ID 197 - Beta-karoten

PL: Beta-karoten
EN: Beta carotene
Pdf: vitamin A

Oświadczenie (2)

1. Charakterystyka żywności / składnika

The food constituent that is the subject of the health claims is beta-carotene ( -carotene). Beta- carotene is a well recognised dietary constituent and is measurable in foods, blood and tissues by established methods. The compound is naturally available from a great variety of fruits and vegetables. Beta-carotene is a precursor of vitamin A (pro-vitamin A) and is authorised for addition to foods and for use in food supplements (Annex II of Regulation (EC) No 1925/20066 and Annex II of Directive 2002/46/EC7). This evaluation applies to beta-carotene naturally present in foods and added to foods (Annex II of Regulation (EC) No 1925/2006 and Annex II of Directive 2002/46/EC).
The Panel considers that the food constituent, beta-carotene, which is the subject of the health claims, is sufficiently characterised.

2.1. Ochrona DNA, białek i lipidów przed uszkodzeniem oksydacyjnym (ID 19, 197, 1262, 1460)

The claimed effects are “antioxidants and aging”, “protection of tissues and skin against oxidant agents (sun rays exposure)”, “antioxidant activity” and “protection of DNA”. The Panel assumes that the target population is the general population.
No definition has been provided of “aging” or “premature aging” in relation to the antioxidant properties of foods. The Panel considers that the claimed effect is general and non-specific, and does not comply with the criteria laid down in Regulation (EC) No 1924/2006. The Panel also considers that claims made on the antioxidant capacity/content or properties of food/food constituents 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 capability exerts a beneficial physiological effect in humans as required by Regulation (EC) No 1924/2006.
In the context of the proposed wordings, the Panel assumes that the claimed effects relate to the protection of body cells and molecules from oxidative damage caused by free radicals.
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 biologically relevant 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 178, 197, 1263, 1461, 1968, 2320)

The claimed effects are “skin health”, “peau”, “skin aging” and “protection of tissues and skin against oxidant agents (sun rays exposure), antioxidant activity”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings, the Panel assumes that the claimed effects refer to protection of the skin from UV-induced damage, including photo-oxidative damage, and to “promotion of the pigmentation and tanning of the skin”. Promotion of pigmentation of the skin is a mechanism by which the skin can be protected from UV-induced damage.
The Panel considers that protection of the skin from UV-induced (including photo-oxidative) damage is a beneficial physiological effect.

3.1. Ochrona DNA, białek i lipidów przed uszkodzeniem oksydacyjnym (ID 19, 197, 1262, 1460)

A number of the references provided were narrative reviews or consensus opinions on the health effects of beta-carotene which did not allow an evaluation of original data, or reported on intervention studies that assessed the effects of beta-carotene in combination with other carotenoids or antioxidant vitamins on health outcomes unrelated to the claimed effect, including UV-induced erythema or UV- induced immunomodulation, which are not reliable markers of photo-oxidative damage. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
The human intervention studies provided, which investigated the effects of beta-carotene on oxidative damage to molecules in blood, were not controlled (i.e. did not include a control arm with no treatment). In addition, these studies assessed changes in DNA strand breaks (Zhao et al., 2006), changes in ex vivo DNA damage after challenge with hydrogen peroxide (Torbergsen and Collins, 2000; Zhao et al., 2006) or changes in susceptibility of LDL to oxidation determined in the presence of copper ions and analysed by measuring thiobarbituric acid-reactive substances (TBARS) (Levy et
al., 2000), which are not reliable markers of oxidative damage to DNA and lipids, respectively. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
The Panel concludes that a cause and effect relationship has not been established between the dietary intake of beta-carotene and protection of DNA, proteins and lipids from oxidative damage.

3.2. Ochrona skóry przed uszkodzeniem promieniami ultrafioletowymi (UV) (ID 178, 197, 1263, 1461, 1968, 2320)

A number of the references provided were narrative reviews or consensus opinions on the health effects of beta-carotene that did not allow the evaluation of original data, or reported on intervention studies that assessed the effects of beta-carotene in combination with other carotenoids or antioxidant vitamins 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.
Green et al. (1999) investigated the effect of daily sunscreen application and beta-carotene supplementation on the prevention of skin basal cell and squamous cell carcinomas in a community-based randomised controlled trial. Individuals were assigned to four treatment groups: beta-carotene (30 mg/day) supplementation (n=404), daily application of a sun screen (SPF 15) plus placebo (n=408), beta-carotene plus sunscreen (n=416), placebo only (n=393). Study participants were randomly selected residents of Nambour (Queensland, Australia) aged 20 to 69 years. The endpoints after 4.5 years of follow-up were the incidence of basal cell and squamous cell carcinomas both in terms of number of subjects with newly diagnosed disease and in terms of the numbers of tumours. Out of the 1,621 subjects randomised (n=820 to beta-carotene; n=801 to placebo), 1,383 completed the study and 250 of them developed 758 new skin cancers. All analyses were performed on an intention-to-treat basis. No statistically significant differences between the beta-carotene and placebo groups were observed in the incidence (number of subjects with newly diagnosed disease) of basal cell carcinoma (rate ratio (95% CI) = 1.04 (0.73–1.27)) in the incidence of squamous cell carcinoma (rate ratio (95% CI) = 1.35 (0.84–2.19)) or in the number of tumours diagnosed as basal cell carcinoma (rate ratio (95% CI) = 0.89 (0.64-1.10)) or squamous cell carcinoma (rate ratio (95% CI) = 1.19 (0.89-1.41). There were no significant differences in the incidence of basal cell carcinoma (rate ratio (95% CI) = 1.03 (0.73–1.46)) or squamous cell carcinoma (rate ratio (95% CI) = 0.88 (0.50–1.56)) between groups randomly assigned daily sunscreen and no daily sunscreen. In terms of number of tumours, there was no effect of sunscreen use on incidence of basal cell carcinoma, but the incidence of squamous cell carcinoma was significantly lower in the daily sunscreen group than in the no daily sunscreen group (1,115 vs. 1,832 per 100,000; rate ratio (95% CI) = 0.61 (0.46–0.81)). The Panel considers that this study does not support a role of beta-carotene dietary intake in the protection of the skin against chronic UV-induced damage.
Köpcke and Krutmann (2008) provided data from a meta-analysis of studies on the sunburn-preventing effects of beta-carotene. They included seven small studies all with less than 40 participants, daily doses from 15-180 mg and treatment periods of 3-24 weeks. However, some of the studies included in the meta-analysis were uncontrolled, and therefore the Panel considers that no conclusions can be drawn from this meta-analysis for the scientific substantiation of the claimed effect. All the individual studies included in the meta-analysis are discussed separately below.
Three of the studies included in the meta-analysis were small uncontrolled interventions using skin erythema as a marker of UV-protection (Lee et al., 2000; McArdle et al., 2004; Stahl et al., 2000), and skin malondialdehyde (MDA) concentrations as a marker of UV-induced photo-oxidative damage (Lee et al., 2000). The Panel considers that no conclusions can be drawn from these uncontrolled studies for the scientific substantiation of the claimed effect.
In a double-blind, placebo-controlled study, Garmyn et al. (1995) investigated the effect of synthetic beta-carotene supplementation (90 mg/day) over 23 days on sunburn after a single solar simulated light exposure of three minimal erythemal doses (MED) in 16 healthy Caucasian women (skin type II or III) aged 66±4 years (n=8 per group). Induction of sunburn (apoptotic) cells 24 h after exposure was determined clinically (intensity of erythema) and histologically (number of sunburn cells/mm epidermis) in skin biopsies, which is a direct marker of UV-induced damage to the skin. After supplementation blood and skin concentrations of beta-carotene were significantly higher (more than double) in the beta-carotene group than in the placebo group. No clinical or histologically detectable protection against exposure to 3 MED was observed in the beta-carotene group as compared to the placebo group. The Panel notes that this study does not support a role of beta-carotene dietary intake in the protection of the skin from acute UV-induced damage.
Gollnick et al. (1996) reported a randomised, placebo-controlled, double-blind study with 20 healthy females (20-25 years) of skin type II or III supplemented with 30 mg beta-carotene per day for 10 weeks. After 10 weeks of supplementation, 14 volunteers were exposed, time and intensity
controlled, to natural sunlight (30 latitude, Red Sea, Israel) for 13 days. Skin erythema was assessed by chromatometry in selected skin areas with and without topical sunscreen. Blood concentrations of beta-carotene, epidermal Langerhans cell (LHC) density (per square millimetre of epidermis) by biopsy in the UV-exposed area, delayed type hypersensitivity (DTH) by recall antigens in the volar forearm and lymphocyte counts were assessed at baseline, and before and after UV-radiation exposure. Blood concentrations of beta-carotene did not fall during sun exposure in the beta-carotene group, whereas in the placebo group beta-carotene concentrations decreased significantly to sub-physiological concentrations. Development of erythema in selected exposed skin areas was reported to be lower in the beta-carotene group, but differences between the beta-carotene and placebo group appeared not to be significant. LHC density increased significantly after beta-carotene supplementation. After UV-exposure, LHC density significantly decreased in both groups; however, compared to baseline, this was significant only for the placebo group in the temporarily exposed skin region. Differences in changes between the intervention group and the placebo group with respect to LHC density during UV-exposure were not reported, although they appeared not to be significant. No differences between groups were observed in DTH responses to the different recall antigens. The Panel notes that this study does not support a role of beta-carotene dietary intake in protection of the skin from acute UV-induced damage.
Fuller et al. (1992) performed a parallel designed, double-blind, placebo-controlled intervention study in 24 males (aged 19-39), in which capsules with 30 mg beta-carotene or placebo were given daily, while on a low-carotenoid diet. After 28 days, all subjects received 12 exposures to a UV-A/B radiation source over a 16-day period. The total UV-A dose received ranged from 15.9 to 19.3 J/cm2. The total shorter-wave ultraviolet-radiation (UV-B) dose varied from 1.59 to 1.96 J/cm2. Blood concentrations of carotenoids and DTH tests were assessed at baseline, pre-UV, post-UV and after follow-up. The DTH-test responses were significantly suppressed in the placebo group after UV treatments; the suppression was inversely related to blood beta-carotene concentrations in this group. There was no significant suppression of DTH test responses in the beta-carotene group. The Panel notes that UV-induced suppression of DTH responses may be a consequence of skin damage following overexposure to UV (sun) radiation, i.e. damage to skin LHC. Hence, maintenance of DTH responses may indicate protection of skin from UV-radiation damage. However, the Panel also notes that a reduction in UV-induced suppression of DTH may be a consequence of an immunomodulatory action on the DTH response as such, and therefore may not necessarily be interpreted as a direct consequence of protection from damage to skin LHC. The Panel notes that the data provided in this study did not allow an assessment of whether the maintenance of DTH responses after UV radiation indicates a reduction in UV-induced skin damage or whether it reflects an immunomodulatory effect on DTH responses. The Panel also notes that the difference between the beta-carotene and placebo groups with respect to DTH responses was not statistically significant. The Panel considers that this
study does not support a role of beta-carotene dietary intake in the protection of the skin against acute UV-induced damage.
Herraiz et al. (1998) performed a placebo-controlled, randomised trial in 14 healthy men (mean age 65.5 years). They received 30 mg beta-carotene or placebo daily for 47 days while on a low carotenoid diet. After 28 days half of each group received 12 suberythemic exposures to UV over a 16-day period. DTH tests and plasma carotenoid concentrations were assessed at baseline, and at pre-UV and post-UV time points, with DTH testing performed on an area of skin protected from UV exposure. UV exposure resulted in significantly suppressed DTH responses in the placebo group but not in the beta-carotene group. Higher blood beta-carotene concentrations were significantly associated with maintenance of DTH response. The Panel notes that the difference between the beta-carotene and placebo groups after UV-exposure was not statistically significant and that the data provided in this study did not allow an assessment of whether the maintenance of DTH responses after UV radiation indicates a reduction in UV-induced skin damage or whether it reflects an immunomodulatory effect on DTH responses. The Panel notes that this study does not support a role of beta-carotene dietary intake in protection of the skin against acute UV-induced damage.
Heinrich et al. (2003) reported on a randomised, placebo-controlled, double-blind study with 36 healthy volunteers (22-55 years; 24 female) of skin type II supplemented with either beta-carotene (extract from Dunaliella salina, 24 mg/day) a carotenoid mixture (24 mg/day, equal mixture of beta- carotene, lutein and lycopene) or placebo for 12 weeks. At day 0, and weeks 6 and 12, erythema was induced with 1.25 MED and evaluated by chromametry. Erythema intensity (a-value) significantly decreased in both verum groups compared to placebo (from baseline to week 6, p<0.05 and week 12, p<0.001), whereas no significant differences were observed between the two verum groups. The Panel notes that UV-induced erythema (sunburn or skin reddening) is a primary reaction of the skin following overexposure to UV (sun) radiation, and that it represents an inflammatory response of cutaneous tissue as a consequence of UV radiation-dependent molecular and cellular damage. However, the Panel also notes that while a reduction in skin erythema after UV radiation or sun exposure 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 that the data provided in this study did not allow such effects to be distinguished.
In a randomised, placebo-controlled intervention, 30 male volunteers (prisoners) aged 21-49 years with fair skin were randomly assigned to consume 180 mg/day of synthetic beta-carotene (n=18) or placebo (n=12) for 10 weeks (Mathews-Roth et al., 1972). MED, erythema grade assessed visually and by reflectometer, and degree of pigmentation were measured after 1 and 2 hours of sun exposure. MED was significantly lower in the beta-carotene group than in the placebo group (p<0.025), whereas no significant differences in the intensity of erythema graded visually or by a reflectometer were observed. Skin pigmentation 96 hours after exposure was significantly higher in the beta-carotene group than in the placebo group. The Panel notes that the data provided in this study did not allow an assessment of whether the reduction in skin erythema after UV radiation or sun exposure indicates a reduction in UV-induced skin damage, or whether it reflects a reduction in the capacity of the skin to react to molecular and cellular damage.
In weighing the evidence, the Panel took into account that most of the human intervention studies provided were either uncontrolled or used inappropriate measures of UV-damage to the skin, and that the studies which assessed UV-induced damage to the skin did not find a significant effect of beta-carotene supplementation as compared to placebo.
The Panel concludes that a cause and effect relationship has not been established between the dietary intake of beta-carotene and protection of the skin from UV-induced (including photo-oxidative) damage.

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