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急性研究 (-)-表儿茶素对健康男性志愿者血管功能的剂量依赖性影响:一项随机对照试验。

Acute study of dose-dependent effects of (-)-epicatechin on vascular function in healthy male volunteers: A randomized controlled trial.

机构信息

Regional Institute for Applied Scientific Research (IRICA), Area of Food Science and Technology, University of Castilla-La Mancha, Avd. Camilo José Cela 10, 13071, Ciudad Real, Spain; Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, PO Box 226, RG2 6AP, Reading, United Kingdom.

Department of Food and Nutritional Sciences, School of Chemistry, Food and Pharmacy, University of Reading, PO Box 226, RG2 6AP, Reading, United Kingdom.

出版信息

Clin Nutr. 2020 Mar;39(3):746-754. doi: 10.1016/j.clnu.2019.03.041. Epub 2019 Apr 9.

DOI:10.1016/j.clnu.2019.03.041
PMID:31014775
Abstract

BACKGROUND & AIMS: There is convincing clinical evidence to suggest that flavanol-containing foods/beverages are capable of inducing improvements in human vascular function. However, whilst (-)-epicatechin has been tested for efficacy, a full dose-dependency has yet to be established, particularly at doses below 1 mg/kg BW. The current study examined the dose-dependent effects of (-)-epicatechin on human vascular function with concurrent measurement of plasma (-)-epicatechin metabolites and levels of circulating nitrite and nitrate species, NO.

METHODS

An acute, double-blind, placebo-controlled, crossover intervention trial was conducted in 20 healthy males with 4 treatment arms: water-based (-)-epicatechin (0.1, 0.5 and 1.0 mg/kg BW) and a water only as control. Vascular function was assessed by flow-mediated dilatation (FMD) measured at the brachial artery, laser Doppler imaging with iontophoresis (LDI) at the subcutaneous capillaries of the forearm (response to Ach and SNP) and peripheral blood pressure (BP) at baseline, 1, 2, 4 and 6 h post-intervention. Plasma analysis of epicatechin metabolites was conducted by LC-MS and circulating plasma of nitrite and nitrate species were performed using an HPLC-based system (ENO-30).

RESULTS

Significant increases in % FMD were found to occur at 1 and 2 h following intake of 1 mg/kg BW, and at 2 h for the 0.5 mg/kg BW intake. There were no significant changes in LDI or BP at any time-points or intake levels. Increases in FMD over the 6 h timeframe were closely paralleled by the appearance of total plasma (-)-epicatechin metabolites. Non-significant changes in circulating NOx was observed.

CONCLUSIONS

Our data add further evidence that (-)-epicatechin is a causal vasoactive molecule within flavanol-containing foods/beverages. In addition, we show for the first time that intake levels as low as 0.5 mg/kg BW are capable of inducing acute improvements in vascular function (FMD) in healthy volunteers.

摘要

背景与目的

有确凿的临床证据表明,含有黄烷醇的食物/饮料能够改善人体血管功能。然而,尽管已经对(-)-表儿茶素的功效进行了测试,但尚未确定其完全的剂量依赖性,特别是在低于 1mg/kgBW 的剂量下。本研究检查了(-)-表儿茶素对人体血管功能的剂量依赖性影响,同时测量了血浆(-)-表儿茶素代谢物以及循环亚硝酸盐和硝酸盐种类(NO)的水平。

方法

在 20 名健康男性中进行了一项急性、双盲、安慰剂对照、交叉干预试验,有 4 种治疗组:水基(-)-表儿茶素(0.1、0.5 和 1.0mg/kgBW)和仅水作为对照。血管功能通过肱动脉的血流介导扩张(FMD)、前臂皮下毛细血管的激光多普勒成像(LDI)与离子电渗(Ach 和 SNP 的反应)和基础、1、2、4 和 6h 后干预的外周血压(BP)进行评估。通过 LC-MS 对儿茶素代谢物进行血浆分析,使用基于 HPLC 的系统(ENO-30)对循环血浆中亚硝酸盐和硝酸盐进行分析。

结果

发现 1mg/kgBW 摄入后 1 和 2h,以及 0.5mg/kgBW 摄入后 2h,%FMD 显著增加。在任何时间点或摄入水平下,LDI 或 BP 均无显著变化。在 6h 时间框架内,FMD 的增加与总血浆(-)-表儿茶素代谢物的出现密切相关。观察到循环 NOx 无显著变化。

结论

我们的数据进一步证明(-)-表儿茶素是黄烷醇类食物/饮料中一种因果性血管活性分子。此外,我们首次表明,低至 0.5mg/kgBW 的摄入水平就能在健康志愿者中诱导血管功能(FMD)的急性改善。

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