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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
1R01DK069341-01A1
Application #
6969060
Study Section
Integrative Nutrition and Metabolic Processes Study Section (INMP)
Program Officer
May, Michael K
Project Start
2005-09-30
Project End
2009-07-31
Budget Start
2005-09-30
Budget End
2006-07-31
Support Year
1
Fiscal Year
2005
Total Cost
$317,685
Indirect Cost
Name
Tufts University
Department
Type
Schools of Medicine
DUNS #
039318308
City
Boston
State
MA
Country
United States
Zip Code
02111
Traber, Maret G; Leonard, Scott W; Bobe, Gerd et al. (2015) ?-Tocopherol disappearance rates from plasma depend on lipid concentrations: studies using deuterium-labeled collard greens in younger and older adults. Am J Clin Nutr 101:752-9
Rehder, Douglas S; Gundberg, Caren M; Booth, Sarah L et al. (2015) Gamma-carboxylation and fragmentation of osteocalcin in human serum defined by mass spectrometry. Mol Cell Proteomics 14:1546-55
Booth, Sarah L; Centi, Amanda; Smith, Steven R et al. (2013) The role of osteocalcin in human glucose metabolism: marker or mediator? Nat Rev Endocrinol 9:43-55
Truong, Jennifer T; Fu, Xueyan; Saltzman, Edward et al. (2012) Age group and sex do not influence responses of vitamin K biomarkers to changes in dietary vitamin K. J Nutr 142:936-41
Al Rajabi, Ala; Booth, Sarah L; Peterson, James W et al. (2012) Deuterium-labeled phylloquinone has tissue-specific conversion to menaquinone-4 among Fischer 344 male rats. J Nutr 142:841-5
Zwart, Sara R; Booth, Sarah L; Peterson, James W et al. (2011) Vitamin K status in spaceflight and ground-based models of spaceflight. J Bone Miner Res 26:948-54
Buell, J S; Dawson-Hughes, B; Scott, T M et al. (2010) 25-Hydroxyvitamin D, dementia, and cerebrovascular pathology in elders receiving home services. Neurology 74:18-26
Fu, Xueyan; Peterson, James W; Hdeib, Mona et al. (2009) Measurement of deuterium-labeled phylloquinone in plasma by high-performance liquid chromatography/mass spectrometry. Anal Chem 81:5421-5