Polyphenol levels in human urine after intake of six different polyphenol-rich beverages

Dietary polyphenols are suggested to participate in the prevention of CVD and cancer. It is essential for epidemiological studies to be able to compare intake of the main dietary polyphenols in populations. The present paper describes a fast method suitable for the analysis of polyphenols in urine, selected as potential biomarkers of intake. This method is applied to the estimation of polyphenol recovery after ingestion of six different polyphenol-rich beverages. Fifteen polyphenols including mammalian lignans (enterodiol and enterolactone), several phenolic acids (chlorogenic, caffeic, m-coumaric, gallic, and 4-Omethylgallic acids), phloretin and various flavonoids (catechin, epicatechin, quercetin, isorhamnetin, kaempferol, hesperetin, and naringenin) were simultaneously quantified in human urine by HPLC coupled with electrospray ionisation mass-MS (HPLC-electrospray-tandem mass spectrometry) with a run time of 6 min per sample. The method has been validated with regard to linearity, precision, and accuracy in intra- and inter-day assays. It was applied to urine samples collected from nine volunteers in the 24 h following consumption of either green tea, a grape-skin extract, cocoa beverage, coffee, grapefruit juice or orange juice. Levels of urinary excretion suggest that chlorogenic acid, gallic acid, epicatechin, naringenin or hesperetin could be used as specific biomarkers to evaluate the consumption of coffee, wine, tea or cocoa, and citrus juices respectively

How to better consider and understand interindividual variability in response to polyphenols in clinical trials

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Increased bioavailability of hesperetin-7-glucoside compared with hesperidin results in more efficient prevention of bone loss in adult ovariectomised rats

Hesperidin (Hp), a citrus flavonoid predominantly found in oranges, shows bone-sparing effects in ovariectomised (OVX) animals. In human subjects, the bioavailability of Hp can be improved by the removal of the rhamnose group to yield hesperetin-7-glucoside (H-7-glc). The aim of the present work was to test whether H-7-glc was more bioavailable and therefore more effective than Hp in the prevention of bone loss in the OVX rat. Adult 6-month-old female Wistar rats were sham operated or OVX, then pair fed for 90d a casein-based diet supplemented or not with freeze-dried orange juice enriched with Hp or H-7-glc at two dose equivalents of the hesperetin aglycone (0·25 and 0·5%). In the rats fed 0·5%, a reduction in OVX-induced bone loss was observed regarding total bone mineral density (BMD):+7·0% in OVX rats treated with Hp (HpOVX) and +6·6% in OVX rats treated with H-7-glc (H-7-glcOVX) v. OVX controls (P<0·05). In the rats fed 0·25% hesperetin equivalents, the H-7-glcOVX group showed a 6·6% improvement in total femoral BMD v. the OVX controls (P<0·05), whereas the Hp diet had no effect at this dose. The BMD of rats fed 0·25% H-7-glc was equal to that of those given 0·5% Hp, but was not further increased at 0·5% H-7-glc. Plasma hesperetin levels and relative urinary excretion were significantly enhanced in the H-7-glc v. Hp groups, and the metabolite profile showed the absence of eriodictyol metabolites and increased levels of hesperetin sulphates. Taken together, improved bioavailability of H-7-glc may explain the more efficient bone protection of this compoun

Hesperidin Displays Relevant Role in the Nutrigenomic Effect of Orange Juice on Blood Leukocytes in Human Volunteers: A Randomized Controlled Cross-Over Study

We previously showed, in healthy, middle-aged, moderately overweight men, that orange juice decreases diastolic blood pressure and significantly improves postprandial microvascular endothelial reactivity and that hesperidin could be causally linked to the observed beneficial effect of orange juice. The objective was to determine the effect of chronic consumption of orange juice on the gene expression profile of leukocytes in healthy volunteers and to assess to what extent hesperidin is involved in the effect of orange juice.Volunteers were included in a randomized, controlled, crossover study. Throughout three 4-week periods, volunteers consumed daily: 500 ml orange juice, 500 ml control drink plus hesperidin or 500 ml control drink and placebo. Blood samplings were performed on 10 overnight-fasted subjects after the 4-week treatment period. Global gene expression profiles were determined using human whole genome cDNA microarrays. Both orange juice and hesperidin consumption significantly affected leukocyte gene expression. Orange juice consumption induced changes in expression of, 3,422 genes, while hesperidin intake modulated the expression of 1,819 genes. Between the orange juice and hesperidin consumption groups, 1,582 regulated genes were in common. Many of these genes are implicated in chemotaxis, adhesion, infiltration and lipid transport, which is suggestive of lower recruitment and infiltration of circulating cells to vascular wall and lower lipid accumulation.This study shows that regular consumption of orange juice for 4 weeks alters leukocyte gene expression to an anti-inflammatory and anti-atherogenic profile, and hesperidin displays a relevant role in the genomic effect of this beverage.ClinicalTrials.gov NCT 00983086

Nutrigenomic modification induced by anthocyanin-rich bilberry extract in the hippocampus of ApoE-/- mice

Dietary anthocyanins may slow cognitive decline, improve cognitive performance and exert neuroprotective effects against neurodegenerative disorders. However, the underlying mechanisms of their action are not fully understood. This study investigated the effects of 12-week anthocyanin-rich bilberry extract supplementation (0.02%) on global gene expression in the hippocampus of ApoE-/- mice to help the understanding of molecular mechanisms underlying anthocyanin neuroprotective effects. Gene expression analysis identified 1698 differently expressed genes, with 611 downregulated and 1087 upregulated genes. Bioinformatics revealed that these genes regulate different biological processes, including neurogenesis, inflammation, metabolism, cell to cell adhesion, cytoskeleton organization, and Alzheimer's and Parkinson's disease pathology. The bioinformatic analysis also proposed potential miRNAs and transcription factors that could be involved in the mediation of these nutrigenomic effects. Results from molecular docking also suggested that anthocyanins could bind to top transcription factors with, as potential consequence, an impact on their gene expression regulation. Taken together, integrated analysis revealed a multi-target mode of action of anthocyanin-rich bilberry extract in the hippocampus underlying their neuroprotective properties

Improving the reporting quality of intervention trials addressing the inter-individual variability in response to the consumption of plant bioactives: quality index and recommendations

PURPOSE: The quality of the study design and data reporting in human trials dealing with the inter-individual variability in response to the consumption of plant bioactives is, in general, low. There is a lack of recommendations supporting the scientific community on this topic. This study aimed at developing a quality index to assist the assessment of the reporting quality of intervention trials addressing the inter-individual variability in response to plant bioactive consumption. Recommendations for better designing and reporting studies were discussed. METHODS: The selection of the parameters used for the development of the quality index was carried out in agreement with the scientific community through a survey. Parameters were defined, grouped into categories, and scored for different quality levels. The applicability of the scoring system was tested in terms of consistency and effort, and its validity was assessed by comparison with a simultaneous evaluation by experts' criteria. RESULTS: The "POSITIVe quality index" included 11 reporting criteria grouped into four categories (Statistics, Reporting, Data presentation, and Individual data availability). It was supported by detailed definitions and guidance for their scoring. The quality index score was tested, and the index demonstrated to be valid, reliable, and responsive. CONCLUSIONS: The evaluation of the reporting quality of studies addressing inter-individual variability in response to plant bioactives highlighted the aspects requiring major improvements. Specific tools and recommendations favoring a complete and transparent reporting on inter-individual variability have been provided to support the scientific community on this field

Grapefruit Juice Flavanones Modulate the Expression of Genes Regulating Inflammation, Cell Interactions and Vascular Function in Peripheral Blood Mononuclear Cells of Postmenopausal Women

Grapefruit is a rich source of flavanones, phytochemicals suggested excreting vasculoprotective effects. We previously showed that flavanones in grapefruit juice (GFJ) reduced postmenopausal women's pulse-wave velocity (PWV), a measure of arterial stiffness. However, mechanisms of flavanone action in humans are largely unknown. This study aimed to decipher molecular mechanisms of flavanones by multi-omics analysis in PBMCs of volunteers consuming GFJ and flavanone-free control drink for 6 months. Modulated genes and microRNAs (miRNAs) were identified using microarrays. Bioinformatics analyses assessed their functions, interactions and correlations with previously observed changes in PWV. GFJ modified gene and miRNA expressions. Integrated analysis of modulated genes and miRNA-target genes suggests regulation of inflammation, immune response, cell interaction and mobility. Bioinformatics identified putative mediators of the observed nutrigenomic effect (STAT3, NF-κB) and molecular docking demonstrated potential binding of flavanone metabolites to transcription factors and cell-signaling proteins. We also observed 34 significant correlations between changes in gene expression and PWV. Moreover, global gene expression was negatively correlated with gene expression profiles in arterial stiffness and hypertension. This study revealed molecular mechanisms underlying vasculoprotective effects of flavanones, including interactions with transcription factors and gene and miRNA expression changes that inversely correlate with gene expression profiles associated with cardiovascular risk factors.Clinical trial registration[ClinicalTrials.gov], identifier [NCT01272167]

Effects of anthocyanins and their gut metabolites on adenosine diphosphate-induced platelet activation and their aggregation with monocytes and neutrophils

Accumulating evidence suggests that anthocyanins play an important role in the cardioprotective effects associated with consumption of anthocyanin-rich foods. These benefits may partly be attributed to their effects on platelets, significant contributors to cardiovascular disease development. This study aimed to investigate the impact of physiologically relevant concentrations of anthocyanins and their metabolites on platelet activation and platelet-leukocyte aggregation. Whole blood from seven healthy volunteers was treated with anthocyanins: cyanidin-3-arabinoside, cyanidin-3-glucoside, cyanidin-3-galactoside, delphinidin-3-glucoside and peonidin-3-glucoside at 0.1 mu M concentration or gut metabolites: 4-hydroxybenzaldehyde, protocatechuic, vanillic, ferulic and hippuric acids at 0.5 mu M, 0.2 mu M, 2 mu M, 1 mu M, 2 mu M concentration, respectively. Markers of adenosine diphosphate-induced platelet activation (P-selectin and GPIIb-IIIa expression) and platelet-monocyte and platelet-neutrophil aggregation were analyzed using flow cytometry. Cyanidin-3-arabinoside, delphinidin-3-glucoside, and peonidin-3-glucoside decreased agonist-induced P-selectin expression, while cyanidin-3-galactoside and cyanidin-3-arabinoside reduced platelet-neutrophil aggregation. Hippuric and protocatechuic acids inhibited P-selectin expression, ferulic acid reduced platelet-monocyte aggregation, while 4-hydroxybenzaldehyde affected P-selectin expression, platelet-neutrophil and monocyte aggregation. Only cyanidin-3-glucoside and protocatechuic acid decreased GPIIb-IIIa expression. These results demonstrate the bioactivity of anthocyanins and their gut metabolites at physiologically relevant concentrations on platelet function and interaction with leukocytes, presenting mechanisms by which they contribute to the beneficial effects of habitual consumption of anthocyanin-rich foods on cardiovascular health

Prevalence and association of asthma and allergic sensitization with dietary factors in schoolchildren: data from the french six cities study

International audienceBackground: The prevalence of asthma and allergy has recently risen among children. This increase in prevalence might be related to various factors, particularly diet. The aim of this study is to assess the prevalence and association of asthma and allergic sensitization with dietary factors in the French Six Cities Study. Methods: Cross-sectional studies were performed among 7432 schoolchildren aged 9-11 years in Bordeaux, Clermont-Ferrand, Creteil, Marseille, Reims, and Strasbourg. Parental questionnaires, based on the International Study on Asthma and Allergies in Childhood (ISAAC), were used to collect information on allergic diseases and potential exposure factors including a food frequency questionnaire to evaluate dietary habits. Skin prick testing to common allergens for allergic sensitization and bronchial hyper-responsiveness (BHR) testing to exercise were performed. Confounders control was performed with multiple logistic regressions. Results: Asthma symptoms, asthma and allergic sensitization were more prevalent in boys than in girls and were more prevalent in the South than in the North of France. After adjustment for confounders, fruit juice intake was associated with a low prevalence of lifetime asthma (ORa [95 % CI]; 0.73 [0.56-0.97]), butter intake was positively associated with atopic wheeze (1.48 [1.07-2.05]) and having lunch at the canteen 1-2 times/week compared to never or occasionally was associated with a lower prevalence of past year wheeze (0.71 [0.52-0.96]), lifetime asthma (0.76 [0.60-0.96]) and allergic sensitization (0.80 [0.67-0.95]). Meat intake was inversely related to past year wheeze among atopic children (0.68 [0.50-0.98]) while fast food consumption and butter intake were associated with an increase prevalence of asthma (2.39 [1.47-3.93] and 1.51 [1.17-2.00] respectively). Fish intake was associated with a lower prevalence of asthma among non-atopic children (0.61 [0.43-0.87]. None of the dietary factors was associated with BHR. Conclusions: Diet is associated with wheeze, asthma and allergic sensitization but not with BHR in children. These results provide further evidence that adherence to a healthy diet including fruits, meat and fish seems to have a protective effect on asthma and allergy in childhood. However, prospective and experimental studies are needed to provide causal evidence concerning the effect of diet on asthma and atopy