Fatty Acids, Cognition, School Performance, and Mental Well-being in Children and Adolescents

A number of studies show that essential fatty acids and their longer chain derivatives (longchainpolyunsaturated fatty acids, LCPUFA), play a significant role in brain functioning,because they are important constituents of the cell membrane. A sufficient LCPUFA statushas been related to better cognitive functioning of both children and adults, as well as lesscognitive decline in elderly. The relationship between LCPUFA and school performancehas been studied to a lesser extent. In adults, a beneficial LCPUFA status has been relatedto less depression.Because the brain of children and adolescents is still profoundly developing, it can bepresumed that LCPUFA might be especially important, as building blocks, in these periodsof development. The goal of this dissertation was to study the relationship betweenLCPUFA and school performance in children, and to study the influence of LCPUFAsupplementation on cognition and mental well-being in adolescents.In Chapter 1 a general and theoretical introduction to this dissertation is provided,information on the following topics is given: fatty acid metabolism, importance of intake ofLCPUFA, in what foods LCPUFA are present, and the advantages of krill oilsupplementation (the form of supplementation used in the studies in this dissertation) overfish oil supplementation. Next, six possible mechanisms in which LCPUFA can possiblyinfluence brain functioning are elaborated upon. Then the brain development from birththroughout childhood and adolescence is explained. To finish, theoretical backgroundinformation on the outcome variables investigated in this dissertation (i.e., schoolperformance, cognition, and mental well-being) is provided.In this dissertation data, collected in two studies, were used to answer the goalsdescribed above. In Chapter 2 an overview of one of these studies, the MaastrichtEssential Fatty Acids Birth Cohort (MEFAB cohort) is given. The MEFAB cohort was setup in 1989 to study the change in fatty acid concentrations during pregnancy and how thisrelates to the fatty acid concentrations of the neonate. Moreover, the association betweenthe fatty acid concentrations and a number of birth outcomes (e.g., weight, length and headcircumference) was assessed. The MEFAB cohort has three follow-up studies at age 4, 7and 12 of the child. Data on cognitive development, asthma/atopy, growth, andcardiovascular disease risk factors among others, were collected. Besides the description ofthe design, the main earlier findings of the MEFAB cohort are discussed.In Chapter 3 data from the MEFAB cohort is used to assess the associations betweenmaternal LCPUFA concentrations during pregnancy, at birth, and child’s LCPUFAconcentration at age 7, and school performance at age 7. Analyses with correction forcovariates showed a negative association between maternal DHA concentration duringpregnancy, maternal and child’s DHA concentration at birth, and child’s arithmetic score atage 7. Moreover, maternal Osbond acid (ObA) levels at 22 and 32 weeks of pregnancy, andObA level in umbilical cord blood plasma were positively associated with arithmetic scoreat age 7. This last finding confirms the negative relationship between DHA status andarithmetic scores, as ObA is a deficiency marker of DHA (i.e., higher ObA levels reflectlower DHA levels). In contrast, child’s DHA concentration at age 7 was positivelyassociated with both the reading and spelling score at age 7.Chapter 4 concerns the design of the second study, Food2Learn. In Chapter 4 theunique characteristics and the rationale behind the research design are presented.Food2Learn was a double-blind, randomised, placebo controlled intervention trial inadolescents (age 13–15 years) attending lower general secondary education. The goal of Food2Learn was to determine the influence of increasing Omega-3 Index (O3I) oncognitive functioning, academic achievement and mental well-being of typically developingadolescents. Unique characteristics of Food2Learn are among others the fact that:participants were recruited based on a low O3I at baseline, students were asked to take krilloil capsules at dinner time to increase LCPUFA absorption, a personalized krill oil doseadjustment was planned, and the study focused on students of a lower educational level.In Chapters 5 and 6, baseline results of Food2Learn are presented. In Chapter 5 theassociations between baseline O3I of the participants of Food2Learn and scores on thecognitive measures are reported. Analyses revealed a significant positive associationbetween the O3I and score on the Letter Digit Substitution Task (i.e., measure forinformation processing speed). Moreover, a significant negative association between theO3I and errors of omission on the D2 (i.e., measure for inattention/impulsivity) wasshown. Thus, participants with a higher O3I had a higher information processing speed,and less inattention/impulsivityIn Chapter 6 the associations between baseline O3I and other fatty acids (DHA,eicosapentaenoic acid (EPA), arachidonic acid (AA), docosapentaenoic acid (DPA), andObA) and both depressive feelings and self-esteem are reported. Bayesian analyses showeda weak negative association between ObA and depression score, and a weak positiveassociation between ObA and self-esteem score. In other words, more ObA measured inblood corresponded with less depression and more self-esteem. There was no evidence foran association between DHA, EPA, and O3I, and depression and/or self-esteem.In Chapter 7 and 8 the effects of one year of krill oil supplementation on respectivelycognitive measures (chapter 7) and mental well-being measures (chapter 8) are reported.There was no significant effect of krill oil supplementation on either the cognitive measuresor mental well-being measures. The most likely explanation for these non-significanteffects, is the high amount of drop-out and non-adherence with the protocol. Due to theseproblems, it cannot be concluded that a relationship between krill oil supplementation andcognition, and mental well-being does not exist.While executing Food2Learn, there were difficulties with recruiting participants, dropout,and adherence. It was however unknown how common those problems are inLCPUFA supplementation studies in children and adolescents. Therefore, a systematicreview focussing on recruitment, adherence, and drop-out rates in LCPUFAsupplementation studies in children and adolescents was executed in Chapter 9. Problemswith recruitment and drop-out were common in LCPUFA supplementation trials inchildren and adolescents. Techniques to improve recruitment, adherence and dropout rateswere identified in the literature and are reported in Chapter 9 as well.In Chapter 10, the main results of the studies in this dissertation are discussed, andusing an additional literature review, evaluated and put into a broader perspective.To conclude, MEFAB and Food2Learn do not provide conclusive evidence for arelationship between LCPUFA and school performance, cognition and mental well-beingin children and adolescents. However, associations between LCPUFA concentrations andboth school performance, and cognition were found. Future studies should pay attentionto, among other things, objectively measuring LCPUFA concentrations, long-term highdose LCPUFA supplementation, personalised dose adjustment, and focus on adolescence,as this is a period of profound brain development. The relevance for society of bothMEFAB and Food2Learn can be translated into the advice to consume either two servings of fatty fish per week or, based on the literature review in chapter 10, take a supplementwith at least 400mg DHA + EPA per day, as this amount has by all means a positive effecton general health, and possibly a positive effect on brain functioning as well