The EFSA Journal (2008) 904, 1-10 SCIENTIFIC OPINION Eye q and concentration Scientific substantiation of a health claim related to Eye q and concentration pursuant to Article 14 of Regulation (EC) No 1924/2006 1 Scientific Opinion of the Panel on Dietetic Products, Nutrition and Allergies (Question No EFSA-Q-2008-330) Adopted on 4 December 2008 PANEL MEMBERS Jean-Louis Bresson, Albert Flynn, Marina Heinonen, Karin Hulshof, Hannu Korhonen, Pagona Lagiou, Martinus Løvik, Rosangela Marchelli, Ambroise Martin, Bevan Moseley, Andreu Palou, Hildegard Przyrembel, Seppo Salminen, Sean (J.J.) Strain, Stephan Strobel, Inge Tetens, Henk van den Berg, Hendrik van Loveren and Hans Verhagen. SUMMARY Following an application from Potters Limited submitted pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of United Kingdom, the Panel on Dietetic Products, Nutrition and Allergies was asked to deliver an opinion on the scientific substantiation of a health claim related to: Eye q and concentration. The scope of the application was proposed to fall under a health claim referring to children s development and health. The food which is the subject of the health claim is Eye q, a combination of the n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and the n-6 PUFA, gamma-linolenic acid (GLA). The Panel notes that the complete fatty acid spectrum of Eye q is not reported in the application. The Panel considers that the food for which the claim is made (i.e., Eye q ) is sufficiently characterised regarding the content of DHA, EPA and GLA. The claimed effect is helps children maintain concentration levels. The target population is children of 2 to 18 years of age. The Panel considers that promoting concentration (interpreted as attention) is beneficial to children s development and health. 1 For citation purposes: Scientific Opinion of the Panel on Dietetic Products, Nutrition and Allergies on a request from Potters Limited on the scientific substantiation of a health claim related to Eye q and concentration. The EFSA Journal (2008) 904, 1-10 European Food Safety Authority, 2008
A total of 30 publications were initially identified. Of these, six randomised controlled clinical trials (RCTs) and one observational study were considered by the applicant as pertinent to the health claim under evaluation. Two of these RCTs were conducted with intervention foods that differed from the PUFA combination present in Eye q products. The Panel considers that these two studies are not suitable sources of data to substantiate the claimed effect. Three RCTs (one unpublished) investigating the effects of PUFA on children with attention deficit hyperactivity disorder and one RCT investigating the effects of PUFA on children with developmental coordination disorder were performed using Eye q as the source of EPA, DHA and GLA. One additional RCT using Eye q as intervention was presented in summary form only. The Panel notes that most of the studies presented by the applicant are not pertinent to the claim as the study populations are not representative of the target population (healthy children from 2 to 18 years of age). On the basis of the data presented, the Panel concludes that a cause and effect relationship has not been established between the consumption of Eye q, a combination of the n-3 PUFAs EPA and DHA and the n-6 PUFA GLA, and the maintenance of concentration (interpreted as attention) in healthy children between 2 and 18 years of age. Key words: Eye q, polyunsaturated fatty acids, eicosapentaenoic acid, docosahexaenoic acid, gamma-linolenic acid, concentration, attention, children. The EFSA Journal (2008) 904, 2-10
TABLE OF CONTENTS Panel Members...1 Summary...1 Table of Contents...3 Background...4 Terms of reference...4 EFSA Disclaimer...4 Acknowledgements...5 1. Information provided by the applicant...6 1.1. Food/constituent as stated by the applicant...6 1.2. Health relationship as claimed by the applicant...6 1.3. Wording of the health claim as proposed by the applicant...6 1.4. Specific conditions of use as proposed by the applicant...6 2. Assessment...6 2.1. Characterisation of the food/constituent...6 2.2. Relevance of the claimed effect to human health...7 2.3. Scientific substantiation of the claimed effect...7 Conclusions...9 Documentation provided to EFSA...9 References...9 Glossary / Abbreviations...10 The EFSA Journal (2008) 904, 3-10
BACKGROUND Regulation (EC) No 1924/2006 2 establishes rules governing the Community authorisation of health claims made on foods. Health claims are prohibited unless they comply with the general and specific requirements of that Regulation and are authorised in accordance with this Regulation and included in the lists of authorised claims provided for in Articles 13 and 14 thereof. In particular, Article 14 of that Regulation lays down provisions for the authorisation and subsequent inclusion of reduction of disease risk claims and claims referring to children s development and health in a Community list of permitted claims. According to Article 15 of that Regulation, an application for authorisation shall be submitted by the applicant to the national competent authority of a Member State, who will make the application and any supplementary information supplied by the applicant available to European Food Safety Authority (EFSA). Steps taken by EFSA: The application was received on 11/02/2008. The scope of the application was proposed to fall under a health claim referring to children s development and health. During the check for completeness 3 of the application, the applicant was requested to provide missing information on 03/03/2008 and on 22/05/2008. The applicant provided the missing information on 22/05/2008 and on 17/06/2008. The scientific evaluation procedure started on 15/07/2008. During the meeting on 04/12/2008, the NDA Panel, after having evaluated the overall data submitted, adopted an opinion on the scientific substantiation of a health claim related to Eye q and concentration. TERMS OF REFERENCE EFSA is requested to evaluate the scientific data submitted by the applicant in accordance with Article 16 of Regulation (EC) No 1924/2006. On the basis of that evaluation, EFSA will issue an opinion on the scientific substantiation of a health claim related to: Eye q and concentration. EFSA DISCLAIMER The present opinion does not constitute, and cannot be construed as, an authorisation to the marketing of Eye q, a positive assessment of its safety, nor a decision on whether Eye q is, or is not, classified as a foodstuff. It should be noted that such an assessment is not foreseen in the framework of Regulation (EC) No 1924/2006. It should also be highlighted that the scope, the proposed wording of the claim and the conditions for use as proposed by the applicant may be subject to changes, pending the 2 European Parliament and Council (2006). Regulation (EC) No 1924/2006 of the European Parliament and of the Council of 20 December 2006 on nutrition and health claims made on foods. Official Journal of the European Union OJ L 404, 30.12.2006. Corrigendum OJ L 12, 18.1.2007, p. 3 18. 3 In accordance with EFSA Scientific and Technical guidance for the Preparation and Presentation of the Application for Authorisation of a Health Claim The EFSA Journal (2008) 904, 4-10
scientific evaluation by EFSA and pending the outcome of the authorisation procedure foreseen in Articles17 of Regulation (EC) No 1924/2006. ACKNOWLEDGEMENTS The European Food Safety Authority wishes to thank Jacques Rigo and the members of the Working Group for the preparation of this opinion: Jean-Louis Bresson, Albert Flynn, Marina Heinonen, Hannu Korhonen, Ambroise Martin, Andreu Palou, Hildegard Przyrembel, Seppo Salminen, Sean (J.J.) Strain, Inge Tetens, Henk van den Berg, Hendrik van Loveren and Hans Verhagen. The EFSA Journal (2008) 904, 5-10
1. Information provided by the applicant Applicant s name and address: Potters Limited, 1 Botanic Court, Martland Park, Wigan WN5 0JZ, United Kingdom. The application includes proprietary data. 1.1. Food/constituent as stated by the applicant Eye q, a combination of the n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the n-6 PUFA gamma-linolenic acid (GLA) 1.2. Health relationship as claimed by the applicant The applicant states that n-3 and n-6 fatty acids are important membrane components of the brain, which modify neuronal membrane fluidity, membrane activity-bound enzymes, number and affinity of receptors, function of neuronal membrane ion channels and production of neurotransmitters and brain peptides, and that a deficiency of n-3 PUFAs or an imbalance between n-3 and n-6 PUFAs can lead to developmental disturbances. 1.3. Wording of the health claim as proposed by the applicant Eye q provides the nourishment that help children to maintain concentration levels. 1.4. Specific conditions of use as proposed by the applicant Children of 2-18 years of age should receive a daily dosage of 550-558 mg EPA, 174-200 mg DHA, and 60-62 mg GLA. 2. Assessment 2.1. Characterisation of the food/constituent The food which is the subject of the health claim is Eye q, a combination of the n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the n-6 PUFA gamma-linolenic acid (GLA). High-EPA oil is derived from sardines and pilchards from the southern ocean and Indian oceans. High-DHA oil is derived from South Pacific tuna. GLA is derived from evening primrose (Oenothera biennis) seed oil. Absorption of these PUFAs has been demonstrated in humans. Eye q is presented in different dosage forms: Eye q capsules: 29 mg DHA, 93 mg EPA, 10 mg GLA per capsule. Recommended daily dose (RDD) = 6 capsules. Eye q chewable: 29 mg DHA, 93 mg EPA, 10 mg GLA per capsule. RDD = 6 capsules. Eye q emulsion: 100 mg DHA, 275 mg EPA, 31 mg GLA per sachet. RDD= 2 sachets. Eye q liquid: 58 mg DHA, 186 mg EPA, 20 mg GLA per 5 ml. RDD: 15ml. The Panel notes that the complete fatty acid spectrum of Eye q is not reported in the application. The Panel considers that the food for which the claim is made (i.e., Eye q ) is sufficiently characterised regarding the content of DHA, EPA and GLA. The EFSA Journal (2008) 904, 6-10
2.2. Relevance of the claimed effect to human health Eye q and concentration The claimed effect is helps children to maintain concentration levels. The target population is children of 2 to 18 years of age. Even though concentration has not been defined by the applicant, the applicant has referred to studies which have considered a range of psychological constructs, some of which can be measured with a questionnaire and could be considered as markers for attention, which is a well defined psychological construct. The Panel considers that promoting concentration (interpreted as attention) is beneficial to children s development and health. 2.3. Scientific substantiation of the claimed effect The applicant searched the Web of Science (Institute of Scientific Information) using combinations of the following search terms: long chain polyunsaturated fatty acids, docosahexaenoic acid, eicosapentaenoic acid, linolenic acid, arachidonic acid, linoleic acid, omega-3 fatty acids, omega-6 fatty acids, children, preschoolers, cognition, development, mental, learning, brain. In addition, the applicant states that hand searching was performed. Search dates are not reported. According to the applicant, the studies pertinent to the health claim had been selected using as exclusion criteria: children below 2 or older than 18 years of age, studies supplementing with a daily dose lower than 100 mg DHA or less than 12 weeks intervention period, non-fish oil sources of DHA, animal studies, subjects with major physical or mental conditions like epilepsy, diabetes mellitus, depression, chronic fatigue syndrome or retardation, and as inclusion criteria: randomised, double-blind and placebo-controlled studies, observational studies on PUFA deficiencies and cognition, EPA + DHA supplementation, assessment of cognitive brain function. A total of 30 publications were initially identified. Of these, six randomised controlled clinical trials (RCTs) and one observational study were considered by the applicant as pertinent to the health claim under evaluation. Four of the RCTs presented had evaluated the effect of PUFA supplementation on children with attention deficit hyperactivity disorder (ADHD) at 5-8 years to 12-18 years of life (Richardson and Puri, 2002; Stevens et al., 2003; Sinn and Bryan, 2007; Johnson et al., 2008, unpublished). Two of these RCTs were conducted with intervention foods that differed from the PUFA combination present in Eye q products. The Panel considers that these two studies are not suitable sources of data to substantiate the claimed effect (Richardson and Puri, 2002; Stevens et al., 2003). The remaining two RCTs, which investigated the effects of PUFA on children with ADHD were performed using Eye q as the source of EPA, DHA and GLA (Sinn and Bryan, 2007; Johnson et al., 2008, unpublished, proprietary data). In the first placebo-controlled, double-blind intervention study (Sinn and Bryan, 2007, proprietary data), Conners Parents Rating Scale (CPRS) and Conners Teachers Rating Scale (CTRS) ratings of ADHD symptoms were assessed in children (n=41 on randomisation) who received capsules containing 80% fish oil and 20% evening primrose oil (Eye q, daily dose of 93 mg EPA, 29 mg DHA and 10 mg GLA) together with a multivitamin/mineral supplement, in children (n=36 on randomisation) who received capsules containing the PUFA alone, or in children (n=27 on randomisation) who received control capsules containing palm oil for 15 weeks followed by a one-way cross-over (placebo to both active treatments) for a further 15 weeks. The children, aged 7-12 years, exhibited ADHD-like features assessed using the CPRS. The endpoints which showed significant improvement in both active groups compared with The EFSA Journal (2008) 904, 7-10
placebo were two out of 7 CPRS subscales (cognitive problems/inattention, oppositional) and 5 out of 7 global scales (ADHD index, global index, restless-impulsive, DSM-IV inattentive, hyperactive/impulsive), with similar improvements observed in the original control group after the one-way cross-over. None of the 14 CTRS endpoints improved in the active groups compared with placebo or after the one-way cross-over. The Panel notes that the small sample size, the small size of the effects, the relatively low number of significant endpoints compared to the total tested and the uncertain relevance of these tests to the claimed effect in children who exhibited ADHD-like features limit the conclusions that can be drawn from this study in relation to the health claim under evaluation. In an unpublished RCT provided by the applicant (Johnson et al., 2008, proprietary data), 75 children and adolescents (8 18 years) with clinically diagnosed ADHD were randomly assigned to consume either Eye q capsules (providing 558 mg EPA, 174 mg DHA, 60 mg GLA and 10.8 mg Vitamin E daily) or control capsules (containing olive oil) for 3 months. All subjects (intervention and controls) received the Eye q capsules for an additional 3 months. Investigator-rated ADHD Rating Scale IV and Clinical Global Impression (CGI) scale were outcome measures. Significant differences between intervention and control groups were only observed for CGI after 3 months. The majority of ADHD patients (about 75%) did not respond to the intervention. The Panel notes that the small sample size and the uncertain relevance to the claimed effect of these tests performed in children who exhibited ADHD-like features limit the conclusions that can be drawn from this study in relation to the health claim under evaluation. One study evaluated the effect of Eye q supplementation in children with developmental coordination disorder (DCD) aged 5 to 12 years. In the UK Oxford-Durham placebocontrolled, double-blind study (Richardson and Montgomery, 2005, proprietary data), motor function assessed with the Movement Assessment Battery for Children, reading and spelling achievement assessed with the Wechsler Objective Reading Dimensions, and ADHD-related symptoms assessed with the Conners Teachers Rating Scale (CTRS) were assessed in children (n=60 at randomisation) who received capsules containing 80% fish oil and 20% evening primrose oil (daily dose of 558 mg EPA, 174 mg DHA and 60 mg GLA) and in children (n=57 at randomisation) who received control capsules containing olive oil for 12 weeks followed by a one-way cross-over (placebo to active treatment) for an additional 12 weeks. The children, aged 5-12 years, met DSM-IV criteria for DCD but were not receiving any treatment for this condition. The endpoints which showed significant improvement in the active treatment group compared with placebo were reading and spelling achievement, 4 out of 6 CTRS subscales (opposition, cognitive problems, hyperactivity, anxiety/shyness) and all 7 global scales (ADHD index, global restless-impulsive, global emotional lability, global index and DSM-IV inattentive, hyperactivity, total ADHD) with similar improvements observed in the original control group after the one-way cross-over. The Panel notes that, although some of the significant end-points might be directly relevant to the claimed effect, children with DCD cannot be considered representative of the target population for which the claim is intended, thereby limiting the degree to which conclusions can be drawn from this study in relation to the health claim under evaluation. The last RCT which evaluated the effects of Eye q supplementation (Portwood et al., unpublished, proprietary data) is presented in summary form only. The characteristics of the study population recruited, the methods used to measure the primary outcomes of the study and the results of the outcome measures for each study group are not given in the summary and, therefore, the Panel is unable to consider this study as a source of data to substantiate the claimed effect. The EFSA Journal (2008) 904, 8-10
The Panel notes that most of the studies presented by the applicant are not pertinent to the claim as the study populations are not representative of the target population (healthy children from 2 to 18 years of age). The Panel considers that a cause and effect relationship has not been established between the consumption of Eye q, a combination of the n-3 PUFAs EPA and DHA, and the n-6 PUFA GLA and the maintenance of concentration (interpreted as attention) in healthy children between 2 and 18 years of age. CONCLUSIONS On the basis of the data presented, the Panel concludes the following: The food for which the claim is made (i.e., Eye q ) is sufficiently characterised regarding the content of DHA, EPA and GLA. The claimed effect is to maintain concentration levels. The target population is children 2 to 18 years of age. Concentration can be interpreted as attention, which is a well defined psychological construct. Promoting concentration (interpreted as attention) is beneficial to children s development and health. A cause and effect relationship has not been established between the consumption of Eye q, a combination of the n-3 PUFAs EPA and DHA, and the n-6 PUFA GLA and the maintenance of concentration (interpreted as attention) in healthy children between 2 and 18 years of age. DOCUMENTATION PROVIDED TO EFSA Health claim application on Eye q and concentration pursuant to Article 14 of the Regulation (EC) No 1924/2006 (Claim serial No: 0039d-UK). June 2008. Submitted by Potters Limited. REFERENCES Johnson M, Östlund S, Fransson G, Kadesjö B, Gillberg C, 2008 (proprietary data). Omega- 3/Omega-6 fatty acids for attention-deficit/hyperactivity disorder: A randomized placebocontrolled trial in children and adolescents. J. Attent. Disord. Online. First, published on April 30, 2008. Portwood M, Lowerson S, Coupland K, unpublished (proprietary data). The Middlesbrough Trial: a randomised controlled trial of dietary supplements with omega-3/ omega-6 fatty acids in mainstream school children. Richardson AJ and Puri BK, 2002. A randomized double-blind, placebo-controlled study of the effects of supplementation with highly unsaturated fatty acids on ADHD-related symptoms in children with specific learning difficulties. Prog. Neuropsychopharmacol Biol. Psychiatry 26, 233-239. Richardson AJ and Montgomery P, 2005 (proprietary data). The Oxford-Durham study: a randomized, controlled trial of dietary supplementation with fatty acids in children with developmental coordination disorder, Pediatrics 115, 1360-1366. Sinn N and Bryan J, 2007 (proprietary data). Effect of supplementation with polyunsaturated fatty acids and micronutrients on learning and behaviour problems associated with child ADHD. J. Dev. Behav. Pediatr. 28, 82-91. The EFSA Journal (2008) 904, 9-10
Stevens LJ, Zentall SS, Deck JL, Abate ML, Watkins BA, Lipp SR, Burgess JR, 1995. Essential fatty acid metabolism in boys with attention-deficit hyperactivity disorder. Am. J. Clin. Nutr. 62, 761-8. GLOSSARY / ABBREVIATIONS ADHD DCD DHA EPA GLA PUFA Attention deficit hyperactivity disorder Developmental coordination disorder Docosahexaenoic acid Eicosapentaenoic acid Gamma linolenic acid Polyunsaturated Fatty Acids The EFSA Journal (2008) 904, 10-10