Scientific Opinion on the substantiation of health claims related to vitamin C and protection of DNA, proteins and lipids from oxidative damage (ID
129, 138, 143, 148), antioxidant function of lutein (ID 146), maintenance of vision (ID 141, 142), collagen formation (ID 130, 131, 136, 137, 149),
function of the nervous system (ID 133), function of the immune system (ID 134), function of the immune system during and after extreme physical
exercise (ID 144), non-haem iron absorption (ID 132, 147), energy-yielding metabolism (ID 135), and relief in case of irritation in the upper respiratory
tract (ID 1714, 1715) 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
This scientific output, published on 9 December 2010, replaces the earlier version published on 1 October 20093.
Słowa kluczowe:
Vitamin C
collagen formation
energy metabolism
health claims
immune function
non-haem iron absorption
oxidative damage
physical exercise
1. Charakterystyka żywności / składnika
The food constituent that is the subject of the health claim is vitamin C (L-ascorbic acid, ascorbate), which is a well recognised nutrient and it is measurable in foods by established methods.
Vitamin C occurs naturally in foods. Ascorbic acid and its salts (ascorbates) are the forms authorised for addition to foods and for use in food supplements (Annex II of the Regulation (EC) No 1925/20065 and Annex II of Directive 2002/46/EC6). This evaluation applies to vitamin C naturally present in foods and those forms authorised for addition to foods (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 C, which is the subject of the health claim, is sufficiently characterised.
2. Znaczenie oświadczenia dla zdrowia człowieka
2.1. Ochrona DNA, białek i lipidów przed uszkodzeniem oksydacyjnym (ID 129, 138, 143, 148)
The claimed effects are “protection of body cells from oxidative damage”, “antioxidant activity/antioxidant”, “antioxidants and aging”, “cell protection from free radical damage” and “antioxidant properties”. The Panel assumes that the target population is the general population.
No definition has been provided of what constitutes “aging”, and therefore the Panel cannot evaluate the “anti-aging effects” implied in claim ID 138. Also, it should be noted the difference between the ageing process itself and the increasing risk for specific age-related diseases where oxidative and/or free radical-mediated damage may play a role.
In the context of the proposed wordings, the Panel notes that the claimed effects relate to the protection of body cells form 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, 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 protection of DNA, proteins and lipids from oxidative damage is beneficial to human health.
2.2. Funkcja antyoksydacyjna luteiny (ID 146)
The claimed effect is “promotes the antioxidant function of lutein”. The Panel assumes that the target population is the general population.
The Panel notes that no evidence is provided to establish that having antioxidant activity per se is beneficial to human health.
The Panel considers that the benefit to human health of the promotion of the antioxidant function of lutein is unknown.
2.3. Utrzymanie prawidłowego wzroku (ID 141, 142)
The claimed effects are “eye health, free-radical scavenger” and “eye health”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings, the Panel notes that the claimed effects relates to the maintenance of normal vision.
The Panel considers that maintenance of normal vision is beneficial to human health.
2.4. Tworzenie kolagenu (ID 130, 131, 136, 137, 149)
The claimed effects are “structure and function of blood vessels”, “healthy gums”, “healthy skin” and “cofactor for several enzymes involved in the biosynthesis of collagen”.
Collagen is a structural component of several tissues in the body including bones, cartilage, gums, skin, tendons and blood vessels.
The Panel considers that normal collagen formation is beneficial to human health.
2.5. Funkcjonowanie układu nerwowego (ID 133)
The claimed effect is “neurological system function”. The Panel assumes that the target population is the general population.
The Panel considers that normal function of the nervous system is beneficial to human health.
2.6. Funkcjonowanie układu odpornościowego (ID 134)
The claimed effect is “immune system function”. 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.
2.7. Funkcjonowanie układu odpornościowego podczas i po nasilonym wysiłku fizycznym (ID 144)
The claimed effect is “oxidative stress, acts as antioxidant and helps protect the body tissues against potentially damaging effects of free radicals”. The protection of DNA, proteins and lipids from oxidative damage is considered in sections 2.1. and 2.3. of this opinion.
In the context of the proposed wording, the Panel notes that the claimed effect relates to the maintenance of the normal function of the immune system which may be depressed during and after extreme exercise. The Panel assumes that the target population is subjects performing physical exercise.
The Panel considers that the maintenance of a normal function of the immune system during and after extreme physical exercise is beneficial to human health.
2.8. Wchłanianie żelaza niehemowego (ID 132, 147)
The claimed effect is “iron absorption”. The Panel assumes that the target population is the general population.
The Panel considers that improving non-haem iron absorption may be beneficial to human health.
2.9. Metabolizm energetyczny (ID 135)
The claimed health relationship is “energy metabolism”. The Panel assumes that the target population is the general population.
The Panel considers that normal energy-yielding metabolism is beneficial to human health.
2.10. Ulga w przypadku podrażnienia górnych dróg oddechowych (ID 1714, 1715)
The claimed health relationship is “respiratory health” and “soothing/relief in case of tickle” in the upper respiratory tract. The Panel assumes that the target population is the general population.
Respiratory health is too broad for a scientific evaluation. However, “relief in case of tickle” in the throat could be assessed if adequate validated tests were available.
The Panel considers that relief in case of irritation in the upper respiratory tract might be beneficial to health.
3. Naukowe uzasadnienia wpływu na zdrowie człowieka -
The evidence provided by consensus opinions/reports from authoritative bodies and reviews shows that there is good consensus on the role of vitamin C in the body (Bender, 2003; Garrow et al., 2000; IoM, 2000; NNR, 2004; Sadler et al., 1999; Shils et al., 2006; EVM, 2002). Vitamin C is an electron donor, or reducing agent, and its functions are attributable to this action (Shils et al., 2006). On the one hand, vitamin C acts as a major free-radical scavenger in the body, and as electron donor (and cofactor) for eight human enzymes, three of which participate in the biosynthesis (and cross-linking) of collagen and other components of the connective tissue, two of them are required in the biosynthesis of carnitine, one in tyrosine metabolism and two in the biosynthesis of the catecholamines adrenaline and noradrenaline (which act as neurotransmitters) and in the amidation of peptide hormones.
3.1. Ochrona DNA, białek i lipidów przed uszkodzeniem oksydacyjnym (ID 129, 138, 143, 148)
One human intervention study (Engelhart et al., 2002) and one narrative review (Grundman and Delaney, 2002) on the relationship between dietary intake of antioxidants and risk of Alzheimer disease and one cross-sectional study (Ortega et al., 1997) on the association between nutrient intake and cognitive function in the elderly were also presented to support this claim. The Panel considers that these publications are not pertinent to evaluate the claimed effect.
Evidence for in vivo antioxidant functions of ascorbate include the scavenging of reactive oxidants in activated leukocytes, lung and gastric mucosa, and diminished lipid peroxidation as measured by urinary isoprostane excretion (IoM, 2000). According to a recent systematic Cochrane review, the current evidence does not support the use of antioxidant supplements in the general population or in patients with certain diseases (Bjelakovic et al., 2008).
Vitamin C functions physiologically as a water-soluble antioxidant and plays a major role as a free radical scavenger (Sadler et al., 1999; IoM, 2000). Vitamin C is part of the antioxidant defence system, which is a complex network including endogenous antioxidants and dietary antioxidants, antioxidant enzymes, and repair mechanisms, with mutual interactions and synergetic effects among the various components.
The Panel concludes that a cause and effect relationship has been established between the dietary intake of vitamin C and the protection of DNA, proteins and lipids from oxidative damage.
3.2. Funkcja antyoksydacyjna luteiny (ID 146)
One reference was cited to substantiate the claimed effect which is a human intervention study investigating the effects of vitamin C co-supplementation on crystalline lutein supplement absorption (Tanumihardjo et al., 2005).
The Panel concludes that a cause and effect relationship has not been established between the dietary intake of vitamin C and the promotion of the antioxidant function of lutein.
3.3. Utrzymanie prawidłowego wzroku (ID 141, 142)
The references cited in relation to vitamin C and eye health in humans consist of observational studies (either cross-sectional or prospective cohort studies) reporting associations between vitamin C intake, plasma concentrations of vitamin C or use of vitamin C supplements and lower risk of age-related lens opacities (either nuclear or cortical cataract). Animal, ex vivo and in vitro studies reporting vitamin C concentrations in tears, lens damage in vitamin C deficiency or after UV radiation exposure, and one narrative review on the role of antioxidant compounds in general in cataract prevention were also provided.
All the human studies presented to support this claim have been subject to extensive reviews (Chiu and Taylor, 2007; Meyer and Sekundo, 2005). Eight out of 15 studies found that increased vitamin C intake, supplement use, or blood concentrations were related to diminished risk for nuclear cataract. Long-term duration of supplementation (>10 years) was most frequently associated with the reduction of risk, and the presence of diabetes mellitus could affect this association. Only three out of ten studies found that increased vitamin C intake, supplement use, or blood concentrations were related to diminished risk for cortical cataract. One study found that increased vitamin C supplement use was related to increased risk for cortical cataract in non-diabetic subjects and decreased the risk for cortical cataract in diabetics. The remaining six studies showed no effect, including the AREDS intervention. Only three out of eight studies found that increased vitamin C intake or elevated blood concentrations were related to diminished risk for posterior subcapsular cataract (PSC). The remaining five studies showed no effect, including the AREDS intervention. Two out of four studies found that increased vitamin C supplement use or blood concentrations were related to diminished risk for mixed cataract, including the REACT intervention. Finally, only two out of six studies found that vitamin C supplement use is related to diminished risk for cataract extraction. The four remaining studies showed no effect, including the AREDS intervention (Chiu and Taylor, 2007; Meyer and Sekundo, 2005).
The Panel notes that, despite the fact that vitamin C supplement use and elevated blood concentrations of vitamin C have been inversely associated with at least one type of cataract in many (but not all) epidemiological studies, four out of the seven randomized, double-blinded, placebo-controlled intervention trials investigating the effects of antioxidant vitamin supplements on cataract risk have found no effect of supplementation, and that no large-scale intervention trial on cataract prevention has been reported on which vitamin C has been administered as the sole supplement (Chiu and Taylor, 2007; Levin et al., 2006).
The Panel concludes that the evidence provided is insufficient to establish a cause and effect relationship between the dietary intake of vitamin C and the maintenance of normal vision.
3.4. Tworzenie kolagenu (ID 130, 131, 136, 137, 149)
Vitamin C is a coenzyme for three different dioxygenase enzymes that catalyse the addition of hydroxyl groups to the amino acids proline and lysine of the collagen molecule to stabilize the triple helix structure. Normal collagen formation is required for the normal structure of many tissues in the body, including bones, cartilage, gums, skin, tendons and blood vessels. Vitamin C deficiency (scurvy) is dominated by clinical signs attributable to impaired collagen synthesis, including bone damage, arthralgia and joint effusions, swollen and friable gums, loss of teeth, perifollicular hyperkeratosis, petechial haemorrhage, erythema and purpura, subcutaneous bleeding, and internal haemorrhage in severe cases of scurvy (Sadler et al., 1999; Shils et al., 2006; IoM, 2000).
The Panel concludes that a cause and effect relationship has been established between the dietary intake of vitamin C and normal collagen formation.
3.5. Funkcjonowanie układu nerwowego (ID 133)
Vitamin C is needed as a cofactor of dopamine -monooxygenase for the biosynthesis of noradrenaline (and adrenaline). Both catecholamines act as neurotransmitters. Manifestations of infantile scurvy include irritability, whereas hypochondriasis, depression and confusion have been described in adults with scurvy. These symptoms have been attributed to an impaired function of
dopamine -monooxygenase (Sadler et al., 1999; Shils et al., 2006; IoM, 2000).
The Panel concludes that a cause and effect relationship has been established between the dietary intake of vitamin C and normal function of the nervous system.
3.6. Funkcjonowanie układu odpornościowego (ID 134)
Evidence of effects of vitamin C on both innate and adaptive immune responses is present in the literature provided. Whereas as such the relation of these effects of vitamin C with clinical outcomes is unclear, studies have also shown that altered values of immune parameters, as seen for instance in the individuals with a low vitamin C status, older people, patients exposed to toxic chemicals, or individuals exposed to severe physical exercise can be restored by vitamin C intake (Delafuente et al, 1986; Heuser et al., 1997; Jacob et al., 1991; Kennes et al., 1983; Nieman et al., 2000; Tauler et al, 2003; Buzina-Suboticanec et al., 1998; Chavance et al., 1989).
The Panel concludes that a cause and effect relationship has been established between the dietary intake of vitamin C and the normal function of the immune system.
3.7. Funkcjonowanie układu odpornościowego podczas i po nasilonym wysiłku fizycznym (ID 144)
Studies on vitamin C supplementation or status on clinical outcomes unrelated to the claimed effect (e.g., macular degeneration, bronchial responsiveness in asthma or antioxidant status) were not considered as pertinent to support the claimed effect.
It is known that under conditions of immune depression, resistance to infections may be reduced, and certain diseases such as common cold may occur more frequently. Most of the human studies presented have investigated the relationship between vitamin C supplementation and the prevention of common cold. Three systematic Cochrane reviews (with meta-analyses) investigating the role of vitamin C supplementation in the prevention, severity of symptoms and treatment of common cold include the vast majority of the single studies provided for this outcome (Douglas et al., 2000 and 2004; Hemila et al., 2007). Most studies indicate that vitamin C supplementation with doses above the dietary reference values fail to reduce the incidence of colds in the normal population However, evidence shows that persons exposed to brief periods of severe physical exercise and/or cold environments benefit in terms of duration and severity of the common cold from regular vitamin C intake above 200mg/d.
The Panel concludes that a cause and effect relationship has been established between the dietary intake of vitamin C and the maintenance of the normal function of the immune system during and after extreme physical exercise.
3.8. Wchłanianie żelaza niehemowego (ID 132, 147)
Iron deficiency is one of the most common micronutrient deficiencies with about 30% of world population being anaemic (Ramakrishnan, 2002; WHO, 2008). There is still a significant prevalence of iron deficiency in Europe especially among pregnant women, children and women in reproductive age (WHO, 1992; Badham et al., 2007). The most common consequence of iron deficiency is microcytic anaemia.
Dietary iron is absorbed as Fe2+ and not as Fe3+. Reducing agents, including vitamin C, promote non- haem iron absorption by keeping it reduced (Fe2+). Although the clinical effects of vitamin C intake in raising haemoglobin concentrations when administered with iron are modest, inorganic (non-haem) iron absorption is increased by 1.5 to 10 fold depending on iron status, the dose of vitamin C and the test meal. Vitamin C is administered with iron in clinical practice to increase the absorption of the latter (IoM, 2000, EVM, 2002, Levin et al., 2006).
The Panel concludes that a cause and effect relationship has been established between the dietary intake of vitamin C and the increase of non-haem iron absorption.
3.9. Metabolizm energetyczny (ID 135)
Carnitine is an essential cofactor in the transport of long-chain fatty acids into the mitochondrial matrix and plays an important role in energy production via beta-oxidation. Vitamin C has been considered an absolute requirement for two dioxygenase enzymes involved in the biosynthesis of carnitine (IoM, 2000; EVM, 2002; Levin et al., 2006).
The Panel concludes that a cause and effect relationship has been established between the dietary intake of vitamin C and normal energy-yielding metabolism.
3.10. Ulga w przypadku podrażnienia górnych dróg oddechowych (ID 1714, 1715)
One reference was cited to substantiate the health claim which is the administrative guidance to present applications for the registration of cough drops in Switzerland.
The Panel concludes that a cause and effect relationship has not been established between the dietary intake of vitamin C and relief in case of irritation in the upper respiratory tract.
4. Uwagi do zaproponowanego brzmienia oświadczenia
4.1. Ochrona DNA, białek i lipidów przed uszkodzeniem oksydacyjnym (ID 129, 138, 143, 148)
The Panel considers that the following wordings reflect the scientific evidence: “Vitamin C contributes to the protection of cell constituents from oxidative damage.”
4.2. Tworzenie kolagenu (ID 130, 131, 136, 137, 149)
The Panel considers that the following wordings reflect the scientific evidence: “Vitamin C contributes to normal collagen formation and the normal function of bones, teeth, cartilage, gums, skin and blood vessels.”
4.3. Funkcjonowanie układu nerwowego (ID 133)
The Panel considers that the following wordings reflect the scientific evidence: “Vitamin C contributes to the normal function of the nervous system.”
4.4. Wchłanianie żelaza niehemowego (ID 132, 147)
The Panel considers that the following wordings reflect the scientific evidence: “Vitamin C increases non-haem iron absorption.”
4.5. Funkcjonowanie układu odpornościowego (ID 134)
The Panel considers that the following wordings reflect the scientific evidence: “Vitamin C contributes to a normal function of the immune system.”
4.6. Funkcjonowanie układu odpornościowego podczas i po nasilonym wysiłku fizycznym (ID 144)
The Panel considers that the following wordings reflect the scientific evidence: “Vitamin C contributes to maintain the normal function of the immune system during and after intense physical exercise.”
4.7. Metabolizm energetyczny (ID 135)
The Panel considers that the following wordings reflect the scientific evidence: “Vitamin C contributes to normal energy-yielding metabolism.”
5. Warunki i możliwe ograniczenia stosowania oświadczenia
5.1. Ochrona DNA, białek i lipidów przed uszkodzeniem oksydacyjnym (ID 129, 138, 143, 148), tworzenie kolagenu (ID 130, 131, 136, 137, 149), funkcjonowanie układu nerwowego (ID 133), wchłanianie żelaza niehemowego (ID 132), funkcjonowanie układu odpornościowego (ID 134), and metabolizm energetyczny (ID 135)
The Panel considers that in order to bear the claims a food should be at least a source of vitamin C as per Annex to Regulation 1924/2006. Such amounts can be easily consumed as part of a balanced diet. The target population is the general population.
5.2. Funkcjonowanie układu odpornościowego podczas i po nasilonym wysiłku fizycznym (ID 144)
The Panel considers that in order to bear the claim a food should contain at least 200 mg vitamin C to be consumed daily in addition to the usual diet. Such amounts can be easily consumed as part of a balanced diet. The target population is subjects performing intense physical exercise.
Wnioski
On the basis of the data presented, the Panel concludes that:
The food constituent, vitamin C, which is the subject of the health claims is sufficiently characterised.
Protection of DNA, proteins and lipids from oxidative damage (ID 129, 138, 143, 148)
The claimed effects are “protection of body cells from oxidative damage”, “antioxidant activity/antioxidant”, “antioxidants and aging”, “cell protection from free radical damage” and “antioxidant properties”. 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 been established between the dietary intake of vitamin C and the protection of DNA, proteins and lipids from oxidative damage.
The following wording reflects the scientific evidence: “Vitamin C contributes to the protection of cell constituents from oxidative damage.”
Antioxidant function of lutein (ID 146)
The claimed effects are “promotes the antioxidant function of lutein” The target population is assumed to be the general population. The benefit to human health of the promotion of the antioxidant function of lutein is unknown.
A cause and effect relationship has not been established between the dietary intake of vitamin C and the promotion of the antioxidant function of lutein.
Maintenance of vision (ID 141, 142)
The claimed effects are “eye health, free-radical scavenger” and “eye health”. The target population is assumed to be the general population. Maintenance of normal vision is beneficial to human health.
The evidence provided is insufficient to establish a cause and effect relationship between the dietary intake of vitamin C and the maintenance of normal vision.
Collagen formation (ID 130, 131, 136, 137, 149)
The claimed effects are “structure and function of blood vessels”, “structure and function of blood vessels”, “healthy gums”, “healthy skin” and “cofactor for several enzymes involved in the biosynthesis of collagen”. The target population is assumed to be the general population. Normal collagen formation is beneficial to human health.
A cause and effect relationship has been established between the dietary intake of vitamin C and normal collagen formation.
The following wording reflects the scientific evidence “Vitamin C contributes to normal collagen formation and the normal function of bones, teeth, cartilage, gums, skin and blood vessels.”
Function of the nervous system (ID 133)
The claimed effects are “contributes to neurological function” and “needed for normal mental function”. The target population is assumed to be the general population. Normal function of the nervous system is beneficial to human health.
A cause and effect relationship has been established between the dietary intake of vitamin C and normal function of the nervous system.
The following wording reflects the scientific evidence: “Vitamin C contributes to the normal function of the nervous system”.
Immune function (ID 134)
The claimed effect is “needed for the normal function of the 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 C and a normal function of the immune system
The following wording reflects the scientific evidence: “Vitamin C contributes to a normal function of the immune system.”
Function of the immune system during and after extreme physical exercise (ID 144)
The claimed effect is “oxidative stress, acts as antioxidant and helps protect the body tissues against potentially damaging effects of free radicals”. In the context of the proposed wording it is assumed that the claim relates to the maintenance of the normal function of the immune system which may be depressed during and after extreme exercise. The target population is subjects performing physical exercise. Maintaining the normal function of the immune system during and after extreme physical exercise is beneficial to human health.
A cause and effect relationship has been established between the dietary intake of vitamin C and the maintenance of the normal function of the immune system during and after extreme physical exercise.
The following wording reflects the scientific evidence: “Vitamin C contributes to maintain the normal function of the immune system during and after intense physical exercise.”
Non-haem iron absorption (ID 132, 147)
The claimed effect is “improves non-haem iron absorption”. The target population is the general population. Improving non-haem iron absorption may be beneficial to human health.
A cause and effect relationship has been established between the dietary intake of vitamin C and the increase of non-haem iron absorption.
The following wordings reflect the scientific evidence: “Vitamin C increases non-haem iron absorption.
Energy-yielding metabolism (ID 135)
The claimed effect is “energy metabolism”. The target population is the general population. Normal energy-yielding metabolism is beneficial to health.
A cause and effect relationship has been established between the dietary intake of vitamin C and normal energy-yielding metabolism.
The following wordings reflect the scientific evidence: “Vitamin C contributes to normal energy-yielding metabolism.”
Relief in case of irritation in the upper respiratory tract (ID 1714, 1715)
The claimed effect is “respiratory health” and “soothing/relief in case of tickle” in the upper respiratory tract. The target population is the general population. Relief in case of irritation in the upper respiratory tract might be beneficial to health.
A cause and effect relationship has not been established between the dietary intake of vitamin C and relief in case of irritation in the upper respiratory tract.
Conditions/restrictions of use
In order to bear the claims a food should:
be at least a source of vitamin C as per Annex to Regulation 1924/2006. Such amounts can be easily consumed as part of a balanced diet. The target population is the general population (ID 129, 143, 148, 130, 131, 136, 137, 149, 133, 132, 134).
contain at least 200 mg vitamin C to be consumed daily in addition to the usual diet. Such amounts can be easily consumed as part of a balanced diet. The target population is subjects performing intense physical exercise (ID 144).
