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      A Review of Factors Affecting Anthocyanin Bioavailability: Possible Implications for the Inter-Individual Variability

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          Abstract

          Anthocyanins are dietary bioactive compounds showing a range of beneficial effects against cardiovascular, neurological, and eye conditions. However, there is, as for other bioactive compounds in food, a high inter and intra-individual variation in the response to anthocyanin intake that in many cases leads to contradictory results in human trials. This variability could be caused at two levels, one at the bioavailability level and the other at the effect and mechanisms of action. In this context, we have thoroughly reviewed the scientific literature on anthocyanins variability caused by variation in bioavailability. Based on the literature reviewed, we have concluded that the variability in anthocyanins bioavailability might be produced by the lack of homogeneity introduced at three different levels: food matrix and food processing, enzymes involved in anthocyanin metabolism and transport, and anthocyanin metabolizing gut microbiota. However, it should be noted that the literature on anthocyanins bioavailability considering inter or intra-individual variability is still very scarce, which makes it difficult to reach any firm conclusion on the main metabolizing enzymes or bacteria that would be responsible for the variability in anthocyanin bioavailability.

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          Most cited references57

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          Bioavailability, bioactivity and impact on health of dietary flavonoids and related compounds: an update.

          There is substantial interest in the role of plant secondary metabolites as protective dietary agents. In particular, the involvement of flavonoids and related compounds has become a major topic in human nutrition research. Evidence from epidemiological and human intervention studies is emerging regarding the protective effects of various (poly)phenol-rich foods against several chronic diseases, including neurodegeneration, cancer and cardiovascular diseases. In recent years, the use of HPLC-MS for the analysis of flavonoids and related compounds in foods and biological samples has significantly enhanced our understanding of (poly)phenol bioavailability. These advancements have also led to improvements in the available food composition and metabolomic databases, and consequently in the development of biomarkers of (poly)phenol intake to use in epidemiological studies. Efforts to create adequate standardised materials and well-matched controls to use in randomised controlled trials have also improved the quality of the available data. In vitro investigations using physiologically achievable concentrations of (poly)phenol metabolites and catabolites with appropriate model test systems have provided new and interesting insights on potential mechanisms of actions. This article will summarise recent findings on the bioavailability and biological activity of (poly)phenols, focusing on the epidemiological and clinical evidence of beneficial effects of flavonoids and related compounds on urinary tract infections, cognitive function and age-related cognitive decline, cancer and cardiovascular disease.
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            Deglycosylation by small intestinal epithelial cell beta-glucosidases is a critical step in the absorption and metabolism of dietary flavonoid glycosides in humans.

            Pharmacokinetic studies have shown that the small intestine is the major site of absorption for many flavonoid glucosides. Flavonoids are generally present as glycosylated forms in plants and foods, but there is increasing evidence that the forms reaching the systemic circulation are glucuronidated, sulphated and methylated derivatives. Hence, first-pass metabolism (small intestine-liver) appears to involve a critical deglycosylation step for which the mechanisms are not known. To explore the hypothesis that deglycosylation is a prerequisite to absorption and metabolism of dietary flavonoid glycosides, to identify the enzymes responsible, and relate their specificities with absorption kinetics. Flavonoid glycoside hydrolysing enzymes were isolated from samples of human small intestine and liver using chromatographic techniques. The proteins were characterised with respect to the cellular fraction with which they were associated, molecular weight, specificity for various substrates, and cross-reactions with antibodies. Cellular models were used to mimic the small intestine. Protein extracts from human jejunal mucosa were highly efficient in hydrolysing flavonoid glycosides, consistent with an enterocyte-mediated deglycosylation process. Considerable inter-individual variation was observed [e. g. range, mean and standard deviation for rate of hydrolysis of quercetin-3-glucoside (n = 10) were 6.7-456, 96, and 134 nmol min(-1) (mg protein)(-1), respectively]. Two beta-glucosidases with activity towards flavonoid glycosides were isolated from human small intestine mucosa: lactase-phlorizin hydrolase (LPH; localised to the apical membrane of small intestinal epithelial cells) and cytosolic beta-glucosidase (CBG), indicating a role of human LPH and CBG from small intestine in flavonoid absorption and metabolism. Hydrolysis of flavonoid glycosides was only detected in cultured cells exhibiting beta-glucosidase activity. The absorption of dietary flavonoid glycosides in humans involves a critical deglycosylation step that is mediated by epithelial beta-glucosidases (LPH and CBG). The significant variation in beta-glucosidase activity between individuals may be a factor determining variation in flavonoid bioavailability.
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              Non-thermal stabilization mechanisms of anthocyanins in model and food systems—An overview

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                Author and article information

                Journal
                Foods
                Foods
                foods
                Foods
                MDPI
                2304-8158
                18 December 2019
                January 2020
                : 9
                : 1
                : 2
                Affiliations
                [1 ]Department of Metabolism and Nutrition, Institute of Food Science, Technology and Nutrition (ICTAN-CSIC), Jose Antonio Novais 10, 28040 Madrid, Spain; merveedaeker@ 123456gmail.com
                [2 ]Department of Food Engineering, Ege University, Izmir 35100, Turkey; sedef.el@ 123456ege.edu.tr (S.N.E.); sibel.karakaya@ 123456ege.edu.tr (S.K.); sebnem.simsek@ 123456ege.edu.tr (S.S.)
                [3 ]Nofima, Norwegian Institute of Food, Fisheries and Aquaculture Research, N-1430 Ås, Norway; Kjersti.Aaby@ 123456Nofima.no
                [4 ]Institute for Adriatic Crops and Karst Reclamation, Put Duilova 11, 21000 Split, Croatia; Irena.Budic-Leto@ 123456krs.hr
                [5 ]Faculty of food Technology and Biotechnology, University of Zagreb, Pierottijeva 6, 10000 Zagreb, Croatia; srimacbrncic@ 123456pbf.hr
                [6 ]INRA, Université Clermont-Auvergne, Human Nutrition Unit, CRNH Auvergne, F-63000 Clermont-Ferrand, France; claudine.manach@ 123456inra.fr
                [7 ]Institute of Animal Reproduction and Food Research. Polish Academy of Sciences, 10-748 Olsztyn, Poland; w.wiczkowski@ 123456pan.olsztyn.pl
                Author notes
                [* ]Correspondence: s.depascualteresa@ 123456csic.es ; Tel.: +34-91-5492300 (ext. 231309)
                Author information
                https://orcid.org/0000-0002-5853-9901
                https://orcid.org/0000-0001-6021-5589
                https://orcid.org/0000-0001-8546-8507
                Article
                foods-09-00002
                10.3390/foods9010002
                7023094
                31861362
                9f0e34f9-f269-4a8f-a4d4-70fe61715546
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 22 November 2019
                : 15 December 2019
                Categories
                Review

                anthocyanin,variability,bioavailability,food processing,metabolism,microbiota

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