Quantitation of In Vivo Human Lutein Metabolism

体内人类叶黄素代谢的定量

• 批准号: 7595147
• 负责人: ANDREW JOSEPH CLIFFORD
• 金额: $ 32.3万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7595147
• 关键词: Accounting; Adult; Affect; Age related macular degeneration; American; Antioxidants; Appearance; Banana; Behavior; Beta Carotene; Biological; Blindness; Blood specimen; Body Weight; Carotenoids; Catabolism; Caucasians; Caucasoid Race; Chemicals; Chemistry; Data Analyses; Data Set; Diet; Dietary Carotenoid; Dietary intake; Dose; Drug Formulations; Ensure; Experimental Designs; Exudative age-related macular degeneration; Family; Fatty acid glycerol esters; Feces; Food; High Density Lipoproteins; Hour; Human; Human Resources; Human body; Intake; Intervention Studies; Isotopes; Kinetics; Knowledge; Label; Laboratories; Lipoproteins; Literature; Lutein; Macular degeneration; Maintenance; Measures; Metabolic; Metabolism; Milk; Modeling; Olive oil preparation; Optics; Parents; Pigments; Pilot Projects; Plasma; Population; Population Study; Principal Investigator; Protocols documentation; Radioactive; Recommendation; Recruitment Activity; Retina; Risk; Role; Sampling; Serum; System; Time; Tracer; Ultracentrifugation; United States; Urine; Vegetables; Very low density lipoprotein; Vision; Woman; Work; Xanthophylls; absorption; accelerator mass spectrometry; base; density; design; detector; experience; human subject; in vivo; legally blind; low density lipoprotein inhibitor; macula; men; particle; programs; public health relevance; statistics; uptake; volunteer; zeaxanthin

DESCRIPTION (provided by applicant): Lutein is an oxygenated carotenoid (xanthophyll) found in dark green leafy vegetables. Dietary lutein and zeaxanthin accumulate in the macula region of the retina and are hypothesized to protect the macula by acting as antioxidant and optical filters that may lower the risk of age related macular degeneration. Despite these relationships little is known about the quantitative aspects of lutein and zeaxanthin metabolism as it occurs in vivo in humans. The overall objective of the proposed project is to describe the dynamic and kinetic behavior of lutein metabolism in a small population of healthy men and women who consume a normal diet and do not use supplements. For this purpose 12 volunteers, 6 women and 6 men, will be recruited and administered a single dose of 14C-lutein (70 mcg with 36 nCi) dissolved into olive oil (0.5 g/kg body weight) and incorporated in a banana milk shake. A baseline blood sample (10 mL) will be taken just before the dose is administered and continued at various intervals until 100 days post dose to ensure that the 14C labeled lutein is fully equilibrated into the slowest turning over lutein pool that can affect the plasma kinetics late in a study. The five lipoprotein classes will be separated from plasma in a single ultracentrifugation. Urine and feces will be collected until 21 days post dose. The 14C content of each biological sample will be measured at the Center for the Accelerator Mass Spectrometry (AMS) at Lawrence Livermore National Laboratory (Livermore, CA). The chemical identity of the 14C in plasma and plasma lipoprotein samples will also be determined, parent compound (14C-lutein) and two metabolites (3-hydroxy-b-e-caroten-3'-one and 3'-epilutein) by using non-radioactive standards in an HPLC-photodiode array detector system. Using the dataset, we will construct a kinetic model of human lutein metabolism. We have already demonstrated the feasibility of our approach with one normal adult woman using the protocol we describe in the present application. We used a high sampling density of plasma over a relatively long time since dosing to acquire a much more detailed/complete dataset under steady state conditions than any already existing in the scientific literature. Then if specific metabolic functions for lutein can be stipulated, it will be possible to determine a minimum intake of lutein to sustain these critical functions, such as, maintaining optimum macular pigment optical density and minimizing the risk of macular degeneration. PUBLIC HEALTH RELEVANCE: Lutein is a fat-soluble compound that belongs to the same family as the beta-carotene. Lutein occurs naturally in many foods, but primarily in dark green leafy vegetables. Lutein may protect the macula, a region of the retina, by acting as antioxidant and optical filters which may lower the risk of age related macular degeneration. Despite these relationships little is known about the quantitative aspects of lutein metabolism as it occurs in vivo in humans. Previous pilot studies have shown that a better understanding of the absorption and metabolism of lutein from the diet, and its accumulation in the body is needed to understanding how lutein works to help better vision. Therefore, the purpose of this study is to determine how the human body uses lutein and other related compounds.

描述（由申请人提供）：叶黄素是一种存在于深绿叶蔬菜中的含氧类胡萝卜素（叶黄素）。膳食中的叶黄素和玉米黄质在视网膜黄斑区域积聚，据推测可以通过充当抗氧化剂和光学过滤器来保护黄斑，从而降低年龄相关性黄斑变性的风险。尽管存在这些关系，但人们对叶黄素和玉米黄质在人体体内代谢的定量方面知之甚少。该项目的总体目标是描述一小部分正常饮食且不使用补充剂的健康男性和女性中叶黄素代谢的动态和动力学行为。为此目的，将招募 12 名志愿者（6 名女性和 6 名男性），并给予单剂 14C-叶黄素（70 微克，36 nCi）溶解在橄榄油（0.5 克/公斤体重）中并加入香蕉奶昔中。将在给药前采集基线血样 (10 mL)，并以不同的时间间隔继续采集，直至给药后 100 天，以确保 14C 标记的叶黄素完全平衡为可影响血浆动力学的最慢周转叶黄素库。学习迟到了。通过一次超速离心即可从血浆中分离出五类脂蛋白。将收集尿液和粪便直至给药后 21 天。每个生物样品的 14C 含量将在劳伦斯利弗莫尔国家实验室（加利福尼亚州利弗莫尔）的加速器质谱 (AMS) 中心进行测量。血浆和血浆脂蛋白样品中 14C 的化学特性也将通过使用非放射性标准 HPLC-光电二极管阵列检测器系统。使用该数据集，我们将构建人类叶黄素代谢的动力学模型。我们已经使用我们在本申请中描述的方案对一名正常成年女性证明了我们的方法的可行性。我们在给药后相对较长的时间内使用了血浆的高采样密度，以在稳态条件下获得比科学文献中现有的任何数据更详细/完整的数据集。然后，如果可以规定叶黄素的特定代谢功能，则可以确定维持这些关键功能的叶黄素的最低摄入量，例如维持最佳黄斑色素光密度并最大限度地降低黄斑变性的风险。公共健康相关性：叶黄素是一种脂溶性化合物，与 β-胡萝卜素属于同一家族。叶黄素天然存在于许多食物中，但主要存在于深绿叶蔬菜中。叶黄素可以通过充当抗氧化剂和光学过滤器来保护黄斑（视网膜的一个区域），从而降低与年龄相关的黄斑变性的风险。 尽管存在这些关系，但人们对人类体内叶黄素代谢的定量方面知之甚少。先前的初步研究表明，需要更好地了解饮食中叶黄素的吸收和代谢及其在体内的积累，以了解叶黄素如何发挥作用以帮助改善视力。因此，本研究的目的是确定人体如何利用叶黄素和其他相关化合物。