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BACKGROUND Coffee consumption is associated with a reduced risk of several chronic diseases in a dose-dependent manner. Chronic intake results in the transient appearance of bioactive phenolic metabolites in the circulatory system. However, there is a lack of information on the impact of different patterns of coffee consumption on plasma and urinary profiles of phenolic metabolites. OBJECTIVES Plasma and urinary phenolic metabolites were investigated following regular consumption of different daily dosages of coffee or cocoa-based products containing coffee (CBPCC) under a real-life setting. METHODS A repeated-dose, randomized, crossover human intervention was conducted with 21 healthy volunteers. For 1 mo, participants consumed 1) 1 cup of coffee (1C), 2) 3 cups of coffee (3C), or 3) 1 cup of coffee + 2 CBPCC twice daily (PC). Plasma and urine samples were collected over a 24-h period after each treatment. The nutrikinetics and urinary excretion of native, human phase II, and colonic metabolites were assessed. RESULTS A total of 51 (poly)phenolic metabolites were quantified, with 41 metabolites being strictly related to coffee consumption. Significant differences were observed among treatments for most of the metabolites. The metabolites present in the highest amounts were the hydroxycinnamate, phenylpropanoic acid, benzaldehyde, and benzene classes, along with (-)-epicatechin and phenyl-γ-valerolactone derivatives after PC treatment. Daily average concentrations did not exceed 200 nmol/L and were

Coffee is one of the most popular beverages worldwide and, nowadays, one of the most practical way for its preparation is by prepacked capsules. The aim of this study was comparing the content in caffeine, trigonelline, N-methylpyridinium (NMP), niacin, and chlorogenic acids of 65 different capsule-brewed coffees, commercialised by 5 of the most representative brands in Italy. Coffees were prepared from capsules following manufacturer’s instructions and analysed with an optimized UHPLC-MS/MS method able to assess all these phytochemicals in one single run. Inter-lot and capsule variability were also studied for a subset of coffee capsules. Except for decaffeinated coffees, caffeine amount accounted between 54 and 208 mg/serving. Regular espresso coffees showed higher trigonelline, NMP, and niacin concentrations than large (lungo) and decaffeinated samples, with average serving amounts of 17.96, 1.78, and 0.66 mg, respectively. Regarding chlorogenic acids, caffeoylquinic acids were the most relevant ones (20–117 mg/serving). Feruloylquinic acids were quantified between 8 and 50 mg/serving. Coumaroylquinic acids, hydroxycinnamate dimers, caffeoylshikimic acids, and caffeoylquinic lactones were also present at lower concentrations. Multivariate analysis provided comprehensive information on the phytochemical profile of the different types of coffee, showing a great variability among coffees with some brand-related insights. This study supports the need for accurately characterizing espresso coffees while investigating the beneficial effects of coffee on human health.

Current evidence accounts for the role of (poly)phenolic compounds in the prevention of non-communicable diseases. Detailed information on population-level intakes is required to translate these findings into recommendations. This work aimed to estimate (poly)phenol intake in the UK population using data from a nationally representative survey. Data from 9374 participants (4636 children aged 1.5–18 years and 4738 adults aged 19 years and over) from the National Diet and Nutrition Survey Rolling Programme (NDNS RP) 2008–2014 was used. (Poly)phenol content of foods consumed in the NDNS RP was identified using Phenol-Explorer and through literature searches. Data on flavonoids, phenolic acids, and stilbenes were collected. Total (poly)phenol content was also assessed. Mean total (poly)phenol intake ranged from 266.6 ± 166.1 mg/day in children aged 1.5–3 years to 1035.1 ± 544.3 mg/day in adults aged 65 years and over, with flavan-3-ols and hydroxycinnamic acids being the most consumed (poly)phenols across all age groups. (Poly)phenol intake was higher in males in all age groups except for adults aged 19–34 and 50–64 years, where intakes were marginally higher in females. Energy-adjusted intakes accounted for the pattern of increasing (poly)phenol intakes with age and a higher intake was observed in females across all age groups, with the exception of children aged 1.5–3 years. The main food sources were non-alcoholic beverages and fruits, being the main compounds flavan-3-ols and caffeoylquinic acids. This analysis provides estimates of (poly)phenol intake from a representative sample of the UK general population, which can help inform the health implications of (poly)phenol intake.

International audience; Dietary fibre is a generic term describing non-absorbed plant carbohydrates and small amounts of associated non-carbohydrate components. The main contributors of fibre to the diet are the cell walls of plant tissues, which are supramolecular polymer networks containing variable proportions of cellulose, hemicelluloses, pectic substances, and non-carbohydrate components, such as lignin. Other contributors of fibre are the intracellular storage oligosaccharides, such as fructans. A distinction needs to be made between intrinsic sources of dietary fibre and purified forms of fibre, given that the three-dimensional matrix of the plant cell wall confers benefits beyond fibre isolates. Movement through the digestive tract modifies the cell wall structure and may affect the interactions with the colonic microbes (e.g., small intestinally non-absorbed carbohydrates are broken down by bacteria to short-chain fatty acids, absorbed by colonocytes). These aspects, combined with the fibre associated components (e.g., micronutrients, polyphenols, phytosterols, and phytoestrogens), may contribute to the health outcomes seen with the consumption of dietary fibre. Therefore, where possible, processing should minimise the degradation of the plant cell wall structures to preserve some of its benefits. Food labelling should include dietary fibre values and distinguish between intrinsic and added fibre. Labelling may also help achieve the recommended intake of 14 g/1000 kcal/day.

Coffee is an important source of bioactive compounds, including caffeine, trigonelline, and phenolic compounds. Several studies have highlighted the preventive effects of coffee consumption on major cardiometabolic (CM) diseases, but the impact of different coffee dosages on markers of CM risk in a real-life setting has not been fully understood. This study aimed to investigate the effect of coffee and cocoa-based confectionery containing coffee consumption on several CM risk factors in healthy subjects., info:eu-repo/semantics/published

Coffee is an important source of bioactive compounds, including caffeine, trigonelline, and phenolic compounds. Several studies have highlighted the preventive effects of coffee consumption on major cardiometabolic diseases, but the impact of coffee dosage on markers of cardiometabolic risk is not well understood. Moreover, the pool of coffee-derived circulating metabolites in real-life settings is unknown. This study evaluated the bioavailability and effects on recognised cardiometabolic markers of coffee bioactives, considering different levels of consumption. An innovative experimental design, including both a chronic and an acute sub-study, and a comprehensive analytical approach were used.A 3-arm, randomised, crossover trial was conducted in 21 healthy volunteers (age, 23 ± 2 y; BMI, 22.3 ± 2.5 kg/m2) (Mena et al., Trials 2017, 18, 527). Volunteers were assigned to consume 3 treatments for 4 weeks, including 1 cup of espresso coffee/day, 3 cups of espresso coffee/day, and 1 cup of espresso coffee plus 2 cocoa-based confectionary products containing-coffee twice per day. The last day of each treatment, blood and urine samples were collected at specific time points for 24 hours. Dietary intake, body weight, BMI, waist circumference, blood pressure, fasting glucose, insulin, LDL- and HDL-cholesterol, triglycerides, nitric oxide, inflammatory markers (IL-8, TNFα, VEGF), trimethylamine-N-oxide (TMAO), DNA damage, DNA catabolites, and eicosanoids were assessed. The pool of coffee-derived circulating metabolites was also assessed in acute conditions. Untargeted metabolomics was performed.Energy intake did not change among treatments after 4 weeks, while significant differences were observed in the intake of saturated fatty acids and carbohydrates. The effect of different coffee dosages on the set of cardiometabolic markers assessed was negligible. Plasma and urinary pharmacokinetic profiles were evaluated for 6 caffeine metabolites, 3 trigonelline derivatives, and up to 40 phenolic metabolites. Pharmacokinetics highlighted the different “waves” of circulating metabolites occurring upon repeated coffee consumption. Differences in several pharmacokinetic parameters were observed among treatments, which may support the long-term cardiometabolic benefits of certain patterns of coffee consumption. Multivariate analyses clearly differentiated treatments on the basis of the urinary metabolome.This work provided a comprehensive picture of the impact of different coffee dosages on the pool of coffee-derived circulating metabolites, the urinary metabolome, and a wide number of cardiometabolic markers. Multivariate analyses focused on inter-individual differences are ongoing to better understand the effect of coffee on cardiometabolic health.

Evidence supports an inverse association between nut consumption and cardiovascular disease (CVD) risk and (poly)phenols have been identified as potential co-mediators of these beneficial effects. This study investigated the acute absorption and the bioavailability of (poly)phenols of a hazelnut skin drink in healthy subjects and assessed its acute impact on vascular/endothelial function. A single-blind, non-randomised unilateral cross-over trial involved 41 healthy adults. Blood and urine were collected resulting in the detection of ten plasma and twenty-four urine metabolites. Bioavailability was estimated about 27%. The acute ingestion of the test drink did not show any statistically significant changes to vascular/endothelial function, although a trend was observed with high-producers of certain secondary metabolites. These results indicate that the hazelnut skin drink contains an important fraction of bioavailable bioactive compounds. However, no significant acute effects of the test drink on vascular/endothelial function were observed. The study has been registered on http://www.isrctn.com .

Phenolic compounds have been recognized as promising compounds for the prevention of chronic diseases, including neurodegenerative ones. However, phenolics like flavan-3-ols (F3O) are poorly absorbed along the gastrointestinal tract and structurally rearranged by gut microbiota, yielding smaller and more polar metabolites like phenyl-&gamma, valerolactones, phenylvaleric acids and their conjugates. The present work investigated the ability of F3O-derived metabolites to cross the blood-brain barrier (BBB), by linking five experimental models with increasing realism. First, an in silico study examined the physical-chemical characteristics of F3O metabolites to predict those most likely to cross the BBB. Some of these metabolites were then tested at physiological concentrations to cross the luminal and abluminal membranes of brain microvascular endothelial cells, cultured in vitro. Finally, three different in vivo studies in rats injected with pure 5-(3&prime, 4&prime, dihydroxyphenyl)-&gamma, valerolactone, and rats and pigs fed grapes or a F3O-rich cocoa extract, respectively, confirmed the presence of 5-(hydroxyphenyl)-&gamma, valerolactone-sulfate (3&prime, isomer) in the brain. This work highlighted, with different experimental models, the BBB permeability of one of the main F3O-derived metabolites. It may support the neuroprotective effects of phenolic-rich foods in the frame of the &ldquo, gut-brain axis&rdquo

Grape pomace, the major byproduct of the wine and juice industry, is a relevant source of bioactive phenolic compounds. However, polyphenol bioavailability in humans is not well understood, and the inter-individual variability in the production of phenolic metabolites has not been comprehensively assessed to date. The pharmacokinetic and excretive profiles of phenolic metabolites after the acute administration of a drink made from red grape pomace was here investigated in ten volunteers. A total of 35 and 28 phenolic metabolites were quantified in urine and plasma, respectively. The main circulating metabolites included phenyl-gamma-valerolactones, hydroxybenzoic acids, simple phenols, hydroxyphenylpropionic acids, hydroxycinnamates, and (epi)catechin phase II conjugates. A high inter-individual variability was shown both in urine and plasma samples, and different patterns of circulating metabolites were unravelled by applying unsupervised multivariate analysis. Besides the huge variability in the production of microbial metabolites of colonic origin, an important variability was observed due to phase II conjugates. These results are of interest to further understand the potential health benefits of phenolic metabolites on individual basis.

Purpose. There is much information on the bioavailability of (poly)phenolic compounds following acute intake of various foods. However, there are only limited data on the effects of repeated and combined exposure to specific (poly)phenol food sources and the inter-individual variability in their bioavailability. This study evaluated the combined urinary excretion of (poly)phenols from green tea and coffee following daily consumption by healthy subjects in free-living conditions. The inter-individual variability in the production of phenolic metabolites was also investigated. Methods. Eleven participants consumed both tablets of green tea and green coffee bean extracts daily for 8 weeks and 24-h urine was collected on five different occasions. The urinary profile of phenolic metabolites and a set of multivariate statistical tests were used to investigate the putative existence of characteristic metabotypes in the production of flavan-3-ol microbial metabolites. Results. (Poly)phenolic compounds in the green tea and green coffee bean extracts were absorbed and excreted after simultaneous consumption, with green tea resulting in more inter-individual variability in urinary excretion of phenolic metabolites. Three metabotypes in the production of flavan-3-ol microbial metabolites were tentatively defined, characterized by the excretion of different amounts of trihydroxyphenyl-γ-valerolactones, dihydroxyphenyl-γ-valerolactones, and hydroxyphenylpropionic acids. Conclusions. The selective production of microbiota-derived metabolites from flavan-3-ols and the putative existence of characteristic metabotypes in their production represent an important development in the study of the bioavailability of plant bioactives. These observations will contribute to better understand the health effects and individual differences associated with consumption of flavan-3-ols, arguably the main class of flavonoids in the human diet. This work was partially funded by MRC core funding (Physiological Modelling of Metabolic Risk, MC_UP_A090_1005, and Nutrition, Surveys and Studies, MC_U105960384) and University of Parma core funding (FIL 2014-2017). P.M. was partially funded by a Grant of the Postdoctoral Fellowship Program from Fundación Séneca (Murcia Region, Spain). I.A.L. was supported by a postdoctoral fellowship funded by the Spanish Ministry of Economy and Competitiveness (IJCI-2014-20689).

Background Coffee is an important source of bioactive compounds, including caffeine, phenolic compounds (mainly chlorogenic acids), trigonelline, and diterpenes. Several studies have highlighted the preventive effects of coffee consumption on major cardiometabolic diseases, but the impact of coffee dosage on markers of cardiometabolic risk is not well understood. Moreover, the pool of coffee-derived circulating metabolites and the contribution of each metabolite to disease prevention still need to be evaluated in real-life settings. The aim of this study will be to define the bioavailability and beneficial properties of coffee bioactive compounds on the basis of different levels of consumption, by using an innovative experimental design. The contribution of cocoa-based products containing coffee to the pool of circulating metabolites and their putative bioactivity will also be investigated. Methods A three-arm, crossover, randomized trial will be conducted. Twenty-one volunteers will be randomly assigned to consume three treatments in a random order for 1 month: 1 cup of espresso coffee/day, 3 cups of espresso coffee/day, and 1 cup of espresso coffee plus 2 cocoa-based products containing coffee twice per day. The last day of each treatment, blood and urine samples will be collected at specific time points, up to 24 hours following the consumption of the first product. At the end of each treatment the same protocol will be repeated, switching the allocation group. Besides the bioavailability of the coffee/cocoa bioactive compounds, the effect of the coffee/cocoa consumption on several cardiometabolic risk factors (anthropometric measures, blood pressure, inflammatory markers, trimethylamine N-oxide, nitric oxide, blood lipids, fasting indices of glucose/insulin metabolism, DNA damage, eicosanoids, and nutri-metabolomics) will be investigated. Discussion Results will provide information on the bioavailability of the main groups of phytochemicals in coffee and on their modulation by the level of consumption. Findings will also show the circulating metabolites and their bioactivity when coffee consumption is substituted with the intake of cocoa-based products containing coffee. Finally, the effect of different levels of 1-month coffee consumption on cardiometabolic risk factors will be elucidated, likely providing additional insights on the role of coffee in the protection against chronic diseases. Trial registration ClinicalTrials.gov, NCT03166540. Registered on May 21, 2017. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2271-2) contains supplementary material, which is available to authorized users.

The effect of coffee and cocoa on oxidative damage to macromolecules has been investigated in several studies, often with controversial results. This study aimed to investigate the effect of one-month consumption of different doses of coffee or cocoa-based products containing coffee on markers of DNA damage and lipid peroxidation in young healthy volunteers. Twenty-one volunteers were randomly assigned into a three-arm, crossover, randomized trial. Subjects were assigned to consume one of the three following treatments: one cup of espresso coffee/day (1C), three cups of espresso coffee/day (3C), and one cup of espresso coffee plus two cocoa-based products containing coffee (PC) twice per day for 1 month. At the end of each treatment, blood samples were collected for the analysis of endogenous and H2O2-induced DNA damage and DNA oxidation catabolites, while urines were used for the analysis of oxylipins. On the whole, four DNA catabolites (cyclic guanosine monophosphate (cGMP), 8-OH-2′-deoxy-guanosine, 8-OH-guanine, and 8-NO2-cGMP) were detected in plasma samples following the one-month intervention. No significant modulation of DNA and lipid damage markers was documented among groups, apart from an effect of time for DNA strand breaks and some markers of lipid peroxidation. In conclusion, the consumption of coffee and cocoa-based confectionery containing coffee was apparently not able to affect oxidative stress markers. More studies are encouraged to better explain the findings obtained and to understand the impact of different dosages of these products on specific target groups., This study was partially funded by Soremartec Italia S.r.l. (Alba, Italy). The sponsor approved the final trial protocol but was not involved in any stage of the study as well as in the drafting of the manuscript.

Multiple factors may affect the metabolic fate of carbohydrates. Today, well-standardised and accepted methods may allow for the definitions of the changes in the glucose and insulin curves following the ingestion of either carbohydrate-based and other foods. More debate is still raised on the clinical meaning of these classifications when used at a population level, while emphasis is raised on the approach to carbohydrate metabolism on an individual basis. Within these ranges of applications, other compounds, such as plant polyphenols, may favourably add synergic effects through the modulation of carbohydrate digestion and glucose metabolic steps, resulting in lowering postprandial glucose and insulin levels. Finally, a growing knowledge suggests that the balance of dietary fructose and individual physical activity represent the key point to address the compound towards either positive, energy sparing effects, or a degenerative metabolic burden. The carbohydrate quality within a whole dietary and lifestyle pattern may therefore challenge the individual balance towards health or disease.

Covering: 1958 to June 2018 Phenyl-γ-valerolactones (PVLs) and their related phenylvaleric acids (PVAs) are the main metabolites of flavan-3-ols, the major class of flavonoids in the human diet. Despite their presumed importance, these gut microbiota-derived compounds have, to date, in terms of biological activity, been considered subordinate to their parent dietary compounds, the flavan-3-ol monomers and proanthocyanidins. In this review, the role and prospects of PVLs and PVAs as key metabolites in the understanding of the health features of flavan-3-ols have been critically assessed. Among the topics covered, are proposals for a standardised nomenclature for PVLs and PVAs. The formation, bioavailability and pharmacokinetics of PVLs and PVAs from different types of flavan-3-ols are discussed, taking into account in vitro and animal studies, as well as inter-individual differences and the existence of putative flavan-3-ol metabotypes. Synthetic strategies used for the preparation of PVLs are considered and the methodologies for their identification and quantification assessed. Metabolomic approaches unravelling the role of PVLs and PVAs as biomarkers of intake are also described. Finally, the biological activity of these microbial catabolites in different experimental models is summarised. Knowledge gaps and future research are considered in this key area of dietary (poly)phenol research.

The asymmetric synthesis of a set of hydroxyphenyl γ-valerolactones was achieved starting from 2-silyloxyfuran and alkoxy-substituted benzaldehydes as common precursors. Key synthesis steps included an enantioselective vinylogous Mukaiyama aldol reaction and a Barton–McCombie deoxygenation. Five enantioenriched γ-valerolactone targets were obtained in 5–6 steps, 18–63% overall yields and 82–98 % ee, paving the way for the straightforward entry to this class of biologically effective and poorly available flavan-3-ol metabolites. In parallel, an unprecedented one-pot reductive ring expansion process was fortuitously discovered, yielding racemic δ-lactone analogues from phenolic butanolide precursors.

Scope The present study assesses the absorption, pharmacokinetics, and urinary excretion of coffee pyridines and their metabolites after daily regular exposure to specific dosages of coffee or cocoa-based products containing coffee (CBPCC), considering different patterns of consumption. Methods and results In a three-arm, crossover, randomized trial, 21 volunteers are requested to randomly consume for 1 month: one cup of espresso coffee per day, three cups of espresso coffee per day, or one cup of espresso coffee plus two CBPCC twice per day. The last day of the one-month treatment, blood and urine samples are collected for 24 h. Trigonelline, N-methylpyridinium, N-methylnicotinamide, and N-methyl-4-pyridone-5-carboxamide are quantified. Trigonelline and N-methylpyridinium absorption curves and 24-h urinary excretion reflect the daily consumption of different servings of coffee or CBPCC, showing also significant differences in main pharmacokinetic parameters. Moreover, inter-subject variability due to sex and smoking is assessed, showing sex-related differences in the metabolism of trigonelline and smoking-related ones for N-methylpyridinium. Conclusion The daily exposure to coffee pyridines after consumption of different coffee dosages in a real-life setting is established. This data will be useful for future studies aiming at evaluating the bioactivity of coffee-derived circulating metabolites in cell experiments, mimicking more realistic experimental conditions.

Trimethylamine-N-oxide (TMAO) has been described as a new biomarker of cardiovascular disease (CVD), derived from gut microbial biotransformation of dietary choline and l-carnitine into trimethylamine (TMA) and subsequent hepatic oxidation. (Poly)phenols are among the dietary factors able to interfere with microbial enzymatic activity, possibly modulating TMA biotransformation at the gut level. The aim of this work was to investigate the in vitro biotransformation of choline and carnitine using faecal starters obtained from omnivorous and vegetarian subjects and the effect of (poly)phenol-rich foods on TMA production. Choline and l-carnitine were fermented with vegetarian or omnivorous faecal slurries, alone or in combination with 10 (poly)phenol-rich food items. TMA production from carnitine, but not from choline, was significantly lower when vegetarian faecal starters were used and, among the tested food items, blonde orange juice significantly reduced TMA formation during faecal biotransformation. Consequently, the main compounds of orange juice, namely phenolic compounds, terpenes, limonoids, organic acids and sugars, were tested individually. Sugars exerted the highest inhibitory effect on TMA production. Despite some limitations deriving from the applied in vitro model, this is the first work describing a possible role of some (poly)phenol-rich dietary products on the modulation of TMA colonic production. Free sugars were the main factor responsible for TMA inhibition, suggesting a potential beneficial role of colonic fermentation of carbohydrates in reducing TMA formation from its precursor molecules. This work opens new research directions to evaluate the effect of dietary fermentable fibre on TMA production and, potentially, on circulating TMAO levels.

Scope The Eph-ephrin system comprises emerging proteins involved in many pathophysiological processes. The pharmacological activity of the main metabolites derived from the intake of some classes of (poly)phenolic compounds, such as caffeoylquinic acids, flavan-3-ols, and ellagitannins, on the Eph-ephrin interaction was evaluated at physiological concentrations. Functional studies to elucidate their role in prostate cancer were also performed. Methods and results Among the 21 phenolics screened by an ELISA-binding assay, just urolithin C, urolithin D, and ellagic acid succeeded to inhibit the EphA2-ephrin-A1 binding. Urolithin D, the most active, was a competitive and reversible antagonist of EphA receptors able to discriminate between EphA and EphB receptors, showing intra-classes selectivity. Molecular modeling and structure-activity relationships shed light on the binding mode and selective activity of urolithin D. This catabolite blocked EphA2 phosphorylation mediated by ephrin-A1, while lacking cytotoxicity and anti-proliferative effects, and was inactive on the EphA2 kinase assay. Conclusion The mechanisms behind the cancer preventive properties of foods rich in flavan-3-ols and caffeoylquinic acids are not associated with metabolic pathways directly linked to the Eph-ephrin system. However, the ellagitannin-derived colonic metabolite urolithin D was able to exert remarkable and selective EphA-ephrin-A inhibition, which might impact on prostate cancer prevention.

Trimethylamine-N-oxide (TMAO) is a small organic molecule, derived from the intestinal and hepatic metabolism of dietary choline and carnitine. Although the involvement of TMAO in the framework of many chronic diseases has been recently described, no evidence on its putative role in the central nervous system has been provided. The aim of this study was to evaluate whether TMAO is present at detectable levels in human cerebrospinal fluid (CSF). CSF was collected for diagnostic purposes from 58 subjects by lumbar puncture and TMAO was quantified by using liquid chromatography coupled with multiple-reaction monitoring mass spectrometry. The molecule was detected in all samples, at concentrations ranging between 0.11 and 6.43 µmol/L. Further analysis on CSF revealed that a total of 22 subjects were affected by Alzheimer’s disease (AD), 16 were affected by non-AD related dementia, and 20 were affected by other neurological disorders. However, the stratification of TMAO levels according to the neurological diagnoses revealed no differences among the three groups. In conclusion, we provide the first evidence that TMAO can be assessed in human CSF, but the actual impact of this dietary metabolite in the patho-physiolgy of the central nervous system requires further study.

The market of plant-based nutraceuticals and food supplements is continuously growing due to the increased consumer demand. The introduction of new products with relevant nutritional characteristics represents a new way of providing bioactive compounds and (poly)phenols to consumers, becoming a strategy to ideally guarantee the health benefits attributed to plant foodstuffs and allowing the increase of daily bioactive compound intake. A paramount step in the study of nutraceuticals is the evaluation of the bioavailability and metabolism of their putatively active components. Therefore, the aim of the present study was to investigate the absorption profile of the (poly)phenolic compounds contained in three different plant-based food supplements, made of 36 different plant matrices, which were consumed by 20 subjects in an open one-arm study design. Blood samples were collected at baseline and 1, 2, 5, and 10 h after capsule intake. Twenty quantifiable metabolites deriving from different (poly)phenolic compounds were identified. Results showed that the consumption of the three capsules allowed the effective absorption of several (poly)phenolic compounds and metabolites appearing at different times in plasma, thereby indicating different absorption profiles. The capsules thus ensured potential health-promoting molecules to be potentially available to target tissues and organs.

Urolithins are bioactive ellagitannin-derived metabolites showing a wide phenotypic variation in their production by the gut microbiota. This work represents a first in vitro step toward the development of new strategies focused on the oral supplementation of urolithins with the aim of overcoming their selective production and making their putative health benefits available for the whole population. In order to study their gastrointestinal stability, urolithin A, urolithin B, and urolithin B-glucuronide, as well as ellagic acid, were subjected to a simulated gastrointestinal digestion model consisting of oral, gastric, and pancreatic steps followed by a 24-h fecal fermentation. The effect of the entero-hepatic recirculation on urolithin B-glucuronide, a phase II metabolite, was also investigated. Urolithin B was the molecule able to resist to a greater extent the conditions of the gastrointestinal tract, while urolithin A and ellagic acid were drastically unstable during the colonic step. Conjugation with glucuronic acid, ideally occurring in the liver, conferred to urolithin B an increased stability, which may be interesting in the framework of entero-hepatic recirculation. This set of experiments lets hypothesize that orally supplemented urolithins may come into contact with the colonic epithelium and become accessible for uptake or exert local anti-inflammatory activity, overcoming the limitations of enterotypes unable to convert ellagitannins into these putatively beneficial metabolites.

Urinary biomarkers of mycotoxin exposure were evaluated in a group of celiac patients (n = 55) and in a control group of healthy subjects (n = 50) following their habitual diet. Deoxynivalenol (DON), zearalenone (ZEN), and fumonisin B1 (FB1) were monitored in 105 urinary samples collected from the two groups. Dietary habits were also recorded through compilation of a seven-day weighed dietary diary. Biomarkers of mycotoxin exposure were detected in 21 celiac patients and in 15 control subjects, corresponding to about 34% of total participants. In particular, ZEN was the most detected mycotoxin among all the studied subjects with a total of 19 positive cases. Results did not show a statistically significant difference in mycotoxin exposure between the two groups, and the presence of specific mycotoxins was not related to the intake of any particular food category. Our findings suggest little urgency of specific regulation for gluten free products, although the prevalence of exposure observed in free-living diets of both celiac and healthy subjects underlines the need of a constant surveillance on mycotoxins occurrence at large.

Coffea arabica silverskin (CSS), the inner fruit layer surrounding coffee beans, was analyzed for its (poly)phenolic and caffeine content by means of liquid chromatography–tandem mass spectrometry and evaluated for its antioxidant properties by means of the Folin–Ciocalteu and FRAP methods. The most abundant quantified phenolics were caffeoylquinic acids, with the 5- and 3-isomers being the most relevant (199 mg/100 g and 148 mg/100 g, respectively). The three caffeoylquinic acid isomers reached a total concentration of 432 mg/100 g, corresponding to 74% of the total chlorogenic acids detected in CSS. The level of the three feruloylquinic acids detected was 143 mg/100 g, corresponding to 23%, and the two identified coumaroylquinic acids plus the two caffeoylquinic acid lactones were only marginally contributing to the final figure (only 3% of total hydroxycinnamates). No unconjugated phenolic acid was detected. Caffeine content in CSS was equal to 10 mg/g of product, 3.5 times lower than most coffee brews. The total antioxidant capacity (TAC) of CSS was 139 mmol Fe2 +/kg, a value similar to those of valuable sources of food antioxidants like dark chocolate, herbs and spices. Besides its potential as a food supplement, CSS may represent an innovative functional ingredient exploitable to increase the TAC of a wide range of food products.

Background and aims Trans-resveratrol (RSV) is a natural compound occurring in different foods and plants, which in vivo is rapidly conjugated with glucuronic acid and sulfate. Despite its demonstrated cardioprotective activity, the bioaccumulation of RSV or its metabolites in cardiac tissue is still unknown. Methods and results Diabetic rats were randomized to 1, 3 or 6 weeks of RSV treatment at two different doses (1 or 5 mg/kg/day). A dose and time-dependent accumulation was observed, with no detectable levels of RSV metabolites found in heart tissues after 1 week and significant concentrations of RSV-3-sulfate and RSV-3-glucuronide after 6 weeks of treatment (0.05 nmol/g of tissue and 0.01 nmol/g of tissue, respectively). Tissue accumulation of RSV metabolites was accompanied by an improvement of cardiac function in long-term diabetes, when myocardial morpho-functional damage is more evident, with an almost complete recovery of all hemodynamic parameters, at the highest RSV dose. Conclusion Even if a higher concentration of RSV in tissues cannot be ruled out after constant oral administration, an accumulation coherent with what is usually evaluated in cell based mechanistic studies is largely unattainable and the RSV unconjugated form would not be present in this paradigm. The current investigation provides data on myocardial tissue concentrations of RSV metabolites, after short/medium term RSV treatment. This knowledge constitutes a basic requirement for future studies aimed at reliably defining the molecular pathways underlying RSV-mediated cardioprotective effects and opens up new perspectives for research focused on testing phenolic compounds as adjuvants in degenerative heart diseases.

The possibility of counteracting inflammation-related barrier defects with dietary compounds such as (poly)phenols has raised much interest, but information is still scarce. We have investigated here if (+)-catechin (CAT) and procyanidin B2 (PB2), two main dietary polyphenols, protect the barrier function of intestinal cells undergoing inflammatory stress. The cell model adopted consisted of co-cultured Caco-2 and HT29-MTX cells, while inflammatory conditions were mimicked through the incubation of epithelial cells with the conditioned medium of activated macrophages (MCM). The epithelial barrier function was monitored through trans-epithelial electrical resistance (TEER), and ROS production was assessed with dichlorofluorescein, while the expression of tight-junctional proteins and signal transduction pathways were evaluated with Western blot. The results indicated that MCM produced significant oxidative stress, the activation of NF-&kappa, B and MAPK pathways, a decrease in occludin and ZO-1 expression, and an increase in claudin-7 (CL-7) expression, while TEER was markedly lowered. Neither CAT nor PB2 prevented oxidative stress, transduction pathways activation, ZO-1 suppression, or TEER decrease. However, PB2 prevented the decrease in occludin expression and both polyphenols produced a huge increase in CL-7 abundance. It is concluded that, under the conditions adopted, CAT and PB2 do not prevent inflammation-dependent impairment of the epithelial barrier function of intestinal cell monolayers. However, the two compounds modify the expression of tight-junctional proteins and, in particular, markedly increase the expression of CL-7. These insights add to a better understanding of the potential biological activity of these major dietary flavan-3-ols at intestinal level.

The consumption of foodstuffs yielding circulating compounds able to maintain endothelial function by improving nitric oxide (NO) bioavailability can be considered as an effective strategy for cardiovascular disease prevention. This work assessed the in vitro effects of urolithin A, urolithin B, and urolithin B-glucuronide, ellagitannin-derived metabolites of colonic origin, on NO release and endothelial NO synthase (eNOS) activation in primary human aortic endothelial cells (HAECs). Urolithins were tested both individually at 15 μM and as a mixture of 5 μM each, at different time points. The biotransformation of these molecules in cell media due to cell metabolism was also evaluated by UHPLC-MS(n). The mix of urolithins at 5 μM significantly increased nitrite/nitrate levels following 24 h of incubation, while single urolithins at 15 μM did not modify NO bioavailability. Both the mix of urolithins at 5 μM and urolithin B-glucuronide at 15 μM activated eNOS expression. All urolithins underwent metabolic reactions, but these were limited to conjugation with sulfate moieties. This study represents a step forward in the understanding of cardiovascular health benefits of ellagitannin-rich foodstuffs and backs the idea that peripheral cells may contribute to urolithin metabolism., info:eu-repo/semantics/published

Research on the potential protective effects of coffee and its bioactives (caffeine, chlorogenic acids and diterpenes) against oxidative stress and related chronic disease risk has been increasing in the last years. The present review summarizes the main findings on the effect of coffee consumption on protection against lipid, protein and DNA damage, as well as on the modulation of antioxidant capacity and antioxidant enzymes in human studies. Twenty-six dietary intervention studies (involving acute and chronic coffee intake) have been considered. Overall, the results suggest that coffee consumption can increase glutathione levels and improve protection against DNA damage, especially following regular/repeated intake. On the contrary, the effects of coffee on plasma antioxidant capacity and antioxidant enzymes, as well as on protein and lipid damage, are unclear following both acute and chronic exposure. The high heterogeneity in terms of type of coffee, doses and duration of the studies, the lack of information on coffee and/or brew bioactive composition, as well as the choice of biomarkers and the methods used for their evaluation, may partially explain the variability observed among findings. More robust and well-controlled intervention studies are necessary for a thorough understanding of the effect of coffee on oxidative stress markers in humans.

The asymmetric synthesis of a set of hydroxyphenyl γ-valerolactones was achieved starting from 2-silyloxyfuran and alkoxy-substituted benzaldehydes as common precursors. Key synthesis steps included an enantioselective vinylogous Mukaiyama aldol reaction and a Barton–McCombie deoxygenation. Five enantioenriched γ-valerolactone targets were obtained in 5–6 steps, 18–63% overall yields and 82–98 % ee, paving the way for the straightforward entry to this class of biologically effective and poorly available flavan-3-ol metabolites. In parallel, an unprecedented one-pot reductive ring expansion process was fortuitously discovered, yielding racemic δ-lactone analogues from phenolic butanolide precursors.

cope This work aimed at investigating absorption, metabolism, and bioavailability of phenolic compounds after consumption of wholegrain bread or bread enriched with an aleurone fraction. Methods and results Two commercially available breads were consumed by 15 participants on three occasions and matched for either the amount of ferulic acid in the bread or the amount of bread consumed. Urine was collected for 48 h from all the volunteers for phenolic metabolite quantification. Blood samples were collected for 24 h following bread consumption in five participants. A total of 12 and 4 phenolic metabolites were quantified in urine and plasma samples, respectively. Metabolites were sulfate and glucuronic acid conjugates of phenolic acids, and high concentrations of ferulic acid-4’-O-sulfate, dihydroferulic acid-4’-O-sulfate, and dihydroferulic acid-O-glucuronide were observed. The bioavailability of ferulic acid was significantly higher from the aleurone-enriched bread when all ferulic acid metabolites were accounted for. Conclusions The study shows that low amounts of aleurone-enriched bread resulted in equivalent plasma levels of ferulic acid as wholegrain bread. This could suggest that, if the absorbed phenolic metabolites after wholegrain product intake exert health benefits, equal levels could be reached through the consumption of lower doses of refined products enriched in aleurone fraction.

Wheat aleurone, due to its potentially higher bioaccessibility and bioavailability of micronutrients and phenolic acids, could represent a useful ingredient in the production of commonly consumed cereal-based food. The aim of the present study was to investigate the in vitro bioaccessibility of phenolic acids both from an aleurone-enriched bread and from a whole grain bread. The two bread samples were firstly characterized for the phenolic acid content. An in vitro digestion was then performed in order to evaluate the release of phenolic acids. The results obtained suggest that the bioaccessibility of the phenolic acids in the aleurone-enriched bread is higher than in the whole grain bread. These in vitro results suggest the potential use of aleurone in the production of foods, and this may represent an attractive possibility to vehicle nutritionally interesting components to consumers.

Atherosclerosis, one of the leading causes of death worldwide, is characterized by impaired endothelial function and lipid metabolism, among other factors. Ellagitannins are a class of phenolic compounds that may play a role in cardiovascular health. This work aimed to study the potential atheroprotective effects of urolithins, ellagitannin-derived gut microbiota metabolites, on different key factors in atherosclerosis development: the ability of monocytes to adhere to endothelial cells and the uptake and efflux of cholesterol by macrophages. The biotransformations urolithins undergo in peripheral cells were also evaluated. Results indicated that some urolithins and ellagic acid were able to reduce the adhesion of THP-1 monocytes to human umbilical vein endothelial cells (HUVECs) and the secretion of a cellular adhesion molecule (sVCAM-1) and pro-inflammatory cytokine (IL-6). Urolithin C, a combination of urolithins A and B, and ellagic acid also decreased the accumulation of cholesterol in THP-1-derived macrophages, but they were not able to promote cholesterol efflux. The analysis of cell media by UHPLC-ESI-MS(n) indicated urolithins and ellagic underwent extensive metabolism, with sulfate and methyl conjugation. This evidence indicates that atherosclerotic processes may be attenuated by urolithins, but future human intervention trials are required to establish if is translated in vivo.

Green tea is a popular beverage, prepared with infusion of unfermented dried leaves of Camellia sinensis, and is one of the most relevant sources of polyphenolic compounds in the human diet. This study reports green tea flavan-3-ol absorption, metabolism and complete urinary excretion up to 48 h in 20 healthy volunteers. Urinary and tea samples were analysed by high-performance liquid chromatography coupled with tandem mass spectrometry. Green tea contained monomeric flavan-3-ols and proanthocyanidins with a total polyphenol content of 728 μmol. A total of 41 metabolites were identified in urines, all present in conjugated forms. Among these, six colonic metabolites of green tea flavan-3-ols were identified for the first time after green tea consumption in humans. The average 48 h bioavailability was close to 62%, major contributors being microbial metabolites. Some volunteer showed a 100% absorption/excretion, whereas some others were unable to efficiently absorb/excrete this class of flavonoids. This suggests that colonic ring fission metabolism could be relevant in the putative bioactivity of green tea polyphenols.

One of the most recently proposed candidates as a potential trigger for cardiovascular diseases is trimethylamine-N-oxide (TMAO). Possible direct effects of TMAO on myocardial tissue, independent of vascular damage, have been only partially explored so far. In the present study, we assessed the detrimental direct effects of TMAO on cardiomyocyte contractility and intracellular calcium dynamics, and the ability of urolithin B-glucuronide (Uro B-gluc) in counteracting TMAO-induced cell damage. Cell mechanics and calcium transients were measured, and ultrastructural analysis was performed in ventricular cardiomyocytes isolated from the heart of normal adult rats. Cells were either untreated, exposed to TMAO, or to TMAO and Uro B-gluc. TMAO exposure worsened cardiomyocyte mechanics and intracellular calcium handling, as documented by the decrease in the fraction of shortening (FS) and the maximal rate of shortening and re-lengthening, associated with reduced efficiency in the intracellular calcium removal. Ultrastructurally, TMAO-treated cardiomyocytes also exhibited glycogen accumulation, a higher number of mitochondria and lipofuscin-like pigment deposition, suggesting an altered cellular energetic metabolism and a higher rate of protein oxidative damage, respectively. Uro B-gluc led to a complete recovery of cellular contractility and calcium dynamics, and morphologically to a reduced glycogen accumulation. We demonstrated for the first time a direct negative role of TMAO on cardiomyocyte functional properties and the ability of Uro B-gluc in counteracting these detrimental effects.

Myeloid angiogenic cells (MACs) play a key role in endothelial repairing processes and functionality but their activity may be impaired by the lipotoxic effects of some molecules like stearic acid (SA). Among the dietary components potentially able to modulate endothelial function in vivo, (poly)phenolic compounds represent serious candidates. Here, we apply a comprehensive multidisciplinary approach to shed light on the prospects of Bergamot (Citrus bergamia), a citrus fruit rich in flavanones and other phenolic compounds, in the framework of lipotoxicity-induced MACs impairment. The flavanone profile of bergamot juice was characterized and 16 compounds were identified, with a new 3-hydroxy-3-methylglutaryl (HMG) flavanone, isosakuranetin-7-O-neohesperidoside-6″-O-HMG, described for the first time. Then, a pilot bioavailability study was conducted in healthy volunteers to assess the circulating flavanone metabolites in plasma and urine after consumption of bergamot juice. Up to 12 flavanone phase II conjugates (sulfates and glucuronides of hesperetin, naringenin and eriodyctiol) were detected and quantified. Finally, the effect of some of the metabolites identified in vivo, namely hesperetin-7-O-glucuronide, hesperetin-3'-O-glucuronide, naringenin-7-O-glucuronide and naringenin-4'-O-glucuronide, was tested, at physiological concentrations, on gene expression of inflammatory markers and apoptosis in MACs exposed to SA. Under these conditions, naringenin-4'-O-glucuronide and hesperetin-7-O-glucuronide were able to modulate inflammation, while no flavanone glucuronide was effective in curbing stearate-induced lipoapoptosis. These results demonstrate that some flavanone metabolites, derived from the in vivo transformation of bergamot juice phenolics in humans, may mitigate stearate-induced inflammation in MACs., info:eu-repo/semantics/published

Gluten-free products present major challenges for the food industry in terms of organoleptic, technological and nutritional characteristics. The absence of gluten has been shown to affect starch digestibility, thus increasing the postprandial glycaemic response. However, in recent years, gluten-free technologies have been improved, thus possibly modifying this quality parameter. We investigated the glycaemic index (GI) of 10 commercial foods aiming to update the GI values of the most common gluten-free products consumed in Italy. The in vivo GI was evaluated for six bakery products and four types of pasta. The postprandial glucose response was obtained in two groups with 10 healthy volunteers each. The overall GI values ranged from 37.5 for breakfast biscuits to 66.7 for puffed multigrain cake. Breads and pasta had GI values consistently lower than those previously reported in the literature. The present study showed that several commercial GF products exhibited low and medium GI values, not confirming the previous observations on the high GI of GF. However, considering the multiple formulations and processes for preparation of these products, further studies are recommended.

Following acute ingestion of green tea by six human subjects, HPLC-MS 2 analysis revealed that flavan-3-ol methyl, glucuronide and sulfate metabolites appeared in the bloodstream but did not pass through the blood–cerebrospinal fluid barrier. These observations emphasize the discrepancies between in vitro and in vivo evidence on the neuroprotective role of these compounds. If, as has been proposed, green tea exerts neuroprotective effects, this finding indicates that the active components are not flavan-3-ols or their metabolites. Alternatively, a systemic action may be hypothesised whereby dietary flavan-3-ols up-regulate antioxidant defences and/or reduce inflammation, the benefit of which may be effective throughout the body.

All methods for assessing the total antioxidant capacity (TAC) of food samples are strongly affected by the solvents used during extraction. In recent years a sequential solvent extraction procedure utilising water and acetone has been widely used for TAC measurements of foods. To better understand the efficiency of this procedure in terms of the amount of extracted antioxidants and the subsequent measurement of TAC, two vegetables (onion and spinach) and two fruits (orange and tomato) were sequentially extracted with water, acetone and chloroform. Each extract fraction was analysed separately for its content of known antioxidant compounds by specific procedures and for its TAC by the Trolox equivalent antioxidant capacity assay. The results showed that the compounds in the water and acetone extracts were the main contributors to TAC. The chloroform extracts did not contribute to TAC, with the exception of the spinach extract, owing to the presence of low levels of carotenoids. In conclusion, the analysed extraction procedure was more effective for foods rich in water-soluble antioxidants than for those rich in lipid-soluble antioxidants.

M.A. BIANCHI, D. DEL RIO, N. PELLEGRINI, G. SANSEBASTIANO, E. NEVIANI AND F. BRIGHENTI. 2004. Aims: The ability of probiotic micro-organisms to adhere to the intestinal surface is regarded as a substantial advantage in terms of bacteria persistence in the gastrointestinal tract. The aim of the present study was the development of a method based on fluorescent staining of bacteria and subsequent spectrofluorimetric detection to quantify the adhesion of several strains of Lactobacillus and Bifidobacterium to Caco-2 cells. Methods and Results: Lactic acid bacteria strains were subjected to fluorescent staining using the viable probe carboxyfluorescein diacetate and subsequently incubated on Caco-2 monolayers. The adhesion of the microorganisms was determined by spectrofluorimetry following the lysis of the attached bacterial cells and expressed as adhesion percentage. The values obtained for the micro-organisms tested ranged from 4% for Bifidobacterium infantis Bi1 to 10% for a Bifidobacterium mixture containing three different strains. Conclusions: In the present study we successfully applied fluorescent labelling and fluorimetric detection to investigate the adhesive properties of some Lactobacillus and Bifidobacterium strains and a Bifidobacterium mixture to Caco-2 cells. Significance and Impact of the Study: The results proved that fluorescent labelling is suitable for adhesion studies and provides a reliable and safer alternative to radioactive labelling.

Background: Palm oil (PO) may be an unhealthy fat because of its high saturated fatty acid content.Objective: The objective was to assess the effect of substituting PO for other primary dietary fats on blood lipid–related markers of coronary heart disease (CHD) and cardiovascular disease (CVD).Design: We performed a systematic review and meta-analysis of dietary intervention trials. Studies were eligible if they included original data comparing PO-rich diets with other fat-rich diets and analyzed at least one of the following CHD/CVD biomarkers: total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, TC/HDL cholesterol, LDL cholesterol/HDL cholesterol, triacylglycerols, apolipoprotein A-I and B, very-low-density lipoprotein cholesterol, and lipoprotein(a).Results: Fifty-one studies were included. Intervention times ranged from 2 to 16 wk, and different fat substitutions ranged from 4% to 43%. Comparison of PO diets with diets rich in stearic acid, monounsaturated fatty acids (MUFAs), and polyunsaturated fatty acids (PUFAs) showed significantly higher TC, LDL cholesterol, apolipoprotein B, HDL cholesterol, and apolipoprotein A-I, whereas most of the same biomarkers were significantly lower when compared with diets rich in myristic/lauric acid. Comparison of PO-rich diets with diets rich in trans fatty acids showed significantly higher concentrations of HDL cholesterol and apolipoprotein A-I and significantly lower apolipoprotein B, triacylglycerols, and TC/HDL cholesterol. Stratified and meta-regression analyses showed that the higher concentrations of TC and LDL cholesterol, when PO was substituted for MUFAs and PUFAs, were not significant in young people and in subjects with diets with a lower percentage of energy from fat.Conclusions: Both favorable and unfavorable changes in CHD/CVD risk markers occurred when PO was substituted for the primary dietary fats, whereas only favorable changes occurred when PO was substituted for trans fatty acids. Additional studies are needed to provide guidance for policymaking.

The consumption of wholemeal cereals has been associated with the reduced risk of several chronic diseases, and the mechanisms behind these protective effects may be linked, besides dietary fiber and micronutrients, to an increased intake of hydroxycinnamates contained in the bran. Among bran fractions, aleurone usually contains the highest concentration of ferulic acid and diferulic acid esters linked to arabinoxylans representing the most relevant subclasses. The aim of the present study was to evaluate the absorption of hydroxycinnamates by measuring the urinary metabolite profiles of rats fed with the two different aleurone fractions (the inner part of the aleurone, named wheat aleurone A, WA-A, and the outer part, named wheat aleurone B, WA-B). An acute feeding experiment with two rat groups consuming equivalent amounts of total ferulic acid from the different aleurone fractions was carried out to evaluate ferulic acid bioavailability as affected by different sources. A chronic feeding experiment was also conducted with two rat groups consuming the same amount of the two different aleurone fractions, carried out to investigate the short-term metabolism and absorption of aleurone phenolics. The results revealed higher increases in the 24 h-excretion of phenolic metabolites/catabolites in aleurone fed rats compared to rats fed with a regular diet. Specifically, in the chronic feeding, ferulic acid was more bioavailable when WA-A was ingested. Based on previous observations, demonstrating various positive physiological responses to ferulic acid and aleurone fractions characterized by higher phenolic bioavailability, our results indicate that the WA-A fraction has potentially interesting nutritional characteristics that might be used for the formulation of new wheat based products.

The present study was aimed at evaluating in patients with type 2 diabetes: (1) the glycaemic response to four starchy foods based on wheat, typical of the Italian diet; (2) the importance of some food characteristics in relation to their effects on postprandial glucose response. Seventeen patients with type 2 diabetes (eleven men and six women) participated in the study. All patients consumed, in random order and on alternate days, 50 g available carbohydrate provided by 90 g white bread and, according to a randomised procedure, an equivalent amount of carbohydrate provided by one (n 8) or two (n 9) of three other different test foods (g): pizza 85, potato dumplings 165, hard toasted bread 60. Foods had a similar nutrient composition. Plasma glucose response, measured for 180 min, was significantly lower after the potato dumplings than after white bread at 90 (Pin vitro hydrolysis with α-amylase was about 30 % lower for potato dumplings than for the other foods. However, no differences in the resistant starch content, the rate of diffusion of simple sugars added to a dialysis tube containing the food, and the viscosity of digesta were observed among the test foods. Scanning electron microscopy of potato dumplings showed a compact structure compatible with impaired accessibility of starch to digestive enzymes. In conclusion, carbohydrate-rich foods typical of the Italian diet which are often consumed as an alternative to pasta dishes are not equivalent in terms of metabolic impact in diabetic patients. Due to their low blood glucose response, potato dumplings represent a valid alternative to other starchy foods in the diabetic diet. Food structure plays an important role in determining starch accessibility to digestion, thus influencing the postprandial blood glucose response.

To evaluate the influence of sourdough fermentation on starch digestibility in bread, four experimental breads were obtained, prepared from two different wheat flours (whole or white) by two different leavening techniques (sourdough and with Saccharomyces cerevisiae). Products were analyzed for their starch, fiber and resistant starch (RS) content and then submitted to in vitro hydrolysis with porcine alpha-amylase. On the same breads, postprandial blood glucose was evaluated in healthy human subjects. Both sourdough fermented breads gave glycaemic responses significantly lower (p < 0.001) than the corresponding products leavened with S. cerevisiae. On the contrary, the presence of fiber did not influence the glycaemic potential of breads. RS levels were higher in the sourdough products, whereas no differences were observed either in the rate of starch hydrolysis or in the degree of polymerization of the starch residues after the in vitro hydrolysis. We may conclude that sourdough fermentation is a technique able to reduce the glycaemic response to bread and that the mechanism does not seem related to the rate of starch hydrolysis.

Objective: To investigate the effect of a breakfast cereal containing inulin on blood lipids and colonic ecosystem in normolipidemic young men. Setting: Department of Food Science and Microbiology,University of Milan, Italy. Subjects: Twelve healthy male volunteers, age 23.3±0.5 y, body mass index (BMI) 25.7±1.2 kg/m2 (mean±s.e.m.). Interventions: Subjects consumed daily, for three periods of four weeks, 50 g of a rice-based ready-to-eat cereal (placebo) and the same cereal containing 18% inulin (test) in substitution of their habitual breakfast, then returned to the habitual diet (wash-out). They followed no other dietary restrictions. Results: No changes in body weight, dietary habits, faecal and bile acid output, faecal short-chain fatty acid (SCFA) and faecal pH, were observed at the end of each period, whereas plasma total cholesterol and triacylglycerols significantly decreased at the end of test period by 7.9±5.4 (P

OBJECTIVE: To examine whether Konjac-mannan (KJM) fiber improves metabolic control as measured by glycemia, lipidemia, and blood pressure in high-risk type 2 diabetic patients. RESEARCH DESIGN AND METHODS: A total of 11 hyperlipidemic and hypertensive type 2 diabetic patients treated conventionally by a low-fat diet and drug therapy participated. After an 8-week baseline, all were randomly assigned to take either KJM fiber-enriched test biscuits (0.7 g/412 kJ [100 kcal] of glucomannan) or matched placebo wheat bran fiber biscuits during two 3-week treatment phases separated by a 2-week washout period. The diet in either case was metabolically controlled and conformed to National Cholesterol Education Program Step 2 guidelines, while medications were maintained constant. Efficacy measures included serum fructosamine, lipid profiles, apolipoproteins, blood pressure, body weight, and nutritional analysis. RESULTS: Compared with placebo, KJM significantly reduced the metabolic control primary end points: serum fructosamine (5.7%, P = 0.007, adjusted alpha = 0.0167), total:HDL cholesterol ratio (10%, P = 0.03, adjusted alpha = 0.05), and systolic blood pressure (sBP) (6.9%, P = 0.02, adjusted alpha = 0.025). Secondary end points, including body weight, total, LDL, and HDL cholesterol, triglycerides, apolipoproteins A-1, B, and their ratio, glucose, insulin, and diastolic blood pressure, were not significant after adjustment by the Bonferroni-Hochberg procedure. CONCLUSIONS: KJM fiber added to conventional treatment may ameliorate glycemic control, blood lipid profile, and sBP in high-risk diabetic individuals, possibly improving the effectiveness of conventional treatment in type 2 diabetes.

Resistant starch (RS) has been defined as the sum of starch and starch-degradation products that reach the human large intestine (Champ, 1994), and it is now regarded as a sub-fraction of starch with a positive impact on colonic welfare and lipid metabolism. An early estimate of the RS intake in Europe gave an average value of approximately 4 g/d (Dyssler & Hoffem, 1994a). However, since no information is available for Italy, the aim of the present study was to estimate the intake of RS in the Italian diet by direct analysis of RS in a range of typical foods representing the main sources of starch intake in the country. The selection of representative foods and of food consumption data were based on published results of the National Food Consumption Study conducted during the 1980s by the National Institute of Nutrition on 10 000 households, using weighed-food records plus inventory methodologies (Saba et al. 1990; Turrini et al. 1991). Three main groups of foods were considered: cereals (pasta, rice, bread and bread products, and pastries), potatoes, legumes. Different commercial brands for each sample were purchased, according to the known presence on the market. Samples were prepared ‘as eaten’ and submitted to simulated chewing, followed by total and resistant starch determination using the enzymic procedure published as a result of the EC Concerted Action EURESTA (Champ, 1992). From these results, the estimated average intake of RS in Italy was found to be 8.5 g/d, with regional differences (from 7.2 g/d in the north-west to 9.2 g/d in the south) mainly due to the different consumption of some typical Italian starchy food (bread, pasta, legumes).

Naringenin, together with its glycosidic forms, is a flavanone abundant in grapefruit and orange. It has been detected in human plasma, following citrus juice intake, at sub-µmolar concentrations, and its main phase II conjugated metabolites (naringenin-7-O-glucuronide and narigenin-4'-O-glucuronide) have been identified in urine. Recent evidence suggests a potential active anti-inflammatory role of flavonoids on macrophages, cells actively involved in atherogenesis. The aim of this study was to evaluate the effects of naringenin and its phase II metabolites on the expression of specific genes in differently activated macrophages at concentrations coherent with dietary exposure. Results suggest that phase II metabolites, as well as the aglyconic form of naringenin, were able to perturb macrophage gene expression in directions that are not always consistent with anti-inflammatory effects. Moreover, the effects of metabolites were not always consistent with each other and with those of their aglycone, underlining the paramount importance of testing physiological forms of phytochemicals within in vitro experimental models. In vivo studies are needed to further explore these observations and investigate their practical consequences.

Background and aims Resveratrol, the most investigated dietary compound in studies aimed at linking wine consumption to human health, is an extremely minor component of this beverage and it is generally studied in vitro as the unconjugated aglycone at concentrations largely exceeding those found in the human circulatory system after dietary intake. Moreover, following intestinal absorption, trans -resveratrol and its glucoside, which are naturally present in wine and other food sources, are converted to sulphate and glucuronide metabolites. An estrogenic activity has previously been documented for resveratrol, yet nothing is known about the activity of its blood-circulating metabolic derivatives. Methods and results Using a yeast two-hybrid detection system relying on the interaction between the ligand-binding domain of the human oestrogen receptors α and β and the human coactivator Tif2, we have systematically examined the oestrogen agonist and antagonist activities of the two main resveratrol forms present in planta ( trans -resveratrol and trans -resveratrol-3- O -glucoside) and of the three main metabolites found in human plasma ( trans -resveratrol-3- O -sulphate, trans -resveratrol-3- O -glucuronide and trans -resveratrol-4′- O -glucuronide). Only resveratrol-3- O -sulphate was found to display a fairly strong and oestrogen receptor α-preferential antagonistic activity, which was confirmed in a human breast adenocarcinoma cell line containing a luciferase reporter gene under the control of an oestrogen-responsive promoter. Conclusions We show, for the first time, that resveratrol-3- O -sulphate, but neither of its metabolites, is endowed with anti-estrogenic activity and how human metabolism of phenolic substances plays a pivotal role in modulating their biological effect.

Scope The main objectives of this study were to estimate dietary fumonisin exposure and nutrient intake in a group of patients diagnosed with celiac disease compared to non-celiac subjects. Methods and results The fumonisin level in 118 frequently consumed corn-based products was determined and dietary habits were recorded using a 7-day weighed food record. Data were then compared to those obtained for a control group. The fumonisin intake in the celiac patients was significantly higher than in controls, with mean values (± SE) of 0.395 ± 0.049 and 0.029 ± 0.006 μg/kg body weight per day, respectively. With regard to nutritional habits, celiac patients showed a preference for a high fat diet, coupled with a high intake of sweets and soft drinks and a low intake of vegetables, iron, calcium and folate. Conclusion These findings may have serious health implications for the celiac population due to the widespread occurrence of fumonisins in most of the widely consumed gluten-free products, leading to continuous exposure to this particular mycotoxin. Moreover, the recorded nutritional quality of the celiac patient's diet raises concerns regarding its long-term adequacy and its potential impact on chronic conditions such as type 2 diabetes and cardiovascular diseases.

International audience; The Eph tyrosine kinase receptors and their ephrin ligands play a central role in human cancer as their deregulated expression induces tumorigenesis with aggressive phenotypes. To evaluate their potential contribution to EphA2-ephrinA1 modulation, several colonic catabolites of dietary (poly)phenolics, known to be generated in vivo, were screened using an ELISA-based binding assay. Some of the catabolites inhibited the binding in a dose-dependent manner (IC50 values from 0.26 to 43 mu M). Functional studies on prostate adenocarcinoma cells revealed that pyrogallol and protocatechuic acid specifically antagonized ephrinA1-Fc-induced EphA2 phosphorylation at concentrations that were not cytotoxic. The active concentrations of pyrogallol appear to be close to what can be reached in vivo under physiological conditions. Finally, because of the roles played by the Eph-ephrin system not only in cancer development but also in neurodegeneration and diabetes, pyrogallol and protocatechuic acid are candidates for more detailed functional studies to elucidate their role in these pathophysiological processes.

The aim of the study was to investigate the effect of four weeks ingestion of 10% fiber diets (cellulose, lignocellulose, pectin and guar gum) and a fiber-free diet on cecal microflora composition and its primary bile acid metabolizing activity in vitro in female Sprague Dawley rats. There was no difference in the qualitative and quantitative cecal microflora composition in rats fed cellulose and lignocellulose diets and those fed fiber-free diet. Guar gum and pectin diets significantly increased Bacteroidaceae compared to cellulose and lignocellulose diets. The counts of bifidobacteria were significantly higher in rats fed guar gum than in all the other groups. Clostridia were present in high counts in rats fed guar gum and pectin and generally absent in all the other groups. As regards 7α-dehydroxylating cholic and chenodeoxycholic microorganisms, cellulose and lignocellulose diets significantly decreased these microbial counts compared to all the diets. The results show that dietary fiber can induce alterations of cecal microflora composition and intestinal bile acid metabolism.