Impact of cocoa flavanol intake on age-dependent vascular stiffness in healthy men: a randomized, controlled, double-masked trial

Abstract

Increased vascular stiffness, endothelial dysfunction, and isolated systolic hypertension are hallmarks of vascular aging. Regular cocoa flavanol (CF) intake can improve vascular function in healthy young and elderly at-risk individuals. However, the mechanisms underlying CF bioactivity remain largely unknown. We investigated the effects of CF intake on cardiovascular function in healthy young and elderly individuals without history, signs, or symptoms of cardiovascular disease by applying particular focus on functional endpoints relevant to cardiovascular aging. In a randomized, controlled, double-masked, parallel-group dietary intervention trial, 22 young (<35 years) and 20 elderly (50-80 year) healthy, male non-smokers consumed either a CF-containing drink (450 mg CF) or nutrient-matched, CF-free control drink bi-daily for 14 days. The primary endpoint was endothelial function as measured by flow-mediated vasodilation (FMD). Secondary endpoints included cardiac output, vascular stiffness, conductance of conduit and resistance arteries, and perfusion in the microcirculation. Following 2 weeks of CF intake, FMD improved in young (6.1 ± 0.7 vs. 7.6 ± 0.7 %, p < 0.001) and elderly (4.9 ± 0.6 vs. 6.3 ± 0.9 %, p < 0.001). Secondary outcomes demonstrated in both groups that CF intake decreased pulse wave velocity and lowered total peripheral resistance, and increased arteriolar and microvascular vasodilator capacity, red cell deformability, and diastolic blood pressure, while cardiac output remained affected. In the elderly, baseline systolic blood pressure was elevated, driven by an arterial-stiffness-related augmentation. CF intake decreased aortic augmentation index (-9 %) and thus systolic blood pressure (-7 mmHg; Clinicaltrials.gov: NCT01639781). CF intake reverses age-related burden of cardiovascular risk in healthy elderly, highlighting the potential of dietary flavanols to maintain cardiovascular health.

Fig. 1

a Schematic of cardiovascular system and b physiological parameters reflecting basic components of the cardiovascular system. Cardiac function is determined by heart rate (HR), cardiac output (CO), stroke volume (SV), and total peripheral resistance (TPR); the aorta as an elastic artery is characterized by its physicomechanical properties: central blood pressure (BP), pulse wave velocity (PWV), and augmentation index (AIX); conduit artery function is determined by flow-mediated and nitroglycerin-mediated vasodilation (FMD and NMD, respectively) as well as peripheral blood pressure that can be determined at the upper arm and finger; arteriolar conductance is characterized by forearm blood flow (FBF), cutaneous capillary blood flow by laser Doppler perfusion imaging (LDPI), and blood rheology by red blood cell (RBC) deformability

Fig. 2

a Study flow (CONSORT diagram) and b study protocol ll (RBC) deformability