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      Effects of Quercetin on Blood Pressure: A Systematic Review and Meta‐Analysis of Randomized Controlled Trials

      research-article
      , MD, PhD 1 , 5 , , PharmD 2 , , MD, PhD 3 , , MD, PhD 4 , , DrPH 1 , , PharmD 5 , , PhD 5 , , MD, MPH 6 , , MD 7 , , PhD 1 , , MD 8 , , MD, PhD 9 , , MD, PhD 10 , , MD, PhD 11 , , MD, PhD, FNLA, FAHA, FESC, FASA 11 , , for the Lipid and Blood Pressure Meta‐analysis Collaboration (LBPMC) Group
      Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
      John Wiley and Sons Inc.
      blood pressure, flavonoids, high blood pressure, hypertension, lipids, meta‐analysis, nutrition, quercetin, Hypertension, High Blood Pressure

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          Abstract

          Background

          Quercetin, the most abundant dietary flavonol, has antioxidant effects in cardiovascular disease, but the evidence regarding its effects on blood pressure ( BP) has not been conclusive. We assessed the impact of quercetin on BP through a systematic review and meta‐analysis of available randomized controlled trials.

          Methods and Results

          We searched PUBMED, Cochrane Library, Scopus, and EMBASE up to January 31, 2015 to identify placebo‐controlled randomized controlled trials investigating the effect of quercetin on BP. Meta‐analysis was performed using either a fixed‐effects or random‐effect model according to I 2 statistic. Effect size was expressed as weighted mean difference ( WMD) and 95% CI. Overall, the impact of quercetin on BP was reported in 7 trials comprising 9 treatment arms (587 patients). The results of the meta‐analysis showed significant reductions both in systolic BP ( WMD: −3.04 mm Hg, 95% CI: −5.75, −0.33, P=0.028) and diastolic BP ( WMD: −2.63 mm Hg, 95% CI: −3.26, −2.01, P<0.001) following supplementation with quercetin. When the studies were categorized according to the quercetin dose, there was a significant systolic BP and diastolic BP‐reducing effect in randomized controlled trials with doses ≥500 mg/day ( WMD: −4.45 mm Hg, 95% CI: −7.70, −1.21, P=0.007 and −2.98 mm Hg, 95% CI: −3.64, −2.31, P<0.001, respectively), and lack of a significant effect for doses <500 mg/day ( WMD: −1.59 mm Hg, 95% CI: −4.44, 1.25, P=0.273 and −0.24 mm Hg, 95% CI: −2.00, 1.52, P=0.788, respectively), but indirect comparison tests failed to significant differences between doses.

          Conclusions

          The results of the meta‐analysis showed a statistically significant effect of quercetin supplementation in the reduction of BP, possibly limited to, or greater with dosages of >500 mg/day. Further studies are necessary to investigate the clinical relevance of these results and the possibility of quercetin application as an add‐on to antihypertensive therapy.

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          Most cited references63

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          Trim and Fill: A Simple Funnel-Plot-Based Method of Testing and Adjusting for Publication Bias in Meta-Analysis

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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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              The results of direct and indirect treatment comparisons in meta-analysis of randomized controlled trials.

              When little or no data directly comparing two treatments are available, investigators often rely on indirect comparisons from studies testing the treatments against a control or placebo. One approach to indirect comparison is to pool findings from the active treatment arms of the original controlled trials. This approach offers no advantage over a comparison of observational study data and is prone to bias. We present an alternative model that evaluates the differences between treatment and placebo in two sets of clinical trials, and preserves the randomization of the originally assigned patient groups. We apply the method to data on sulphamethoxazole-trimethoprim or dapsone/pyrimethamine as prophylaxis against Pneumocystis carinii in HIV infected patients. The indirect comparison showed substantial increased benefit from the former (odds ratio 0.37, 95% CI 0.21 to 0.65), while direct comparisons from randomized trials suggests a much smaller difference (risk ratio 0.64, 95% CI 0.45 to 0.90; p-value for difference of effect = 0.11). Direct comparisons of treatments should be sought. When direct comparisons are unavailable, indirect comparison meta-analysis should evaluate the magnitude of treatment effects across studies, recognizing the limited strength of inference.
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                Author and article information

                Journal
                J Am Heart Assoc
                J Am Heart Assoc
                10.1002/(ISSN)2047-9980
                JAH3
                ahaoa
                Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
                John Wiley and Sons Inc. (Hoboken )
                2047-9980
                12 July 2016
                July 2016
                : 5
                : 7 ( doiID: 10.1002/jah3.2016.5.issue-7 )
                : e002713
                Affiliations
                [ 1 ]University of Alabama at Birmingham AL
                [ 2 ] Biotechnology Research CenterMashhad University of Medical Sciences MashhadIran
                [ 3 ] Istituto Auxologico Italiano and Centro Interuniversitario di Fisiologia Clinica e Ipertensione Università di Milano Italy
                [ 4 ] Department of Clinical Biochemistry Royal Free Campus University College London Medical SchoolUniversity College London (UCL) LondonUK
                [ 5 ]University of Medicine and Pharmacy TimisoaraRomania
                [ 6 ]Washington DC Veterans Affairs Medical Center Washington DC
                [ 7 ]New York Medical College Valhalla NY
                [ 8 ]University of Birmingham Centre for Cardiovascular Sciences, City Hospital BirminghamUK
                [ 9 ]Erasmus MC‐University Medical Center Rotterdam the Netherlands
                [ 10 ]University of California Irvine CA
                [ 11 ]Medical University of Lodz Poland
                Author notes
                [*] [* ] Correspondence to: Maciej Banach, MD, PhD, FNLA, FAHA, FESC, FASA, Department of Hypertension, WAM University Hospital in Lodz, Medical University of Lodz, Zeromskiego 113, 90‐549 Lodz, Poland. E‐mail: maciejbanach@ 123456aol.co.uk
                [†]

                A complete list of the Lipid and Blood Pressure Meta‐analysis Collaboration (LBPMC) Group members can be found in the Appendix at the end of the manuscript.

                Article
                JAH31607
                10.1161/JAHA.115.002713
                5015358
                27405810
                0acf7e28-e101-442b-9995-191c78a773fb
                © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

                This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

                History
                : 07 October 2015
                : 24 May 2016
                Page count
                Pages: 15
                Categories
                Original Research
                Original Research
                Hypertension
                Custom metadata
                2.0
                jah31607
                July 2016
                Converter:WILEY_ML3GV2_TO_NLMPMC version:4.9.4 mode:remove_FC converted:01.09.2016

                Cardiovascular Medicine
                blood pressure,flavonoids,high blood pressure,hypertension,lipids,meta‐analysis,nutrition,quercetin

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