Effects of Coffee-Related Bioactive Components on Flow-Mediated Vasodilation: A Meta-Analysis of Randomized, Controlled Intervention Studies in Adults

Context: Coffee contains various bioactive compounds, including chlorogenic acids (CGAs), caffeine, and hydroxyhydroquinone (HHQ), which may differently affect endothelial function. Objective: This meta-analysis of randomized controlled trials (RCTs) examined both longer-term and acute effects of coffee-related bioactive components on endothelial function in adults, measured by brachial artery flow-mediated vasodilation (FMD), a validated marker of cardiovascular disease (CVD) risk. Data sources: A systematic literature search was conducted in Ovid Medline, Embase, Cochrane, and Web of Science up to July 2025. Data extraction: Relevant data were extracted from 19 eligible RCTs. Fixed or random-effects meta-analyses were conducted to estimate weighted mean differences (WMDs) with 95% CIs. Data analysis: Four RCTs investigating longer-term CGA intake (median dose: 300 mg/day) showed a significant increase in fasting FMD of 2.52 percentage points (PP; 95% CI: 1.19, 3.85, P < .001; I-2 = 0.0%). Ten RCTs evaluating acute CGA intake also reported a significant FMD increase of 1.51 PP (95% CI: 0.91, 2.96; P < .001; I-2 = 68.0%). These effects were more pronounced for studies using CGA-rich coffee beverages compared with those using isolated CGA supplements (Delta WMD: 1.41 PP; 95% CI: 0.27, 2.55; P = .016). Caffeine showed no significant effect on FMD across 6 acute studies (WMD: -0.05 PP; 95% CI: -2.78, 2.68, P = .971; I-2 = 95.3%), while FMD was significantly reduced by 1.04 PP (95% CI: 0.20, 1.88; P = .015; I-2 = 0.0%) in the 2 acute studies that examined HHQ. Conclusions: This meta-analysis provides evidence that both longer-term and acute CGA intake significantly improve endothelial function, especially when consumed as part of coffee beverages. These findings support the potential role of moderate coffee consumption in reducing CVD risk.