Mendelian randomization shows sex-specific associations between long-chain PUFA-related genotypes and cognitive performance in Danish schoolchildren.

Background: Dietary and endogenously formed long-chain polyunsaturated fatty acids (LCPUFAs) are hypothesized to improve cognitive development, but results are inconclusive, with suggestions of sex specificity. One study suggested that single-nucleotide polymorphisms (SNPs) rs1535 and rs174448 in the fatty acid desaturase (FADS) gene cluster have opposite effects on erythrocyte LCPUFAs at 9 mo.Objective: To explore whether SNPs in FADS and elongase (ELOVL) genes were associated with school performance in a sex-specific manner, we performed a Mendelian randomization study using data from the Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) School Meal Study with 765 Danish schoolchildren 8-11 y old.Design: Associations between selected FADS1/2 SNPs (rs1535, rs174448, and rs174468) and ELOVL5 rs2397142, whole-blood fatty acid composition, and performance in the d2 Test of Attention and a reading test were analyzed in multiple regression models including all SNPs, SNP-sex interactions, and covariates related to testing conditions.Results:FADS, rs1535 minor allele carriage associated with lower whole-blood arachidonic acid (P ≤ 0.002), and minor alleles of rs174448 tended to associate with lower docosahexaenoic acid (DHA) (P = 0.052). We identified sex interactions in 50% of the SNP performance sets. Sex-dependent associations were observed for rs174448 and rs1535 on the d2 Test of Attention outcomes (P < 0.03) and for the associations between reading scores and rs174448 and rs2397142 (P < 0.01). All of the sex-specific analyses showed associations in opposite directions in girls and boys. The minor allele carriage of rs174448 was associated with lower d2 Test of Attention performance (P < 0.02) and reading scores (P < 0.001) in boys but with better reading scores in girls (P ≤ 0.002). The associations were consistently the opposite for rs1535 minor allele carriage (P < 0.05). Associations with rs2397142 also appeared to be opposite of those of rs174448, but only for reading and not significant after adjustment for parental educational level and whole-blood DHA.Conclusions: This study showed associations between rs1535 minor allele homozygosity and rs174448 major allele carriage and improved performance in 8- to 11-y-old boys but not in girls, thereby counteracting existing sex differences. This may be a consequence of increased endogenous DHA synthesis in infancy but not at school-age. This trial was registered at clinicaltrials.gov as NCT01457794.

Normal weight children have higher cognitive performance - Independent of physical activity, sleep, and diet.

BACKGROUND/OBJECTIVES: Aside from the health consequences, observational studies indicate that being overweight may also negatively affect cognitive function. However, existing evidence has to a large extent not controlled for the possible confounding effect of having different lifestyles. Therefore, the objective was to examine the independent associations between weight status and lifestyle indicators with cognitive performance in 8-11year old Danish children. SUBJECTS/METHODS: The analyses included 828 children (measured in 2011-2012) each having one to three measurement occasions separated by approximately 100days. Dietary intake, physical activity, sedentary time, and sleep duration were measured using dietary records and accelerometers. The Children's Sleep Habits Questionnaire was used to access sleep problems and the Andersen test was carried out to estimate cardio-respiratory fitness (CRF). Weight status (underweight, normal weight, and overweight/obese) was defined according to body mass index and cognitive performance was assessed using the d2-test of attention, a reading test, and a math test. A linear mixed model including a number of fixed and random effects was used to test associations between lifestyle indicators as well as BMI category and cognitive performance. RESULTS: After adjustment for demographics, socioeconomics, and multiple lifestyle indicators, normal weight children had higher cognitive test scores than overweight/obese and underweight children of up to 89% and 48% of expected learning within one school year (P<0.05). Daily breakfast consumption, fewer sleep problems, higher CRF, less total physical activity, more sedentary time, and less light physical activity were associated with higher cognitive performance independently of each other in at least one of the three cognitive tests (P<0.05). CONCLUSIONS: Normal weight children had higher cognitive performance compared to overweight/obese as well as underweight children, independent of multiple lifestyle indicators.

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.

Fe and n-3 long-chain PUFA (n-3 LCPUFA) have both been associated with cognition, but evidence remains inconclusive in well-nourished school-aged children. In the Optimal Well-Being, Development and Health for Danish Children through a Healthy New Nordic Diet (OPUS) School Meal Study, the 3-month intervention increased reading performance, inattention, impulsivity and dietary intake of fish and Fe. This study investigated whether the intervention influenced n-3 LCPUFA and Fe status and, if so, explored how these changes correlated with the changes in cognitive performance. The study was a cluster-randomised cross-over trial comparing school meals with packed lunch (control). At baseline and after each treatment, we measured serum ferritin, whole-blood n-3 LCPUFA and Hb, and performance in reading, mathematics and d2-test of attention. Data were analysed using mixed models (n 726) and principal component analysis of test performances (n 644), which showed two main patterns: 'school performance' and 'reading comprehension'. The latter indicated that children with good reading comprehension were also more inattentive and impulsive (i.e. higher d2-test error%). The intervention improved 'school performance' (P=0·015), 'reading comprehension' (P=0·043) and EPA+DHA status 0·21 (95% CI 0·15, 0·27) w/w % (P<0·001), but it did not affect serum ferritin or Hb. At baseline, having small Fe stores was associated with poorer 'school performance' in girls, but with better 'reading comprehension' in both boys and girls. Both baseline EPA+DHA status and the intervention-induced increase in EPA+DHA status was positively associated with 'school performance', suggesting that n-3 LCPUFA could potentially explain approximately 20 % of the intervention effect. These exploratory associations indicate that increased fish intake might explain some of the increase in reading performance and inattention in the study.

The effects of Nordic school meals on concentration and school performance in 8- to 11-year-old children in the OPUS School Meal Study: a cluster-randomised, controlled, cross-over trial.

It is widely assumed that nutrition can improve school performance in children; however, evidence remains limited and inconclusive. In the present study, we investigated whether serving healthy school meals influenced concentration and school performance of 8- to 11-year-old Danish children. The OPUS (Optimal well-being, development and health for Danish children through a healthy New Nordic Diet) School Meal Study was a cluster-randomised, controlled, cross-over trial comparing a healthy school meal programme with the usual packed lunch from home (control) each for 3 months (NCT 01457794). The d2 test of attention, the Learning Rating Scale (LRS) and standard tests on reading and mathematics proficiency were administered at baseline and at the end of each study period. Intervention effects were evaluated using hierarchical mixed models. The school meal intervention did not influence concentration performance (CP; primary outcome, n 693) or processing speed; however, the decrease in error percentage was 0·18 points smaller (P<0·001) in the intervention period than in the control period (medians: baseline 2·03%; intervention 1·46%; control 1·37%). In contrast, the intervention increased reading speed (0·7 sentence, P=0·009) and the number of correct sentences (1·8 sentences, P<0·001), which corresponded to 11 and 25%, respectively, of the effect of one school year. The percentage of correct sentences also improved (P<0·001), indicating that the number correct improved relatively more than reading speed. There was no effect on overall math performance or outcomes from the LRS. In conclusion, school meals did not affect CP, but improved reading performance, which is a complex cognitive activity that involves inference, and increased errors related to impulsivity and inattention. These findings are worth examining in future trials.

Design of the OPUS School Meal Study: a randomised controlled trial assessing the impact of serving school meals based on the New Nordic Diet.

INTRODUCTION: Danish children consume too much sugar and not enough whole grain, fish, fruit, and vegetables. The Nordic region is rich in such foods with a strong health-promoting potential. We lack randomised controlled trials that investigate the developmental and health impact of serving school meals based on Nordic foods. AIM: This paper describes the rationale, design, study population, and potential implications of the Optimal well-being, development and health for Danish children through a healthy New Nordic Diet (OPUS) School Meal Study. METHODS: In a cluster-randomised cross-over design, 1021 children from 3rd and 4th grades (8-11 years old) at nine Danish municipal schools were invited to participate. Classes were assigned to two 3-month periods with free school meals based on the New Nordic Diet (NND) or their usual packed lunch (control). Dietary intake, nutrient status, physical activity, cardiorespiratory fitness, sleep, growth, body composition, early metabolic and cardiovascular risk markers, illness, absence from school, wellbeing, cognitive function, social and cultural features, food acceptance, waste, and cost were assessed. RESULTS: In total, 834 children (82% of those invited) participated. Although their parents were slightly better educated than the background population, children from various socioeconomic backgrounds were included. The proportion of overweight and obese children (14%) resembled that of earlier examinations of Danish school children. Drop out was 8.3%. CONCLUSIONS: A high inclusion rate and low drop out rate was achieved. This study will be the first to determine whether school meals based on the NND improve children's diet, health, growth, cognitive performance, and early disease risk markers.