Background: There are very limited data regarding the effects of blueberry flavonoid intake on vascular function in healthy humans. Objectives: We investigated the impact of blueberry flavonoid intake on endothelial function in healthy men and assessed potential mechanisms of action by the assessment of circulating metabolites and neutrophil NADPH oxidase activity. Design: Two randomized, controlled, double-blind, crossover humanintervention trials were conducted with 21 healthy men. Initially, the impact of blueberry flavonoid intake on flow-mediated dilation (FMD) and polyphenol absorption and metabolism was assessed at baseline and 1, 2, 4, and 6 h after consumption of blueberry containing 766, 1278, and 1791 mg total blueberry polyphenols or a macronutrientand micronutrient-matched control drink (0 mg total blueberry polyphenols). Second, an intake-dependence study was conducted (from baseline to 1 h) with 319, 637, 766, 1278, and 1791 mg total blueberry polyphenols and a control. Results: We observed a biphasic time-dependent increase in FMD, with significant increases at 1-2 and 6 h after consumption of blueberry polyphenols. No significant intake-dependence was observed between 766 and 1791 mg. However, at 1 h after consumption, FMD increased dose dependently to #766 mg total blueberry polyphenol intake, after which FMD plateaued. Increases in FMD were closely linked to increases in circulating metabolites and by decreases in neutrophil NADPH oxidase activity at 1-2 and 6 h. Conclusions: Blueberry intake acutely improves vascular function in healthy men in a time-and intake-dependent manner. These benefits may be mechanistically linked to the actions of circulating phenolic metabolites on neutrophil NADPH oxidase activity. This trial was registered at clinicaltrials.gov as NCT01292954 and NCT01829542.Am J Clin Nutr 2013;98:1179-91.

We have investigated the bacterial-dependent metabolism of (2 )-epicatechin and (þ )-catechin using a pH-controlled, stirred, batch-culture fermentation system reflective of the distal region of the human large intestine. Incubation of (2)-epicatechin or (þ )-catechin (150 mg/l or 1000 mg/l) with faecal bacteria, led to the generation of 5-(3 0 ,4 0 -dihydroxyphenyl)-g-valerolactone, 5-phenyl-g-valerolactone and phenylpropionic acid. However, the formation of these metabolites from (þ )-catechin required its initial conversion to (þ )-epicatechin. The metabolism of both flavanols occurred in the presence of favourable carbon sources, notably sucrose and the prebiotic fructo-oligosaccharides, indicating that bacterial utilisation of flavanols also occurs when preferential energy sources are available. (þ )-Catechin incubation affected the growth of select microflora, resulting in a statistically significant increase in the growth of the Clostridium coccoides -Eubacterium rectale group, Bifidobacterium spp. and Escherichia coli, as well as a significant inhibitory effect on the growth of the C. histolyticum group. In contrast, the effect of (2)-epicatechin was less profound, only significantly increasing the growth of the C. coccoides -Eubacterium rectale group. These potential prebiotic effects for both (þ )-catechin and (2 )-epicatechin were most notable at the lower concentration of 150 mg/l. As both (2)-epicatechin and (þ )-catechin were converted to the same metabolites, the more dramatic change in the growth of distinct microfloral populations produced by (þ )-catechin incubation may be linked to the bacterial conversion of (þ )-catechin to (þ)-epicatechin. Together these data suggest that the consumption of flavanol-rich foods may support gut health through their ability to exert prebiotic actions. Flavanols: Prebiotics: Faecal microflora: Large intestineRepresenting one of the most important lifestyle factors, diet can strongly influence the incidence and onset of CVD (1) , and thus a healthy diet is an essential factor for healthy ageing (2) . A number of dietary intervention studies in human subjects and animals, in particular those using Vitis vinifera (grape), Camellia sinensis (tea) and Theobroma cacao (cocoa) have demonstrated beneficial effects on vascular function (3 -5) . While such foods and beverages differ greatly in chemical composition and macro-and micronutrient content, they have in common that they are amongst the major dietary sources of flavanols. The in vivo effects of flavanols will be dependent on the absorption and metabolism of flavanols in the gastrointestinal tract. Studies have indicated that flavanols are subject to extensive metabolism by phase I and II enzymes to yield O-methylated, sulfated and glucuronidated forms during transfer from the small-intestinal lumen to the portal blood (6) . However, significant amounts of ingested (2 )-epicatechin, (þ)-catechin, and their structurally related oligomeric forms (procyanidins), escape absorption in the small intestine, instead rea...

A number of vegetables have a high nitrate content which after ingestion can be reduced to nitrite by oral bacteria, and further to vasoprotective NO endogenously. In the present study, two separate randomly controlled, single-blind, cross-over, postprandial studies were performed in normotensive volunteers. Ambulatory blood pressure (BP) was measured over a 24 h period following consumption of either four doses of beetroot juice (BJ), 0, 100, 250 and 500 g (n18), or three bread products, control bread (0 g beetroot), red beetroot- and white beetroot-enriched breads (n14). Total urinary nitrate/nitrite (NOx) was measured at baseline, and at 2, 4 and 24 h post-ingestion. BJ consumption significantly, and in a near dose-dependent manner, lowered systolic BP (SBP,P < 0·01) and diastolic BP (DBP,P < 0·001) over a period of 24 h, compared with water control. Furthermore, bread products enriched with 100 g red or white beetroot lowered SBP and DBP over a period of 24 h (red beetroot-enriched bread,P <0·05), with no statistical differences between the varieties. Total urinary NOxsignificantly increased following the consumption of 100 g (P < 0·01), 250 g (P <0·001) and 500 g BJ (P <0·001) and after red beetroot-enriched bread ingestion (P <0·05), but did not reach significance for white beetroot-enriched bread compared with the no-beetroot condition. These studies demonstrated significant hypotensive effects of a low dose (100 g) of beetroot which was unaffected by processing or the presence of betacyanins. These data strengthen the evidence for cardioprotective BP-lowering effects of dietary nitrate-rich vegetables.

Background: Tart cherries contain numerous polyphenolic compounds that could potentially improve endothelial function and reduce cardiovascular disease risk. Objective: We sought to examine the acute effects of Montmorency tart cherry (MC) juice on vascular function in subjects with early hypertension. Design: A placebo-controlled, blinded, crossover, randomized Latin square design study with a washout period of $14 d was conducted. Fifteen men with early hypertension [systolic blood pressure (SBP) $130 mm Hg, diastolic blood pressure $80 mm Hg, or both] received either a 60-mL dose of MC concentrate or placebo. Microvascular reactivity (laser Doppler imaging with iontophoresis), arterial stiffness (pulse wave velocity and analysis), blood pressure, and phenolic acid absorption were assessed at baseline and at 1, 2, 3, 5, and 8 h postconsumption. Results: MC consumption significantly lowered SBP (P , 0.05) over a period of 3 h, with peak reductions of mean 6 SEM 7 6 3 mm Hg 2 h after MC consumption relative to the placebo. Improvements in cardiovascular disease risk factors were closely linked to increases in circulating protocatechuic and vanillic acid at 1-2 h. Conclusions: MC intake acutely reduces SBP in men with early hypertension. These benefits may be mechanistically linked to the actions of circulating phenolic acids. This study provides information on a new application of MCs in health maintenance, particularly in positively modulating SBP. This trial was registered at clinicaltrials.gov as NCT02234648.Am J Clin Nutr 2016;103:1531-9.

Regular consumption of green tea polyphenols (GTP) is thought to reduce the risk of cardiovascular disease (CVD) but has also been associated with liver toxicity. The present trial aimed to assess the safety and potential CVD health beneficial effects of daily GTP consumption. We conducted a placebo-controlled parallel study to evaluate the chronic effects of GTP on liver function and CVD risk biomarkers in healthy men. Volunteers (treatment: n = 17, BMI 26.7 +/- 3.3 kg/m(2), age 41 +/- 9 y; placebo, n = 16, BMI 25.4 +/- 3.3 kg/m(2), age 40 +/- 10 y) consumed for 3 wk 6 capsules per day (2 before each principal meal) containing green tea extracts (equivalent to 714 mg/d GTP) or placebo. At the beginning and end of the intervention period, we collected blood samples from fasting subjects and measured vascular tone using Laser Doppler Iontophoresis. Biomarkers of liver function and CVD risk (including blood pressure, plasma lipids, and asymmetric dimethylarginine) were unaffected by GTP consumption. After treatment, the ratio of total:HDL cholesterol was significantly reduced in participants taking GTP capsules compared with baseline. Endothelial-dependent and -independent vascular reactivity did not significantly differ between treatments. In conclusion, the present data suggests that the daily consumption of high doses of GTP by healthy men for 3 wk is safe but without effects on CVD risk biomarkers other than the total:HDL cholesterol ratio.