2.1. Utrzymanie prawidłowego ciśnienia tętniczego (ID 502)

The claimed effect is “helps maintain normal blood pressure”. The Panel assumes that the target population is the general population.
Blood pressure (BP) is the pressure (force per unit area) exerted by circulating blood on the walls of blood vessels. Elevated BP, by convention above 140 mmHg (systolic) and/or 90 mmHg (diastolic), may compromise the normal structure and function of the arteries.
The Panel considers that maintenance of a normal blood pressure is beneficial to human health.

2.2. Utrzymanie prawidłowego stężenia cholesterolu HDL we krwi (ID 515)

The claimed effect is “HDL (good) cholesterol”. The Panel assumes that the target population is the general population.
High-density lipoproteins (HDL) act as cholesterol scavengers and are involved in the reverse transport of cholesterol in the body (from peripheral tissues back to the liver). Conversely, low- density lipoproteins (LDL) carry cholesterol from the liver to peripheral tissues, including the arteries.
The Panel considers that maintenance of normal HDL-cholesterol (without increasing LDL- cholesterol) concentrations is beneficial to human health.

2.3. Utrzymanie prawidłowego stężenia trójglicerydów we krwi na czczo (ID 517)

The claimed effect is “healthy triglyceride levels”. The target population is the general population.
In the context of the proposed wordings, 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 triglyceride 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 is beneficial to human health.

2.4. Utrzymanie prawidłowego stężenia cholesterolu LDL we krwi (ID 528, 698)

The claimed effect is “blood lipids”. The target population is the general population.
In the context of the proposed, the Panel assumes that the claim refers to the maintenance of normal blood triglycerides, LDL- and HDL-cholesterol concentrations.
The maintenance of normal HDL-cholesterol and blood triglyceride concentrations has been addressed in sections 2.2 and 2.3 of this Opinion, respectively.
Low-density lipoproteins (LDL) carry cholesterol from the liver to peripheral tissues, including the arteries. Elevated LDL-cholesterol, by convention >160 mg/dL, may compromise the normal structure and function of the arteries.
The Panel considers that maintenance of normal LDL-cholesterol concentrations is beneficial to human health.

2.5. Utrzymanie prawidłowego stanu stawów (ID 503, 505, 507, 511, 518, 524, 526, 535, 537)

The claimed effects are “joint health” and “immunity maintenance”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings the Panel assumes that these claimed effects relate to the maintenance of normal joints.
The Panel considers that maintenance of normal joints is beneficial to human health.

3.1. Utrzymanie prawidłowego ciśnienia tętniczego (ID 502)

The background literature provided includes various statements by authoritative bodies that advocate fish intake (1-2 times per week) and/or EPA plus DHA intake (~250-500 mg/day) for the prevention of coronary heart disease. The statements are based on scientific evidence for a beneficial effect of EPA plus DHA on cardiac mortality. None of the statements recommend increased intake of EPA plus DHA for their antihypertensive properties.
The literature presented refers to three meta-analyses (Appel et al., 1993; Morris et al., 1993; Geleijnse et al., 2002), which include two of the individual clinical trials provided (Knapp, 1989; Schmidt, 1992) and all are considered pertinent to the substantiation of the claim.
Appel et al. (1993) conducted a meta-analysis of 17 clinical trials on the effects of dietary n-3 fatty acids (mainly EPA plus DHA) on BP. Systolic BP was significantly reduced in two out of the 11 trials conducted in normotensive subjects, and in two out of the six trials conducted in untreated hypertensive subjects. Pooled estimates for systolic BP were -1.0 mmHg (95% CI: -2.0 to 0.0) in normotensive subjects and -5.5 mmHg (95% CI: -8.1 to -2.9) in hypertensive subjects. Daily doses of n-3 fatty acids were generally high (>3 g in 11 trials).
Morris et al. (1993) performed a meta-analysis of 31 clinical trials investigating the effects of fish oil consumption (mainly EPA plus DHA) on BP. Systolic BP was reduced on average by -3.0 mmHg (95% CI: -4.5 to -1.5). When grouped by EPA plus DHA dose, effects on systolic BP were -1.3 mmHg at ≤ 3 g/d, -2.9 mmHg at 3.3 to 7 g/d, and -8.1 mmHg at 15 g/d. Both EPA and DHA were related to BP response. Systolic BP was not reduced in "healthy" (i.e., normotensive and normocholesterolemic) subjects, i.e. -0.4 mmHg for a mean fish oil dose of 4.2 g per day. Significant BP reductions were found in hypertensive subjects (-3.4 mmHg at 5.6 g/d of EPA plus DHA) and in hypercholesterolaemic patients (-4.4 mmHg at 4.0 g/d of EPA plus DHA).
More recently, Geleijnse et al. (2002) performed a meta-analysis of 36 randomised controlled trials. Daily doses of fish oil (mainly EPA plus DHA) were <1.0 g in one trial, 1.0-1.9 g/d in five trials, 2.0-2.9 g/d in four trials, and 3.0–15.0 g/d in 26 trials, with a median dose of 3.7 g/d. Fish oil reduced systolic BP by -2.1 mmHg (95% CI: -3.2 to -1.0). Restricting the analysis to randomised controlled trials that were double-blind yielded a systolic BP estimate of -1.7 mmHg (95% CI: -3.1 to -0.3). Effects of EPA plus DHA intake on systolic BP were larger in older (>45y of age) subjects (-2.7 mmHg) and in hypertensive subjects (-3.7 mmHg).
Clinical trials on the effects of low doses of EPA plus DHA on BP are lacking. In a recent trial by Murphy et al. (2007), 86 overweight subjects with high serum triglyceride concentrations were randomised to 1 g of EPA plus DHA daily (by means of enriched foods) or placebo, for 6 months. Dietary intervention with EPA plus DHA improved various cardiovascular risk factors, but did not significantly affect BP (Murphy et al., 2007).
Potential mechanisms by which fish oil could reduce BP were described by Howe (1997). The review refers to animal experiments and results from meta-analyses of clinical trials (Appel et al., 1993; Morris et al., 1993). Howe (1997) concluded that there is uncertainty about the antihypertensive effects of EPA and DHA and about underlying mechanisms in animal models. He also stated that the extent of BP reduction depends on the initial BP level and on the dose of very long chain n-3 fatty acids so that clinically significant effects may be expected in hypertensive but not normotensive subjects, given a mean dose of ~3 g of EPA plus DHA per day.
From the evidence provided, the Panel considers that high doses of EPA + DHA ( 3 grams per day) have a short-term effect on systolic BP in subjects with untreated hypertension (~3-5 mmHg decrease in systolic BP; Mancia et al., 2007), and may have smaller, but statistically significant, effects in normotensives (~1 mmHg decrease in systolic BP).
The Panel concludes that a cause and effect relationship has been established between the consumption of EPA and DHA and the reduction of blood pressure.

3.2. Utrzymanie prawidłowego stężenia cholesterolu HDL we krwi (ID 515)

The effects of fish oils (mainly EPA plus DHA) on serum lipids and lipoproteins have been studied in numerous clinical trials. Harris (1997) published a meta-analysis of 72 studies with high doses
(2-4 g/d) of EPA and DHA. In another, more recent systematic review 21 studies were included (Balk et al., 2006).
Generally EPA plus DHA at high doses (2-4 g/d) have shown a small HDL-raising effect in subjects with hypertriglyceridaemia. In the meta-analysis by Harris (1997), an increase of 1-3% was observed, accompanied by an increase of 5-10% in LDL cholesterol. Balk et al. (2006) found a small average increase of 1.6 mg/dl in HDL cholesterol and 6 mg/dl in LDL cholesterol. The probable mechanism is increased lipoprotein lipase-mediated conversion of VLDL triglycerides to LDL and HDL-cholesterol (Jacobson, 2008). In subjects with normal triglyceride levels, no effects on serum total, LDL- or HDL-cholesterol are found (Harris, 1997).
The Panel considers that high doses of EPA plus DHA slightly increase HDL-cholesterol concentrations together with LDL-cholesterol concentrations in subjects with hypertriglyceridaemia, but do not affect HDL-cholesterol concentrations in normal subjects.
The Panel concludes that a cause and effect relationship has not been established between the dietary intake of EPA and DHA and the maintenance of normal HDL-cholesterol (without increasing LDL- cholesterol) concentrations.

3.3. Utrzymanie prawidłowego stężenia trójglicerydów we krwi na czczo (ID 517)

High doses (2-4 g/d) of EPA plus DHA decrease serum triglycerides in both normo- and hyperlipidaemic individuals. The effect is related both to the dose of EPA plus DHA and to the baseline concentrations of triglycerides (Jacobson, 2008). Harris (1997) observed a mean reduction of 35% in subjects with hypertriglyceridaemia and of 24% in those with serum triglycerides < 2 mmol/L. In the meta-analysis by Balk et al. (2006), a mean reduction of 27% in serum triglyceride concentrations was observed. EPA and DHA seem to have similar effects on serum triglycerides (Grimsgaard et al., 1997). The mechanisms that explain the effect include inhibition of triglyceride synthesis, stimulation of fatty acid beta-oxidation, and increased lipoprotein lipase-mediated clearance of VLDL triglycerides (Jacobsen, 2008).
In the diet and lifestyle recommendations by the American Heart Association (AHA), 2-4 g EPA plus DHA per day provided in capsules under physician‟s supervision are recommended for individuals with hypertriglyceridaemia (Lichtenstein et al., 2006).
The Panel considers that a cause and effect relationship has been established between the consumption of EPA and DHA and the reduction of (fasting) blood concentrations of triglycerides.

3.4. Utrzymanie prawidłowego stężenia cholesterolu LDL we krwi (ID 528, 698)

The effects of DHA and EPA on HDL-cholesterol and on blood triglycerides have been already assessed in sections 3.2. and 3.3.
EPA plus DHA at high doses (2-4 g/d) have multiple effects on blood lipids (Jacobson, 2008). Serum total cholesterol concentrations are generally not affected by this supplementation, but in subjects with hypertriglyceridaemia, LDL-cholesterol concentrations may be increased by 5-10% (Harris, 1997, Balk et al., 2006). The results of more recent studies agree with previous findings (Krebs et al., 2006, Hill et al., 2007).
The Panel concludes that a cause and effect relationship has not been established between the consumption of DHA and EPA and the maintenance of normal LDL-cholesterol concentrations.

3.5. Utrzymanie prawidłowego stanu stawów (ID 503, 505, 507, 511, 518, 524, 526, 535, 537)

A total of 18 human intervention studies, 18 reviews, three meta-analyses and six mechanistic studies on the effects of fish oil/n-3 LCPUFA/DHA plus EPA on joint pain, mobility and inflammation in patients with rheumatoid arthritis (RA) were provided. The submitted references also included two reviews on the treatment of RA with drugs and diet (Rennie et al., 2003; Proudman et al., 2007), several publications on the general properties of n-3 LCPUFA, and some review publications in relation to their effects on bone formation, bone resorption, and chondrocyte metabolism (Watkins et al., 2001; Curtis et al., 2002). The Panel notes that the paper by Curtis et al. (2002) has been retracted by the authors four years after its publication (Curtis et al., 2006).
No dietary requirement of n-3 LCPUFA for the maintenance of joint structure (e.g. of cartilage or other connective tissues) or function (e.g. maintenance of flexibility or mobility of the joints) in healthy humans has been demonstrated by the evidence provided.
All human intervention studies, all reviews and the three meta-analyses presented concern patients with clinical diagnosis of acute or chronic RA. Rheumatoid arthritis is a chronic, symmetric, inflammatory, and destructive autoimmune arthropathy affecting the synovial joints with a prevalence of 0.5 to 2.0% in the population and the pathogenesis of which is not fully understood (Gruenwald et al., 2002; Rennie et al., 2003; Ramsbottom and Lockwood, 2006).
The Panel considers that the evidence provided does not establish that patients with clinical diagnosis of RA are representative of the general population with regard to the status of joint tissues, or that results obtained in subjects with RA relating to the treatment of symptoms of the disease (e.g., joint pain, joint swelling, joint stiffness, erosion of joint cartilage) can be extrapolated to the maintenance of structure and function of joints in the general population. Therefore, no conclusions can be drawn from the human studies presented with respect to the maintenance of normal joints in the general population.
The Panel also considers that the evidence provided in the in vitro studies submitted does not predict the occurrence of an effect of n-3 LCPUFA EPA, DHA and DPA supplementation on the maintenance of normal joints in humans.
The Panel concludes that a cause and effect relationship has not been established between the consumption of EPA, DHA and DPA and the maintenance of normal joints.

4.1. Utrzymanie prawidłowego ciśnienia tętniczego (ID 502)

The Panel considers that the following wording reflects the scientific evidence: “DHA and EPA contribute to the maintenance of normal blood pressure”.

4.2. Utrzymanie prawidłowego stężenia trójglicerydów we krwi na czczo (ID 517)

The Panel considers that the following wording reflects the scientific evidence: “DHA and EPA contribute to the maintenance of normal triglyceride concentrations”.

5.1. Utrzymanie prawidłowego ciśnienia tętniczego (ID 502)

The Panel considers that intakes of EPA and DHA of about 3 g/d are required to obtain the claimed effect. The target population is adult men and women.

5.2. Utrzymanie prawidłowego stężenia trójglicerydów we krwi na czczo (ID 517)

The Panel considers that intakes of EPA and DHA of about 2-4 g/d are required to obtain the claimed effect. The target population is adult men and women.