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: 7602407
• 负责人: ANDREW JOSEPH CLIFFORD
• 金额: $ 4.06万
• 依托单位: UNIVERSITY OF CALIF-LAWRNC LVRMR NAT LAB
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-01 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7602407
• 关键词: Antioxidants; Beta Carotene; Biochemical Reaction; Biological; Biological Availability; Blood; Carbon; Carotene; Collection; Computer Retrieval of Information on Scientific Projects Database; Daily; 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; Resources; Risk; Sampling; Signal Transduction; Source; United States National Institutes of Health; Upper arm; Venipunctures; Vitamin A; Vitamin E; Vitamins; Week; absorption; accelerator mass spectrometry; base; day; 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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 需要稳定的饮食微量营养素（维生素）供应，以维持人类内部的正常生化反应。需要叶酸来维持嘌呤和嘧啶合成，以及同型半胱氨酸与蛋氨酸的代谢。胡萝卜素是一种通常消耗的植物色素（多烯），是一种生物抗氧化剂和维生素A的营养前体。这些和其他微量营养素通常在人类中以稳定的或放射性同位素的稳定剂量进行了较高的非生理剂量。虽然可以安全地用于人类，但稳定的同位素会产生动力学信号，单剂量后迅速接近天然同位素水平。放射性病标签具有足够的不同，可以在更长的时间内提供可追溯的水平，但是辐射暴露的风险限制了这种用途对可能造成的损害的人群，例如老年人或虚弱的男人。加速器的质谱法具有量化长期同位素的敏感性，以至于健康的年轻人现在可以追溯到14C标记的微量营养素，包括尤其是具有育儿的女性。 在辐射剂量为100-200 NCI（6-12 kBQ）时，志愿者的14C标记化合物的志愿者剂量为14c标记的化合物。在第一或两天内，经常从手臂的留置导管收集血液，以提供反映药代动力学的吸收和初始代谢阶段的高密度数据。在暴露前两周，每天进行尿和粪便收集，以提供该化合物的定量生物利用度。然后，在接下来的4-7个月中，偶尔通过静脉穿刺收集血液。标记营养素的循环代谢产物由HPLC分解。通过从样品中至少0.5 mg碳测量AMS测量，将所有样品定量14C浓度。 已经进行了研究以检查各种生效的代谢，包括：β-胡萝卜素，叶酸和维生素E.隔室模型是根据对吸收，代谢和消除过程的当前最佳理解而设计用于营养素的。然后对模型进行修改以符合AMS测量的密集数据集。这样的模型可以深入了解志愿者中最慢的养分库（以及最持续的）池。