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In agricultural production, intercropping is a widely used system with many benefits. Lupin (Lupinus angustifolius L.) is a legume that contains a large variety of plant secondary metabolites, which have multiple functions in the plant, e.g. signalling, nodulation and stress response. An untargeted metabolomics approach was applied to investigate how the metabolome of lupin was affected by intercropped barley (Hordeum vulgare L.). The only primary metabolite of lupin affected by intercropping was tryptophan. Several secondary metabolites were affected by intercropping in lupin, and five flavonoids were annotated hereof. The flavonoid levels were increased, and tryptophan levels decreased in lupin when intercropped. Two flavonoids are prenylated, and prenylated flavonoids are believed to play a role in the plant's stress response. Furthermore, flavonoids are involved in plant defence and the nodulation process. Thus the present flavonoids may affect regulation of lupin N2-fixation activity. Highlights Intercropping caused a change in the secondary metabolites of Lupinus angustifolius L. Prenylated flavonoids were generated in Lupinus angustifolius L. as a response to intercropping Tryptophan was the only identified primary metabolite affected by intercropping [ABSTRACT FROM AUTHOR]

The D-enantiomers of L-amino acids are non-proteinogenic but widely present in foods. This is due to spontaneous racemization or processing, such as heating or alkali treatment, leading to substantial dietary exposure. Additional exposure to D-amino acids (D-AAs) comes from the human microbiota; D-AAs are present in bacterial surface proteoglycans, essential for bacterial competition and growth. Humans and other mammals have a complex set of genes for D-AA transport and degradation, and capacity to synthesize several D-AAs. Free D-AAs are present at low levels in human tissues and body fluids, yet they are apparently of considerable physiological and pathological importance. Amino acid transport regulates their presence and favors specific D-AAs, e.g. D-serine, D-aspartate, D-cysteine, and D-glutamate, over many others. Some of these D-AAs interact with the ubiquitous glutamate-gated Ca2+ channels, affecting signaling functions in most organs, especially the intestine, kidney, and brain. Consequently, the exposures, synthesis, local and systemic transport of D-AAs could be much more biologically important in humans than previously assumed, likely playing a role in gut-organ signaling and in many degenerative diseases. [ABSTRACT FROM AUTHOR]

Purpose: Epidemiological evidence suggests that coffee consumption is associated with a lower risk of type 2 diabetes. Coffee contains caffeine and several other components that may modulate glucose regulation. The chlorogenic acids (CGA) in coffee have been indicated as constituents that may help to normalize the acute glucose response after a carbohydrate challenge. The aim of this study was to investigate whether two coffee beverages that differ in CGA content due to different roasting degrees will differentially affect glucose regulation. Methods: In a controlled crossover trial, 11 healthy fasted volunteers consumed 300 mL of either light (LIR) or dark (DAR) roasted coffee, or water, followed 30 min later by a 75-g oral glucose tolerance test (OGTT). Blood samples were drawn at baseline, 30, 60, and 120 min. Differences in glucose and insulin responses and insulin sensitivity index (ISI) were analyzed. The CGA and caffeine contents in the coffees were analyzed using UPLC-MS/MS. Results: No differences in glucose area under the curve (AUC) were found between treatments. Glucose concentrations were higher at 60 min after ingestion of DAR compared with water, while ingestion of LIR showed similar glucose concentrations as ingestion of water. Insulin AUC was higher after ingestion of DAR compared with water, and both coffees raised insulin concentrations and reduced ISI compared with water, with no difference between the two coffees. Conclusion: Two coffees with different CGA contents did not differentially affect glucose or insulin responses during an OGTT, but both increased the insulin response compared with water. [ABSTRACT FROM AUTHOR]

Purpose: Fruit consumption is associated with a decreased risk of CVD in cohort studies and is therefore endorsed by health authorities as part of the ‘5 or more a day’ campaigns. A glass of fruit juice is generally counted as one serving. Fruit may cause protection by affecting common risk factors of CVD. Methods: Apples are among the most commonly consumed fruits and were chosen for a comprehensive 5 × 4 weeks dietary crossover study to assess the effects of whole apples (550 g/day), apple pomace (22 g/day), clear and cloudy apple juices (500 ml/day), or no supplement on lipoproteins and blood pressure in a group of 23 healthy volunteers. Results: The intervention significantly affected serum total and LDL-cholesterol. Trends towards a lower serum LDL-concentration were observed after whole apple (6.7 %), pomace (7.9 %) and cloudy juice (2.2 %) intake. On the other hand, LDL-cholesterol concentrations increased by 6.9 % with clear juice compared to whole apples and pomace. There was no effect on HDL-cholesterol, TAG, weight, waist-to-hip ratio, blood pressure, inflammation (hs-CRP), composition of the gut microbiota or markers of glucose metabolism (insulin, IGF1 and IGFBP3). Conclusions: Apples are rich in polyphenols and pectin, two potentially bioactive constituents; however, these constituents segregate differently during processing into juice products and clear juice is free of pectin and other cell wall components. We conclude that the fibre component is necessary for the cholesterol-lowering effect of apples in healthy humans and that clear apple juice may not be a suitable surrogate for the whole fruit in nutritional recommendations. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is one of the most common cancers in women. Evidence suggests that genetic variation in antioxidant enzymes could influence BC risk, but to date the relationship between selenoproteins and BC risk remains unclear. In this report, a study population including 975 Danish cases and 975 controls matched for age and hormone replacement therapy (HRT) use was genotyped for five functional single nucleotide polymorphisms (SNPs) in SEPP1, GPX1, GPX4 and the antioxidant enzyme SOD2 genes. The influence of genetic polymorphisms on breast cancer risk was assessed using conditional logistic regression. Additionally pre-diagnosis erythrocyte GPx (eGPx) activity was measured in a sub-group of the population. A 60% reduction in risk of developing overall BC and ductal BC was observed in women who were homozygous Thr carriers for SEPP1 rs3877899. Additionally, Leu carriers for GPX1 Pro198Leu polymorphism (rs1050450) were at ∼2 fold increased risk of developing a non-ductal BC. Pre-diagnosis eGPx activity was found to depend on genotype for rs713041 (GPX4), rs3877899 (SEPP1), and rs1050450 (GPX1) and on HRT use. Moreover, depending on genotype and HRT use, eGPx activity was significantly lower in women who developed BC later in life compared with controls. Furthermore, GPx1 protein levels increased in human breast adenocarcinoma MCF7 cells exposed to β-estradiol and sodium selenite.In conclusion, our data provide evidence that SNPs in SEPP1 and GPX1 modulate risk of BC and that eGPx activity is modified by SNPs in SEPP1, GPX4 and GPX1 and by estrogens. Our data thus suggest a role of selenoproteins in BC development. [ABSTRACT FROM AUTHOR]

ObjectiveTo describe the dietary composition of the New Nordic Diet (NND) and to compare it with the Nordic Nutrition Recommendations (NNR)/Danish Food-based Dietary Guidelines (DFDG) and with the average Danish diet.DesignDietary components with clear health-promoting properties included in the DFDG were included in the NND in amounts at least equivalent to those prescribed by the DFDG. The quantities of the other dietary components in the NND were based on scientific arguments for their potential health-promoting properties together with considerations of acceptability, toxicological concerns, availability and the environment. Calculations were conducted for quantifying the dietary and nutrient composition of the NND.SettingDenmark.SubjectsNone.ResultsThe NND is characterized by a high content of fruits and vegetables (especially berries, cabbages, root vegetables and legumes), fresh herbs, potatoes, plants and mushrooms from the wild countryside, whole grains, nuts, fish and shellfish, seaweed, free-range livestock (including pigs and poultry) and game. Overall, the average daily intakes of macro- and micronutrients in the NND meet the NNR with small adjustments based on evidence of their health-promoting properties.ConclusionsThe NND is a prototype regional diet that takes palatability, health, food culture and the environment into consideration. Regionally appropriate healthy diets could be created on similar principles anywhere in the world. [ABSTRACT FROM AUTHOR]

Abstract: Clotting and anticoagulation of blood samples may give rise to different metabolic profiles of serum and plasma samples, respectively. The anticoagulant used for blood plasma preparation may affect the resulting metabolic profile due to different mechanisms involved in anticoagulation by various agents, e.g. heparin, EDTA and citrate. In the present study, we looked into metabolite and other differences in matched serum and plasma samples and different plasma preparations by using untargeted UPLC-ESI-QTOF/MS profiling and multivariate data analysis (PCA and OPLS-DA). Metabolite differences between serum and plasma samples were mainly related to small peptides reflecting presence or absence of coagulation. Only subtle metabolite differences between the different plasma preparations were noticed, which were primarily related to ion suppression or enhancement caused by citrate and EDTA anticoagulants. For the first time, we also report that anticoagulant counter cation (Na+ or K+) in Na-citrate and K-EDTA plasma can make some metabolites more dominant in ESI-MS. Polymeric material residues originating from blood collection tubes for serum preparation were observed only in serum samples. Hypoxanthine and xanthine were found at higher levels in serum than in plasma samples, possibly due to release from the clot. Mass spectral features of sodium formate and potassium formate ion clusters were detected in citrate and EDTA plasma samples, respectively, originating from formate in mobile phase and Na+ (in Na-citrate tubes) and K+ (in K-EDTA tubes). Among the anticoagulants, heparin is recommended for plasma samples used for LC-ESI/MS-based metabolomics of hydrophilic compounds because no plasma interferences or matrix effects were noticed for this polarity range. Citrate and EDTA should be avoided since interferences and serious matrix effects were encountered on some co-eluting polar metabolites. Serum is recommended as a second choice and an alternative to plasma. In conclusion, heparin plasma or serum should be the order of best choice for LC-ESI/MS-based metabolomics research. [Copyright &y& Elsevier]

Abstract: One of the dietary components in the New Nordic Diet, is plants from the wild countryside. However, these may have a high content of bioactive components, some of which could be toxic in larger quantities. The objective of this paper is to outline a strategy for safety evaluation of wild plants not covered in current food compositional databases and to apply the method for selected plants used in the New Nordic Diet recipes. Four examples of typical wild edible plants were evaluated (stinging nettle, sorrel, chickweed and common lambsquarters), and based on substantial equivalence with known food plants the majority of the bioactive components reported were within the range experienced when eating or drinking typical food stuffs. For most compounds the hazards could be evaluated as minor. The only precaution found was for common lambsquarters because of its presumed high level of oxalic acid. It is concluded that a substance-by-substance evaluation of intake by equivalence to common foods is a useful and efficient strategy to evaluate the safety of newly introduced wild edible plants. Further evaluation and better compositional analyses are warranted before a daily consumption of significant amounts of wild edible plants can be generally regarded as safe. [Copyright &y& Elsevier]

Information on the 2011 Metabomeeting held September 25-28 in Helsinki Congress Paasitorni in Finland is presented. Topics being presented include applied metabolomics in human health and nutrition, analytical advances in metabolomics, and applied metabolomics in plants. Presenters being featured include Asaph Aharoni of Weizmann Institute of Science, Reijo Laaksonen of Zora Biosciences, and Sahar Hassani of Nofima Mat.

Abstract: Objective dietary intake markers for meat would be useful to assess meat intake in observational studies and as compliance markers in dietary intervention studies. A number of compounds are specific to meat compared with most other dietary items but there is some overlap between protein rich foods. A number of single compounds have been analysed in urine, plasma, serum or hair samples in studies of their relationship to meat or total protein intake. Among potential markers of dietary meat intake are urea, creatine, creatinine, carnitine, carnosine, anserine, ophidine, 1- and 3-methylhistidine, and sulphate or sulphite. Anserine and 1-methylhistidine come close to being meat-specific markers but true quantitative biomarker may not exist. Modern profiling techniques are increasingly used to look for useful biomarkers or for constructing them from latent information in complex profiles. Metabolomics by NMR spectroscopy of urine has also been applied to search for meat intake markers. Studies on single compounds or metabolomics markers are shortly reviewed here. [Copyright &y& Elsevier]

Abstract: The efficacy and safety of bioactive compounds depend on a few known and unknown parameters. What is a physiologic dose and how can that dose be defined in cases of bioactive compounds with a poor knowledge of supply and distribution? What safety sets are needed? How can individual aspects such as polymorphisms or differences in absorption be considered? A group of experts tried to answer these and related questions during the 23rd Hohenheim Consensus Meeting at the University of Hohenheim in Stuttgart. [Copyright &y& Elsevier]

Abstract: Biomarkers and their role in evaluating efficacy and safety were the topic of the 23rd Hohenheim Consensus Meeting at the University of Hohenheim in Stuttgart. Scientists who had published and reviewed scientific and regulatory papers on the topic were invited, among them basic researchers, toxicologists, clinicians, and nutritionists. The participants were presented with 11 questions (in bold font), which were discussed and answered (in italic font) at the workshop, with the aim of summarizing the current state of knowledge on the subject. The explicatory text accompanying the short answers was produced and agreed on after the conference and was backed up by corresponding references. [Copyright &y& Elsevier]

Since antioxidant vitamins may affect an organism’s capacity for defence against reactive oxygen species, biological markers of the dietary exposure to these vitamins is of importance. There is also a need of effect biomarkers for determining the ability of these and other antioxidants to increase the overall antioxidant capacity and decrease the oxidative damage occurring in biological samples. This review is concerned with exposure markers and markers of lipid- or protein damage following intervention with vitamins A, C and E. While there are several high quality exposure markers available it is not possible to identify functional markers of lipid or protein oxidation, which respond reliably to human dietary intervention with vitamins A, C or E. [ABSTRACT FROM AUTHOR]

At the present time the recommended daily intake or allowance (RDA) and the safe upper level (UL) of intake of micronutrients are given as single values. The recommended daily intake is considered to cover the requirements of 97.5% of the population while the safe upper level is a value for the whole population. These values provide only limited guidance to risk managers. A method has been developed recently which models the relationships between intake and risks of either deficiency or excess using an observed incidence for each effect and population distribution characteristics. Using this model it is possible to formulate advice to risk managers on the incidence (prevalence) of adverse effects, due to either deficiency or excess, at different levels of intake. Application of the model to the data used to derive the RDA and UL for selenium shows that it can predict the impact of changes in nutrient intake on the balance between benefit (absence of deficiency) and risk (development of toxicity). Application of the model has illustrated the utility of this approach, but highlighted the need for a comprehensive evaluation of the data and a critical appraisal of the validity of the relationships that are analyzed. In addition, the derived incidences will usually relate to effects with different biological or health impacts, so that the final balance between benefit and risk should be developed by a dialogue between the risk assessor and the risk manager. [ABSTRACT FROM AUTHOR]

The purpose of the present study was to compare the effect of sucrose and cornstarch on colon and liver carcinogenesis induced by 0.02% of the food-borne carcinogen 2-amino-3-methylimidazo [4,5-f]quinoline (IQ) in the feed. Male F344 rats were allocated to four groups. Two groups were fed diets high in either cornstarch (68%) or sucrose (34% sucrose/34% cornstarch) and were initiated with IQ. The remaining two groups received the same two diets but did not receive any IQ.In both liver and colon, administration of IQ resulted in a higher level of DNA adducts. In animals not dosed with IQ, sucrose increased the adduct level in both organs but to a lower level than IQ. However, simultaneous administration of IQ and sucrose did not further increase the adduct level. Both IQ and sucrose increased the expression of the DNA-repair enzyme ERCC1 in the liver. In the colon, the number of large and medium aberrant crypt foci (ACF) of the group fed IQ and cornstarch was significantly higher than that in the other groups. There was no statistically significant difference in any tumour incidence in IQ dosed-animals fed either cornstarch or sucrose. In conclusion, no difference in effect on liver carcinogenesis was seen between sucrose and cornstarch-based diets, however, the number of tumours per animal tended to be slightly higher in the rats fed cornstarch (P=0.08). Cornstarch enhanced ACF development induced by IQ when compared to sucrose whereas due to a low intestinal tumour incidence no correlation to diet and tumour incidence could be established. [Copyright &y& Elsevier]

Background: Pancreatic cancer is a highly deadly disease with a poor prognosis. There is limited knowledge about prevention of the disease; thus, identification of risk factors is important to reduce the disease incidence.Objective: The aim of the present study was to prospectively investigate associations between incidence of pancreatic cancer and whole-grain intake measured in 2 ways: as whole-grain product intake (g whole-grain products/d) and as whole-grain intake (grams of whole grains/d). Moreover, the intake of subgroups of these was also investigated: whole-grain products (rye bread, whole-grain bread, and oatmeal/muesli) and cereals (rye, wheat, and oats).Methods: In total, 55,995 Danish adults aged 50-64 y, of whom 446 developed pancreatic cancer (17.5 y mean follow-up), were included in the study. Detailed information on daily intake of whole-grain products was available from a validated self-administered FFQ, and intake of whole-grain cereals (wheat, rye, and oats) was estimated using information from a 24-h dietary recall. The association between the whole-grain exposures and incidence of pancreatic cancer was investigated by Cox regression analyses adjusted for potential confounders.Results: Total whole-grain product intake was associated with a 7% lower incidence of pancreatic cancer per serving (50 g/d) (HR: 0.93; 95% CI: 0.86, 1.00), and in the sex-specific analyses, an inverse association was found only in men. No association was found for total whole-grain intake (per 16-g serving size; HR: 0.96; 95% CI: 0.89, 1.03). When investigating specific whole-grain products and cereals individually, none were alone associated with lower incidence of pancreatic cancer.Conclusion: Our findings indicate that intake of whole grains is associated with lower risk of pancreatic cancer in middle-aged men. Consuming ample amounts of whole grains may prove beneficial in terms of lowering pancreatic cancer risk. [ABSTRACT FROM AUTHOR]

Highlights • Crude extract of brown seaweed of Undaria pinnatifida could be a source of α-glucosidase activity inhibitor. • Fucoxanthin from Undaria pinnatifida is a bioactive compound responsible for the inhibition of α-glucosidase activity. • Fucoxanthin inhibits α-glucosidase activity through mixed type of inhibition. Abstract A 5 mg/mL solution of water, methanol and acetone extracts of seaweeds were used for α-glucosidase inhibition assay hyphenated with high performance liquid chromatography–mass spectrometry (HPLC–HRMS). The results showed acetone extracts of Undaria pinnatifida has the strongest inhibitory effect against α-glucosidase activity with IC 50 0.08 ± 0.002 mg/mL. The active compound found in Undaria pinnatifida was identified as fucoxanthin. Analytical standard sample of fucoxanthin significantly inhibited α-glucosidase with IC 50 value 0.047 ± 0.001 mg/mL. An inhibition kinetics study indicates that fucoxanthin is showing mixed-type inhibition. These results suggest that Undaria pinnatifida has a potential to inhibit α-glucosidase and may be used as a bioactive food ingredient for glycaemic control. [ABSTRACT FROM AUTHOR]

Introduction: Uzbekistan is one of the countries with the highest number of diet-related chronic diseases, which is believed to be associated with high animal fat intake. Sheep meat is high in fats (~ 5% in muscle), including saturated and monounsaturated fatty acids, and it contains nearly twice the higher amounts of n-3 polyunsaturated fatty acids and conjugated linoleic acids compared to beef. Nevertheless, sheep meat is considered health promoting by the locals in Uzbekistan and it accounts for around 1/3 of red meat intake in the country. Objectives: The aim of this study was to apply a metabolomics approach to investigate if sheep meat intake frequency (SMIF) is associated with alterations in fasting blood plasma metabolites and lipoproteins in healthy Uzbek adults. Methods: The study included 263 subjects, 149 females and 114 males. For each subject a food intake questionnaire, including SMIF, was recorded and fasting blood plasma samples were collected for metabolomics. Blood plasma metabolites and lipoprotein concentrations were determined using 1H NMR spectroscopy. Results and Conclusion: The results showed that SMIF was confounded by nationality, sex, body mass index (BMI), age, intake frequency of total meat and fish in ascending order (p < 0.01). Multivariate and univariate data analyses showed differences in the levels of plasma metabolites and lipoproteins with respect to SMIF. The effect of SMIF after statistical adjustment by nationality, sex, BMI, age, intake frequency of total meat and fish decreased but remained significant. Pyruvic acid, phenylalanine, ornithine, and acetic acid remained significantly lower in the high SMIF group, whereas choline, asparagine, and dimethylglycine showed an increasing trend. Levels of cholesterol, apolipoprotein A1, as well as low- and high-density lipoprotein subfractions all displayed a decreasing trend with increased SMIF although the difference were not significant after FDR correction. [ABSTRACT FROM AUTHOR]

Edible seaweeds are valuable because of their organoleptic properties and complex polysaccharide content. A study was conducted to investigate the potential of dried edible seaweed extracts, its potential phenolic compounds and alginates for α-amylase inhibitory effects. The kinetics of inhibition was assessed in comparison with acarbose. The methanol extract of Laminaria digitata and the acetone extract of Undaria pinnatifida showed inhibitory activity against α-amylase, IC 50 0.74 ± 0.02 mg/ml and 0.81 ± 0.03 mg/ml, respectively; both showed mixed-type inhibition. Phenolic compound, 2,5-dihydroxybenzoic acid was found to be a potent inhibitor of α-amylase with an IC 50 value of 0.046 ± 0.004 mg/ml. Alginates found in brown seaweeds appeared to be potent inhibitors of α-amylase activity with an IC 50 of (0.075 ± 0.010–0.103 ± 0.017) mg/ml, also a mixed-type inhibition. Overall, the findings provide information that crude extracts of brown edible seaweeds, phenolic compounds and alginates are potent α-amylase inhibitors, thereby potentially retarding glucose liberation from starches and alleviation of postprandial hyperglycaemia. [ABSTRACT FROM AUTHOR]

Dark green leafy vegetables are primary food sources for lutein and β-carotene, however these bioactives have low bioavailability. The effects of mechanical and thermal processing as well as fat addition and fat type on lutein and β-carotene liberation and in vitro accessibility from spinach were investigated. Lutein liberation and in vitro accessibility were three-fold higher from spinach puree compared to whole leaves. Results for β-carotene liberation were similar, whereas that of β-carotene accessibility was only about two-fold. Steaming had no or a negative effect on carotenoid liberation. Fat addition increased β-carotene liberation from raw and steamed puree, but reduced lutein liberation from steamed leaves and raw puree. Fat types affected β-carotene differently. Butter addition led to a 2.5 fold increased liberation from raw spinach puree, while the effect of olive and peanut oil was significantly lower, but only minor effects were observed for lutein. [ABSTRACT FROM AUTHOR]

Green-leafy vegetables are rich in nutritionally important constituents including carotenoids. Their potential health benefits depend among others on their liberation from the plant matrix. The aim of the present study was to evaluate the effect of particle size and heat treatments on lutein and β-carotene liberation from spinach and Asia salads by applying an in vitro digestion protocol and UHPLC analysis. Reduction of particle size resulted in a three- to fourfold increase in liberation of lutein and β-carotene when comparing whole leaf and puree preparations of spinach. However, this positive effect was shown to be nullified by the severe heat impact during stir-frying of minced spinach, showing that domestic treatments need to be chosen carefully to maximise carotenoid liberation. Steaming significantly improved lutein liberation from Asia salads, but had no or a negative effect in spinach samples, possibly due to differences in liberation or degradation between the two plant matrices. [ABSTRACT FROM AUTHOR]

Purpose: Replacing saturated fatty acids (SFA) with polyunsaturated fatty acids (PUFA) is associated with a reduced risk of cardiovascular disease. Yet, the changes in the serum metabolome after this replacement is not well known. Therefore, the present study aims to identify the metabolites differentiating diets where six energy percentage SFA is replaced with PUFA and to elucidate the association of dietary metabolites with cardiometabolic risk markers. Methods: In an 8-week, double-blind, randomized, controlled trial, 99 moderately hyper-cholesterolemic adults (25–70 years) were assigned to a control diet (C-diet) or an experimental diet (Ex-diet). Both groups received commercially available food items with different fatty acid compositions. In the Ex-diet group, products were given where SFA was replaced mostly with n-6 PUFA. Fasting serum samples were analysed by untargeted ultra-performance liquid chromatography high-resolution mass spectrometry (UPLC-HRMS). Pre-processed data were analysed by double cross-validated Partial Least-Squares Discriminant Analysis (PLS-DA) to detect features differentiating the two diet groups. Results: PLS-DA differentiated the metabolic profiles of the Ex-diet and the C-diet groups with an area under the curve of 0.83. The Ex-diet group showed higher levels of unsaturated phosphatidylcholine plasmalogens, an unsaturated acylcarnitine, and a secondary bile acid. The C-diet group was characterized by odd-numbered phospholipids and a saturated acylcarnitine. The Principal Component analysis scores of the serum metabolic profiles characterizing the diets were significantly associated with low-density lipoprotein cholesterol, total cholesterol, and triglyceride levels but not with glycaemia. Conclusion: The serum metabolic profiles confirmed the compliance of the participants based on their diet-specific metabolome after replacing SFA with mostly n-6 PUFA. The participants' metabolic profiles in response to the change in diet were associated with cardiovascular disease risk markers. This study was registered at clinicaltrials.gov as NCT 01679496 on September 6th 2012. [ABSTRACT FROM AUTHOR]

Context Moderate alcohol consumption is associated with decreased risk of cardiovascular disease (CVD) and improvement in cardiovascular risk markers, including lipoproteins and lipoprotein subfractions. Objective To systematically review the relationship between moderate alcohol intake, lipoprotein subfractions, and related mechanisms. Data sources Following PRISMA, all human and ex vivo studies with an alcohol intake up to 60 g/d were included from 8 databases. Data extraction A total of 17 478 studies were screened, and data were extracted from 37 intervention and 77 observational studies. Results Alcohol intake was positively associated with all HDL subfractions. A few studies found lower levels of small LDLs, increased average LDL particle size, and nonlinear relationships to apolipoprotein B–containing lipoproteins. Cholesterol efflux capacity and paraoxonase activity were consistently increased. Several studies had unclear or high risk of bias, and heterogeneous laboratory methods restricted comparability between studies. Conclusions Up to 60 g/d alcohol can cause changes in lipoprotein subfractions and related mechanisms that could influence cardiovascular health. Systematic Review Registration PROSPERO registration no. 98955 [ABSTRACT FROM AUTHOR]

In this paper, we describe data processing and metabolite identification approaches which lead to a rapid and semi-automated interpretation of metabolomics experiments. Data from metabolite fingerprinting using LC-ESI-Q-TOF/MS were processed with several open-source software packages, including XCMS and CAMERA to detect features and group features into compound spectra. Next, we describe the automatic scheduling of tandem mass spectrometry (MS) acquisitions to acquire a large number of MS/MS spectra, and the subsequent processing and computer-assisted annotation towards identification using the R packages MetShot, Rdisop, and the MetFusion application. We also implement a simple retention time prediction model using predicted lipophilicity log D, which predicts retention times within 42 s (6 min gradient) for most compounds in our setup. We putatively identified 44 common metabolites including several amino acids and phospholipids at metabolomics standards initiative (MSI) levels two and three and confirmed the majority of them by comparison with authentic standards at MSI level one. To aid both data integration within and data sharing between laboratories, we integrated data from two labs and mapped retention times between the chromatographic systems. Despite the different MS instrumentation and different chromatographic gradient programs, the mapped retention times agree within 26 s (20 min gradient) for 90 % of the mapped features. [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

Abstract: This work describes an analytical platform based on a high-resolution α-glucosidase inhibition assay in combination with hyphenation of high-performance liquid chromatography, solid-phase extraction, and tube-transfer nuclear magnetic resonance spectroscopy, i.e., HPLC-SPE-ttNMR/high-resolution α-glucosidase assay. The platform enables fast screening for individual α-glucosidase inhibitory analytes in complex matrices, followed by structural identification targeted these α-glucosidase inhibitors, as demonstrated by a proof-of-concept study with extract of ‘Pink Lady’ apple peel. A scout-separation produced a high-resolution biochromatogram and a HPLC chromatogram, which were used for pinpointing HPLC peaks displaying α-glucosidase inhibition. Active analytes were cumulatively trapped on SPE cartridges and the structures identified by 1H NMR experiments obtained in the HPLC-SPE-ttNMR mode. (−)-Epicatechin (1), reynoutrin (3) and avicularin (4) were identified as active compounds. IC50 of the active compounds were determined along with six structurally related compounds. Quercetin was the most potent inhibitor with an IC50 of 8.1±0.4μM. The platform proved to be an efficient method for the identification of α-glucosidase inhibitors. [Copyright &y& Elsevier]

Advanced glycation endproducts (AGEs) are formed when sugars react with peptides and proteins without the help of enzymes and by thermal processing of food such as baking and frying. AGEs and especially Nϵ-(carboxymethyl)lysine (CML) has been used as general key biomarkers for oxidative stress and a number of diseases associated with poor lifestyle. Herein we present the first synthetic pathway to the free zwitter ion of CML via a protected intermediate. [ABSTRACT FROM AUTHOR]

In order to investigate exposure end effect markers of fruit and fruit fibre intake we investigated how fresh apple or apple-pectin affects the urinary metabolome of rats. Twenty-four Fisher 344 male rats were randomized into three groups and fed a standard diet with different supplementations added in two of the groups (7% apple-pectin or 10 g raw apple). After 24 days of feeding, 24 h urine was collected and analyzed by UPLC-QTOF-MS in positive and negative ionization mode. Metabolites that responded to the apple or pectin diets were selected and classified as either potential exposure or effect markers based on the magnitude and pattern of their response. An initial principal component analysis (PCA) of all detected metabolites showed a clear separation between the groups and during marker identification several new apple and/or pectin markers were found. Quinic acid, m-coumaric acid and (-)epicatechin were identified as exposure markers of apple intake whereas hippuric acid behaved as an effect marker. Pyrrole-2-carboxylic acid and 2-furoylglycine behaved as pectin exposure markers while 2-piperidinone was recognized as a potential pectin effect marker. None of them has earlier been related to intake of pectin or other fibre products. We discuss these new potential exposure and effect markers and their interpretation. [ABSTRACT FROM AUTHOR]

Aims: The aim of the present study was to describe the intake of whole grain (WG) in Norway, Sweden and Denmark, and to investigate what proportion of the study population that met the new WG recommendation (75 g WG/day per 10 MJ). Methods: Descriptive study. Data is from one 24h dietary recall (24HDR) collected in 1995–2000 from a subset (n = 8,702) of the large Scandinavian cohort “HELGA” consisting of participants aged 30–65 years from three cohorts. Results: The mean WG intake was far below the recommended level. Between 16% (Danish men) and 35% (Norwegian women) consumed at least the recommended intake of WG. Among women, the median intake of WG products (g WG products/day) was 114 g/day in Norway and 108 g/day in Denmark, whereas the intake was much lower in Sweden (64 g/day). For women, the median intake of WG in absolute amounts (g WG/day) was again highest in Norway (44 g/day), but lower in both Sweden (35 g/day) and Denmark (31 g/day). For men (no data available for Norwegian men), the intake of WG products was higher in Denmark (138 g/day) compared to Sweden (79 g/day), but when looking at the WG intake in absolute amounts, the intake was highest in Sweden (49 g/day) compared to Denmark (41 g/day). Conclusions: The present study described the intake of WG as well as the sources of WG in Norway, Sweden and Denmark. Between 16% and 35% met the new recommendations on intake of WG. [ABSTRACT FROM PUBLISHER]

ObjectiveTo identify the dietary, lifestyle and socio-economic factors associated with the intake of whole grains (WG) in Norway, Sweden and Denmark.DesignA cross-sectional study.SettingSubsample of the Scandinavian cohort ‘HELGA’ consisting of three prospective cohorts: The Norwegian Women and Cancer Study; The Northern Sweden Health and Disease Study; and the Danish Diet, Cancer and Health Study.SubjectsA total of 8702 men and women aged 30–65 years. Dietary data are from one 24 h dietary recall and data on socio-economic status and lifestyle factors including anthropometric values are from the baseline collection of data.ResultsVegetables, fruits, dairy products, fish and shellfish, coffee, tea and margarine were directly associated with the intake of WG, whereas red meat, white bread, alcohol and cakes and biscuits were inversely associated. Smoking and BMI were consistently inversely associated with the intake of WG. Furthermore, length of education was directly associated with the intake of WG among women.ConclusionsThe intake of WG was found to be directly associated with healthy diet, lifestyle and socio-economic factors and inversely associated with less healthy factors, suggesting that these factors are important for consideration as potential confounders when studying WG intake and disease associations. [ABSTRACT FROM AUTHOR]

The metabolome following intake of onion by-products is evaluated. Thirty-two rats were fed a diet containing an onion by-product or one of the two derived onion by-product fractions: an ethanol extract and the residue. A 24 hour urine sample was analyzed using 1H NMR spectroscopy in order to investigate the effects of onion intake on the rat metabolism. Application of interval extended canonical variates analysis (ECVA) proved to be able to distinguish between the metabolomic profiles from rats consuming normal feed and rats fed with an onion diet. Two dietary biomarkers for onion intake were identified as dimethyl sulfone and 3-hydroxyphenylacetic acid. The same two dietary biomarkers were subsequently revealed by interval partial least squares regression (PLS) to be perfect quantitative markers for onion intake. The best PLS calibration model yielded a root mean square error of cross-validation (RMSECV) of 0.97% (w/w) with only 1 latent variable and a squared correlation coefficient of 0.94. This indicates that urine from rats on the by-product diet, the extract diet, and the residue diet all contain the same dietary biomarkers and it is concluded that dimethyl sulfone and 3-hydroxyphenylacetic acid are dietary biomarkers for onion intake. Being able to detect specific dietary biomarkers is highly beneficial in the control of nutritionally enhanced functional foods. [ABSTRACT FROM AUTHOR]

Abstract: The purpose of this study was to compare the effect of carbohydrate structure and digestibility on azoxymethane (AOM)-induced colon carcinogenesis. Five groups of male Fischer 344 rats each comprising 30 animals were injected with AOM and fed a high-fat diet with 15% of various carbohydrates. The carbohydrate sources used were sucrose, cornstarch (a linear starch, reference group), potato starch (a branched starch), a short-chained oligofructose (Raftilose®), and a long-chained inulin-type fructan (Raftiline®). An interim sacrifice was performed after 9 wk to investigate markers of carbohydrate digestibility, including caecal fermentation (caecum weight and pH) and glucose and lipid metabolism [glucose, fructoseamine, HbA1c, triglycerides, and insulin-like growth factor (IGF) 1]. In addition potential early predictors of carcinogenicity [cell proliferation and aberrant crypt foci (ACF)] at 9 wk and their correlation to colon cancer risk after 32 wk were investigated. Tumor incidence was significantly reduced in animals fed oligofructose, and the number of tumors per animal was significantly reduced in animals fed inulin and oligofructose at 32 wk after AOM induction compared to the reference group fed sucrose. Increased caecum weight and decreased caecal pH were seen in groups fed oligofructose, inulin, and potato starch. Plasma triglyceride was decreased in rats fed oligofructose and inulin. Cell proliferation was increased in the proximal colon of rats fed sucrose, oligofructose, and inulin, and the number of cells per crypt decreased in rats fed oligofructose and inulin. The total number of ACF's was unaffected by treatment, and the size and multiplicity of ACF was unrelated to tumor development. It was concluded that less digestible carbohydrates with an early effect on caecum fermentation and plasma triglyceride decreased subsequent tumor incidence and multiplicity. This was unrelated to ACF, cell proliferation, and other markers of glucose and lipid metabolism. [ABSTRACT FROM AUTHOR]

Addition of vitamins and minerals to foods must be done without health risk to any consumer group. International expert groups have aimed at establishing tolerable upper intake levels (ULs) for vitamins and minerals although lack of solid data on their safety is a major obstacle to this work. In this paper, we summarize the existing ULs and suggest the use of guidance levels (GLs) set by others and temporary guidance levels (TGLs) proposed here, whenever no consensus UL has been established for adults. We suggest the use of body surface area ratios to establish similar levels for younger age groups. The levels are applied in a model for calculation of safe fortification levels for all ages.We have estimated the upper 95th percentile intake of vitamins and minerals from food in various Danish age and gender groups and suggest that a daily multivitaminmineral pill is included in the calculation of total dietary intake levels of all vitamins and minerals. By subtracting this dietary intake level from the UL, GL or TGL, we calculate the amount that can be safely used for fortification. Since safety must be assured for all age groups, the smallest difference relative to energy intake calculated for any age group is proposed as the maximal allowance (MA) for fortification with each nutrient. We suggest that the MA should be expressed in weight units per energy unit in order to distribute it equally between potentially fortifiable food groups according to their usual contribution to total energy intakes. [ABSTRACT FROM AUTHOR]

Gavage administration of the citrus flavonoid naringenin, 3′,4,5,7-tetrahydroxyflavanon for 4 consecutive days, to immature female mice (postnatal day 17–20) at 4 or 100 mg/kg b.wt. significantly increased uterine weights 3 and 4 times, respectively. Analysis of uterine oestrogen receptor α revealed that naringenin significantly increased the cytosolic concentration of oestrogen receptor α, whereas in nuclei the oestrogen receptor α concentration was significantly decreased as compared to the solvent control. This was in contrast to the positive control 17β-oestradiolacetate which acted as a true oestrogen by increasing the concentration of both total and nuclear oestrogen receptor α. Both naringenin and 17β-oestradiolacetate, however, significantly, induced nuclear oestrogen receptor α in the liver, suggesting a tissue specific effect of naringenin on oestrogen receptor α distribution. In order to investigate the tissue levels at which the uterotrophic effect was observed, the distribution of an oral dose of tritiated naringenin (4 mg/kg) was investigated in 3-week-old female mice. The radioactivity content (ng naringenin equivalents/g tissue) was found to be highest in the gastrointestinal-tract, followed by the kidneys and liver. Uterus and ovaries were also found to contain relatively high and approximately equal amounts of naringenin. The concentration of naringenin in uterus and ovaries was found to be ten times higher as compared to the mammary tissue. The urinary excretion of more than 25% of the administered dose, within 8 hr after dosing indicated that naringenin is absorbed extensively in mice. The plasma concentration of 0.5 μM found in the present study is similar to the peak plasma concentration of naringenin (0.6 μM) observed in man following ingestion of 400–760 ml of orange juice (Erlund et al. 2001). This could be taken to suggests that ingestion of orange juice and other citrus fruits and juices may give rise to sufficiently high tissue levels of naringenin in man to exert a biological effect. [ABSTRACT FROM AUTHOR]

Investigates human exposure to genotoxic compounds present in ambient air using selected biomarkers in non-smoking Danish bus drivers and postal workers. Detection of higher levels of bulky carcinogen-DNA adducts in bus drivers; Negative correlation between bulky carcinogen-DNA adducts and polycyclic aromatic hydrocarbon-albumin adducts.

Background: Biomarkers of meat intake hold promise in clarifying the health effects of meat consumption, yet the differentiation between red and white meat remains a challenge. We measure meat intake objectively in a free-living population by applying a newly developed, three-step strategy for biomarker-based assessment of dietary intakes aimed to indicate if (1) any meat was consumed, (2) what type it was and (3) the quantity consumed. Methods: Twenty-four hour urine samples collected in a four-way crossover RCT and in a cross-sectional analysis of a longitudinal lifestyle intervention (the PREVIEW Study) were analyzed by untargeted LC–MS metabolomics. In the RCT, healthy volunteers consumed three test meals (beef, pork and chicken) and a control; in PREVIEW, overweight participants followed a diet with high or moderate protein levels. PLS-DA modeling of all possible combinations between six previously reported, partially validated, meat biomarkers was used to classify meat intake using samples from the RCT to predict consumption in PREVIEW. Results: Anserine best separated omnivores from vegetarians (AUROC 0.94–0.97), while the anserine to carnosine ratio best distinguished the consumption of red from white meat (AUROC 0.94). Carnosine showed a trend for dose–response between non-consumers, low consumers and high consumers for all meat categories, while in combination with other biomarkers the difference was significant. Conclusion: It is possible to evaluate red meat intake by using combinations of existing biomarkers of white and general meat intake. Our results are novel and can be applied to assess qualitatively recent meat intake in nutritional studies. Further work to improve quantitation by biomarkers is needed. [ABSTRACT FROM AUTHOR]

Supplemental digital content is available in the text. Purpose: Autologous blood transfusion is performance enhancing and prohibited in sport but remains difficult to detect. This study explored the hypothesis that an untargeted urine metabolomics analysis can reveal one or more novel metabolites with high sensitivity and specificity for detection of autologous blood transfusion. Methods: In a randomized, double-blinded, placebo-controlled, crossover design, exercise-trained men (n = 12) donated 900 mL blood or were sham phlebotomized. After 4 wk, red blood cells or saline were reinfused. Urine samples were collected before phlebotomy and 2 h and 1, 2, 3, 5, and 10 d after reinfusion and analyzed by ultraperformance liquid chromatography–quadrupole time-of-flight mass spectrometry. Models of unique metabolites reflecting autologous blood transfusion were attained by partial least-squares discriminant analysis. Results: The strongest model was obtained 2 h after reinfusion with a misclassification error of 6.3% and 98.8% specificity. However, combining only a few of the strongest metabolites selected by this model provided a sensitivity of 100% at days 1 and 2 and 66% at day 3 with 100% specificity. Metabolite identification revealed the presence of secondary di-2-ethylhexyl phtalate metabolites and putatively identified the presence of (iso)caproic acid glucuronide as the strongest candidate biomarker. Conclusions: Untargeted urine metabolomics revealed several plasticizers as the strongest metabolic pattern for detection of autologous blood transfusion for up to 3 d. Importantly, no other metabolites in urine seem of value for antidoping purposes. [ABSTRACT FROM AUTHOR]

Purpose: We examined the effect on the postprandial plasma metabolome of protein pre-meals before a fat-rich main meal. Methods: Two randomized, cross-over meal studies were conducted to test the dose–response effect (0 g, 10 g, 20 g) of a pre-meal with whey protein (WP) (PREMEAL I), and the effect of protein quality (10 g WP, casein, or gluten) and timing (− 15 min vs − 30 min) of the pre-meal (PREMEAL II). Participants with metabolic syndrome received one of the test meals on each test day, − 15 min (or − 30 min) prior to a standardized fat-rich breakfast. Plasma samples were collected at − 15 min (or − 30 min), 0, 120, 240 a nd 360 min and analyzed using liquid chromatography–mass spectrometry with an untargeted method. Results: Pre-meal WP intake elevated plasma branched-chain amino acids (BCAA), aromatic amino acids and methionine and decreased plasma LPC (16:0) and PC (32:1) levels before the main meal. Early (− 15 to 0 min) aromatic amino acids and BCAA in response to pre-meal WP partially predict the glucose and insulin response after the main meal. A pre-meal with WP altered the postprandial plasma metabolic pattern of acyl-carnitines, specific PCs, LPCs and LPEs, betaine, citric acid, linoleic acid, and β-hydroxypalmitic acid compared to no pre-meal. The casein and WP pre-meals exhibited similar postprandial amino acid responses whereas a pre-meal with gluten resulted in lower levels of plasma amino acids and its metabolites. Conclusion: A pre-meal with protein affects the postprandial metabolic pattern indicating facilitated glucose and lipid disposal from plasma in participants with metabolic syndrome. [ABSTRACT FROM AUTHOR]

Background and aims: Adipose tissue plays a pivotal role in storing excess fat and its composition reflects the history of person's lifestyle and metabolic health. Broad profiling of lipids with mass spectrometry has potential for uncovering new knowledge on the pathology of obesity, metabolic syndrome, diabetes and other related conditions. Here, we developed a lipidomic method for analyzing human subcutaneous adipose biopsies. We applied the method to four body areas to understand the differences in lipid composition between these areas. Materials and methods: Adipose tissue biopsies from 10 participants were analyzed using ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. The sample preparation optimization included the optimization of the lipid extraction, the sample amount and the sample dilution factor to detect lipids in an appropriate concentration range. Lipidomic analyses were performed for adipose tissue collected from the abdomen, breast, thigh and lower back. Differences in lipid levels between tissues were visualized with heatmaps. Results: Lipidomic analysis on human adipose biopsies lead to the identification of 186lipids in 2 mg of sample. Technical variation of the lipid-class specific internal standards were below 5%, thus indicating acceptable repeatability. Triacylglycerols were highly represented in the adipose tissue samples, and lipids from 13 lipid classes were identified. Long polyunsaturated triacylglycerols in higher levels in thigh (q<0.05), when compared with the abdomen, breast and lower back, indicating that the lipidome was area-specific. Conclusion: The method presented here is suitable for the analysis of lipid profiles in 2 mg of adipose tissue. The amount of fat across the body is important for health but we argue that also the distribution and the particular profile of the lipidome may be relevant for metabolic outcomes. We suggest that the method presented in this paper could be useful for detecting such aberrations. [ABSTRACT FROM AUTHOR]

Background: Banana is one of the most widely consumed fruits in the world. However, information regarding its health effects is scarce. Biomarkers of banana intake would allow a more accurate assessment of its consumption in nutrition studies.Objectives: Using an untargeted metabolomics approach, we aimed to identify the banana-derived metabolites present in urine after consumption, including new candidate biomarkers of banana intake.Methods: A randomized controlled study with a crossover design was performed on 12 healthy subjects (6 men, 6 women, mean ± SD age: 30.0 ± 4.9 y; mean ± SD BMI: 22.5 ± 2.3 kg/m2). Subjects underwent 2 dietary interventions: 1) 250 mL control drink (Fresubin 2 kcal fiber, neutral flavor; Fresenius Kabi), and 2) 240 g banana + 150 mL control drink. Twenty-four-hour urine samples were collected and analyzed with ultra-performance liquid chromatography coupled to a quadrupole time-of-flight MS and 2-dimensional GC-MS. The discovered biomarkers were confirmed in a cross-sectional study [KarMeN (Karlsruhe Metabolomics and Nutrition study)] in which 78 subjects (mean BMI: 22.8; mean age: 47 y) were selected reflecting high intake (126-378 g/d), low intake (47.3-94.5 g/d), and nonconsumption of banana. The confirmed biomarkers were examined singly or in combinations, for established criteria of validation for biomarkers of food intake.Results: We identified 33 potentially bioactive banana metabolites, of which 5 metabolites, methoxyeugenol glucuronide (MEUG-GLUC), dopamine sulfate (DOP-S), salsolinol sulfate, xanthurenic acid, and 6-hydroxy-1-methyl-1,2,3,4-tetrahydro-β-carboline sulfate, were confirmed as candidate intake biomarkers. We demonstrated that the combination of MEUG-GLUC and DOP-S performed best in predicting banana intake in high (AUCtest = 0.92) and low (AUCtest = 0.87) consumers. The new biomarkers met key criteria establishing their current applicability in nutrition and health research for assessing the occurrence of banana intake.Conclusions: Our metabolomics study in healthy men and women revealed new putative bioactive metabolites of banana and a combined biomarker of intake. These findings will help to better decipher the health effects of banana in future focused studies. This study was registered at clinicaltrials.gov as NCT03581955 and with the Ethical Committee for the Protection of Human Subjects Sud-Est 6 as CPP AU 1251, IDRCB 2016-A0013-48; the KarMeN study was registered with the German Clinical Trials Register (DRKS00004890). Details about the study can be obtained from https://www.drks.de. [ABSTRACT FROM AUTHOR]

Purpose: Berries and mixed berry products exert acute effects on postprandial glycaemia and insulinemia, but very few berries have been studied, and primarily in normal weight subjects. Sea buckthorn and strawberry are compositionally widely different berries and may likely produce different responses. The effects of strawberry and sea buckthorn on postprandial glycaemia and insulinemia were examined in overweight or obese male subjects. Subjective appetite sensations and ad libitum intake were also examined.Methods: The study was conducted as a randomised, controlled, single-blinded, three-way crossover study. Eighteen subjects were studied in three 2-h meal tests followed by a subsequent ad libitum meal. Test meals contained added sucrose and either sea buckthorn, strawberry or no berries with added fructose (control). Blood samples were collected at t = 0, 30, 45, 60, 90 and 120 min. Subjective appetite sensations were recorded at t = 0, 15, 30, 45, 60, 90, 120, and 140 min and subsequent ad libitum intake was recorded. Statistical differences in all continuous measures were evaluated based on the existence of a meal or a time-meal interaction by repeated measures linear model analyses or by differences in AUC by linear mixed models.Results: None of the berries affected postprandial glucose. However, sea buckthorn improved glycaemic profile (44.7%, p < 0.01) compared to control. Sea buckthorn also resulted in a decrease in plasma insulin concentration at 30 min (39.6%, p < 0.01) and at 45 min (16.5%, p < 0.05) compared to control and the maximal increase in plasma insulin was lower following sea buckthorn compared with control (23.6%, p < 0.01). Strawberry did not affect postprandial insulin concentrations compared to control. No differences between control and each of the two berries were observed for any of the appetite parameters, except for desire for something sweet, which was increased following the sea buckthorn meal compared to control.Conclusions: There was no effect on postprandial glucose response to a sugar challenge given together with purees of strawberry or sea buckthorn. Sea buckthorn decreased and delayed the insulin response and improved glycaemic profile compared with control. Strawberry had no such effects. No important differences were seen for the appetite measures. Sea buckthorn might be useful as a culinary tool for lowering meal insulin response. [ABSTRACT FROM AUTHOR]

The colonic epithelium harbors a large number of endocrine cells, but little is known about the endocrine functions of the colon. However, the high density of glucagon like peptide-1 (GLP-1)- and peptide-YY (PYY)-secreting L cells is of great interest because of the potential antidiabetic and antiobesity effects of GLP-1 and PYY. Short-chain fatty acids (SCFAs) produced by local bacterial fermentation are suggested to activate the colonic free fatty acid receptors FFAR2 (GPR43) and FFAR3 (GPR41), stimulating the colonic L cells. We used the isolated perfused rat colon as a model of colonic endocrine secretion and studied the effects of the predominant SCFAs formed: acetate, propionate, and butyrate. We show that luminal and especially vascular infusion of acetate and butyrate significantly increases colonic GLP-1 secretion, and to a minor extent also PYY secretion, but only after enhancement of intracellular cAMP. Propionate neither affected GLP-1 nor PYY secretion whether administered luminally or vascularly. A FFAR2- and FFAR3--specific agonist [(S)-2-(4-chlorophenyl)-3,3-dimethyl-N-(5-phenylthiazol-2-yl)butamide (CFMB)/AR420626] had no effect on colonic GLP-1 output, and a FFAR3 antagonist (AR399519) did not decrease the SCFA-induced GLP-1 response. However, the voltage-gated Ca2+-channel blocker nifedipine, the KATP-channel opener diazoxide, and the ATP synthesis inhibitor 2,4-dinitrophenol completely abolished the responses. FFAR2 receptor studies confirmed low-potent partial agonism of acetate, propionate, and butyrate, compared with CFMB, which is a full agonist with ~750-fold higher potency than the SCFAs. In conclusion, SCFAs may increase colonic GLP-1/PYY secretion, but FFAR2/FFAR3 do not seem to be involved. Rather, SCFAs are metabolized and appear to function as a colonocyte energy source. NEW & NOTEWORTHY By the use of in situ isolated perfused rat colon we show that short-chain fatty acids (SCFAs) primarily are used as a colonocyte energy source in the rat, subsequently triggering glucagon like peptide-1 (GLP-1) secretion independent of the free fatty acid receptors FFAR2 and FFAR3. Opposite many previous studies on SCFAs and FFAR2/FFAR3 and GLP-1 secretion, this experimental model allows investigation of the physiological interactions between luminal nutrients and secretion from cells whose function depend critically on their blood supply as well as nerve and paracrine interactions. [ABSTRACT FROM AUTHOR]

Background: Joint data analysis from multiple nutrition studies may improve the ability to answer complex questions regarding the role of nutritional status and diet in health and disease.Objective: The objective was to identify nutritional observational studies from partners participating in the European Nutritional Phenotype Assessment and Data Sharing Initiative (ENPADASI) Consortium, as well as minimal requirements for joint data analysis.Methods: A predefined template containing information on study design, exposure measurements (dietary intake, alcohol and tobacco consumption, physical activity, sedentary behavior, anthropometric measures, and sociodemographic and health status), main health-related outcomes, and laboratory measurements (traditional and omics biomarkers) was developed and circulated to those European research groups participating in the ENPADASI under the strategic research area of "diet-related chronic diseases." Information about raw data disposition and metadata sharing was requested. A set of minimal requirements was abstracted from the gathered information.Results: Studies (12 cohort, 12 cross-sectional, and 2 case-control) were identified. Two studies recruited children only and the rest recruited adults. All studies included dietary intake data. Twenty studies collected blood samples. Data on traditional biomarkers were available for 20 studies, of which 17 measured lipoproteins, glucose, and insulin and 13 measured inflammatory biomarkers. Metabolomics, proteomics, and genomics or transcriptomics data were available in 5, 3, and 12 studies, respectively. Although the study authors were willing to share metadata, most refused, were hesitant, or had legal or ethical issues related to sharing raw data. Forty-one descriptors of minimal requirements for the study data were identified to facilitate data integration.Conclusions: Combining study data sets will enable sufficiently powered, refined investigations to increase the knowledge and understanding of the relation between food, nutrition, and human health. Furthermore, the minimal requirements for study data may encourage more efficient secondary usage of existing data and provide sufficient information for researchers to draft future multicenter research proposals in nutrition. [ABSTRACT FROM AUTHOR]

Reduced absorption capacity in patients with intestinal resections (IR) could result in malabsorption of fat-soluble components like carotenoids, which are of clinical interest in relation to visual health. In this case cohort, we investigated the association between IR and serum lutein, zeaxanthin, β-carotene and macular pigment optical density, when compared with healthy controls. Ten patients with IR and twelve healthy controls were included in the study. Baseline characteristics were comparable between groups, except for higher serum TAG (P < 0·05) and shorter bowel length (P < 0·0001) in the group with IR. Serum lutein, zeaxanthin, β-carotene and macular pigment optical density were >15% lower in the patient group compared with healthy controls (P < 0·05, adjusted for age) and, in the case of serum lutein and zeaxanthin, also for dietary intake of carotenoids. Results suggest that for a test of macular carotenoid supplementation, subjects with a potentially clinically significant carotenoid deficit could be recruited among patients with IR. [ABSTRACT FROM AUTHOR]

Drinking within recommended limits is highly prevalent in much of the world, and strong epidemiological associations exist between moderate alcohol consumption and risk of several major chronic diseases, including coronary heart disease, diabetes, and breast cancer. In many cases, plausible biological mediators for these associations have been identified in randomized trials, but gold standard evidence that moderate drinking causes or prevents any chronic disease remains elusive and important concerns about available evidence have been raised. Although long-term randomized trials to test the observed associations have been termed impossible, clinical investigators have now successfully completed randomized trials of complex nutritional interventions in a variety of settings, along with trials of alcohol consumption itself of up to 2 years duration. The successful completion of these trials suggests that objections to the execution of a full-scale, long-term clinical trial of moderate drinking on chronic disease are increasingly untenable. We present potential lessons learned for such a trial and discuss key features to maximize its feasibility and value. [ABSTRACT FROM AUTHOR]

Background: Alcohol consumption is associated with increased risk of breast cancer (BC), and the underlying mechanism is thought to be sex-hormone driven. In vitro and observational studies suggest a mechanism involving peroxisome proliferator-activated receptor gamma (PPARγ) in a complex with peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and interaction with aromatase (encoded by CYP19A1). Use of non-steroidal anti-inflammatory drugs (NSAID) may also affect circulating sex-hormone levels by modifying PPARγ activity.Methods: In the present study we assessed whether genetic variation in CYP19A1 is associated with risk of BC in a case-control study group nested within the Danish "Diet, Cancer and Health" cohort (ncases = 687 and ncontrols = 687) and searched for gene-gene interaction between CYP19A1 and PPARGC1A, and CYP19A1 and PPARG, and gene-alcohol and gene-NSAID interactions. Association between the CYP19A1 polymorphisms and hormone levels was also examined among 339 non-HRT users. Incidence rate ratios were calculated based on Cox' proportional hazards model. Furthermore, we performed a pilot randomised controlled trial to determine the effect of the PPARG Pro(12)Ala polymorphism and the PPARγ stimulator Ibuprofen on sex-hormone levels following alcohol intake in postmenopausal women (n = 25) using linear regression.Results: Genetic variations in CYP19A1 were associated with hormone levels (estrone: P rs11070844 = 0.009, estrone sulphate: P rs11070844 = 0.01, P rs749292 = 0.004, P rs1062033 = 0.007 and P rs10519297 = 0.03, and sex hormone-binding globulin (SHBG): P rs3751591 = 0.03) and interacted with alcohol intake in relation to hormone levels (estrone sulphate: P interaction/rs2008691 = 0.02 and P interaction/rs1062033= 0.03, and SHBG: P interaction/rs11070844 = 0.03). CYP19A1/rs3751591 was both associated with SHBG levels (P = 0.03) and with risk of BC (Incidence Rate Ratio = 2.12; 95 % Confidence Interval: 1.02-4.43) such that homozygous variant allele carriers had increased levels of serum SHBG and were at increased risk of BC. Acute intake of alcohol decreased blood estrone (P = <0.0001), estrone sulphate (P = <0.0001), and SHBG (P = 0.009) levels, whereas Ibuprofen intake and PPARG Pro(12)Ala genotype had no effect on hormone levels.Conclusions: Our results suggest that genetically determined variation in CYP19A1 is associated with differences in sex hormone levels. However, the genetically determined differences in sex hormone levels were not convincingly associated with BC risk. The results therefore indicate that the genetically determined variation in CYP19A1 contributes little to BC risk and to alcohol-mediated BC risk.Trial Registration: NCT02463383, June 3, 2015. [ABSTRACT FROM AUTHOR]

Breast cancer is a major cause of death for women. To improve treatment, current oncology research focuses on discovering and validating new biomarkers for early detection of cancer; so far with limited success. Metabolic profiling of plasma samples and auxiliary lifestyle information was combined by chemometric data fusion. It was possible to create a biocontour, which we define as a complex pattern of relevant biological and phenotypic information. While single markers or known risk factors have close to no predictive value, the developed biocontour provides a forecast which, several years before diagnosis, is on par with how well most current biomarkers can diagnose current cancer. Hence, while e.g. mammography can diagnose current cancer with a sensitivity and specificity of around 75 %, the currently developed biocontour can predict that there is an increased risk that breast cancer will develop in a subject 2-5 years after the sample is taken with sensitivity and specificity well above 80 %. The model was built on data obtained in 1993-1996 and tested on persons sampled a year later in 1997. Metabolic forecasting of cancer by biocontours opens new possibilities for early prediction of individual cancer risk and thus for efficient screening. This may provide new avenues for research into disease mechanisms. [ABSTRACT FROM AUTHOR]

Apple is one of the most commonly consumed fruits worldwide and it has been associated with several health effects, especially on plasma cholesterol and risk of cardiovascular disease both in human and animal studies. By using an untargeted metabolomics approach we wanted to investigate whether supplementation of whole apple or processed apple products affect the human plasma metabolome. Therefore, 24 healthy volunteers were recruited for a comprehensive 5 × 4 weeks dietary crossover study and receiving supplement of whole apples (550 g/day), clear and cloudy apple juices (500 ml/day), dried apple pomace (22 g/day), or no supplement. Plasma was collected for analysis after an overnight fast and analysed by UPLC-ESI-TOF-MS. Discriminative features revealed by Partial Least Square-Discriminant Analysis showed whole apple and apple pomace having generally a stronger modifying effect of the plasma metabolome than the other apple products. We observed an effect on branched-chain amino acids and aromatic amino acids degradation, and a decreased use of lipid fuels indicating an improvement in glucose utilisation. A reduced level of plasma bile acids after apple consumption may indicate less re-absorption from the gut. Some lysoPCs and a steroid hormone precursor decreased as well, indicating a reduced outbound cholesterol transport from the liver and less use of cholesterol for steroid synthesis. In the light of these results, we speculate that apple and/or apple pomace seems to affect cholesterol homeostasis by several mechanisms. [ABSTRACT FROM AUTHOR]

Cheese intake has been shown to decrease total cholesterol and LDL cholesterol concentrations when compared to butter of equal fat content. An untargeted metabolite profiling may reveal exposure markers of cheese but may also contribute with markers which can help explain how the intake of cheese affects cholesterol concentrations. Twenty-three subjects collected 2 × 24 h urine samples after 6 weeks of cheese and 6 weeks of butter intake with equal amounts of fat in a cross-over intervention study. The samples were analyzed by UPLC-QTOF/MS. A two-step univariate data analysis approach using linear mixed model was applied separately for positive and negative ionization mode: In the first step a total of 44 features related to treatment were identified and in the second step 36 of these features were related to total cholesterol concentrations. Cheese intake resulted in increased urinary indoxyl sulfate, xanthurenic acid, tyramine sulfate, 4-hydroxyphenylacetic acid, isovalerylglutamic acid and several acylglycines including isovalerylglycine, tiglylglycine and isobutyrylglycine when compared to butter intake of equal fat content. The biological mechanisms of action linking the metabolites to cholesterol concentrations need to be further explored. [ABSTRACT FROM AUTHOR]

Assessment of compliance with dietary interventions is necessary to understand the observed magnitude of the health effects of the diet per se. To avoid reporting bias, different dietary biomarkers (DBs) could be used instead of self-reported data. However, few studies investigated a combination of DBs to assess compliance and its influence on cardiometabolic risk factors. The objectives of this study were to use a combination of DBs to assess compliance and to investigate how a healthy Nordic diet (ND) influences cardiometabolic risk factors in participants with high apparent compliance compared with the whole study population. From a recently conducted isocaloric randomized trial, SYSDIET (Systems Biology in Controlled Dietary Interventions and Cohort Studies), in 166 individuals with metabolic syndrome, several DBs were assessed to reflect different key components of the ND: canola oil (serum phospholipid α-linolenic acid), fatty fish [eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)], vegetables (plasma β-carotene), and whole grains (plasma alkylresorcinols). High-fat dairy intake (expectedly low in the ND) was reflected by serum pentadecanoic acid. All participants with biomarker data (n = 154) were included in the analyses. Biomarkers were combined by using a biomarker rank score (DB score) and principal component analysis (PCA). The DB score was then used to assess compliance. During the intervention, median concentrations of alkylresorcinols, α-linolenic acid, EPA, and DHA were >25% higher in the ND individuals than in the controls (P<0.05), whereas median concentrations of pentadecanoic acid were 14% higher in controls (P<0.05). Median DB score was 57% higher in the ND than in controls (P < 0.001) during the intervention, and participants were ranked similarly by DB score and PCA score. Overall, estimates of group difference in cardiometabolic effects generally appeared to be greater among compliant participants than in the whole study population (e.g., estimates of treatment effects on blood pressure and lipoproteins were ~ 1.5- to 2-fold greater in the most compliant participants), suggesting that poor compliance attenuated the dietary effects. With adequate consideration of their limitations, DB combinations (e.g., DB score) could be useful for assessing compliance in intervention studies investigating cardiometabolic effects of healthy dietary patterns. The study was registered at clinicaltrials.gov as NCT00992641. [ABSTRACT FROM AUTHOR]