Vitamin E Requirements in Women,Obese Women and Diabetic Obese Women

女性、肥胖女性和糖尿病肥胖女性的维生素 E 需求量

• 批准号: 7785268
• 负责人: MARET G TRABER
• 金额: $ 36.55万
• 依托单位: OREGON STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-06-01 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7785268
• 关键词: Address; Age; American; Antioxidants; Ascorbic Acid; Biological Availability; Biological Markers; Body Size; Body fat; Chronic Disease; Clinical Research; Collaborations; Data; Deuterium; Diabetes Mellitus; Dose; Drug Formulations; Drug Kinetics; Epidemiologic Studies; Equipment; Extramural Activities; Fatty acid glycerol esters; Food; Funding; Heart Diseases; Human; Human body; Inflammation; Intake; Intravenous; Kinetics; Label; Laboratories; Lipid Peroxidation; Lipids; Measurement; Measures; Methods; Modeling; Normal tissue morphology; Obesity; Oral; Oxidative Stress; Pilot Projects; Plasma; Postmenopause; Research Personnel; Sampling; Sampling Studies; Solubility; Stable Isotope Labeling; Study Subject; Techniques; Tissues; Tocopherols; United States National Institutes of Health; Vitamin E; Weight; Woman; Work; absorption; adverse outcome; alpha Tocopherol; base; cardiovascular disorder risk; diabetic; disorder risk; evidence base; experience; high risk; insight; intravenous administration; mathematical model; men; nutrition; oxidation; peroxidation; public health relevance; response

DESCRIPTION (provided by applicant): Epidemiologic studies suggest that chronic disease risk can be reduced by a lifetime of consuming higher dietary vitamin E intakes. However, more than 90% of Americans consume less than 40% of the 15 mg (22 IU) 1-tocopherol recommended daily by the Food and Nutrition Board. Is the usual 6 mg consumed sufficient? The necessary evidence-based data are currently unavailable to answer this question; the proposed study seeks to fill this gap. Our previous studies show that oxidative stress in humans more rapidly depletes plasma vitamin E and sufficient vitamin C intake counters the accelerated vitamin E depletion. The proposed studies will use optimized methods for pharmacokinetic measurements to address how much vitamin E is needed by the body in response to either or both oxidative stress or depleted vitamin C status. This study is unique in that it is a collaboration between NIH intra- and extramural investigators. The proposed studies will be carried out with Dr. Mark Levine and his group at the NIH in the Clinical Research Center, who have extensive experience in measuring vitamin C pharmacokinetics and bioavailability. Our laboratory has the necessary expertise, experience and equipment to measure the low concentrations of stable isotope labeled vitamin E, its metabolites, and peroxidation biomarkers. This proposal seeks funding for the Traber group for the analysis of deuterium-labeled alpha-tocopherol samples and lipid peroxidation biomarkers. Specific Aim 1. Determine alpha-tocopherol pharmacokinetics in normal weight women. Vitamin E kinetic studies will allow determination of key measures of vitamin E status including fractional absorption, rates of delivery to tissues, and whole body efflux. Pilot Study 1: Determine the optimal fat content in the accompanying meal necessary to optimize alpha-tocopherol absorption. Pilot Study 2: Determine the optimal alpha-tocopherol dose for turnover kinetics. Specific Aims 2 & 3. Determine alpha-tocopherol pharmacokinetics before and after vitamin C depletion in normal-weight women, obese women and obese women with diabetes. Our working hypothesis is that alpha-tocopherol concentrations are maintained by adequate vitamin C (ascorbic acid) concentrations. Thus, the delivery of alpha-tocopherol to the target tissues will be increased if ascorbic acid is limiting. Furthermore to maintain tissue alpha-tocopherol concentrations, rates of delivery of alpha-tocopherol increase due to increased turnover resulting from oxidative stress caused by obesity and from obesity with diabetes. The successful completion of these studies will provide essential key measures of alpha-tocopherol status, including fractional absorption, rates of delivery to tissues, and whole body efflux, for formulation of recommended daily intakes in healthy women, as well as women with conditions associated with increased oxidative stress. PUBLIC HEALTH RELEVANCE: We have shown that alpha-tocopherol is the most potent vitamin E form because the human body actively regulates its plasma concentrations and delivery to tissues while other vitamin E forms are actively metabolized and excreted. The proposed studies will use optimized methods for pharmacokinetic measurements and apply these to the problem of assessing "how much vitamin E is needed by the body?", and do these needs change with increased oxidative stress or decreased vitamin C status.

描述（由申请人提供）：流行病学研究表明，一生中摄入较高的膳食维生素 E 可以降低慢性病风险。然而，超过 90% 的美国人摄入的 1-生育酚每日摄入量还不到美国食品和营养委员会建议的 15 毫克（22 国际单位）的 40%。平时摄入的6毫克够吗？目前无法提供必要的循证数据来回答这个问题；拟议的研究旨在填补这一空白。我们之前的研究表明，人类的氧化应激会更快地消耗血浆维生素 E，而摄入足够的维生素 C 可以抵消维生素 E 的加速消耗。拟议的研究将使用优化的药代动力学测量方法来确定身体需要多少维生素 E 来应对氧化应激或维生素 C 耗尽状态。这项研究的独特之处在于它是 NIH 内部和外部研究人员之间的合作。拟议的研究将由 NIH 临床研究中心的 Mark Levine 博士及其团队进行，他们在测量维生素 C 药代动力学和生物利用度方面拥有丰富的经验。我们的实验室拥有必要的专业知识、经验和设备来测量低浓度的稳定同位素标记的维生素 E、其代谢物和过氧化生物标志物。该提案为 Traber 小组寻求资金，用于分析氘标记的 α-生育酚样品和脂质过氧化生物标志物。具体目标 1. 确定正常体重女性的 α-生育酚药代动力学。维生素 E 动力学研究将有助于确定维生素 E 状态的关键指标，包括吸收分数、组织输送率和全身流出。试点研究 1：确定优化 α-生育酚吸收所需的膳食中的最佳脂肪含量。初步研究 2：确定周转动力学的最佳 α-生育酚剂量。具体目标 2 和 3. 确定正常体重女性、肥胖女性和患有糖尿病的肥胖女性在维生素 C 消耗前后的 α-生育酚药代动力学。我们的工作假设是，α-生育酚浓度是通过足够的维生素 C（抗坏血酸）浓度来维持的。因此，如果抗坏血酸受到限制，则α-生育酚向靶组织的递送将会增加。此外，为了维持组织α-生育酚浓度，由于肥胖引起的氧化应激和糖尿病性肥胖导致的周转增加，因此α-生育酚的递送速率增加。这些研究的成功完成将为α-生育酚状态提供重要的关键指标，包括吸收分数、组织输送率和全身流出率，以制定健康女性以及患有氧化应激增加相关疾病的女性的每日推荐摄入量。 公共健康相关性：我们已经证明，α-生育酚是最有效的维生素 E 形式，因为人体会主动调节其血浆浓度并输送到组织，而其他形式的维生素 E 会积极代谢和排泄。拟议的研究将使用优化的药代动力学测量方法，并将其应用于评估“身体需要多少维生素E？”的问题，以及这些需求是否会随着氧化应激的增加或维生素C状态的降低而变化。