The health benefits of green tea catechins (GTC) are becoming increasingly recognised. Amongst the proposed benefits are a reduction in atherosclerosis and cardiovascular disease risk, which is thought to be in part attributable to the maintenance of endothelial function and vascular homeostasis. Catechol-O- methyltransferase (COMT) is centrally involved in GTC metabolism, with a valine to methionine amino acid substitution at position 108/158 (soluble/membrane-bound form) of the protein reported to result in a reduction in enzyme activity. The current research investigated the impact of the COMT genotype on, GTC metabolism, and the acute impact of GTC on endothelial function and its associated phenotype. Firstly, a pilot human study was performed primarily investigating the acute effects of COMT genotype on GTC metabolism. Twenty participants, prospectively recruited according to COMT genotype, were given an acute dose of GTC extract followed by the collection of frequent blood samples to assess plasma GTC and associated metabolites. Although no significant differences between genotype groups were found, a tendancy towards a difference in EGCG methylation was observed. The study design also included a high carbohydrate breakfast meal, consumed 60 min after the green tea catechin extract. Subsequent assessment of plasma glucose and insulin identified an unexpected difference in insulin response between genotype groups. Thus, an insulin sensitivity assessment was incorporated into the main human study design to investigate this further. The main human study, a randomized, placebo- controlled, double-blind acute intervention study involved fifty volunteers, twenty five of each homozygous genotype. Vascular function, assessed by digital volume pulse (DVP) and Endo-PAT, and insulin sensitivity, assessed by an oral glucose tolerance test, was measured before and 90-105 min after 836 mg green tea extract or placebo. Blood samples were collected at regular intervals throughout the study day together with a 24 h urine collection. Firstly, we reported no significant treatment differences for vascular function for the entire study population group. However, genotypic differences were evident, with the proposed low activity COMT genotype group demonstrating an attenuation of the DVP reflection index (measure of small arterial tone) after the green tea extract compared to placebo (p = 0.014). Secondly, we found no significant treatment differences in insulin sensitivity and resistance for the entire study population group. Although, evidence was found for an improvement in the fasting insulin sensitivity index HOMA, in the proposed low activity COMT genotype group after the green tea extract compared to placebo (p = 0.043). Finally, concentrations of methylated EGC in the urine was significantly different between genotype groups with the proposed low activity COMT genotype group demonstrating a lower concentration (p = 0.049). No significant differences in the appearance of GTC and EGCG metabolites in the plasma between COMT genotype groups were evident. Together, our data suggests some improvements in vascular function and markers of insulin sensitivity with GTC supplementation, an effect which appears to be influenced by the COMT genotype. However, the effect size was modest and of questionable clinical relevance.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:553125 |
| Date | January 2011 |
| Creators | Miller, Rosalind Jane |
| Publisher | University of Reading |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
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