Determinants of Vitamin K Metabolism

• Urinary excretion of VK metabolites at VK depletion and repletion [ Time Frame: 2 months ] [ Designated as safety issue: No ]
• Bone turnover markers at VK depletion and repletion [ Time Frame: 2 months ] [ Designated as safety issue: No ]

• Urinary excretion of VK metabolites at VK depletion and repletion
• Bone turnover markers at VK depletion and repletion
• Vitamin K (VK) status markers at VK depletion and repletion

• Plasma triglyceride levels at VK depletion and repletion [ Time Frame: 2 months ] [ Designated as safety issue: No ]
• Glucose metabolism measures at VK depletion and repletion [ Time Frame: 2 months ] [ Designated as safety issue: No ]
• Mood assessment at VK depletion and repletion [ Time Frame: 2 months ] [ Designated as safety issue: No ]

• Plasma triglyceride levels at VK depletion and repletion
• Glucose metabolism measures at VK depletion and repletion
• Mood assessment at VK depletion and repletion

The purpose of this study is to learn how the body responds to different amounts of vitamin K in the diet in order to understand the roles that vitamin K may have in the body. We also need to determine if older adults need more or less vitamin K in their diet compared to younger adults in order to maintain normal body stores of vitamin K.

Vitamin K has a role in bone health, but little is known about vitamin K metabolism in aging and in maintenance of bone mass. The limited understanding of vitamin K metabolism impedes the establishment of dietary recommendations for vitamin K, and the interpretation of results from clinical trials on vitamin K supplementation and bone health of women in a narrow age group. This study is the first to assess the role of dietary and other factors that influence the response to vitamin K status and bone turnover to vitamin K depletion and repletion in adults. This study also compares the absorption efficiency and body retention of vitamin K relative to current vitamin K status. Men and women [21 younger (18-40y) and 21 older (55+y)] will participate in a 62-d metabolic study, with a 5d run-in period, followed by a 28d dietary vitamin K restriction period (10 ug/d), and ending with a 28d dietary vitamin K supplementation period (500 ug/d). Coagulation times will be monitored during the dietary restriction period. Serial measurements of vitamin K status markers and of bone turnover markers will show the response of vitamin K to dietary manipulation for both age groups under identically controlled dietary conditions. Deuterium-labeled vitamin K in collards will be used to compare the absorption of vitamin K during a vitamin K-deplete state to that of a vitamin K-replete state. Vitamin K is transported in triglyceride-rich lipoproteins, which may vary among individuals due to differences in adiposity and lipid homeostasis. Therefore, measurement of body composition by DXA and plasma lipids will provide insight into the role of lipids in absorption and transport of vitamin K. The findings of this study are critical for the interpretation of the epidemiologic and clinical data used to determine the protective role vitamin K may have in chronic disease prevention.

• Aging
• Osteoporosis

• Harrington DJ, Soper R, Edwards C, Savidge GF, Hodges SJ, Shearer MJ. Determination of the urinary aglycone metabolites of vitamin K by HPLC with redox-mode electrochemical detection. J Lipid Res. 2005 May;46(5):1053-60. Epub 2005 Feb 1.
• Erkkila AT, Lichtenstein AH, Dolnikowski GG, Grusak MA, Jalbert SM, Aquino KA, Peterson JW, Booth SL. Plasma transport of vitamin K in men using deuterium-labeled collard greens. Metabolism. 2004 Feb;53(2):215-21.
• Booth SL, Martini L, Peterson JW, Saltzman E, Dallal GE, Wood RJ. Dietary phylloquinone depletion and repletion in older women. J Nutr. 2003 Aug;133(8):2565-9.
• Booth SL, Lichtenstein AH, O'Brien-Morse M, McKeown NM, Wood RJ, Saltzman E, Gundberg CM. Effects of a hydrogenated form of vitamin K on bone formation and resorption. Am J Clin Nutr. 2001 Dec;74(6):783-90.

Inclusion Criteria:

-

Exclusion Criteria:

• kidney, GI, or liver disease requiring treatment
• prescribed osteoporosis medications in the previous 3 months
• use of acid reducers more than twice per week
• blood clotting disorder and/or abnormal clotting time
• warfarin or anticoagulant use in the previous 12 months
• diabetes
• smoking
• hormone therapy in the previous 3 months
• oral contraceptive use in the previous 3 months; pregnancy
• strict vegetarian diet