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      Measuring exposure to the polyphenol metabolome in observational epidemiologic studies: current tools and applications and their limits 1 2 3

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          Abstract

          Much experimental evidence supports a protective role of dietary polyphenols against chronic diseases such as cardiovascular diseases, diabetes, and cancer. However, results from observational epidemiologic studies are still limited and are often inconsistent. This is largely explained by the difficulties encountered in the estimation of exposure to the polyphenol metabolome, which is composed of ∼500 polyphenols distributed across a wide variety of foods and characterized by diverse biological properties. Exposure to the polyphenol metabolome in epidemiologic studies can be assessed by the use of detailed dietary questionnaires or the measurement of biomarkers of polyphenol intake. The questionnaire approach has been greatly facilitated by the use of new databases on polyphenol composition but is limited by bias as a result of self-reporting. The use of polyphenol biomarkers holds much promise for objective estimation of polyphenol exposure in future metabolome-wide association studies. These approaches are reviewed and their advantages and limitations discussed by using examples of epidemiologic studies on polyphenols and cancer. The current improvement in these techniques, along with greater emphasis on the intake of individual polyphenols rather than polyphenols considered collectively, will help unravel the role of these major food bioactive constituents in disease prevention.

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          Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies.

          Polyphenols are abundant micronutrients in our diet, and evidence for their role in the prevention of degenerative diseases is emerging. Bioavailability differs greatly from one polyphenol to another, so that the most abundant polyphenols in our diet are not necessarily those leading to the highest concentrations of active metabolites in target tissues. Mean values for the maximal plasma concentration, the time to reach the maximal plasma concentration, the area under the plasma concentration-time curve, the elimination half-life, and the relative urinary excretion were calculated for 18 major polyphenols. We used data from 97 studies that investigated the kinetics and extent of polyphenol absorption among adults, after ingestion of a single dose of polyphenol provided as pure compound, plant extract, or whole food/beverage. The metabolites present in blood, resulting from digestive and hepatic activity, usually differ from the native compounds. The nature of the known metabolites is described when data are available. The plasma concentrations of total metabolites ranged from 0 to 4 mumol/L with an intake of 50 mg aglycone equivalents, and the relative urinary excretion ranged from 0.3% to 43% of the ingested dose, depending on the polyphenol. Gallic acid and isoflavones are the most well-absorbed polyphenols, followed by catechins, flavanones, and quercetin glucosides, but with different kinetics. The least well-absorbed polyphenols are the proanthocyanidins, the galloylated tea catechins, and the anthocyanins. Data are still too limited for assessment of hydroxycinnamic acids and other polyphenols. These data may be useful for the design and interpretation of intervention studies investigating the health effects of polyphenols.
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            Flavonoid intake and long-term risk of coronary heart disease and cancer in the seven countries study.

            To determine whether flavonoid intake explains differences in mortality rates from chronic diseases between populations. Cross-cultural correlation study. Sixteen cohorts of the Seven Countries Study in whom flavonoid intake at baseline around 1960 was estimated by flavonoid analysis of equivalent food composites that represented the average diet in the cohorts. Mortality from coronary heart disease, cancer (various sites), and all causes in the 16 cohorts after 25 years of follow-up. Average intake of antioxidant flavonoids was inversely associated with mortality from coronary heart disease and explained about 25% of the variance in coronary heart disease rates in the 16 cohorts. In multivariate analysis, intake of saturated fat (73%; P = 0.0001), flavonoid intake (8%, P = .01), and percentage of smokers per cohort (9%; P = .03) explained together, independent of intake of alcohol and antioxidant vitamins, 90% of the variance in coronary heart disease rates. Flavonoid intake was not independently associated with mortality from other causes. Average flavonoid intake may partly contribute to differences in coronary heart disease mortality across populations, but it does not seem to be an important determinant of cancer mortality.
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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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                Author and article information

                Journal
                Am J Clin Nutr
                Am. J. Clin. Nutr
                ajcn
                The American Journal of Clinical Nutrition
                American Society for Nutrition
                0002-9165
                1938-3207
                July 2014
                30 April 2014
                30 April 2014
                : 100
                : 1
                : 11-26
                Affiliations
                [1 ]From the Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France (RZ-R, JAR, IR, and AS); the Unit of Nutrition, Environment, and Cancer, Catalan Institute of Oncology, Bellvitge Biomedical Research Institute (IDIBELL), Barcelona, Spain (RZ-R); and the Cancer and Environment Unit, Centre Léon Bérard, Lyon, France (MT).
                Author notes
                [2]

                Supported by the Institut National du Cancer, Paris (INCa 2011-105) and by Wereld Kanker Onderzoek Fonds (WCRF NL 2012/604). RZ-R is the recipient of a grant for the postdoctoral fellowship programme Fondo de Investigación Sanitaria (FIS; no. CD09/00133) from the Spanish Ministry of Science and Innovation. This is a free access article, distributed under terms ( http://www.nutrition.org/publications/guidelines-and-policies/license/) that permit unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                [3 ]Address correspondence to A Scalbert, Biomarker Group, Nutrition and Metabolism Section, International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, F-69372 Lyon Cedex 08, France. E-mail: scalberta@ 123456iarc.fr .
                Article
                077743
                10.3945/ajcn.113.077743
                4144095
                24787490
                d5adcdad-c03d-4bb5-ac21-f6ebd2aae409
                © 2014 American Society for Nutrition

                This is a free access article, distributed under terms ( http://www.nutrition.org/publications/guidelines-and-policies/license/) that permit unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 9 October 2013
                : 25 March 2014
                Page count
                Pages: 16
                Categories
                Narrative Review

                Nutrition & Dietetics
                Nutrition & Dietetics

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