ABSTRACT Background Long-chain n–3 PUFAs (n–3 LCPUFAs) accrete in the brain during childhood and affect brain development. Randomized trials in children show inconsistent effects of n–3 LCPUFAs on cognitive and socioemotional function, and few have investigated effects of fish per se. Objectives We aimed to investigate the effects of oily fish consumption on overall and domain-specific cognitive and socioemotional scores and explore sex differences. Methods Healthy 8–9-y-old children (n = 199) were randomly allocated to receive ∼300 g/wk oily fish or poultry (control) for 12 ± 2 wk. At baseline and endpoint, we assessed attention, processing speed, executive functions, memory, emotions, and behavior with a large battery of tests and questionnaires and analyzed erythrocyte fatty acid composition. Results One hundred and ninety-seven (99%) children completed the trial. Children in the fish group consumed 375 (25th–75th percentile: 325–426) g/wk oily fish resulting in 2.3 (95% CI: 1.9, 2.6) fatty acid percentage points higher erythrocyte n–3 LCPUFA than in the poultry group. The overall cognitive performance score tended to improve by 0.17 (95% CI: −0.01, 0.35) points in children who received fish compared with poultry, supported by n–3 LCPUFA dose dependency. This was driven mainly by fewer errors [−1.9 (95% CI: −3.4, −0.3)] in an attention task and improved cognitive flexibility measured as faster reaction time [−51 ms (95% CI: −94, −7 ms)] in a complex relative to a simple task (“mixing cost”). The fish intervention furthermore reduced parent-rated Strength and Difficulties Questionnaire total difficulties by −0.89 (95% CI: −1.60, −0.18) points mainly due to a −0.63 (95% CI: −1.11, −0.16) points reduction in internalizing problems that was reflected in tendency to a decrease in the overall socioemotional problems score of −0.13 (95% CI: −0.26, 0.01) points. The overall effects were similar in boys and girls. Conclusions Oily fish dose-dependently improved cognitive function, especially attention and cognitive flexibility, and reduced socioemotional problems. The results support the importance of n–3 LCPUFAs for optimal brain function and fish intake recommendations in children. The trial was registered at www.clinicaltrials.gov as NCT02809508.

NCAM1 and NCAM2 have ectodomains consisting of 5 Ig domains followed by 2 membrane-proximal FnIII domains. In this study we investigate and compare the structures and functions of these FnIII domains. The NCAM1 and -2 FnIII2 domains both contain a Walker A motif. In NCAM1 binding of ATP to this motif interferes with NCAM1 binding to FGFR. We obtained a structural model of the NCAM2 FnIII2 domain by NMR spectroscopy, and by titration with an ATP analogue we show that the NCAM2 Walker A motif does not bind ATP. Small angle X-ray scattering (SAXS) data revealed that the NCAM2 FnIII1-2 double domain exhibits a very low degree of flexibility. Moreover, recombinant NCAM2 FnIII domains bind FGFR in vitro, and the FnIII1-2 double domain induces neurite outgrowth in a concentration-dependent manner through activation of FGFR. Several synthetic NCAM1-derived peptides induce neurite outgrowth via FGFR. Only 2 of 5 peptides derived from similar regions in NCAM2 induce neurite outgrowth, but the most potent of these peptides stimulates neurite outgrowth through FGFR-dependent activation of the Ras-MAPK pathway. These results reveal that the NCAM2 FnIII domains form a rigid structure that binds and activates FGFR in a manner related to, but different from NCAM1.

Background Fish oil improves cardiometabolic markers in adults, but results in children are inconsistent. Few children meet the recommended fish intake and no randomized trials have investigated how fish intake per se affects children's cardiometabolic profile. Objective We investigated whether oily fish consumption modulated serum triacylglycerol and diastolic blood pressure (coprimary outcomes) and other cardiometabolic markers in healthy Danish children and whether effects were sex-specific. Methods In a randomized controlled 12-wk trial, 199 children (aged 8–9 y) received ∼300 g/wk of oily fish or poultry (control). We measured blood pressure, heart rate, and heart rate variability (HRV) via 3-h continuous electrocardiograms and collected fasting blood samples for analysis of erythrocyte EPA [20:5n–3 (ω-3)] + DHA (22:6n–3) and serum triacylglycerol, LDL and HDL cholesterol, glucose, and insulin. Results One hundred and ninety-seven children (99%) completed the trial. The fish group consumed a median (IQR) of 375 (325–426) g oily fish/wk and the poultry group consumed 400 (359–452) g poultry/wk, which resulted in 2.25 (95% CI: 1.88, 2.62) fatty acid percentage-point higher erythrocyte EPA + DHA in the fish group (P < 0.001). In the fish group, serum triacylglycerol decreased by 0.05 mmol/L (95% CI: 0.00, 0.11 mmol/L) (P = 0.04) and HDL cholesterol increased by 0.07 mmol/L (95% CI: 0.01, 0.13 mmol/L) (P = 0.02); the triacylglycerol effect showed dose-dependency with erythrocyte EPA + DHA (r = −0.15, P = 0.04), whereas HDL showed a tendency for such an association(r = 0.13, P = 0.08). Additional analyses indicated sex-specificity (Pdiet*sex < 0.10), because triacylglycerol was reduced by 0.09 mmol/L (95% CI: 0.02, 0.16 mmol/L) in boys only (girls: −0.00; 95% CI: −0.07, 0.07 mmol/L) and heart rate was reduced by 3.4 bpm (95% CI: 0.2, 6.6 bpm) in girls only (boys: 0.6; 95% CI: −2.6, 3.8 bpm). Blood pressure, HRV, and glucose homeostasis were unaffected. Conclusions Oily fish intake improved serum triacylglycerol and HDL cholesterol in a dose-dependent manner in 8- to 9-y-old children, but had no effect on blood pressure, HRV, or glucose homeostasis. This supports recommendations for fish intake in children and underlines the importance of initiatives to increase children's intake of oily fish. This trial was registered at clinicaltrials.gov as NCT02809508.

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BackgroundMost children in Western populations do not meet recommendations for fish consumption. Oily fish is an important source of n-3 long-chain polyunsaturated fatty acids (LCPUFA), which reduce blood pressure and plasma triacylglycerol in adults and may affect cognitive development and behavior. However, to our knowledge, the potential effects of oily fish on cardiometabolic health, cognitive function, and behavior in children have not been investigated. The aim of the FiSK Junior study is to investigate the effects of oily fish consumption on cardiovascular risk markers, cognitive function, and behavior in healthy children.Methods/designWe are conducting a randomized controlled trial with 8- to 9-year-old Danish children, comparing the effect of consuming 300 g/week of oily fish with poultry (control) for 12 weeks between August 2016 and June 2017. The primary outcomes are blood pressure and fasting plasma triacylglycerol, which will be measured at baseline and endpoint. In addition, we will assess erythrocyte fatty acid composition (compliance), heart rate, plasma cholesterol, markers of glucose homeostasis, growth and body composition, dietary intake, and physical activity and sleep. We will also examine effects on cognitive function (attention, memory, and executive functions) by using standardized tests, behavior and emotions by administering parent-rated questionnaires and child interviews, and we will measure physiological stress response and cortisol levels. We need 150 children to complete the trial to detect a between-groups difference of 2.7 mmHg in diastolic blood pressure and 0.13 mmol/L in plasma triacylglycerol; thus, we aim to recruit 200 children. All outcomes will be analyzed in completer analysis supplemented with sensitivity analyses for the primary outcomes, and attention will be given to potential sex and genotype specificity.DiscussionThe results of the FiSK Junior study are expected to fill important gaps in the current knowledge about the importance of dietary fish and n-3 LCPUFA for children’s health and development, and may be used when setting dietary recommendations.Trial registrationClinicalTrials.gov identifier: NCT02809508. Registered on 22 June 2016.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-016-1647-z) contains supplementary material, which is available to authorized users.