(Scanned from the applicant's description): Usual dietary intakes of vitamin K among adults are low. These intakes do not support complete carboxylation of osteocalcin, a vitamin K-dependent protein in bone, and short-term dietary vitamin K deficiency may increase bone turnover in adults. Epidemiological evidence has shown associations between biochemical markers of vitamin K nutrition and age-related bone loss in elderly men and women. However it is not known if these markers of vitamin K nutrition are indicators of generalized poor total nutritional status in these studies. Furthermore, the impact of long-term vitamin K supplementation on bone mineral density (BMD) and bone turnover has not been examined. In a 3-year, double-blind, placebo controlled trial, we propose to study the effect of vitamin K supplementation (500 ug/d on femoral neck BMD and markers of bone turnover in 450 men and women, aged 60-80 years. All participants will also be receiving calcium and vitamin D supplements, in addition to a multivitamin, to prevent any potential bone loss associated with dietary inadequacy of these nutrients. We will measure plasma vitamin K concentrations and percent undercarboxylated osteocalcin (markers of vitamin K status), serum osteocalcin and collagen Type-1-crosslink N-telopeptides (markers of bone turnover) and BMD of the hip, as well as the heel, spine and total body at 1, 6, 12, 24, and 36 months of vitamin K supplementation. Plasma 25-hydroxyvitamin D and 1, 25-dihydroxyvitamin D concentrations and urinary calcium will be measured at the same time points to be used as covanates in this assessment. Other covariates collected through the course of the study include age, anthropometric data, physical activity, medication used, smoking, and dietary intakes of energy, protein, alcohol and caffeine. The proposed trial provides a unique opportunity to determine if supplemental vitamin K will reduce age-related bone loss in elderly men and women, above that achieved by supplemental calcium and vitamin D alone.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG019147-02
Application #
6509961
Study Section
Nutrition Study Section (NTN)
Program Officer
Sherman, Sherry
Project Start
2001-09-30
Project End
2006-06-30
Budget Start
2002-07-15
Budget End
2003-06-30
Support Year
2
Fiscal Year
2002
Total Cost
$707,205
Indirect Cost
Name
Tufts University
Department
Type
Schools of Medicine
DUNS #
604483045
City
Boston
State
MA
Country
United States
Zip Code
02111
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
Al Rajabi, Ala; Peterson, James; Choi, Sang-Woon et al. (2010) Measurement of menadione in urine by HPLC. J Chromatogr B Analyt Technol Biomed Life Sci 878:2457-60
Shea, M Kyla; Dallal, Gerard E; Dawson-Hughes, Bess et al. (2008) Vitamin K, circulating cytokines, and bone mineral density in older men and women. Am J Clin Nutr 88:356-63
Moselewski, Fabian; Ferencik, Maros; Achenbach, Stephan et al. (2006) Threshold-dependent variability of coronary artery calcification measurements -- implications for contrast-enhanced multi-detector row-computed tomography. Eur J Radiol 57:390-5
O'Donnell, Christopher J; Shea, M Kyla; Price, Paul A et al. (2006) Matrix Gla protein is associated with risk factors for atherosclerosis but not with coronary artery calcification. Arterioscler Thromb Vasc Biol 26:2769-74
Cury, Ricardo C; Ferencik, Maros; Hoffmann, Udo et al. (2004) Epidemiology and association of vascular and valvular calcium quantified by multidetector computed tomography in elderly asymptomatic subjects. Am J Cardiol 94:348-51
Ferencik, Maros; Ferullo, Ashley; Achenbach, Stephan et al. (2003) Coronary calcium quantification using various calibration phantoms and scoring thresholds. Invest Radiol 38:559-66