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载脂蛋白E4基因型健康男性中氘标记的天然和合成α-生育酚的非竞争性血浆生物动力学

Noncompetitive plasma biokinetics of deuterium-labeled natural and synthetic alpha-tocopherol in healthy men with an apoE4 genotype.

作者信息

Proteggente Anna R, Turner Rufus, Majewicz Jonathan, Rimbach Gerald, Minihane Anne Marie, Krämer Klaus, Lodge John K

机构信息

Centre for Nutrition and Food Safety, School of Biomedical and Molecular Sciences, University of Surrey, Guildford GU2 7XH, UK.

出版信息

J Nutr. 2005 May;135(5):1063-9. doi: 10.1093/jn/135.5.1063.

DOI:10.1093/jn/135.5.1063
PMID:15867282
Abstract

Previous studies comparing the biokinetics of deuterated natural (RRR) and synthetic (all-rac) alpha-tocopherol (vitamin E) used a simultaneous ingestion or competitive uptake approach and reported relative bioavailability ratios close to 2:1, higher than the accepted biopotency ratio of 1.36:1. The aim of the current study was to compare the biokinetics of deuterated natural and synthetic vitamin E using a noncompetitive uptake model both before and after vitamin E supplementation in a distinct population. Healthy men (n = 10) carrying the apolipoprotein (apo)E4 genotype completed a randomized crossover study, comprised of two 4-wk treatments with 400 mg/d (RRR-alpha-tocopheryl and all-rac-alpha-tocopheryl acetate) with a 12-wk washout period between treatments. Before and after each treatment period, the subjects consumed a capsule containing 150 mg deuterated alpha-tocopheryl acetate in either the RRR or all-rac form depending on their treatment regimen. Blood was obtained up to 48 h after ingestion, and tocopherols analyzed by LC/MS. After deuterated all-rac administration, plasma deuterated tocopherol maximum concentrations and area under the concentration vs. time curves (AUC) were lower than those following RRR administration. The RRR:all-rac ratios determined from the deuterated biokinetic profiles (maximum concentration; C(max)) and AUCs were 1.35:1 +/- 0.17 and 1.33:1 +/- 0.18, respectively. The 4-wk supplementation with either RRR or all-rac significantly increased plasma alpha-tocopherol concentrations (P < 0.001), but decreased the plasma response to newly absorbed deuterated RRR or all-rac alpha-tocopherol. Using a noncompetitive uptake approach, the relative bioavailability of natural to synthetic vitamin E in apoE4 males was close to the currently accepted biopotency ratio of 1.36:1.

摘要

以往比较氘代天然(RRR)和合成(全消旋)α-生育酚(维生素E)生物动力学的研究采用同时摄入或竞争性摄取方法,并报告相对生物利用度比值接近2:1,高于公认的生物效价比1.36:1。本研究的目的是在一个特定人群中,使用非竞争性摄取模型比较维生素E补充前后氘代天然和合成维生素E的生物动力学。携带载脂蛋白(apo)E4基因型的健康男性(n = 10)完成了一项随机交叉研究,包括两个为期4周的治疗,每天服用400毫克(RRR-α-生育酚和全消旋-α-生育酚醋酸酯),治疗期间间隔12周洗脱期。在每个治疗期前后,受试者根据其治疗方案服用一粒含有150毫克RRR或全消旋形式氘代α-生育酚醋酸酯的胶囊。摄入后长达48小时采集血液,并用液相色谱/质谱法分析生育酚。给予氘代全消旋体后,血浆氘代生育酚的最大浓度和浓度-时间曲线下面积(AUC)低于给予RRR后的水平。从氘代生物动力学曲线(最大浓度;C(max))和AUC确定的RRR:全消旋体比值分别为1.35:1±0.17和1.33:1±0.18。RRR或全消旋体进行4周补充均显著提高了血浆α-生育酚浓度(P < 0.001),但降低了血浆对新吸收的氘代RRR或全消旋体α-生育酚的反应。采用非竞争性摄取方法,apoE4男性中天然维生素E相对于合成维生素E的相对生物利用度接近目前公认的生物效价比1.36:1。

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