Fatty fish intake and cognitive function: FINS-KIDS, a randomized controlled trial in preschool children

Jannike Øyen, Ingrid Kvestad, Lisa Kolden Midtbø, Ingvild Eide Graff, Mari Hysing, Kjell Morten Stormark, Maria Wik Markhus, Valborg Baste, Livar Frøyland, Berthold Koletzko, Hans Demmelmair, Lisbeth Dahl, Øyvind Lie, Marian Kjellevold, Jannike Øyen, Ingrid Kvestad, Lisa Kolden Midtbø, Ingvild Eide Graff, Mari Hysing, Kjell Morten Stormark, Maria Wik Markhus, Valborg Baste, Livar Frøyland, Berthold Koletzko, Hans Demmelmair, Lisbeth Dahl, Øyvind Lie, Marian Kjellevold

Abstract

Background: Marine resources including fatty fish are important sources of n-3 long chain polyunsaturated fatty acids (n-3 LC-PUFAs), which are important for brain development. To our knowledge, this is the first randomized controlled trial (RCT) investigating the impact of fatty fish on cognition in preschool children. The purpose of the trial was to investigate whether an increased intake of fatty fish compared to meat improves cognitive function in children 4-6 years old.

Methods: The children (n = 232) in this two-armed RCT, Fish Intervention Studies-KIDS (FINS-KIDS) were recruited from 13 kindergartens in Bergen, Norway. They were randomly assigned to lunch meals with fatty fish (herring/mackerel) or meat (chicken/lamb/beef) three times a week for 16 weeks. The fish and meat were weighed before and after the meals to record the exact consumption (dietary compliance). The primary outcome was cognitive function measured by the Wechsler Preschool and Primary Scale of Intelligence, 3rd edition (WPPSI-III) and fine-motor coordination measured by the 9-Hole Peg Test (9-HPT) at pre- and post-intervention. Biological samples (blood, urine, hair), and questionnaires to the caregivers were included at both time points. Linear mixed effect models with a random intercept for kindergarten were used to analyze changes from pre- to post-intervention in the primary outcome variables.

Results: There were 218 children included in the trial (105 in the fish, and 113 in the meat group). The children consumed a mean (standard deviation) of 2070 (978) g fish or 2675 (850) g meat from the study meals (p < 0.0001). The fish group had a significant increase of red blood cell n-3 LC-PUFAs. The intervention had no effect on the WPPSI-III scores (mean change total raw score; fish group 17.7, 95% confidence interval (CI) 14.8-20.7 vs meat group 17.8, 95% CI 15.0-20.6, p = 0.97) in the main analyses. In the sub-analyses, adjusting for dietary compliance, the fish group showed a higher improvement on total raw score (20.4, 95% CI 17.5-23.3) compared to the meat group (15.2, 95% CI 12.4-18.0, p = 0.0060); docosahexaenoic acid mediated this effect.

Conclusions: There was no beneficial effect of fatty fish compared to meat on cognitive functioning in the preschool children. When considering dietary compliance, we found a beneficial effect of fatty fish on cognitive scores.

Trial registration: ClinicalTrials.gov, NCT02331667 December 17, 2014.

Keywords: 9-Hole Peg Test; Cognitive function; Docosahexaenoic acid; Eicosapentaenoic acid; Fatty fish; Omega-3 index; Preschoolers; Vitamin D; Wechsler Preschool and Primary Scale of Intelligence.

Conflict of interest statement

Ethics approval and consent to participate

The trial has approval from the Regional Committees for Medical and Health Research Ethics North (2014/1396) and is registered in Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interest.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Flowchart showing the study population
Fig. 2
Fig. 2
Scatter plots of changes in the Wechsler Preschool and Primary Scale of Intelligence, 3rd edition (WPPSI-III) from pre- to post-intervention vs amount fish (blue)/meat (red) consumed in kilograms (kg) (dietary compliance). The estimated regression line from an adjusted mixed effect model including the interaction between intervention and compliance, together with regression coefficient (β) and a 95% confidence interval are presented. Panel a shows WPPSI-III Total raw score, b Verbal raw score, c Performance raw score, and d Processing speed raw score

References

    1. Lauritzen L, Brambilla P, Mazzocchi A, Harslof LB, Ciappolino V, Agostoni C. DHA effects in brain development and function. Nutrients. 2016;8:6. doi: 10.3390/nu8010006.
    1. Innis SM. Dietary (n-3) fatty acids and brain development. J Nutr. 2007;137:855–859. doi: 10.1093/jn/137.4.855.
    1. Koletzko B, Lien E, Agostoni C, Bohles H, Campoy C, Cetin I, et al. The roles of long-chain polyunsaturated fatty acids in pregnancy, lactation and infancy: review of current knowledge and consensus recommendations. J Perinat Med. 2008;36:5–14.
    1. Stonehouse W. Does consumption of LC omega-3 PUFA enhance cognitive performance in healthy school-aged children and throughout adulthood? Evidence from clinical trials. Nutrients. 2014;6:2730–2758. doi: 10.3390/nu6072730.
    1. Dalton A, Wolmarans P, Witthuhn RC, van Stuijvenberg ME, Swanevelder SA, Smuts CM. A randomised control trial in schoolchildren showed improvement in cognitive function after consuming a bread spread, containing fish flour from a marine source. Prostaglandins Leukot Essent Fatty Acids. 2009;80:143–149. doi: 10.1016/j.plefa.2008.12.006.
    1. Ryan AS, Nelson EB. Assessing the effect of docosahexaenoic acid on cognitive functions in healthy, preschool children: a randomized, placebo-controlled, double-blind study. Clin Pediatr (Phila). 2008;47:355–362. doi: 10.1177/0009922807311730.
    1. Portillo-Reyes V, Perez-Garcia M, Loya-Mendez Y, Puente AE. Clinical significance of neuropsychological improvement after supplementation with omega-3 in 8-12 years old malnourished Mexican children: a randomized, double-blind, placebo and treatment clinical trial. Res Dev Disabil. 2014;35(4):861–870. doi: 10.1016/j.ridd.2014.01.013.
    1. McNamara RK, Carlson SE. Role of omega-3 fatty acids in brain development and function: potential implications for the pathogenesis and prevention of psychopathology. Prostaglandins Leukot Essent Fatty Acids. 2006;75:329–349. doi: 10.1016/j.plefa.2006.07.010.
    1. Osendarp SJ, Baghurst KI, Bryan J, Calvaresi E, Hughes D, Hussaini M, et al. Effect of a 12-mo micronutrient intervention on learning and memory in well-nourished and marginally nourished school-aged children: 2 parallel, randomized, placebo-controlled studies in Australia and Indonesia. Am J Clin Nutr. 2007;86:1082–1093. doi: 10.1093/ajcn/86.4.1082.
    1. Muthayya S, Eilander A, Transler C, Thomas T, van der Knaap HC, Srinivasan K, et al. Effect of fortification with multiple micronutrients and n-3 fatty acids on growth and cognitive performance in Indian schoolchildren: the CHAMPION (Children's Health and Mental Performance Influenced by Optimal Nutrition) Study. Am J Clin Nutr. 2009;89:1766–1775. doi: 10.3945/ajcn.2008.26993.
    1. Jiao J, Li Q, Chu J, Zeng W, Yang M, Zhu S. Effect of n-3 PUFA supplementation on cognitive function throughout the life span from infancy to old age: a systematic review and meta-analysis of randomized controlled trials. Am J Clin Nutr. 2014;100:1422–1436. doi: 10.3945/ajcn.114.095315.
    1. Gordon RC, Rose MC, Skeaff SA, Gray AR, Morgan KM, Ruffman T. Iodine supplementation improves cognition in mildly iodine-deficient children. Am J Clin Nutr. 2009;90:1264–1271. doi: 10.3945/ajcn.2009.28145.
    1. Morales E, Guxens M, Llop S, Rodriguez-Bernal CL, Tardon A, Riano I, et al. Circulating 25-hydroxyvitamin D3 in pregnancy and infant neuropsychological development. Pediatrics. 2012;130:e913–e920. doi: 10.1542/peds.2011-3289.
    1. Whitehouse AJ, Holt BJ, Serralha M, Holt PG, Kusel MM, Hart PH. Maternal serum vitamin D levels during pregnancy and offspring neurocognitive development. Pediatrics. 2012;129:485–493. doi: 10.1542/peds.2011-2644.
    1. Abel MH, Caspersen IH, Meltzer HM, Haugen M, Brandlistuen RE, Aase H, et al. Suboptimal maternal iodine intake is associated with impaired child neurodevelopment at 3 years of age in the Norwegian Mother and Child Cohort Study. J Nutr. 2017;147:1314–1324. doi: 10.3945/jn.117.250456.
    1. Murru E, Banni S, Carta G. Nutritional properties of dietary omega-3-enriched phospholipids. Biomed Res Int. 2013;2013:965417. doi: 10.1155/2013/965417.
    1. Aberg MA, Aberg N, Brisman J, Sundberg R, Winkvist A, Toren K. Fish intake of Swedish male adolescents is a predictor of cognitive performance. Acta Paediatr. 2009;98:555–560. doi: 10.1111/j.1651-2227.2008.01103.x.
    1. de Groot RH, Ouwehand C, Jolles J. Eating the right amount of fish: inverted U-shape association between fish consumption and cognitive performance and academic achievement in Dutch adolescents. Prostaglandins Leukot Essent Fatty Acids. 2012;86:113–117. doi: 10.1016/j.plefa.2012.01.002.
    1. Kim JL, Winkvist A, Aberg MA, Aberg N, Sundberg R, Toren K, Brisman J. Fish consumption and school grades in Swedish adolescents: a study of the large general population. Acta Paediatr. 2010;99:72–77. doi: 10.1111/j.1651-2227.2010.01752.x.
    1. Hibbeln JR, Davis JM, Steer C, Emmett P, Rogers I, Williams C, et al. Maternal seafood consumption in pregnancy and neurodevelopmental outcomes in childhood (ALSPAC study): an observational cohort study. Lancet. 2007;369:578–585. doi: 10.1016/S0140-6736(07)60277-3.
    1. Wechsler D, editor. Wechsler Preschool and Primary Scale of Intelligence™ - Third Edition (WPPSI™ - III) 2002.
    1. Poole JL, Burtner PA, Torres TA, McMullen CK, Markham A, Marcum ML. Measuring dexterity in children using the Nine-hole Peg Test. J Hand Ther. 2005;18:348–351. doi: 10.1197/j.jht.2005.04.003.
    1. Gordon B. Test Review: Wechsler, D. (2002) The Wechsler Preschool and Primary Scale of Intelligence, Third Edition (WPPSI-III). San Antonio, TX: The Psychological Corporation. Can J Sch Psychol. 2004;19:205–220. doi: 10.1177/082957350401900111.
    1. Eilertsen B, Johnsen IMB. Manual for Wechsler Intelligence Scale for Children. 3rd ed., Norwegian version. Assessio: Oslo; 2003.
    1. Smith YA, Hong E, Presson C. Normative and validation studies of the Nine-Hole Peg Test with children. Perceptual Motor Skills. 2000;90:823–843. doi: 10.2466/pms.2000.90.3.823.
    1. Dahl L, Maeland CA, Bjorkkjaer T. A short food frequency questionnaire to assess intake of seafood and n-3 supplements: validation with biomarkers. Nutr J. 2011;10:127. doi: 10.1186/1475-2891-10-127.
    1. Markhus MW, Graff IE, Dahl L, Seldal CF, Skotheim S, Braarud HC, et al. Establishment of a seafood index to assess the seafood consumption in pregnant women. Food Nutr Res. 2013;57 10.3402/fnr.v57i0.19272.
    1. Handeland K, Kjellevold M, Wik Markhus M, Eide Graff I, Froyland L, Lie O, et al. A diet score assessing Norwegian adolescents’ adherence to dietary recommendations—development and test-retest reproducibility of the score. Nutrients. 2016;8 10.3390/nu8080467
    1. Norwegian Directorate of Health. Food-based dietary guidelines for public health promotion and prevention of chronic diseases - Methodology and scientific evidence (in Norwegian). Oslo, Norway. 2011. . Accessed 23 Feb 2018.
    1. Araujo P, Nguyen TT, Froyland L, Wang J, Kang JX. Evaluation of a rapid method for the quantitative analysis of fatty acids in various matrices. J Chromatogr A. 2008;1212:106–113. doi: 10.1016/j.chroma.2008.10.006.
    1. Kissmeyer AM, Sonne K, Binderup E. Determination of the vitamin D analog EB 1089 (seocalcitol) in human and pig serum using liquid chromatography-tandem mass spectrometry. J Chromatogr B Biomed Sci Appl. 2000;740:117–128. doi: 10.1016/S0378-4347(00)00091-8.
    1. Dahl L, Meltzer HM, Opsahl JA, Julshamn K. Iodine intake and status in two groups of Norwegians. Scan J Nutr. 2003;47:170–178. doi: 10.1080/11026480310018131.
    1. Lincoln RA, Shine JP, Chesney EJ, Vorhees DJ, Grandjean P, Senn DB. Fish consumption and mercury exposure among Louisiana recreational anglers. Environ Health Perspect. 2011;119:245–251. doi: 10.1289/ehp.1002609.
    1. White RF, Campbell R, Echeverria D, Knox SS, Janulewicz P. Assessment of neuropsychological trajectories in longitudinal population-based studies of children. J Epidemiol Community Health. 2009;63(Suppl 1):i15–i26. doi: 10.1136/jech.2007.071530.
    1. Baron RM, Kenny DA. The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. J Pers Soc Psychol. 1986;51:1173–1182. doi: 10.1037/0022-3514.51.6.1173.
    1. Cooper RE, Tye C, Kuntsi J, Vassos E, Asherson P. Omega-3 polyunsaturated fatty acid supplementation and cognition: a systematic review and meta-analysis. J Psychopharmacol. 2015;29:753–763. doi: 10.1177/0269881115587958.
    1. Rice KM, Walker EM, Jr, Wu M, Gillette C, Blough ER. Environmental mercury and its toxic effects. J Prev Med Public Health. 2014;47:74–83. doi: 10.3961/jpmph.2014.47.2.74.
    1. Beblo S, Reinhardt H, Demmelmair H, Muntau AC, Koletzko B. Effect of fish oil supplementation on fatty acid status, coordination, and fine motor skills in children with phenylketonuria. J Pediatr. 2007;150:479–484. doi: 10.1016/j.jpeds.2006.12.011.
    1. Sorensen LB, Damsgaard CT, Dalskov SM, Petersen RA, Egelund N, Dyssegaard CB, et al. Diet-induced changes in iron and n-3 fatty acid status and associations with cognitive performance in 8-11-year-old Danish children: secondary analyses of the Optimal Well-Being, Development and Health for Danish Children through a Healthy New Nordic Diet School Meal Study. Br J Nutr. 2015;114:1623–1637. doi: 10.1017/S0007114515003323.
    1. Dean AJ, Bellgrove MA, Hall T, Phan WM, Eyles DW, Kvaskoff D, et al. Effects of vitamin D supplementation on cognitive and emotional functioning in young adults—a randomised controlled trial. PLoS One. 2011;6:e25966. doi: 10.1371/journal.pone.0025966.
    1. Venkatramanan S, Armata IE, Strupp BJ, Finkelstein JL. Vitamin B-12 and cognition in children. Adv Nutr. 2016;7:879–888. doi: 10.3945/an.115.012021.
    1. Leermakers ET, Moreira EM, Kiefte-de Jong JC, Darweesh SK, Visser T, Voortman T, et al. Effects of choline on health across the life course: a systematic review. Nutr Rev. 2015;73:500–522. doi: 10.1093/nutrit/nuv010.
    1. Harris WS, Von Schacky C. The Omega-3 Index: a new risk factor for death from coronary heart disease? Prev Med. 2004;39:212–220. doi: 10.1016/j.ypmed.2004.02.030.

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