The metabolome of [2-(14)C](-)-epicatechin in humans: implications for the assessment of efficacy, safety, and mechanisms of action of polyphenolic bioactives.
The metabolome of [2-(14)C](-)-epicatechin in humans: implications for the assessment of efficacy, safety, and mechanisms of action of polyphenolic bioactives.
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DOI：
10.1038/srep29034
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发表时间：
2016-07-01
影响因子：
4.6
通讯作者：
Schroeter H
中科院分区：
文献类型：
--
作者：
Ottaviani JI;Borges G;Momma TY;Spencer JP;Keen CL;Crozier A;Schroeter H
饮食是影响人类健康的主要生活方式因素，因此强调需要循证饮食指南进行初级疾病预防。虽然目前的建议促进水果和蔬菜的摄入，但我们对植物源性生物活性食品成分的了解有限，而不是代表少量必需营养素和矿物质的成分。这种有限的理解可以在一定程度上归因于缺乏描述生物活性化合物的吸收，分布，代谢和排泄（ADME）的基本数据。因此，我们选择黄烷醇（-）-表儿茶素（EC）作为广泛研究的生物活性食品成分的一个例子，并研究了人体中[2- 14 C]（-）-表儿茶素（300 μCi，60 mg）的ADME（n = 8）。我们证明了82 ± 5%的摄入EC被吸收。我们还建立了药代动力学曲线，并鉴定和定量了>20种不同的代谢物。肠道微生物组被证明是EC代谢的关键驱动力。此外，我们注意到EC的代谢存在显著的种属差异，这是一种对EC有益作用的作用机制研究具有重要意义的见解。在评估人体摄入氨基甲酸乙酯的安全性时，需要考虑这些差异。我们还确定了一个潜在的生物标志物，可以帮助加强流行病学调查的EC摄入量的客观评估。
Diet is a major life style factor affecting human health, thus emphasizing the need for evidence-based dietary guidelines for primary disease prevention. While current recommendations promote intake of fruit and vegetables, we have limited understanding of plant-derived bioactive food constituents other than those representing the small number of essential nutrients and minerals. This limited understanding can be attributed to some extent to a lack of fundamental data describing the absorption, distribution, metabolism and excretion (ADME) of bioactive compounds. Consequently, we selected the flavanol (−)-epicatechin (EC) as an example of a widely studied bioactive food constituent and investigated the ADME of [2-14C](−)-epicatechin (300 μCi, 60 mg) in humans (n = 8). We demonstrated that 82 ± 5% of ingested EC was absorbed. We also established pharmacokinetic profiles and identified and quantified >20 different metabolites. The gut microbiome proved to be a key driver of EC metabolism. Furthermore, we noted striking species-dependent differences in the metabolism of EC, an insight with significant consequences for investigating the mechanisms of action underlying the beneficial effects of EC. These differences need to be considered when assessing the safety of EC intake in humans. We also identified a potential biomarker for the objective assessment of EC intake that could help to strengthen epidemiological investigations.