Polyphenols ameliorate high-fat meal-induced endothelial dysfunction: findings from systematic reviews and meta-analyses
J FewkesAbstract
Background
Endothelial dysfunction is the first step towards atherosclerosis and a key predictor of cardiovascular disease (CVD). High-fat meals, characteristic of Western diets, acutely impair endothelial function and represent an early, modifiable risk factor for vascular disease. Dietary polyphenols have been proposed to protect vascular health through antioxidant and anti-inflammatory pathways. However, the magnitude of high-fat meal-induced endothelial impairment and whether polyphenols can attenuate this effect remained unquantified.
Purpose
To quantify the postprandial endothelial response to a single high-fat meal and determine whether concurrent polyphenol consumption attenuates meal-induced vascular impairment, using flow-mediated dilation (FMD), a non-invasive ultrasound marker of endothelial function.
Methods
Two complementary systematic reviews and meta-analyses were prospectively registered and conducted in accordance with PRISMA guidelines. Comprehensive searches across six databases (MEDLINE, EMBASE, CINAHL, Cochrane, Scopus, and Web of Science) identified 92 trials (N = 2904) measuring brachial artery FMD before and after a single high-fat meal, consumed alone or with a polyphenol-rich food or supplement. These contributed 90 study arms to the high-fat meal analysis and 27 study arms to the polyphenol co-ingestion analysis. A random-effects meta-analysis using restricted maximum likelihood (REML) estimation examined postprandial FMD responses at hourly intervals from 1 to 7 hours post-consumption. Meta-regression explored the influence of key moderating variables, including age, BMI, health status, meal fat content, and total polyphenol dose.
Results
High-fat meals reduced postprandial FMD at 2 hours (-1.02 pp [95% CI: -1.34, -0.70]; P < 0.01), with consistent reductions observed at 3 and 4 hours, indicating transient vascular dysfunction. Effects were greatest in younger, healthy-weight participants, with age (B = -0.11, P < 0.001) and BMI (B = -0.47, P < 0.001) independently predicting fasting FMD. Polyphenol co-ingestion effectively reversed the high-fat-induced impairment by 0.97 pp ([95% CI: 0.66, 1.28]; P < 0.0001) at peak postprandial response, with fruit and vegetable-derived polyphenols demonstrating the strongest protective effect. The vascular benefits of polyphenol co-administration were greatest in those with lower BMI (B = -0.11, P < 0.0001).
Conclusions
A single high-fat meal transiently impairs endothelial function, with effects varying by age, BMI, and health status. Concurrent consumption of polyphenol-rich foods effectively ameliorates this impairment, demonstrating the potential of dietary polyphenols to protect vascular health and delay atherosclerosis progression in the context of Western dietary patterns. The inclusion of polyphenol-rich foods alongside high-fat meals is a practical, accessible dietary strategy for cardiovascular disease prevention.