Dietary & non-dietary components of vitamin K metabolism

描述（由申请人提供）：维生素K在骨骼健康中发挥着新的作用。然而，人们对维生素K的代谢知之甚少，特别是在衰老和维持骨量方面。这种对维生素K代谢的有限理解目前阻碍了建立维生素K的膳食建议的能力，并解释了最近在维生素K补充和骨骼健康方面的临床试验的结果，目前主要是在一个狭窄年龄组的女性中进行的。这项拟议的研究将首次评估饮食和非饮食因素对维生素K状态和骨骼转换对年轻和老年男性和女性维生素K消耗和补充的影响。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）]将参加为期65天的代谢研究，其中5天为磨合期，随后是30天的膳食维生素K限制期（10 μ g/d），最后是30天的膳食维生素K补充期（500 μ g/d）。对维生素K状态标志物（血浆叶绿醌、尿Gla、血清ucOC %和血浆PIVKA-II）和骨转换标志物（血清骨钙素和NTx）进行系列测量，将提供在相同的控制饮食条件下，两个年龄组对维生素K饮食操纵的反应信息。稳定同位素示踪剂（羽衣甘蓝中氘标记的维生素K）将用于比较维生素K耗尽状态（21 d膳食维生素）期间维生素K的吸收

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.