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      DHA-Induced Perturbation of Human Serum Metabolome. Role of the Food Matrix and Co-Administration of Oat β-glucan and Anthocyanins

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          Abstract

          Docosahexaenoic acid (DHA) has been reported to have a positive impact on many diet-related disease risks, including metabolic syndrome. Although many DHA-enriched foods have been marketed, the impact of different food matrices on the effect of DHA is unknown. As well, the possibility to enhance DHA effectiveness through the co-administration of other bioactives has seldom been considered. We evaluated DHA effects on the serum metabolome administered to volunteers at risk of metabolic syndrome as an ingredient of three different foods. Foods were enriched with DHA alone or in combination with oat beta-glucan or anthocyanins and were administered to volunteers for 4 weeks. Serum samples collected at the beginning and end of the trial were analysed by NMR-based metabolomics. Multivariate and univariate statistical analyses were used to characterize modifications in the serum metabolome and to evaluate bioactive-bioactive and bioactive-food matrix interactions. DHA administration induces metabolome perturbation that is influenced by the food matrix and the co-presence of other bioactives. In particular, when co-administered with oat beta-glucan, DHA induces a strong rearrangement in the lipoprotein profile of the subjects. The observed modifications are consistent with clinical results and indicate that metabolomics represents a possible strategy to choose the most appropriate food matrices for bioactive enrichment.

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          Quantitative metabolomics using NMR

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            Standard operating procedures for pre-analytical handling of blood and urine for metabolomic studies and biobanks.

            (1)H NMR metabolic profiling of urine, serum and plasma has been used to monitor the impact of the pre-analytical steps on the sample quality and stability in order to propose standard operating procedures (SOPs) for deposition in biobanks. We analyzed the quality of serum and plasma samples as a function of the elapsed time (t = 0-4 h) between blood collection and processing and of the time from processing to freezing (up to 24 h). The stability of the urine metabolic profile over time (up to 24 h) at various storage temperatures was monitored as a function of the different pre-analytical treatments like pre-storage centrifugation, filtration, and addition of the bacteriostatic preservative sodium azide. Appreciable changes in the profiles, reflecting changes in the concentration of a number of metabolites, were detected and discussed in terms of chemical and enzymatic reactions for both blood and urine samples. Appropriate procedures for blood derivatives collection and urine preservation/storage that allow maintaining as much as possible the original metabolic profile of the fresh samples emerge, and are proposed as SOPs for biobanking.
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              (n-3) fatty acids and cardiovascular health: are effects of EPA and DHA shared or complementary?

              Considerable research supports cardiovascular benefits of consuming omega-3 PUFA, also known as (n-3) PUFA, from fish or fish oil. Whether individual long-chain (n-3) PUFA have shared or complementary effects is not well established. We reviewed evidence for dietary and endogenous sources and cardiovascular effects on biologic pathways, physiologic risk factors, and clinical endpoints of EPA [20:5(n-3)], docosapentaenoic acid [DPA, 22:5(n-3)], and DHA [22:6(n-3)]. DHA requires direct dietary consumption, with little synthesis from or retroconversion to DPA or EPA. Whereas EPA is also largely derived from direct consumption, EPA can also be synthesized in small amounts from plant (n-3) precursors, especially stearidonic acid. In contrast, DPA appears principally derived from endogenous elongation from EPA, and DPA can also undergo retroconversion back to EPA. In experimental and animal models, both EPA and DHA modulate several relevant biologic pathways, with evidence for some differential benefits. In humans, both fatty acids lower TG levels and, based on more limited studies, favorably affect cardiac diastolic filling, arterial compliance, and some metrics of inflammation and oxidative stress. All three (n-3) PUFA reduce ex vivo platelet aggregation and DHA also modestly increases LDL and HDL particle size; the clinical relevance of such findings is uncertain. Combined EPA+DHA or DPA+DHA levels are associated with lower risk of fatal cardiac events and DHA with lower risk of atrial fibrillation, suggesting direct or indirect benefits of DHA for cardiac arrhythmias (although not excluding similar benefits of EPA or DPA). Conversely, EPA and DPA, but not DHA, are associated with lower risk of nonfatal cardiovascular endpoints in some studies, and purified EPA reduced risk of nonfatal coronary syndromes in one large clinical trial. Overall, for many cardiovascular pathways and outcomes, identified studies of individual (n-3) PUFA were relatively limited, especially for DPA. Nonetheless, the present evidence suggests that EPA and DHA have both shared and complementary benefits. Based on current evidence, increasing consumption of either would be advantageous compared to little or no consumption. Focusing on their combined consumption remains most prudent given the potential for complementary effects and the existing more robust literature on cardiovascular benefits of their combined consumption as fish or fish oil for cardiovascular benefits.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                27 December 2019
                January 2020
                : 12
                : 1
                : 86
                Affiliations
                [1 ]Center of Magnetic Resonance (CERM), University of Florence, via Luigi Sacconi, 6-50019 Sesto Fiorentino (FI), Italy; ghini@ 123456cerm.unifi.it (V.G.); luchinat@ 123456cerm.unifi.it (C.L.)
                [2 ]Department of Experimental and Clinical Medicine, University of Florence, Largo Brambilla, 3-50134 Florence (FI), Italy; tenori@ 123456cerm.unifi.it
                [3 ]Department of Agricultural and Food Sciences, Alma Mater Studiorum University of Bologna, Piazza G. Goidanich, 60, 47521 Cesena (FC), Italy; alessandra.bordoni@ 123456unibo.it
                [4 ]Interdepartmental Centre for Industrial Agrofood Research, Alma Mater Studiorum University of Bologna, Via Q. Bucci 336, 47521 Cesena (FC), Italy
                [5 ]Department of Chemistry, University of Florence, via della Lastruccia, 3-50019 Sesto Fiorentino (FI), Italy
                [6 ]GIOTTO Biotech S.r.l., Via Madonna del Piano, 6-50019 Sesto Fiorentino (FI), Italy
                [7 ]Max Rubner-Institute, Federal Research Centre for Nutrition and Food, Haid-und-NeuStrasse 9, DE-76131 Karlsruhe, Germany; achim.bub@ 123456mri.bund.de
                [8 ]Université Clermont Auvergne, INRA, UNH, Unité de Nutrition Humaine, CRNH Auvergne, F63000 Clermont-Ferrand, France; corinne.malpuech-brugere@ 123456uca.fr
                [9 ]School of Food Science and Nutrition, University of Leeds, Woodhouse Ln, Leeds LS2 9JT, UK; C.Orfila@ 123456leeds.ac.uk
                [10 ]Department of Medical and Surgical Sciences, Alma Mater Studiorum University of Bologna, via Massarenti 9, 40138 Bologna (BO), Italy; luigi.ricciardiello@ 123456unibo.it
                Author notes
                [* ]Correspondence: francesco.capozzi@ 123456unibo.it ; Tel.: +39-0547-338106
                Author information
                https://orcid.org/0000-0001-6438-059X
                https://orcid.org/0000-0003-2271-8921
                https://orcid.org/0000-0001-6907-5519
                https://orcid.org/0000-0003-4579-1662
                Article
                nutrients-12-00086
                10.3390/nu12010086
                7019822
                31892215
                2aba038e-ef8a-480f-a454-581907e8c567
                © 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
                : 25 November 2019
                : 23 December 2019
                Categories
                Article

                Nutrition & Dietetics
                anthocyanins,bioactive enriched food,docosahexaenoic acid,nmr-based metabolomics,oat beta glucans

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