Scientific Opinion on the substantiation of health claims related to selenium
and protection of DNA, proteins and lipids from oxidative damage (ID 277,
283, 286, 1289, 1290, 1291, 1293, 1751), function of the immune system
(ID 278), thyroid function (ID 279, 282, 286, 1289, 1290, 1291, 1293),
function of the heart and blood vessels (ID 280), prostate function (ID 284),
cognitive function (ID 285) and spermatogenesis (ID 396) 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:
Selenium
antioxidant
cardiovascular
cognitive
health claims
immune system
iodine utilisation
minerals
prostate
spermatogenesis
thyroid hormone
1. Charakterystyka żywności / składnika
The food constituent that is the subject of the health claims is selenium, which is a well recognised nutrient and is measurable in foods by established methods.
Selenium occurs naturally in foods and is authorised for addition to foods and for use in food supplements (Annex I of the Regulation (EC) No 1925/20064 and Annex I of Directive 2002/46/EC5). This evaluation applies to selenium naturally present in foods and to 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, selenium, which is the subject of the health claims is sufficiently characterised.
2. Znaczenie oświadczenia dla zdrowia człowieka
2.1. Ochrona DNA, białek i lipidów przed uszkodzeniem oksydacyjnym (ID 277, 283, 286, 1289, 1290, 1291, 1293, 1751)
The claimed effects are “protection of body tissues and cells from oxidative damage/stress”, “antioxidant activity” and “aging”. 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.
No definition has been provided of what constitutes “aging”, and therefore the Panel cannot evaluate the “anti-aging effects” implied in claim ID 283. Also, the difference should be noted 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.
The Panel considers that the protection of biologically relevant molecules such as DNA, proteins and lipids from oxidative damage is beneficial to human health.
2.2. Funkcjonowanie układu odpornościowego (ID 278)
The claimed effects are “immune system” and “normal immune function”. 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. Funkcjonowanie tarczycy (ID 279, 282, 286, 1289, 1290, 1291, 1293)
The claimed effects are “thyroid function”, “iodine utilisation”, “thyroid hormone production” and “normal thyroid hormone metabolism”. The Panel assumes that the target population is the general population.
The Panel considers that normal thyroid function is beneficial to human health.
2.4. Funkcjonowanie serca i naczyń krwionośnych (ID 280)
The claimed effects are “normal cardiovascular function” and “cardiovascular health”. The Panel assumes that the target population is the general population.
Cardiovascular health has not been defined in the consolidated list and is interpreted by the Panel as function of the heart and blood vessels in order to allow a scientific evaluation.
The Panel considers that normal function of the heart and blood vessels is beneficial to human health.
2.5. Funkcjonowanie prostaty (ID 284)
The claimed effect is “prostate health”. The Panel assumes that the target population is the general male population.
The Panel considers that normal prostate function is beneficial to human health.
2.6. Funkcje poznawcze (ID 285)
The claimed effect is “brain health”. The Panel assumes that the target population is the general population.
Brain health has not been sufficiently defined in the list and is interpreted by the Panel as cognitive function in order to allow a scientific evaluation.
The Panel considers that normal cognitive function is beneficial to human health
2.7. Spermatogeneza (tworzenie plemników) (ID 396)
The claimed effect is “spermatogenesis”. The Panel assumes that the target population is the general male population.
The Panel considers that normal spermatogenesis is beneficial to human health.
3. Naukowe uzasadnienia wpływu na zdrowie człowieka -
Selenium is an essential trace element. Twenty-five selenoprotein genes have been identified in the human genome (Kryukov et al., 2003). Selenoproteins have a number of functions, comprising various catalytic roles (glutathione peroxidases, thioredoxin reductases, and iodothyronine
deiodinases), structural roles, detoxifying functions (e.g. selenoprotein P) and storage and transport activities. Selenium is present in foods mainly as selenomethionine and selenocysteine. It is absorbed efficiently by the intestine over a wide range of concentrations and across a variety of different molecular forms (Bates, 2005).
3.1. Ochrona DNA, białek i lipidów przed uszkodzeniem oksydacyjnym (ID 277, 283, 286, 1289, 1290, 1291, 1293, 1751)
The role of selenium as an indirect component of the antioxidant network is well established. This defence system comprises low molecular weight antioxidants and antioxidant enzymes like glutathione peroxidases which catalyse the reduction of hydrogen peroxide or organic hydroperoxides using reduced glutathione as a co-substrate (Papp et al., 2007). These enzymes and other selenoenzymes, such as the thioredoxin reductases, which are also involved in antioxidant defence are selenium-dependent and can respond to selenium supplementation.
The Panel concludes that a cause and effect relationship has been established between the dietary intake of selenium and the protection of DNA, proteins and lipids from oxidative damage. However, the evidence provided does not establish that inadequate intake of selenium leading to impaired protection of DNA, proteins and lipids from oxidative damage occurs in the general EU population.
3.2. Funkcjonowanie układu odpornościowego (ID 278)
Selenium appears to play a role in cell-mediated immunity. Human supplementation with selenium was able to stimulate the proliferation of activated T cells of the immune system. It elicited an enhanced response to antigen stimulation, an enhanced ability to generate cytotoxic lymphocytes, an enhanced ability to destroy tumour cells, and increased natural killer cell activity. Growth-regulatory interleukin-2 receptors on the surface of activated lymphocytes and natural killer cells became upregulated (Bates, 2005).
The Panel concludes that a cause and effect relationship has been established between the dietary intake of selenium and normal function of the immune system. However, the evidence provided does not establish that inadequate intake of selenium leading to impaired function of the immune system occurs in the general EU population.
3.3. Funkcjonowanie tarczycy (ID 279, 282, 286, 1289, 1290, 1291, 1293)
Deiodination is a pathway of thyroid hormone metabolism implicated in activation and deactivation of thyroid hormones. The metabolism is catalysed by three iodothyronine deiodinases (D1-3) which are homologous selenoproteins. In humans the enzymes are found in various tissues; D1 and D2 but not D3 also occur in the thyroid gland (Kuiper et al., 2005). Thus, the known biological functions of selenium include regulation of thyroid hormone action. 2005).
The Panel concludes that a cause and effect relationship has been established between the dietary intake of selenium and normal thyroid function. However, the evidence provided does not establish that inadequate intake of selenium leading to impaired thyroid function occurs in the general EU population.
3.4. Funkcjonowanie serca i naczyń krwionośnych (ID 280)
A total of nine references were provided in the consolidated list to support this claim. These included six reviews, one opinion from a scientific body, one textbook and one human study.
Selenium deficiency has been found to play a role in Keshan disease, an endemic cardiomyopathy, postulated to have a mutated coxsackie B virus also as part of its aetiology and which particularly affects children and women of child-bearing age in China. The acute form is characterised by sudden onset of insufficient heart function, whereas patients with chronic disease exhibit moderate to severe heart enlargement with varying degrees of heart insufficiency (Burk and Levander, 2006). However, selenium supplements were not able to restore the ultrastructural changes in the myocardium of latent Keshan disease patients and new latent and naturally-occurring chronic cases were found in the endemic area even after selenium status had been elevated. Thus, selenium might be a conditional predisposing factor for the occurrence of Keshan disease (Xu et al., 1997).
Flores-Mateo et al. (2006) performed a meta-analysis on the association of selenium biomarkers with coronary heart disease endpoints and reported that few randomised trials have addressed the cardiovascular efficacy of selenium supplementation, and, moreover, that the findings from these trials are inconclusive.
The Panel concludes that the evidence provided is insufficient to establish a cause and effect relationship between the dietary intake of selenium and normal function of the heart and blood vessels.
3.5. Funkcjonowanie prostaty (ID 284)
A total of 11 references were provided in the consolidated list to support this claim. These included four reviews, one opinion from a scientific body, three human studies and three in vitro studies.
Nine references provided in the consolidated list dealt with selenium as a potential chemopreventive agent against prostate cancer. Two references were concerned with the general requirements of selenium in human nutrition. It has been suggested that selenium may have chemoprotective effects that are mediated through the antioxidant properties of selenoenzymes (Peters et al., 2007). However, expert reviews of the evidence show that there is no consensus about the role of selenium in prostate cancer prevention (Burk and Levander, 2006; Combs, 2005; Gupta, 2007; Thomson, 2004). A recent large randomised placebo-controlled trial in men aged ≥ 50 years (n=35,533) showed that daily supplementation with selenium (200 µg) had no significant effect on risk of development of prostate cancer over three years with a median overall follow-up of 5.5 years (Lippman et al., 2009).
In weighing the evidence, the Panel took into account that the evidence provided by expert reviews shows that there is no consensus about the role of selenium in prostate cancer prevention and that a recent large randomized controlled trial in men aged ≥ 50 years showed no significant effect of selenium on risk of development of prostate cancer over three years with a median overall follow-up of 5.5 years.
The Panel concludes that a cause and effect relationship has not been established between the dietary intake of selenium and normal prostate function.
3.6. Funkcje poznawcze (ID 285)
A total of 11 references were provided in the consolidated list to support this claim. These included five reviews, one opinion from a scientific body, two animal studies and three in vitro studies.
Selenium is particularly well maintained in the brain, even upon prolonged dietary selenium deficiency. The preferential retention of selenium was suggested to reflect important functions of selenium in the brain. Changes in selenium concentration in blood and brain have been reported in Alzheimer's disease and brain tumors. Several selenoproteins are expressed in the brain, but many questions remain about their roles in neuronal function. Genetic inactivation of selenoprotein P in mice leads to a marked reduction of brain selenium content, and to a movement disorder and
spontaneous seizures (Chen and Berry, 2003; Schweizer et al., 2004). A protective role of selenium against cerebral ischaemia-induced neuronal damage has been reported in two animal studies (Ansari et al., 2004; Yousuf et al., 2007). Two in vitro studies reported an involvement of selenium in the protection of neuronal cells from oxidative damage; another in vitro study examined the antimigratory role of selenium on microglial cells, possibly attenuating the secondary cell death cascade after stroke or excitotoxicity (Dalla Puppa et al., 2007).
Selenium deficiency has been well documented in humans. Impairment in neurological function is not among the established signs and symptoms of selenium deficiency described in humans (Burk and Levander, 2006). No evidence has been provided on the effects of selenium supplementation on cognitive or neurological function.
The Panel concludes that a cause and effect relationship has not been established between the dietary intake of selenium and cognitive function.
3.7. Spermatogeneza (tworzenie plemników) (ID 396)
The sperm mitochondrial capsule selenoprotein has a structural as well as an enzymatic role, and it is responsible for both the maintenance of motility and the structural integrity of the tail of the sperm. Both human and other mammals exhibit reduced sperm motility and increased sperm rupture under conditions of low selenium supply (Bates, 2005).
The Panel concludes that a cause and effect relationship has been established between the dietary intake of selenium and normal spermatogenesis. However, the evidence provided does not establish that inadequate intake of selenium leading to impaired spermatogenesis occurs in the general EU population.
4. Uwagi do zaproponowanego brzmienia oświadczenia
4.1. Ochrona DNA, białek i lipidów przed uszkodzeniem oksydacyjnym (ID 277, 283, 286, 1289, 1290, 1291, 1293, 1751)
The Panel considers that the following wording reflects the scientific evidence: “selenium contributes to the protection of cell constituents from oxidative damage”.
4.2. Funkcjonowanie układu odpornościowego (ID 278)
The Panel considers that the following wording reflects the scientific evidence: “selenium contributes to the normal function of the immune system”.
4.3. Funkcjonowanie tarczycy (ID 279, 282, 286, 1289, 1290, 1291, 1293)
The Panel considers that the following wording reflects the scientific evidence: “selenium contributes to normal thyroid function”.
4.4. Spermatogeneza (tworzenie plemników) (ID 396)
The Panel considers that the following wording reflects the scientific evidence: “selenium contributes to normal spermatogenesis”.
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 selenium 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) have been established as 300 µg/day for adults and for pregnant and lactating woman. For children and adolescents UL were established as 60 µg/day for 1-3 years, 90 µg/day for 4-6 years, 130 µg/day for 7-10 years, 200 µg/day for 11-14 years and 250 µg/day for 15-17 years (SCF, 2000).
Wnioski
On the basis of the data presented, the Panel concludes that:
The food constituent, selenium, which is the subject of the health claims is sufficiently characterised.
Protection of DNA, proteins and lipids from oxidative damage (ID 277, 283, 286, 1289, 1290, 1291, 1293, 1751)
The claimed effects are “protection of body tissues and cells from oxidative damage/stress”, “antioxidant activity” and “aging”. The target population is assumed to be the general population. The 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 selenium and the protection of DNA, proteins and lipids from oxidative damage.
The evidence provided does not establish that inadequate intake of selenium 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: “selenium contributes to the protection of body cell constituents from oxidative damage”.
Function of the immune system (ID 278)
The claimed effects are “immune system” and “normal immune function”. 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 selenium and normal function of the immune system.
The evidence provided does not establish that inadequate intake of selenium leading to impaired function of the immune system occurs in the general EU population.
The following wording reflects the scientific evidence: “selenium contributes to the normal function of the immune system”.
Thyroid function (ID 279, 282, 286, 1289, 1290, 1291, 1293)
The claimed effects are “thyroid function”, “iodine utilisation”, “thyroid hormone production”, “normal thyroid hormone metabolism”. The target population is assumed to be the general population. Normal thyroid function is beneficial to human health.
A cause and effect relationship has been established between the dietary intake of selenium and normal thyroid function.
The evidence provided does not establish that inadequate intake of selenium leading to impaired thyroid function occurs in the general EU population.
The following wording reflects the scientific evidence: “selenium contributes to normal thyroid function”.
Function of the heart and blood vessels (ID 280)
The claimed effects are “normal cardiovascular function” and “cardiovascular health”. The target population is assumed to be the general population. Normal function of the heart and blood vessels is beneficial to human health.
The evidence provided is insufficient to establish a cause and effect relationship between the dietary intake of selenium and normal function of the heart and blood vessels.
Prostate function (ID 284)
The claimed effect is “prostate health”. The target population is assumed to be the general male population. Normal prostate function is beneficial to human health.
A cause and effect relationship has not been established between the dietary intake of selenium and normal prostate function.
Cognitive function (ID 285)
The claimed effect is “brain health”. The target population is assumed to be the general population. Normal cognitive function is beneficial to human health.
A cause and effect relationship has not been established between the dietary intake of selenium and normal cognitive function.
Spermatogenesis (ID 396)
The claimed effect is “spermatogenesis”. The target population is assumed to be the general male population. Normal spermatogenesis is beneficial to human health.
A cause and effect relationship has been established between the dietary intake of selenium and normal spermatogenesis.
The evidence provided does not establish that inadequate intake of selenium leading to impaired spermatogenesis occurs in the general EU population.
The following wording reflects the scientific evidence: “selenium contributes to normal spermatogenesis”.
Conditions and possible restrictions of use
The Panel considers that in order to bear the claims a food should be at least a source of selenium 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.
