Quantitation of In Vivo Human Lutein Metabolism

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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.