{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:31:25Z","timestamp":1791919885425,"version":"4.3.4"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"14","license":[{"start":{"date-parts":[[2025,3,24]],"date-time":"2025-03-24T00:00:00Z","timestamp":1742774400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Lipton Teas & Infusions"},{"name":"BHF Basic Science Research","award":["FS\/15\/59\/31839"],"award-info":[{"award-number":["FS\/15\/59\/31839"]}]},{"name":"BHF Basic Science Research","award":["FS\/SBSRF\/21\/31025"],"award-info":[{"award-number":["FS\/SBSRF\/21\/31025"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Aims<\/jats:title>\n                  <jats:p>Flavan-3-ols, found in cocoa, tea, and certain fruits, show promise in improving blood pressure (BP) and vascular function, but are currently not used for cardiovascular prevention. This meta-analysis evaluated the effects of flavan-3-ol-rich interventions on BP and endothelial function.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and results<\/jats:title>\n                  <jats:p>PubMed was searched for randomized controlled trials (RCTs) published 1946-03\/2024 on BP and flow-mediated dilation after flavan-3-ol-rich food, beverage, or supplement intake. Random-effects meta-analysis of 109 publications including 145 RCTs and 5205 participants was performed (PROSPERO: CRD42023454691). Flavan-3-ol interventions included epicatechin, epigallocatechin-gallate, cocoa products, tea, grape extract, and apples delivering 586\u2005mg (95% CI 510, 662) total flavan-3-ols. Interventions decreased office (\u22122.8 [95% CI \u22123.9, \u22121.7]\/\u22122.0 [\u22122.6, \u22121.3] mmHg) and 24\u2005h-ambulatory BP (\u22123.7 [\u22125.8, \u22121.6]\/\u22122.6 [\u22124.5, \u22120.8] mmHg) after chronic repetitive consumption. Effects were larger with elevated and hypertensive baseline BP or categorical hypertension (office: \u22125.9 [\u221210.0, \u22121.8]\/\u22122.7 [\u22124.4, \u22121.0] mmHg, 24\u2005h ABP: \u22126.8 [\u221216.3, 2.8]\/\u22125.1 [\u221212.5, 2.2] mmHg). Meta-regression analysis confirmed that the magnitude of BP lowering was inversely related to baseline BP, but not to proportion of participants with CVD, diabetes mellitus, and study duration across all studies, and was dose-dependently related to epicatechin dose only in cocoa studies. Flow-mediated dilation increased after acute (+2.0% [1.6, 2.3]) and repetitive (+1.7% [1.3, 2.2]) consumption independent of BP. Reported adverse events were minor and low (0.4%). The considerable heterogeneity of effect sizes (I2 &amp;gt; 50%) between studies was not explained by the investigated factors limiting the strength of evidence to \u2018moderate\u2019.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Flavan-3-ol-rich foods considerably reduce elevated BP and improve endothelial function independent of blood pressure supporting their use for cardiovascular prevention.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/eurjpc\/zwaf173","type":"journal-article","created":{"date-parts":[[2025,3,29]],"date-time":"2025-03-29T00:09:24Z","timestamp":1743206964000},"page":"1322-1334","source":"Crossref","is-referenced-by-count":22,"title":["Impact of flavan-3-ols on blood pressure and endothelial function in diverse populations: a systematic review and meta-analysis of randomized controlled trials"],"prefix":"10.1093","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3165-8940","authenticated-orcid":false,"given":"Vasiliki","family":"Lagou","sequence":"first","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Faculty of Health and Medical Sciences, University of Surrey , Stag Hill, Guildford GU2 7XH , (Institution where work was performed)","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9633-1546","authenticated-orcid":false,"given":"Arno","family":"Greyling","sequence":"additional","affiliation":[{"name":"Unilever Food Innovation Centre , Wageningen ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1384-2672","authenticated-orcid":false,"given":"Mario G","family":"Ferruzzi","sequence":"additional","affiliation":[{"name":"Arkansas Children\u2019s Nutrition Center, Department of Pediatrics, University of Arkansas for Medical Sciences , 15 Children\u2019s Way, Little Rock, AR 72202 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7828-3122","authenticated-orcid":false,"given":"Simon S","family":"Skene","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Faculty of Health and Medical Sciences, University of Surrey , Stag Hill, Guildford GU2 7XH , (Institution where work was performed)","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joy","family":"Dubost","sequence":"additional","affiliation":[{"name":"Lipton Teas and Infusions Research & Innovation, Amsterdam Science Park , Amsterdam ,","place":["The Netherlands"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7546-0867","authenticated-orcid":false,"given":"Ayse","family":"Demirkan","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Faculty of Health and Medical Sciences, University of Surrey , Stag Hill, Guildford GU2 7XH , (Institution where work was performed)","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1624-7457","authenticated-orcid":false,"given":"Inga","family":"Prokopenko","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Faculty of Health and Medical Sciences, University of Surrey , Stag Hill, Guildford GU2 7XH , (Institution where work was performed)","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Shlisky","sequence":"additional","affiliation":[{"name":"Arkansas Children\u2019s Nutrition Center, Department of Pediatrics, University of Arkansas for Medical Sciences , 15 Children\u2019s Way, Little Rock, AR 72202 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3242-402X","authenticated-orcid":false,"given":"Ana","family":"Rodriguez-Mateos","sequence":"additional","affiliation":[{"name":"Department of Nutritional Sciences, School of Life Course and Population Sciences, Faculty of Life Sciences and Medicine, King\u2019s College London , London SE1 9NH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3212-8995","authenticated-orcid":false,"given":"Christian","family":"Heiss","sequence":"additional","affiliation":[{"name":"Department of Clinical and Experimental Medicine, Faculty of Health and Medical Sciences, University of Surrey , Stag Hill, Guildford GU2 7XH , (Institution where work was performed)","place":["UK"]},{"name":"Vascular Medicine Department, East Surrey Hospital, Surrey and Sussex Healthcare NHS Trust , Canada Avenue, Redhill RH1 5RH ,","place":["UK"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,3,24]]},"reference":[{"key":"2025100919514936700_zwaf173-B1","doi-asserted-by":"crossref","first-page":"3227","DOI":"10.1093\/eurheartj\/ehab484","article-title":"2021 ESC Guidelines on cardiovascular disease prevention in clinical practice","volume":"42","author":"Visseren","year":"2021","journal-title":"Eur Heart J"},{"key":"2025100919514936700_zwaf173-B2","doi-asserted-by":"crossref","first-page":"3538","DOI":"10.1093\/eurheartj\/ehae179","article-title":"2024 ESC Guidelines for the management of peripheral arterial and aortic diseases: developed by the task force on the management of peripheral arterial and aortic diseases of the European Society of Cardiology (ESC) Endorsed by the European Association for Cardio-Thoracic Surgery (EACTS), the European Reference Network on Rare Multisystemic Vascular Diseases (VASCERN), and the European Society of Vascular Medicine (ESVM)","volume":"45","author":"Mazzolai","year":"2024","journal-title":"Eur Heart J"},{"key":"2025100919514936700_zwaf173-B3","doi-asserted-by":"crossref","first-page":"3912","DOI":"10.1093\/eurheartj\/ehae178","article-title":"2024 ESC Guidelines for the management of elevated blood pressure and hypertension: developed by the task force on the management of elevated blood pressure and hypertension of the European Society of Cardiology (ESC) and endorsed by the European Society of Endocrinology (ESE) and the European Stroke Organisation (ESO)","volume":"45","author":"McEvoy","year":"2024","journal-title":"Eur Heart J"},{"key":"2025100919514936700_zwaf173-B4","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1093\/eurjpc\/zwad057","article-title":"Promotion of healthy nutrition in primary and secondary cardiovascular disease prevention: a clinical consensus statement from the European Association of Preventive Cardiology","volume":"30","author":"Vassiliou","year":"2023","journal-title":"Eur J Prev Cardiol"},{"key":"2025100919514936700_zwaf173-B5","doi-asserted-by":"crossref","first-page":"1490","DOI":"10.1093\/ajcn\/nqac055","article-title":"Effect of cocoa flavanol supplementation for prevention of cardiovascular disease events: the COSMOS randomized clinical trial","volume":"115","author":"Sesso","year":"2022","journal-title":"Am J Clin Nutr"},{"key":"2025100919514936700_zwaf173-B6","doi-asserted-by":"crossref","first-page":"2070","DOI":"10.1093\/advances\/nmac105","article-title":"Flavan-3-ols and cardiometabolic health: first ever dietary bioactive guideline","volume":"13","author":"Crowe-White","year":"2022","journal-title":"Adv Nutr"},{"key":"2025100919514936700_zwaf173-B7","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1093\/ajcn\/nqz178","article-title":"Dietary intakes of flavan-3-ols and cardiometabolic health: systematic review and meta-analysis of randomized trials and prospective cohort studies","volume":"110","author":"Raman","year":"2019","journal-title":"Am J Clin Nutr"},{"key":"2025100919514936700_zwaf173-B8","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.numecd.2013.12.014","article-title":"Inverse association between habitual polyphenol intake and incidence of cardiovascular events in the PREDIMED study","volume":"24","author":"Tresserra-Rimbau","year":"2014","journal-title":"Nutr Metab Cardiovasc Dis"},{"key":"2025100919514936700_zwaf173-B9","doi-asserted-by":"crossref","first-page":"740","DOI":"10.3945\/ajcn.111.023457","article-title":"Effects of chocolate, cocoa, and flavan-3-ols on cardiovascular health: a systematic review and meta-analysis of randomized trials","volume":"95","author":"Hooper","year":"2012","journal-title":"Am J Clin Nutr"},{"key":"2025100919514936700_zwaf173-B10","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1017\/S0007114513003930","article-title":"Assessment of the dietary intake of total flavan-3-ols, monomeric flavan-3-ols, proanthocyanidins and theaflavins in the European union","volume":"111","author":"Vogiatzoglou","year":"2014","journal-title":"Br J Nutr"},{"key":"2025100919514936700_zwaf173-B11","doi-asserted-by":"crossref","first-page":"695","DOI":"10.1097\/01.fjc.0000211762.06271.ce","article-title":"Red wine induced modulation of vascular function: separating the role of polyphenols, ethanol, and urates","volume":"47","author":"Boban","year":"2006","journal-title":"J Cardiovasc Pharmacol"},{"key":"2025100919514936700_zwaf173-B12","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/bcpt.12360","article-title":"Dietary flavonoids added to pharmacological antihypertensive therapy are effective in improving blood pressure","volume":"117","author":"de Jesus Romero-Prado","year":"2015","journal-title":"Basic Clin Pharmacol Toxicol"},{"key":"2025100919514936700_zwaf173-B13","doi-asserted-by":"crossref","first-page":"1281","DOI":"10.1136\/heartjnl-2021-320171","article-title":"Antihypertensive drug effects on long-term blood pressure: an individual-level data meta-analysis of randomised clinical trials","volume":"108","author":"Canoy","year":"2022","journal-title":"Heart"},{"key":"2025100919514936700_zwaf173-B14","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1136\/bmj.326.7404.1427","article-title":"Value of low dose combination treatment with blood pressure lowering drugs: analysis of 354 randomised trials","volume":"326","author":"Law","year":"2003","journal-title":"BMJ"},{"key":"2025100919514936700_zwaf173-B15","doi-asserted-by":"crossref","first-page":"1625","DOI":"10.1016\/S0140-6736(21)00590-0","article-title":"Pharmacological blood pressure lowering for primary and secondary prevention of cardiovascular disease across different levels of blood pressure: an individual participant-level data meta-analysis","volume":"397","author":"Blood Pressure Lowering Treatment Trialists Collaboration","year":"2021","journal-title":"Lancet"},{"key":"2025100919514936700_zwaf173-B16","doi-asserted-by":"crossref","first-page":"e040524","DOI":"10.1136\/bmjopen-2020-040524","article-title":"Antihypertensive drug effects according to the pretreatment self-measured home blood pressure: the HOMED-BP study","volume":"10","author":"Sano","year":"2020","journal-title":"BMJ Open"},{"key":"2025100919514936700_zwaf173-B17","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1093\/cvr\/cvac095","article-title":"Flow-mediated dilation reference values for evaluation of endothelial function and cardiovascular health","volume":"119","author":"Heiss","year":"2023","journal-title":"Cardiovasc Res"},{"key":"2025100919514936700_zwaf173-B18","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.1093\/eurheartj\/ehz350","article-title":"Expert consensus and evidence-based recommendations for the assessment of flow-mediated dilation in humans","volume":"40","author":"Thijssen","year":"2019","journal-title":"Eur Heart J"},{"key":"2025100919514936700_zwaf173-B19","doi-asserted-by":"crossref","first-page":"344","DOI":"10.1016\/j.ijcard.2012.09.047","article-title":"Flow-mediated dilation and cardiovascular risk prediction: a systematic review with meta-analysis","volume":"168","author":"Ras","year":"2013","journal-title":"Int J Cardiol"},{"key":"2025100919514936700_zwaf173-B20","doi-asserted-by":"crossref","first-page":"505","DOI":"10.1016\/S0735-1097(02)01976-9","article-title":"Prognostic role of reversible endothelial dysfunction in hypertensive postmenopausal women","volume":"40","author":"Modena","year":"2002","journal-title":"J Am Coll Cardiol"},{"key":"2025100919514936700_zwaf173-B21","doi-asserted-by":"crossref","first-page":"e2100991","DOI":"10.1002\/mnfr.202100991","article-title":"Flavanol consumption in healthy men preserves integrity of immunological\u2013endothelial barrier cell functions: nutri(epi)genomic analysis","volume":"66","author":"Milenkovic","year":"2022","journal-title":"Mol Nutr Food Res"},{"key":"2025100919514936700_zwaf173-B22","first-page":"1","article-title":"Impact of grapefruit juice on the antiplatelet activity of loading and maintenance doses of clopidogrel in healthy volunteers","volume":"5","author":"Campbell","year":"2014","journal-title":"Cardiol Res"},{"key":"2025100919514936700_zwaf173-B23","doi-asserted-by":"crossref","first-page":"10414","DOI":"10.1039\/D4FO03546A","article-title":"Development of a food frequency questionnaire for the estimation of dietary (poly)phenol intake","volume":"15","author":"Li","year":"2024","journal-title":"Food Funct"},{"key":"2025100919514936700_zwaf173-B24","doi-asserted-by":"crossref","first-page":"746","DOI":"10.1016\/j.clnu.2019.03.041","article-title":"Acute study of dose-dependent effects of (-)-epicatechin on vascular function in healthy male volunteers: a randomized controlled trial","volume":"39","author":"Alanon","year":"2020","journal-title":"Clin Nutr"},{"key":"2025100919514936700_zwaf173-B25","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.freeradbiomed.2014.12.009","article-title":"Interactions between cocoa flavanols and inorganic nitrate: additive effects on endothelial function at achievable dietary amounts","volume":"80","author":"Rodriguez-Mateos","year":"2015","journal-title":"Free Radic Biol Med"},{"key":"2025100919514936700_zwaf173-B26","doi-asserted-by":"crossref","first-page":"1276","DOI":"10.1016\/j.jacc.2005.06.055","article-title":"Acute consumption of flavanol-rich cocoa and the reversal of endothelial dysfunction in smokers","volume":"46","author":"Heiss","year":"2005","journal-title":"J Am Coll Cardiol"},{"key":"2025100919514936700_zwaf173-B27","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1097\/HJH.0b013e328326066c","article-title":"Black tea consumption dose-dependently improves flow-mediated dilation in healthy males","volume":"27","author":"Grassi","year":"2009","journal-title":"J Hypertens"},{"key":"2025100919514936700_zwaf173-B28","doi-asserted-by":"crossref","first-page":"352","DOI":"10.3945\/ajcn.116.140046","article-title":"Methylxanthines enhance the effects of cocoa flavanols on cardiovascular function: randomized, double-masked controlled studies","volume":"105","author":"Sansone","year":"2017","journal-title":"Am J Clin Nutr"},{"key":"2025100919514936700_zwaf173-B29","doi-asserted-by":"crossref","first-page":"e05239","DOI":"10.2903\/j.efsa.2018.5239","article-title":"Scientific opinion on the safety of green tea catechins","volume":"16","author":"EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS)","year":"2018","journal-title":"EFSA J"},{"key":"2025100919514936700_zwaf173-B30","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1038\/426787b","article-title":"Nutrition: milk and absorption of dietary flavanols","volume":"426","author":"Schroeter","year":"2003","journal-title":"Nature"},{"key":"2025100919514936700_zwaf173-B31","doi-asserted-by":"crossref","first-page":"1229","DOI":"10.1093\/ajcn\/nqy229","article-title":"Assessing the respective contributions of dietary flavanol monomers and procyanidins in mediating cardiovascular effects in humans: randomized, controlled, double-masked intervention trial","volume":"108","author":"Rodriguez-Mateos","year":"2018","journal-title":"Am J Clin Nutr"},{"key":"2025100919514936700_zwaf173-B32","doi-asserted-by":"crossref","first-page":"886597","DOI":"10.3389\/fnut.2022.886597","article-title":"Assessing variability in vascular response to cocoa with personal devices: a series of double-blind randomized crossover n-of-1 trials","volume":"9","author":"Bapir","year":"2022","journal-title":"Front Nutr"}],"container-title":["European Journal of Preventive Cardiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/eurjpc\/advance-article-pdf\/doi\/10.1093\/eurjpc\/zwaf173\/62571439\/zwaf173.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjpc\/article-pdf\/32\/14\/1322\/62571439\/zwaf173.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/eurjpc\/article-pdf\/32\/14\/1322\/62571439\/zwaf173.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T23:52:11Z","timestamp":1760053931000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/eurjpc\/article\/32\/14\/1322\/8092214"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,24]]},"references-count":32,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2025,3,24]]},"published-print":{"date-parts":[[2025,10,10]]}},"URL":"https:\/\/doi.org\/10.1093\/eurjpc\/zwaf173","relation":{},"ISSN":["2047-4873","2047-4881"],"issn-type":[{"value":"2047-4873","type":"print"},{"value":"2047-4881","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,10]]},"published":{"date-parts":[[2025,3,24]]}}}