Neurotrophic factors and brain health in children with overweight and obesity: The role of cardiorespiratory fitness.

ABSTRACTNeurotrophic factors and cardiorespiratory fitness are both considered important in developmental trajectories but their link to brain health remains poorly understood. The aims of the study were to examine whether levels of plasma-derived neurotrophic factors were associated with brain health indicators in children with overweight or obesity; and to test whether these associations were moderated by cardiorespiratory fitness. 100 children (41% girls) were included in this analysis. Plasma levels of brain-derived neurotrophic factor, insulin-like growth factor-1, vascular endothelial growth factor A, and epidermal growth factor were determined by XMap technology. Academic performance and executive function were assessed using validated neuropsychological tests. Hippocampal volume was measured using magnetic resonance imaging. Cardiorespiratory fitness was assessed using the 20-m Shuttle Run Test. Insulin-like growth factor-1 was positively associated with cognitive flexibility. Stratified analyses by fitness categories (i.e. unfit vs. fit) showed that brain-derived neurotrophic factor was positively associated with right posterior hippocampal volume in fit children, and epidermal growth factor was negatively associated with right hippocampal, and right anterior hippocampal volumes in their unfit peers, with a moderating role of cardiorespiratory fitness in these associations. However, all these significant associations disappeared after correction for multiple comparisons. The association between neurotrophic factors and brain health indicators in children with overweight/obesity was neither strong nor consistent. These results could help enhance our understanding of determinants of brain health in children with overweight/obesity.HighlightsThis study provides novel findings on the associations between neurotrophic factors and a wide range of brain health indicators in children.This study additionally explored the role of cardiorespiratory fitness in these associations.The association between neurotrophic factors and brain health in children with overweight/obesity was neither strong nor consistent.Cardiorespiratory fitness moderated the associations of brain-derived neurotrophic factor and epidermal growth factor with right hippocampal volume.

Effects of fish oil supplementation on the fatty acid profile in erythrocyte membrane and plasma phospholipids of pregnant women and their offspring: a randomised controlled trial.

We aimed to investigate the effects of fish oil (FO) supplementation to pregnant women on the maternal and fetal fatty acid profile in plasma and erythrocyte phospholipids (PL) and to identify the best compartment for the assessment of fatty acid status. A multi-centre, double-blind, controlled trial was conducted. Healthy pregnant women from three European centres were randomly assigned to receive from week 20 of gestation until delivery a daily dietary supplement with either FO (500 mg DHA+150 mg EPA), 400 µg 5-methyltetrahydrofolate, both or placebo. Fatty acids in plasma and erythrocyte PL were determined in maternal blood (week 20, week 30 of pregnancy and delivery) and in cord blood (delivery). FO supplementation increased DHA levels in maternal and cord plasma and erythrocyte PL. Higher percentage changes were observed in erythrocyte PL than in plasma PL. There were significant correlations between plasma and erythrocyte fatty acid levels in maternal and cord blood. Significant correlations between maternal and cord fatty acid levels at delivery in plasma and erythrocytes were also observed; however, correlation coefficients were higher for erythrocyte phophatidylethanolamine. FO supplementation increases maternal and fetal DHA status. Both plasma and erythrocytes appear to be suitable to evaluate the fatty acid status of mothers but erythrocytes seem to be a more reliable marker in neonates.

Prenatal DHA status and neurological outcome in children at age 5.5 years are positively associated.

Beneficial effects of perinatal DHA supply on later neurological development have been reported. We assessed the effects of maternal DHA supplementation on the neurological development of their children. Healthy pregnant women from Spain, Germany, and Hungary were randomly assigned to a dietary supplement consisting of either fish oil (FO) (500 mg/d DHA + 150 mg/d EPA), 400 µg/d 5-methyltetrahydrofolate, both, or placebo from wk 20 of gestation until delivery. Fatty acids in plasma and erythrocyte phospholipids (PL) were determined in maternal blood at gestational wk 20 and 30 and in cord and maternal blood at delivery. Neurological development was assessed with the Hempel examination at the age of 4 y and the Touwen examination at 5.5 y. Minor neurological dysfunction, neurological optimality score (NOS), and fluency score did not differ between groups at either age, but the odds of children with the maximal NOS score increased with every unit increment in cord blood DHA level at delivery in plasma PL (95% CI: 1.094-2.262), erythrocyte phosphatidylethanolamine (95% CI: 1.091-2.417), and erythrocyte phosphatidylcholine (95% CI: 1.003-2.643). We conclude that higher DHA levels in cord blood may be related to a better neurological outcome at 5.5 y of age.

Characterization and solubility study of solid dispersions of flunarizine and polyvinylpyrrolidone.

Flunarizine is a selective calcium entry blocker poorly water-soluble. In this report, the interactions of this drug with polyvinylpyrrolidone in solid dispersions, prepared according to the dissolution method using methanol as the solvent, have been investigated. For purposes of comparison physical mixtures were prepared by simple mixture and homogeneization of the two pulverized components. Combinations of flunarizine/polyvinylpyrrolidone of the following percentage proportions were prepared: 10/90, 20/80, 30/70, 40/60, 50/50, 60/40 and 80/20 (mean particle size of 0.175 mm). The physicochemical properties of solid dispersions were investigated with X-ray diffraction, infrared spectroscopy, differential scanning calorimetry and solubility in equilibrium. X-ray patterns and differential scanning calorimetry have shown that polyvinylpyrrolidone inhibits the crystallization of flunarizine when percentages drug/polymer are 10/90, 20/80 and 30/70. The infrared spectra suggest that there was no chemical interaction between flunarizine and polyvinylpyrrolidone. Equilibrium solubility studies showed that drug solubility was enhanced as the polymer content increased. In general, the solubility increase was greater in solid dispersions than in physical mixtures and the solubility in equilibrium for solid dispersions and physical mixtures at the same drug/polymer proportion showed significant differences (P < 0.05).