Project Number: 1950-51000-069-02
Project Type: Specific Cooperative Agreement

Start Date: Mar 16, 2009
End Date: Mar 15, 2014

Objective:
1. Determine the amounts of individual dietary forms of vitamin K in nationally representative samples of frequently consumed U.S. foods and dietary supplements. 2. Characterize the effects of dietary and non-dietary factors, such as age, lipid profile and body fat, on the bioavailability and utilization of different forms of vitamin K in humans. 3. Identify mechanisms of action for vitamin K, other than its classic role as an enzyme cofactor, using cellular and animal models. 4. Determine the associations between vitamin K nutritional status and risk of abnormal non-skeletal calcification.

Approach:
Laboratory analysis of different forms of vitamin K will be conducted in selected foods obtained through collaboration with the USDA Nutrient and Data Laboratory (NDL), as part of the Food and Nutrient Analysis Program. Priorities for food analysis will include dietary supplements, food purchased in family style restaurants, foods common to the Hispanic/Latino diet, and foods associated with high calorie diets. Food composition data will be transferred to the NDL for entry into national food composition databases. To identify dietary and non-dietary factors that determine how much vitamin K obtained from foods is utilized, we will apply stable isotope techniques to measures of vitamin K metabolism. Data obtained from ongoing metabolic studies in men and women, in addition to pilot feasibility studies, will be used to refine the study design to test the response of these measures to intake of different vitamin K-rich food sources. Animal models will be used to identify tissue-specific effects of interactions between vitamin K and other fat-soluble vitamins, with an emphasis on vitamins A and D. To identify mechanisms of action for vitamin K other than its classic role as an enzyme cofactor, urinary and serum levels of vitamin K metabolites will be measured in response to vitamin K supplementation using archived samples from human and animal studies. We will then focus on the role of different forms of vitamin K in inflammation through the inactivation of nuclear receptors in macrophages.