Dietary & non-dietary components of vitamin K metabolism

描述（由申请人提供）：维生素K在骨骼健康中具有新兴作用。然而，人们对维生素K的代谢知之甚少，特别是在衰老和骨质维持方面。对维生素K代谢的这种有限的理解目前阻碍了建立维生素K饮食建议的能力，并解释了目前主要在狭窄年龄组的妇女中进行的最近关于维生素K补充和骨骼健康的临床试验的结果。这项拟议的研究将是第一个评估饮食和非饮食因素的作用，这些因素影响年轻和老年男性和女性对维生素K状态和骨转换对维生素K消耗和补充的反应。这项研究还将比较维生素K的吸收效率，相对于目前的维生素K状态。男性和女性[21名年轻人（21- 40岁）和21名老年人（60- 80岁）]将参加一项为期65天的代谢研究，其中包括5天的导入期，随后是30天的饮食维生素K限制期（10 μ g/ g/d），并以30天的饮食维生素K补充期（500 μ g/d）结束。维生素K状态标志物（血浆叶绿醌、尿Gla、血清%ucOC和血浆PIVKA-II）和骨转换（血清骨钙素和NTx）的系列测量将提供两个年龄组在相同控制饮食条件下对维生素K饮食控制的反应信息。将使用稳定同位素示踪剂（羽衣甘蓝中的氘标记维生素K）比较维生素K耗尽状态（21天膳食维生素K）期间维生素K的吸收 维生素K缺乏）到维生素K充足状态（膳食维生素K充足21天）。由于维生素K是在富含维生素K的脂蛋白中转运的，由于肥胖的差异，个体之间可能会有所不同，因此通过DXA和血浆脂质（总脂蛋白和单个脂蛋白）测量身体组成将有助于了解脂质在维生素K吸收和转运中的作用。拟议研究的结果对于解释用于确定维生素K可能对骨骼健康具有保护作用的最佳摄入量的流行病学和临床数据至关重要。

DESCRIPTION (provided by applicant): Vitamin K has an emerging role in bone health. However, little is known about the vitamin K metabolism, particularly in regards to aging, and maintenance of bone mass. Such limited understanding about vitamin K metabolism currently impedes the ability to establish dietary recommendations for vitamin K, and interpret the results from recent clinical trials on vitamin K supplementation and bone health currently being conducted in primarily women of a narrow age group. The proposed study will be the first to assess the role of dietary and non-dietary factors that influence the response to measures of vitamin K status and bone turnover to vitamin K depletion and repletion in younger and older men and women. This study will also compare the absorption efficiency of vitamin K, relative to current vitamin K status. Men and women [21 younger (21-40y) and 21 older (60-80y)] will participate in a 65-d metabolic study, with a 5-d run-in period, followed by a 30 d dietary vitamin K restriction period (10 mu/ g/d), and ending with a 30 d dietary vitamin K supplementation period (500 mu g/d). Serial measurements of markers of vitamin K status (plasma phylloquinone, urinary Gla, serum %ucOC and plasma PIVKA-II) and bone turnover (serum osteocalcin and NTx) will provide information on their response to dietary manipulation of vitamin K for both age groups under identical controlled dietary conditions. A stable isotope tracer (deuterium-labeled vitamin K in collards) will be used to compare the absorption of vitamin K during a vitamin K-deplete state (21 d of dietary vitamin K depletion) to that of a vitamin K-replete state (21 d of dietary vitamin K repletion). Because vitamin K is transported in triglyceride-rich lipoproteins, which may vary among individuals due to differences in adiposity, measurement of body composition by DXA and plasma lipids (total and individual lipoproteins) will provide insight into the role of lipids in absorption and transport of vitamin K. The findings of the proposed study are critical for the interpretation of the epidemiologic and clinical data used to determine optimal intakes at which vitamin K may have a protective role in bone health.