Gut Microbiome and Its Cofactors Are Linked to Lipoprotein Distribution Profiles.

Increasing evidence indicates that the gut microbiome (GM) plays an important role in dyslipidemia. To date, however, no in-depth characterization of the associations between GM with lipoproteins distributions (LPD) among adult individuals with diverse BMI has been conducted. To determine such associations, we studied blood-plasma LPD, fecal short-chain fatty acids (SCFA) and GM of 262 Danes aged 19-89 years. Stratification of LPD segregated subjects into three clusters displaying recommended levels of lipoproteins and explained by age and body-mass-index. Higher levels of HDL2a and HDL2b were associated with a higher abundance of Ruminococcaceae and Christensenellaceae. Increasing levels of total cholesterol and LDL-1 and LDL-2 were positively associated with Lachnospiraceae and Coriobacteriaceae, and negatively with Bacteroidaceae and Bifidobacteriaceae. Metagenome-sequencing showed a higher abundance of biosynthesis of multiple B-vitamins and SCFA metabolism genes among healthier LPD profiles. Metagenomic-assembled genomes (MAGs) affiliated to Eggerthellaceae and Clostridiales were contributors of these genes and their relative abundance correlated positively with larger HDL subfractions. The study demonstrates that differences in composition and metabolic traits of the GM are associated with variations in LPD among the recruited subjects. These findings provide evidence for GM considerations in future research aiming to shed light on mechanisms of the GM-dyslipidemia axis.

Plasma vitamin B12 concentration is positively associated with cognitive development in healthy Danish 3-year-old children: the SKOT cohort studies.

Adequate vitamin B12 (B12) and folate concentrations are essential for neural development in early childhood, but studies in well-nourished children are lacking. We investigated the relation between plasma B12 and folate at 9 and 36 months and psychomotor development at 36 months in well-nourished Danish children. Subjects from the SKOT cohorts with B12 measurement and completed Ages and Stages Questionnaire, 3rd edition (ASQ-3) at 36 months were included (n 280). Dietary intake, B12 and folate concentrations were collected at 9 and 36 months, and ASQ-3 was assessed at 36 months. Associations between B12 and folate at 9 and 36 months and ASQ-3 were analysed using regression models. Associations between diet and B12 were also investigated. No children had insufficient B12 (<148 pmol/l) at 36 months. B12 at 36 month was positively associated with total ASQ-3 corresponding to an increase of 100 pmol/l B12 per 1·5 increase in total ASQ-3 score (P = 0·019) which remained significant after adjustment for potential confounders including 9 months values. B12 at 9 months or folate at any time point was not associated with total ASQ-3. Intake of milk products was associated with B12 at 36 months (P = 0·003) and showed a trend at 9 months (P = 0·069). Intake of meat products was not associated with B12. In conclusion, B12 was positively related to psychomotor development at 3 years in well-nourished children, indicating that the impact of having marginally low B12 status on psychomotor development in well-nourished children should be examined further.

Human Blood Lipoprotein Predictions from 1H NMR Spectra: Protocol, Model Performances, and Cage of Covariance.

Lipoprotein subfractions are biomarkers for the early diagnosis of cardiovascular diseases. The reference method, ultracentrifugation, for measuring lipoproteins is time-consuming, and there is a need to develop a rapid method for cohort screenings. This study presents partial least-squares regression models developed using 1H nuclear magnetic resonance (NMR) spectra and concentrations of lipoproteins as measured by ultracentrifugation on 316 healthy Danes. This study explores, for the first time, different regions of the 1H NMR spectrum representing signals of molecules in lipoprotein particles and different lipid species to develop parsimonious, reliable, and optimal prediction models. A total of 65 lipoprotein main and subfractions were predictable with high accuracy, Q2 of >0.6, using an optimal spectral region (1.4-0.6 ppm) containing methylene and methyl signals from lipids. The models were subsequently tested on an independent cohort of 290 healthy Swedes with predicted and reference values matching by up to 85-95%. In addition, an open software tool was developed to predict lipoproteins concentrations in human blood from standardized 1H NMR spectral recordings.

Physical fitness in community-dwelling older adults is linked to dietary intake, gut microbiota, and metabolomic signatures.

When humans age, changes in body composition arise along with lifestyle-associated disorders influencing fitness and physical decline. Here we provide a comprehensive view of dietary intake, physical activity, gut microbiota (GM), and host metabolome in relation to physical fitness of 207 community-dwelling subjects aged +65 years. Stratification on anthropometric/body composition/physical performance measurements (ABPm) variables identified two phenotypes (high/low-fitness) clearly linked to dietary intake, physical activity, GM, and host metabolome patterns. Strikingly, despite a higher energy intake high-fitness subjects were characterized by leaner bodies and lower fasting proinsulin-C-peptide/blood glucose levels in a mechanism likely driven by higher dietary fiber intake, physical activity and increased abundance of Bifidobacteriales and Clostridiales species in GM and associated metabolites (i.e., enterolactone). These factors explained 50.1% of the individual variation in physical fitness. We propose that targeting dietary strategies for modulation of GM and host metabolome interactions may allow establishing therapeutic approaches to delay and possibly revert comorbidities of aging.

Repeatability and reproducibility of lipoprotein particle profile measurements in plasma samples by ultracentrifugation.

Background Characterization of lipoprotein particle profiles (LPPs) (including main classes and subclasses) by means of ultracentrifugation (UC) is highly requested given its clinical potential. However, rapid methods are required to replace the very labor-intensive UC method and one solution is to calibrate rapid nuclear magnetic resonance (NMR)-based prediction models, but the reliability of the UC-response method required for the NMR calibration has been largely overlooked. Methods This study provides a comprehensive repeatability and reproducibility study of various UC-based lipid measurements (cholesterol, triglycerides [TGs], free cholesterol, phospholipids, apolipoprotein [apo]A1 and apoB) in different main classes and subclasses of 25 duplicated fresh plasma samples and of 42 quality control (QC) frozen pooled plasma samples of healthy individuals. Results Cholesterol, apoA1 and apoB measurements were very repeatable in all classes (intraclass correlation coefficient [ICC]: 92.93%-99.54%). Free cholesterol and phospholipid concentrations in main classes and subclasses and TG concentrations in high-density lipoproteins (HDL), HDL subclasses and low-density lipoproteins (LDL) subclasses, showed worse repeatability (ICC: 19.21%-99.08%) attributable to low concentrations, variability introduced during UC and assay limitations. On frozen QC samples, the reproducibility of cholesterol, apoA1 and apoB concentrations was found to be better than for the free cholesterol, phospholipids and TGs concentrations. Conclusions This study shows that for LPPs measurements near or below the limit of detection (LOD) in some of the subclasses, as well as the use of frozen samples, results in worsened repeatability and reproducibility. Furthermore, we show that the analytical assay coupled to UC for free cholesterol and phospholipids have different repeatability and reproducibility. All of this needs to be taken into account when calibrating future NMR-based models.

Abdominal adiposity and cardiometabolic risk factors in children and adolescents: a Mendelian randomization analysis.

BACKGROUND: Mendelian randomization studies in adults suggest that abdominal adiposity is causally associated with increased risk of type 2 diabetes and coronary artery disease in adults, but its causal effect on cardiometabolic risk in children remains unclear. OBJECTIVE: We aimed to study the causal relation of abdominal adiposity with cardiometabolic risk factors in children by applying Mendelian randomization. METHODS: We constructed a genetic risk score (GRS) using variants previously associated with waist-to-hip ratio adjusted for BMI (WHRadjBMI) and examined its associations with cardiometabolic factors by linear regression and Mendelian randomization in a meta-analysis of 6 cohorts, including 9895 European children and adolescents aged 3-17 y. RESULTS: WHRadjBMI GRS was associated with higher WHRadjBMI (ß = 0.021 SD/allele; 95% CI: 0.016, 0.026 SD/allele; P = 3 × 10-15) and with unfavorable concentrations of blood lipids (higher LDL cholesterol: ß = 0.006 SD/allele; 95% CI: 0.001, 0.011 SD/allele; P = 0.025; lower HDL cholesterol: ß = -0.007 SD/allele; 95% CI: -0.012, -0.002 SD/allele; P = 0.009; higher triglycerides: ß = 0.007 SD/allele; 95% CI: 0.002, 0.012 SD/allele; P = 0.006). No differences were detected between prepubertal and pubertal/postpubertal children. The WHRadjBMI GRS had a stronger association with fasting insulin in children and adolescents with overweight/obesity (ß = 0.016 SD/allele; 95% CI: 0.001, 0.032 SD/allele; P = 0.037) than in those with normal weight (ß = -0.002 SD/allele; 95% CI: -0.010, 0.006 SD/allele; P = 0.605) (P for difference = 0.034). In a 2-stage least-squares regression analysis, each genetically instrumented 1-SD increase in WHRadjBMI increased circulating triglycerides by 0.17 mmol/L (0.35 SD, P = 0.040), suggesting that the relation between abdominal adiposity and circulating triglycerides may be causal. CONCLUSIONS: Abdominal adiposity may have a causal, unfavorable effect on plasma triglycerides and potentially other cardiometabolic risk factors starting in childhood. The results highlight the importance of early weight management through healthy dietary habits and physically active lifestyle among children with a tendency for abdominal adiposity.

Human Milk Oligosaccharide Composition Is Associated With Excessive Weight Gain During Exclusive Breastfeeding-An Explorative Study.

Background: Some infants experience excessive weight gain during exclusive breastfeeding. The cause is unknown, but variation in human milk composition might play a role. Several human milk koligosaccharides (HMOs) have been associated with growth velocity in breastfed infants, and it has been suggested that the mechanism could be through an effect on infant gut microbiota composition. Objective: The purpose of this exploratory study was to evaluate if HMO composition was different in milk fed to infants with excessive weight gain compared to infants with normal weight gain. Furthermore, we aimed to examine if HMO composition was associated with growth velocity and change in body composition and if there were maternal determinants of HMO composition. Materials and Methods: We recruited 13 high weight-gain (HW) and 17 normal weight-gain (NW) breastfed infants, collected human milk and anthropometry data at 5 and 9 months, and analyzed HMO composition by high performance liquid chromatography. Results: In the HW group eight out of 11 infants received milk from secretor mothers and in the NW group 15 out of 17. Comparing milk from Secretor mothers only, four HMO's were significantly different between the HW and NW group at 5 months and two remained significant at 9 months. Total HMO concentrations as well as total HMO-bound fucose at 5 months were positively associated with both fat mass index (FMI) and weight velocity from 0 to 5 months (all p < 0.025). 2'-fucosyllactose (2'-FL) was positively associated with weight velocity from 0 to 5 months and FMI at 5 months. In contrast, lacto-N-neotetraose was lower in the HW group (p = 0.012) and negatively associated with height-for-age Z-scores (p = 0.008), weight velocity from 0 to 5 months (p = 0.009) and FMI (p = 0.033). Maternal BMI at 5 months was negatively associated with 6'-sialyllactose and sialyl-lacto-N-tetraose (LSTb) and positively with 2'-FL, total HMO and total HMO-bound fucose (all p ≤ 0.03). Conclusion: In a small cohort, we found significantly different HMO concentrations in milk to exclusively breastfed infants with excessive weight gain, suggesting that some HMOs, including 2'-FL, which is the most abundant HMO and currently added to some infant formula, could be part of the cause for the excessive weight gain.

Genetic predisposition to higher body fat yet lower cardiometabolic risk in children and adolescents.

BACKGROUND: Most obese children show cardiometabolic impairments, such as insulin resistance, dyslipidemia, and hypertension. Yet some obese children retain a normal cardiometabolic profile. The mechanisms underlying this variability remain largely unknown. We examined whether genetic loci associated with increased insulin sensitivity and relatively higher fat storage on the hip than on the waist in adults are associated with a normal cardiometabolic profile despite higher adiposity in children. METHODS: We constructed a genetic score using variants previously linked to increased insulin sensitivity and/or decreased waist-hip ratio adjusted for body mass index (BMI), and examined the associations of this genetic score with adiposity and cardiometabolic impairments in a meta-analysis of six cohorts, including 7391 European children aged 3-18 years. RESULTS: The genetic score was significantly associated with increased degree of obesity (higher BMI-SDS beta = 0.009 SD/allele, SE = 0.003, P = 0.003; higher body fat mass beta = 0.009, SE = 0.004, P = 0.031), yet improved body fat distribution (lower WHRadjBMI beta = -0.014 SD/allele, SE = 0.006, P = 0.016), and favorable concentrations of blood lipids (higher HDL cholesterol: beta = 0.010 SD/allele, SE = 0.003, P = 0.002; lower triglycerides: beta = -0.011 SD/allele, SE = 0.003, P = 0.001) adjusted for age, sex, and puberty. No differences were detected between prepubertal and pubertal/postpubertal children. The genetic score predicted a normal cardiometabolic profile, defined by the presence of normal glucose and lipid concentrations, among obese children (OR = 1.07 CI 95% 1.01-1.13, P = 0.012, n = 536). CONCLUSIONS: Genetic predisposition to higher body fat yet lower cardiometabolic risk exerts its influence before puberty.

FADS and PPARG2 Single Nucleotide Polymorphisms are Associated with Plasma Lipids in 9-Mo-Old Infants.

BACKGROUND: Dietary intake of polyunsaturated fatty acids (PUFAs), e.g., linoleic acid and n-3 (ω-3) long-chain PUFAs, has been shown in adults to affect plasma cholesterol and triglycerides (TGs), respectively. Little is known about the effects of PUFAs on plasma lipids in early life. OBJECTIVE: The aim of this study was to explore the associations between plasma concentrations of total, LDL, and HDL cholesterol and TGs in infants and 2 single nucleotide polymorphisms (SNPs) in the fatty acid desaturase genes (FADS) oppositely associated with docosahexaenoic acid (rs1535 and rs174448) and potential effect modification by a functional peroxisome proliferator-activated receptor-γ2 gene variant (PPARG2 Pro12Ala). METHODS: In 9-mo-old infants (n = 561) from 3 Danish cohorts, we analyzed associations between plasma lipids, erythrocyte PUFAs, and FADS SNPs, and interactions with PPARG2 Pro12Ala genotype, by multiple linear regression. We also examined potential effect modification by breastfeeding, as 46% of the infants were still being breastfed. RESULTS: Minor allele carriage of rs174448 was associated with lower total cholesterol (difference: -0.22 mmol/L; 95% CI: -0.37, -0.06 mmol/L; P = 0.006) and LDL cholesterol (difference: -0.15 mmol/L; 95% CI: -0.29, -0.01 mmol/L; P = 0.035), but no associations were observed with TGs or for rs1535. Minor allele carriage of both FADS SNPs was associated with 1 SD lower HDL cholesterol, but only in currently breastfed infants (rs174448 × breastfeeding, P = 0.080; rs1535 × breastfeeding, P = 0.030) and PPARG2 minor allele carriers (rs174448 × PPARG2, P = 0.001; rs1535 × PPARG2, P = 0.004). Erythrocyte arachidonic acid and eicosapentaenoic acid were inversely associated with LDL cholesterol [estimated effect (ß): -0.3 mmol/L; 95% CI: -0.06, -0.00 mmol/L per percentage of fatty acids (FA%); P = 0.035] and TGs (ß: -0.23 mmol/L; 95% CI: -0.41, -0.05 mmol/L per FA%; P = 0.015), respectively. CONCLUSIONS: The observed associations with FADS variants indicate that PUFAs are involved in plasma lipid regulation in 9-mo-old infants. Observed FADS SNP differences and interactions with breastfeeding and PPARG2 warrant additional studies to explore the effects of individual FADS SNPs on PUFA status and potential genetic modification of dietary PUFA effects.

Corrigendum: Human Milk Oligosaccharide Composition Is Associated With Excessive Weight Gain During Exclusive Breastfeeding-An Explorative Study.

[This corrects the article DOI: 10.3389/fped.2019.00297.].

A low-gluten diet induces changes in the intestinal microbiome of healthy Danish adults.

Adherence to a low-gluten diet has become increasingly common in parts of the general population. However, the effects of reducing gluten-rich food items including wheat, barley and rye cereals in healthy adults are unclear. Here, we undertook a randomised, controlled, cross-over trial involving 60 middle-aged Danish adults without known disorders with two 8-week interventions comparing a low-gluten diet (2 g gluten per day) and a high-gluten diet (18 g gluten per day), separated by a washout period of at least six weeks with habitual diet (12 g gluten per day). We find that, in comparison with a high-gluten diet, a low-gluten diet induces moderate changes in the intestinal microbiome, reduces fasting and postprandial hydrogen exhalation, and leads to improvements in self-reported bloating. These observations suggest that most of the effects of a low-gluten diet in non-coeliac adults may be driven by qualitative changes in dietary fibres.

Excessive Weight Gain Followed by Catch-Down in Exclusively Breastfed Infants: An Exploratory Study.

Some infants experience excessive weight gain (EWG) during exclusive breastfeeding, but causes and consequences are unknown. The objective was to identify factors associated with early EWG. Infants with EWG (HW-group) were examined at 5, 9 and 18 mo and compared to a breastfed group with normal weight gain (NW-group). Anthropometry, body composition, milk and blood samples, and milk intake were measured. Mean body-mass-index-for-age z-scores (BAZ) increased 1.93 from birth to 5 mo in the HW-group (n = 13) while the NW-group (n = 17) was unchanged (-0.01). The HW-group had 70% more fat mass at 5 mo, and then showed marked catch-down in BAZ from 5 to 18 mo (-0.84). Milk intake at 5⁻6 mo did not differ between the groups. In the HW-group milk-leptin was lower at 5 mo and serum-leptin was considerably higher at 5 and 9 mo compared to the NW-group. Serum-leptin at 5 mo was positively associated with weight-for-age z-score (WAZ) and fat mass and negatively with WAZ change from 5 to 9 mo. In conclusion, breastfed infants with EWG had catch-down growth when other foods were introduced. Low milk-leptin in the HW-group may have stimulated appetite and milk intake when weight gain was high. High serum-leptin in the HW-group suggests early leptin resistance, which could impact cerebral regulation of energy intake. Larger studies are needed to confirm these results.

Human milk composition and infant growth.

PURPOSE OF REVIEW: This review highlights relevant studies published between 2015 and 2017 on human milk composition and the association with infant growth. RECENT FINDINGS: High-quality studies investigating how human milk composition is related to infant growth are sparse. Recent observational studies show that human milk concentrations of protein, fat, and carbohydrate likely have important influence on infant growth and body composition. Furthermore, some observational studies examining human milk oligosaccharides and hormone concentrations suggest functional relevance to infant growth. For human milk micronutrient concentrations and microbiota content, and other bioactive components in human milk, the association with infant growth is still speculative and needs further investigation. The included studies in this review are all limited in their methodological design and methods but have interesting potential in understanding infant growth. SUMMARY: Available evidence on human milk composition in relation to infant growth is sparse. This review summarizes recent publications investigating human milk composition; including micro- and macronutrients, human milk oligosaccharides, hormones and other bioactive components, and the association with infant weight, length, body mass index, and body composition.

In Vivo and Ex Vivo Inflammatory Markers of Common Metabolic Phenotypes in Humans.

BACKGROUND: Low-grade systemic inflammation (LGSI) is often characterized by elevated levels of interleukin (IL)6, tumor necrosis factor (TNF)α, and C-reactive protein (CRP). Other serum proteins, ex vivo-stimulated cytokine production, and leukocyte count have, however, also been suggested LGSI-markers, but their associations with the metabolic syndrome (MS) are less clear. We aimed to evaluate mutual relationships between in vivo and ex vivo inflammatory markers and their association with MS and its subcomponents. METHODS: A cross-sectional study of 118 overweight adults with one or several features of MS. Inflammatory markers included fasting serum levels of IL6, TNFα, CRP, and pentraxin-3 (PTX3), IL1-receptors, leukocytes, and whole-blood ex vivo-produced IL1ß, IL6, TNFα, and IL8 after lipopolysaccharide stimulation. RESULTS: All classical serum LGSI-markers correlated with each other, and IL6 and CRP were also correlated with leukocyte count. Ex vivo-produced cytokines were intercorrelated and correlated with leukocyte count, but did not correlate with the serum immune markers. MS score, body mass index, and glycated hemoglobin (HbA1c) were associated with 8%-16% higher inflammatory score per standard deviation increment (P = 0.030, 0.001, and 0.034, respectively), primarily driven by higher serum IL6. Serum PTX3 was only significantly associated with high-density lipoprotein cholesterol (1.19[1.04; 1.37], P = 0.013). HbA1c was inversely associated with surface expression of IL1R1 on monocytes and IL1R2 on granulocytes (P < 0.01) and with a 3%-9% lower ex vivo production of cytokines when adjusting for leukocyte count, as were plasma triacylglycerol (9%-10% lower IL1ß and IL6). Leukocyte count was most consistently associated with MS and its subcomponents, although not with HbA1. CONCLUSIONS: The classical fasting serum markers of LGSI and leukocyte counts associated best with measures of MS-associated LGSI, whereas ex vivo cytokine production was only associated with prevailing glycemia and dyslipidemia. Taken together, this indicates that the relationship between in vivo and ex vivo inflammatory markers is complex and may depend on the MS phenotype.

Higher intake of fish and fat is associated with lower plasma s-adenosylhomocysteine: a cross-sectional study.

Several B-vitamins act as co-factors in one-carbon metabolism, a pathway that plays a central role in several chronic diseases. However, there is a lack of knowledge of how diet affects markers in one-carbon metabolism. The aim of this study was to explore dietary patterns and components associated with one-carbon metabolites. We hypothesized that intake of whole-grains and fish would be associated with lower Hcy, and higher SAM:SAH ratio due to their nutrient content. We assessed dietary information using a four-day dietary record in 118 men and women with features of the metabolic syndrome. In addition we assessed whole-blood fatty acid composition and plasma alkylresorcinols. Plasma s-adenosylmethionine (SAM), s-adenosylhomocysteine (SAH), homocysteine (Hcy) and vitamin B12 was included as one-carbon metabolism markers. We used principal component analysis (PCA) to explore dietary patterns and multiple linear regression models to examine associations between dietary factors and one-carbon metabolites. PCA separated subjects based on prudent and unhealthy dietary patterns, but the dietary pattern score was not related to the one-carbon metabolites. Whole grain intake was found to be inversely associated to plasma Hcy (-4.7% (-9.3; 0.0), P=.05) and total grain intake tended to be positively associated with SAM and SAH (2.4% (-0.5; 5.5), P=.08; 5.8% (-0.2; 12.1), P=.06, respectively, per SD increase in cereal intake). Fish intake was inversely associated with plasma Hcy and SAH concentrations (-5.4% (-9.7; -0.8), P=.02 and -7.0% (-12.1; -1.5), P=.01, respectively) and positively associated with the SAM:SAH ratio (6.2% (1.6; 11.0), P=.008). In conclusion, intake and fish and whole-grain appear to be associated with a beneficial one-carbon metabolism profile. This indicates that dietary components could play a role in regulation of one-carbon metabolism with a potential impact on disease prevention.

Toward Reliable Lipoprotein Particle Predictions from NMR Spectra of Human Blood: An Interlaboratory Ring Test.

Lipoprotein profiling of human blood by 1H nuclear magnetic resonance (NMR) spectroscopy is a rapid and promising approach to monitor health and disease states in medicine and nutrition. However, lack of standardization of measurement protocols has prevented the use of NMR-based lipoprotein profiling in metastudies. In this study, a standardized NMR measurement protocol was applied in a ring test performed across three different laboratories in Europe on plasma and serum samples from 28 individuals. Data was evaluated in terms of (i) spectral differences, (ii) differences in LPD predictions obtained using an existing prediction model, and (iii) agreement of predictions with cholesterol concentrations in high- and low-density lipoproteins (HDL and LDL) particles measured by standardized clinical assays. ANOVA-simultaneous component analysis (ASCA) of the ring test spectral ensemble that contains methylene and methyl peaks (1.4-0.6 ppm) showed that 97.99% of the variance in the data is related to subject, 1.62% to sample type (serum or plasma), and 0.39% to laboratory. This interlaboratory variation is in fact smaller than the maximum acceptable intralaboratory variation on quality control samples. It is also shown that the reproducibility between laboratories is good enough for the LPD predictions to be exchangeable when the standardized NMR measurement protocol is followed. With the successful implementation of this protocol, which results in reproducible prediction of lipoprotein distributions across laboratories, a step is taken toward bringing NMR more into scope of prognostic and diagnostic biomarkers, reducing the need for less efficient methods such as ultracentrifugation or high-performance liquid chromatography (HPLC).

Whole-Grain Intake, Reflected by Dietary Records and Biomarkers, Is Inversely Associated with Circulating Insulin and Other Cardiometabolic Markers in 8- to 11-Year-Old Children.

Background: Whole-grain consumption seems to be cardioprotective in adults, but evidence in children is limited.Objective: We investigated whether intakes of total whole grain and dietary fiber as well as specific whole grains were associated with fat mass and cardiometabolic risk profile in children.Methods: We collected cross-sectional data on parental education, puberty, diet by 7-d records, and physical activity by accelerometry and measured anthropometry, fat mass index by dual-energy X-ray absorptiometry, and blood pressure in 713 Danish children aged 8-11 y. Fasting blood samples were obtained and analyzed for alkylresorcinols, biomarkers of whole-grain wheat and rye intake, HDL and LDL cholesterol, triacylglycerols, insulin, and glucose. Linear mixed models included puberty, parental education, physical activity, and intakes of energy, fruit and vegetables, saturated fat, and n-3 (ω-3) polyunsaturated fatty acids.Results: Median (IQR) whole-grain and dietary fiber intakes were 52 g/d (35-72 g/d) and 17 g/d (14-22 g/d), respectively. Fourteen percent of children were overweight or obese and most had low-risk cardiometabolic profiles. Dietary whole-grain and fiber intakes were not associated with fat mass index but were inversely associated with serum insulin [both P < 0.01; e.g., with 0.68 pmol/L (95% CI: 0.26, 1.10 pmol/L) lower insulin · g whole grain-1 · MJ-1]. Whole-grain oat intake was inversely associated with fat mass index, systolic blood pressure, and LDL cholesterol (all P < 0.05) as well as insulin (P = 0.003), which also tended to be inversely associated with whole-grain rye intake (P = 0.11). Adjustment for fat mass index did not change the associations. The C17-to-C21 alkylresorcinol ratio, reflecting whole-grain rye to wheat intake, was inversely associated with insulin (P < 0.001).Conclusions: Higher whole-grain intake was associated with lower serum insulin independently of fat mass in 8- to 11-y-old Danish children. Whole-grain oat intake was linked to an overall protective cardiometabolic profile, and whole-grain rye intake was marginally associated with lower serum insulin. This supports whole grains as healthy dietary components in childhood. This trial was registered at clinicaltrials.gov as NCT01577277.