Abstract/Summary

Background: Strong evidence supports the vasoactivity of cocoa flavanols, particularly (-)-epicatechin (EC). However, full dose-dependency of EC remains unclear, emphasising the need for further research and clinical trials to inform public health and future dietary recommendations. Objective: To conduct a clinical trial-based investigation in healthy men to elucidate dose-dependent vascular effects, primarily assessing FMD at doses ≤ 1 mg/kg BW of pure compound over an acute timeframe (6 h), and secondly, assessing bidaily intake of high-flavanol milk chocolate (HFMC) over 2 weeks for a longer-term insight of dietary flavanol intake. Design: Two randomised, controlled, double-blind intervention trials were conducted in 20 and 33 healthy men (18-40 y). Acute study subjects crossed over 4 treatment arms (control 0.0, 0.1, 0.5, and 1 mg/kg BW pure EC) and plasma samples and vascular measures were taken at baseline, 1, 2, 4 and 6 h post-treatment. Acute-on-chronic study subjects followed bidaily intake of either HFMC (35 mg EC/d) or LFMC (0 mg EC/d) over 2 weeks. Plasma samples and FMD measures were taken at the first (day 0) and last day of intervention (day 14), and post-intervention (≥ day 28). Acute measures (2 h) were also assessed at day 0 and day 14. Results: In the acute study we observed significant improvements in FMD% (>1.2%) after ingestion of doses 0.5 and 1 mg/kg BW at 2 h post-ingestion (P <0.01-0.001). Results of the acute-on-chronic study demonstrated significant improvements in FMD% within the HFMC group; I) acutely (2 h) at day 0 (0.7 %; P<O.OI); 2) chronically at day 14 (1.0%;P<O.OOI), and 3) a sustained increase in FMD post-intervention (0.9%; P<O.OOI). EC metabolites were able to predict changes in both trials, although, no other vascular or haematological markers were changed significantly. Conclusion: We show for t,le first time 0.5 mg/kg BW of pure EC can significantly induce acute improvements in FMD. We also conclude that long-term (>2 weeks) bidaily intake of HFMC results in sustained improvements in FMD. Both studies demonstrated clinically relevant increased in FMD. Our data supports the vasoactivity, linking to cardioprotection, of EC, and stereoisomer-specific foods, by demonstrating enhanced vascular function in a 'low-risk' population.