Tea-induced improvement of endothelial function in humans: No role for epigallocatechin gallate (EGCG)

Abstract

Consumption of tea is inversely associated with cardiovascular diseases. However, the active compound(s) responsible for the protective effects of tea are unknown. Although many favorable cardiovascular effects in vitro are mediated by epigallocatechin gallate (EGCG), its contribution to the beneficial effects of tea in vivo remains unresolved. In a randomised crossover study, a single dose of 200 mg EGCG was applied in three different formulas (as green tea beverage, green tea extract (GTE), and isolated EGCG) to 50 healthy men. Flow-mediated dilation (FMD) and endothelial-independent nitro-mediated dilation (NMD) was measured before and two hours after ingestion. Plasma levels of tea compounds were determined after each intervention and correlated with FMD. FMD significantly improved after consumption of green tea containing 200 mg EGCG (p < 0.01). However, GTE and EGCG had no significant effect on FMD. NMD did not significantly differ between interventions. EGCG plasma levels were highest after administration of EGCG and lowest after consumption of green tea. Plasma levels of caffeine increased after green tea consumption. The results show that EGCG is most likely not involved in improvement of flow-mediated dilation by green tea. Instead, other tea compounds, metabolites or combinations thereof may play a role.

Figure 1

Flow-chart of the study.

Figure 2

Only green tea increased flow-mediated dilation (FMD). Subjects consumed 200 mg of EGCG as isolated EGCG, GTE, or green tea after fasting overnight. An equal volume of hot water served as control. Green tea significantly increased FMD compared to GTE, EGCG, and water as control. Water slightly decreased FMD, whereas EGCG and GTE had little effects. Data are means ± SEM from n = 50 subjects. All p-values by repeated measures ANOVA followed by post hoc Bonferroni.

Figure 3

EGCG plasma levels did not correlate with changes in FMD. Shown are the sum of free and conjugated EGCG plasma levels two hours after consumption (a). Data are means ± SEM from n = 50 subjects for water, EGCG, and green tea and n = 49 for GTE. *p < 0.05 versus GTE and green tea, ^#p < 0.05 versus EGCG and green tea (Wilcoxon test). Correlations of EGCG plasma levels with changes in FMD after green tea, GTE, and EGCG (b). There were no significant correlations between EGCG plasma levels and FMD for all treatments (Spearman’s). Data are from n = 50 subjects for EGCG and green tea and n = 49 for GTE.

Figure 4

No correlations of catechin plasma levels with changes in FMD. Plasma levels of EC (epicatechin), EGC (epigallocatechin), and ECG (epicatechin gallate) after hydrolysis (sum of free and conjugated catechins) two hours after consumption (a). The scale of the y axes are equal to Fig. 3 to facilitate comparisons with EGCG levels. Data are means ± SEM from n = 50 subjects for water, EGCG, and green tea and n = 49 for GTE. Correlations of catechin plasma levels with FMD changes after tea consumption (b). Non-significant negative correlations were observed between catechin plasma levels and FMD changes (Spearman’s). Data are from n = 50 subjects.

Figure 5

Caffeine but not theobromine plasma levels correlate with FMD changes after green tea consumption. Plasma levels of caffeine and theobromine before and two hours after interventions (a). For comparison, the scale is identical for both compounds. Data are means ± SEM from n = 50 subjects for water, EGCG, and green tea and n = 49 for GTE. Significant positive correlations between plasma levels and changes in FMD after green tea consumption were obtained for caffeine, but not for theobromine (Spearman’s) (b). Data are from n = 50 subjects.

Figure 6

Inverse relationship between FMD and EGCG plasma levels after the interventions. FMD gradually increased with the number of compounds present (i.e., with the complexity) of the intervention (upper panel), but EGCG plasma levels are inversely proportional.