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.

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.

Fracture Risk in Relation to Serum 25-Hydroxyvitamin D and Physical Activity: Results from the EPIC-Norfolk Cohort Study.

Vitamin D deficiency and physical inactivity have been associated with bone loss and fractures, but their combined effect has scarcely been studied either in younger or older adults. Therefore, we aimed to assess the associations between physical activity, age and 25-hydroxyvitamin D (25(OH)D) status separately and in combination with the incidence of fracture risk in the EPIC-Norfolk cohort study. Baseline (1993-1998) self-reported physical activity and serum 25(OH)D concentrations at follow-up (1998-2000) were collected in 14,624 men and women (aged 42-82 y between 1998 and 2000). Fracture incidence was ascertained up to March 2015. Cox proportional hazard model was used to determine HRs of fractures by plasma 25(OH)D (<30, 30 to <50, 50 to <70, 70 to <90, >90 nmol/L), age (<65 y and >65 y) and physical activity (inactive and active) categories, by follow-up time per 20 nmol/L increase in serum 25(OH)D and to explore age-25(OH)D and physical activity-25(OH)D interactions. The age-, sex-, and month-adjusted HRs (95% CIs) for all fractures (1183 fractures) by increasing vitamin D category were not significantly different. With additional adjustment for body mass index, smoking status, alcohol intake, supplement use and history of fractures, the fracture risk was 29% lower in those participants with 50 to 70 nmol/L compared with those in the lowest quintile (<30 nmol/L). Physical inactivity based on a single baseline assessment was not associated with fracture risk. Vitamin D status appeared inversely related to fractures in middle aged adults. In older adults, the relationship between vitamin D status and fracture risk was observed to be J-shaped. Clinical and public health practice in vitamin D supplementation could partially explain these findings, although definitive conclusions are difficult due to potential changes in exposure status over the long follow up period.

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.

Serum plant sterols as surrogate markers of dietary compliance in familial dyslipidemias.

BACKGROUND & AIMS: A well-balanced diet is the first-line treatment in hyperlipidemia. The objective was to study the association between serum phytosterols and dietary patterns to use them as surrogate markers of dietary compliance in primary dyslipidemias. METHODS: 288 patients with primary hyperlipidemias (192 autosomal dominant hypercholesterolemia (ADH) and 96 familial combined hyperlipidemia (FCHL)) were included. Principal factor analysis identified 2 major dietary patterns using a 137-item food frequency questionnaire. "Vegetable & Fruits pattern" was characterized by higher intake of fruits, green beans, nuts, tomatoes, roasted or boiled potatoes, lettuce and chard and lower of processed baked goods, pizza and beer. "Western pattern" was positively characterized by hamburgers, pasta, sunflower oil, rice, chickpeas, whole milk, veal, red beans and negatively with white fish. Serum non-cholesterol sterols were determined by HPLC-MS/MS. RESULTS: Plant sterols to-total cholesterol (TC) levels were lower with a higher adherence to a "Vegetable & Fruits pattern" (P = 0.009), mainly in ADH subjects (R(2) = 0.019). Their concentration was greater with higher compliance to "Western pattern" especially in FCHL (P = 0.014). Higher levels of synthesis markers-to-TC with a greater adherence to "Vegetable & Fruits pattern" were found (P = 0.001) (R(2) = 0.033 and R(2) = 0.109 in ADH and FCHL respectively). CONCLUSION: In subjects with primary dislipidemia, dietary patterns associate with serum absorption and synthesis markers, but no with lipid concentrations. The influence of diet on non-cholesterol sterols levels is not powerful enough to use them as subrogate markers.

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.

EURRECA-Estimating zinc requirements for deriving dietary reference values.

Zinc was selected as a priority micronutrient for EURRECA, because there is significant heterogeneity in the Dietary Reference Values (DRVs) across Europe. In addition, the prevalence of inadequate zinc intakes was thought to be high among all population groups worldwide, and the public health concern is considerable. In accordance with the EURRECA consortium principles and protocols, a series of literature reviews were undertaken in order to develop best practice guidelines for assessing dietary zinc intake and zinc status. These were incorporated into subsequent literature search strategies and protocols for studies investigating the relationships between zinc intake, status and health, as well as studies relating to the factorial approach (including bioavailability) for setting dietary recommendations. EMBASE (Ovid), Cochrane Library CENTRAL, and MEDLINE (Ovid) databases were searched for studies published up to February 2010 and collated into a series of Endnote databases that are available for the use of future DRV panels. Meta-analyses of data extracted from these publications were performed where possible in order to address specific questions relating to factors affecting dietary recommendations. This review has highlighted the need for more high quality studies to address gaps in current knowledge, in particular the continued search for a reliable biomarker of zinc status and the influence of genetic polymorphisms on individual dietary requirements. In addition, there is a need to further develop models of the effect of dietary inhibitors of zinc absorption and their impact on population dietary zinc requirements.

Factors associated with vitamin D deficiency in European adolescents: the HELENA study.

Evidence indicates low 25-hydroxyvitamin D [(25(OH)D] concentrations in European adolescents. Identification of potential determinants is therefore essential to guide public health initiatives aiming at optimizing vitamin D status across Europe. The aim of the study was to identify potential influencing factors of 25(OH)D concentrations in European adolescents aged 12.5 to 17.5 y, participating in the multi-centre cross-sectional Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) study. A subset of 1,006 participants (46.8% males) was drawn from the main study. Measures of body composition, biochemical markers, socioeconomic status, dietary intake, physical activity, fitness, sleep time and vitamin D genetic polymorphism (rs1544410) were assessed. Stepwise multivariate linear regression analysis was conducted stratified by gender. In males, linear regression of 25(OH)D, suggested that (1) winter season (ß=-0.364; p<0.01), (2) higher latitudes (ß=-0.246; p<0.01), (3) BMI z-score (ß=-0.198; p<0.05) and (4) retinol concentration (ß=0.171; p<0.05) independently influenced 25(OH)D concentrations. In females, (1) winter season (ß=-0.370; p<0.01), (2) sleep time (ß=-0.231; p<0.01), (3) supplement intake (ß=0.221; p<0.05), (4) flexibility (ß=0.184; p<0.05), (5) body fat % (ß=0.201; p<0.05) (6), BMI z-score (ß=-0.272; p<0.05), (7) higher latitudes (ß=-0.219; p<0.01) and (8) handgrip strength (ß=0.206; p<0.05) independently influenced 25(OH)D concentrations. Season, latitude, fitness, adiposity, sleep time and micronutrient supplementation were highly related to 25(OH)D concentrations found in European adolescents.

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.

Health effects related to low vitamin D concentrations: beyond bone metabolism.

BACKGROUND: Vitamin D is essential for a vast number of physiologic processes, and thus adequate levels are necessary or advantageous for optimal health. During childhood and adolescence, an adequate vitamin D status is needed due to its important role in cell growth, skeletal structure, and development. AIMS: To review the extraskeletal effects of vitamin D, focusing especially on children. METHODS: Narrative review. RESULTS: Low vitamin D concentrations seem to be significantly associated with all-cause mortality. Regular sunlight exposure and vitamin D supplementation in early childhood may offer protection against the development of type 1 diabetes. Epidemiological evidence supports the importance of adequate vitamin D levels for the prevention of a number of cancers, mainly breast and colorectal ones. There seems to be an inverse relation between 25(OH)D serum concentrations and cardiovascular diseases, some components of the metabolic syndrome, and physical fitness. CONCLUSIONS: Lifestyle and appropriate nutrition may prevent the long-term effect of hypovitaminosis D beyond mineral and bone metabolism.

Supplementation of N-3 LCPUFA to the diet of children older than 2 years: a commentary by the ESPGHAN Committee on Nutrition.

The aim of this commentary is to review data on the effect of supplementation of paediatric patients ages 2 years or older with n-3 long-chain polyunsaturated fatty acids (LCPUFA). Some evidence for a positive effect on functional outcome in children with attention-deficit/hyperactivity disorder (ADHD) was found; however, benefit was seen in only about half of the randomised controlled trials (RCT), and studies varied widely not only in dose and form of supplementation but also in the functional outcome parameter tested. The committee concludes that there are insufficient data to recommend n-3 LCPUFA supplementation in the treatment of children with ADHD, but further research on n-3 LCPUFA supplementation in ADHD may be worthwhile. The committee was unable to find evidence of a favourable effect of n-3 LCPUFA supplementation on cognitive function in children. Although no benefit of n-3 LCPUFA supplementation was seen for major clinical outcome parameters in children with cystic fibrosis, a potentially beneficial shift towards less-inflammatory eicosanoid profiles seen in 2 studies provides grounds for further investigation; it is possible that earlier and longer supplementation periods may be needed to demonstrate clinical effect. For children with phenylketonuria, the limited data available suggest that supplementation of n-3 LCPUFA to the diet is both feasible and safe, but offers only transient benefit in visual function. For children with bronchial asthma there are insufficient data to suggest that LCPUFA supplementation has a beneficial effect. The committee advises paediatricians that most health claims about supplementation of n-3 LCPUFA in various diseases in children and adolescents are not supported by convincing scientific data.

Critical issues in setting micronutrient recommendations for pregnant women: an insight.

The European Micronutrient Recommendations Aligned (EURRECA) Network aims to provide standardized approaches to reveal and beneficially influence variability within the European Union in micronutrient recommendations for vulnerable population groups. Characterization of the 'vulnerability' together with the 'variability' of micronutrient needs represents the first step to creating guidelines for setting micronutrient recommendations within target populations. This paper describes some of the key factors and characteristics relevant to assess micronutrient requirements and formulate recommendations of micronutrients in pregnancy. Nutritional requirements during pregnancy increase to support fetal growth and development as well as maternal metabolism and tissue accretion. Micronutrients are involved in both embryonal and fetal organ development and overall pregnancy outcomes. Several factors may affect directly or indirectly fetal nourishment and the overall pregnancy outcomes, such as the quality of diet including intakes and bioavailability of micronutrients, maternal age, and the overall environment. The bioavailability of micronutrients during pregnancy varies depending on specific metabolic mechanisms because pregnancy is an anabolic and dynamic state orchestrated via hormones acting for both redirection of nutrients to highly specialized maternal tissues and transfer of nutrients to the developing fetus. The timing of prenatal intakes or supplementations of specific micronutrients is also crucial as pregnancy is characterized by different stages that represent a continuum, up to lactation and beyond. Consequently, nutrition during pregnancy might have long-lasting effects on the well-being of the mother and the fetus, and may further influence the health of the baby at a later age.