ID 1603 - Luteina

PL: Luteina
EN: Lutein
Pdf: lutein

Oświadczenie (2)

1. Charakterystyka żywności / składnika

The food constituent that is the subject of the health claim is lutein, which is a xanthophyll carotenoid naturally present in food, especially in green leafy vegetables such as spinach and kale. The group of xanthophyll carotenoids also includes zeaxanthin, β-cryptoxanthin, neoxanthin and violaxanthin, among others. Lutein can be measured by established methods.
The Panel considers that the food constituent, lutein, which is the subject of the health claim, is sufficiently characterised.

2. Znaczenie oświadczenia dla zdrowia człowieka

The claimed effect, which is eligible for further assessment, is maintenance of normal vision. The proposed target population is the general population.
For ID 1604, a request was made to interpret the claimed effect as contribution to the protection of the retina and the lens from oxidative damage. The Panel notes that ID 1604 together with ID 1603 have been previously assessed as a claim on maintenance of normal vision, and this is the claim which is eligible for further assessment as agreed by the European Commission and Member States.
Visual function, including visual acuity and contrast sensitivity, can be assessed by established methods.
The Panel considers that maintenance of normal vision is a beneficial physiological effect.

3. Naukowe uzasadnienia wpływu na zdrowie człowieka - Utrzymanie prawidłowego wzroku

The Panel has issued two opinions in relation to a claim on lutein and maintenance of normal vision. The first opinion (EFSA Panel on Dietetic Products Nutrition and Allergies (NDA), 2010) was based on over 200 references which were collectively submitted under IDs 1603, 1604 and 1931. The second opinion (EFSA Panel on Dietetic Products Nutrition and Allergies (NDA), 2011) was based
on the references submitted under IDs 1779 and 2080, which did not provide any additional scientific data for the scientific substantiation of the claim.
In the framework of further assessment, the additional information provided (i.e. not evaluated previously by the Panel) included three human intervention studies (Berson et al., 2010; Ma et al., 2009; Rodriguez-Carmona et al., 2006), of which only two were on healthy subjects (Ma et al., 2009; Rodriguez-Carmona et al., 2006), one human observational study and one case report, as well as a number of animal, in vitro and ex vivo studies.
This evaluation is based on the scientific references provided in the present and the previous submissions which addressed the effects of lutein on maintenance of vision and/or on the mechanisms by which lutein could exert the claimed effect in the target population.
In this context, the Panel considers that human intervention studies which addressed the effects of lutein on functional measures of vision in the target population (i.e. subjects with normal vision) are pertinent for the scientific substantiation of the claim (Kvansakul et al., 2006; Ma et al., 2009; Rodriguez-Carmona et al., 2006).
Two publications (Kvansakul et al., 2006; Rodriguez-Carmona et al., 2006) reported on outcomes related to visual performance in a subgroup of subjects participating in a larger study (LUXEA) which aimed to address the safety of zeaxanthin and lutein supplements, and the accumulation of these carotenoids in the eye (Schalch et al., 2007). The LUXEA study was a double-blind, placebo-controlled, two phase trial in which 92 healthy male subjects (18-40 years) were randomised (23 subjects per group) to receive either lutein (L, 10 mg/day), zeaxanthin (Z, 10 mg/day), lutein and zeaxanthin (L+Z, 10 mg/day of each), or placebo (P, unspecified) for six months (phase 1). Five subjects per group agreed to continue the intervention for an additional six-month period (phase 2) during which they received double daily doses of the single carotenoids (L and Z groups), the same dose of the combination (L+Z group), or the combination of carotenoids (P group, 10 mg of each carotenoid per day). An additional group of 10 subjects was recruited at the end of phase 1 to serve as placebo in phase 2 of the study. Scattered light and high mesopic contrast acuity thresholds (CAT) (Kvansakul et al., 2006), as well as colour vision (Rodriguez-Carmona et al., 2006), were measured at the end of phase 1 in 34 out of 73 subjects who completed phase 1 (in 6, 8, 9 and 11 subjects from groups L, Z, L+Z and P) and in four (Kvansakul et al., 2006) or six (Rodriguez-Carmona et al., 2006) out of the 10 subjects from the new placebo group. These measures were repeated at the end of phase 2 in the 18 subjects who agreed to continue with the intervention (five subjects in groups Z, L+Z and P receiving L+Z, three subjects in group L), and in four (Kvansakul et al., 2006) or six (Rodriguez-Carmona et al., 2006) from the new placebo group. Macular pigment optical density (MPOD) was also measured at the end of phase 2 in these subjects. Between and within group changes in scattered light and CAT between phases 1 and 2 were assessed, as well as the relationship between changes in these outcomes as well as colour vision and MPOD measurements. The Panel notes that the visual performance study was not randomised, that no information was provided on how subjects were selected from the LUXEA study, that the statistical methods used for data analysis are poorly described in the publications, and that no information is provided about the baseline characteristics of the subjects for the variables of interest, or about their comparability between groups. The Panel also notes that the final sample size analysed for visual performance outcomes (five subjects per group or less) is small, and that the study was likely to be underpowered for such outcomes. The Panel considers that no conclusions can be drawn from the study reported in these two publications for the scientific substantiation of the claim.
A third publication (Ma et al., 2009) reported on a randomised, double-blind, placebo-controlled study which compared measures of visual function in 37 healthy subjects (22-30 years) who had long- term computer display light exposure (average computer usage time >10 h/day during the previous 2 years), and who received either a placebo (maltodextrin, n=12) or lutein supplementation (6 or
12 mg/day; n=12 and 13 respectively) for 12 consecutive weeks. Uncorrected visual acuity and best- spectacle corrected visual acuity were measured with decimal charts in standardised lighting conditions, and contrast sensitivity and glare sensitivity were measured with a contrast glare tester using concentric ring-shaped visual targets equivalent to visual angles of 6.3, 4.0, 2.5, 1.6 and 0.7°. Results for all these outcomes were expressed in logarithm. Habitual diet was assessed using a food- frequency questionnaire and three-day weighed food record at baseline and at the final study visit. Differences at baseline between groups were tested with the χ2-test or ANOVA, intra-group comparisons before and after supplementation were assessed using paired t-tests, and inter-group comparisons after supplementation were assessed with ANOVA. No power calculation was reported. The three groups did not differ at baseline in lutein intakes or in visual parameters, except for lower contrast sensitivity at 4.0° in the lutein group receiving 12 mg/day compared to placebo (p=0.045). This study did not find a significant effect of lutein supplementation (6 or 12 mg/day) on measures of visual acuity compared with placebo. Compared to placebo, contrast sensitivity was significantly higher at 2.5° (p=0.003) in the group supplemented with 6 mg/day lutein, but not in the group supplemented with 12 mg/day. No significant differences in glare sensitivity were observed between lutein (either group) and placebo. The Panel considers that this study does not show an effect of lutein on visual acuity or glare sensitivity, and that the results are inconsistent as regards contrast sensitivity.
The remaining human intervention studies in healthy populations either used lutein in combination with other components (e.g. antioxidant vitamins and other carotenoids), or examined the relationship between blood concentrations of lutein and health outcomes following dietary manipulations. The Panel considers that no conclusions can be drawn from these studies for the scientific substantiation of a claim on lutein, particularly considering that the relationship between lutein intake and blood concentrations of lutein was not described in these studies.
A number of human intervention studies conducted in healthy populations investigated the effects of lutein on MPOD. The Panel notes that MPOD is not a measurement of visual function or a surrogate marker for age-related macular degeneration (AMD). The Panel also notes that significant changes in MPOD may not be accompanied by changes in functional outcomes related to vision or AMD risk, and that the predictive value of changes in MPOD as an indicator of improved vision has not been established (Bernstein et al., 2010; Davies and Morland, 2004; FDA, 2005). The Panel considers that no conclusions can be drawn from these studies for the scientific substantiation of a claim on vision.
Human intervention studies in patients with cataracts, diabetic retinopathy, age-related maculopathy or macular degeneration (designated together as ARM), or inherited retinal degeneration (e.g. retinitis pigmentosa), were also provided. The Panel notes that the majority of these studies used lutein in combination with other components (e.g. antioxidant vitamins and other carotenoids) and/or did not assess any functional outcomes related to vision, but rather changes in MPOD, whereas only a few studies assessed visual function. The Panel also notes that the evidence provided does not establish that results obtained in these patient population subgroups with respect to functional outcomes related to vision can be extrapolated to the target population for the claim. The Panel considers that no conclusions can be drawn from these studies for the scientific substantiation of the claim.
A number of the observational studies provided, addressed endpoints unrelated to vision (e.g. plasma antioxidant capacity). Other observational studies investigated the association between estimated dietary intakes of lutein and zeaxanthin combined, or between lutein concentrations in blood, adipose tissue or the retina as markers of lutein intake, and different outcomes (e.g. MPOD; eye-related diseases such as ARM, cataracts, or diabetic retinopathy). The Panel notes that the relationship between estimated dietary intakes of lutein alone and these outcomes was not addressed in the studies. The Panel also notes that blood concentrations of lutein reflect lutein intakes over a short period of time, and therefore may not be representative of long-term consumption, and that blood and tissue concentrations of lutein are poorly correlated with dietary lutein intakes (FDA, 2005). The Panel
considers that no conclusions can be drawn from these observational studies for the scientific substantiation of the claim.
One cross-sectional study investigated the association between dietary intakes of lutein and the presence (or history) of cataracts (Rodriguez-Rodriguez et al., 2006) in 183 institutionalised men and women aged 65 years and over. Dietary intakes of some vitamins and carotenoids, including lutein, were estimated using a seven-day weighed food record. After exclusion of subjects who died soon after the beginning of the study or had congenital cataracts, 177 subjects were included in the analyses, of which 91 had cataracts or history of cataracts (cases) and 86 had not (controls). It is unclear from the publication how subjects were selected for the study and whether the examination of the medical history for cataracts was performed prior to or after recruitment. The Panel also notes that no information is provided on the extent to which current lutein intakes (i.e. retrieved after diagnosis of cataracts) may relate to past lutein intakes (i.e. which may have contributed to the development of cataracts). The Panel considers that no conclusions can be drawn from this study for the scientific substantiation of the claim.
With respect to the mechanism by which lutein could exert the claimed effect, a number of human intervention studies, narrative reviews and text books were provided in relation to the bioavailability and metabolism of lutein, and in relation to its role as a structural component of the eye. The Panel notes that dietary lutein is bioavailable, and that it is one of the carotenoids found in the macula of the human eye. A number of in vitro and ex vivo studies investigated the antioxidant activity of carotenoids, including lutein. These included four studies on the effect of lutein in eye tissues subjected to oxidative stress (two in cultures of rat retinal cells, one in porcine retinal homogenates, and one in cultured human retinal cells) and one study which investigated light-induced singlet oxygen generation in post-mortem human macula and retinal pigment epithelium/choroid. The Panel notes that lutein can act as a free radical scavenger in vitro. However, the Panel considers that the evidence provided in these ex vivo and in vitro studies does not establish that these models could predict the occurrence of an effect of lutein on the protection of cells or molecules (e.g. DNA, proteins and lipids) in the human eye from oxidative damage in vivo.
Sasaki et al. (2011) investigated in mice, after light exposure, the effect of lutein intake on visual function assessed with electroretinograms, thickness of outer nuclear layer of the enucleated eyes, photoreceptor cell apoptosis and light-induced DNA damage. Two groups of mice received a standard chow and another group received for 10 days the same chow supplemented with 0.1 % lutein, providing a daily lutein intake estimated to be 170 mg/kg body weight, which is about 500 times the maximum dose used in human interventions. One group on the control diet, and the supplemented group, were dark-adapted for 12 hours, then exposed to a single light exposure with 5,000 lux of a white fluorescence lamp over three hours. The number of animals per group varied between five and eight according to the results reported. The Panel notes that no evidence was provided on how this high dose of lutein in animals relates to a dose in humans. The Panel considers that no conclusions can be drawn from this animal study with respect to the mechanisms by which lutein could exert the claimed effect.
The remaining animal, in vitro and ex vivo studies provided were either not designed to assess the effects of lutein per se on the proposed outcomes (e.g. addressed the effects of carotenoids other than lutein, the effects of lutein in combination with other carotenoids (e.g. zeaxanthin), or the effects of xanthophyll-depleted diets with or without lutein supplementation), assessed outcomes unrelated to vision (e.g. inflammation; and cell damage and/or oxidative stress in bone marrow, blood or liver), or provided insufficient information for a scientific evaluation (e.g. letters to the editor). The Panel considers that no conclusions can be drawn from these references with respect to the mechanisms by which lutein could exert the claimed effect.
In weighing the evidence, the Panel took into account that one human intervention study in healthy subjects did not show an effect of lutein on visual acuity or glare sensitivity, that the results of this study were inconsistent as regards contrast sensitivity, and that the evidence provided for a mechanism by which lutein could exert the claimed effect in vivo in humans is weak.
The Panel concludes that the evidence provided is insufficient to establish a cause and effect relationship between the consumption of lutein and maintenance of normal vision.

Warunki i możliwe ograniczenia stosowania oświadczenia

Maximum Lutein /Zeaxanthin ADI level is 2mg/Kg of Body Weight. In the various human clinical studies the dosage of Lutein administered varies from 2.4 to 30 mg per day 10 mg/day 30 mg/day 15 mg/day Supplementation of AMD patients with a vitamin/antioxidant cocktail that included 15 mg of lutein for 18 months resulted in a two-fold higher improvement in visual acuity Patients ingesting the lutein supplement 10 mg/day experienced 50% increase in macular pigment density and significant improvements in several objective measurements of visual function including glare recovery, contrast sensitivity, and visual acuity versus placebo