The relationship between dose of vitamin E and suppression of oxidative stress in humans
The relationship between dose of vitamin E and suppression of oxidative stress in humans
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DOI：
10.1016/j.freeradbiomed.2007.06.019
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发表时间：
2007-11-15
影响因子：
7.4
通讯作者：
Morrow, Jason D.
中科院分区：
文献类型：
--
作者：
Roberts, L. Jackson, II;Oates, John A.;Morrow, Jason D.
动脉粥样硬化形成的氧化假说是过去 20 年来许多研究的焦点。然而，评估维生素E总体预防心血管事件功效的随机安慰剂对照试验未能显示出有益效果。这些试验隐含的一点是，测试的维生素 E 剂量可以有效抑制氧化应激状态，但这一点从未得到确定。我们定义了维生素 E（RRR-α-生育酚）在多基因高胆固醇血症和氧化应激增强（有心血管事件风险的人群）的参与者中抑制 F-2-异前列腺素（自由基介导的脂质过氧化的生物标志物）血浆浓度的剂量依赖性作用。首先对每天补充 3200 IU 维生素 E 的参与者进行了为期 20 周的时程研究。然后对参与者进行了一项剂量范围研究，每天补充 0、100、200、400、800、1600 或 3200 IU 的维生素 E，持续 16 周。在时程研究中，直到补充 16 周后才出现血浆 F-2-异前列烷浓度的最大抑制。在剂量范围研究中，维生素 E 剂量与血浆 F2-异前列烷浓度下降百分比之间存在线性趋势，在剂量为 1600 M（35±2%，p < 0.035）和 3200 IU（49 +/- 10%，p < 0.005）时达到显着性。这项研究提供了有关减少人体体内全身氧化应激的维生素 E 剂量的信息，并为评估维生素 E 减轻疾病功效的临床研究的规划和评估提供了信息。 (C) 2007 Elsevier Inc. 保留所有权利。
The oxidation hypothesis of atherogenesis has been the focus of much research over the past 2 decades. However, randomized placebo-controlled trials evaluating the efficacy of vitamin E in preventing cardiovascular events in aggregate have failed to show a beneficial effect. Implicit in these trials is that the dose of vitamin E tested effectively suppressed oxidative stress status but this was never determined. We defined the dose-dependent effects of vitamin E (RRR-alpha-tocopherol) to suppress plasma concentrations of F-2-isoprostanes, a biomarker of free radical-mediated lipid peroxidation, in participants with polygenic hypercholesterolemia and enhanced oxidative stress, a population at risk for cardiovascular events. A time-course study was first performed in participants supplemented with 3200 IU/day of vitamin E for 20 weeks. A dose-ranging study was then performed in participants supplemented with 0, 100, 200, 400, 800, 1600, or 3200 IU/day of vitamin E for 16 weeks. In the time-course study, maximum suppression of plasma F-2-isoprostane concentrations did not occur until 16 weeks of supplementation. In the dose-ranging study there was a linear trend between the dosage of vitamin E and percentage reduction in plasma F2-isoprostane concentrations which reached significance at doses of 1600 M (35 2%, p < 0.035) and 3200 IU (49 +/- 10%, p< 0.005). This study provides information on the dosage of vitamin E that decreases systemic oxidant stress in vivo in humans and informs the planning and evaluation of clinical studies that assess the efficacy of vitamin E to mitigate disease. (C) 2007 Elsevier Inc. All rights reserved.