The role of cocoa flavanols in modulating peripheral and cerebral microvascular function in healthy individuals and populations at-risk of cardiovascular disease: a systematic review

Abstract Background Cocoa flavanols (CFs) are polyphenolic molecules with proposed cardioprotective effects. Whilst extensive evidence supports their ability to ameliorate vasodilator responses within conduit vessels, their actions in the microvasculature are less clear. This systematic review of the literature aimed to determine whether CF interventions lead to improvements in microvascular vasodilator responses in healthy populations and those with increased cardiovascular disease risk. Methods Database searches were conducted up to September 2023 using Medline, Embase, Pubmed and Web of Science Core Collection to identify randomised, placebo-controlled, human studies investigating the effect of CF interventions on the microvasculature (at rest and vasodilator responses). All studies were assessed for risk of-bias according to Cochrane Collaboration recommendations for randomised-controlled trials, data were extracted from studies and findings collated by vote-counting. Results Searches identified 511 unique articles for screening, of which 19 were selected for data extraction. Vasodilator responses were enhanced in 85.7% (80.4–91.0%, p = 0.013) of all acute studies (n = 13), and in 81.8% (74.1–89.4%, p = 0.065) of studies in healthy subgroups (n = 11). Importantly, this effect was apparent in all studies with ‘low risk of bias’ (n = 8, p = 0.008). In contrast, there was no effect of acute CF interventions at rest. For chronic studies (n = 7), the effect of CFs was less clear, with a significant benefit reported at rest only, in all young, healthy subgroups (n = 7, p = 0.016), but no evidence of improvements in vasodilator responses. Conclusions CFs have the potential to improve microvascular function, particularly in healthy individuals, with benefits appearing more pronounced following acute CF supplementation. Despite this, interpretations are limited by the small number of comparable studies identified and the heterogeneity of populations studied. Overall, the effects of CFs on the microvasculature seem to be less consistent than previous evidence in the macrovasculature, suggesting that the microvessels may be less susceptible to the effect of CFs than conduit arteries. Registration The PROSPERO registration number for this review is CRD42023483814.