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      The Effects of Flavonoids on Cardiovascular Health: A Review of Human Intervention Trials and Implications for Cerebrovascular Function

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          Abstract

          Research has suggested a number of beneficial effects arising from the consumption of dietary flavonoids, found in foods such as cocoa, apples, tea, citrus fruits and berries on cardiovascular risk factors such as high blood pressure and endothelial dysfunction. These effects are thought to have a significant impact upon both vascular and cerebrovascular health, ultimately with the potential to prevent cardiovascular and potentially neurodegenerative disease with a vascular component, for example vascular dementia. This review explores the current evidence for the effects of flavonoid supplementation on human endothelial function and both peripheral and cerebral blood flow (CBF). Evidence presented includes their potential to reduce blood pressure in hypertensive individuals, as well as increasing peripheral blood perfusion and promoting CBF in both healthy and at-risk populations. However, there is great variation in the literature due to the heterogeneous nature of the randomised controlled trials conducted. As such, there is a clear need for further research and understanding within this area in order to maximise potential health benefits.

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          Most cited references81

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          Benefits of polyphenols on gut microbiota and implications in human health.

          The biological properties of dietary polyphenols are greatly dependent on their bioavailability that, in turn, is largely influenced by their degree of polymerization. The gut microbiota play a key role in modulating the production, bioavailability and, thus, the biological activities of phenolic metabolites, particularly after the intake of food containing high-molecular-weight polyphenols. In addition, evidence is emerging on the activity of dietary polyphenols on the modulation of the colonic microbial population composition or activity. However, although the great range of health-promoting activities of dietary polyphenols has been widely investigated, their effect on the modulation of the gut ecology and the two-way relationship "polyphenols ↔ microbiota" are still poorly understood. Only a few studies have examined the impact of dietary polyphenols on the human gut microbiota, and most were focused on single polyphenol molecules and selected bacterial populations. This review focuses on the reciprocal interactions between the gut microbiota and polyphenols, the mechanisms of action and the consequences of these interactions on human health. Copyright © 2013 Elsevier Inc. All rights reserved.
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            (-)-Epicatechin mediates beneficial effects of flavanol-rich cocoa on vascular function in humans.

            Epidemiological and medical anthropological investigations suggest that flavanol-rich foods exert cardiovascular health benefits. Endothelial dysfunction, a prognostically relevant key event in atherosclerosis, is characterized by a decreased bioactivity of nitric oxide (NO) and impaired flow-mediated vasodilation (FMD). We show in healthy male adults that the ingestion of flavanol-rich cocoa was associated with acute elevations in levels of circulating NO species, an enhanced FMD response of conduit arteries, and an augmented microcirculation. In addition, the concentrations and the chemical profiles of circulating flavanol metabolites were determined, and multivariate regression analyses identified (-)-epicatechin and its metabolite, epicatechin-7-O-glucuronide, as independent predictors of the vascular effects after flavanol-rich cocoa ingestion. A mixture of flavanols/metabolites, resembling the profile and concentration of circulating flavanol compounds in plasma after cocoa ingestion, induced a relaxation in preconstricted rabbit aortic rings ex vivo, thus mimicking acetylcholine-induced relaxations. Ex vivo flavanol-induced relaxation, as well as the in vivo increases in FMD, were abolished by inhibition of NO synthase. Oral administration of chemically pure (-)-epicatechin to humans closely emulated acute vascular effects of flavanol-rich cocoa. Finally, the concept that a chronic intake of high-flavanol diets is associated with prolonged, augmented NO synthesis is supported by data that indicate a correlation between the chronic consumption of a cocoa flavanol-rich diet and the augmented urinary excretion of NO metabolites. Collectively, our data demonstrate that the human ingestion of the flavanol (-)-epicatechin is, at least in part, causally linked to the reported vascular effects observed after the consumption of flavanol-rich cocoa.
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              Flavonoid Bioavailability and Attempts for Bioavailability Enhancement

              Flavonoids are a group of phytochemicals that have shown numerous health effects and have therefore been studied extensively. Of the six common food flavonoid classes, flavonols are distributed ubiquitously among different plant foods whereas appreciable amounts of isoflavones are found in leguminous plant-based foods. Flavonoids have shown promising health promoting effects in human cell culture, experimental animal and human clinical studies. They have shown antioxidant, hypocholesterolemic, anti-inflammatory effects as well as ability to modulate cell signaling and gene expression related disease development. Low bioavailability of flavonoids has been a concern as it can limit or even hinder their health effects. Therefore, attempts to improve their bioavailability in order to improve the efficacy of flavonoids are being studied. Further investigations on bioavailability are warranted as it is a determining factor for flavonoid biological activity.
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                Author and article information

                Journal
                Nutrients
                Nutrients
                nutrients
                Nutrients
                MDPI
                2072-6643
                1 December 2018
                December 2018
                : 10
                : 12
                : 1852
                Affiliations
                Department of Food and Nutritional Sciences, University of Reading, Whiteknights, Reading RG6 6AP, UK; a.j.rees@ 123456pgr.reading.ac.uk (A.R.); g.dodd@ 123456reading.ac.uk (G.F.D.)
                Author notes
                [* ]Correspondence: j.p.e.spencer@ 123456reading.ac.uk ; Tel.: +44-0118-378-8724
                Article
                nutrients-10-01852
                10.3390/nu10121852
                6315948
                30513729
                1018a60c-0ff9-4d73-9045-e9562ad4fdf3
                © 2018 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
                : 05 November 2018
                : 22 November 2018
                Categories
                Review

                Nutrition & Dietetics
                flavonoid,cocoa,blood pressure,flow-mediated dilation,cerebral blood flow,cardiovascular disease,cerebrovascular function

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