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United States Department of Agriculture

Agricultural Research Service

Research Project: VITAMIN K: FOOD COMPOSITION, BIOAVAILABILITY AND IT'S ROLE IN HUMAN HEALTH

Location: Human Nutrition Research Center on Aging

Title: Circulating uncarboxylated matrix gla protein is associated with vitamin K nutritional status, but not coronary artery calcium, in older adults

Authors
item Shea, Kyla -
item O'Donnell, Christopher -
item Vermeer, Cees -
item Magdeleyns, Elke Jp -
item Crosier, Michael -
item Gundberg, Caren -
item Ordovas, Jose -
item Kritchevsky, Steven -
item Booth, Sarah -

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 5, 2011
Publication Date: August 15, 2011
Citation: Shea, K.M., O'Donnell, C.J., Vermeer, C., Magdeleyns, E., Crosier, M.D., Gundberg, C.M., Ordovas, J.M., Kritchevsky, S.B., Booth, S.L. 2011. Circulating uncarboxylated matrix gla protein is associated with vitamin K nutritional status, but not coronary artery calcium, in older adults. Journal of Nutrition. 141(8):1529-1534.

Interpretive Summary: Matrix Gla protein (MGP) is a protein that inhibits calcification in vascular tissue. To function, MGP requires vitamin K. Recent evidence suggests that blood concentrations of non-functional MGP (ucMGP) are elevated in patients with vascular calcification. The extent to which these findings reflect vitamin K’s role in calcification among healthy adults is unknown. The purpose of this study was to determine cross-sectional and longitudinal associations between plasma ucMGP, vitamin K status and coronary artery calcium (CAC) in older adults free of coronary heart disease. Cross-sectional associations between baseline plasma ucMGP, vitamin K status biomarkers and CAC were examined in community-dwelling adults (n=438 men and women, age range 60-80 yrs). The effect of vitamin K supplementation (500 ug/day for 3 years) on plasma ucMGP was determined among 374 men and women. Prior to supplementation, vitamin K status was lower among those individuals with elevated amounts of nonfunctional MGP. Plasma ucMGP was significantly reduced among the 190 participants who received vitamin K supplementation compared to the 184 who did not. However, CAC did not differ according to ucMGP concentrations. Similarly, in the vitamin K supplementation group, the change ucMGP was not associated with the change in CAC. Plasma ucMGP was associated with known biomarkers of vitamin K status and was reduced following phylloquinone supplementation, suggesting it may be a useful marker of vitamin K status in vascular tissue. However, plasma ucMGP did not appear to reflect CAC in healthy older adults.

Technical Abstract: Matrix Gla protein (MGP) is a calcification inhibitor in vascular tissue. To function, MGP must be carboxylated by vitamin K. Evidence suggests that circulating uncarboxylated MGP (ucMGP) is elevated in diseased individuals with vascular calcification. The extent to which this reflects vitamin K’s role in calcification is unknown. The purpose of this study was to determine cross-sectional and longitudinal associations between plasma ucMGP, vitamin K status and coronary artery calcium (CAC) in older adults free of coronary heart disease. Cross-sectional associations between baseline plasma ucMGP, vitamin K status biomarkers [plasma phylloquinone, uncarboxylated prothrombin (PIVKA-II), serum uncarboxylated osteocalcin (%ucOC)], and CAC were examined in community-dwelling adults (n=438, 60-80 yrs old, 59% women). The effect of phylloquinone supplementation (500 ug/day, 3 years) on plasma ucMGP was determined among 374 participants. At baseline plasma phylloquinone was lower, and %ucOC and PIVKA-II were higher across increasing quartiles of plasma ucMGP (all p<0.001, age-adjusted). Plasma ucMGP was significantly reduced among the 190 participants who received phylloquinone supplementation compared to the 184 who did not [mean±SE change= -345 +/- 251pmol/L vs -40 +/- 250pmol/L, p<0.0001)]. After age adjustment, CAC did not differ according to ucMGP quartile (p=0.35). In the phylloquinone supplementation group the change ucMGP was not associated with the change in CAC [unstandard B(SE) =-0.02(0.02), p=0.44]. Plasma ucMGP was associated with known biomarkers of vitamin K status and was reduced following phylloquinone supplementation, suggesting it may be a useful marker of vitamin K status in vascular tissue. However, plasma ucMGP did not appear to reflect CAC in healthy older adults.

Last Modified: 9/21/2014
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