Impact of flavonols on cardiometabolic biomarkers:  A meta-analysis of randomized controlled human  trials to explore the role of inter-individual variability

This article is based upon work from COST Action FA1403-POSITIVe "Interindividual variation in response to consumption of plant food bioactives and determinants involved" supported by COST (European Cooperation in Science and Technology, http://www.cost.eu/). The authors thank the financial support of the COST Action FA1403 "POSITIVe" to conduct two short-term scientific missions to P.P. and A.G.-S. at the University of Glasgow (E.C.) during which the data analysis was performed, and to M.G.-A at the University College Dublin (E.G.) during which the protocol was developed. A.G.-S. is holder of a "Juan de la Cierva" contract from MINECO (Spain). S.P.-D. is in receipt of a CONACyT scholarship. T.R. and V.M. are supported by the Fund for scientific research of Goce Delcev University, Stip. RM acknowledges iNOVA4Health Research Unit (LISBOA-01-0145-FEDER-007344), which is cofunded by Fundacao para a Ciencia e Tecnologia/Ministerio da Ciencia e do Ensino Superior, through national funds, and by FEDER under the PT2020 Partnership Agreement. C.A.-L. thanks the grant PCIN-2014-133 (FoodBAll project) from the Spanish Ministry of Economy and Competitiveness (MINECO) within the Joint Programming Initiative Healthy Diet for Healthy Life (JPI-HDHL)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 level