Scientific Opinion on the substantiation of health claims related to
eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA),
docosapentaenoic acid (DPA) and maintenance of normal cardiac function
(ID 504, 506, 516, 527, 538, 703, 1128, 1317, 1324, 1325), maintenance of
normal blood glucose concentrations (ID 566), maintenance of normal
blood pressure (ID 506, 516, 703, 1317, 1324), maintenance of normal blood
HDL-cholesterol concentrations (ID 506), maintenance of normal (fasting)
blood concentrations of triglycerides (ID 506, 527, 538, 1317, 1324, 1325),
maintenance of normal blood LDL-cholesterol concentrations (ID 527, 538,
1317, 1325, 4689), protection of the skin from photo-oxidative (UV-
induced) damage (ID 530), improved absorption of EPA and DHA (ID 522,
523), contribution to the normal function of the immune system by
decreasing the levels of eicosanoids, arachidonic acid-derived mediators
and pro-inflammatory cytokines (ID 520, 2914), and “immunomodulating
agent” (ID 4690) pursuant to Article 13(1) of Regulation (EC) No 1924/2006[sup]1[/sup]
EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA)2, 3
European Food Safety Authority (EFSA), Parma, Italy
Słowa kluczowe:
DHA
DPA
EPA
HDL-cholesterol
LDL- cholesterol
blood lipids
blood pressure
cardiovascular
health claims
triglycerides
1. Charakterystyka żywności / składnika
The food constituent which is the subject of the health claims is mixed long-chain n-3 polyunsaturated fatty acids (n-3 LCPUFA), namely docosahexaenoic acid (DHA) in combination with eicosapentaenoic acid (EPA) and, for ID 703, with docosapentaenoic acid (DPA).
The n-3 LCPUFA EPA, DHA and DPA are recognised nutrients and are measurable in foods by established methods. They are well absorbed when consumed in the form of triglycerides. This evaluation applies to EPA, DHA and, for ID 703, DPA from all sources with suitable bioavailability in the specified amounts.
The Panel considers that the food constituent, EPA, DHA and DPA, which is the subject of the health claims, is sufficiently characterised.
2. Znaczenie oświadczenia dla zdrowia człowieka
2.1. Utrzymanie prawidłowego funkcjonowania serca (ID 504, 506, 516, 527, 538, 703, 1128, 1317, 1324, 1325)
The claimed effects are “cardiovascular system: maintenance and promotion of heart health and healthy circulation”, “normal cardiovascular function”, “eye, brain and heart health”, “cardiovascular health” and “heart health”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings and clarifications provided by Member States, the Panel notes that the claimed effects relate to the maintenance of normal cardiac function.
The Panel considers that maintenance of normal cardiac function is a beneficial physiological effect.
2.2. Utrzymanie prawidłowego stężenia glukozy we krwi (ID 566)
The claimed effect is “carbohydrate metabolism and insulin sensitivity”. The Panel assumes that the target population is the general population.
In the context of the proposed wording, the Panel assumes that the claimed effect refers to the long- term maintenance or achievement of normal blood glucose concentrations.
The Panel considers that long-term maintenance of normal blood glucose concentrations is a beneficial physiological effect.
2.3. Utrzymanie prawidłowego ciśnienia tętniczego (ID 506, 516, 703, 1317, 1324)
The claimed effects are “cardiovascular health”, “heart health”, “normal cardiovascular function” and “heart health”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings or clarifications provided by Member States, the Panel assumes that the claimed effect relates to the maintenance of normal blood pressure.
A claim on EPA and DHA and the maintenance of normal blood pressure has already been assessed with a favourable outcome (EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA), 2009).
2.4. Utrzymanie prawidłowego stężenia cholesterolu HDL we krwi (ID 506)
The claimed effect is “normal cardiovascular function”. The Panel assumes that the target population is the general population.
In the context of the clarifications provided by Member States, the Panel assumes that the claimed effect refers to the maintenance of normal blood HDL-cholesterol concentrations.
A claim on EPA and DHA and the maintenance of normal blood HDL-cholesterol concentrations has already been assessed with an unfavourable outcome (EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA), 2009) and the references cited for this claim did not provide any additional scientific data that could be used to substantiate the claim.
2.5. Utrzymanie prawidłowego stężenia trójglicerydów we krwi na czczo (ID 506, 527, 538, 1317, 1324, 1325)
The claimed effects are “normal cardiovascular function”, “cardiovascular health”, “heart health”, “for cardiovascular system metabolism (cholesterol, triglycerides)” and “decrease triglycerides”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings and clarifications provided by Member States, the Panel assumes that the claimed effect relates to the maintenance of normal (fasting) blood concentrations of triglycerides.
Triglycerides in plasma are either derived from dietary fats or synthesised in the body from other energy sources like carbohydrates. In fasting conditions, serum triglycerides are mainly transported in very-low-density lipoproteins (VLDL) synthesised in the liver. Excess calorie intake with a meal is converted to triglycerides and transported to the adipose tissue for storage. Hormones regulate the release of triglycerides from adipose tissue in order to meet energy needs between meals.
The Panel considers that maintenance of normal (fasting) blood concentrations of triglycerides may be a beneficial physiological effect.
2.6. Utrzymanie prawidłowego stężenia cholesterolu LDL we krwi (ID 527, 538, 1317, 1325, 4689)
The claimed effects are “cardiovascular health”, “heart health”, “cholesterol-lowering” and “for cardiovascular system metabolism (cholesterol, triglycerides)”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings and clarifications provided by Member States, the Panel assumes that the claimed effect refers to the maintenance of normal blood LDL-cholesterol concentrations.
A claim on EPA and DHA and the maintenance of normal blood LDL-cholesterol concentrations has already been assessed with an unfavourable outcome (EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA), 2009) and the references cited for this claim did not provide any additional scientific data that could be used to substantiate the claim.
2.7. Ochrona skóry przed uszkodzeniem promieniami ultrafioletowymi (UV) (ID 530)
The claimed effect is “skin health”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings and clarifications provided by Member States, the Panel assumes that the claim refers to the protection of the skin from photo-oxidative (UV-induced) damage.
The Panel considers that the protection of the skin from photo-oxidative (UV-induced) damage is a beneficial physiological effect.
2.8. Zwiększenie biodostępności kwasów EPA i DHA (ID 522, 523)
The claimed effects are “intake of emulsified fish oil improves the digestion and absorption of omega- 3 fatty acids” and “intake of emulsified cod liver oil improves the digestion and absorption of omega- 3 fatty acids”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings and clarifications provided by Member States, the Panel assumes that the claimed effects relate to an improved absorption of EPA and DHA from emulsified fish oils as compared to other (non emulsified) sources of EPA and DHA.
Regulation (EC) No 1924/2006 defines health claims made on foods as “any claim that states, suggests or implies that a relationship exists between a food category, a food or one of its constituents and health” (Article 2.5), whereas that “the nutrient or other substance for which the claim is made is in a form that is available to be used by the body” (Article 5.1(c)) is a general condition for all claims.
The Panel notes that the claimed effects relate to the improved absorption of the food constituents (EPA and DHA) rather than to the relationship between a food constituent and health as required by
Regulation (EC) No 1924/2006.
2.9. Wpływ na prawidłowe funkcjonowanie układu odpornościowego poprzez zmniejszenie mediatorów stanu zapalnego (pochodnych kwasu arachidonowego) i cytokin prozapalnych (ID 520, 2914)
The claimed effects are “immune function” and “normal immune system function”. The target population is assumed to be the general population.
From the proposed wordings and clarifications provided by Member States, the Panel assumes that the claimed effect refers to supporting a normal/healthy immune function in the context of decreasing the level or production of eicosanoids, arachidonic acid-derived mediators and pro-inflammatory cytokines.
Inflammation is a non-specific physiological response to tissue damage that is mediated by the immune system. Adequate inflammatory responses are of primary importance for the defence against injury of any origin. Changes in markers of inflammation such as decreasing the levels of eicosanoids, arachidonic acid-derived mediators and pro-inflammatory cytokines do not indicate a beneficial physiological effect per se.
Chronic inflammation is associated with a number of diseases, and under certain circumstances reducing levels of markers of inflammation might indicate a beneficial physiological effect.
Whether or not reduction of inflammatory markers is considered beneficial would depend on the context in which the claim is made. The Panel considers that the evidence provided does not define the context whereby decreasing the level or production of eicosanoids, arachidonic acid-derived mediators and pro-inflammatory cytokines might be a beneficial physiological effect in the general healthy population.
The Panel concludes that a cause and effect relationship has not been established between the consumption of DHA and EPA and a beneficial physiological effect related to the contribution to the normal function of the immune system by decreasing the levels of eicosanoids, arachidonic acid- derived mediators and pro-inflammatory cytokines.
2.10. Czynnik wpływający na odpowiedź immunologiczną (ID 4690)
The claimed effect is “immunomodulating agent due to EPA and DHA”. The Panel assumes that the target population is the general population.
“Immunomodulating agent” is not sufficiently defined and no further details are given in the proposed wording. In the references, that were cited for the scientific substantiation of the claimed effect several effects were mentioned (related for example to coronary heart disease, rheumatoid arthritis, asthma or eczema) and it is not possible to establish which specific effect is the target for the claim.
In the absence of such information, the Panel considers that the claimed effect is not sufficiently defined for a scientific evaluation.
The Panel considers that the claimed effect is general and non-specific and does not refer to any specific health claim as required by Regulation (EC) No 1924/2006.
3. Naukowe uzasadnienia wpływu na zdrowie człowieka -
3.1. Utrzymanie prawidłowego funkcjonowania serca (ID 504, 506, 516, 527, 538, 703, 1128, 1317, 1324, 1325)
National and international bodies have based their recommendations for dietary intake of EPA and DHA on the inverse relationship observed between the consumption of these long-chain n-3 PUFAs (primarily from fish and fish oils) and a lower risk of coronary artery disease. Such recommendations range from 200 mg to 500 mg per day (EFSA, 2005, 2009; EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA), 2010). Most recent evidence derived from meta-analyses of randomised trials and large prospective studies shows that, when only healthy subjects are considered, the intake of EPA plus DHA is negatively related to coronary heart disease mortality in a dose- dependent way up to about 250 mg per day (1–2 servings of oily fish per week), with little additional
benefit observed at higher intakes (Mozaffarian and Rimm, 2006; Mozaffarian, 2008; Harris et al., 2008, 2009a, b; EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA), 2010).
EPA and DHA intakes could reduce the risk of coronary heart disease mortality by different (but often overlapping) mechanisms (e.g. through antiarrhythmic and antithrombotic effects, by reducing blood pressure, heart rate and plasma concentrations of triglycerides), and the doses of EPA and DHA (100->2,500 mg/d) as well as the time required to observe clinical effects and/or alter clinical events (weeks to years) through each mechanism may vary widely (Mozaffarian and Rimm, 2006).
The Panel concludes that a cause and effect relationship has been established between the consumption of EPA and DHA and maintenance of normal cardiac function.
3.2. Utrzymanie prawidłowego stężenia glukozy we krwi (ID 566)
Three references were provided for the scientific substantiation of this claim. One was a narrative review on n-3 fatty acids and the metabolic syndrome, one reported on an intervention study on the effects of a hypocaloric low-fat dietary intervention limiting intake of fatty fish and fish oil supplements on membrane fatty acid composition and insulin sensitivity, and the third reference reported on an intervention study investigating the acute effects of n-3 long-chain polyunsaturated fatty acids on dexamethasone-induced insulin resistance in healthy human volunteers. No measures of blood glucose control were reported in any of these studies. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
The Panel concludes that a cause and effect relationship has not been established between the consumption of EPA and DHA and long-term maintenance of normal blood glucose concentrations.
3.3. Utrzymanie prawidłowego stężenia trójglicerydów we krwi na czczo (ID 506, 527, 538, 1317, 1324, 1325)
A claim on EPA and DHA and the maintenance of normal (fasting) blood concentrations of triglycerides has been already assessed with a favourable outcome (EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA), 2009). The Panel considered that intakes of EPA and DHA of about 2-4 g per day were required to obtain the claimed effect.
The Panel is aware of a recently published meta-analysis which aimed to investigate dose-response relationships between the intake of EPA and DHA and changes in blood concentrations of triglycerides to estimate the effects of doses between 200-500 mg per day (Musa-Veloso et al., 2010). A total of 15 studies published between 2002 and 2007 were considered. The reason given to exclude publications prior to 2002 was “to avoid duplication of previously reported findings”. Of these, only 12 studies conducted statistical comparisons between intervention and placebo groups. Average intakes of EPA and DHA were 2.3 g per day (range 209 mg to 5.6 g per day). The Panel notes that four studies were conducted with DHA only (Maki et al., 2003, 2005; Stark and Holub, 2004; Wu et al., 2006). The Panel also notes that only two studies were included using doses of DHA or EPA plus DHA in the range for which an effect on blood triglycerides was aimed for, that neither of these found a significant decrease in blood triglycerides in the intervention group compared to controls (Maki et al., 2003; Castro et al., 2007), and that one of them is considered as “flawed” by the authors of the meta-analysis (Castro et al., 2007). The Panel notes that exclusion of pertinent studies published before 2002 is scientifically unjustified. The Panel considers that no scientific conclusions can be drawn from this meta-analysis to establish conditions of use for the claim.
In addition to Maki et al. (2003) and Castro et al. (2007), only one study included in the meta-analysis used doses of EPA plus DHA <1 g per day (0.860 mg per day). In this study, additional intakes in the intervention and placebo groups of about 1,200 mg per day from dietary sources were estimated but were not taken into account in the analysis (Hamazaki et al., 2003). A further two studies using EPA
and DHA at doses of 1 and 1.6 g per day were included in the meta-analysis (Goyens and Mensink, 2006; Murphy et al., 2007), none of these reported statistically significant differences between the intervention and control groups with respect to changes in blood concentrations of triglycerides.
With reference to its previous opinion, the Panel considers that intakes of EPA and DHA of 2 g per day are required to obtain the claimed effect.
3.4. Ochrona skóry przed uszkodzeniem promieniami ultrafioletowymi (UV) (ID 530)
Among the 26 references provided for the scientific substantiation of this claim, most reported on food constituents (e.g. vitamin E) and/or health effects (e.g. coronary heart disease, sudden cardiac death, blood lipids, blood glucose control, infertility, pregnancy, inflammation, psoriasis, non- melanoma skin cancer) unrelated to the claimed effect. The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
Two of the references are general reviews on the role of n-3 fatty acids on the pathogenesis of skin cancer (Black and Rhodes, 2006) and photo-protection (Rhodes, 1998) but did not provide original data for the scientific substantiation of the claimed effect.
An open label intervention study in humans on the effects of fish oil supplementation on the minimal erythemal dose of UVB irradiation, and on the threshold UVB irradiation dose for papule provocation in patients with polymorphic light eruption, was presented (Rhodes et al., 1995). The Panel notes that no conclusions can be drawn from this uncontrolled study for the scientific substantiation of the claimed effect.
A double-blind, placebo controlled intervention study was presented on the effects of EPA alone (4 g per day) on a range of indicators of ultraviolet radiation (UVR)-induced responses and damage in humans, as well as on basal and post-UVR oxidative status (Rhodes et al., 2003). The Panel considers that no conclusions can be drawn from this study on EPA alone for the scientific substantiation of a claim on the combination of EPA and DHA.
The Panel concludes that a cause and effect relationship has not been established between the consumption of EPA and DHA and the protection of the skin from photo-oxidative (UV-induced) damage.
4. Uwagi do zaproponowanego brzmienia oświadczenia
4.1. Utrzymanie prawidłowego funkcjonowania serca (ID 504, 506, 516, 527, 538, 703, 1128, 1317, 1324, 1325)
The Panel considers that the following wording reflects the scientific evidence: “EPA and DHA contribute to the normal function of the heart”.
5. Warunki i możliwe ograniczenia stosowania oświadczenia
5.1. Utrzymanie prawidłowego funkcjonowania serca (ID 504, 506, 516, 527, 538, 703, 1128, 1317, 1324, 1325)
The Panel considers that intakes of EPA and DHA of about 250 mg per day are required to obtain the claimed effect. Such an amount can be consumed as part of a balanced diet. The target population is the general population.
5.2. Utrzymanie prawidłowego stężenia trójglicerydów we krwi na czczo (ID 506, 527, 538, 1317, 1324, 1325)
The Panel considers that intakes of EPA and DHA of 2 g per day are required to obtain the claimed effect. Such an amount can be consumed as part of a balanced diet. The target population is adult men and women.
Wnioski
On the basis of the data presented, the Panel concludes that:
The food constituent, EPA, DHA and DPA, which is the subject of the health claims, is sufficiently characterised.
Maintenance of normal cardiac function (ID 504, 506, 516, 527, 538, 703, 1128, 1317, 1324, 1325)
The claimed effects are “cardiovascular system: maintenance and promotion of heart health and healthy circulation”, “normal cardiovascular function”, “eye, brain and heart health”, “cardiovascular health” and “heart health”. The target population is assumed to be the general population. Maintenance of normal cardiac function is a beneficial physiological effect.
A cause and effect relationship has been established between the consumption of EPA and DHA and maintenance of normal cardiac function.
The following wording reflects the scientific evidence: “EPA and DHA contribute to the normal function of the heart”.
Intakes of EPA and DHA of about 250 mg per day are required to obtain the claimed effect. Such an amount can be consumed as part of a balanced diet. The target population is the general population.
Maintenance of normal blood glucose concentrations (ID 566)
The claimed effect is “carbohydrate metabolism and insulin sensitivity”. The target population is assumed to be the general population. Long-term maintenance of normal blood glucose concentrations is a beneficial physiological effect.
A cause and effect relationship has not been established between the consumption of EPA and DHA and long-term maintenance of normal blood glucose concentrations.
Maintenance of normal blood pressure (ID 506, 516, 703, 1317, 1324)
The claimed effects are “cardiovascular health”, “heart health”, “normal cardiovascular function” and “heart health”. The target population is assumed to be the general population.
A claim on EPA and DHA and the maintenance of normal blood pressure has already been assessed with a favourable outcome.
Maintenance of normal blood HDL-cholesterol concentrations (ID 506)
The claimed effect is “normal cardiovascular function”. The target population is assumed to be the general population.
A claim on EPA and DHA and the maintenance of normal blood HDL-cholesterol concentrations has already been assessed with an unfavourable outcome and the references cited for this claim did not provide any additional scientific data that could be used to substantiate the claim.
Maintenance of normal (fasting) blood concentrations of triglycerides (ID 506, 527, 538, 1317,
1324, 1325)
The claimed effects are “normal cardiovascular function”, “cardiovascular health”, “heart health”, “for cardiovascular system metabolism (cholesterol, triglycerides)” and “decrease triglycerides”. The target population is assumed to be the general population. Maintenance of normal (fasting) blood concentrations of triglycerides may be a beneficial physiological effect.
A claim on EPA and DHA and the maintenance of normal (fasting) blood concentrations of triglycerides has been already assessed with a favourable outcome.
Intakes of EPA and DHA of 2 g per day are required to obtain the claimed effect. Such an amount can be consumed as part of a balanced diet. The target population is adult men and women.
Maintenance of normal blood LDL-cholesterol concentrations (ID 527, 538, 1317, 1325, 4689)
The claimed effects are “cardiovascular health”, “heart health”, “cholesterol-lowering” and “for cardiovascular system metabolism (cholesterol, triglycerides)”. The target population is assumed to be the general population.
A claim on EPA and DHA and the maintenance of normal blood LDL-cholesterol concentrations has already been assessed with an unfavourable outcome and the references cited for this claim did not provide any additional scientific data that could be used to substantiate the claim.
Protection of the skin from photo-oxidative (UV-induced) damage (ID 530)
The claimed effect is “skin health”. The target population is assumed to be the general population. Protection of the skin from photo-oxidative (UV-induced) damage is a beneficial physiological effect.
A cause and effect relationship has not been established between the consumption of EPA and DHA and protection of the skin from photo-oxidative (UV-induced) damage.
Improved absorption of EPA and DHA (ID 522, 523)
The claimed effects are “intake of emulsified fish oil improves the digestion and absorption of omega-3 fatty acids” and “intake of emulsified cod liver oil improves the digestion and absorption of omega-3 fatty acids”. The target population is assumed to be the general population.
The claimed effects relate to the bioavailability of the food constituents (EPA and DHA) rather than to the relationship between a food constituent and health as required by Regulation (EC) No 1924/2006.
Contribution to the normal function of the immune system by decreasing the levels of
eicosanoids, arachidonic acid-derived mediators and pro-inflammatory cytokines (ID 520, 2914)
The claimed effects are “immune function” and “normal immune system function”. The target population is assumed to be the general population. It is assumed that the claimed effect refers to supporting a normal/healthy immune function in the context of decreasing the level or production of eicosanoids, arachidonic acid-derived mediators and pro- inflammatory cytokines. The evidence provided does not define the context whereby decreasing the level or production of eicosanoids, arachidonic acid-derived mediators and pro-inflammatory cytokines might be a beneficial physiological effect in the general healthy population.
A cause and effect relationship has not been established between the consumption of DHA and EPA and a beneficial physiological effect related to the contribution to the normal
function of the immune system by decreasing the levels of eicosanoids, arachidonic acid- derived mediators and pro-inflammatory cytokines.
“Immunomodulating agent” (ID 4690)
The claimed effect is “immunomodulating agent due to EPA and DHA”. The target population is assumed to be the general population.
The claimed effect is general and non-specific and does not refer to any specific health claim as required by Regulation (EC) No 1924/2006.
