The metabolism of α-tocopherol (α-TOH, vitamin E) shows marked interindividual variability, which may influence the response to nutritional and therapeutic interventions with this vitamin. Recently, new metabolomics protocols have fostered the possibility to explore such variability for the different metabolites of α-TOH so far identified in human blood, i.e., the “vitamin E metabolome”, some of which have been reported to promote important biological functions. Such advances prompt the definition of reference values and degree of interindividual variability for these metabolites at different levels of α-TOH intake. To this end, a one-week oral administration protocol with 800 U RRR-α-TOH/day was performed in 17 healthy volunteers, and α-TOH metabolites were measured in plasma before and at the end of the intervention utilizing a recently validated LC-MS/MS procedure; the expression of two target genes of α-TOH with possible a role in the metabolism and function of this vitamin, namely pregnane X receptor (PXR) and the isoform 4F2 of cytochrome P450 (CYP4F2) was assessed by immunoblot in peripheral blood leukocytes. The levels of enzymatic metabolites showed marked interindividual variability that characteristically increased upon supplementation. With the exception of α-CEHC (carboxy-ethyl-hydroxychroman) and the long-chain metabolites M1 and α-13′OH, such variability was found to interfere with the possibility to utilize them as sensitive indicators of α-TOH intake. On the contrary, the free radical-derived metabolite α-tocopheryl quinone significantly correlated with the post-supplementation levels of α-TOH. The supplementation stimulated PXR, but not CYP4F2, expression of leucocytes, and significant correlations were observed between the baseline levels of α-TOH and both the baseline and post-supplementation levels of PXR. These findings provide original analytical and molecular information regarding the human metabolism of α-TOH and its intrinsic variability, which is worth considering in future nutrigenomics and interventions studies.

中文翻译：

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补充过程中的α-生育酚代谢物（维生素E代谢组）及其个体间的差异

α-生育酚（α-TOH，维生素E）的代谢表现出明显的个体差异，这可能会影响该维生素对营养和治疗干预的反应。最近，新的代谢组学方案已为探索迄今为止在人类血液中鉴定出的α-TOH不同代谢物（即“维生素E代谢组”）的这种变异性提供了可能性，据报道其中一些可促进重要的生物学功能。这些进展提示了在不同水平的α-TOH摄入量下这些代谢物的参考值和个体间差异程度的定义。为此，对17名健康志愿者进行了为期一周的口服给药方案，每天800URR-α-TOH。在干预之前和结束时，血浆中的α-TOH代谢物采用最近验证过的LC-MS / MS方法进行了测定；在外周血白细胞中通过免疫印迹评估了可能在该维生素的代谢和功能中起作用的两个α-TOH靶基因的表达，即孕烷X受体（PXR）和细胞色素P450的同工型4F2（CYP4F2）。酶促代谢产物的水平显示出明显的个体间变异性，该变异性在补充时会增加。除了α-CEHC（羧基-乙基-羟基苯并二氢吡喃）和长链代谢物M1和α-13'OH之外，发现这种可变性干扰了将它们用作α-TOH摄入敏感指标的可能性。反之，自由基衍生的代谢产物α-生育酚醌与α-TOH的补充后水平显着相关。补充刺激PXR，但不是CYP4F2，刺激白细胞表达，并且在α-TOH的基线水平与PXR的基线水平和补充后水平之间均存在显着相关性。这些发现提供了有关人类α-TOH代谢及其固有变异性的原始分析和分子信息，这在未来的营养学和干预研究中值得考虑。