采用 3 相交叉设计，应用 2 种氘标记 α-生育酚研究了健康妇女中维生素 E 的吸收和动力学，其受食物和脂肪调节。
Vitamin E absorption and kinetics in healthy women, as modulated by food and by fat, studied using 2 deuterium-labeled α-tocopherols in a 3-phase crossover design.
机构信息
Linus Pauling Institute, Oregon State University, Corvallis, OR, USA.
School of Biological and Population Health Sciences, College of Public Health and Human Sciences, Oregon State University, Corvallis, OR, USA.
出版信息
Am J Clin Nutr. 2019 Nov 1;110(5):1148-1167. doi: 10.1093/ajcn/nqz172.
BACKGROUND
Determining the human vitamin E [α-tocopherol (α-T)] requirement is difficult, and novel approaches to assess α-T absorption and trafficking are needed.
OBJECTIVE
We hypothesized that the dual-isotope technique, using 2 deuterium-labeled [intravenous (IV) d6- and oral d3-] α-T, would be effective in determining α-T fractional absorption. Further, defined liquid meal (DLM) fat or fasting would modulate α-T fractional absorption and lipoprotein transport.
METHODS
A 3-phase cr ossover design was used. At 0 h, participants received IV d6-α-T and consumed d3-α-T with a 600-kcal DLM (40% or 0% fat) followed by controlled meals or by the 0% fat DLM, a 12-h fast, and then controlled meals. Blood samples and fecal samples were collected at intervals and analyzed by LC-MS. Pharmacokinetic parameters were calculated from plasma tracer concentrations and enrichments. Fractional absorption was calculated from d3- to d6-α-T areas under the curve, from a novel mathematical model, and from the balance method (oral d3-α-T minus fecal d3-α-T excreted).
RESULTS
Estimated α-T fractional absorption during the 40% fat intervention was 55% ± 3% (mean ± SEM; n = 10), which was 9% less than during the 0% fat intervention (64% ± 3%, n = 10; P < 0.02). Fasting had no apparent effect (56% ± 3%, n = 7), except it slowed plasma oral d3-α-T appearance. Both balance data and model outcomes confirmed that the DLM fat did not potentiate d3-α-T absorption. During the IV emulsion clearance, HDL rapidly acquired d6-α-T (21 ± 2 nmol/L plasma per minute). During the first 8 h postdosing, triglyceride-rich lipoproteins (TRLs) were preferentially d3-α-T enriched relative to LDL or HDL, showing the TRL precursor role.
CONCLUSIONS
Quantitatively, α-T absorption is not limited by fat absence or by fasting. However, α-T leaves the intestine by a process that is prolonged during fasting and potentiated by eating, suggesting that α-T absorption is highly dependent on chylomicron assembly processes. This trial was registered at clinicaltrials.gov as NCT00862433.
背景
确定人体维生素 E [α-生育酚（α-T）] 的需求量很困难，因此需要新的方法来评估 α-T 的吸收和转运。
目的
我们假设使用 2 种氘标记的 [静脉内（IV）d6-和口服 d3-] α-T 的双同位素技术将有效确定 α-T 的分数吸收。此外，定义的液体餐（DLM）脂肪或禁食会调节 α-T 的分数吸收和脂蛋白转运。
方法
采用 3 期交叉设计。在 0 小时，参与者接受 IV d6-α-T 并摄入含有 600 卡路里 DLM（40%或 0%脂肪）的 d3-α-T，然后接受控制饮食或 0%脂肪 DLM、12 小时禁食，然后接受控制饮食。在不同时间采集血样和粪便样，并通过 LC-MS 进行分析。药代动力学参数由血浆示踪剂浓度和丰度计算得出。分数吸收由 d3-至 d6-α-T 曲线下面积、新的数学模型和平衡法（口服 d3-α-T 减去粪便 d3-α-T 排泄量）计算得出。
结果
在 40%脂肪干预期间，α-T 的估计分数吸收为 55%±3%（平均值±SEM；n=10），比 0%脂肪干预期间（64%±3%，n=10；P<0.02）低 9%。禁食似乎没有明显的影响（56%±3%，n=7），只是它减缓了口服 d3-α-T 在血浆中的出现速度。平衡数据和模型结果均证实 DLM 脂肪不会增强 d3-α-T 的吸收。在 IV 乳剂清除期间，HDL 迅速获得 d6-α-T（每分钟 21±2 nmol/L 血浆）。在给药后 8 小时内，富含甘油三酯的脂蛋白（TRLs）相对于 LDL 或 HDL 优先被 d3-α-T 富集，表明其具有 TRL 前体作用。
结论
从定量上看，α-T 的吸收不受脂肪缺乏或禁食的限制。然而，α-T 通过在禁食期间延长的过程离开肠道，并因进食而增强，这表明 α-T 的吸收高度依赖于乳糜微粒的组装过程。本试验在 clinicaltrials.gov 上注册为 NCT00862433。
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