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Scientific Opinion on the substantiation of health claims related to lutein and maintenance of vision (ID 1603, 1604, 1931) pursuant to Article 13(1) of Regulation (EC) No 1924/2006[sup]1[/sup] EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA)2, 3 European Food Safety Authority (EFSA), Parma, Italy
Słowa kluczowe: Lutein   health claims   vision  
ID:    1603      1604      1931  
Produkty: Luteina  

1. Charakterystyka żywności / składnika

The food constituent that is the subject of the health claim is lutein which is a carotenoid naturally present in food, especially in green leafy vegetables such as spinach and kale. 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 effects are “required for macular pigmentation in the eyes which helps maintenance of healthy eye functions”, “eye health” and “macular pigment blue light filter in eyes antioxidant activity”. The Panel assumes that the target population is the general population.
From the data provided, it has not been established that a change in macular pigment in people with healthy eyes is related to eye function. Normal vision, however, is a function of the eye which 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

A total of 232 references were cited to substantiate the claimed effects, including 36 textbooks or opinions from authoritative bodies. Some data, however, were not considered as pertinent by the Panel, because the constituent (n=13) or the endpoint (n=23) that were studied differed from those proposed for this particular claim. Some 57 of the remaining references were narrative reviews and there was one comprehensive review. Collectively, the texts and narrative reviews establish that lutein is one of the carotenoids found in the macula of the eye and some of the narrative reviews discuss a putative protective role for lutein based on proposed antioxidant mechanisms against possible oxidative damage by blue light of the photoreceptor layer of the retina. The comprehensive review (Bartlett and Eperjesi, 2003) included seven randomised controlled trials (RCTs) that have investigated the role of nutritional supplementation with antioxidant vitamins or minerals on progression of age-related macular degeneration (AMD). A positive effect of supplementation was found in three of the seven studies and one of these, the Lutein Antioxidant Supplementation Trial (LAST), involved lutein either alone or in combination with other antioxidants (the LAST trial is discussed later with the other human interventions).
A total of 86 references detailing human studies were considered to be pertinent and 42 of these were intervention studies. The remainder reported on epidemiological studies of various designs. The human intervention studies could be divided into those which investigated end points relevant to vision (n=34) and those which investigated the bioavailability of lutein (n=8). Those 34 studies which investigated end points relevant to vision could be sub-divided into those which investigated lutein supplementation in patients with inherited retinal degeneration (n=5), patients with cataracts (n=1), patients with diabetic retinopathy (n=1), patients with age related maculopathy or macular degeneration (designated together as ARM; n=9), and the remaining 18 intervention studies were undertaken in healthy people.
The five studies in patients with various forms of inherited retinal degeneration do not provide data that can be extrapolated to the general population. Nevertheless, it is interesting that three of these studies (Aleman et al., 2001; Duncan et al., 2002; Adackapara et al., 2008) did not provide evidence that lutein supplementation could ameliorate the various conditions by improving measures of visual function even though lutein supplementation increased the macular pigment optical density (MPOD) of the eye in some patients. The very small randomised double-blind study (Olmedilla et al., 2003) in 10 patients with cataracts provides little support for the hypothesis that dietary lutein is beneficial to eye function in the general population. The study of Cangemi (2007) in 37 patients with diabetic retinopathy had several major weaknesses; foremost amongst these weaknesses was that the study did not have a control group and, moreover, used a nutritional supplement that contained 10 additional nutrients along with lutein.
The nine references on interventions in patients with ARM describe seven studies. The Panel notes the poor design and the small number of ARM patients in the majority of these studies and the confounding of lutein supplementation with other nutrients in all except the double-blinded placebo- controlled LAST study and the small uncontrolled studies of Olmedilla et al. (2001) in five patients and Koh et al. (2004) in seven patients. Although the LAST study showed that lutein (10 mg/day) improved visual acuity and contrast sensitivity in 29 patients, it is difficult to extrapolate findings from this one study involving a small number of ARM patients to the general population. The Panel also notes that findings from these studies identify a substantial number of patients who do not respond to lutein or antioxidant supplementation with increases in MPOD and the uncertainty surrounding small changes in this measure as an indicator of improved vision.
There were 18 intervention studies cited in healthy people and these studies were of varied quality and design. Berendschot et al. (2000) showed an increase in MPOD in eight people (no control group) given 10 mg/day lutein over 12 weeks. Bone et al. (2003) demonstrated similar increases in MPOD in three subjects taking a range (2.4-30 mg/day) of lutein supplements for up to 30 days. Landrum et al. (1997) gave two subjects 30 mg/day equivalent of lutein for 140 days and also found MPOD to increase. Schweitzer et al. (2002) in 10 volunteers who took 6 mg/day lutein over 40 days assessed MPOD by objective methods of imaging spectrometry and evaluation of laser scanner images and found MPOD to plateau at day 30. In contrast, Cardinault et al. (2003) found that supplementing with lutein (9 mg/day) for five weeks in 12 young (mean age 26.9 years) and 17 older (mean age 67.3 years) people did not increase MPOD in either group (no placebo control). In a much larger and placebo-controlled study compared with the aforementioned studies, Schalch et al. (2007) showed that lutein (10 mg/day) supplementation (one of four supplementation groups) in 23 subjects increased MPOD and decreased blue light sensitivity in the fovea of the retina compared with 23 subjects given placebo. Johnson et al. (2008) randomly assigned 49 women to placebo, lutein (12 mg/day), or lutein plus docosahexaenoic acid and found increased MPOD in both lutein groups. In the intervention of Kvansakul et al. (2006), 34 subjects from a carotenoid supplementation trial were assessed for MPOD, wavefront aberrations, scattered light and high mesopic contrast acuity thresholds (CAT). Six subjects were tested from phase 1 (10 mg/day lutein for six months) and three from phase 2 (20 mg/day lutein for six months) of the lutein arm and a further nine and 10 subjects were tested from phase 1 and phase 2 respectively of the lutein plus zeaxanthin arm and 11 and four subjects from
placebo in phase 1 and 2 respectively. There was a statistically significant lowering of CAT in the lutein arms but there was no correlation of CAT with MPOD.
Those intervention studies which showed that lutein alone could increase MPOD are supported by some but not all of the cited studies which used supplements containing lutein along with antioxidants. Some of these studies also investigated the effect of supplemental lutein on eye function. Morganti et al. (2004) found a relationship between global visual function as determined by different visual surveillance tests and oral intake of lutein in 50 volunteers. Bartlett and Eperjesi (2008), however, found no evidence that a lutein (6 mg/day) and antioxidant supplement in a nine and 18 month double-blinded placebo-controlled trial (n=21 active and n=25 placebo) affected visual function assessed by distance and near-visual acuity, contrast sensitivity and photostress recovery time in people with healthy eyes.
There is also support from some but not all of the studies which intervened with dietary modifications that dietary lutein might influence MPOD. Hammond et al. (1997) showed that in 11 subjects who modified their diet to increase carotenoid intake, MPOD was increased along with serum lutein in most (n=8) but not all of the subjects. Kopsell et al. (2006) also showed in 10 volunteers who consumed 50 g spinach servings five days per week for 12 weeks that serum lutein and MPOD were increased. Johnson et al. (2000) found in seven subjects who consumed spinach and maize with their daily diets for 15 weeks that MPOD increased during the intervention and remained elevated for two months post intervention. Francois et al. (2006), however, found that although both dietary modification and an antioxidant supplement containing lutein increased, inter alia, serum lutein concentrations neither intervention had an effect on MPOD in 48 older subjects over 12 weeks. In addition, Muth et al. (2001) could not demonstrate any effect of bilberry extracts (160 mg/day) taken for 21 days on night visual acuity or night contrast in 15 young subjects with good vision using a cross-over design.
In weighing the evidence from these dietary interventions, the Panel notes that, although many of the interventions were in very small numbers of people and of poor design, it is established that supplemental lutein can increase macular pigment in most but not all healthy eyes. It remains unclear, however, whether such changes in macular pigment are associated with any beneficial physiological effect in the longer term. Rather the little evidence that was presented on the effect of dietary lutein on vision during the supplemental period is weighted strongly towards the conclusion that there is no functional benefit for healthy eyes.
The 41 epidemiological studies cited were comprised of prospective studies which investigated: associations of estimates of dietary lutein with incidence of ARM (n=5) and cataracts (n=4); associations of blood measures of lutein with incidence of cataracts (n=1); case-control studies which investigated: relationships between estimates of dietary lutein in ARM (n=4); blood measures of lutein in ARM (n=5) and in cataract (n=1) cases and controls; macular lutein content (n=1) in ARM cases and controls; cross-sectional studies of associations of estimates of dietary lutein with ARM (n=3) and cataract (n=2) prevalence. Studies were also cited that evaluated: MPOD (n=1) in ARM cases and controls; MPOD (n=2) as a risk factor for ARM; relationships of either dietary estimates (n=5) or blood measures (n=2) of lutein and MPOD; relationships between estimates of dietary lutein and diabetic retinopathy (n=1); and associations of age (n=3) or smoking (n=1) on MPOD or visual function in cross-sectional studies.
In general, consistent epidemiological relationships were found between dietary or blood lutein measures and ARM or cataract incidence in prospective studies and prevalence of these eye diseases in cross-sectional or case-control studies. Estimates of food intake in epidemiological studies, however, are fraught with measurement error and the variable content of lutein in foods make it difficult to derive accurate amounts of lutein consumed. Moreover, the presence of other nutrients in food makes it impossible to study any effect of lutein in isolation. Blood measures often correlate
poorly with dietary intake of lutein and also can be affected by a host of unknown environmental and physiological factors including the presence of the disease. Similarly, although there were generally consistent relationships between dietary or blood measures of lutein and MPOD, the relevance of such relationships is further limited by the fact that there is no evidence that high macular density confers a protective effect in ARM or is related to vision (Davies and Morland, 2004; Broekmans et al., 2002).
A total of 12 references describing ex vivo or in vitro work were cited. These references fall under the broad headings of carotenoid composition of donor retina or eyes (n=8), metabolism of carotenoids (n=1) and antioxidant activity of carotenoids (n=3). The studies establish that lutein is a carotenoid found in the retina of the eye and that lutein has antioxidant activity in vitro. A further five references were cited of animal studies: two in quail on mainly zeaxanthin effects on photoreceptor cell death; and one each in the rat (on effects of lutein and zeaxanthin taken together on retinal oxidative damage in a diabetes model), mouse (inhibition of inflammatory effects by lutein) and rhesus monkey (bioavailability and accumulation of lutein and zeaxanthin) which add little relevant data to the total body of evidence presented on lutein in the human and ex vivo/in vitro studies.
In weighing the evidence, the Panel considered that the generally consistent epidemiological evidence indicating a possible role for lutein in vision was not supported by the weight of evidence from the human intervention studies. While it is established that lutein can increase macular pigment density in most but not all healthy subjects, it has not been established that such increases in macular density is related to vision.
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.

Wnioski

On the basis of the data presented, the Panel concludes that:
The food constituent, lutein, which is the subject of the health claims is sufficiently characterised.
The claimed effects are “required for macular pigmentation in the eyes which helps maintenance of healthy eye functions”, “eye health” and “macular pigment blue light filter in eyes antioxidant activity”. The target population is assumed to be the general population. Maintenance of normal vision is a beneficial physiological effect.
The evidence provided is insufficient to establish a cause and effect relationship between the consumption of lutein and maintenance of normal vision.