Theobromine consumption does not improve fasting and postprandial vascular function in overweight and obese subjects

Abstract

Backgound Theobromine, a component of cocoa, may favorably affect conventional lipid-related cardiovascular risk markers, but effects on flow-mediated dilation (FMD) and other vascular function markers are not known. Objective To evaluate the effects of 4-week theobromine consumption (500 mg/day) on fasting and postprandial vascular function markers. Design In a randomized, double-blind crossover study, 44 apparently healthy overweight (N = 30) and obese (N = 14) men and women with low HDL-C concentrations, consumed daily 500 mg theobromine or placebo for 4 weeks. After 4 weeks, FMD, peripheral arterial tonometry (PAT), augmentation index (AIx), pulse wave velocity (PWV), blood pressure (BP) and retinal microvasculature measurements were performed. These measurements were carried out under fasting conditions and 2.5 h after a high-fat mixed meal challenge. Results 4-week theobromine consumption did not change fasting vascular function markers, except for a decrease in central AIx (cAIx, − 1.7 pp, P = 0.037) and a trend towards smaller venular calibers (− 2 µm, P = 0.074). Consuming a high-fat mixed meal decreased FMD (0.89 pp, P = 0.002), reactive hyperemia index (RHI, − 0.30, P < 0.001), peripheral systolic BP (SBP, − 3 mmHg, P ≤ 0.001), peripheral diastolic BP (DBP, − 2 mmHg, P ≤ 0.001), central SBP (− 6 mmHg, P ≤ 0.001) and central DBP (− 2 mmHg, P ≤ 0.001), but increased heart rate (HR, 2 bpm, P < 0.001). Theobromine did not modify these postprandial effects, but increased postprandially the brachial artery diameter (0.03 cm, P = 0.015), and decreased the cAIx corrected for a HR of 75 (cAIx75, − 5.0 pp, P = 0.004) and peripheral AIx (pAIx, − 6.3 pp, P = 0.017). Conclusion Theobromine consumption did not improve fasting and postprandial endothelial function, but increased postprandial peripheral arterial diameters and decreased the AIx. These findings do not suggest that theobromine alone contributes to the proposed cardioprotective effects of cocoa. This trial was registered on clinicaltrials.gov under study number NCT02209025.

A comprehensive insight into the molecular effect of theobromine on cardiovascular‐related risk factors: A systematic review of in vitro and in vivo studies

“…differential effects on peripheral and central BP(van den Bogaard et al, 2010) Smolders et al (2019). also reported similar findings for the effect of TB on fasting and postprandial AIx.…”

“…In the animal studies ( Tables 1–3 ) , duration of supplementation with TB mainly ranged between 4 days and 5 months. Three (Baggott et al, 2013; Mitchell et al, 2011; Smolders et al, 2017) of the included RCTs ( Tables 2 and 3 ) involved acute follow‐up, and four (Neufingerl et al, 2013; Smolders et al, 2018; Smolders et al, 2019; van den Bogaard et al, 2010) assessed the short‐term (3–4 weeks) effect of TB supplementation on study outcomes. Of the seven RCTs, six had a crossover design.…”

“…Three (Baggott et al, 2013;Mitchell et al, 2011;Smolders et al, 2017) of the included RCTs (Tables 2 and 3) involved acute follow-up, and four (Neufingerl et al, 2013;Smolders et al, 2018;Smolders et al, 2019;van den Bogaard et al, 2010)…”

“…In individuals with prehypertension, intake of TB‐enriched cocoa powder for 3 weeks resulted in significant decreases in central systolic blood pressure (SBP) and augmentation index (AIx) compared with controls, but results for other factors such as flow‐mediated dilation (FMD), pulse wave velocity (PWV), and peripheral arterial tonometry (PAT) were inconclusive (van den Bogaard et al, 2010). In another study conducted on healthy overweight subjects with low baseline HDL‐c, daily consumption of TB had a lowering effect on central and peripheral Aix without significant effects on other vascular function markers (Smolders et al, 2019), plasma glucose, or insulin (Jacobs et al, 2017). Although, the modulatory effect of TB on some CVD risk factors has been reported in above‐mentioned studies, findings from other studies are equivocal.…”

A single, high-fat meal adversely affects postprandial endothelial function: a systematic review and meta-analysis

“…Sixty-three studies measured the FMD at multiple time points and 62 studies only measured the FMD at 1 time point. Of the remaining 6 studies, 4 did not report FMD results ( 42 , 82 , 105 , 149 ) and 2 only reported FMD results at fractions of the whole hour ( 52 , 136 ); thus, all 6 studies were dropped from the meta-analyses ( Figure 1 ). There were 102 studies that performed FMD with the vascular cuff placed on the forearm, distal to the ultrasound probe placed on the brachial artery, compared to 29 studies that placed the cuff on the upper arm.…”