Abstract
Numerous epidemiological and dietary intervention studies have reported that plant-rich diets and consumption of (poly)phenols may delay or prevent chronic diseases such as cardiovascular diseases. However, a high interindividual variability has consistently been observed in the cardiovascular response to (poly)phenol interventions. This thesis aims to investigate which are the main factors responsible for such variability, with a particular focus on the role of (poly)phenol gut microbial metabolism. To do so we conducted an open-label single arm study in a healthy UK-based cohort. Cardiovascular measurements were performed at baseline and after consumption of a (poly)phenol-rich breakfast containing red raspberry ellagitannins for three consecutive days. Urine, plasma and faecal samples were collected to quantify the different (poly)phenol metabolite produced as well as to establish the gut microbial composition of the volunteers. It was hypothesized that the capacity of the gut microbiome to metabolize urolithins would be the most important factor affecting the vascular response to ellagitannin consumption.The analysis performed on 156 healthy volunteers showed overall significant improvements in endothelial function measured by endothelial-dependent flow-mediated dilation (FMD) after three days of consumption of the (poly)phenol breakfast (ΔFMD=+0.4±0.8 %, p<0.001), with no changes in blood pressure or arterial stiffness. A stratification by age, sex, BMI and baseline blood pressure was conducted to assess the differences in response. The highest responders were found in the pre-hypertensive subgroup (ΔSBP=-5.3±7.0 mmHg, p<0.001; ΔDBP=-2.7±5.0 mmHg, p<0.001; ΔCSBP=-4.4±7.9 mmHg, p<0.001; ΔCDBP=-2.1±4.8 mmHg, p=0.007; ΔFMD=0.4±1.0 %, p=0.006). Only female participants showed significant improvements in arterial stiffness (ΔAIx=-2.0±9.7 %, p=0.041) along with improvements in FMD. Improvements in blood pressure along with FMD improvements were observed in the 40-70 years old subgroup (ΔSBP=-2.6±8.3 mmHg, p=0.011), male subgroup (ΔSBP=-3.1±7.9 mmHg, p=0.023; ΔDBP=-2.2±5.9 mmHg, p=0.030) and the overweight or with obesity subgroup (ΔSBP=-2.4±6.8 mmHg, p=0.013). The variability in gut microbial metabolism of ellagitannins was conducted by stratifying the population according to their urolithin metabotypes (UM). The distribution of metabotypes in our study was 60 % UMA, 38 % UMB and 2 % UMO. Significantly higher HDL-cholesterol levels were found in UMA participants at baseline in comparison with UMB. Both metabotypes showed significant improvements in FMD, along with blood pressure decreases in UMA only (ΔSBP=-1.9±8.1 mmHg, p=0.032). Finally, analysis of the habitual diet of volunteers suggested that healthier dietary patterns (higher intakes of PUFA, flavone and anthocyanins) led to a lower beneficial cardiovascular response to the (poly)phenol intervention.
In conclusion, baseline cardiovascular risk (characterized by baseline blood pressure levels) was identified as the main determinant of interindividual variability. Additionally, we conclude that introducing more (poly)phenol-rich food as part of the normal diet may help prevent cardiovascular events, especially in pre-hypertensive populations.
| Date of Award | 1 Sept 2022 |
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| Original language | English |
| Awarding Institution |
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| Supervisor | Ana Maria Rodriguez Mateos (Supervisor) & Rachel Gibson (Supervisor) |