Observational and intervention evidence to date indicates that polyphenol- rich foods, in particular berries and dark chocolate, may have the potential to influence cardiovascular disease risk. However, there are very few polyphenol-specific dietary intervention studies, and none of sufficiently robust design that assess the effect polyphenol-rich foods on vascular function tests of known prognostic significance and a range of cardiovascular endpoints in hypertensive patients. The study described in this thesis was based on the hypothesis that increasing overall polyphenol dietary intake, through increasing fruit and vegetable intake, and specifically including berries, and dark chocolate, would improve microvascular function and would also have a beneficial effect on platelet function, heart rate variability and other markers of cardiovascular risk in patients with hypertension.
The study was a twelve-week randomised controlled, single blinded dietary intervention design. The study commenced with a four week run-in phase for all participants, during which they were asked to consume two portions or less of fruit and vegetables, excluding berries and dark chocolate. At the end of this period, subjects were randomised to continue with the low polyphenol diet for a further eight weeks or to consume a high polyphenol diet of six portions F&V (including one portion of berries per day) and 50g of dark chocolate per day. The primary endpoint was endothelium-dependent arterial vasodilator responses, assessed by venous occlusion plethysmography pre- and post-intervention. This is an invasive marker of microvascular function of known prognostic significance. Compliance was assessed with four-day food diaries and biochemical markers of nutritional status, including vitamin C, carotenoids and epicatechin. Other measures of cardiovascular risk included biochemical markers, such as lipid profile, hsCRP, PAI-1, 11-dehydrothromboxane B2 and heart rate variability on 24 hour ambulatory ECG monitor.ResultsA total of 99 volunteers completed the study, of whom a further six were excluded due to at least one hsCRP reading over the course of this intervention being >10mg/L The intervention was well tolerated by all participants and objective markers of compliance indicated significant between group change in self-reported polyphenol intake, and biochemical markers of nutritional status including vitamin C, a panel of carotenoids and epicatechin. Between group comparison of maximum % response to Ach (infusedmon-infused arm ratios) was significantly improved in the high polyphenol group (p=0.02) relative to the control group. Results were reanalysed with polyphenol-rich foods as a continuous variable, which revealed that an extra daily portion of fruit & vegetables was predicted to promote an absolute increase in the maximum response to acetylcholine of 14.0% (95%CI: 3.82%, 24.1%, p=0.008). An extra daily portion of dark chocolate was predicted to stimulate an absolute increase in the maximum response to acetylcholine of 112.5% (95%CI: 44.5%, 180.5%, p=0.020). There was no significant difference in between group change in response to sodium nitroprusside.There was a trend towards a larger reduction in systolic blood pressure (p=0.059) and 11-dehydrothromboxane B2 levels (p=0.066), as well as a significant decrease in total cholesterol (p=0.042), in the high polyphenol group compared to the low polyphenol group. Inflammatory markers did not improve following the intervention, although there was a significantly larger decrease in hsCRP in the low polyphenol group (p=0.026) compared to the high polyphenol group. No significant between group differences in heart rate variability indices were found, following the intervention, although there was a significantly larger change in average heart rate (p=0.037) and NN intervals (p=0.023) in the high polyphenol group than in the low polyphenol group.
This current work has shown that increasing intake of polyphenol-rich foods, fruit and vegetables, berries and dark chocolate, results in a significant improvement in endothelium-dependent vasodilation following an eight-week intervention in hypertensive participants. This is the first time that a polyphenol-rich diet has achieved an improvement in a vascular function measure of known prognostic significance in a hypertensive cohort. These findings suggest that continuing to promote current general F&V guidelines, alongside advice to consume berries and dark chocolate could impact significantly on markers of cardiovascular risk, and may contribute to a reduced risk of cardiovascular disease.
|Date of Award||Jul 2014|
|Supervisor||Pascal McKeown (Supervisor), Jayne Woodside (Supervisor) & Michelle McKinley (Supervisor)|