Impact of flavan-3-ols on blood pressure and endothelial function in diverse populations: a systematic review and meta-analysis of randomized controlled trials

Aims 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. Methods and results 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 mg (95% CI 510, 662) total flavan-3-ols. Interventions decreased office (-2.8 [95% CI -3.9, -1.7]/-2.0 [-2.6, -1.3] mmHg) and 24 h-ambulatory BP (-3.7 [-5.8, -1.6]/-2.6 [-4.5, -0.8] mmHg) after chronic repetitive consumption. Effects were larger with elevated and hypertensive baseline BP or categorical hypertension (office: -5.9 [-10.0, -1.8]/-2.7 [-4.4, -1.0] mmHg, 24 h ABP: -6.8 [-16.3, 2.8]/-5.1 [-12.5, 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 (I-2 > 50%) between studies was not explained by the investigated factors limiting the strength of evidence to 'moderate'. Conclusion Flavan-3-ol-rich foods considerably reduce elevated BP and improve endothelial function independent of blood pressure supporting their use for cardiovascular prevention. [GRAPHICS] .