Dietary Polyphenols and Cardiovascular Health: From Bioavailability to Clinical Relevance.

Dietary polyphenols, abundant in fruits, vegetables, tea, coffee, cocoa, and wine, have been widely investigated for their potential relevance to cardiovascular health. Their proposed protective effects extend beyond classical antioxidant activity, encompassing regulation of redox-sensitive signaling, attenuation of inflammation, improvement in endothelial function, modulation of lipid metabolism, and mitochondrial protection. Yet, their biological impact is strongly dependent on bioavailability and metabolic fate, as most compounds undergo extensive conjugation and gut microbiota-dependent transformation. Conjugated metabolites and microbial derivatives increasingly appear as key mediators of systemic vascular responses. Epidemiological studies associate polyphenol-rich dietary patterns with reduced cardiovascular risk, while clinical trials report modest and variable effects on intermediate outcomes such as vascular function, blood pressure, and plasma lipids. However, heterogeneity in study design, dosing, and compound source contributes to inconsistent outcomes and limits translation into practice. This review integrates current knowledge on classification, dietary sources, metabolism, and molecular mechanisms of polyphenols, emphasizing the interplay between host and microbiota in shaping cardioprotective responses. By bridging mechanistic insights with clinical observations, we highlight both the therapeutic promise and the translational challenges of polyphenols. Standardized intervention protocols, physiologically relevant dosing strategies, and precision nutrition approaches are essential to fully realize their potential in cardiovascular prevention.