Background/objectives: Sufficient vitamin A levels are important for many functions-and both too little and too much may have detrimental health effects. The aim of the study was to describe the distribution of retinol levels in Norwegian adolescents, the relation between lifestyle factors and retinol levels, and the relation between retinol levels and bone mineral density (BMD). Subjects/methods: Serum retinol was measured in 414 girls and 474 boys aged 15-19 years, participating in the Tromsø Study: Fit Futures. Questionnaires regarding health and lifestyle factors were filled in, and physical examinations, body composition, and bone mineral density measurements (DEXA) performed. Multiple regression analyses were used to discover associations between retinol and exposure variables. Results: Retinol levels ranged from 0.26 to 6.46 μmol/L with a median (2.5-97.5 percentile) of 2.35 (1.01-4.67) μmol/L. There was no gender difference. In the multivariate models, fat mass, albumin level, physical activity, and lunch habits were positively associated with retinol levels in boys. In girls, fat mass and height were negatively associated with retinol levels, and lean mass, vitamin D, calcium, total cholesterol, and the use of contraceptives were positively associated with retinol levels (p < 0.05). The models explained 18.3% and 14.6% of the variation (R2) in girls and boys, respectively. Retinol levels were not independently associated with BMD. Conclusion: Retinol levels in Norwegian adolescents are higher than reported elsewhere, and are to a low degree explained by lifestyle and physical measurements. No independent association with BMD was found.

Elevated hepatic ceramides levels have been implicated in both insulin resistance (IR) and hepatic steatosis. To understand the factors contributing to hepatic ceramide levels in mice of both sexes, we have quantitated ceramides in a reference population of mice, the Hybrid Mouse Diversity Panel (HMDP) that has been previously characterized for a variety of metabolic syndrome traits. We observed significant positive correlations between Cer(d18:1/16:0) and IR/hepatic steatosis, consistent with previous findings, although the relationship broke down between sexes, as females were less insulin resistant but had higher Cer(d18:1/16:0) levels than males. The sex difference was due in part to testosterone mediated repression of ceramide synthase 6. One ceramide species, Cer(d18:1/20:0), was present at higher levels in males and was associated with insulin resistance only in males. Clear evidence of gene-by-sex and gene-by-diet interactions was observed, including sex-specific genome-wide associations (GWAS) results. Thus, our studies show clear differences in how hepatic ceramides are regulated between the sexes, which again suggests that the physiological roles of certain hepatic ceramides differ between the sexes.

Vitamin D is a steroid hormone precursor that is associated with a range of human traits and diseases. Previous GWAS of serum 25-hydroxyvitamin D concentrations have identified four genome-wide significant loci (GC, NADSYN1/DHCR7, CYP2R1, CYP24A1). In this study, we expand previous SUNLIGHT Consortium GWAS discovery sample size from 16,125 to 79,366 (all European descent). This larger GWAS yields two additional loci harboring genome-wide significant variants (P=4.710-9 at rs8018720 in SEC23A, and P=1.910-14 at rs10745742 in AMDHD1). The overall estimate of heritability of 25-hydroxyvitamin D serum concentrations attributable to GWAS common SNPs is 7.5%, with statistically significant loci explaining 38% of this total. Further investigation identifies signal enrichment in immune and hematopoietic tissues, and clustering with autoimmune diseases in cell-type-specific analysis. Larger studies are required to identify additional common SNPs, and to explore the role of rare or structural variants and gene-gene interactions in the heritability of circulating 25-hydroxyvitamin D levels.

The main objective of "Lifebrain" is to identify the determinants of brain, cognitive and mental (BCM) health at different stages of life. By integrating, harmonising and enriching major European neuroimaging studies across the life span, we will merge fine-grained BCM health measures of more than 5,000 individuals. Longitudinal brain imaging, genetic and health data are available for a major part, as well as cognitive and mental health measures for the broader cohorts, exceeding 27,000 examinations in total. By linking these data to other databases and biobanks, including birth registries, national and regional archives, and by enriching them with a new online data collection and novel measures, we will address the risk factors and protective factors of BCM health. We will identify pathways through which risk and protective factors work and their moderators. Exploiting existing European infrastructures and initiatives, we hope to make major conceptual, methodological and analytical contributions towards large integrative cohorts and their efficient exploitation. We will thus provide novel information on BCM health maintenance, as well as the onset and course of BCM disorders. This will lay a foundation for earlier diagnosis of brain disorders, aberrant development and decline of BCM health, and translate into future preventive and therapeutic strategies. Aiming to improve clinical practice and public health we will work with stakeholders and health authorities, and thus provide the evidence base for prevention and intervention.

FFQ, food diaries and 24 h recall methods represent the most commonly used dietary assessment tools in human studies on nutrition and health, but food intake biomarkers are assumed to provide a more objective reflection of intake. Unfortunately, very few of these biomarkers are sufficiently validated. This review provides an overview of food intake biomarker research and highlights present research efforts of the Joint Programming Initiative ‘A Healthy Diet for a Healthy Life’ (JPI-HDHL) Food Biomarkers Alliance (FoodBAll). In order to identify novel food intake biomarkers, the focus is on new food metabolomics techniques that allow the quantification of up to thousands of metabolites simultaneously, which may be applied in intervention and observational studies. As biomarkers are often influenced by various other factors than the food under investigation, FoodBAll developed a food intake biomarker quality and validity score aiming to assist the systematic evaluation of novel biomarkers. Moreover, to evaluate the applicability of nutritional biomarkers, studies are presently also focusing on associations between food intake biomarkers and diet-related disease risk. In order to be successful in these metabolomics studies, knowledge about available electronic metabolomics resources is necessary and further developments of these resources are essential. Ultimately, present efforts in this research area aim to advance quality control of traditional dietary assessment methods, advance compliance evaluation in nutritional intervention studies, and increase the significance of observational studies by investigating associations between nutrition and health.