Effects of the pure flavonoids epicatechin and quercetin on vascular function and cardiometabolic health: a randomized, double-blind, placebo-controlled, crossover trial.

Randomized, double-blind, placebo-controlled crossover trial conducted in apparently healthy older adults in the Netherlands. Participants were men and women aged 40-80 years with mildly elevated systolic blood pressure, nonsmokers, and generally free of major cardiometabolic disease; for each active intervention arm, 37 were randomized/enrolled and 35 completed and were analyzed.

In the active treatment periods, participants received oral (2)-epicatechin 100 mg/day or quercetin-3-glucoside 160 mg/day, each provided as 2 capsules per day, one with breakfast and one with dinner, for 4 weeks. Placebo capsules served as the control in the crossover design.

Overall, epicatechin did not significantly improve the primary vascular endpoint, and quercetin-3-glucoside did not improve vascular function or most cardiometabolic markers. For epicatechin, chronic flow-mediated dilation was not significant (1.08, 95% CI -0.09 to 2.26; P=0.07), but fasting insulin and insulin resistance improved (insulin -1.46, 95% CI -2.74 to -0.18; P=0.03; HOMA-IR -0.38, 95% CI -0.74 to -0.01; P=0.04). Most other outcomes, including blood pressure, pulse wave velocity, lipids, glucose, and body weight, were unchanged. These findings suggest a possible insulin-sensitivity effect for epicatechin, but little evidence that either pure flavonoid meaningfully improves vascular function over 4 weeks.

The active arms were small and the intervention periods were short at 4 weeks, limiting power to detect modest effects and long-term clinical relevance. The study involved relatively healthy older adults with mildly elevated systolic blood pressure at a single Dutch site, which limits generalizability. Most endpoints were null, and the crossover design cannot fully address whether longer exposure would produce different vascular or cardiometabolic effects.