Effect of dark chocolate on flow-mediated dilatation: Systematic review, meta-analysis, and dose-response analysis of randomized controlled trials

Background & aims: We aimed to investigate the effect of dark chocolate on flow-mediated dilatation (FMD) using randomized clinical trials.

Methods: In order to find relevant papers, PubMed and Scopus were searched up to November 2018. Mean differences of eligible trials were pooled using random-effects models (the Der Simonian-Laird estimator). Subgroup analysis was conducted to assess the potential source of heterogeneity. Fractional polynomial modeling was used to explore dose-response relationships.

Results: Seventeen studies involving 615 participants assessed the effect of dark chocolate and six included studies involving 179 participants investigated the effect of flavonoids on FMD. Chronic consumption of dark chocolate and flavan-3-ols both increased FMD (0.69, 95% CI 0.22-1.16, p < 0.001, 1.16, 95% CI 0.52-1.80 p = 0.001, respectively). Pooling chronic consumption of dark chocolate and flavonoids improved FMD (p < 0.001) with significant heterogeneity among studies (p < 0.001; I² = 64.2%). Type of intervention (flavonoid or cocoa, p = 0.230-dark chocolate, p < 0.001) was a source of heterogeneity. Also, we found that acute consumption of dark chocolate (p < 0.001) and both dark chocolate and flavonoids (p < 0.001) had beneficial effects on FMD. Consumption of flavonoids more than 40 g/day increases FMD with the highest mean of FMD in doses around 40-60 g/day. A non-linear dose-response has been also found after the chronic consumption of dark chocolate on FMD with a greater reduction in doses lower than 20 g/day.

Conclusion: Current evidence indicated the beneficial effect of acute and chronic consumption of dark chocolate and flavonoids on FMD. Non-linear associations should be considered when investigating the effects of dietary intakes on FMD.