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      Flavonoid intake is associated with lower mortality in the Danish Diet Cancer and Health Cohort

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          Abstract

          Flavonoids, plant-derived polyphenolic compounds, have been linked with health benefits. However, evidence from observational studies is incomplete; studies on cancer mortality are scarce and moderating effects of lifestyle risk factors for early mortality are unknown. In this prospective cohort study including 56,048 participants of the Danish Diet, Cancer, and Health cohort crosslinked with Danish nationwide registries and followed for 23 years, there are 14,083 deaths. A moderate habitual intake of flavonoids is inversely associated with all-cause, cardiovascular- and cancer-related mortality. This strong association plateaus at intakes of approximately 500 mg/day. Furthermore, the inverse associations between total flavonoid intake and mortality outcomes are stronger and more linear in smokers than in non-smokers, as well as in heavy (>20 g/d) vs. low-moderate (<20 g/d) alcohol consumers. These findings highlight the potential to reduce mortality through recommendations to increase intakes of flavonoid-rich foods, particularly in smokers and high alcohol consumers.

          Abstract

          The studies showing health benefits of flavonoids and their impact on cancer mortality are incomplete. Here, the authors perform a prospective cohort study in Danish participants and demonstrate an inverse association between regular flavonoid intake and both cardiovascular and cancer related mortality.

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          Most cited references20

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          Gut microbiome, obesity, and metabolic dysfunction.

          The prevalence of obesity and related disorders such as metabolic syndrome has vastly increased throughout the world. Recent insights have generated an entirely new perspective suggesting that our microbiota might be involved in the development of these disorders. Studies have demonstrated that obesity and metabolic syndrome may be associated with profound microbiotal changes, and the induction of a metabolic syndrome phenotype through fecal transplants corroborates the important role of the microbiota in this disease. Dietary composition and caloric intake appear to swiftly regulate intestinal microbial composition and function. As most findings in this field of research are based on mouse studies, the relevance to human biology requires further investigation.
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            Flavonoid intake and cardiovascular disease mortality: a prospective study in postmenopausal women.

            Dietary flavonoids may have beneficial cardiovascular effects in human populations, but epidemiologic study results have not been conclusive. We used flavonoid food composition data from 3 recently available US Department of Agriculture databases to improve estimates of dietary flavonoid intake and to evaluate the association between flavonoid intake and cardiovascular disease (CVD) mortality. Study participants were 34 489 postmenopausal women in the Iowa Women's Health Study who were free of CVD and had complete food-frequency questionnaire information at baseline. Intakes of total flavonoids and 7 subclasses were categorized into quintiles, and food sources were grouped into frequency categories. Proportional hazards rate ratios (RR) were computed for CVD, coronary heart disease (CHD), stroke, and total mortality after 16 y of follow-up. After multivariate adjustment, significant inverse associations were observed between anthocyanidins and CHD, CVD, and total mortality [RR (95% CI) for any versus no intake: 0.88 (0.78, 0.99), 0.91 (0.83, 0.99), and 0.90 (0.86, 0.95)]; between flavanones and CHD [RR for highest quintile versus lowest: 0.78 (0.65, 0.94)]; and between flavones and total mortality [RR for highest quintile versus lowest: 0.88 (0.82, 0.96)]. No association was found between flavonoid intake and stroke mortality. Individual flavonoid-rich foods associated with significant mortality reduction included bran (added to foods; associated with stroke and CVD); apples or pears or both and red wine (associated with CHD and CVD); grapefruit (associated with CHD); strawberries (associated with CVD); and chocolate (associated with CVD). Dietary intakes of flavanones, anthocyanidins, and certain foods rich in flavonoids were associated with reduced risk of death due to CHD, CVD, and all causes.
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              The Bioavailability, Transport, and Bioactivity of Dietary Flavonoids: A Review from a Historical Perspective

              Flavonoids are plant-derived dietary components with a substantial impact on human health. Research has expanded massively since it began in the 1930s, and the complex pathways involved in bioavailability of flavonoids in the human body are now well understood. In recent years, it has been appreciated that the gut microbiome plays a major role in flavonoid action, but much progress still needs to be made in this area. Since the first publications on the health effects of flavonoids, their action is understood to protect against various stresses, but the mechanism of action has evolved from the now debunked simple direct antioxidant hypothesis into an understanding of the complex effects on molecular targets and enzymes in specific cell types. This review traces the development of the field over the past 8 decades, and indicates the current state of the art, and how it was reached. Future recommendations based on this historical analysis are (a) to focus on key areas of flavonoid action, (b) to perform human intervention studies focusing on bioavailability and protective effects, and (c) to carry out cellular in vitro experiments using appropriate cells together with the chemical form of the flavonoid found at the site of action; this could be the native form of compounds found in the food for studies on digestion and the intestine, the conjugated metabolites found in the blood after absorption in the small intestine for studies on cells, or the chemical forms found in the blood and tissues after catabolism by the gut microbiota.
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                Author and article information

                Contributors
                n.bondonno@ecu.edu.au
                Journal
                Nat Commun
                Nat Commun
                Nature Communications
                Nature Publishing Group UK (London )
                2041-1723
                13 August 2019
                13 August 2019
                2019
                : 10
                : 3651
                Affiliations
                [1 ]ISNI 0000 0004 0389 4302, GRID grid.1038.a, School of Medical and Health Sciences, , Edith Cowan University, ; Perth, Western Australia Australia
                [2 ]School of Biomedical Sciences, University of Western Australia, Royal Perth Hospital, Perth, Western Australia Australia
                [3 ]ISNI 0000 0004 0646 7402, GRID grid.411646.0, Department of Cardiology, , Herlev & Gentofte University Hospital, ; Copenhagen, Denmark
                [4 ]ISNI 0000 0001 2175 6024, GRID grid.417390.8, The Danish Cancer Society Research Centre, ; Copenhagen, Denmark
                [5 ]ISNI 0000 0004 1936 7910, GRID grid.1012.2, School of Population and Global Health, , University of Western Australia, ; Crawley, Western Australia Australia
                [6 ]ISNI 0000 0001 0728 0170, GRID grid.10825.3e, The National Institute of Public Health, , University of Southern Denmark, ; Odense, Denmark
                [7 ]ISNI 0000 0004 0646 9598, GRID grid.453951.f, The Danish Heart Foundation, ; Copenhagen, Denmark
                [8 ]ISNI 0000000405980095, GRID grid.17703.32, International Agency for Research on Cancer, ; Lyon, France
                [9 ]ISNI 0000 0004 0374 7521, GRID grid.4777.3, Institute for Global Food Security, , Queen’s University Belfast, ; Belfast, Northern Ireland
                [10 ]ISNI 0000 0001 1956 2722, GRID grid.7048.b, Department of Public Health, , Aarhus University, ; Aarhus, Denmark
                [11 ]ISNI 0000 0004 0646 7349, GRID grid.27530.33, Aalborg University Hospital, ; Aalborg, Denmark
                Author information
                http://orcid.org/0000-0001-5905-444X
                http://orcid.org/0000-0002-7287-4191
                http://orcid.org/0000-0002-9083-8960
                http://orcid.org/0000-0002-8856-6046
                http://orcid.org/0000-0001-8509-439X
                http://orcid.org/0000-0003-1003-8443
                http://orcid.org/0000-0003-1596-4913
                http://orcid.org/0000-0001-6651-6710
                http://orcid.org/0000-0003-0048-5602
                http://orcid.org/0000-0003-4385-2097
                http://orcid.org/0000-0001-6429-7921
                http://orcid.org/0000-0001-6184-7764
                Article
                11622
                10.1038/s41467-019-11622-x
                6692395
                31409784
                e7ac5ccd-a925-4cd6-8e32-a1ef2c2c54ca
                © The Author(s) 2019

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 23 February 2019
                : 22 July 2019
                Funding
                Funded by: FundRef https://doi.org/10.13039/100007405, Hjerteforeningen (Heart Foundation);
                Award ID: 17-R115-A7443-22062
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100008218, Gangstedfonden (Gangsted Foundation);
                Award ID: A35136
                Award Recipient :
                Funded by: FundRef https://doi.org/10.13039/501100000925, Department of Health | National Health and Medical Research Council (NHMRC);
                Award ID: APP1116937
                Award Recipient :
                Categories
                Article
                Custom metadata
                © The Author(s) 2019

                Uncategorized
                diseases,cancer,cardiology
                Uncategorized
                diseases, cancer, cardiology

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