Scientific Opinion on the substantiation of health claims related to copper and protection of DNA, proteins and lipids from oxidative damage (ID 263, 1726), function of the immune system (ID 264), maintenance of connective
tissues (ID 265, 271, 1722), energy-yielding metabolism (ID 266), function of the nervous system (ID 267), maintenance of skin and hair pigmentation (ID 268, 1724), iron transport (ID 269, 270, 1727), cholesterol metabolism
(ID 369), and glucose metabolism (ID 369) 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:
Copper
cholesterol metabolism
connective tissues
energy-yielding metabolism
glucose metabolism
health claims
immune system
iron transport
nervous system
oxidative damage
skin and hair pigmentation
1. Charakterystyka żywności / składnika
The food constituent that is the subject of the health claim is copper which is a well recognised nutrient and is measurable in foods by established methods.
Copper occurs naturally in foods and is authorised for addition to foods (Annex I of the Regulation (EC) No 1925/20064 and Annex I of Directive 2002/46/EC5). This evaluation applies to copper 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, copper, 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 263, 1726)
The claimed effect is “protection of body tissues and cell from oxidative damage; antioxidant activity”. 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 DNA, proteins and lipids from oxidative damage is beneficial to human health.
2.2. Funkcjonowanie układu odpornościowego (ID 264)
The claimed effect is “immune system”. The Panel assumes that the target population is the general population.
The Panel considers that normal function of the immune system is beneficial to human health.
2.3. Utrzymanie prawidłowego stanu tkanki łącznej (ID 265, 271, 1722)
The claimed effect is “connective tissues” and “hair, nail connective tissue formation”. The Panel assumes that the target population is the general population.
The connective tissue is a structural component of several body structures including bone, cartilage, gums, skin, hair follicles, nails, tendons and blood vessels.
The Panel considers that maintenance of normal connective tissues is beneficial to human health.
2.4. Metabolizm energetyczny (ID 266)
The claimed effect is “energy production”. The Panel assumes that the target population is the general population.
The Panel considers that normal energy-yielding metabolism is beneficial to human health.
2.5. Funkcjonowanie układu nerwowego (ID 267)
The claimed effect is “neurological system structure and 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. Utrzymanie pigmentacji skóry i włosów (ID 268, 1724)
The claimed effect is “skin and hair pigment”. The Panel assumes that the target population is the general population.
Skin and hair pigment (melanin) serves as a light filter for the protection of tissues against ultraviolet light damage.
The Panel considers that maintenance of normal skin and hair pigmentation is beneficial to human health.
2.7. Transport żelaza (ID 269, 270, 1727)
The claimed effect is “transport and metabolism of iron” and “iron metabolism”. The Panel assumes that the target population is the general population.
The Panel considers that normal iron transport is beneficial to human health.
2.8. Metabolizm cholesterolu (ID 369)
The claimed effect is “cholesterol and glucose metabolism”. The Panel assumes that the target population is the general population.
The Panel considers that normal cholesterol metabolism is beneficial to human health.
2.9. Metabolizm glukozy (ID 369)
The claimed effect is “cholesterol and glucose metabolism”. The Panel assumes that the target population is the general population.
The Panel considers that normal glucose metabolism is beneficial to human health.
3. Naukowe uzasadnienia wpływu na zdrowie człowieka
Copper is a component of some enzymes, cofactors, and proteins in the body. Among those copper metalloenzymes that have been identified in humans are: monoamine oxidase, diamine oxidase, lysyl oxidase, peptidylglycine-α-amidating monooxygenase, caeruloplasmin, ferrooxidase II, cytohrome c oxidase, dopamine β-hydroxylase, copper/zinc superoxide dismutase, and tyrosinase. The biochemical role of copper is primarily catalytic, with many copper metalloenzymes acting as oxidases to achieve the reduction of molecular oxygen (Biesalski et al., 1997; Garrow et al., 2000; EVM, 2002; Gibney et al., 2002; Mann and Truswell, 2001; Sadler et al., 1999; Wenzel, 1999).
3.1. Ochrona DNA, białek i lipidów przed uszkodzeniem oksydacyjnym (ID 263, ID 1726)
Copper functions as a component of a number of metalloenzymes acting as oxidases to achieve the reduction of molecular oxygen, such as cytochrome c oxidase, and copper/zinc superoxide dismutase (SOD) enzyme (IoM, 2001). This latter enzyme is localized in the cytosol of mammalian cells and provides a defence against oxidative damage from superoxide radicals that, if uncontrolled, can lead to the formation of other damaging reactive oxygen species (ROS). Its activity is related to copper intake (Turnlund, 1998), albeit other factors, such as the induction of oxidative stress, also affect superoxide dismutase (SOD) activity (Knasmuller et al., 2008). Caeruloplasmin is the predominant copper protein in plasma and may have antioxidant functions (IoM, 2001; Klotz et al., 2003).
The Panel considers that a cause and effect relationship has been established between the dietary intake of copper and the protection of DNA, proteins and lipids from oxidative damage. However, the evidence provided does not establish that inadequate intake of copper leading to impaired protection of DNA, proteins and lipids from oxidative damage occurs in the general EU population.
3.2. Funkcjonowanie układu odpornościowego (ID 264)
Copper-related enzyme cytochrome c oxidase is needed for energy production of immune cells. Another cuproenzyme – superoxide dismutase - plays a role in the protection of immune cells against reactive oxygen species. Moderate and even marginal copper deficiency affects some activities of T-lymphocytes and phagocytic cells adversely (Kelley et al, 1995, Hopkins et al., 1999). Severe copper deficiency generally changes the phenotypic profiles of immune cells in blood, bone marrow, and lymphoid tissues. It also suppresses a number of activities of lymphocytes and phagocytic cells.
Cells of animals fed diets with marginally low copper had markedly impaired in vitro DNA synthesis and IL-2 secretion by mitogen-treated splenic T-lymphocytes and respiratory burst activity of neutrocytes (Hopkins, 1995).
Neutropenia is a hallmark of copper deficiency in humans (Heresi et al. 1985, Prohaska, 2006). However, clinical data confirming the importance of copper in the function of the immune system is sparse. Copper deficiency in humans results in thymus atrophy (Munoz et al., 2007). Hypocupraemic infants fed cow's milk formula containing copper showed normalization of copper and caeruloplasmin concentrations, and phagocytic index recovery to normal levels (Heresi et al, 1985). Infants with Menkes disease, a genetic disorder that results in severe copper deficiency in some tissues, suffer from frequent and severe infections (Percival, 1998; Failla and Hopkins, 1998).
The Panel concludes that a cause and effect relationship has been established between dietary intake of copper and the normal function of the immune system. However, the evidence provided does not establish that inadequate intake of copper leading to impaired function of the immune system occurs in the general EU population.
3.3. Utrzymanie prawidłowego stanu tkanki łącznej (ID 265, 271, 1722)
The evidence provided by consensus opinions/reports from authoritative bodies and reviews shows that there is good consensus on the role of copper in the formation of elastin and collagen, which constitute the structure of connective tissues.
Copper is a cofactor of lysyl oxidase (LO), which is an extracellular enzyme critical to the formation and function of connective tissue throughout the body. The reaction of oxidative deamination of specific lysine residues in the extracellular matrix initiates the formation of cross-links that stabilise newly formed elastin and collagen (Linder and Hazegh-Azam, 1996).
Symptoms of severe copper deficiency include lack of collagen maturation and defective sheathing of blood vessels, which can result in aneurysms (Rodriguez et al., 2008).
The Panel concludes that a cause and effect relationship has been established between the dietary intake of copper and maintenance of normal connective tissues. However, the evidence provided does not establish that intake of copper inadequate for the maintenance of normal connective tissues occurs in the general EU population.
3.4. Metabolizm energetyczny (ID 266)
Copper participates as a cofactor for specific enzymes and electron transport proteins involved in many oxidative reactions that break down fats in fat tissue to produce energy in the form of ATP.
The copper-dependent enzyme cytochrome c oxidase plays a critical role in cellular energy production. Copper deficiency results in a decrease of cytochrome c oxidase activity and the respiratory capacity of mitochondria, particularly in liver, heart, and brain (Linder, 1991).
The Panel concludes that a cause and effect relationship has been established between the dietary intake of copper and normal energy-yielding metabolism. However, the evidence provided does not establish that inadequate intake of copper leading to impaired energy yielding metabolism occurs in the general EU population.
3.5. Funkcjonowanie układu nerwowego (ID 267)
Copper is required for the formation and maintenance of myelin. Myelin is composed primarily of phospholipids. Their synthesis depends on the activity of the cuproenzyme cytochrome c oxidase. In copper deficient animals, poor myelination, necrosis of nerve tissue, and neonatal ataxia are found (Desai and Kaler, 2008). Copper has also a function in catecholamine metabolism and therefore in normal neurotransmission (Prohaska and Bailey, 1994).
The Panel concludes that a cause and effect relationship has been established between dietary intake of copper and normal function of the nervous system. However, the evidence provided does not establish that inadequate intake of copper leading to impaired function of the nervous system occurs in the general EU population.
3.6. Utrzymanie pigmentacji skóry i włosów (ID 268, 1724)
The role of copper in the pigmentation of skin, hair, and eyes is related to the requirement of the cuproenzyme tyrosinase (monophenol oxidase) for melanin synthesis. Mutational loss of this catalytic function leads to albinism. Achromotrichia is observed in domestic and laboratory animals consuming diets low in copper (Arredondo and Nunez, 2005; Linder, 1991).
The Panel concludes that a cause and effect relationship has been established between the dietary intake of copper and maintenance of normal skin and hair pigmentation. However, the evidence provided does not establish that intake of copper inadequate for the maintenance of normal skin and hair pigmentation occurs in the general EU population.
3.7. Transport żelaza (ID 269, 270, 1727)
Anaemia is a clinical sign of copper deficiency, and iron has been found to accumulate in the livers of copper deficient animals, indicating that copper (probably in the form of caeruloplasmin) is required for iron transport to the bone marrow for red blood cell formation (Turnlund, 1998). During severe copper deficiency, iron transport within the body is adversely affected, and iron tends to accumulate in many tissues. Copper deficiency is accompanied by a hypochromic microcytic anaemia similar to that produced by iron deficiency (Linder, 1991, Prohaska, 2006).
The Panel concludes that a cause and effect relationship has been established between dietary intake of copper and normal iron transport. However, the evidence provided does not establish that inadequate intake of copper leading to impaired iron transport occurs in the general EU population.
3.8. Metabolizm cholesterolu (ID 369)
A textbook and three consensus opinions/reports from authoritative bodies were cited to substantiate the claimed effect.
The role of copper on cholesterol metabolism is not well understood nor well established in humans (Turnlund, 2006). Blood cholesterol increases in animals fed copper-deficient diets, but the effects of
either copper deficiency or copper supplementation in humans are not consistent (Strain, 1994; Medeiros and Wildman, 1997, JHCI, 2003).
The Panel concludes that a cause and effect relationship has not been established between dietary intake of copper and normal cholesterol metabolism in humans.
3.9. Metabolizm glukozy (ID 369)
A textbook and three consensus opinions/reports from authoritative bodies were cited to substantiate the claimed effect.
The role of copper in the regulation of glucose metabolisms in not well understood nor well established in humans (Turnlund, 2006; JHCI, 2003)
The Panel concludes that a cause and effect relationship has not been established between dietary intake of copper and normal glucose metabolism in humans.
4. Uwagi do zaproponowanego brzmienia oświadczenia
4.1. Ochrona DNA, białek i lipidów przed uszkodzeniem oksydacyjnym (ID 263, 1726)
The Panel considers that the following wording reflects the scientific evidence: “Copper contributes to the protection of cell constituents from oxidative damage”.
4.2. Funkcjonowanie układu odpornościowego (ID 264)
The Panel considers that the following wording reflects the scientific evidence: “Copper contributes to normal function of the immune system”.
4.3. Utrzymanie prawidłowego stanu tkanki łącznej (ID 265, 271, 1722)
The Panel considers that the following wording reflects the scientific evidence: “Copper contributes to maintenance of normal connective tissues”.
4.4. Metabolizm energetyczny (ID 266)
The Panel considers that the following wording reflects the scientific evidence: “Copper contributes to normal energy yielding metabolism”.
4.5. Funkcjonowanie układu nerwowego (ID 267)
The Panel considers that the following wording reflects the scientific evidence: “Copper contributes to normal function of the nervous system”.
4.6. Utrzymanie pigmentacji skóry i włosów (ID 268, 1724)
The Panel considers that the following wording reflects the scientific evidence: “Copper contributes to normal skin and hair pigmentation”.
4.7. Transport żelaza (ID 269, 270, 1727)
The Panel considers that the following wording reflects the scientific evidence: “Copper contributes to normal iron transport in the body”.
5. Warunki i możliwe ograniczenia stosowania oświadczenia
The Panel considers that in order to bear the claim a food should be at least a source of copper as per Annex to Regulation (EC) 1924/2006. Such amounts can be easily consumed as part of a balanced diet. Tolerable Upper Intake Level (UL) has been established for copper as 5 mg/day in adults and
during pregnancy and lactation. For children and adolescents UL was established as 1 mg/day for 1-3 years, 2 mg/day for 4-6 years, 3 mg/day for 7-10 years, 4 mg/day for 11-17 years (SCF, 2003).
Wnioski
On the basis of the data presented, the Panel concludes that:
The food constituent, copper, which is the subject of the health claim, is sufficiently characterised.
Protection of DNA, proteins and lipids from oxidative damage (ID 263, 1726)
The claimed effect is “protection of body tissues and cell from oxidative damage; antioxidant activity”. The target population is assumed to be the general population. Protection of DNA, proteins and lipids from oxidative damage is beneficial to human health.
The Panel considers that a cause and effect relationship has been established between the dietary intake of copper and the protection of DNA, proteins and lipids from oxidative damage.
The evidence provided does not establish that inadequate intake of copper leading to impaired protection of DNA, proteins and lipids from oxidative damage occurs in the general EU population.
The following wording reflects the scientific evidence: “Copper contributes to the protection of cell constituents from oxidative damage”.
Function of the immune system (ID 264)
The claimed effect is “immune system”. The target population is assumed to be the general population. Normal function of the immune system is beneficial to human health.
A cause and effect relationship has been established between the dietary intake of copper and normal function of the immune system.
The evidence provided does not establish that inadequate intake of copper leading to impaired function of the immune system occurs in the general EU population
The following wording reflects the scientific evidence: “Copper contributes to normal function of the immune system”.
Maintenance of connective tissues (ID 265, 271, 1722)
The claimed effect is “connective tissues” and “hair, nail connective tissue formation”. The target population is assumed to be the general population. Maintenance of normal connective tissues is beneficial to human health.
A cause and effect relationship has been established between the dietary intake of copper and maintenance of normal connective tissues.
The evidence provided does not establish that intake of copper inadequate for the maintenance of normal connective tissues occurs in the general EU population.
The following wording reflects the scientific evidence: “Copper contributes to maintenance of normal connective tissues”.
Energy-yielding metabolism (ID 266)
The claimed effect is “energy production”. The target population is assumed to be the general population. Normal energy-yielding metabolism is beneficial to human health.
A cause and effect relationship has been established between the dietary intake of copper and normal energy-yielding metabolism.
The evidence provided does not establish that inadequate intake of copper leading to impaired energy-yielding metabolism occurs in the general EU population.
The following wording reflects the scientific evidence: “Copper contributes to normal energy-yielding metabolism”.
Function of the nervous system (ID 267)
The claimed effect is “neurological system structure and 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 intake of copper and normal function of the nervous system.
The evidence provided does not establish that inadequate intake of copper leading to impaired function of the nervous system occurs in the general EU population.
The following wording reflects the scientific evidence: “Copper contributes to normal function of the nervous system”.
Maintenance of skin and hair pigmentation (ID 268, 1724)
The claimed effect is “skin and hair pigment”. The target population is assumed to be the general population. Maintenance of normal skin and hair pigmentation is beneficial to human health.
A cause and effect relationship has been established between the intake of copper and maintenance of normal skin and hair pigmentation.
The evidence provided does not establish that intake of copper inadequate for the maintenance of normal skin and hair pigmentation occurs in the general EU population.
The following wording reflects the scientific evidence: “Copper contributes to normal skin and hair pigmentation”.
Iron transport (ID 269, 270, 1727)
The claimed effect is “transport and metabolism of iron” and “iron metabolism”. The target population is assumed to be the general population. Normal iron transport is beneficial to human health.
A cause and effect relationship has been established between the dietary intake of copper and normal iron transport.
The evidence provided does not establish that inadequate intake of copper leading to impaired iron transport occurs in the general EU population
The following wording reflects the scientific evidence: “Copper contributes to normal iron transport in the body”.
Cholesterol metabolism (ID 369)
The claimed effect is “cholesterol and glucose metabolism”. The target population is assumed to be the general population. Normal cholesterol metabolism is beneficial to human health.
A cause and effect relationship has not been established between the dietary intake of copper and normal cholesterol metabolism.
Glucose metabolism (ID 369)
The claimed effect is “cholesterol and glucose metabolism”. The target population is assumed to be the general population. Normal glucose metabolism is beneficial to human health.
A cause and effect relationship has not been established between the dietary intake of copper and normal glucose metabolism.
Conditions and possible restrictions of use
In order to bear the claims a food should be at least a source of copper as per Annex to Regulation (CE) 1924/2006. Such amounts can be easily consumed as part of a balanced diet.
