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

描述（由申请人提供）：流行病学研究表明，终身食用较高的膳食维生素E摄入量可以降低慢性疾病的风险。然而，超过90%的美国人每天摄入的1-生育酚不到食品和营养委员会推荐的15毫克（22 IU）的40%。通常的6毫克摄入量足够吗？目前还没有必要的循证数据来回答这个问题;拟议的研究试图填补这一空白。我们以前的研究表明，人类的氧化应激更快地消耗血浆维生素E，充足的维生素C摄入量可以对抗加速的维生素E消耗。拟议的研究将使用优化的方法进行药代动力学测量，以解决机体在应对氧化应激或维生素C耗尽状态时需要多少维生素E。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。拟议的研究将由美国国立卫生研究院临床研究中心的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具有丰富的经验。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，其代谢产物和过氧化生物标志物。该提案旨在为Traber小组提供资金，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。测定正常体重女性的α-生育酚药代动力学。维生素E动力学研究将允许确定维生素E状态的关键指标，包括吸收分数、递送至组织的速率和全身外排。初步研究1：确定优化α-生育酚吸收所需的伴随膳食中的最佳脂肪含量。初步研究2：确定转换动力学的最佳α-生育酚剂量。具体目标2和3。测定正常体重女性、肥胖女性和肥胖糖尿病女性维生素C缺乏前后α-生育酚的药代动力学。我们的工作假设是，α-生育酚浓度是由足够的维生素C（抗坏血酸）浓度维持的。因此，如果抗坏血酸是限制性的，则α-生育酚向靶组织的递送将增加。此外，为了维持组织α-生育酚浓度，α-生育酚的递送速率增加，这是由于肥胖引起的氧化应激和肥胖伴糖尿病引起的周转增加。这些研究的成功完成将提供α-生育酚状态的基本关键指标，包括吸收分数、递送至组织的速率和全身外排，用于制定健康女性以及患有与氧化应激增加相关的疾病的女性的推荐每日摄入量。

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.