Dose-response relationship between cocoa flavanols and human endothelial function: a systematic review and meta-analysis of randomized trials.

Background: Several intervention studies have investigated the relationship between cocoa flavanols and endothelial function. However, the shape of the association and the type of compounds responsible for the effects are largely unknown. Objective: To examine the dose-response association between the consumption of cocoa flavanols and endothelial function, measured by flow-mediated dilation (FMD). Design: Two investigators searched Scopus (R) for the relevant human intervention studies, which were pooled and meta-analysed. Heterogeneity in the findings was explored with various subgroup analyses. Results: Fifteen published articles with 18 intervention arms met the inclusion criteria. Participants in these intervention groups received 80 to 1248 mg (mean: 704 mg) more flavanols than control groups. A significant improvement of FMD by 1.17% (95% CI: 0.76% to 1.57%) was calculated, with strong evidence of a non-linear association (inverted U-shape) between cocoa flavanols and FMD. Conclusions: This meta-analysis provides evidence that cocoa flavanols could significantly improve endothelial function, with an optimal effect observed with 710 mg total flavanols, 95 mg (-)-epicatechin or 25 mg (+)-catechin. However, there was substantial variation in the results that could not be explained by the characteristics that we explored, and there were significant risk-of-bias concerns with a large majority of the studies.