Effects of Tea on Peripheral and Cerebral Micro- and Macrovascular Function in Humans
Cardiovascular disease (CVD) is the leading cause of global mortality, with the incidence of cardiovascular related pathologies remaining a public health burden. CVD encompasses pathologies of the vascular tree and heart, including, for example, peripheral artery disease, coronary heart disease and ischaemic stroke. Atherosclerosis is the primary pathological process leading to CVD and is characterised by a multifactorial pathophysiology that first manifests in the vascular endothelium. Termed endothelial dysfunction, this early marker of atherosclerosis has become a focus of interest for identifying individuals at risk of a profound cardiovascular insult, particularly arising from lifestyle choices such as physical inactivity and calorie-rich diets. Dietary interventions have received increasing attention in recent years as inexpensive strategies to potentially combat the ever-increasing global burden of CVD. A high dietary flavonoid intake is associated with a reduction in CVD risk and several studies have revealed a strong, inverse relation between the regular intake of tea, a major source of dietary flavonoids, and CVD risk. Tea has demonstrated improved conduit artery endothelial function and glucose handling in both healthy individuals and in those with overt CVD. However, the effects of tea on the microvasculature and cerebrovasculature are not yet understood, particularly in relation to lifestyle factors. The primary aim of this thesis was to explore the impact of tea ingestion on peripheral and cerebral micro- and macrovascular function in humans. In an initial methodological study, the day-to-day reproducibility of thermally stimulated cutaneous microvascular function was assessed. Fifteen, healthy males (28 ± 5 yrs, BMI 25 ± 2 kg/m2) attended two experimental trials 2-7 days 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/5-s), 2. Rapid 42°C (0.5°C/5-s) 3. Gradual 42°C (0.5°C/2-min 30-s) and 4. Slow 42°C (0.5°C/5-min). 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). 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 (21%). Reproducibility at 44°C was 12-15% for flux and CVC across all protocols. The good-to-moderate reproducibility of the Rapid, Gradual and Slow 42°C protocols supported their (simultaneous) use to assess peripheral microvascular function. The aim of Chapter 5 was to examine the acute (2-hour) cutaneous vascular responses to local skin heating following ingestion of black tea in a healthy adult population. Twenty healthy participants (58 ± 5 yrs, BMI 26 ± 4 kg/m2, 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 microvascular function using LDF and three distinct local skin heating protocols 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 cutaneous microvascular function during Gradual 42°C. Data were analysed as CVC and %CVCmax. 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. The aim of the study outlined in Chapter 6 was to examine the effect of daily green tea consumption (equivalent to 6 cups/day) on changes in peripheral vascular function and glucose handling after a 7-day ‘unhealthy’ lifestyle in healthy males. Twelve healthy males (29 ± 6 yrs, BMI 25 ± 2 kg/m2) underwent two periods of 7-days ‘unhealthy’ lifestyle (UL) comprising of combined physical activity reduction (-50% steps per day) and high fat, high carbohydrate overfeeding (+50% kcal per day, comprising 65% fat) in a randomised, controlled, double-blind, cross-over design. Each intervention period was separated by a 2-week washout. During each 7-day UL-period, participants ingested three doses of an active green tea drink (UL-Tea) or a placebo drink (UL-Placebo) per day at regular intervals. Participants attended the laboratory before and after each 7-day intervention (a total of 4 visits). During each visit the following were examined: mean arterial blood pressure (MAP), dominant forearm cutaneous microvascular function using LDF and local heating protocols 1. Rapid 42°C, 2. Rapid 39°C and 3. Gradual 42°C, macrovascular function using brachial artery and femoral artery endothelium-dependent function via flow-mediated dilation (FMD), carotid artery vasoreactivity to the cold pressor test (CAR%), cerebrovascular function via CO2 reactivity and dynamic cerebral autoregulation, and insulin sensitivity and glucose handling through a mixed-meal (1200kcal, comprising 60% carbohydrates, 33% fat and 7% protein) tolerance test. Linear mixed models (main effects of intervention and time) were used to examine the impact of the lifestyle intervention (pre vs post) and green tea ingestion (UL-Tea vs UL-Placebo). Body mass demonstrated a slight increase following both UL-Tea and UL-Placebo (P>0.05). MAP was increased after UL-Placebo, whereas it was reduced after UL-Tea (P=0.06). LDF responses to rapid local heating demonstrated non-significant reductions in CVC following UL-Placebo but no difference following UL-Tea (P>0.05), with a significant interaction of time*condition*temperature observed following Gradual 42°C (P=0.02). Brachial artery FMD was not different pre vs post or between UL-Placebo and UL-Tea (P>0.05), whereas femoral artery FMD decreased after UL-Placebo, which was prevented during UL-Tea (P<0.001). CAR% decreased following UL-Placebo, which was prevented during UL-Tea (P=0.04). CO2 reactivity and dynamic cerebral autoregulation demonstrated no differences between UL-Placebo and UL-Tea or over time. Postprandial glucose was increased after UL-Placebo, whereas a reduction in postprandial glucose occurred after UL-Tea (P=0.03). Postprandial insulin levels were higher after UL-Placebo, consistent with insulin resistance, whereas following UL-Tea the insulin response was reduced and demonstrated an interaction of time*condition (P<0.001). The aim of Chapter 7 was to examine the effect of acute oral (-)-epicatechin ingestion on cerebrovascular function in healthy adults. Seven healthy males (32 ± 13 yrs, BMI 25 ± 1 kg/m2) attended two experimental trials ((-)-epicatechin and placebo) 7-days apart in a randomised, controlled, double-blind, cross-over design. Participants underwent baseline assessment of cerebrovascular function using transcranial Doppler ultrasound (TCD), comprising CO2 reactivity to hypercapnia and dynamic cerebral autoregulation via squat-stand manoeuvres at 0.10 Hz and 0.05 Hz. Following completion of the baseline measures, participants immediately consumed an oral dose of the test product (2 x 50 mg capsules of (-)-epicatechin or 2 capsules of colour-matched placebo) together with a glass of water, following which participants relaxed in the laboratory. 2-hours post-ingestion repeat measures of cerebrovascular function were performed. Linear mixed models (main effects of condition and time) examined the differences between (-)-epicatechin and placebo interventions (pre vs post) on cerebrovascular function. No differences were observed at pre vs post baseline for middle cerebral artery velocity (MCAv) or MAP (all P>0.05). There were no differences in the cerebrovascular responses to CO2 or dynamic autoregulation between (-)-epicatechin and placebo. The findings from this thesis suggest that, firstly, use of simultaneous skin local heating protocols provides a valuable means of interrogating the cutaneous microvessels for mechanistic insight in intervention studies. Secondly, current findings evidence improved cutaneous microvascular function following acute black tea consumption. Furthermore, the research work undertaken in this thesis provides important insight into the effects of tea consumption on peripheral (micro- and macro-) vascular function and insulin sensitivity, particularly its abrogative effects on lifestyle-induced vascular impairments. However, the effects of tea consumption on the cerebrovasculature remain uncertain. Overall, based on the current findings, tea consumption presents a simple, inexpensive, non-pharmacological cardioprotective strategy to help combat the ever-increasing global burden of CVD.
TX341 Nutrition. Foods and food supply, RC1200 Sports Medicine
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