Scientific Opinion on the substantiation of health claims related to
vitamin A and cell differentiation (ID 14), function of the immune system
(ID 14), maintenance of skin and mucous membranes (ID 15, 17),
maintenance of vision (ID 16), maintenance of bone (ID 13, 17),
maintenance of teeth (ID 13, 17), maintenance of hair (ID 17), maintenance
of nails (ID 17), metabolism of iron (ID 206), and protection of DNA,
proteins and lipids from oxidative damage (ID 209) pursuant to
Article 13(1) of Regulation (EC) No 1924/2006[sup]1[/sup]
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA)2
European Food Safety Authority (EFSA), Parma, Italy
Słowa kluczowe:
Vitamin A
bone
cell differentiation
hair
health claims
immune system
iron
nails
oxidative damage
skin
teeth
vision
1. Charakterystyka żywności / składnika
The food constituent that is the subject of the health claims is vitamin A which is a well recognised nutrient. It is measurable in foods by established methods.
The term vitamin A describes a group of lipid soluble compounds related metabolically to all-trans-retinol. In the diet, vitamin A is found in products of animal origin, as retinyl esters, mainly retinyl palmitate. Other esters (oleate, stearate, myristate), and retinol contribute to the dietary vitamin A intake. Some carotenoids (α- and β-carotenes, β-cryptoxanthine) can be cleaved into retinol, via an enzymatic process in the small intestine. Retinoic acids are considered as the molecular species responsible for all the functions attributed to vitamin A, with the exception of vision, where only retinal is able to exert an action (SCF, 2002).
Different forms of vitamin A are authorised for addition to foods and for use in food supplements (Annex II of the Regulation (EC) No 1925/20064 and Annex II of Directive 2002/46/EC5). This evaluation applies to vitamin A naturally present in foods and those forms authorised for addition to foods and for use in food supplements (Annex II of the Regulation (EC) No 1925/2006 and Annex II of Directive 2002/46/EC).
The Panel considers that the food constituent, vitamin A, which is the subject of the health claims is sufficiently characterised.
2. Znaczenie oświadczenia dla zdrowia człowieka
2.1. Różnicowanie komórek (ID 14)
The claimed effect is “cell differentiation including immune system”. The Panel assumes that the target population is the general population.
The Panel considers that normal cell differentiation is beneficial to human health.
2.2. Funkcjonowanie układu odpornościowego (ID 14)
The claimed effect is “cell differentiation including immune system”. The Panel assumes that the target population is the general population.
The Panel considers that a normal function of the immune system is beneficial to human health.
2.3. Utrzymanie prawidłowego stanu skóry i błon śluzowych (ID 15, 17)
The claimed effects are “structure and function of the skin and mucous membranes (such as in the lung, intestines, nose, eyes and female reproductive tract)” and “Bone/Teeth/Hair/Skin and Nail health”. The Panel assumes that the target population is the general population.
The Panel considers that maintenance of normal skin and mucous membranes is beneficial to human health.
2.4. Utrzymanie prawidłowego wzroku (ID 16)
The claimed effect is “vision”. The Panel assumes that the target population is the general population.
The Panel considers that maintenance of normal vision is beneficial to human health.
2.5. Utrzymanie prawidłowego stanu kości (ID 13, 17)
The claimed effects are “bone/teeth/hair/skin and nail health” and “bone growth and development of teeth”. The Panel assumes that the target population is the general population.
The Panel considers that maintenance of normal bone is beneficial to human health.
2.6. Utrzymanie prawidłowego stanu zębów (ID 13, 17)
The claimed effects are “bone/teeth/hair/skin and nail health” and “bone growth and development of teeth”. The Panel assumes that the target population is the general population.
The Panel considers that maintenance of normal teeth is beneficial to human health.
2.7. Utrzymanie prawidłowego stanu włosów (ID 17)
The claimed effect is “bone/teeth/hair/skin and nail health”. The Panel assumes that the target population is the general population.
The Panel considers that maintenance of normal hair is beneficial to human health.
2.8. Utrzymanie prawidłowego stanu paznokci (ID 17)
The claimed effect is “bone/teeth/hair/skin and nail health”. The Panel assumes that the target population is the general population.
The Panel considers that maintenance of normal nails is beneficial to human health.
2.9. Metabolizm żelaza (ID 206)
The claimed effect is “metabolism of iron”. The Panel assumes that the target population is the general population.
The Panel considers that normal metabolism of iron is beneficial to human health.
2.10. Ochrona DNA, białek i lipidów przed uszkodzeniem oksydacyjnym (ID 209)
The claimed effect is “oxidative stress. Acts as antioxidant and helps protect the body tissues against the potentially damaging effects of free radicals”. The Panel assumes that the target population is the general population.
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, 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 like antioxidant nutrients.
The Panel considers that the protection of biologically relevant molecules such as DNA, proteins and lipids from oxidative damage is beneficial to human health.
3. Naukowe uzasadnienia wpływu na zdrowie człowieka
It is recognised that vitamin A is important for normal vision, gene expression, reproduction, embryonic development, growth and immune function (IoM, 2001). Vitamin A deficiency signs include impaired dark adaptation, abnormal electroretinograms, follicular hyperkeratosis and lowered blood haemoglobin (SCF, 1992).
3.1. Różnicowanie komórek (ID 14)
Vitamin A binds to nuclear retinoid receptors leading to either the activation or the inhibition of gene expression. Depending on the cell line and dosage, cell differentiation can be stimulated or inhibited. In animal models, it has been shown that vitamin A is involved in the differentiation of the epithelium, mainly in the respiratory tract (Biesalski et al., 1995). In rapidly dividing cells, retinoids efficiently inhibit progression through the cell cycle and induce cell differentiation. Although almost all studies of retinoid mechanisms have been conducted in isolated cells, good congruence exists between their action in cells and their effect in intact animals or humans (Ross, 2006).
The Panel notes that vitamin A is involved in the differentiation of many cells showing either an inhibiting or stimulating effect.
The Panel concludes that a cause and effect relationship has been established between the dietary intake of vitamin A and normal cell differentiation. However, the evidence provided does not establish that inadequate intake of vitamin A leading to impaired cell differentiation occurs in the general EU population.
3.2. Funkcjonowanie układu odpornościowego (ID 14)
It has been reported that all-trans-retinoic acid stimulates the proliferation of T-lymphoid cells, while it inhibits the proliferation of B-cells and B-cell precursors. In particular, the lymphocyte response to mitogens is highly retinoid dependent. Retinoic acid also exerts an effect on the T-helper cell balance by suppressing Th1 development and enhancing Th2 development. In addition, it is has been indicated that vitamin A deficiency enhances macrophage-mediated inflammation by increasing production of IL-12 and IFN-γ, but impairs the ability of macrophages to ingest and kill bacteria. Dentritic cells are also a target of retinoic acid. It regulates the survival and antigen presentation by immature dentritic cells, as well as the maturation of immature to mature dentritic cells. Other effects of vitamin A on the immune system are related to apoptotic effects on immune-competent cells during back regulation of immune reactions and during thymic selection and to the alteration of genes relevant to the immune response (Ruhl, 2007).
The efficacy of supplementing vitamin A on infection rates has been examined in several randomised, double-blind, placebo-controlled trials of malnourished children in various regions of the developing world. Antibody-mediated immunity has been shown to be severely impaired in children with vitamin A deficiency. Providing vitamin A supplements has been found to improve the antibody titer response to measles vaccines, maintain gut integrity, lower the incidence of respiratory tract infections, and reduce mortality associated with diarrhoea and measles but not pneumonia. There are clinical data suggesting that vitamin A deficiency in HIV-1-infected individuals contributes to mortality, disease progression, and maternal-infant disease transfer (Field et al., 2002).
The Panel concludes that a cause and effect relationship has been established between the dietary intake of vitamin A and a normal function of the immune system. However, the evidence provided does not establish that inadequate intake of vitamin A leading to impaired function of the immune system occurs in the general EU population.
3.3. Utrzymanie prawidłowego stanu skóry i błon śluzowych (ID 15, 17)
Vitamin A is required for the integrity of epithelial cells throughout the body. Retinoic acid, through the activation of retinoic acid and retinoid X receptors in the nucleus, regulates the expression of various genes that encode for structural proteins, enzymes, extracellular matrix proteins, and retinol binding proteins and receptors (IoM, 2001).
The systemic effects of vitamin A deficiency include dryness of the skin (follicular hyperkeratosis), loss of mucus-secreting goblet cells in the trachea and respiratory tract, and a generalised flattening of epithelia (squamous metaplasia, sometimes with keratinisation) throughout the body (Ross, 2005).
The Panel concludes that a cause and effect relationship has been established between dietary intake of vitamin A and maintenance of normal skin and mucous membranes. However, the evidence provided does not establish that intake of vitamin A inadequate for the maintenance of normal skin and mucous membranes occurs in the general EU population.
3.4. Utrzymanie prawidłowego wzroku (ID 16)
11-cis-retinaldehyde (retinal) is required by the eye for the transduction of light into neural signals necessary for vision. In the rods 11-cis-retinal is bound to opsin, thus forming the visual pigment, rhodopsin. The absorption of light catalyses the photoisomerisation of 11-cis-retinal to all-trans-retinal, which triggers the signalling to neuronal cells associated with the brains neuronal cortex. Without an adequate level of vitamin A in the retina the function of the rods in dim light situations becomes compromised, resulting in abnormal dark adaptation (night blindness) (IoM, 2001).
In a very different role, the cornea of the eye depends on vitamin A delivered in tear fluid to maintain cell differentiation and structural integrity. Vitamin A deficiency leads to a reduction in mucus production by the goblet cells of the conjunctival membranes and the cornea becomes dry (xerosis). Also Bitôt spots (cellular debris) may develop, usually at the outer quadrant of the eyes (Ross, 2006).
The Panel concludes that a cause and effect relationship has been established between the dietary intake of vitamin A and maintenance of normal vision. However, the evidence provided does not establish that intake of vitamin A inadequate for the maintenance of normal vision occurs in the general EU population.
3.5. Utrzymanie prawidłowego stanu kości (ID 13, 17)
A total of 32 references were cited to substantiate the claimed effect. Some 13 of these were textbooks or opinions from scientific bodies in which the claimed effect was not stated. A further 19 references were related to vitamins other than vitamin A or minerals. The Panel notes that the references cited provided no scientific data that could be used to substantiate the claimed effect.
The Panel concludes that a cause and effect relationship has not been established between the dietary intake of vitamin A and maintenance of normal bone.
3.6. Utrzymanie prawidłowego stanu zębów (ID 13, 17)
A total of 32 references were cited to substantiate the claimed effect. Some 13 were textbooks or opinions from scientific bodies in which the claimed effect was not stated. A further 19 references were related to vitamins other than vitamin A or minerals. The Panel notes that the references cited provided no scientific data that could be used to substantiate the claimed effect.
The Panel concludes that a cause and effect relationship has not been established between the dietary intake of vitamin A and maintenance of normal teeth.
3.7. Utrzymanie prawidłowego stanu włosów (ID 17)
A total of 17 references were cited to substantiate the claimed effect from which 7 were related to vitamins other than vitamin A, 5 were textbooks and 5 were opinions from scientific bodies in which the claimed effect was not stated. The Panel notes that the reference cited provided no scientific data that could be used to substantiate the claimed effect.
The Panel concludes that a cause and effect relationship has not been established between the dietary intake of vitamin A and maintenance of normal hair.
3.8. Utrzymanie prawidłowego stanu paznokci (ID 17)
A total of 17 references were cited to substantiate the claimed effect from which 7 were related to vitamins other than vitamin A, 5 were textbooks and 5 were opinions from scientific bodies in which the claimed effect was not stated. The Panel notes that the reference cited provided no scientific data that could be used to substantiate the claimed effect.
The Panel concludes that a cause and effect relationship has not been established between the dietary intake of vitamin A and maintenance of normal nails.
3.9. Metabolizm żelaza (ID 206)
A direct correlation between haemoglobin and serum retinol concentrations has been observed. Various studies suggest that vitamin A deficiency impairs iron mobilisation from stores and vitamin A supplementation improves haemoglobin concentration (IoM, 2001).
The Panel concludes that a cause and effect relationship has been established between dietary intake of vitamin A and normal metabolism of iron. However, the evidence provided does not establish that inadequate intake of vitamin A leading to impaired metabolism of iron occurs in the general EU population.
3.10. Ochrona DNA, białek i lipidów przed uszkodzeniem oksydacyjnym (ID 209)
One reference to a textbook on sports nutrition was cited to substantiate the claimed effect in which the claimed effect was not stated. The Panel notes that the reference cited provided no scientific data that could be used to substantiate the claimed effect.
The Panel concludes that a cause and effect relationship has not been established between the dietary intake of pre-formed vitamin A and protection of DNA, proteins and lipids from oxidative damage.
4. Uwagi do zaproponowanego brzmienia oświadczenia
4.1. Różnicowanie komórek (ID 14)
The Panel considers that the following wording reflects the scientific evidence: “Vitamin A contributes to normal cell differentiation.”
4.2. Funkcjonowanie układu odpornościowego (ID 14)
The Panel considers that the following wording reflects the scientific evidence: “Vitamin A contributes to a normal function of the immune system.”
4.3. Utrzymanie prawidłowego stanu skóry i błon śluzowych (ID 15, 17)
The Panel considers that the following wording reflects the scientific evidence: “Vitamin A contributes to the maintenance of normal skin and mucous membranes.”
4.4. Utrzymanie prawidłowego wzroku (ID 16)
The Panel considers that the following wording reflects the scientific evidence: “Vitamin A contributes to the maintenance of normal vision.”
4.5. Metabolizm żelaza (ID 206)
The Panel considers that the following wording reflects the scientific evidence: “Vitamin A contributes to normal iron metabolism.”
5. Warunki i możliwe ograniczenia stosowania oświadczenia
The Panel considers that in order to bear the claims a food should be at least a source of vitamin A as per Annex to Regulation (EC) No 1924/2006. Such amounts can be easily consumed as part of a balanced diet. The target population is the general population. Tolerable Upper Intake Levels (UL) for pre-formed vitamin A have been established for children and adults. The Tolerable Upper Intake Level for adults has been set at 3000 µg RE/day (SCF, 2002).
Wnioski
On the basis of the data presented, the Panel concludes that:
The food constituent, vitamin A, which is the subject of the health claims, is sufficiently characterised.
Cell differentiation (ID 14)
The claimed effect is “cell differentiation including immune system”. The target population is assumed to be the general population. Normal cell differentiation is beneficial to human health.
A cause and effect relationship has been established between the dietary intake of vitamin A and normal cell differentiation.
The evidence provided does not establish that inadequate intake of vitamin A leading to impaired cell differentiation occurs in the general EU population.
The following wording reflects the scientific evidence: “Vitamin A contributes to normal cell differentiation”.
Function of the immune system (ID 14)
The claimed effect is “cell differentiation including immune system”. The target population is assumed to be the general population. A normal function of the immune system is beneficial to human health.
A cause and effect relationship has been established between the dietary intake of vitamin A and a normal function of the immune system.
The evidence provided does not establish that inadequate intake of vitamin A leading to impaired function of the immune system occurs in the general EU population.
The following wording reflects the scientific evidence: “Vitamin A contributes to a normal function of the immune system”.
Maintenance of skin and mucous membranes (ID 15, 17)
The claimed effects are “structure and function of the skin and mucous membranes (such as in the lung, intestines, nose, eyes and female reproductive tract)” and “bone/teeth/hair/skin and nail health”. The target population is assumed to be the general population. Maintenance of normal skin and mucous membranes is beneficial to human health.
A cause and effect relationship has been established between the dietary intake of vitamin A and maintenance of normal skin and mucous membranes.
The evidence provided does not establish that intake of vitamin A inadequate for the maintenance of normal skin and mucous membranes occurs in the general EU population.
The following wording reflects the scientific evidence: “Vitamin A contributes to the maintenance of normal skin and mucous membranes”.
Maintenance of vision (ID 16)
The claimed effect is “vision”. The target population is assumed to be the general population. Maintenance of normal vision is beneficial to human health.
A cause and effect relationship has been established between the dietary intake of vitamin A and maintenance of normal vision.
The evidence provided does not establish that intake of vitamin A inadequate for the maintenance of normal vision occurs in the general EU population.
The following wording reflects the scientific evidence: “Vitamin A contributes to the maintenance of normal vision”.
Maintenance of bone (ID 13, 17)
The claimed effects are “bone/teeth/hair/skin and nail health” and “bone growth and development of teeth”. The target population is assumed to be the general population. Maintenance of normal bone is beneficial to human health.
A cause and effect relationship has not been established between the dietary intake of vitamin A and maintenance of normal bone.
Maintenance of teeth (ID 13, 17)
The claimed effects are “bone/teeth/hair/skin and nail health” and “bone growth and development of teeth”. The target population is assumed to be the general population. Maintenance of normal teeth is beneficial to human health.
A cause and effect relationship has not been established between the dietary intake of vitamin A and maintenance of normal teeth.
Maintenance of hair (ID 17)
The claimed effect is “bone/teeth/hair/skin and nail health”. The target population is assumed to be the general population. Maintenance of normal hair is beneficial to human health.
A cause and effect relationship has not been established between the dietary intake of vitamin A and maintenance of normal hair.
Maintenance of nails (ID 17)
The claimed effect is “bone/teeth/hair/skin and nail health”. The target population is assumed to be the general population. Maintenance of normal nails is beneficial to human health.
A cause and effect relationship has not been established between the dietary intake of vitamin A and maintenance of normal nails.
Metabolism of iron (ID 206)
The claimed effect is “metabolism of iron” (ID 206). The target population is assumed to be the general population. Normal metabolism of iron is beneficial to human health.
A cause and effect relationship has been established between the dietary intake of vitamin A and normal metabolism of iron.
The evidence provided does not establish that inadequate intake of vitamin A leading to impaired metabolism of iron occurs in the general EU population.
The following wordings reflect the scientific evidence: “Vitamin A contributes to normal iron metabolism”.
Protection of DNA, proteins and lipids from oxidative damage (ID 209)
The claimed effect is “oxidative stress”. The target population is assumed to be the general population. Protection of DNA, proteins and lipids from oxidative damage is beneficial to human health.
A cause and effect relationship has not been established between the dietary intake of vitamin A and the protection of DNA, proteins and lipids from oxidative damage.
Conditions and restrictions of use
In order to bear the claims a food should be at least a source of vitamin A as per Annex to Regulation (EC) No 1924/2006. Such amounts can be easily consumed as part of a balanced diet. The target population is the general population.
