Scientific Opinion on the substantiation of health claims related to iron and
formation of red blood cells and haemoglobin (ID 249, ID 1589), oxygen
transport (ID 250, ID 254, ID 256), energy-yielding metabolism (ID 251,
ID 1589), function of the immune system (ID 252, ID 259), cognitive
function (ID 253) and cell division (ID 368) 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:
Iron
cell division
cognitive function
energy-yielding metabolism
haemoglobin
health claims
immune system
oxygen transport
red blood cells
1. Charakterystyka żywności / składnika
The food constituent that is the subject of the health claims is iron which is a well recognised nutrient and is measurable in foods by established methods.
Iron occurs naturally in foodstuffs in different oxidation states. The primarily occurring oxidation states in biological systems are +2 (ferrous state) and +3 (ferric state).
Iron occurs naturally in foods in two forms, haem iron which is primarily derived from haemoglobin and myoglobin in meat and non-haem iron from plants in the form of iron complexes (IoM, 2001). Different forms of iron are authorised for addition to foods (Annex I of Regulation (EC) No 1925/20064 and Annex II of Directive 2002/46/EC5). This evaluation applies to iron 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, iron, which is the subject of the health claims, is sufficiently characterised.
2. Znaczenie oświadczenia dla zdrowia człowieka
2.1. Tworzenie erytrocytów (czerwonych krwinek) i hemoglobiny (ID 249, ID 1589)
The claimed effect is “red blood cell and haemoglobin formation”. The Panel assumes that the target population is the general population.
The Panel considers that normal formation of red blood cells and haemoglobin are beneficial to human health.
2.2. Transport tlenu (ID 250, ID 254, ID 256)
The claimed effect is “oxygen transport”. The Panel assumes that the target population is the general population.
The Panel considers that normal oxygen transport is beneficial to human health.
2.3. Metabolizm energetyczny (ID 251, ID 1589)
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.
2.4. Funkcjonowanie układu odpornościowego (ID 252, ID 259)
The claimed effect is “normal functioning of the 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.
2.5. Funkcje poznawcze (ID 253)
The claimed effect is “cognitive development and function”. The Panel assumes that the target population is the general population.
The Panel considers that cognitive development is related to children's development and health. Cognitive function includes different functions such as memory, attention (concentration), learning, intelligence and problem solving.
The Panel considers that normal cognitive function is beneficial to human health.
2.6. Podziały komórek (ID 368)
The claimed effect is “cell division”. The Panel assumes that the target population is the general population.
The Panel notes that cell division is a crucial process for tissue growth and development and for tissue maintenance through cell turnover.
The Panel considers that normal cell division is beneficial to human health.
3. Naukowe uzasadnienia wpływu na zdrowie człowieka
Iron is an essential trace element that has important metabolic functions, including oxygen transport and is involved in many redox reactions. Insufficient intake results in the deficiency condition anaemia, adverse outcomes of pregnancy, impaired psychomotor development and cognitive performance and reduced immune function (EFSA, 2004).
3.1. Tworzenie erytrocytów (czerwonych krwinek) i hemoglobiny (ID 249, ID 1589)
In humans, iron is mainly found in porphyrins. In haemproteins (haemoglobin and myoglobin) iron is found in its ferrous state (Fe2+) which allows it to bind oxygen reversibly. Haemoglobin transports oxygen in the erythrocytes to the tissues (Hunt, 2005).
It is well established that inadequate dietary iron intake in humans leads to hypochromic and microcytic anaemia.
The Panel concludes that a cause and effect relationship has been established between the intake of iron and normal formation of red blood cells and haemoglobin.
3.2. Transport tlenu (ID 250, ID 254, ID 256)
In humans, iron is mainly found in porphyrins. In haemproteins (haemoglobin and myoglobin) iron is found in its ferrous state (Fe2+) which allows it to bind oxygen reversibly. Haemoglobin transports oxygen in the erythrocytes to the tissues (Hunt, 2005).
It is well established that inadequate dietary iron intake in humans leads to hypochromic and microcytic anemia.
The Panel concludes that a cause and effect relationship has been established between the dietary intake of iron and normal oxygen transport to tissues.
3.3. Metabolizm energetyczny (ID 251, ID 1589)
Iron containing porphyrins are also found in cytochromes of the electron transport chains. Cytochromes are electron transport enzymes in mitochondria and other cellular membranes. They are able to undergo reversible oxidation by way of changes in the oxidation state of iron and are essential for the oxidative production of cellular energy in the form of ATP. Other non-haem iron containing enzymes are also involved in the electron transport chain. These are for example cytochrome c reductase, NADH-dehydrogenase and succinate dehydrogenase which are involved in energy-yielding metabolism (Elmadfa and Leitzmann, 1988). Impaired oxygen transport caused by anaemia exerts an indirect effect on the electron transport chain where oxygen acts as electron acceptor (Koolman and Röhm, 1994). It is difficult to determine whether any particular functional abnormality caused by iron deficiency is a specific consequence of the anaemia per se and impaired oxygen delivery or the result of iron deficiency in tissues. However, it has been shown that anaemia and tissue iron deficiency exert independent effects on skeletal muscle (IoM, 2001).
The Panel concludes that a cause and effect relationship has been established between the dietary intake of iron and normal energy-yielding metabolism.
3.4. Funkcjonowanie układu odpornościowego (ID 252, ID 259)
It has been demonstrated, mainly with the use of in vitro tests and animal models, that iron deficiency is associated with changes in the cell-mediated immune response. Amongst other effects, the following effects of iron deficiency in the immune system have been described: impaired neutrophil function, reduction of numbers of T-cells, B-cells and natural killer cells, defective T-lymphocyte- induced proliferative response, reduction of secretory IgA, reduction of levels of complement C3 and C4, and inhibition of the activity of IFN-γ (Biesalski et al., 1995; FAO/WHO, 2004; IoM, 2001; Oppenheimer, 2001; Hunt, 2005; Weiss, 2002). Data confirming these effects of iron on immune parameters in humans are scarce. In a review by Munoz et al. (2007), a decrease in the numbers of naïve T-helper and T-cytotoxic cells in blood from iron deficient subjects was reported, suggesting that iron is required for the regeneration of new CD4+ T lymphocytes and maintenance of T cell cytolytic processes. It is also reported that serum IL-2 and IL-6 were reduced in iron-deficient children, suggesting that iron alters the balance between pro- and anti-inflammatory cytokines. In a study conducted in iron-deficient women, secretion and mRNA levels of TNF-α, but not its membrane expression, was significantly lower in iron deficient subjects (Munoz et al., 2007).
The Panel concludes that a cause and effect relationship has been established between the dietary intake of iron and a normal function of the immune system.
3.5. Funkcje poznawcze (ID 253)
A total of 84 references were provided to substantiate the claimed effect. The great majority of the human studies were in infants and children. One study by Murray-Kolb and Beard (2007) showed an effect of iron supplementation on cognitive function in healthy women between 18-35 years of age.
It is well established that inadequate dietary iron intake in humans leads to reduced oxygen transport, which could have an impact on cognitive function. The cognitive deficiency symptoms observed with iron-deficient anaemia include deficits in attention, perceptual motor speed, memory and verbal fluency (Malestrom, 2002).
The Panel concludes that a cause and effect relationship has been established between the dietary intake of iron and normal cognitive function.
3.6. Podziały komórek (ID 368)
No references have been provided to substantiate the claimed effect.
As all essential nutrients, iron is needed for cell division. Iron's role in this process is connected to its function in oxygen transport and energy-yielding metabolism, and more specific through the control of the activities of iron containing enzymes involved either in DNA synthesis (ribonucleotide reductase) or in the phase progression during the cell cycle (cyclin-dependent kinase complexes 4 and 6) (Bohnsack and Hirschi, 2004).
The Panel concludes that a cause and effect relationship has been established between the dietary intake of iron and normal cell division.
4. Uwagi do zaproponowanego brzmienia oświadczenia
4.1. Tworzenie erytrocytów (czerwonych krwinek) i hemoglobiny (ID 249, 1589)
The Panel considers that the following wording reflects the scientific evidence: “Iron contributes to normal formation of red blood cells and haemoglobin.”
4.2. Transport tlenu (ID 250, 254, 256)
The Panel considers that the following wording reflects the scientific evidence: “Iron contributes to normal oxygen transport in the body.”
4.3. Metabolizm energetyczny (ID 251, 1589)
The Panel considers that the following wording reflects the scientific evidence: ”Iron contributes to normal energy-yielding metabolism.”
4.4. Funkcjonowanie układu odpornościowego (ID 252, 259)
The Panel considers that the following wording reflects the scientific evidence: “Iron contributes to a normal function of the immune system.”
4.5. Funkcje poznawcze (ID 253)
The Panel considers that the following wording reflects the scientific evidence: “Iron contributes to normal cognitive function.”
4.6. Podziały komórek (ID 368)
The Panel considers that the following wording reflects the scientific evidence: “Iron contributes to normal cell division.”
5. Warunki i możliwe ograniczenia stosowania oświadczenia
In order to bear the claims a food should be at least source of iron 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. No Upper Tolerable Intake Levels (UL) have been set for iron (EFSA, 2004).
Wnioski
On the basis of the data presented, the Panel concludes that:
The food constituent, iron, which is the subject of the health claims is sufficiently characterised.
Formation of red blood cells and haemoglobin (ID 249, 1589)
The claimed effect is “red blood cell and haemoglobin formation”. The target population is assumed to be the general population. Normal formation of red blood cells and haemoglobin are beneficial to human health.
A cause and effect relationship has been established between the dietary intake of iron and normal formation of red blood cells and haemoglobin.
The following wording reflects the scientific evidence: “Iron contributes to normal formation of red blood cells and haemoglobin”.
Oxygen transport (ID 250, 254, 256)
The claimed effect is “oxygen transport”. The target population is assumed to be the general population. Normal oxygen transport is beneficial to human health.
A cause and effect relationship has been established between the dietary intake of iron and normal oxygen transport to tissues.
The following wording reflects the scientific evidence: “Iron contributes to normal oxygen transport in the body”.
Energy-yielding metabolism (ID 251, 1589)
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 iron and normal energy-yielding metabolism.
The following wording reflects the scientific evidence: “Iron contributes to normal energy- yielding metabolism”.
Function of the immune system (ID 252, 259)
The claimed effect is “normal functioning of the 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 iron and a normal function of the immune system.
The following wording reflects the scientific evidence: “Iron contributes to a normal function of the immune system”.
Cognitive development and function (ID 253)
The claimed effect is “cognitive development and function”. The target population is assumed to be the general population. Normal cognitive function is beneficial to human health.
A cause and effect relationship has been established between the dietary intake of iron and normal cognitive function.
The following wording reflects the scientific evidence: “Iron contributes to normal cognitive function”.
Cell division (ID 368)
The claimed effect is “cell division”. The target population is assumed to be the general population. Normal cell division is beneficial to human health.
A cause and effect relationship has been established between the dietary intake of iron and normal cell division.
The following wording reflects the scientific evidence: “Iron contributes to normal cell division”.
Conditions and possible restrictions of use
In order to bear the claims a food should be at least a source of iron as per Annex to Regulation (EC) No 1924/2006. The target population is the general population. Such amounts can be easily consumed as part of a balanced diet.
