MICRONUTRIENT KINETICS IN HUMANS AT PHYSIOLOGIC DOSES

生理剂量下人体微量营养素动力学

• 批准号: 7977071
• 负责人: ANDREW JOSEPH CLIFFORD
• 金额: $ 4.5万
• 依托单位: UNIVERSITY OF CALIF-LAWRNC LVRMR NAT LAB
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-04 至 2010-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7977071
• 关键词: Antioxidants; Beta Carotene; Biochemical Reaction; Biological; Biological Availability; Blood; Carbon; Carotene; Collection; Computer Retrieval of Information on Scientific Projects Database; Data; Data Set; Dose; Drug Kinetics; Elderly; Exposure to; Female of child bearing age; Folate; Funding; Grant; High Pressure Liquid Chromatography; Homocysteine; Homocystine; Human; Indwelling Catheter; Institution; Isotopes; Kinetics; Label; Life; Measurement; Metabolism; Methionine; Micronutrients; Modeling; Nutrient; Nutritional; Phase; Physiological; Pigments; Plants; Polyenes; Population; Process; Purines; Pyrimidine; Pyrimidines; Radiation; Radioisotopes; Research; Research Personnel; Resource Development; Resources; Risk; Sampling; Signal Transduction; Source; United States National Institutes of Health; Upper arm; Venipunctures; Vitamin A; Vitamin E; Vitamins; absorption; accelerator mass spectrometry; base; density; insight; men; purine; stable isotope; urinary; volunteer

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. A steady supply of dietary micronutrients (vitamins) is needed to maintain normal biochemical reactions within humans. Folate is needed to maintain purine and pyrimidine synthesis, and metabolism of homocysteine to methionine. Carotene is a commonly consumed plant pigment (polyene) that is a biological antioxidant and a nutritional precursor of vitamin A. These and other micronutrients have generally been studied within humans at high, non-physiologic, doses in the past using stable or radioactive isotopes. While safe for use in humans, stable isotopes produce kinetic signals that quickly approach natural isotopic levels after a single dose. Radioisotopic labels are sufficicently distinct to provide traceable levels for longer periods, but the risks of radiation exposure limit such uses to populations that are less concerned with possible damage, such as elderly or infirm men. Accelerator mass spectrometry has such high sensitivity for quantifying long-lived isotopes that 14C-labeled micronutrients can now be traced in healthy young people, including particularly women of child-bearing age. Volunteers are given microgram doses of 14C-labeled compounds at radiative doses of 100-200 nCi (6-12 kBq). Blood is frequently collected from an indwelling catheter in the arm during the first day or two to provide high density data reflecting the absorption and initial metabolism phases of the pharmacokinetics. Urinary and fecal collections are made daily during the first two weeks past exposure to provide the quantitative bioavailability of the compound. Blood is then collected occasionally by venipuncture over the next 4-7 months post exposure. Circulating metabolites of the labeled nutrient are seprarted by HPLC. All samples are quantified for 14C concentration by AMS measurement of at least 0.5 mg carbon from the sample. Studies have been performed to examine the metabolism of various nutients including: beta-carotene, folate and vitamin E. Compartmental models are devised for the nutrient based on present best understanding of the absorption, metabolism, and elimination processes. The models are then modified to fit the dense data set of AMS measurements. Such models provide insight into the slowest turning ( and thus the most sustained) pools of nutrients in the volunteers.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 需要稳定供应膳食微量营养素（维生素）来维持人体正常的生化反应。叶酸是维持嘌呤和嘧啶合成以及同型半胱氨酸代谢为蛋氨酸所必需的。胡萝卜素是一种常用的植物色素（多烯），是一种生物抗氧化剂和维生素 A 的营养前体。过去通常使用稳定或放射性同位素以高、非生理剂量在人体中研究这些和其他微量营养素。虽然稳定同位素可安全用于人类，但其产生的动力学信号在单次剂量后可迅速接近天然同位素水平。放射性同位素标签足够明显，可以在较长时间内提供可追踪的水平，但辐射暴露的风险限制了这种用途，只适用于不太关心可能造成的损害的人群，例如老年人或体弱的男性。加速器质谱法对于量化长寿命同位素具有如此高的灵敏度，以至于现在可以在健康年轻人（尤其是育龄妇女）中追踪到 14C 标记的微量营养素。 志愿者接受微克剂量的 14C 标记化合物，辐射剂量为 100-200 nCi (6-12 kBq)。通常在第一天或第二天从手臂留置导管采集血液，以提供反映药代动力学吸收和初始代谢阶段的高密度数据。在接触后的前两周内每天收集尿液和粪便，以提供化合物的定量生物利用度。然后在暴露后的 4-7 个月内偶尔通过静脉穿刺采集血液。通过 HPLC 分离标记营养素的循环代谢物。所有样品均通过 AMS 测量样品中至少 0.5 mg 的碳来量化 14C 浓度。 已经进行了研究来检查各种营养素的代谢，包括：β-胡萝卜素、叶酸和维生素 E。根据目前对吸收、代谢和消除过程的最佳理解，为营养素设计了房室模型。然后修改模型以适应 AMS 测量的密集数据集。这些模型提供了对志愿者体内最慢的营养物质库（因此也是最持久的）的了解。