Associations of whole blood polyunsaturated fatty acids and insulin resistance among European children and adolescents.

This study aims to examine the association of whole blood n-3 and n-6 polyunsaturated fatty acids (PUFA) with insulin resistance (IR) in children. Whole blood fatty acids were measured in 705 children aged 2-9 years of the European IDEFICS/I.Family cohort using gas chromatography in units of weight percentage of all detected fatty acids (%wt/wt). IR was determined by the Homeostasis Model Assessment for IR (HOMA). Mixed effect models were used to assess the associations between selected baseline PUFA and HOMA z-scores at baseline and after 2- and 6-year follow-ups using models with basic and additional confounder adjustment as well as stratified by sex and weight status. In the basic model, α-linolenic (ß = 1.46 SD/%wt/wt, p = 0.006) and eicosapentaenoic acid (ß = 1.17 SD/%wt/wt, p = 0.001) were positively associated with baseline HOMA z-score. In the stratified analyses, α-linolenic acid was positively associated with HOMA z-score in girls only (ß = 1.98 SD/%wt/wt, p = 0.006) and arachidonic acid was inversely associated with baseline HOMA in thin/normal-weight children (ß = - 0.13 SD/%wt/wt, p = 0.0063). In the fully adjusted model, no statistically significant associations were seen.Conclusions: Our overall results do not indicate a protective role of higher blood n-3 PUFA or an adverse role of higher blood arachidonic acid proportion on the risk of IR. What is Known: •Intervention studies reported a beneficial effect of n-3 PUFA supplementation on insulin resistance compared with placebo while observational studies in cildren are inconclusive. •Studies have shown a positive association of n-6 arachidonic acid and insulin resistance indicating an adverse role of arachidonic acid. What is New: •Cross-sectional and longitudinal analyses based on circulating blood fatty acid concentrations in a large cohort of European children and adolescents. •Overall results do not support a protective role of n-3 PUFA or an adverse role of arachidonic acid in insulin resistance.

Use of Nutritional Supplements in Youth with Medicated and Unmedicated Attention-Deficit/Hyperactivity Disorder.

OBJECTIVE: To find out whether use of nutritional supplements (NUS) differs between children and adolescents with attention-deficit/hyperactivity disorder (ADHD; medicated or unmedicated), compared with those without the disorder. METHODS: We used cross-sectional data from the population-based I.Family study conducted between 2013 and 2014 in eight European countries. Parents completed questionnaires and participated in interviews, for example, on health and medical history of their child. Data from 5067 children and adolescents aged 5-17 years were included. Exposures were medicated (with ADHD-approved medication) and unmedicated ADHD. The outcome was the use of NUS, measured by use of any or multiple different NUS. Multivariable logistic regression adjusted for sociodemographics and health determinants was used to find ADHD-depending differences. RESULTS: The study sample comprised 4490 children and adolescents without ADHD and 51 medicated and 76 unmedicated subjects with ADHD. Regarding the use of any NUS, no statistically significant differences were found between children and adolescents without ADHD (18%) and those with medicated (18%) or unmedicated ADHD (22%). However, discrepancies appear when considering multiple use of NUS, not reported for any medicated ADHD subject but remarkably often for unmedicated ADHD subjects (13%), resulting in an adjusted odds ratio of 2.6 (95% confidence interval, 1.2-5.6) when compared with those without ADHD (5%). CONCLUSION: Children and adolescents who were not using medication for treating ADHD potentially took NUS as oral remedies. Given the potential for a delay of indicated treatments and for use of those NUS which have no proven effectiveness, pediatricians should actively explore whether NUS have been used to treat ADHD core symptoms, and families should be informed that the average effect size has to be considered small.

25-hydroxyvitamin D is differentially associated with calcium intakes of Northern, Central, and Southern European adolescents: Results from the HELENA study.

OBJECTIVES: Adolescents in the European Union (EU) exhibit a higher prevalence of vitamin D (VitD) deficiency than other age groups. The degree to which sunlight exposure 25-hydroxyvitamin D [25(OH)D] concentrations depends on a variety of factors, including diet. Nevertheless, the relationship between calcium and VitD intake and 25(OH)D concentrations has not been previously studied among adolescents living in different EU countries and consequently in different latitudes. Therefore, the aim of this study was to examine whether calcium and VitD intakes are differentially associated with 25(OH)D in adolescents from northern, central and southern EU countries. METHODS: The present analysis included 178 adolescents from northern EU countries, 251 from central EU countries, and 212 from southern EU countries (ages 12.5-17.5 y). Mixed model linear regression analyses stratified by geographic location were used to verify associations between calcium and VitD intake and 25(OH)D concentrations. Age, Tanner stage, seasonality, energy intake, and supplement use were entered as covariates. RESULTS: Only the calcium intake of central EU adolescents was positively associated with 25(OH)D (α = 0.005; 95% confidence interval, 0.007-0.028). CONCLUSIONS: Further longitudinal studies should confirm these observations, as this could be important for future public health interventions aiming to increase 25(OH)D concentrations in adolescents.

Associations of Whole Blood n-3 and n-6 Polyunsaturated Fatty Acids with Blood Pressure in Children and Adolescents - Results from the IDEFICS/I.Family Cohort.

BACKGROUND: Polyunsaturated n-3 and n-6 polyunsaturated fatty acids (PUFA) are precursors of biologically active metabolites that affect blood pressure (BP) regulation. This study investigated the association of n-3 and n-6 PUFA and BP in children and adolescents. METHODS: In a subsample of 1267 children aged 2-9 years at baseline of the European IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) cohort whole blood fatty acids were measured by a validated gas chromatographic method. Systolic and diastolic BP was measured at baseline and after two and six years. Mixed-effects models were used to assess the associations between fatty acids at baseline and BP z-scores over time adjusting for relevant covariables. Models were further estimated stratified by sex and weight status. RESULTS: The baseline level of arachidonic acid was positively associated with subsequent systolic BP (ß = 0.08, P = 0.002) and diastolic BP (ß = 0.07, P<0.001). In thin/normal weight children, baseline alpha-linolenic (ß = -1.13, P = 0.003) and eicosapentaenoic acid (ß = -0.85, P = 0.003) levels were inversely related to baseline and also to subsequent systolic BP and alpha-linolenic acid to subsequent diastolic BP. In overweight/obese children, baseline eicosapentaenoic acid level was positively associated with baseline diastolic BP (ß = 0.54, P = 0.005). CONCLUSIONS: Low blood arachidonic acid levels in the whole sample and high n-3 PUFA levels in thin/normal weight children are associated with lower and therefore healthier BP. The beneficial effects of high n-3 PUFA on BP were not observed in overweight/obese children, suggesting that they may have been overlaid by the unfavorable effects of excess weight.

The n-3 long-chain PUFAs modulate the impact of the GCKR Pro446Leu polymorphism on triglycerides in adolescents.

Dietary n-3 long-chain PUFAs (LC-PUFAs) are associated with improvement in the parameters of the metabolic syndrome (MetS). Glucokinase regulatory protein (GCKR) is a key protein regulating intracellular glucose disposal. Our aim was to investigate: i) the relationship between the GCKR rs1260326 (Pro446Leu) polymorphism and parameters of the MetS; and ii) a potential influence of n-3 and n-6 LC-PUFA levels on this relationship in the HELENA study (1,155 European adolescents). Linear regression analyses were performed to study the association between rs1260326 and the outcomes of interest. Interactions between rs1260326 and LC-PUFA levels on outcomes were explored. The T allele of rs1260326 was associated with higher serum TG concentrations compared with the C allele. In contrast to n-6 LC-PUFA levels, a significant interaction (P = 0.01) between rs1260326 and total n-3 LC-PUFA levels on serum TG concentrations was observed. After stratification on the n-3 LC-PUFA median values, the association between rs1260326 and TG concentration was significant only in the group with high n-3 LC-PUFA levels. In conclusion, this is the first evidence that n-3 LC-PUFAs may modulate the impact of the GCKR rs1260326 polymorphism on TG concentrations in adolescents. Several molecular mechanisms, in link with glucose uptake, could explain these findings.

Impact of physical activity and cardiovascular fitness on total homocysteine concentrations in European adolescents: The HELENA study.

We examined the association of physical activity (PA), cardiovascular fitness (CVF) and fatness with total homocysteine (tHcy) concentrations in European adolescents. The present study comprised 713 European adolescents aged 14.8 ± 1.2 y (females 55.3%) from the multicenter HELENA cross-sectional study. PA was assessed through accelerometry, CVF by the 20-m shuttle run test, and body fat by skinfold thicknesses with the Slaughter equation. Plasma folate, cobalamin, and tHcy concentrations were measured. To examine the association of tHcy with PA, CVF, and fatness after controlling for a set of confounders including age, maturity, folate, cobalamin, creatinine, smoking, supplement use, and methylenetetrahydrofolate reductase 677 genotype (CC 47%, CT 43%, TT 10%), bivariate correlations followed by multiple regression models were performed. In the bivariate correlation analysis, tHcy concentrations were slightly negatively correlated (p<0.05) with CVF in females (measured both by stages: r=-0.118 and by VO2max: r=-0.102) and positively with body mass index (r=0.100). However, daily time spent with moderate and vigorous PA showed a weak positive association with tHcy in females (p<0.05). tHcy concentrations showed a tendency to decrease with increasing CVF and increase with increasing BMI in female European adolescents. However, tHcy concentrations were positively associated with moderate and vigorous PA in female European adolescents.

Dietary lipid intake only partially influences variance in serum phospholipid fatty acid composition in adolescents: impact of other dietary factors.

The present study aimed to assess the correlation between food and fatty acid (FA) intake and the serum phospholipid (PL) FA status in European adolescents and explored the percentage of variation in serum PL FA that could be attributed to dietary habits. Participants included 528 adolescents recruited in the HELENA Study. Dietary intake was assessed by two, self-administered, non-consecutive 24-h recalls. PL FA concentrations were measured in fasting venous serum samples. Reduced rank regressions were applied to examine the combined effect of food intakes. Results indicated that the variance in serum PL FA in adolescents, that could be explained by diet varied from 7.0% for MUFA to 14.2% for n-3FA. The variance in the long-chain n-3FA was mainly explained by fish intake but also by coffee and tea consumption. In conclusion this study indicated that dietary intake influences the serum PL FA status to a limited amount but that also other factors interfere. However, dietary intake is important as it is among those factors that could be modified. Furthermore, the results suggest that the overall dietary habits should be considered instead of only the consumption of single foods or nutrients, as the medium of the food or concomitant intake of foods and nutrients might interact and as such influence absorption or metabolism.

Dietary fatty acid intake, its food sources and determinants in European adolescents: the HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) Study.

Dietary fatty acids (FA) play a role in several (patho)physiological processes at any age, and different FA have different effects on lipid status and health outcome. The present study aims to describe the FA intake and its main food sources in a population of healthy European adolescents and to assess the variation in intake as a function of non-dietary factors. FA intake was assessed with 24 h recall interviews in 1804 adolescents aged 12·5-17·5 years. Usual intakes were calculated using the multiple source method. Multilevel analyses, adjusting for study centre, were used to investigate the influence of non-dietary factors. The mean total fat intake was 33·3 (sd 1·2) % of total energy intake (%E). The mean SFA intake was 13·8 (sd 1·2) %E, with 99·8 % of the population exceeding the recommendations. SFA was mainly delivered by meat and cake, pies and biscuits. In most adolescents, the PUFA intake was too low, and 35·5 % of the population did not achieve the minimum recommended intake for α-linolenic acid (ALA). The main determinants of FA intake in the present study population were age and sex, as well as physical activity in the male subgroup. No contributions of body composition, socio-economic status or sexual maturation to the variance in FA intake were observed. In conclusion, the most important public health concerns regarding FA intake in this adolescent population were the low intake of ALA and the high intake of SFA, mainly seen in the younger-aged boys. In this group the major contributor to SFA was meat.

Polymorphisms in the CD36/FAT gene are associated with plasma vitamin E concentrations in humans.

BACKGROUND: Blood vitamin E concentrations are modulated by dietary, metabolic, and genetic factors. CD36 (cluster of differentiation 36), a class B scavenger receptor, might be involved in tissue vitamin E uptake and thus would influence blood vitamin E concentrations. OBJECTIVE: The goal of the study was to assess the association between CD36 single nucleotide polymorphisms (SNPs) and plasma α-tocopherol concentrations in humans. DESIGN: A subsample from the adult SU.VI.MAX (SUpplementation en VItamines et Minéraux AntioXydants) cohort (n = 621) and the adolescent cross-sectional HELENA (Healthy Lifestyle in Europe by Nutrition in Adolescence) Study (n = 993) were genotyped for CD36 SNPs (4 and 10 SNPs, respectively). Fasting plasma α-tocopherol concentrations were assayed by using HPLC. Associations were determined by haplotype analyses and by general linear regression models. RESULTS: In the SU.VI.MAX subsample, haplotype analyses showed that some haplotypes of SNPs rs1984112, rs1527479, rs7755, and rs1527483 tended to be associated with plasma α-tocopherol concentrations (P = 0.08 and P = 0.09 for haplotypes 1222 and 1122, respectively). We then investigated the whole known common genetic variability (10 SNPs) of CD36 in the HELENA Study. Three SNPs were associated with lower plasma α-tocopherol concentrations (rs1984112: -3.2%, P = 0.053; rs1761667: -2.9%, P = 0.046; rs1527479: -3.7%, P = 0.0061). After correction for multiple testing, the association between rs1527479 and α-tocopherol concentrations remained significant. This association was modulated by concentrations of fasting serum triglycerides (P for interaction = 0.006) and long-chain polyunsaturated fatty acids (P for interaction = 0.005). CONCLUSION: Our results suggest that CD36 can modulate blood α-tocopherol concentrations and may therefore be involved in the intestinal absorption or tissue uptake of vitamin E.

[Dietary supplementation of obese children with 1000 mg alpha-linolenic acid per day: a placebo-controlled double blind study]. / Elhízott gyermekek étrendjének kiegészítése napi 1000 mg alfa-linolénsavval. Placebóval kontrollált, kettosen vakvizsgálat.

INTRODUCTION: Enhanced dietary intake of omega-3 fatty acids may benefit persons with increased cardiovascular risk, among them obese subjects. Incorporation of omega-3 fatty acids into the plasma lipids is a prerequisite to achieve the favorable effects; however, only very few data are available on the dose of omega-3 fatty acid supplementation in children. The aim of our study was to examine the effects of the consumption of a diet supplemented with 1000 mg alpha-linolenic acid daily on plasma lipids in obese children. METHODS: In this two times six-week-long, placebo-controlled, crossover study, 9 obese children (age: 13.1 [2.5] years, body mass index: 31.2 [6.2] kg/m 2 ), median [IQR]) incorporated into their diet one egg and one meatball (50 g) per day from hens fed diets containing flaxseed oil, i.e. supplementary dietary intake of 1000 mg alpha-linolenic acid per day was provided. The fatty acid composition of plasma lipids was determined by high-resolution gas-liquid chromatography. RESULTS: Tendencies of increase were observed in the alpha-linolenic acid content of plasma lipids in the phospholipid, triacyl-glycerine and sterol-ester fractions after the supplementation with alpha-linolenic acid. In the non-esterified fatty acid fraction, the values of alpha-linolenic acid were significantly higher after the supplementation (0.11 [0.08] versus 0.14 [0.20], % weight/weight, p < 0.05), indicating the beginning of the accumulation of alpha-linolenic acid in plasma lipids. CONCLUSION: In obese children a six-week-long supplementation of the diet with 1000 mg alpha-linolenic acid per day increased significantly the contribution of omega-3 fatty acids only to the non-esterified fatty acids of plasma lipids, but had no significant effect on the esterified fractions. Increase of the dose of supplementation may be needed to influence omega-3 fatty acid status in obese children.