2.1. Udział w utrzymaniu lub osiągnięciu prawidłowej masy ciała (ID 686, 726, 1516, 1518, 2892, 3165)

The claimed effects are “weight management”, “body weight management” and “weight management, fat metabolism enhancement”. The Panel assumes that the target population is the general population.
The Panel assumes that the claimed effects refer to contribution to the maintenance or achievement of a normal body weight.
Weight management can be interpreted as contribution to the maintenance of a normal body weight. In this context, weight loss in overweight individuals even without achieving a normal body weight is considered to be a beneficial physiological effect.
The Panel considers that contribution to the maintenance or achievement of a normal body weight is a beneficial physiological effect.

2.2. Zwiększenie beztłuszczowej masy ciała (ID 498, 731)

The claimed effect is “supports lean body mass”. 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 an increase in lean body mass.
The Panel considers that an increase in lean body mass is a beneficial physiological effect.

2.3. Zwiększenie wrażliwości na insulinę (ID 1517)

The claimed effect is “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 an increase in insulin sensitivity.
The Panel considers that an increase in insulin sensitivity is a beneficial physiological effect.

2.4. Ochrona DNA, białek i lipidów przed uszkodzeniem oksydacyjnym (ID 564, 1937)

The claimed effects are “antioxidativity” and “antioxidant capability”. The Panel assumes that the target population is the general population.
In the context of the proposed wordings, the Panel assumes that the claimed effect refers to the antioxidant properties of the food component and to the protection of body cells and molecules from oxidative damage caused by free radicals.
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 such as antioxidant nutrients.
The Panel considers that protection of DNA, proteins and lipids from oxidative damage may be a beneficial physiological effect.

2.5. Udział w obronie immunologicznej poprzez stymulację produkcji przeciwciał odpornościowych w odpowiedzi na szczepienie (ID 687, 1519)

The claimed effect is “immune 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 claimed effect refers to the modulation of immune defences against pathogens by
stimulation of production of protective antibodies in response to vaccination, as measured by increased numbers of individuals attaining protective levels of antibodies as well as by increments in antibody titres in groups of individuals.
The Panel considers that contribution to immune defences by stimulation of production of protective antibodies in response to vaccination is a beneficial physiological effect.

3.1. Udział w utrzymaniu lub osiągnięciu prawidłowej masy ciała (ID 686, 726, 1516, 1518, 2892, 3165)

Most of the randomised, placebo-controlled trials (RCTs) which investigated the effects of CLA supplementation on body weight and body composition in humans that were cited in the consolidated list were included in the meta-analysis by Whigham et al. (2007) described below. One additional RCT not included in the meta-analysis was cited in relation to this claim (Steck et al., 2007).
Whigham et al. (2007) conducted a meta-analysis of randomised, double-blinded, placebo-controlled trials which investigated the effects of interventions using either equimolar mixtures of purified CLA isomers c9, t11 and t10, c12 (15 studies, doses ranging from 1g per day to 6.8 g per day, mean dose 3.2 g per day) or purified t10, c-12 and/or c9, t11 CLA isomers alone (three studies) on body weight and body composition either during or after weight loss. One of the weight loss studies considered was a 12-month uncontrolled follow-up of a previous 12-month intervention (Gaullier et al., 2005). Most interventions lasted 12 weeks or less. Among the 15 original RCTs which investigated the effects of supplementation with equimolar mixtures of the purified CLA isomers c9, t11 and t10, c12 on body weight during weight loss, only two found a significant reduction in body weight in the CLA group compared to the placebo (Watras et al., 2007; Gaullier et al., 2007), whereas no differences between groups were observed in the remaining 13 RCTs (Blankson et al., 2000; Gaullier et al., 2004; Mougios et al., 2001; Smedman and Vessby, 2001; Pinkoski et al., 2006; Berven et al., 2000; Riserus et al., 2002; Malpuech-Brugere et al., 2004; Atkinson, 1999; Petridou et al., 2003; Eyjolfson et al., 2004; Taylor et al., 2006; Lambert et al., 2007). No significant differences in body weight between CLA and the placebo group were observed using either 3.2 g per day CLA or 6.4 g per day CLA (equimolar combination of the c9, t11 and t10, c12 isomers) for 12 weeks in the RCT by Steck et al. (2007) which was not included in the meta-analysis.
The meta-analysis by Whigham et al. (2007) also reviewed three studies on the effects of CLA supplementation on body weight maintenance after weight loss (Kamphuis et al., 2003; Larsen et al., 2006; Whigham et al., 2004), none of which observed significant differences between CLA and placebo groups with regard to body weight changes.
In weighing the evidence, the Panel took into account that 14 out of 16 intervention studies in humans did not report a significant effect of CLA on body weight, that most of the studies considered were short-term (12 weeks or less), and that none of the three studies on body weight maintenance after weight loss showed a significant effect of CLA compared to placebo.
The Panel concludes that a cause and effect relationship has not been established between the consumption of an equimolar mixture of the CLA isomers c9, t11 and t10, c12 and contribution to the
maintenance or achievement of a normal body weight.

3.2. Zwiększenie beztłuszczowej masy ciała (ID 498, 731)

Most of the randomised, placebo-controlled trials (RCTs) which investigated the effects of CLA supplementation on body composition in humans that were cited in the consolidated list were included in the meta-analysis by Whigham et al. (2007). One RCT not included in the meta-analysis was also considered by the Panel as pertinent to this claim (Steck et al., 2007). An additional study by Lowery et al. (1998) was available only in abstract form, and could not be fully evaluated by the Panel in relation to the claimed effect.
Among the 15 weight loss RCTs considered in the meta-analysis by Whigham et al. (2007) described in section 3.1, which used an equimolar mixture of the CLA isomers c9, t11 and t10, c12, three did not report on changes in lean body mass (Mougios et al., 2001; Smedman and Vessby, 2001; Atkinson, 1999) and nine did not find statistically significant differences between the CLA and control groups in lean body mass changes (Berven et., al., 2000; Eyjolfson et al., 2004; Lambert et al., 2007; Malpuech-Brugere et al., 2004; Petridou et al., 2003; Riserus et al., 2002; Taylor et al., 2006; Gaullier et al., 2007; Watras et al., 2007), whereas three reported an effect of CLA intake on lean body mass during weight loss (Blankson et al., 2000; Gaullier et al., 2004; Pinkoski et al., 2006) in addition to the study by Steck et al. (2007). In the studies by Blankson et al. (2000) and Steck et al. (2007), a significant effect of CLA on lean body mass was observed only at the highest doses of CLA administered (6.8g per day and 6.4g per day of an equal mixture of the c9, t11 and t10, c12 CLA isomers, respectively). The Panel notes that these daily doses of CLA are about twice the doses proposed in the conditions of use. The Panel also notes that in the study by Gaullier et al. (2004), the effect was only significant when 3.4 g per day of the CLA isomers, an equal mixture of the c9, t11 and t10, c12 isomers, were given as free fatty acids (FFA), but not as triacylglycerols. In addition, only one (Kamphuis et al., 2003) out of the three studies (Kamphuis et al., 2003; Larsen et al., 2006; Whigham et al., 2004) which investigated the effects of CLA supplementation on body composition showed an effect in preserving lean body mass after weight loss independent of physical activity.
The two RCTs with the largest sample size per intervention group and which used appropriate methods to assess body composition and appropriate duration (at least 12 weeks) under the proposed conditions of use (using up to about 3.4g per day of the CLA equimolar mixture) were considered further by the Panel (Gaullier et al., 2004, 2007).
The 108 subjects who participated in the RCT by Gaullier et al. (2004) were selected on the basis of being overweight (BMI 25–30 kg/m2, age range 18–65 years) and were randomly assigned to consume either 4.5 g olive oil (placebo, n=59, 47 women), 4.5 g 80 % CLA in the FFA form (3.6 g active CLA isomers, equal mixture of the c9, t11 and t10, c12, n= 61, 51 women), or 4.5 g 76 % CLA in the triacylglycerol form (3.4 g active CLA isomers, n=60, 51 women) per day for 12 months. Body composition was measured by dual-energy x-ray absorptiometry (DXA). A significant increase in lean body mass was observed only in the CLA-FFA group compared to placebo. No significant differences were observed between the two CLA groups regarding changes in lean body mass during the study. No evidence has been provided to establish that CLA administered as triacylglycerols or as FFA could have differential effects on changes in lean body mass.
The 115 subjects, who participated in another RCT by Gaullier et al. (2007), were selected on the basis of being overweight and obese (BMI 28–32 kg/m2, age range 18–65 years) and were randomised to consume either 3.4 g per day of the c9, t11 and t10, c12 CLA mixture or placebo (4.5 g per day olive oil) for 6 months. Whether the CLA supplement was administered in the FFA form or in the triacylglycerol form was not reported. A total of 105 (84 women) completed the intervention (n=55 in the CLA group), 83 of them with >70 % pill count compliance. No significant changes in lean body mass were observed in the CLA group as compared to placebo in completers or in the subgroup of subjects who reported good compliance.
The Panel notes that the studies by Gaullier et al. (2004, 2007) had similar design and sample size, used the same dose of the CLA equimolar mixture and the same method to assess changes in body composition (dual-energy x-ray absorptiometry), but lead to conflicting results regarding the effects of CLA consumption on lean body mass.
In weighing the evidence, the Panel took into account that most of the human studies provided did not observe a significant effect of CLA consumption on lean body mass, and that results from the studies with the largest sample size per intervention group, which used appropriate methods to assess changes in body composition and had an appropriate duration under the proposed conditions of use, are inconsistent with respect to the effects of consumption of an equimolar mixture of the CLA isomers c9, t11 and t10, c12 on lean body mass.
The Panel concludes that a cause and effect relationship has not been established between the consumption of an equimolar mixture of the CLA isomers c9, t11 and t10, c12 and an increase in lean body mass.

3.3. Zwiększenie wrażliwości na insulinę (ID 1517)

The references provided in the consolidated list for health claims on CLA included six intervention studies in humans, one animal study (ex vivo) and one in vitro study which were related to the claim (Belury et al., 2003; Moloney et al., 2004, 2007; Riserus et al., 2002; Syvertsen et al., 2007; Smedman and Vessby, 2001; Eyjolfson et al., 2004).
Two double-blind, randomised, control trials (RCTs) were conducted in patients with type 2 diabetes. The study by Belury et al. (2003) did not assess any markers of insulin sensitivity or blood glucose control (but rather changes in body weight and serum leptin) and was therefore not considered pertinent to the claim. In the study by Moloney et al. (2004), 32 subjects with stable, diet-controlled type 2 diabetes were randomly assigned to consume either CLA (3.0 g per day; 50:50 blend of c-9, t-11 CLA and t-10, c-12 CLA) or a control fat mix (blend of palm oil and soya bean oil) for eight weeks. A three-hour 75 g oral glucose-tolerance test was performed at baseline and at the end of the intervention to assess insulin sensitivity. CLA supplementation significantly increased fasting glucose concentrations (by 6.3 %; p<0.05) and reduced insulin sensitivity as measured by the homeostasis model assessment of insulin resistance (HOMA-IR), the quantitative insulin sensitivity check index (QUICKI) and the insulin sensitivity index (ISI) composite. Fasting insulin concentrations did not change significantly between groups.
Two double-blind RCTs were conducted in obese subjects. In the study by Riserus et al. (2002), a total of 60 abdominally obese men with metabolic syndrome were randomised to consume either 3.4 g per day CLA (equimolar isomer mixture) or placebo for 12 weeks. Insulin sensitivity was assessed by means of the euglycaemic-hyperinsulinaemic clamp. A total of 19 subjects per group entered data analysis. The CLA equimolar isomer mixture did not significantly change glucose metabolism, body composition or body weight compared to placebo. In the study by Syvertsen et al. (2007), 118 subjects were randomly assigned to consume either CLA (3.4 g per day, equal amounts of the c9, t11 and t10, c12 isomers) or placebo (4.5 g per day olive oil) for 6 months. Insulin sensitivity was assessed by means of the euglycaemic-hyperinsulinaemic clamp in 41 subjects who completed the study (24 interventions, 17 controls). No significant differences were observed between groups with respect to glucose metabolism, insulin sensitivity or HbA1c during the study.
Two double-blind RCTs were conducted in healthy volunteers. In the study by Smedman and Vessby (2001), 53 healthy men and women aged 23-63 years were randomly assigned to supplementation with CLA (4.2 g per day, equal amounts of the CLA isomers c9, t11 and t10, c12), or the same amount of olive oil, during 12 weeks in a double-blind fashion. No significant differences were observed between the groups in fasting plasma insulin or blood glucose. In the study by Eyjolfson et
al. (2004), 16 young sedentary subjects were randomised to consume 4 g per day of mixed CLA isomers (35.5 % c-9, t-11; 36.8 % t-10, c-12, n=10), or placebo (safflower oil, n=6) for eight weeks. Oral glucose tolerance tests were performed at baseline, at four and at eight weeks of supplementation. The Panel notes the small sample size of the study, and that direct comparisons between changes in the insulin sensitivity index (ISI) between the intervention and control groups were not reported. The Panel considers that no conclusions can be drawn from this study for the scientific substantiation of the claimed effect.
The animal, ex vivo, study showed an effect of c9, t11-CLA supplementation in down-regulating the insulin receptor substrate 1 (IRS1) and GLUT4 mRNA expression, and an increase in insulin- stimulated glucose transport in 3T3-L1 adipocytes compared with linoleic acid (Moloney et al., 2007), whereas the in vitro study reported that the t-10, c-12 CLA isomer promoted NFkappaB activation and subsequent induction of IL-6, which are at least in part responsible for t-10, c-12 CLA-mediated insulin-resistance in mature human adipocytes (Chung et al., 2005). The Panel considers that the evidence provided in animal and in vitro studies is not sufficient to predict the occurrence of an effect of the consumption of an equimolar mixture of the CLA isomers c9, t11 and t10, c12 on the increase in insulin sensitivity in humans.
In weighing the evidence, the Panel took into account that none of the studies from which conclusions could be drawn for the scientific substantiation of the claimed effect observed a CLA-mediated improvement in insulin sensitivity.
The Panel concludes that a cause and effect relationship has not been established between the
consumption of an equimolar mixture of the CLA isomers c9, t11 and t10, c12 and an increase in insulin sensitivity.

3.4. Ochrona DNA, białek i lipidów przed uszkodzeniem oksydacyjnym (ID 564, 1937)

Four references were provided in the list in relation to this claim. Two reviews and one intervention study were on the effects of CLA consumption on outcomes unrelated to the claimed effect (e.g. cancer prevention, immune function). The fourth reference reported on an in vitro study which assessed the capacity of CLA in scavenging free radicals (Yu, 2001). The Panel notes that the capacity of a food to scavenge free radicals in vitro does not predict the occurrence of an effect in the protection of cells or molecules from oxidative damage in vivo.
No human studies which investigated the effects of CLA on markers of oxidative damage to DNA, proteins or lipids have been provided.
The Panel concludes that a cause and effect relationship has not been established between the
consumption of an equimolar mixture of the CLA isomers c9, t11 and t10, c12 and the protection of DNA, proteins or lipids from oxidative damage.

3.5. Udział w obronie immunologicznej poprzez stymulację produkcji przeciwciał odpornościowych w odpowiedzi na szczepienie (ID 687, 1519)

Nine references were cited for the substantiation of the claimed effect. These included a narrative review, a poster presentation, two human intervention studies which assessed the effects of CLA isomer mixtures other than the equimolar mixture of the CLA isomers c9, t11 and t10, c12 which is the subject of the health claims (Kelley et al., 2000; Tricon et al., 2004), one human study investigating the effects of CLA on outcome measures other than vaccination titres (Song et al., 2005), and three animal studies which addressed the effects of CLA on outcomes unrelated to the claimed effect (Bassaganya-Riera et al. 2001, 2003, 2004). The Panel considers that no conclusions can be drawn from these references for the scientific substantiation of the claimed effect.
One human intervention study was considered pertinent to the claim.
Albers et al. (2003) performed a double-blind, randomised, parallel, controlled study on 71 healthy males (aged 31-69 years) to compare the effects of a 50:50 mixture of the CLA isomers c9, t11 and t10, c12 as free fatty acids (CLA 50:50; 1.7 g per day) to those of an 80:20 mixture of the CLA isomers c9, t11 and t10, c12 as triacylglycerols (CLA 80:20; 1.6 g per day), as compared to a control oil (sunflower oil) on the immune (antibody and cellular) response to a hepatitis B vaccination. The dietary treatment lasted 12 weeks. Subjects received the hepatitis B antigen after 40, 54 and 68 days of treatment. Geometric means of antibody titres, mean integrated lymphocyte stimulation indices or
seroprotection rates (i.e. the number of subjects with antibody titres 10 UI/L) did not differ between groups.
In weighing the evidence, the Panel took into account that the only study from which conclusions could be drawn for the scientific substantiation of the claim did not report a significant effect of CLA on antibody titres or seroprotection rates after vaccination.
The Panel concludes that a cause and effect relationship has not been established between the consumption of an equimolar mixture of the CLA isomers c9, t11 and t10, c12 and contribution to immune defences by stimulation of production of protective antibodies in response to vaccination.