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Diet is an important, modifiable lifestyle factor of cardiometabolic disease risk, and an improved diet can delay or even prevent the onset of disease. Recent evidence suggests that individuals could benefit from diets adapted to their genotype and phenotype: that is, personalized nutrition. A novel strategy is to tailor diets for groups of individuals according to their metabolic phenotypes (metabotypes). Randomized controlled trials evaluating metabotype-specific responses and nonresponses are urgently needed to bridge the current gap of knowledge with regard to the efficacy of personalized strategies in nutrition. In this Perspective, we discuss the concept of metabotyping, review the current literature on metabotyping in the context of cardiometabolic disease prevention, and suggest potential strategies for metabotype-based nutritional advice for future work. We also discuss potential determinants of metabotypes, including gut microbiota, and highlight the use of metabolomics to define effective markers for cardiometabolic disease–related metabotypes. Moreover, we hypothesize that people at high risk for cardiometabolic diseases have distinct metabotypes and that individuals grouped into specific metabotypes may respond differently to the same diet, which is being tested in a project of the Joint Programming Initiative: A Healthy Diet for a Healthy Life.

BACKGROUND: A diet rich in whole grains may provide benefits for pregnant women due to whole grains' high nutritional value and dietary fiber content. OBJECTIVES: To study the associations of whole-grain consumption, as well as the plasma alkylresorcinol concentration, a whole-grain consumption biomarker, in early pregnancy with gestational diabetes mellitus (GDM) diagnoses. METHODS: Subjects were women from the prospective study Pregnant Women in Iceland II (PREWICE II; n = 853) who attended their ultrasound appointment in gestational weeks 11-14 during the period from October 2017 to March 2018. During that visit, whole-grain consumption was estimated using a diet screening questionnaire, and blood samples were collected for analysis of plasma alkylresorcinols (ARs). Information on GDM diagnoses was later extracted from medical records. Multivariate log-binomial regression was used to evaluate the association of dietary whole-grain and AR concentrations with GDM. RESULTS: In total, 14.9% of the women adhered to the national food-based dietary guidelines (n = 127), which recommend 2 portions of whole grains daily. GDM was diagnosed in 127 women (14.9%). The frequency of whole-grain consumption was lower in women who were later diagnosed with GDM compared to the women without GDM (median, 5 times/week vs. 6 times/week, respectively; P = 0.02). This difference was reflected in the lower median concentration of total AR in women diagnosed with GDM (163 nmol/L vs. 209 nmol/L, respectively; P

Background Observational studies have shown that higher cereal fiber intake is associated with reduced type 2 diabetes risk. However, it remains uncertain whether this association is causal. Objective This study evaluated the feasibility of an intervention to increase cereal fiber intake in children using breakfast cereals. Methods The study was a 2-arm parallel group randomized controlled trial in 9–10-y-old children, who received free supplies of high-fiber breakfast cereals (g3.5 g/portion) or low-fiber breakfast cereals (l1.0 g/portion) to eat daily for 1 mo with behavioral support to promote adherence. Children provided baseline and 1-mo fasting blood samples, physical measurements, and 24-h dietary recalls. The primary outcome was the group difference in change in plasma total alkylresorcinol (AR) concentration; secondary outcomes were group differences in nutrient intakes and adiposity indices. Analyses (complete case and multiple imputation) were conducted by regressing the final AR concentration on baseline AR in models adjusted for sex, ethnicity, age, and school (random effect). Results Two-hundred seventy-two children were randomly assigned (137 receiving a low-fiber and 135 a high-fiber diet) and 193 (71%) provided fasting blood samples at baseline and follow-up. Among randomized participants, median (IQR) of baseline AR was 43.1 (24.6–85.5) nmol/L and of cereal fiber intake was 4.5 (2.7–6.4) g; 87% of participants reported consuming the cereal on most or all days. Compared with changes in the low-fiber group, the high-fiber group had greater increases in AR (40.7 nmol/L; 95% CI: 21.7, 59.8 nmol/L, P l 0.0001) and in reported cereal fiber intake (2.9g/d; 95% CI: 2.0, 3.7 g; P l 0.0001). There were no appreciable differences in other secondary outcomes. Conclusions We have developed a simple and acceptable nutritional intervention that increases markers of daily cereal fiber intake in children. This intervention could be used to test whether increases in cereal fiber intake in children might reduce insulin resistance. This trial was registered at www.isrctn.com as ISRCTN33260236.

Background/objectives Whole-grain (WG) intake has been associated with a lowered risk of developing type 2 diabetes, cardiovascular disease, and some cancers in epidemiological studies. Reduced subclinical inflammation could be one important mechanism behind such associations. This study investigated whether high long-term WG rye and wheat intakes were associated with lower concentrations of biomarkers of inflammation, endothelial function, and protein biomarkers associated with cardiovascular disease. Subjects/methods We assessed WG intake by food frequency questionnaire (FFQ) and by measuring alkylresorcinols (ARs) in plasma and adipose tissue, respectively. Selected biomarkers in free-living 109 women and 149 men were analyzed from two clinical subcohort studies (Swedish Mammography Cohort-Clinical (SMC-C) and Cohort of Swedish Men-Clinical (COSM-C), respectively. Total WG rye and wheat (WGRnW) and the ratio of WG rye to WG rye and wheat (WGR/WGRnW) were estimated from FFQs. ARs were measured in plasma and adipose tissue by gas chromatography-mass spectrometry (GC-MS) and the biomarkers by ELISA. Results We found no consistent associations between WG intake assessed by different methods and the selected biomarkers. However, WGRnW intake was inversely associated with cathepsin S (P-trend < 0.05) and total AR and C17:0/C21:0 in plasma were inversely associated with the endostatin concentration (P-trend < 0.05) adjusted for BMI, age, and sex. Conclusion The results give limited support to the hypothesis that a high WG wheat and rye intake is associated with lower concentrations of common biomarkers of inflammation and CVD that have previously been reported inversely associated with WG intake or an overall healthy lifestyle.

Rye consumption has shown beneficial effects on prostate cancer tumors, as indicated by slower initial tumor growth in animal models and lowering of prostate-specific antigen (PSA) in humans. This study evaluated the effects of whole grain/bran rye consumption on low-grade inflammation and endothelial function biomarkers in men with prostate cancer.Seventeen men with untreated, low-grade prostate cancer consumed 485 g rye whole grain and bran products (RP) per day or refined wheat products with added cellulose (WP) in a randomized crossover design. Fasting blood samples were taken before and after 2, 4, and 6 weeks of treatment.Concentrations of tumor nuclear factor-receptor 2 (TNF-R2), e-selectin, and endostatin were significantly lower after consumption of the RP diet compared with WP (p 0.05). Cathepsin S concentration was positively correlated to TNF-R2 and endostatin concentrations across all occasions. Strong correlations were consistently found between intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) and between interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1RA). No effect of intervention was found in 92 inflammation-related protein biomarkers measured in a proximity extension assay.RP diet lowered TNF-R2, e-selectin, and endostatin, compared with WP in men with prostate cancer. These effects were accompanied by a reduction in PSA.

Cereal grains are the main dietary source of energy, carbohydrates, and plant proteins world-wide. Currently, only 41% of grains are used for human consumption, and up to 35% are used for animal feed. Cereals have been overlooked as a source of environmentally sustainable and healthy plant proteins and could play a major role in transitioning towards a more sustainable food system for healthy diets. Cereal plant proteins are of good nutritional quality, but lysine is often the limiting amino acid. When consumed as whole grains, cereals provide health-protecting components such as dietary fiber and phytochemicals. Shifting grain use from feed to traditional foods and conceptually new foods and ingredients could improve protein security and alleviate climate change. Rapid development of new grain-based food ingredients and use of grains in new food contexts, such as dairy replacements and meat analogues, could accelerate the transition. This review discusses recent developments and outlines future perspectives for cereal grain use.

Background Bilberries from Sweden, rich in polyphenols, have shown cholesterol-lowering effects in small studies, and the cholesterol-lowering properties of oats, with abundant beta-glucans and potentially bioactive phytochemicals, are well established. Both may provide cardiometabolic benefits following acute myocardial infarction (AMI), but large studies of adequate statistical power and appropriate duration are needed to confirm clinically relevant treatment effects. No previous study has evaluated the potential additive or synergistic effects of bilberry combined with oats on cardiometabolic risk factors. Our primary objective is to assess cardioprotective effects of diet supplementation with dried bilberry or with bioprocessed oat bran, with a secondary explorative objective of assessing their combination, compared with a neutral isocaloric reference supplement, initiated within 5 days following percutaneous coronary intervention (PCI) for AMI. Methods The effects of Bilberry and Oat intake on lipids, inflammation and exercise capacity after Acute Myocardial Infarction (BIOAMI) trial is a double-blind, randomized, placebo-controlled clinical trial. A total of 900 patients will be randomized post-PCI to one of four dietary intervention arms. After randomization, subjects will receive beverages with bilberry powder (active), beverages with high-fiber bioprocessed oat bran (active), beverages with bilberry and oats combined (active), or reference beverages containing no active bilberry or active oats, for consumption twice daily during a 3-month intervention. The primary endpoint is the difference in LDL cholesterol change between the intervention groups after 3 months. The major secondary endpoint is exercise capacity at 3 months. Other secondary endpoints include plasma concentrations of biochemical markers of inflammation, metabolomics, and gut microbiota composition after 3 months. Discussion Controlling hyperlipidemia and inflammation is critical to preventing new cardiovascular events, but novel pharmacological treatments for these conditions are expensive and associated with negative side effects. If bilberry and/or oat, in addition to standard medical therapy, can lower LDL cholesterol and inflammation more than standard therapy alone, this could be a cost-effective and safe dietary strategy for secondary prevention after AMI. Trial registration ClinicalTrials.gov NCT03620266. Registered on August 8, 2018.

IntroductionFatty acid (FA) concentrations have previously been associated with gestational diabetes mellitus (GDM). However, few studies on GDM have examined FA profiles in early pregnancy or before diagnosis. This study aimed to compare early pregnancy plasma FA profiles of women with and without GDM diagnoses as well as their reported dietary consumption.Research design and methodsThe subjects comprised 853 women from the prospective study: Pregnant Women in Iceland II (PREWICE II), attending their 11–14 weeks ultrasound appointment in 2017–2018. During the visit, blood samples were collected for plasma FA analysis, and dietary habits were assessed using a short food frequency questionnaire. Information on GDM diagnoses was then later extracted from medical records. Differences in FA profile between GDM cases and non-cases were evaluated using the Mann-Whitney U test.ResultsGDM was diagnosed in 127 women (14.9%). Concentrations of saturated fatty acids, monounsaturated fatty acids, polyunsaturated fatty acids (PUFA) n-6, PUFA n-3 and total FA were higher in the women who later developed GDM compared with those who did not (p≤0.05). The medians for total FA were 2898 μg/mL for the women with GDM and 2681 μg/mL for those without GDM. Mean adjusted difference for total FA between the groups was 133 μg/mL (95% CI 33 to 233). Similar results were observed in prepregnancy normal-weight women and overweight women/women with obesity. Overall diet quality in early pregnancy appeared to be lower among the women later diagnosed with GDM.ConclusionWe found that plasma FA profiles in early pregnancy were different for women later diagnosed with GDM compared with those who were not, independent of the women’s body mass index.

There is conflicting evidence regarding the association between fish intake and type 2 diabetes (T2D) incidence, possibly owing to measurement errors in self-reported intake and coexposure to persistent organic pollutants (POPs) present in fish.The aim of this study was to identify plasma metabolites associated with fish intake and to assess their association with T2D risk, independently of POPs, in Swedish adults.In a case-control study nested in the Swedish Västerbotten Intervention Programme, fasting plasma samples from 421 matched T2D case-control pairs of men and women aged 30-60 y at baseline and 10-y follow-up samples from a subset of 149 pairs were analyzed using untargeted metabolomics. Moreover, 16 plasma POPs were analyzed for the 149 pairs who had repeated samples available. Fish-related plasma metabolites were identified using multivariate modelling and partial correlation analysis. Reproducibility of metabolites and metabolite patterns, derived via principal component analysis (PCA), was assessed by intraclass correlation. A unique component of metabolites unrelated to POPs was dissected by integrating metabolites and POPs using 2-way orthogonal partial least squares regression. ORs of T2D were estimated using conditional logistic regression.We identified 31 metabolites associated with fish intake that had poor to good reproducibility. A PCA-derived metabolite pattern strongly correlated with fish intake (ρ = 0.37, P 0.001) but showed no association with T2D risk. Integrating fish-related metabolites and POPs led to a unique metabolite component independent of POPs, which tended to be inversely associated with T2D risk (OR: 0.75; 95% CI: 0.54, 1.02, P = 0.07). This component mainly consisted of metabolites reflecting fatty fish intake.Our results suggest that fatty fish intake may be beneficial for T2D prevention, after removing the counteractive effects of coexposure to POPs in Swedish adults. Integrating metabolite markers and POP exposures appears a promising approach to advance the understanding of associations between fish intake and T2D incidence.

Motivation Validation of variable selection and predictive performance is crucial in construction of robust multivariate models that generalize well, minimize overfitting and facilitate interpretation of results. Inappropriate variable selection leads instead to selection bias, thereby increasing the risk of model overfitting and false positive discoveries. Although several algorithms exist to identify a minimal set of most informative variables (i.e. the minimal-optimal problem), few can select all variables related to the research question (i.e. the all-relevant problem). Robust algorithms combining identification of both minimal-optimal and all-relevant variables with proper cross-validation are urgently needed. Results We developed the MUVR algorithm to improve predictive performance and minimize overfitting and false positives in multivariate analysis. In the MUVR algorithm, minimal variable selection is achieved by performing recursive variable elimination in a repeated double cross-validation (rdCV) procedure. The algorithm supports partial least squares and random forest modelling, and simultaneously identifies minimal-optimal and all-relevant variable sets for regression, classification and multilevel analyses. Using three authentic omics datasets, MUVR yielded parsimonious models with minimal overfitting and improved model performance compared with state-of-the-art rdCV. Moreover, MUVR showed advantages over other variable selection algorithms, i.e. Boruta and VSURF, including simultaneous variable selection and validation scheme and wider applicability. Availability and implementation Algorithms, data, scripts and tutorial are open source and available as an R package (‘MUVR’) at https://gitlab.com/CarlBrunius/MUVR.git. Supplementary information Supplementary data are available at Bioinformatics online.

The epidemiological evidence regarding the association of coffee and tea consumption with prostate cancer risk is inconclusive, and few cohort studies have assessed these associations by disease stage and grade. We examined the associations of coffee (total, caffeinated and decaffeinated) and tea intake with prostate cancer risk in the European Prospective Investigation into Cancer and Nutrition. Among 142,196 men, 7,036 incident prostate cancer cases were diagnosed over 14 years of follow-up. Data on coffee and tea consumption were collected through validated country-specific food questionnaires at baseline. We used Cox proportional hazards regression models to compute hazard ratios (HRs) and 95% confidence intervals (CI). Models were stratified by center and age, and adjusted for anthropometric, lifestyle and dietary factors. Median coffee and tea intake were 375 and 106 mL/day, respectively, but large variations existed by country. Comparing the highest (median of 855 mL/day) versus lowest (median of 103 mL/day) consumers of coffee and tea (450 vs. 12 mL/day) the HRs were 1.02 (95% CI, 0.94–1.09) and 0.98 (95% CI, 0.90–1.07) for risk of total prostate cancer and 0.97 (95% CI, 0.79–1.21) and 0.89 (95% CI, 0.70–1.13) for risk of fatal disease, respectively. No evidence of association was seen for consumption of total, caffeinated or decaffeinated coffee or tea and risk of total prostate cancer or cancer by stage, grade or fatality in this large cohort. Further investigations are needed to clarify whether an association exists by different preparations or by concentrations and constituents of these beverages.

BackgroundColorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions.MethodsThe CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50–74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period.DiscussionThe CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome-based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high.Trial registrationClinicalTrials.govIdentifier:NCT01538550.

Background Irritable bowel syndrome (IBS) has been associated with diets rich in fermentable oligo-, di-, monosaccharides and polyols (FODMAPs), and gluten. Most previous studies have been single-blind and have focused on elimination of FODMAPs or provocation with single FODMAPs. The effect of gluten is unclear, large trials isolating the effect of gluten from that of FODMAPs are needed. Objective The aims of this study were to ensure high intakes of a wide range of FODMAPs, gluten, or placebo, and to evaluate the effects on IBS symptoms using the IBS severity scoring system (IBS-SSS). Methods The study was carried out with a double-blind, placebo-controlled, randomized three-way crossover design in a clinical facility in Uppsala in September 2018-June 2019. In all, 110 participants fulfilling the IBS Rome IV criteria, with moderate to severe IBS, were randomized; 103 (90 female, 13 male) completed the trial. Throughout, IBS participants maintained a diet with minimal FODMAP content and no gluten. Participants were block-randomized to one-week interventions with FODMAPs (50 g/day), gluten (17.3 g/day), or placebo, separated by one week washout. All participants who completed at least one intervention were included in the intention-to-treat analysis. Results In participants with IBS (n = 103), FODMAPs caused higher IBS-SSS scores (mean 240 [95% CI 222, 257]) than placebo (198 [180, 215]; 0.00056) or gluten (208 [190, 226]; P = 0.013); no differences were found between the placebo and gluten groups (P = 1.0). There were large inter-individual differences in IBS-SSS scores associated with treatment. No adverse events were reported. Conclusion In participants with IBS, FODMAPs had a modest effect on typical IBS symptoms, whereas gluten had no effect. The large inter-individual differences in responses to the interventions warrant further detailed studies to identify possible underlying causes and enable individual prediction of responses. Trial registration www.ClinicalTrials.gov (NCT03653689).

Background: High dietary fiber intake has been associated with reduced risk of Helicobacter pylori infection and co-morbidities such as gastric cancer but also with reduced risk of cardiovascular disease. It has been suggested that fermented rye could affect Helicobacter pylori bacterial load and that high- fiber rye may be superior to wheat for improvement of several cardiometabolic risk factors, but few long-term interventions with high fiber rye foods have been conducted.Objective: To examine the effect of high-fiber wholegrain rye foods with added fermented rye bran vs. refined wheat on Helicobacter pylori infection and cardiometabolic risk markers in a Chinese population with a low habitual consumption of high fiber cereal foods.Design: A parallel dietary intervention was set up and 182 normal- or overweight men and women were randomized to consume wholegrain rye products containing fermented rye bran (FRB) or refined wheat (RW) for 12 weeks. Anthropometric measurements, fasting blood sample collection and 13C-urea breath test (13C-UBT) were performed at baseline and after 6 and 12 weeks of intervention as well as 12 weeks after the end of the intervention.Results: No difference between diets on Helicobacter pylori bacterial load measured by 13C-UBT breath test or in virulence factors of Helicobacter pylori in blood samples were found. Low density lipoprotein cholesterol (LDL-C) and high sensitivity C-reactive protein (hs-CRP) were significantly lower in the FRB group, compared to the RW group after 12 weeks of intervention. The intervention diets did not affect markers of glucose metabolism or insulin sensitivity.Conclusions: While the results of the present study did not support any effect of FRB on Helicobacter pylori bacterial load, beneficial effects on LDL-C and hs-CRP were clearly shown. This suggest that consumption of high fiber rye foods instead of refined wheat could be one strategy for primary prevention of cardiovascular disease.Clinical Trial Registration: The trial was registered at www.clinicaltrials.gov, Identifier: NCT03103386.

Background and aim: A high intake of whole grain foods is inversely associated with body mass index (BMI) and body fat in observational studies, but mixed results have been found in interventional studies. Among whole grains, rye is the richest source of dietary fiber and meals containing high-fiber rye foods have shown increased satiety up to 8 h, compared to meals containing refined wheat products. The aim of the study was to determine the effect of consuming high fiber rye products, compared to refined wheat products, on body weight and body fat loss in the context of an energy restricted diet.Methods: After a 2-week run-in period, 242 males and females with overweight or obesity (BMI 27-35 kg/m(2)), aged 30-70 years, were randomized (1:1) to consume high fiber rye products or refined wheat products for 12 weeks, while adhering to a hypocaloric diet. At week 0, week 6 and week 12 body weight and body composition (dual energy x-ray absorptiometry) was measured and fasting blood samples were collected. Subjective appetite was evaluated for 14 h at week 0, 6 and 12.Results: After 12 weeks the participants in the rye group had lost 1.08 kg body weight and 0.54% body fat more than the wheat group (95% confidence interval (CI): 0.36; 1.80, p < 0.01 and 0.05; 1.03, p 1/4 0.03, respectively). C-reactive protein was 28% lower in the rye vs wheat group after 12 weeks of intervention (CI: 7; 53, p < 0.01). There were no consistent group differences on subjective appetite or on other cardiometabolic risk markers.Conclusion: Consumption of high fiber rye products as part of a hypocaloric diet for 12 weeks caused a greater weight loss and body fat loss, as well as reduction in C-reactive protein, compared to refined wheat. The difference in weight loss could not be linked to differences in appetite response. (C) 2021 The Author(s). Published by Elsevier Ltd on behalf of European Society for Clinical Nutrition and Metabolism.

BackgroundColorectal cancer (CRC) screening reduces CRC incidence and mortality. However, current screening methods are either hampered by invasiveness or suboptimal performance, limiting their effectiveness as primary screening methods. To aid in the development of a non-invasive screening test with improved sensitivity and specificity, we have initiated a prospective biomarker study (CRCbiome), nested within a large randomized CRC screening trial in Norway. We aim to develop a microbiome-based classification algorithm to identify advanced colorectal lesions in screening participants testing positive for an immunochemical fecal occult blood test (FIT). We will also examine interactions with host factors, diet, lifestyle and prescription drugs. The prospective nature of the study also enables the analysis of changes in the gut microbiome following the removal of precancerous lesions.MethodsThe CRCbiome study recruits participants enrolled in the Bowel Cancer Screening in Norway (BCSN) study, a randomized trial initiated in 2012 comparing once-only sigmoidoscopy to repeated biennial FIT, where women and men aged 50-74 years at study entry are invited to participate. Since 2017, participants randomized to FIT screening with a positive test result have been invited to join the CRCbiome study. Self-reported diet, lifestyle and demographic data are collected prior to colonoscopy after the positive FIT-test (baseline). Screening data, including colonoscopy findings are obtained from the BCSN database. Fecal samples for gut microbiome analyses are collected both before and 2 and 12 months after colonoscopy. Samples are analyzed using metagenome sequencing, with taxonomy profiles, and gene and pathway content as primary measures. CRCbiome data will also be linked to national registries to obtain information on prescription histories and cancer relevant outcomes occurring during the 10 year follow-up period.DiscussionThe CRCbiome study will increase our understanding of how the gut microbiome, in combination with lifestyle and environmental factors, influences the early stages of colorectal carcinogenesis. This knowledge will be crucial to develop microbiome- based screening tools for CRC. By evaluating biomarker performance in a screening setting, using samples from the target population, the generalizability of the findings to future screening cohorts is likely to be high.Trial RegistrationClinicalTrials.gov Identifier: NCT01538550

A vegetarian diet has been associated with a lower risk of coronary artery disease (CAD). Plasma triacylglycerols, ceramides, and phosphatidylcholines may improve prediction of recurrent coronary events. We sought to investigate effects of a lacto-ovo-vegetarian diet (VD) on plasma lipidome in CAD patients and simultaneously assess associations of plasma lipids with the extent of coronary atherosclerotic burden. We analyzed 214 plasma lipids within glycerolipid, sphingolipid, and sterol lipid classes using lipidomics from a randomized controlled, crossover trial comprising 31 CAD patients on standard medical therapy. Subjects completed a four-week intervention with VD and isocaloric meat diet (MD), separated by a four-week washout period. The VD increased levels of 11 triacylglycerols and lowered 7 triacylglycerols, 21 glycerophospholipids, cholesteryl ester (18:0), and ceramide (d18:1/16:0) compared with MD. VD increased triacylglycerols with long-chain polyunsaturated fatty acyls while decreased triacylglycerols with saturated fatty acyls, phosphatidylcholines, and sphingomyelins than MD. The Sullivan extent score (SES) exhibited on coronary angiograms were inversely associated with triacylglycerols with long-chain polyunsaturated fatty acyls. Phosphatidylcholines that were lower with VD were positively associated with SES and the total number of stenotic lesions. The VD favorably changed levels of several lipotoxic lipids that have previously been associated with increased risk of coronary events in CAD patients.

The performance of the human brain is based on an interplay between the inherited genotype and external environmental factors, including diet. Food and nutrition, essential in maintenance of brain performance, also aid in prevention and treatment of mental disorders. Both the overall composition of the human diet and specific dietary components have been shown to have an impact on brain function in various experimental models and epidemiological studies. This narrative review provides an overview of the role of diet in 5 key areas of brain function related to mental health and performance, including: (1) brain development, (2) signaling networks and neurotransmitters in the brain, (3) cognition and memory, (4) the balance between protein formation and degradation, and (5) deteriorative effects due to chronic inflammatory processes. Finally, the role of diet in epigenetic regulation of brain physiology is discussed.

BackgroundA vegetarian diet (VD) may reduce future cardiovascular risk in patients with ischemic heart disease.Methods and ResultsA randomized crossover study was conducted in subjects with ischemic heart disease, assigned to 4‐week intervention periods of isocaloric VD and meat diet (MD) with individually designed diet plans, separated by a 4‐week washout period. The primary outcome was difference in oxidized low‐density lipoprotein cholesterol (LDL‐C) between diets. Secondary outcomes were differences in cardiometabolic risk factors, quality of life, gut microbiota, fecal short‐chain and branched‐chain fatty acids, and plasma metabolome. Of 150 eligible patients, 31 (21%) agreed to participate, and 27 (87%) participants completed the study. Mean oxidized LDL‐C (−2.73 U/L), total cholesterol (−5.03 mg/dL), LDL‐C (−3.87 mg/dL), and body weight (−0.67 kg) were significantly lower with the VD than with the MD. Differences between VD and MD were observed in the relative abundance of several microbe genera within the families Ruminococcaceae, Lachnospiraceae, and Akkermansiaceae. Plasma metabolites, includingl‐carnitine, acylcarnitine metabolites, and phospholipids, differed in subjects consuming VD and MD. The effect on oxidized LDL‐C in response to the VD was associated with a baseline gut microbiota composition dominated by several genera of Ruminococcaceae.ConclusionsThe VD in conjunction with optimal medical therapy reduced levels of oxidized LDL‐C, improved cardiometabolic risk factors, and altered the relative abundance of gut microbes and plasma metabolites in patients with ischemic heart disease. Our results suggest that composition of the gut microbiota at baseline may be related to the reduction of oxidized LDL‐C observed with the VD.RegistrationURL:https://www.clini​caltr​ials.gov; Unique identifier: NCT02942628.

Adults with central adiposity and other features of the metabolic syndrome have a markedly elevated risk of developing type 2 diabetes (T2D) and cardiovascular disease (CVD). A Mediterranean-style healthy eating pattern (MED-HEP) and consumption of foods with a lower glycemic index (GI) are potential dietary approaches to curb the T2D and CVD epidemic. However, experimental evidence of the effectiveness of MED-HEP and of the contribution of GI towards improving indices of glucose homeostasis, especially among non-diabetic people, are lacking. Therefore, we developed the MedGI-Carb trial, a multi-center (Italy, Sweden, and United States) intervention in adults with at least two components of the metabolic syndrome (elevated waist circumference + one other component) that aims to improve markers of glucose homeostasis through dietary modification. All participants were randomized to consume an isocaloric high- or low-GI MED-HEP for 12 weeks. We hypothesized that indexes of insulinemia (primary outcome: postprandial insulin and glucose after standardized breakfast and lunch; secondary outcomes: fasting plasma glucose and insulin, HbA1c, 24-h continuous glucose monitoring) would be improved more with the low-GI versus the high-GI MED-HEP. Additionally, we hypothesized that consumption of a MED-HEP would improve other markers of cardiometabolic health and well-being (fasting blood pressure, fasting lipid profile, sleep quality, satiety, global metabolic alterations in the plasma metabolome, changes in the gut microbiota, subjective health and well-being), with no difference between groups. Collectively, the design of MEDGI-Carb allows several different research questions to be explored. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03410719.

Phytoestrogens may influence prostate cancer development. This study aimed to examine the association between prediagnostic circulating concentrations of isoflavones (genistein, daidzein, equol) and lignans (enterolactone and enterodiol) and the risk of prostate cancer. Individual participant data were available from seven prospective studies (two studies from Japan with 241 cases and 503 controls and five studies from Europe with 2,828 cases and 5,593 controls). Because of the large difference in circulating isoflavone concentrations between Japan and Europe, analyses of the associations of isoflavone concentrations and prostate cancer risk were evaluated separately. Prostate cancer risk by study-specific fourths of circulating concentrations of each phytoestrogen was estimated using multivariable-adjusted conditional logistic regression. In men from Japan, those with high compared to low circulating equol concentrations had a lower risk of prostate cancer (multivariable-adjusted OR for upper quartile [Q4] vs. Q1 = 0.61, 95% confidence interval [CI] = 0.39–0.97), although there was no significant trend (OR per 75 percentile increase = 0.69, 95 CI = 0.46–1.05, ptrend = 0.085); Genistein and daidzein concentrations were not significantly associated with risk (ORs for Q4 vs. Q1 = 0.70, 0.45–1.10 and 0.71, 0.45–1.12, respectively). In men from Europe, circulating concentrations of genistein, daidzein and equol were not associated with risk. Circulating lignan concentrations were not associated with the risk of prostate cancer, overall or by disease aggressiveness or time to diagnosis. There was no strong evidence that prediagnostic circulating concentrations of isoflavones or lignans are associated with prostate cancer risk, although further research is warranted in populations where isoflavone intakes are high.

BACKGROUND: Type 2 diabetes is a major health concern worldwide. Whole grains and cereal fiber may offer protective effects on type 2 diabetes risk. However, few studies have been conducted in cohorts with detailed information on whole-grain cereal intakes and product types and with wide ranges of intake.Objective: We investigated the associations between whole-grain intake, including intakes of different cereal types and products, and the risk of type 2 diabetes in a population with wide and diverse whole-grain intake.Methods: We used data from the Danish Diet, Cancer, and Health cohort including 55,465 participants aged 50-65 y at baseline. Of these, 7417 participants were diagnosed with type 2 diabetes during follow-up (median: 15 y). Detailed information on the intake of whole-grain products was available from a food-frequency questionnaire, and total whole-grain intake and whole-grain cereal types (wheat, rye, oats) were calculated in grams per day. Associations were examined by using Cox proportional hazards models with adjustment for potential confounders.Results: Whole-grain intake was associated with an 11% and 7% lower risk of type 2 diabetes per whole-grain serving (16 g) per day for men and women, respectively [HR (95% CI)-men: 0.89 (0.87, 0.91); women: 0.93 (0.91, 0.96)]. For men, the intake of all whole-grain cereal types investigated (wheat, rye, oats) was significantly associated with a lower risk of type 2 diabetes, but only wheat and oats intake was significantly associated for women. Among the different whole-grain products, rye bread, whole-grain bread, and oatmeal/muesli were significantly associated with a lower risk of type 2 diabetes for both men and women.Conclusions: In this cohort study, we found consistent associations between high whole-grain intake and lower risk of type 2 diabetes. Overall, an association was found for all different cereals and whole-grain products tested.

BACKGROUND: Epidemiologic evidence on the association of a healthy Nordic diet and future type 2 diabetes (T2D) is limited. Exploring metabolites as biomarkers of healthy Nordic dietary patterns may facilitate investigation of associations between such patterns and T2D. OBJECTIVES: We aimed to identify metabolites related to a priori-defined healthy Nordic dietary indexes, the Baltic Sea Diet Score (BSDS) and Healthy Nordic Food Index (HNFI), and evaluate associations with the T2D risk in a case-control study nested in a Swedish population-based prospective cohort. DESIGN: Plasma samples from 421 case-control pairs at baseline and samples from a subset of 151 healthy controls at a 10-y follow-up were analyzed with the use of untargeted liquid chromatography-mass spectrometry metabolomics. Index-related metabolites were identified through the use of random forest modelling followed by partial correlation analysis adjustment for lifestyle confounders. Metabolite patterns were derived via principal component analysis (PCA). ORs of T2D were estimated via conditional logistic regression. Reproducibility of metabolites was assessed by intraclass correlation (ICC) in healthy controls. Associations were also assessed for 10 metabolites previously identified as linking a healthy Nordic diet with T2D. RESULTS: In total, 31 metabolites were associated with BSDS and/or HNFI (−0.19 ≤ r ≤ 0.21, 0.10 ≤ ICC ≤ 0.59). Two PCs were determined from index-related metabolites: PC1 strongly correlated to the indexes (r = 0.27 for BSDS, r = 0.25 for HNFI, ICC = 0.45) but showed no association with T2D risk. PC2 was weakly associated with the indexes, but more strongly with foods not part of the indexes, e.g., pizza, sausages, and hamburgers. PC2 was also significantly associated with T2D risk. Predefined metabolites were confirmed to be reflective of consumption of whole grains, fish, or vegetables, but not related to T2D risk. CONCLUSIONS: Our study did not support an association between healthy Nordic dietary indexes and T2D. However, foods such as hamburger, sausage, and pizza not covered by the indexes appeared to be more important for T2D risk in the current population.

Sourdough fermentation is considered to have beneficial effects on postprandial satiety and metabolic responses, but studies demonstrating effects at physiological conditions are lacking. The aim of this acute breakfast intervention study was to determine the effect of consumption of sourdough-fermented and unfermented rye crispbread on self-rated appetite, postprandial glucose and insulin response in healthy subjects. In all, twenty-four Swedish adults were included in a single-blinded, randomised cross-over trial. Three crispbreads (sourdough-fermented and unfermented whole grain rye and yeast-fermented refined wheat as control) were consumed as part of a standardised breakfast. Subjective appetite score, assessed using visual analogue scale, and plasma glucose and insulin concentrations were measured at baseline and postprandially until 360 and 240 min, respectively. Structural changes and viscosity during mastication and gastric digestion were investigated usingin vitromethods. Hunger and desire to eat were lower (P

OBJECTIVES: Prostate cancer is a common cancer diagnosis among men, but the role of diet and food components remains controversial. Benzoxazinoids (BXs) is a potent group of bioactive compounds found in rye foods that seem to have the potential to inhibit prostate cancer growth in vitro but studies in humans are lacking. We therefore aimed to investigate the concentrations of different BXs and their metabolites after whole grain rye consumption in comparison to refined wheat and to correlate these compounds to PSA levels in men with indolent prostate cancer. METHODS: In a randomized controlled crossover study, men with prostate cancer (n = 24) consumed 485 gram of whole grain/bran rye and refined wheat foods for six weeks, with two weeks of washout in-between. The diets were isocaloric and contained the same amount of fiber by addition of cellulose in the refined wheat intervention. BXs in plasma samples were analyzed with HPLC- QTRAP/MS-ESI. RESULTS: Seventeen men finished the trial and were included in data analysis. For most BXs, the concentrations were significantly higher after the whole grain rye compared to the refined wheat intervention. The BXs or BXs metabolites HBOA-glc, HHPAA, HBOA-glcA, HPAA-glcA (∼19.4–0.4 nmol/L in plasma after interventions) were significantly inversely correlated to PSA level. CONCLUSIONS: In men with indolent prostate cancer, most BXs were significantly higher after an intervention with whole grain rye compared to refined wheat. The inverse correlation between four BXs or BXs metabolites and PSA may indicate on an inhibitory effect on prostate cancer cell growth. This could open for new preventive food-based strategies, but results would need to be replicated. FUNDING SOURCES: Independent Research Fund Denmark - Technology and Production Formas Swedish Research Council.

OBJECTIVES: Irritable bowel syndrome (IBS) symptoms have been associated with fermentable oligo-, di-, monosaccharides and polyols (FODMAPs) as well as gluten. We aimed to evaluate the effects of provocations with diets rich in such components on IBS symptoms. We further aimed to study effects of FODMAPs and gluten on microbiota and if the microbiota composition was related to the severity of IBS symptoms. METHODS: A double-blind, placebo-controlled, randomised three-way crossover design (n = 110) was conducted. From run-in and throughout the study, IBS subjects maintained a diet with minimal FODMAP content and no gluten. Participants were block-randomised to one-week interventions with FODMAPs (50 g/day), gluten (17.3 g/day) or placebo, separated by one week of wash-out. Fecal samples were collected after each study week and analyzed for gut microbiota composition by sequencing of 16S rRNA gene amplicons. IBS symptoms were monitored by the IBS severity scoring system (IBS-SSS). RESULTS: In subjects with moderate to severe IBS (n = 103), FODMAPs caused higher total IBS-SSS (mean [SE] = 240 [9]) than placebo (208 [9]; p = 0.00056) or gluten (198 [9]; p = 0.013), but with no difference between gluten and placebo (p = 1.0). Relative abundance of Anaerostipes, Bifidobacterium and Faecalibacterium were higher after FODMAP compared to placebo. We found no difference in gut microbiota composition between gluten and placebo and no significant correlations between genera and severity of IBS-SSS. CONCLUSIONS: In subjects with IBS, FODMAPs had an adverse but modest effect on typical IBS symptoms, whereas gluten had no effect. The microbiota composition was affected by the FODMAP but not the gluten intervention, in comparison to placebo. None of these differences were correlated to the severity of symptoms reflected in IBS-SSS, suggesting no apparent link between gut microbiota composition and IBS symptoms following intervention. FUNDING SOURCES: Formas and the Swedish Research Council.

OBJECTIVES: We hypothesize that individuals can be grouped into robust metabolic phenotypes (metabotypes) based on biochemical, anthropometric, gut microbial and metabolomics data and that such metabotypes will reflect differences in cardiometabolic disease risk and can act as targets for tailored nutritional prevention. We furthermore hypothesize that diet-gut microbiota interactions will be major determinants of the metabotypes. METHODS: Metabotyping is currently performed based on baseline data from 628 Danish adults from a validation sub-study of the Danish Diet Cancer and Health-Next Generation cohort. Participants were followed for one year, also providing data at 6 and 12 months. Dietary data was obtained by food frequency questionnaire and repeated 24h recalls and data on physical activity, smoking, sociodemographic factors, disease prevalence and use of medication was collected by questionnaires. Untargeted metabolomics and gut microbiota are currently determined. Metabotypes will be identified using clustering algorithms, variable optimization and data integration of the plasma metabolome, the 16S rRNA microbiota and 14 biochemical and anthropometric variables. Differences in habitual diet and physical activity across metabotypes will be determined as well as main metabotype determinants and potential plasma metabolite biomarkers. We will also assess the reproducibility of the metabotypes and biomarkers over time. RESULTS: Two clusters of individuals were identified by using the currently available clinical and anthropometric data. One of the clusters presented with mean values consistent with overweight, hypertension and dyslipidemia. Next, we will integrate the plasma metabolomics and gut microbial data into the analysis to determine the metabotypes. CONCLUSIONS: We have identified one higher risk group and one lower risk group for cardiometabolic disease and will identify and characterize metabotypes based on more extensive data. Future research will assess whether individuals belonging to different metabotypes respond differently to dietary interventions. FUNDING SOURCES: Formas, Sweden.

Purpose Rye products have been reported to elicit postprandial insulin and glucose responses which may be beneficial for prevention of type-2 diabetes. However, mechanisms underlying variations in responses related to processing techniques are not fully understood. Methods Five differently processed rye products (sourdough-fermented bread, fermented and unfermented crispbread, extrusion-cooked rye, and porridge) and refined wheat bread were characterised. Two in vitro methods, a dynamic method simulating digestion in the stomach and small intestine and a static method, simulating conditions in the stomach were used to determine viscosity development, structural changes and release of glucose during digestion. Results Structural and compositional differences induced by processing influenced product digestion. Gastric disintegration and digesta particle size were related to characteristics of the starch/protein matrix, while digesta viscosity was reduced due to fibre degradation during fermentation. More cohesive boluses were associated with slower glucose release. Sourdough fermentation increased amylose leakage and appeared to inhibit starch hydrolysis despite low digesta viscosity and rapid disintegration. Conclusions The net release of glucose during digestion of foods is determined by several factors which may vary in their importance depending on product specific properties.

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

BACKGROUND/OBJECTIVES: Whole grain intake has been associated with a small but significant lower body weight gain in observational studies, but there is limited knowledge about the associations with specific whole grain types. The objective was to investigate the association between whole grains, different sources of whole grains and biomarkers of whole grain intake (alkylresorcinols) in relation to subsequent changes in waist circumference (WC) and body weight.SUBJECTS/METHODS: Cohort study of 57 053 participants with baseline information on whole grain intake from questionnaires (FFQ) and biomarkers of whole grain rye and wheat intake, plasma alkylresorcinols, for a subset. WC and body weight were measured at baseline and again at follow-up. The associations were estimated using multiple linear regression analyses and logistic regression.RESULTS: For women, overall whole grain intake was not related to changes in WC or body weight. For men, total whole grain intake was associated with gains in WC (ΔWC per 25 g increment: 0.44 cm, 95% CI: 0.34 cm; 0.54 cm) and body weight (Δweight per 25 g increment: 150 g, 95% CI: 78 g; 222 g), but the results changed to null or changed direction when adjusting for baseline anthropometry. For the different sources of whole grains, rye (women) and crispbread was significantly associated with gains in WC and body weight. Plasma alkylresorcinol concentration was associated with reduced WC, but not body weight, for women (ΔWC per 50 nmol/l increment: -0.69 cm, 95% CI:-1.26 cm;-0.13 cm), but no association was found for men.CONCLUSIONS: Overall, no strong relationship between whole grain intake, measured from questionnaires or using biomarkers was found in relation to changes in body weight and WC.European Journal of Clinical Nutrition advance online publication, 8 February 2017; doi:10.1038/ejcn.2016.233.

Background A vegetarian diet (VD) in patients diagnosed with ischemic heart disease (IHD) may reduce future cardiovascular risk. Purpose The study hypothesis was that patients diagnosed with IHD can benefit from a VD assessed by multiple risk markers for this type of disease. Methods In a crossover study patients diagnosed with IHD, treated by percutaneous coronary intervention and on optimal medical therapy were randomly allocated to a 4-week intervention with ready-made (lunch and dinner) isocaloric VD or meat diet (MD). The primary outcome was change in oxidized low-density lipoprotein cholesterol (LDL-C) levels. Secondary outcomes were difference in changes of blood lipids, weight, body mass index (BMI), blood pressure, heart rate, glycated haemoglobin (HbA1c), number of participants reaching guideline target values, quality of life, gut microbiota, and trimethylamine N-oxide between the two interventions. Results 31 participants were recruited (median age: 67 years, male sex: 93.5%). Significant between-intervention differences (VD vs MD) were found in oxidized LDL-C (−2.73 U/L; p=0.015), total cholesterol (TC) (−0.13 mmol/L, p=0.01), LDL-C (−0.10 mmol/L; p=0.02), weight (−0.67 kg, p=0.008) and BMI (−0.21 kg/m2, p=0.009). After VD, numerically more subjects reached guideline LDL-C target values (87% vs 77%) but this did not reach statistical significance (p=0.07). During VD intervention the diet led to a significant reduction in oxidized LDL-C, TC, LDL-C, HDL-C, ApoB, and ApoB/ApoA1 ratio. Conclusions Our results suggest that in patients with IHD a VD compared to a MD, lowers oxidative stress, improves lipid profile and lowers BMI. Acknowledgement/Funding This study is partially funded by ALF and the Swedish Heart and Lung Foundation.

Abdominal obesity is associated with elevated postprandial triglycerides (TG), an independent risk factor for cardiovascular diseases. Previous studies show that whey protein (WP) and dietary fiber may separately reduce postprandial TG. However, few studies have investigated the long-term effects of WP and dietary fiber on postprandial TG. We aimed to investigate the separate and combined long-term effects of WP and dietary fiber from wheat bran on postprandial TG and markers of lipid metabolism in subjects with abdominal obesity. We conducted a 12-week, double-blind, randomized, controlled, parallel intervention study. In a 2 &times, 2 factorial design, 73 adults were randomized to receive 60 g/day of either WP hydrolysate or maltodextrin (MD) combined with high-fiber wheat bran products (HiFi, 30 g dietary fiber/day) or low-fiber refined wheat products (LoFi, 10 g dietary fiber/day). A high-fat meal test was conducted before and after the intervention. Sixty-five subjects were included in the final analyses. There were no differences between intervention groups in postprandial TG assessed as incremental area under the curve (iAUC). WP-LoFi had reduced postprandial TG assessed as total area under the curve (tAUC) and reduced fasting TG compared with all other groups, and reduced fasting apolipoprotein B-48 compared with MD-LoFi. There were no changes in lipoprotein lipase activity. Total cholesterol and apolipoprotein B-100 were reduced after WP intake compared with MD. Total cholesterol was increased after HiFi intake compared with LoFi. In conclusion, intake of WP in combination with low-fiber cereal products for 12 weeks had beneficial effects on postprandial TG tAUC and fasting TG, but not on postprandial TG iAUC in subjects with abdominal obesity. Combining WP with high-fiber wheat bran products did not improve lipid profile.

Lignans are diphenolic plant compounds with potential health modulating properties that are absorbed to the circulation and metabolized to the enterolignans enterodiol (END) and enterolactone (ENL) by gut microbiota. Epidemiological studies have inconsistently shown that a high lignan intake and circulating ENL are associated with reduced risk of breast‐, prostate‐, and colorectal cancer as well as cardiovascular disease and total and cause‐specific mortality. Inconsistencies can be due to interpersonal variation of ENL formation or responses. The aim of this review is to identify and evaluate the impact of factors influencing variability in plasma concentrations of the main enterolignan, ENL. The main determinants of plasma ENL concentrations are intake of lignan and lignan‐rich foods, composition and activity of intestinal microflora, antimicrobial use, nutrient intake, BMI, smoking, sex, and age. Composition and activity of the intestinal microbiota appear to be the most critical factor governing interpersonal variability in plasma ENL concentration followed by the use of antibiotics. Future studies with combined data from gut microbiota and metabolomics with food intake and life style data can be used to estimate the relative contribution of the different factors to ENL concentration in quantitative terms., Lignans are bioactive compounds from plants with potential health modulating properties. Plant lignans are absorbed or passed through the colon and metabolized to the enterolignans enterodiol (END) and enterolactone (ENL) by gut microbiota. Studies on the role of lignans in human health, and ENL in particular, have been inconsistent. One reason for inconsistency can be due to large interpersonal variability in the factors that affect lignan concentrations and their activity in vivo. The current study describes the most important factors that determine the plasma ENL concentrations as well as the most important sources of interpersonal variability.

Habitual coffee intake has been associated with a lower risk of developing type 2 diabetes (T2D), but few studies used biomarkers to reflect intake and investigated different coffee brews, that is boiled and filtered, separately.To identify plasma metabolites associated with boiled or filtered coffee intake and to examine their association with T2D risk in Swedish adults.In a case-control study nested within the Västerbotten Intervention Programme, baseline plasma samples from 421 case-control pairs and samples from a subset of 149 pairs at a 10-year follow-up were analysed using untargeted LC-MS metabolomics. We identified metabolites associated with food frequency questionnaires (FFQ)-estimated coffee intake and assessed odds ratios of T2D.In total, 24 and 32 metabolites were associated with boiled or filtered coffee intake. We determined robust metabolite panels for highly specific prediction of boiled or filtered coffee. We observed an inverse association between the metabolite panel of filtered coffee and T2D risk. No association with T2D was observed for the panel of boiled coffee intake. Similar results were observed for FFQ-estimated coffee intake.We identified plasma metabolites specifically associated with boiled or filtered coffee intake, which might be used as selective biomarkers. Our study supports a protective role of habitual intake of filtered coffee on T2D development. The lack of association for boiled coffee intake might be due to the lack of a protective effect of boiled coffee or due to the limited number of boiled coffee consumers in this population, but it warrants further investigation.

Whole grain rye (WGR) and whole grain wheat (WGW) have been suggested to protect against the development of breast cancer. In this study, we estimated long-term intake of WGR and WGW, using both a food frequency questionnaire (FFQ) and alkylresorcinol concentrations in adipose tissue biopsies, in relation to the risk of developing invasive breast cancer in a case-cohort study (n = 414 in the case group, n = 933 in the subcohort group) on the Danish &ldquo, Diet, Cancer and Health&rdquo, cohort. The median follow-up time of the subcohort was 5.3 years. Total WGR and WGW intake estimated with FFQ or reflected by total alkylresorcinol concentration in adipose tissue was not significantly associated with risk of breast cancer. However, after adjustment for total WGR and WGW intake, women in the highest quartile of relative WGR intake, reflected by the alkylresorcinol C17:0/C21:0 ratio, had a higher risk of overall breast cancer and estrogen-receptor-positive (ER+) breast cancer than women in the lowest quartile of relative WGR intake, while the risk of estrogen-receptor-negative (ER-) breast cancer incidence was unaffected. Similar results were obtained with the FFQ data. Based on these data, further investigation of the role of specific grain types in reducing or increasing breast cancer risk, and their overall impact on health, is warranted.

Background A healthy diet and optimal lifestyle choices are amongst the most important actions for the prevention of cardiometabolic diseases. Despite this, it appears difficult to convince consumers to select more nutritious foods. Furthermore, the development and production of healthier foods do not always lead to economic profits for the agro-food sector. Most dietary recommendations for the general population represent a “one-size-fits-all approach” which does not necessarily ensure that everyone has adequate exposure to health-promoting constituents of foods. Indeed, we now know that individuals show a high variability in responses when exposed to specific nutrients, foods, or diets. Purpose This review aims to highlight our current understanding of inter-individual variability in response to dietary bioactives, based on the integration of findings of the COST Action POSITIVe. We also evaluate opportunities for translation of scientific knowledge on inter-individual variability in response to dietary bioactives, once it becomes available, into practical applications for stakeholders, such as the agro-food industry. The potential impact from such applications will form an important impetus for the food industry to develop and market new high quality and healthy foods for specific groups of consumers in the future. This may contribute to a decrease in the burden of diet-related chronic diseases., Key messages Individual differences in ADME (Absorption, Digestion, Metabolism and Excretion) is believed to underpin much of the inter-individual variation in responses.Recent developments in the area of food metabolome databases and fast improvements in innovative metabotyping technologies hold great promise for improved profiling of dietary intake, exposure to individual ingredients, foods and dietary patterns, as well as our ability to identify individual responsiveness.The food industry needs well-defined population clusters or targets in order to be able to design “personalized products”.There are indeed excellent industrial opportunities for foods that modulate gut microbiota, and thereby enable the delivery of food bioactive metabolites.It is currently not clear whether knowledge on individual nutrient needs, based on genetic or metagenomic data, would affect long-term dietary and health behaviours.Data to support the development of dietary recommendations may need to be generated by new n-of-1-based study designs in the future.

Background A Web-based dietary assessment tool—RiksmatenFlex—was developed for the national dietary survey of adolescents in Sweden. Objective This study aimed to describe the Web-based method RiksmatenFlex and to test the validity of the reported dietary intake by comparing dietary intake with 24-hour dietary recalls (recall interviews), estimated energy expenditure, and biomarkers. Methods Adolescents aged 11-12, 14-15, and 17-18 years were recruited through schools. In total, 78 students had complete dietary information and were included in the study. Diet was reported a few weeks apart with either RiksmatenFlexDiet (the day before and a random later day) or recall interviews (face-to-face, a random day later by phone) in a cross-over, randomized design. At a school visit, weight and height were measured and blood samples were drawn for biomarker analyses. Students wore an accelerometer for 7 days for physical activity measurements. Dietary intake captured by both dietary methods was compared, and energy intake captured by both methods was compared with the accelerometer-estimated energy expenditure (EEest). Intake of whole grain wheat and rye and fruit and vegetables by both methods was compared with alkylresorcinol and carotenoid concentrations in plasma, respectively. Results The mean of the reported energy intake was 8.92 (SD 2.77) MJ by RiksmatenFlexDiet and 8.04 (SD 2.67) MJ by the recall interviews (P=.01). Intake of fruit and vegetables was 224 (169) g and 227 (150) g, and whole grain wheat and rye intake was 12.4 (SD 13.2) g and 12.0 (SD 13.1) g, respectively; the intakes of fruit and vegetables as well as whole grain wheat and rye did not differ between methods. Intraclass correlation coefficients ranged from 0.57 for protein and carbohydrates to 0.23 for vegetables. Energy intake by RiksmatenFlexDiet was overreported by 8% (P=.03) but not by the recall interviews (P=.53) compared with EEest. The Spearman correlation coefficient between reported energy intake and EEest was 0.34 (P=.008) for RiksmatenFlexDiet and 0.16 (P=.21) for the recall interviews. Spearman correlation coefficient between whole grain wheat and rye and plasma total alkylresorcinol homologs was 0.36 (P=.002) for RiksmatenFlexDiet and 0.29 (P=.02) for the recall interviews. Spearman correlations between intake of fruit and vegetables and plasma carotenoids were weak for both dietary tools. The strongest correlations were observed between fruit and vegetable intake and lutein/zeaxanthin for RiksmatenFlexDiet (0.46; P Conclusions RiksmatenFlexDiet provides information on energy, fruit, vegetables, and whole grain wheat and rye intake, which is comparable with intake obtained from recall interviews in Swedish adolescents. The results are promising for cost-effective dietary data collection in upcoming national dietary surveys and other studies in Sweden. Future research should focus on how, and if, new technological solutions could reduce dietary reporting biases.

Bilberries, Vaccinium myrtillus, have a high content of phenolic compounds including anthocyanins, which could provide cardiometabolic health benefits following acute myocardial infarction (AMI). We hypothesized that standard medical therapy supplemented with freeze-dried bilberry after AMI would have a more beneficial effect on cardiovascular risk markers and exercise capacity than medical therapy alone. Patients were allocated in a 1:1 ratio within 24 hours of percutaneous coronary intervention in an 8-week trial either to V myrtillus powder (40 g/d, equivalent to 480 g fresh bilberries) and standard medical therapy or to a control group receiving standard medical therapy alone. High-sensitivity C-reactive protein and exercise capacity measured with the 6-minute walk test were the primary biochemical and clinical end points, respectively. Fifty subjects completed the study. No statistically significant difference in high-sensitivity C-reactive protein was detected between groups. The mean 6-minute walk test distance increased significantly more in the bilberry group compared to the control group: mean difference 38 m at follow-up (95% confidence interval 14-62, P = .003). Ex vivo oxidized low-density lipoprotein was significantly lowered in the bilberry group compared to control, geometric mean ratio 0.80 (95% confidence interval 0.66-0.96, P = .017), whereas total cholesterol and low-density lipoprotein cholesterol did not differ significantly between groups. Anthocyanin-derived metabolites in blood increased significantly in the bilberry group during the intervention and were different after 8 weeks between the bilberry group and control. Findings in the present study suggest that bilberries may have clinically relevant beneficial effects following AMI; a larger, double-blind clinical trial is warranted to confirm this.

Background: A diet comprising low fiber intake, high consumption of red meat, and alcohol drinking, are all established risk factors for colorectal cancer (CRC). Identifying metabolic fingerprints associated with data-driven dietary patterns may provide insight into potential mechanisms linking diet and risk of CRC. Objective: The aim of this study was to first identify robust data-driven dietary factors derived from food frequency data and to assess their relationships with CRC risk. Second, to investigate plasma metabolic profiles in relation to CRC-associated diet factors. Methods: We used self-reported food frequency data and fasting plasma samples from 860 incident CRC cases (median 12 years from sampling to diagnosis) individually matched to controls by cohort, sex, age at diagnosis, year of blood draw and data collection (+/-1yr), fasting status and number of sample freeze thaw cycles from the population-based Northern Sweden Health and Disease Study (NSHDS). Diet factors were identified from combined exploratory/confirmatory factor analysis on random half-splits of the dietary data. Factors that appeared reproducible between repeated half-splits were retained, and their associations with CRC risk were assessed by multivariable conditional logistic regression, adjusted for age, BMI, smoking, physical activity, total energy intake, education and marital status. Factors associated with CRC risk were related to LC-MS metabolic profiles using random forest regression. Preliminary Results: We identified 12 dietary factors that were robustly associated with CRC risk: red meat, alcohol, snacks, fish, healthy breakfast, fast food, spread, full fat, low-fat, smoked fish/meat, vegetables, and an additional factor consisting of rice and fruit/syrup soup. Both alcohol (OR 1.16, 95% CI 1.00-1.34, p=0.047, fdr=0.283) and the healthy breakfast factor (OR 0.89, 95%CI 0.80-0.99, p=0.030, fdr=0.283) were associated with CRC in the adjusted model. Of these two factors, alcohol was also weakly associated with the metabolic profile (Q2=0.19). Conclusion: The data-driven factor analysis successfully identified dietary exposures, of which several corresponded to established CRC risk factors. Alcohol and healthy breakfast habits associated with CRC risk after adjustment for potential confounders. We also identified a metabolic profile in plasma potentially linked to alcohol consumption which merits further investigation. Citation Format: Stina Bodén, Rikard Landberg, Sophia Harlid, Ingegerd Johansson, Marc J. Gunter, Richard Palmqvist, Rui Zheng, Bethany Van Guelpen, Carl Brunius. Data-driven dietary patterns and their association with metabolic fingerprints and risk of colorectal cancer - a nested case-control study from Northern Sweden [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-156.

OBJECTIVES: A Mediterranean-style healthy eating pattern (MED-HEP) and consumption of foods with a lower glycemic index (GI) are potential dietary approaches to reduce the incidence of type 2 diabetes and cardiovascular disease. However, experimental evidence for the effectiveness of MED-HEP and firm evidence of the contribution of GI towards improving indices of cardiometabolic health are lacking. Therefore, the purpose of this study was to assess the effects of MED-HEPs differing in GI on cardiometabolic health indices. METHODS: Fifty-four subjects (33 F, 21 M; age 49 ± 11 y; BMI: 31.3 ± 3.1) completed the randomized, controlled MedGI-Carb Trial. All participants were randomized to consume either an energy-sufficient, isocaloric Low-GI or High-GI MED-HEP, differing only in the GI of half the carbohydrate-foods (CHO), for 12 weeks. Both groups consumed 270 g/d of metabolizable CHO; 135 g of CHO in the Low-GI group came from foods with GI values 70. All foods were provided to participants and consumed as part of a 7-day rotating menu. Higher or lower energy content was achieved through modulation of dietary fat and protein in the menus. Fasting plasma glucose, HbA1c, total cholesterol, triglycerides, HDL, LDL, systolic blood pressure (BP), and diastolic BP were assessed before and after the 12-week dietary intervention. Significance level was set at P

The coordination of EPIC is financially supported by the European Commission (DG-SANCO); and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer; Institut Gustave Roussy; Mutuelle Generale de l’Education Nationale; and Institut National de la Sante et de la Recherche Medicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum; and Federal Ministry of Education and Research (Germany); Hellenic Health Foundation; Stavros Niarchos Foundation; and the Hellenic Ministry of Health and Social Solidarity (Greece); Italian Association for Research on Cancer (AIRC); National Research Council; and Associazione Iblea per la Ricerca Epidemiologica (AIRE-ONLUS) Ragusa, Associazione Volontari Italiani Sangu (AVIS) Ragusa, Sicilian Government (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS); Netherlands Cancer Registry (NKR); LK Research Funds; Dutch Prevention Funds; Dutch ZON (Zorg Onderzoek Nederland); World Cancer Research Fund (WCRF); and Statistics Netherlands (the Netherlands); European Research Council (ERC) (grant number ERC-2009-AdG 232997) and Nordforsk; and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS); Regional Governments of Andalucia, Asturias, Basque Country, Murcia (No. 6236) and Navarra; and the Centro de Investigacion Biomedica en Red en Epidemiologia y Salud Publica and Instituto de Salud Carlos II (ISCIII RETIC) (RD06/0020) (Spain); Swedish Cancer Society; Swedish Scientific Council; and Regional Government of Skane and Vasterbotten (Sweden); Cancer Research UK; Medical Research Council; Stroke Association; British Heart Foundation; Department of Health; Food Standards Agency; and the Wellcome Trust (UK). Funding for the biomarker measurements in the random sub-cohort was provided by grants to EPIC-InterAct from the European Community Framework Programme 6 and to EPIC-Heart from the Medical Research Council and British Heart Foundation (Joint Award G0800270). We thank Nicola Kerrison (MRC Epidemiology Unit, Cambridge) for managing the data for the InterAct Project. Funding for the InterAct project was provided by the EU FP6 programme (grant number LSHM_CT_2006_037197). The work undertaken by David C Muller was done during the tenure of an IARC, Australia postdoctoral fellowship, supported by the Cancer Council Australia. Domenico Palli was supported by a grant from the Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Little is known regarding metabolic benefits of weight loss (WL) on the metabolically healthy obese (MHO) patients. We aimed to examine the impact of a lifestyle weight loss (LWL) treatment on the plasma metabolomic profile in MHO individuals. Plasma samples from 57 MHO women allocated to an intensive LWL treatment group (TG, hypocaloric Mediterranean diet and regular physical activity, n = 30) or to a control group (CG, general recommendations of a healthy diet and physical activity, n = 27) were analyzed using an untargeted 1H NMR metabolomics approach at baseline, after 3 months (intervention), and 12 months (follow-up). The impact of the LWL intervention on plasma metabolome was statistically significant at 3 months but not at follow-up and included higher levels of formate and phosphocreatine and lower levels of LDL/VLDL (signals) and trimethylamine in the TG. These metabolites were also correlated with WL. Higher myo-inositol, methylguanidine, and 3-hydroxybutyrate, and lower proline, were also found in the TG; higher levels of hippurate and asparagine, and lower levels of 2-hydroxybutyrate and creatine, were associated with WL. The current findings suggest that an intensive LWL treatment, and the consequent WL, leads to an improved plasma metabolic profile in MHO women through its impact on energy, amino acid, lipoprotein, and microbial metabolism. Keywords: NMR; hypocaloric diet; metabolically healthy obesity; metabolomics; physical activity.

Aims/hypothesis The aims of the present work were to identify plasma metabolites that predict future type 2 diabetes, to investigate the changes in identified metabolites among individuals who later did or did not develop type 2 diabetes over time, and to assess the extent to which inclusion of predictive metabolites could improve risk prediction. Methods We established a nested case–control study within the Swedish prospective population-based Västerbotten Intervention Programme cohort. Using untargeted liquid chromatography-MS metabolomics, we analysed plasma samples from 503 case–control pairs at baseline (a median time of 7 years prior to diagnosis) and samples from a subset of 187 case–control pairs at 10 years of follow-up. Discriminative metabolites between cases and controls at baseline were optimally selected using a multivariate data analysis pipeline adapted for large-scale metabolomics. Conditional logistic regression was used to assess associations between discriminative metabolites and future type 2 diabetes, adjusting for several known risk factors. Reproducibility of identified metabolites was estimated by intra-class correlation over the 10 year period among the subset of healthy participants; their systematic changes over time in relation to diagnosis among those who developed type 2 diabetes were investigated using mixed models. Risk prediction performance of models made from different predictors was evaluated using area under the receiver operating characteristic curve, discrimination improvement index and net reclassification index. Results We identified 46 predictive plasma metabolites of type 2 diabetes. Among novel findings, phosphatidylcholines (PCs) containing odd-chain fatty acids (C19:1 and C17:0) and 2-hydroxyethanesulfonate were associated with the likelihood of developing type 2 diabetes; we also confirmed previously identified predictive biomarkers. Identified metabolites strongly correlated with insulin resistance and/or beta cell dysfunction. Of 46 identified metabolites, 26 showed intermediate to high reproducibility among healthy individuals. Moreover, PCs with odd-chain fatty acids, branched-chain amino acids, 3-methyl-2-oxovaleric acid and glutamate changed over time along with disease progression among diabetes cases. Importantly, we found that a combination of five of the most robustly predictive metabolites significantly improved risk prediction if added to models with an a priori defined set of traditional risk factors, but only a marginal improvement was achieved when using models based on optimally selected traditional risk factors. Conclusions/interpretation Predictive metabolites may improve understanding of the pathophysiology of type 2 diabetes and reflect disease progression, but they provide limited incremental value in risk prediction beyond optimal use of traditional risk factors. Electronic supplementary material The online version of this article (10.1007/s00125-017-4521-y) contains peer-reviewed but unedited supplementary material, which is available to authorised users.

We recently showed that provision of Nordic school meals rich in fish, vegetables and potatoes and with reduced intakes of fat improved blood pressure, insulin resistance assessed by the homeostatic model (HOMA-IR), and plasma triacylglycerol despite increasing waist circumference in Danish 8-11-year-olds. This study explored whether intake or biomarkers of key dietary components in the schools meals were associated with these metabolic syndrome (MetS) markers during the 6-month intervention.Data from 7-day dietary records and measurements of whole-blood docosahexaenoic acid (DHA, 22:6n-3), blood pressure, fasting blood MetS markers, waist circumference and android/total fat mass assessed by dual-energy X-ray absorptiometry collected at baseline, 3 and 6 months from 523 children were analyzed in linear mixed-effects models adjusted for puberty, growth and fasting.After adjustment for multiple testing, whole-blood DHA was negatively associated with HOMA-IR (P 0.001) and triacylglycerol (P 0.0001). Potato intake was positively associated with waist circumference (P 0.01), but not with android/total fat mass (P = 0.94). Intakes of whole-grain as well as dietary fiber, protein and fat were not associated with any of the MetS markers.DHA in whole-blood, an indicator of DHA and fish intake, seemed to be the main diet-related predictor of the beneficial effects of the school meals on MetS markers. Increased potato intake was associated with increased waist circumference, but this may not only be due to an increase in abdominal fat, as no association was seen with fat distribution.