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.
Am J Clin Nutr. 2019 Nov 1;110(5):1148-1167. doi: 10.1093/ajcn/nqz172.
Determining the human vitamin E [α-tocopherol (α-T)] requirement is difficult, and novel approaches to assess α-T absorption and trafficking are needed.
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.
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).
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.
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.
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。
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。
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。
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。
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。
