The impact of the catechol-O-methyltransferase genotype on the acute responsiveness of vascular reactivity to a green tea extract

Abstract

The beneficial effects of green tea catechins, such as the proposed improvement in endothelial function, may be influenced by phase II metabolism during and after absorption. The methylation enzyme, catechol-O-methyltransferase (COMT), has a missense mutation rs4680 (G to A), proposed to result in a 40 % reduction in enzyme activity. In the present pilot study, twenty subjects (ten of each homozygous COMT genotype) were recruited. Green tea extract capsules (836 mg green tea catechins) were given in a fasted state, and a high-carbohydrate breakfast was given after 60 min. Blood samples and vascular function measurements were taken at regular intervals. The change in digital volume pulse stiffness index (SI) from baseline was shown to be different between genotype groups at 120 and 240 min, with a lower SI in the GG individuals (P# 0·044). The change in blood pressure from baseline also differed between genotype groups, with a greater increase in systolic (P¼ 0·023) and diastolic (P¼ 0·034) blood pressure at 120 min in the GG group. The AA group was shown to have a greater increase in insulin concentrations at 120 min (P¼ 0·019) and 180 min (P¼ 0·008) compared with baseline, despite similar glucose profiles. No genotypic differences were found in vascular reactivity measured using laser Doppler iontophoresis, total nitrite, lipids, plasma total antioxidant capacity or inflammatory markers after ingestion of the green tea extract. In conclusion, SI and insulin response to the glucose load differed between the COMT genotype groups, and this may be suggestive of a green tea extract and genotype interaction. Green tea contains high levels of polyphenols (approximately 70 % of dry weight), which are mainly green tea catechins belonging to the flavan-3-ol family of polyphenols. Of highest abundance is epigallocatechin gallate, followed by epigallocatechin, epicatechin and epicatechin gallate. Epidemiological studies have repeatedly observed a beneficial effect of green tea consumption on the risk of CVD (1 -5) . In addition, acute and chronic human intervention studies have demonstrated benefits of green tea and its constituent catechins on vascular function and reactivity (6 -9) . Proposed molecular mechanisms for improved vascular reactivity include increased endothelial NO synthase activity (10) , reduced cytokine (11,12) and prooxidant production (13) and NADPH oxidase inhibition (14) .Flavan-3-ol O-methylation is a major pathway of flavonoid metabolism, which mainly occurs in the intestinal tract, liver and kidney. This phase II metabolism is thought to reduce the biological activity of flavan-3-ol polyphenols. Indeed, variability in flavonoid O-methylation has been shown to influence the effect of dietary flavonoids on endothelial function (15) . O-Methylation of flavonoids is catalysed by the enzyme catechol-O-methyltransferase (COMT). A common genetic missense mutation (G to A base change) results in a valine-to-methionine amino acid substitution at position 108 in the soluble protein and at position ...

Green tea extract and catechol‐O‐methyltransferase genotype modify the post‐prandial serum insulin response in a randomised trial of overweight and obese post‐menopausal women

“…The significance of an increased insulin response to a high-carbohydrate meal in participants with the G/G genotype taking GTE is unclear, although it could be indicative of the need to secrete additional insulin to manage blood glucose concentrations over time compared to individuals with other forms of the COMT genotype and those not taking GTE; yet, the sample size of this group was small, making it difficult to draw definitive conclusions. Our results are in agreement with those of another study (23) that reported finding greater post-prandial insulin concentrations after the consumption of GTE (836 mg catechins) in individuals with the G/G genotype compared to those with the G/A or A/A COMT genotypes. Similarly, Kring, et al (33) determined that there was an 11.6% increased frequency of the G/G COMT genotype in individuals with impaired glucose tolerance or type 2 diabetes.…”

“…Insulin has also been associated with energy balance (18) , and several RCTs have demonstrated increased insulin sensitivity with the consumption of GTC (19)(20)(21) . However, few human studies examining the immediate post-prandial effects of GTC on these hormones have been conducted (22,23) . To date, the results are inconclusive, with one study finding no differences in the area under the curve (AUC) for glucose and insulin after meal consumption, although higher satiety was reported among participants (22) , whereas another single-arm study did not provide a control group to enable a comparison of the results (23) .…”

The vascular endothelium in diabetes—a therapeutic target?

“…In animals, concurrent effects on insulin resistance and vascular function have been reported [172]. To date one study has been published evaluating these parameters in humans, and found significant effect of green tea extract on post-meal blood pressure and insulin response, with interesting differences by catechol-O-methyl transferase (COMT) genotype [175]. The fact of shared mechanisms with insulin signaling in endothelium and promising pre-clinical data in animals suggests that green tea-based therapies may be of particular benefit in insulin resistance-associated vascular dysfunction, but this has not yet been rigorously assessed.…”

Interindividual Variability in Biomarkers of Cardiometabolic Health after Consumption of Major Plant-Food Bioactive Compounds and the Determinants Involved

“…Eight studies have reported the impact of genetic polymorphisms on the cardiometabolic health effects of green tea (57, 58), coffee or caffeine (59–61), and plant sterols (62–64) (Table 1). The beneficial effects of green tea catechins may be predisposed by polymorphisms in genes encoding phase II metabolism enzymes during and after the consumption.…”

“…The missense mutation rs4680 (G to A) in the COMT gene, coding for methylation enzyme, results in a 40% decrease in enzyme activity. In a pilot study performed by Miller et al (58), 20 subjects (10 homozygous COMT GG or 10 AA genotype) were given green tea extract capsules (836 mg green tea catechins) in a fasted state and with a high-carbohydrate breakfast. The modification in digital volume pulse (DVP) stiffness index from baseline was observed to be different between genotype groups at 120 and 240 min, with a lower stiffness index in the GG individuals.…”