title: Impact of Flavonols on Cardiometabolic Biomarkers:  A Meta-Analysis of Randomized Controlled Human  Trials to Explore the Role of Inter-Individual  Variability.
abstract: Several  epidemiological  studies  have  linked  flavonols  with  decreased  risk  of  cardiovascular  disease  (CVD).  However,  some  heterogeneity  in  the  individual  physiological  responses to the consumption of these compounds has been identified. This meta-analysis aimed to  study the effect of flavonol supplementation on biomarkers of CVD risk such as, blood lipids, blood  pressure and plasma glucose, as well as factors affecting their inter-individual variability. Data from  18 human randomized controlled trials were pooled and the effect was estimated using fixed or  random effects meta-analysis model and reported as difference in means (DM). Variability in the  response of blood lipids to supplementation with flavonols was assessed by stratifying various  population subgroups: age, sex, country, and health status. Results showed significant reductions  in total cholesterol (DM = -0.10 mmol/L; 95% CI: -0.20, -0.01), LDL cholesterol (DM = -0.14 mmol/L;  Nutrients 2017, 9, 117  2 of 21  95% CI: -0.21, 0.07), and triacylglycerol (DM = -0.10 mmol/L; 95% CI: -0.18, 0.03), and a significant  increase in HDL cholesterol (DM = 0.05 mmol/L; 95% CI: 0.02, 0.07). A significant reduction was also  observed in fasting plasma glucose (DM = -0.18 mmol/L; 95%CI: -0.29, -0.08), and in blood pressure  (SBP: DM = -4.84 mmHg; 95% CI: -5.64, -4.04; DBP: DM = -3.32 mmHg; 95% CI: -4.09, -2.55).  Subgroup analysis showed a more pronounced effect of flavonol intake in participants from Asian  countries and in participants with diagnosed disease or dyslipidemia, compared to healthy and  normal baseline values. In conclusion, flavonol consumption improved biomarkers of CVD risk,  however, country of origin and health status may influence the effect of flavonol intake on blood  lipid levels.
authors.affiliation: BET/ITQB, Molecular Nutrition & Health Laboratory, 2780-157 Oeiras, Portugal. rmenezes@ibet.pt.
authors.forename: Regina
authors.initials: R
authors.lastname: Menezes
authors.affiliation: Division of Diabetes and Nutritional Sciences, Faculty of Life Sciences and Medicine, King's College London, London SE1 9NH, UK. mateos@kcl.ac.uk.
authors.forename: Ana
authors.initials: A
authors.lastname: Rodriguez-Mateos
authors.affiliation: FAME Laboratory, School of Exercise Science, University of Thessaly, 42100 Volos, Greece. akaltsat@gmail.com.
authors.forename: Antonia
authors.initials: A
authors.lastname: Kaltsatou
authors.affiliation: CEBAS-CSIC, E-30100 Murcia, Spain. agsarrias@cebas.csic.es.
authors.forename: Antonio
authors.initials: A
authors.lastname: González-Sarrías
authors.affiliation: Unilever R&D, 3133AT Vlaardingen, The Netherlands. Arno.Greyling@unilever.com.
authors.forename: Arno
authors.initials: A
authors.lastname: Greyling
authors.affiliation: University of Nicosia, CY1700 Engomi, Cyprus. giannaki.c@unic.ac.cy.
authors.forename: Christoforos
authors.initials: C
authors.lastname: Giannaki
authors.affiliation: Biomarkers and Nutrimetabolomic Laboratory, Department of Nutrition, Food Sciences and Gastronomy, Campus Torribera, Faculty of Pharmacy and Food Sciences, University of Barcelona, CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 08028 Barcelona, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Andres-Lacueva
authors.affiliation: INRA, UMR 1019, UNH, CRNH Auvergne, F-63000 Clermont-Ferrand, Clermont Université, Université d'Auvergne, Unité de Nutrition Humaine, BP 10448, F-63000 Clermont-Ferrand, France. dragan.milenkovic@clermont.inra.fr.
authors.forename: Dragan
authors.initials: D
authors.lastname: Milenkovic
authors.affiliation: University College Dublin, D4 Dublin, Ireland. eileen.gibney@ucd.ie.
authors.forename: Eileen R
authors.initials: ER
authors.lastname: Gibney
authors.affiliation: Université Lille, INSERM, Institut Pasteur de Lille, U1167-RID-AGE-Facteurs de Risque et Déterminants Moléculaires des Maladies Liées au Vieillissement, F-59000 Lille, France. eileen.gibney@ucd.ie.
authors.forename: Julie
authors.initials: J
authors.lastname: Dumont
authors.affiliation: Department of Food and Nutritional Sciences, University of Reading, Reading RG6 6AP, UK. rmenezes@ibet.pt.
authors.forename: Manuel
authors.initials: M
authors.lastname: Schär
authors.affiliation: Biomarkers and Nutrimetabolomic Laboratory, Department of Nutrition, Food Sciences and Gastronomy, Campus Torribera, Faculty of Pharmacy and Food Sciences, University of Barcelona, CIBER de Fragilidad y Envejecimiento Saludable (CIBERFES), Instituto de Salud Carlos III, 08028 Barcelona, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Garcia-Aloy
authors.affiliation: Human Nutrition, University of Glasgow, Glasgow G31 2ER, UK. mateos@kcl.ac.uk.
authors.forename: Susana Alejandra
authors.initials: SA
authors.lastname: Palma-Duran
authors.affiliation: Goce Delcev University, 2000 Stip, Macedonia. akaltsat@gmail.com.
authors.forename: Tatjana
authors.initials: T
authors.lastname: Ruskovska
authors.affiliation: Goce Delcev University, 2000 Stip, Macedonia. akaltsat@gmail.com.
authors.forename: Viktorija
authors.initials: V
authors.lastname: Maksimova
authors.affiliation: Human Nutrition, University of Glasgow, Glasgow G31 2ER, UK. mateos@kcl.ac.uk.
authors.forename: Emilie
authors.initials: E
authors.lastname: Combet
authors.affiliation: BET/ITQB, Molecular Nutrition & Health Laboratory, 2780-157 Oeiras, Portugal. paula.pinto@esa.ipsantarem.pt.|Polytechnic Institute of Santarem, ESA, Department of Food Technology, Biotechnology and Nutrition, 2001-904 Santarém, Portugal. paula.pinto@esa.ipsantarem.pt.
authors.forename: Paula
authors.initials: P
authors.lastname: Pinto
mesh_terms: D000328:Adult; D001208:Asia; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure; D002318:Cardiovascular Diseases / Q000209:etiology / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D019587:Dietary Supplements; D005260:Female; D044948:Flavonols / Q000008:administration & dosage*; D006801:Humans; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D012307:Risk Factors
chemical_list: D015415:Biomarkers; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D044948:Flavonols; D008055:Lipids; D002784:Cholesterol
keywords: flavonols;   Interindividual variability;   cardiovascular  disease;   meta‐analysis;   quercetin;   systematic  review;  blood lipids;  blood pressure;  glucose