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      Addressing the inter‐individual variation in response to consumption of plant food bioactives: Towards a better understanding of their role in healthy aging and cardiometabolic risk reduction

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          Abstract

          Bioactive compounds in plant‐based foods have health properties that contribute to the prevention of age‐related chronic diseases, particularly cardiometabolic disorders. Conclusive proof and understanding of these benefits in humans is essential in order to provide effective dietary recommendations but, so far, the evidence obtained from human intervention trials is limited and contradictory. This is partly due to differences between individuals in the absorption, distribution, metabolism and excretion of bioactive compounds, as well as to heterogeneity in their biological response regarding cardiometabolic health outcomes. Identifying the main factors underlying inter‐individual differences, as well as developing new and innovative methodologies to account for such variability constitute an overarching goal to ultimately optimize the beneficial health effects of plant food bioactives for each and every one of us. In this respect, this position paper from the COST Action FA1403‐POSITIVe examines the main factors likely to affect the individual responses to consumption of plant food bioactives and presents perspectives for assessment and consideration of inter‐individual variability.

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          Flavonoids, flavonoid-rich foods, and cardiovascular risk: a meta-analysis of randomized controlled trials.

          The beneficial effects of flavonoid consumption on cardiovascular risk are supported by mechanistic and epidemiologic evidence. We aimed to systematically review the effectiveness of different flavonoid subclasses and flavonoid-rich food sources on cardiovascular disease (CVD) and risk factors--ie, lipoproteins, blood pressure, and flow-mediated dilatation (FMD). Methods included a structured search strategy on MEDLINE, EMBASE, and Cochrane databases; formal inclusion or exclusion, data extraction, and validity assessment; and meta-analysis. One hundred thirty-three trials were included. No randomized controlled trial studied effects on CVD morbidity or mortality. Significant heterogeneity confirmed differential effects between flavonoid subclasses and foods. Chocolate increased FMD after acute (3.99%; 95% CI: 2.86, 5.12; 6 studies) and chronic (1.45%; 0.62, 2.28; 2 studies) intake and reduced systolic (-5.88 mm Hg; -9.55, -2.21; 5 studies) and diastolic (-3.30 mm Hg; -5.77, -0.83; 4 studies) blood pressure. Soy protein isolate (but not other soy products or components) significantly reduced diastolic blood pressure (-1.99 mm Hg; -2.86, -1.12; 9 studies) and LDL cholesterol (-0.19 mmol/L; -0.24, -0.14; 39 studies). Acute black tea consumption increased systolic (5.69 mm Hg; 1.52, 9.86; 4 studies) and diastolic (2.56 mm Hg; 1.03, 4.10; 4 studies) blood pressure. Green tea reduced LDL (-0.23 mmol/L; -0.34, -0.12; 4 studies). For many of the other flavonoids, there was insufficient evidence to draw conclusions about efficacy. To date, the effects of flavonoids from soy and cocoa have been the main focus of attention. Future studies should focus on other commonly consumed subclasses (eg, anthocyanins and flavanones), examine dose-response effects, and be of long enough duration to allow assessment of clinically relevant endpoints.
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            Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials.

            There is substantial interest in chocolate and flavan-3-ols for the prevention of cardiovascular disease (CVD). The objective was to systematically review the effects of chocolate, cocoa, and flavan-3-ols on major CVD risk factors. We searched Medline, EMBASE, and Cochrane databases for randomized controlled trials (RCTs) of chocolate, cocoa, or flavan-3-ols. We contacted authors for additional data and conducted duplicate assessment of study inclusion, data extraction, validity, and random-effects meta-analyses. We included 42 acute or short-term chronic (≤18 wk) RCTs that comprised 1297 participants. Insulin resistance (HOMA-IR: -0.67; 95% CI: -0.98, -0.36) was improved by chocolate or cocoa due to significant reductions in serum insulin. Flow-mediated dilatation (FMD) improved after chronic (1.34%; 95% CI: 1.00%, 1.68%) and acute (3.19%; 95% CI: 2.04%, 4.33%) intakes. Effects on HOMA-IR and FMD remained stable to sensitivity analyses. We observed reductions in diastolic blood pressure (BP; -1.60 mm Hg; 95% CI: -2.77, -0.43 mm Hg) and mean arterial pressure (-1.64 mm Hg; 95% CI: -3.27, -0.01 mm Hg) and marginally significant effects on LDL (-0.07 mmol/L; 95% CI: -0.13, 0.00 mmol/L) and HDL (0.03 mmol/L; 95% CI: 0.00, 0.06 mmol/L) cholesterol. Chocolate or cocoa improved FMD regardless of the dose consumed, whereas doses >50 mg epicatechin/d resulted in greater effects on systolic and diastolic BP. GRADE (Grading of Recommendations, Assessment, Development and Evaluation, a tool to assess quality of evidence and strength of recommendations) suggested low- to moderate-quality evidence of beneficial effects, with no suggestion of negative effects. The strength of evidence was lowered due to unclear reporting for allocation concealment, dropouts, missing data on outcomes, and heterogeneity in biomarker results in some studies. We found consistent acute and chronic benefits of chocolate or cocoa on FMD and previously unreported promising effects on insulin and HOMA-IR. Larger, longer-duration, and independently funded trials are required to confirm the potential cardiovascular benefits of cocoa flavan-3-ols.
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              Age-related changes in pharmacokinetics and pharmacodynamics: basic principles and practical applications.

              Advancing age is characterized by impairment in the function of the many regulatory processes that provide functional integration between cells and organs. Therefore, there may be a failure to maintain homeostasis under conditions of physiological stress. The reduced homeostatic ability affects different regulatory systems in different subjects, thus explaining at least partly the increased interindividual variability occurring as people get older. Important pharmacokinetic and pharmacodynamic changes occur with advancing age. Pharmacokinetic changes include a reduction in renal and hepatic clearance and an increase in volume of distribution of lipid soluble drugs (hence prolongation of elimination half-life) whereas pharmacodynamic changes involve altered (usually increased) sensitivity to several classes of drugs such as anticoagulants, cardiovascular and psychotropic drugs. This review focuses on the main age-related physiological changes affecting different organ systems and their implications for pharmacokinetics and pharmacodynamics of drugs.
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                Author and article information

                Contributors
                christine.morand@clermont.inra.fr
                Journal
                Mol Nutr Food Res
                Mol Nutr Food Res
                10.1002/(ISSN)1613-4133
                MNFR
                Molecular Nutrition & Food Research
                John Wiley and Sons Inc. (Hoboken )
                1613-4125
                1613-4133
                15 November 2016
                June 2017
                : 61
                : 6 , Reviews ( doiID: 10.1002/mnfr.v61.6 )
                : 1600557
                Affiliations
                [ 1 ] INRA, UMR 1019, UNH, CRNH Auvergne, F‐63000 Clermont‐Ferrand; Clermont Université Université d'AuvergneUnité de Nutrition Humaine BP 10448 F‐63000 Clermont‐FerrandFrance
                [ 2 ] Center for Microbial Ecology and Technology (CMET)Ghent University GhentBelgium
                [ 3 ] Division of Cardiology, Pulmonology and Vascular Medicine Medical FacultyUniversity of Düsseldorf Germany
                [ 4 ] Rowett Institute of Nutrition and HealthUniversity of Aberdeen AberdeenUK
                [ 5 ] Research Group on Quality, Safety and Bioactivity of Plant FoodsCEBAS‐CSIC Campus de Espinardo MurciaSpain
                [ 6 ] Department of Food ScienceSwedish University of Agricultural Sciences UppsalaSweden
                [ 7 ] Nutritional Epidemiology Unit Institute of Environmental MedicineKarolinska Institutet SolnaSweden
                [ 8 ] UCD Institute of Food and HealthUniversity College Dublin DublinRepublic of Ireland
                [ 9 ] Department of Food and Environmental Sciences Food ChemistryUniversity of Helsinki Finland
                Author notes
                [*] [* ] Correspondence: Dr. Christine Morand, INRA, UNH‐UMR 1019, Auvergne Rhone Alpes Research Center, ‐ F‐63122 Saint Genès Champanelle, France

                E‐mail: christine.morand@ 123456clermont.inra.fr

                [†]

                These authors contributed equally to this work.

                Article
                MNFR2764
                10.1002/mnfr.201600557
                5484307
                27687784
                e64aa4ac-1464-4385-ae3e-b28933f7ed2c
                © 2016 The Authors. Molecular Nutrition & Food Research published by WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 03 July 2016
                : 08 September 2016
                : 13 September 2016
                Page count
                Figures: 2, Tables: 2, Pages: 16, Words: 9624
                Funding
                Funded by: COST
                Categories
                Review
                Reviews
                Custom metadata
                2.0
                mnfr2764
                June 2017
                Converter:WILEY_ML3GV2_TO_NLMPMC version:5.1.2 mode:remove_FC converted:26.06.2017

                Nutrition & Dietetics
                bioavailability and metabolism,biological responsiveness,cardiometabolic health,inter‐individual variation,plant food bioactives

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