Cocoa-flavanols enhance moderate-intensity pulmonary [Formula: see text] kinetics but not exercise tolerance in sedentary middle-aged adults.

INTRODUCTION: Cocoa flavanols (CF) may exert health benefits through their potent vasodilatory effects, which are perpetuated by elevations in nitric oxide (NO) bioavailability. These vasodilatory effects may contribute to improved delivery of blood and oxygen (O2) to exercising muscle. PURPOSE: Therefore, the objective of this study was to examine how CF supplementation impacts pulmonary O2 uptake ([Formula: see text]) kinetics and exercise tolerance in sedentary middle-aged adults. METHODS: We employed a double-blind cross-over, placebo-controlled design whereby 17 participants (11 male, 6 female; mean ± SD, 45 ± 6 years) randomly received either 7 days of daily CF (400 mg) or placebo (PL) supplementation. On day 7, participants completed a series of 'step' moderate- and severe-intensity exercise tests for the determination of [Formula: see text] kinetics. RESULTS: During moderate-intensity exercise, the time constant of the phase II [Formula: see text] kinetics ([Formula: see text]) was decreased by 15% in CF as compared to PL (mean ± SD; PL 40 ± 12 s vs. CF 34 ± 9 s, P = 0.019), with no differences in the amplitude of [Formula: see text] (A[Formula: see text]; PL 0.77 ± 0.32 l min-1 vs. CF 0.79 ± 0.34 l min-1, P = 0.263). However, during severe-intensity exercise, [Formula: see text], the amplitude of the slow component ([Formula: see text]) and exercise tolerance (PL 435 ± 58 s vs. CF 424 ± 47 s, P = 0.480) were unchanged between conditions. CONCLUSION: Our data show that acute CF supplementation enhanced [Formula: see text] kinetics during moderate-, but not severe-intensity exercise in middle-aged participants. These novel effects of CFs, in this demographic, may contribute to improved tolerance of moderate-activity physical activities, which appear commonly present in daily life. TRIAL REGISTRATION: Registered under ClinicalTrials.gov Identifier no. NCT04370353, 30/04/20 retrospectively registered.

Reproducibility and agreement of different non-invasive methods of endothelial function assessment.

Flow-mediated dilatation (FMD) is an established, but investigator-demanding method, used to non-invasively determine nitric oxide (NO)-dependent endothelial function in humans. Local thermal hyperemia (LTH) or post-occlusive reactive hyperemia (PORH) of the skin measured with a laser Doppler flow imager may be a less demanding alternative of FMD. We investigated the reproducibility of the different measures of vascular function, their interrelationship and the NO-dependency of LTH. Measurements were performed twice in 27 healthy men (8 smokers), one week apart. Local application of NG-monomethyl-l-arginine (L-NMMA) by means of iontophoresis was used to determine the NO-dependency of LTH. Using L-NMMA, the peak and plateau responses of LTH were reduced by 31% (p < .001) and 65% (<0.001), respectively. For all measurements the coefficient of variation (CV) was higher in smokers than in non-smokers. For non-smokers the CV of FMD was 12%, of LTH peak response 17%, of LTH plateau response 12%, of PORH peak response 14% and of PORH area under the curve response 11%. FMD correlated weakly with the PORH peak and area under the curve response (r = 0.39 and 0.43, p < .05), whereas the LTH-plateau response correlated with the PORH peak response (r = 0.68, p < .01) in non-smokers, but FMD and LTH peak or plateau responses were unrelated. In conclusion, the LTH plateau response is for two-third NO-dependent, but unrelated to FMD. Furthermore, despite easy to perform the LTH responses are not more reproducible than FMD. Given the weak associations, the different methods of vascular function assessment are not interchangeable.

The association between diabetes and dermal microvascular dysfunction non-invasively assessed by laser Doppler with local thermal hyperemia: a systematic review with meta-analysis.

BACKGROUND/INTRODUCTION: Diabetes and cardiovascular disease develop in concert with metabolic abnormalities mirroring and causing changes in the vasculature, particularly the microcirculation. The microcirculation can be affected in different parts of the body of which the skin is the most easily accessible tissue. PURPOSE: The association between diabetes and dermal microvascular dysfunction has been investigated in observational studies. However, the strength of the association is unknown. Therefore we conducted a systematic review with meta-analysis on the association between diabetes and dermal microvascular dysfunction as assessed by laser Doppler/laser speckle contrast imaging with local thermal hyperaemia as non-invasive indicator of microvascular functionality. METHODS: PubMed and Ovid were  systematically searched for eligible studies through March 2015. During the first selection, studies were included if they were performed in humans and were related to diabetes or glucose metabolism disorders and to dermal microcirculation. During the second step we selected studies based on the measurement technique, measurement location (arm or leg) and the inclusion of a healthy control group. A random effects model was used with the standardised mean difference as outcome measure. Calculations and imputation of data were done according to the Cochrane Handbook. RESULTS: Of the 1445 studies found in the first search, thirteen cross-sectional studies were included in the meta-analysis, comprising a total of 857 subjects. Resting blood flow was similar between healthy control subjects and diabetes patients. In contrast, the microvascular response to local skin heating was reduced in diabetic patients compared to healthy control subjects [pooled effect of -0.78 standardised mean difference (95% CI -1.06, -0.51)]. This effect is considered large according to Cohen's effect size definition. The variability in effect size was high (heterogeneity 69%, p < 0.0001). However, subgroup analysis revealed no difference between the type and duration of diabetes and other health related factors, indicating that diabetes per se causes the microvascular dysfunction. CONCLUSION: Our meta-analysis shows that diabetes is associated with a large reduction of dermal microvascular function in diabetic patients. The local thermal hyperaemia methodology may become a valuable non-invasive tool for diagnosis and assessing progress of diabetes-related microvascular complications, but standardisation of the technique and quality of study conduct is urgently required.

Reproducibility of four frequently used local heating protocols to assess cutaneous microvascular function.

BACKGROUND: Skin microvascular responses to local heating are frequently used to assess microvascular function. Several local heating protocols have been developed, all varying slightly in execution. The aim of this study was to determine the inter-day reproducibility of the four most commonly used local heating protocols in healthy young subjects. METHODS: Fifteen, healthy males (28±5yrs, BMI 25±2kg/m2) attended two experimental trials 2-7days apart. During each trial, baseline and maximal thermally stimulated forearm skin responses were examined simultaneously at four sites on the dominant forearm using laser Doppler flowmetry (LDF). The following heating protocols were adopted: 1. Rapid 39°C (0.5°C/5s), 2. Rapid 42°C (0.5°C/5s) 3. Gradual 42°C (0.5°C/2min 30s) and 4. Slow 42°C (0.5°C/5min). The coefficient of variation (CV) was calculated for absolute flux, cutaneous vascular conductance (CVC; flux/mean arterial pressure, MAP) and CVC expressed as a percentage of maximal CVC at 44°C (%CVCmax) at three different time points; baseline (33°C), plateau (39/42°C) and maximal (44°C). RESULTS: Reproducibility of baseline flux, CVC and %CVCmax was 17-29% across all protocols. During the plateau, Rapid, Gradual and Slow 42°C demonstrated a reproducibility of 13-18% for flux and CVC and 5-11% for %CVCmax. However, Rapid 39°C demonstrated a lower reproducibility for flux, CVC and %CVCmax (all 21%). Reproducibility at 44°C was 12-15% for flux and CVC across all protocols. CONCLUSION: This is the first study examining inter-day reproducibility across four local heating protocols. The good-to-moderate reproducibility of the Rapid, Gradual and Slow 42°C protocols support their (simultaneous) use to assess microvascular function. Using Rapid 39°C may require a greater number of subjects to detect differences within subjects.

Effect of polyphenol-rich grape seed extract on ambulatory blood pressure in subjects with pre- and stage I hypertension.

Dietary polyphenols, such as those from grape products, may exert beneficial effects on cardiovascular health, including anti-hypertensive effects. We investigated the effect of a specific grape seed extract (GSE) rich in low-molecular-weight polyphenolic compounds on ambulatory blood pressure (ABP) in untreated subjects with pre- and stage I hypertension. In addition, potential mechanisms that could underlie the hypothesised effect of GSE on blood pressure (BP), and platelet aggregation, were explored. The study was designed as a double-blind, placebo-controlled, randomised, parallel-group intervention study including seventy healthy subjects with systolic BP between 120 and 159 mmHg. A 1-week run-in period was followed by an 8-week intervention period, during which subjects consumed capsules containing either 300 mg/d of GSE or a placebo (microcrystalline cellulose). Before and after the intervention, daytime ABP readings, 24 h urine samples and fasting and non-fasting blood samples were taken. The mean baseline systolic BP was 135.8 (SE 1.3) mmHg and diastolic BP was 81.5 (SE 0.9) mmHg. BP values were modestly, but not significantly, affected by the polyphenol-rich GSE treatment v. placebo with an effect of - 3.0 mmHg for systolic BP (95% CI - 6.5, 0.5) and - 1.4 mmHg for diastolic BP (95% CI - 3.5, 0.6). Vasoactive markers including endothelin-1, NO metabolites and asymmetric dimethylarginine, plasma renin activity and platelet aggregation were not affected by the GSE intervention. Our findings show that consumption of polyphenol-rich GSE does not significantly lower ABP in untreated subjects with pre- and stage I hypertension.

SPE-NMR metabolite sub-profiling of urine.

NMR-based metabolite profiling of urine is a fast and reproducible method for detection of numerous metabolites with diverse chemical properties. However, signal overlap in the (1)H NMR profiles of human urine may hamper quantification and identification of metabolites. Therefore, a new method has been developed using automated solid-phase extraction (SPE) combined with NMR metabolite profiling. SPE-NMR of urine resulted in three fractions with complementary and reproducible sub-profiles. The sub-profile from the wash fraction (100 % water) contained polar metabolites; that from the first eluted fraction (10 % methanol-90 % water) semi-polar metabolites; and that from the second eluted fraction (100 % methanol) aromatic metabolites. The method was validated by analysis of urine samples collected from a crossover human nutritional intervention trial in which healthy volunteers consumed capsules containing a polyphenol-rich mixture of red wine and grape juice extract (WGM), the same polyphenol mixture dissolved in a soy drink (WGM_Soy), or a placebo (PLA), over a period of five days. Consumption of WGM clearly increased urinary excretion of 4-hydroxyhippuric acid, hippuric acid, 3-hydroxyphenylacetic acid, homovanillic acid, and 3-(3-hydroxyphenyl)-3-hydroxypropionic acid. However, there was no difference between the excreted amounts of these metabolites after consumption of WGM or WGM_Soy, indicating that the soy drink is a suitable carrier for WGM polyphenols. Interestingly, WGM_Soy induced a significant increase in excretion of cis-aconitate compared with WGM and PLA, suggesting a higher demand on the tricarboxylic acid cycle. In conclusion, SPE-NMR metabolite sub-profiling is a reliable and improved method for quantification and identification of metabolites in urine to discover dietary effects and markers of phytochemical exposure.

(-)-Epicatechin Alters Reactive Oxygen and Nitrogen Species Production Independent of Mitochondrial Respiration in Human Vascular Endothelial Cells.

INTRODUCTION: Vascular endothelial dysfunction is characterised by lowered nitric oxide (NO) bioavailability, which may be explained by increased production of reactive oxygen species (ROS), mitochondrial dysfunction, and altered cell signalling. (-)-Epicatechin (EPI) has proven effective in the context of vascular endothelial dysfunction, but the underlying mechanisms associated with EPI's effects remain unclear. Objective(s). Our aim was to investigate whether EPI impacts reactive oxygen and nitrogen species (RONS) production and mitochondrial function of human vascular endothelial cells (HUVECs). We hypothesised that EPI would attenuate ROS production, increase NO bioavailability, and enhance indices of mitochondrial function. METHODS: HUVECs were treated with EPI (0-20 µM) for up to 48 h. Mitochondrial and cellular ROS were measured in the absence and presence of antimycin A (AA), an inhibitor of the mitochondrial electron transport protein complex III, favouring ROS production. Genes associated with mitochondrial remodelling and the antioxidant response were quantified by RT-qPCR. Mitochondrial bioenergetics were assessed by respirometry and signalling responses determined by western blotting. RESULTS: Mitochondrial superoxide production without AA was increased 32% and decreased 53% after 5 and 10 µM EPI treatment vs. CTRL (P < 0.001). With AA, only 10 µM EPI increased mitochondrial superoxide production vs. CTRL (25%, P < 0.001). NO bioavailability was increased by 45% with 10 µM EPI vs. CTRL (P = 0.010). However, EPI did not impact mitochondrial respiration. NRF2 mRNA expression was increased 1.5- and 1.6-fold with 5 and 10 µM EPI over 48 h vs. CTRL (P = 0.015 and P = 0.001, respectively). Finally, EPI transiently enhanced ERK1/2 phosphorylation (2.9 and 3.2-fold over 15 min and 1 h vs. 0 h, respectively; P = 0.035 and P = 0.011). Conclusion(s). EPI dose-dependently alters RONS production of HUVECs but does not impact mitochondrial respiration. The induction of NRF2 mRNA expression with EPI might relate to enhanced ERK1/2 signalling, rather than RONS production. In humans, EPI may improve vascular endothelial dysfunction via alteration of RONS and activation of cell signalling.

Are acute sitting-induced changes in inflammation and cerebrovascular function related to impaired mood and cognition?

PURPOSE: Sedentary behaviour is negatively associated with mood and cognition, yet how acute sitting contributes to these overall associations is unknown. Since sitting heightens inflammation and impairs cerebrovascular function, this study investigated the hypothesis that these sitting-induced changes are related to impaired mood and cognition. METHODS: Twenty-five healthy desk workers (18 male, 28.3 ± 7.5 years, BMI: 24.2 ± 3.3 kg∙m-2) were recruited. During laboratory visit one, participants were familiarised with cognitive performance tests measuring executive function, attention and working memory. During laboratory visit two, participants completed 6 h of continuous, uninterrupted sitting. At baseline and after 6 h, serum markers of inflammation, middle cerebral artery blood flow velocity (MCAv), cerebrovascular carbon dioxide reactivity (CVR), dynamic cerebral autoregulation (CA), cognitive performance and mood (positive and negative affect, alert, contented and calm) were assessed. Data were analysed using paired-samples t tests and correlation analyses. RESULTS: Following sitting, C-reactive protein (∆-1.0 µg/ml) and tissue plasminogen activator (∆-360.4 pg/ml) decreased (p < 0.05), MCAv reduced (∆-2.9 cm∙s-1, p = 0.012) and normalised gain increased in the very low frequency range, indicating impaired CA (∆ + 0.22%·mmHg-1, p = 0.016). Positive affect (∆-4.6, p < 0.001), and alert (∆-10.6 p = 0.002) and contented (∆-7.4, p = 0.006) mood states also decreased following sitting. No significant changes in interleukin-6, tumour necrosis factor-alpha, von Willebrand factor, CVR or cognitive performance were observed (p > 0.05). The observed changes in inflammation and cerebrovascular function were not related to changes in mood (p > 0.05). CONCLUSION: Alterations in inflammation or cerebrovascular function following six hours of prolonged, uninterrupted sitting are not related to the observed reductions in mood, indicating other mechanisms underlie the relationship between acute sitting and mood disturbances.

Impact of green tea on the deleterious cardiometabolic effects of 7-days unhealthy lifestyle in young healthy males.

PURPOSE: The aim of this study was to examine if catechin-rich green tea abrogates the negative effects of 7-days of physical inactivity and excessive calorie-intake on insulin homeostasis and peripheral vascular function. METHODS: Using a randomized, double-blind, crossover design, twelve healthy men (29 ± 6 yrs) underwent 7-days unhealthy lifestyle (UL), including physical inactivity (-50% steps/day) and overfeeding (+50% kcal/day). This was combined with green tea consumption (UL-tea; 3 doses/day) or placebo (UL-placebo). Before and after each intervention, we examined postprandial blood glucose and insulin (3-h after a 1,202 kcal meal) and upper and lower limb vascular function (flow-mediated dilation (FMD%)) and carotid artery reactivity (CAR%). RESULTS: UL-placebo increased postprandial glucose and insulin, while UL-tea decreased postprandial glucose and insulin (Time*Intervention interaction effects: both p < 0.05). UL-placebo decreased CAR% and femoral FMD%, while UL-tea prevented these effects (Time*Intervention interaction effects of p < 0.04 and p < 0.001, respectively). There was no main effect of Time or Time*Intervention interaction (both p > 0.05) for brachial FMD%. CONCLUSION: Seven days of physical inactivity and overfeeding impair insulin homeostasis and vascular function. These effects were mitigated by a daily intake of catechin-rich green tea.

Grape polyphenols do not affect vascular function in healthy men.

Data suggest that polyphenol-rich products may improve endothelial function and other cardiovascular health risk factors. Grape and wine contain high amounts of polyphenols, but effects of these polyphenols have hardly been investigated in isolation in randomized controlled studies. Our objective in this study was to test the chronic effect of polyphenol-rich solids derived from either a wine grape mix or grape seed on flow-mediated dilation (FMD). Blood pressure and other vascular function measures, platelet function, and blood lipids were secondary outcomes. Thirty-five healthy males were randomized in a double-blind, placebo-controlled crossover study consisting of three 2-wk intervention periods separated by 1-wk washout periods. The test products, containing 800 mg of polyphenols, were consumed as capsules. At the end of each intervention period, effects were measured after consumption of a low-fat breakfast (~751 kJ, 25% fat) and a high-fat lunch (~3136 kJ, 78% fat). After the low-fat breakfast, the treatments did not significantly affect FMD. The absolute difference after the wine grape solid treatment was -0.4% (95% CI = -1.8 to 0.9; P = 0.77) and after grape seed solids, 0.2% (95% CI = -1.2 to 1.5; P = 0.94) compared with after the placebo treatment. FMD effects after the high-fat lunch and effects on secondary outcomes also showed no consistent differences between both of the grape solids and placebo treatment. In conclusion, consumption of grape polyphenols has no major impact on FMD in healthy men. Future studies should address whether grape polyphenols can improve FMD and other cardiovascular health risk factors in populations with increased cardiovascular risk.

Effect of α-linolenic acid on vascular function and metabolic risk markers during the fasting and postprandial phase: A randomized placebo-controlled trial in untreated (pre-)hypertensive individuals.

BACKGROUND: Only a limited number of studies have examined the vascular and postprandial effects of α-linolenic acid (ALA, C18:3n-3). Therefore, we performed a well-controlled trial focusing specifically on the effects of ALA on vascular function and metabolic risk markers during the fasting and postprandial phase in untreated (pre-)hypertensive individuals. METHODS: In a double-blind randomized, placebo-controlled parallel study, 59 overweight and obese adults (40 men and 19 women, aged 60 ± 8 years) with a high-normal blood pressure or mild (stage I) hypertension consumed daily either 10 g of refined cold-pressed flaxseed oil, providing 4.7 g ALA (n = 29), or 10 g of high-oleic sunflower (control) oil (n = 30) for 12 weeks. RESULTS: As compared with the high-oleic oil control, intake of flaxseed oil did not change brachial artery flow-mediated vasodilation, carotid-to-femoral pulse wave velocity, retinal microvascular calibers and plasma markers of microvascular endothelial function during the fasting and postprandial phase. Fasting plasma concentrations of free fatty acid (FFA) and TNF-α decreased by 58 µmol/L (P = 0.02) and 0.14 pg/mL (P = 0.03), respectively. No differences were found in other fasting markers of lipid and glucose metabolism, and low-grade systemic inflammation. In addition, dietary ALA did not affect postprandial changes in glucose, insulin, triacylglycerol, FFA and plasma inflammatory markers after meal intake. CONCLUSION: A high intake of ALA, about 3-5 times the recommended daily intake, for 12 weeks decreased fasting FFA and TNF-α plasma concentrations. No effects were found on other metabolic risk markers and vascular function during the fasting and postprandial phase in untreated high-normal and stage I hypertensive individuals.

Relationship Between Sedentary Behavior and Physical Activity at Work and Cognition and Mood.

BACKGROUND: Sedentary behavior is negatively associated with cognition and mood. Adults often engage in high levels of sedentary behavior at work through sitting, which may impact productivity. Consequently, replacing sitting with standing and physical activity (PA) is recommended. However, the associations between sitting, standing, and PA at work and cognition and mood are unknown; this study, therefore, aimed to explore these relationships. METHODS: A total of 75 healthy full-time workers (33 male, mean [SD]; 33.6 [10.4] y, 38 [7] work hr/wk) wore sedentary behavior (activPAL) and PA (SenseWear Pro) monitors for 7 days and recorded their work hours. The day after this monitoring period, participants completed cognitive tests (executive function, attention, and working memory) and mood questionnaires (affect, alert, content, and calm). Multiple linear regression analyses examined the associations between cognition and mood and the time spent sitting, standing, and in each PA intensity during work hours, weekday leisure time, and weekends. RESULTS: Workplace sitting, standing, or PA were not significantly associated with cognition or mood (P > .05). No significant associations were observed between these variables during weekday leisure time or weekends (P > .05). CONCLUSIONS: In a cohort of healthy workers, workplace sitting, standing, and PA are not associated with cognition or mood. Further research in this population is needed, examining the influence of workplace behaviors on cognition and mood, because this will contribute to evidence-based workplace guidelines to increase productivity.

Using an e-Health Intervention to Reduce Prolonged Sitting in UK Office Workers: A Randomised Acceptability and Feasibility Study.

Low-cost workplace interventions are required to reduce prolonged sitting in office workers as this may improve employees' health and well-being. This study aimed to assess the acceptability and feasibility of an e-health intervention to reduce prolonged sitting among sedentary UK-based office workers. Secondary aims were to describe preliminary changes in employee health, mood and work productivity after using an e-health intervention. Healthy, university office workers (n = 14) completed this study. An 8 week randomised crossover design was used, consisting of two trials: Intervention (computer-based prompts) and Control. Eligibility and retention rates were recorded to assess the feasibility of the trial and interviews were conducted following the intervention to explore its acceptability. Sitting, standing and stepping were objectively assessed prior to and during week 8 of each trial. Before and after each trial, measurements of vascular function, cerebrovascular function, mood and work productivity were obtained. This study had eligibility and retention rates of 54.5% and 77.8%, respectively. Participants expressed a lack of autonomy and disruption to their workflow when using the e-health intervention, raising concerns over its acceptability and long-term implementation. Preliminary data indicate that the intervention may improve the patterning of activity accrued during work hours, with increases in the number of standing and stepping bouts completed, in addition to improving vascular function. This e-health intervention is feasible to deliver in a cohort of university office workers. However, adaptations to its implementation, such as personalised settings, are needed to increase acceptability before larger trials can be conducted.

Effect of different walking break strategies on superficial femoral artery endothelial function.

Breaking up prolonged sitting with physical activity (PA) breaks prevents conduit artery dysfunction. However, the optimal break strategy to achieve this, in terms of the frequency or duration of PA, is not known. This study assessed the effect of breaking up sitting with different PA break strategies on lower limb peripheral artery endothelial function. Fifteen participants (10 male, 35.8 ± 10.2 years, BMI: 25.5 ± 3.2 kg m-2 ) completed, on separate days, three 4-h conditions in a randomized order: (1) uninterrupted sitting (SIT), (2) sitting with 2-min light-intensity walking breaks every 30 min (2WALK), or (3) sitting with 8-min light-intensity walking breaks every 2 h (8WALK). At baseline and 4 h, superficial femoral artery function (flow-mediated dilation; FMD), blood flow, and shear rate (SR) were assessed using Doppler ultrasound. For each condition, the change in outcome variables was calculated and data were statistically analyzed using a linear mixed model. There was no significant main effect for the change in FMD (P = 0.564). A significant main effect was observed for the change in blood flow (P = 0.022), with post hoc analysis revealing a greater reduction during SIT (-42.7 ± 14.2 mL·min) compared to 8WALK (0.45 ± 17.7 mL·min; P = 0.012). There were no significant main effects for mean, antegrade, or retrograde SR (P > 0.05). Superficial femoral artery blood flow, but not FMD, was reduced following uninterrupted sitting. This decline in blood flow was prevented with longer duration, less frequent walking breaks rather than shorter, more frequent breaks suggesting the dose (duration and frequency) of PA may influence the prevention of sitting-induced decreases in blood flow.

Polyphenols and Microvascular Function in Humans: A Systematic Review.

BACKGROUND: Polyphenol-rich dietary sources are acknowledged to have potential cardiovascular health benefits, particularly in reducing cardiovascular disease risk. METHODS: This systematic review sought to determine the effect of polyphenol-rich foods and beverages upon microvascular function, which is of considerable importance in its contribution towards the pathophysiology of microvascular-related complications but also in the future development of (macro-vessel) cardiovascular disease. RESULTS: Overall, consumption of polyphenol-rich foods and beverages demonstrate improved microvascular function, although this is dependent upon the polyphenol source, the dose of the product, the duration of consumption and the population group studied. Most subgroups reviewed suggest an overall beneficial effect on microvascular function, particularly grape-derived products, cocoa, tea, pine bark and Rutaceae aurantiae. Other groups remain equivocal and require further study due to the limited research performed to date. CONCLUSION: Polyphenols are abundant in the human diet and this systematic review demonstrates that they are an inexpensive, non-pharmacological approach for improving cardiovascular health in currently healthy individuals and in populations with microvascular dysfunction.

Acute black tea consumption improves cutaneous vascular function in healthy middle-aged humans.

BACKGROUND & AIMS: Dietary flavonoids, such as those present in black tea, are associated with reduced risk of cardiovascular disease (CVD), possibly through improving nitric oxide (NO) mediated vascular function. The aim of this study was to examine the effect of acute black tea ingestion on cutaneous microvascular function. METHODS: Twenty healthy participants (58 ± 5 y, 9 men) attended two experimental trials (tea, placebo), 7-days apart in a randomised, controlled, double-blind, cross-over design. Participants ingested a single dose of 200 ml black tea or placebo, followed by assessment of forearm cutaneous perfusion using laser-Doppler flowmetry (LDF) using three distinct heating protocols, enabling us to distinguish between axon- and endothelium-dependent vasodilation: 1. rapid 42°C, 2. rapid 39°C and 3. gradual 42°C. On the contralateral arm, full-field laser perfusion imaging (FLPI) was used to assess forearm perfusion during gradual 42°C. Data were presented as cutaneous vascular conductance (CVC; flux/mean arterial pressure, MAP) and CVC expressed as a percentage of maximal CVC (%CVCmax). RESULTS: Rapid local heating to 39°C or 42°C demonstrated no effect of tea for flux, CVC or %CVCmax (all P > 0.05). Gradual local heating to 42 °C, however, produced a higher skin blood flow following black tea ingestion for absolute CVC (P = 0.04) when measured by LDF, and higher absolute flux (P < 0.001) and CVC (P < 0.001) measured with FLPI. No effect of tea was found for %CVCmax when assessed by either LDF or FLPI. CONCLUSIONS: Acute tea ingestion enhanced cutaneous vascular responses to gradual local heating to 42 °C in healthy, middle-aged participants, possibly through a mechanism related to activation of endothelium-derived chemical mediators, such as NO. These improvements may contribute to the cardiovascular health benefits of regular tea ingestion.

Regular walking breaks prevent the decline in cerebral blood flow associated with prolonged sitting.

Decreased cerebrovascular blood flow and function are associated with lower cognitive functioning and increased risk of neurodegenerative diseases. Prolonged sitting impairs peripheral blood flow and function, but its effects on the cerebrovasculature are unknown. This study explored the effect of uninterrupted sitting and breaking up sitting time on cerebrovascular blood flow and function of healthy desk workers. Fifteen participants (10 male, 35.8 ± 10.2 yr, body mass index: 25.5 ± 3.2 kg/m2) completed, on separate days, three 4-h conditions in a randomized order: 1) uninterrupted sitting (SIT), 2) sitting with 2-min light-intensity walking breaks every 30 min (2WALK), or 3) sitting with 8-min light-intensity walking breaks every 2 h (8WALK). At baseline and 4 h, middle cerebral artery blood flow velocity (MCAv) and CO2 reactivity (CVR) of the MCA and carotid artery were measured using transcranial Doppler (TCD) and duplex ultrasound, respectively. Cerebral autoregulation (CA) was assessed with TCD using a squat-stand protocol and analyzed to generate values of gain and phase in the very low, low, and high frequencies. There was a significant decline in SIT MCAv (-3.2 ± 1.2 cm/s) compared with 2WALK (0.6 ± 1.5 cm/s, P = 0.02) but not between SIT and 8WALK (-1.2 ± 1.0 cm/s, P = 0.14). For CA, the change in 2WALK very low frequency phase (4.47 ± 4.07 degrees) was significantly greater than SIT (-3.38 ± 2.82 degrees, P = 0.02). There was no significant change in MCA or carotid artery CVR ( P > 0.05). Results indicate that prolonged uninterrupted sitting in healthy desk workers reduces cerebral blood flow; however, this is offset when frequent short-duration walking breaks are incorporated. NEW & NOTEWORTHY Prolonged uninterrupted sitting in healthy desk workers reduces cerebral blood flow. However, this reduction in cerebral blood flow is offset when frequent short-duration walking breaks are incorporated into this sitting period. For those who engage in long periods of sedentary behavior, chronically breaking up these sitting periods with frequent active break strategies may have important implications for cerebrovascular health; however, further research should explore this hypothesis.

Folic acid improves vascular reactivity in humans: a meta-analysis of randomized controlled trials.

BACKGROUND: The effect of folic acid on endothelial function, a prognostic factor for cardiovascular diseases, is not well established. We calculated this effect in a meta-analysis of randomized, double-blind, placebo-controlled trials in humans. OBJECTIVE: The objective of the study was to quantify the effect of folic acid on endothelial function, as measured with the use of flow-mediated dilatation (FMD). DESIGN: We conducted a meta-analysis of randomized, double-blind, placebo-controlled folic acid trials evaluating endothelial function. Trials were identified through MEDLINE (1966-15 Sept 2005), by hand-searching of references, and by contact with investigators for unpublished results. Two of us (AdB and RD) independently extracted trial data. A pooled estimate was calculated by using random-effects meta-analysis. Previously defined stratified analyses were conducted to explore the influence of study characteristics. RESULTS: Of 163 identified studies, 14 met inclusion criteria and provided data on 732 persons. Evidence for publication bias was not obvious. In the overall pooled estimate, folic acid improved FMD by 1.08 (95% CI: 0.57,1.59; P = 0.0005) percentage points over placebo. Of the study characteristics, only folic acid dose significantly influenced the outcome. Post hoc analysis, which should be interpreted with caution, seemed to indicate a dose-response effect: the change in FMD was -0.07 (95% CI: -0.37, 0.22) percentage points at doses between 400 and 800 microg/d, 1.37 (95% CI: 1.12, 1.54) percentage points at doses of 5000 microg/d, and 2.04 (95% CI: 1.43, 2.65) percentage points at doses of 10,000 microg/d. CONCLUSION: This study indicates that high doses of folic acid improve endothelial function, which could potentially reduce the risk of cardiovascular disease.

Black Tea Increases Circulating Endothelial Progenitor Cells and Improves Flow Mediated Dilatation Counteracting Deleterious Effects from a Fat Load in Hypertensive Patients: A Randomized Controlled Study.

(1) Background: Endothelial dysfunction predicts cardiovascular events. Circulating angiogenic cells (CACs) maintain and repair the endothelium regulating its function. Tea flavonoids reduce cardiovascular risk. We investigated the effects of black tea on the number of CACs and on flow-mediated dilation (FMD) before and after an oral fat in hypertensives; (2) Methods: In a randomized, double-blind, controlled, cross-over study, 19 patients were assigned to black tea (150 mg polyphenols) or a placebo twice a day for eight days. Measurements were obtained in a fasted state and after consuming whipping cream, and FMD was measured at baseline and after consumption of the products; (3) Results: Compared with the placebo, black tea ingestion increased functionally active CACs (36 ± 22 vs. 56 ± 21 cells per high-power field; p = 0.006) and FMD (5.0% ± 0.3% vs. 6.6% ± 0.3%, p < 0.0001). Tea further increased FMD 1, 2, 3, and 4 h after consumption, with maximal response 2 h after intake (p < 0.0001). Fat challenge decreased FMD, while tea consumption counteracted FMD impairment (p < 0.0001); (4) Conclusions: We demonstrated the vascular protective properties of black tea by increasing the number of CACs and preventing endothelial dysfunction induced by acute oral fat load in hypertensive patients. Considering that tea is the most consumed beverage after water, our findings are of clinical relevance and interest.