1a. Objectives (from AD-416):
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.
1b. Approach (from AD-416):
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.
3. Progress Report:
To conduct studies for guidance on the health benefits of vitamin K, accurate and up-to-date food composition information is required. Foods obtained from restaurants and markets from various locations were analyzed for vitamin K. The vitamin K food composition data were transferred to the Nutrient Data Laboratory at BHNRC for entry into the USDA National Nutrient Database for Standard Reference. These data will be used in research and for nutrition monitoring. Despite the popularity of genetically modified mouse models for mechanistic studies of human disease, little is known about the vitamin K requirements for mice. We performed a pilot study to determine the amount of time required to induce a subclinical deficiency of vitamin K in a mouse strain commonly used for genetic studies. Within one week of being fed a low vitamin K diet, there was a reduction of vitamin K concentrations in all tissues measured, with the exception of body fat. At the end of one month, vitamin K was not detectable in liver, which is the site for production of the vitamin K-dependent clotting factors, yet there were no clinical signs of vitamin K-deficiency. We concluded that a vitamin K deficient diet can be used to induce low vitamin K tissue concentrations in mouse models within one week and could be sustained for at least one month without creating clinical effects of vitamin K deficiency, such as abnormal bleeding. The primary dietary form of vitamin K, phylloquinone, is converted to a different vitamin K form, menaquinone-4, in certain tissues. However little is known about the mechanism and location of this conversion. In collaboration with our colleagues at CNRC, we fed deuterium-labeled phylloquinone to male rats and measured the conversion of phylloquinone to menaquinone-4. Our data demonstrated that menaquinone-4 is the major form of vitamin K in multiple tissues, including the brain, and originates from dietary phylloquinone. Our data did not support the hypothesis proposed by others that intestinal cells are involved in this conversion. Instead our research supports the hypothesis that formation of menaquinone-4 occurs within those tissues that appear to prefer this vitamin K form. Furthermore, the menaquinone-4 concentrations appear to be highly regulated in certain tissues, whereas other tissues appear to fluctuate more according to short-term manipulation of phylloquinone intake. This research provides insight into the metabolic fate of dietary vitamin K and provides the foundation for studies on the potential unique role of menaquinone-4 in human health.
1. Vitamin K status in U.S. adults differs according to race and ethnicity. Vitamin K is a nutrient that is essential for health, but little is known about racial and/or ethnic differences in vitamin K status. To address this gap in knowledge, ARS-Funded scientists from Tufts University in Boston, Massachusetts, in collaboration with scientists from Wake Forest Medical Center, studied the racial and ethnic differences in circulating vitamin K concentrations of adults participating in the Multiethnic Study of Atherosclerosis. Very few of the Chinese Americans had low concentrations of circulating vitamin K. In comparison, about one-third of African Americans and Hispanics had low concentrations of circulating vitamin K, which is related to increased risk of abnormal coronary artery calcification and osteoarthritis. These findings suggest that vitamin K status differs by race and ethnicity in U.S. adults, which may partially explain the observed racial and ethnic differences in health outcomes related to vitamin K.