelated to the claimed effect. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
Among the references provided, three reported on human intervention studies on the effects of lycopene on measures of UV-induced damage to the skin (Aust et al., 2005; Stahl et al., 2001; 2006).
The study by Aust et al. (2005) was an uncontrolled intervention where the effects of synthetic (pure) lycopene were compared to those of lycopene in a tomato extract. The Panel considers that no conclusions can be drawn from this study for the scientific substantiation of the claimed effect.
Stahl et al. (2001) reported on a controlled, non-blinded human study with lycopene from tomato paste in 22 healthy adults (26-67 years; 14 female), skin type II, over a period of 10 weeks. The verum group (n=9 finished) consumed 40 g tomato paste with 10 g of olive oil per day providing 16 mg/day of lycopene; controls (n=10 finished) received olive oil only. At day 0, and at 4 and 10 weeks, serum lycopene and skin carotenoid concentrations were measured. Erythema formation (skin reddening) in response to 1.25 minimal erythemal dose (MED) was measured at the same time by chromametry. Serum concentrations of lycopene and skin carotenoids significantly increased in supplemented subjects. At week 10, erythema formation significantly decreased in the group which consumed tomato paste compared to controls, whereas no significant difference between groups was found at week 4 of the intervention. The Panel notes the small number of subjects recruited and that the study was not blinded. The Panel also notes that UV-induced erythema (sunburn or skin reddening) is a primary reaction of the skin following overexposure to UV (sun)light, and that it represents an inflammatory response of cutaneous tissue as a consequence of light-dependent molecular and cellular damage. However, whereas a reduction in skin erythema may indicate a reduction in UV-induced skin damage, it can also reflect a reduction in the capacity of the skin to react to molecular and cellular damage, and the data provided in this study did not allow such effects to be distinguished. The Panel considers that no conclusions can be drawn from this study for the scientific substantiation of the claimed effect.
The review by Stahl et al. (2006) reported on the studies by Stahl et al. (2001) and Aust et al. (2005), and presented data from a non-controlled intervention with a lycopene-rich carrot juice. The juice contained considerable amounts of beta-carotene (10 mg lycopene plus 5 mg beta-carotene/day). The Panel considers that no conclusions can be drawn from this reference for the scientific substantiation of the claimed effect.
The Panel notes that none of the studies provided addressed the effects of lycopene consumption on reliable markers of UV-induced (including photo-oxidative) damage to the skin.
The Panel concludes that a cause and effect relationship has not been established between the consumption of lycopene and protection of the skin from UV-induced (including photo-oxidative) damage.

3.3. Udział w prawidłowym funkcjonowaniu serca (ID 1610, 2372)

A number of the references provided were narrative reviews or consensus opinions on the health effects of lycopene which did not allow evaluation of original data, or reports on intervention studies which assessed the effects of other carotenoids or antioxidant vitamins, either alone or in combination with lycopene, on health outcomes unrelated to the claimed effect, e.g. on lipid peroxidation and on the susceptibility of lipoproteins to oxidative stress. The three animal studies provided reported on health outcomes unrelated to the claimed effect, i.e. on the effect of probucol on atherosclerosis in rabbits, on the role of lycopene on adriamycin-induced heart and kidney toxicity in rats, and on the effect of lycopene in a rat model of myocardial ischemia-reperfusion injury. The three in vitro studies provided related to the involvement of reactive oxygen species in the generation of mitochondrial DNA lesions in human fibroblasts, to the effect of carotenoids on macrophage cholesterol metabolism, and to the ageing of cultured retinal pigment epithelial cells. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
Among the references provided, three human observational studies addressed the association between blood concentrations of lycopene and combined risk for coronary heart disease and stroke (Rissanen et al., 2001; Sesso et al., 2004), intima-media thickness (Rissanen et al., 2001), or blood concentrations of C-reactive protein and E-selectin (Rowley et al., 2003). None of these studies reported on dietary intakes of lycopene. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
Three human observational studies addressed the association between blood concentrations of lycopene and risk of coronary heart disease (Ito et al., 2006; Kristenson et al., 1997; Sesso et al., 2003). The Panel notes that in one prospective cohort study (Ito et al., 2006) and in one cross- sectional study (Kristenson et al., 1997) lycopene dietary intakes were not reported, and that the nature of the relationship between dietary lycopene and blood concentrations of lycopene has not been established in these studies. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
Only one of the three human observational studies reported on lycopene dietary intakes (Sesso et al., 2003).
Sesso et al. (2003) reported on a prospective cohort study of 39,876 middle-aged and older women initially free of cardiovascular disease and cancer. Dietary lycopene intakes were divided into quintiles, and primary lycopene food sources (total tomato-based products, including tomatoes, tomato juice, tomato sauce and pizza) were categorised. During 7.2 years of follow-up, 719 cardiovascular disease cases (including myocardial infarction, stroke, revascularisation and cardiovascular disease death) occurred. Compared with women in the 1st quintile of lycopene intake, multivariate relative risks (95 % CI) for increasing quintiles of lycopene intake in relation to myocardial infarction were 1.10 (0.72-1.69), 1.01 (0.65-1.57), 0.90 (0.57-1.44) and 0.69 (0.41-1.15) (p for trend=0.09). For the consumption of tomato-based products, women consuming 1.5 to <4, 4 to
<7, 7 to <10 and 10 servings/week had relative risks (95 % CI) for myocardial infarction of 0.94 (0.65-1.37), 0.67 (0.43-1.06), 0.70 (0.38-1.29) and 0.39 (0.12-1.30) (p for trend=0.033) compared with women consuming <1.5 servings/week. The Panel notes that lycopene intake was not associated with a decreased risk of myocardial infarction in this study.
In weighing the evidence, the Panel took into account that one observational study did not show an association between lycopene dietary intakes and risk of myocardial infarction (Sesso et al., 2003),
and that the nature of the relationship between dietary lycopene and blood concentrations of lycopene was not established in the two observational studies provided, which did not report on lycopene intakes (Ito et al., 2006; Kristenson et al., 1997).
The Panel concludes that a cause and effect relationship has not been established between the consumption of lycopene and contribution to normal cardiac function.

3.4. Utrzymanie prawidłowego wzroku (ID 1827)

Three references have been provided in relation to the claimed effect.
One reference (Cardinault et al., 2005) reported on the determination of carotenoids, including lycopene, in serum and lipoprotein fractions in 34 subjects diagnosed for age-related macular degeneration, compared to 21 control subjects. Another reference (Simonelli et al., 2002) reported on the measurement of carotenoids (including serum lycopene) in 48 patients with age-related maculopathy, compared to 46 controls. The Panel considers that the nature of the relationship between dietary lycopene and blood concentrations of lycopene has not been established in these studies, and notes that there was no measurement of dietary lycopene.
The Panel notes that no human studies have been provided from which conclusions can be drawn for the scientific substantiation of the claimed effect.
The remaining reference (Nilsson et al., 2003) was an in vitro study undertaken in cultured retinal pigment epithelial cells. The Panel considers that evidence provided in in vitro studies alone is not sufficient to predict the occurrence of an effect of lycopene consumption on maintenance of normal vision in humans.
The Panel concludes that a cause and effect relationship has not been established between the consumption of lycopene and maintenance of normal vision.