Am J Clin Nutr 89: 1799-1807, 2009. First published April 22, 2009 ORIGINAL RESEARCH COMMUNICATION

Vitamin K supplementation and progression of coronary artery calcium in older men and women^1,2,3,4

M Kyla Shea, Christopher J O'Donnell, Udo Hoffmann, Gerard E Dallal, Bess Dawson-Hughes, José M Ordovas, Paul A Price, Matthew K Williamson and Sarah L Booth

¹ From the US Department of Agriculture, Human Nutrition Research Center on Aging, Tufts University, Boston, MA (MKS, BD-H, JMO, and SLB); the National Heart, Lung, and Blood Institute's Framingham Heart Study, Bethesda, MD (CJO); the Cardiology Division, Massachusetts General Hospital, Boston, MA (CJO); CIMIT, Massachusetts General Hospital, Boston, MA (UH); and the Division of Biological Sciences, University of California, San Diego, CA (PAP and MKW).

² Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors, and do not necessarily reflect the view of the US Department of Agriculture.

³ Supported by the US Department of Agriculture, Agricultural Research Service, under Cooperative Agreement no. 58-1950-7-707; National Institutes of Health (AG14759, HL69272, and T32HL69772); and the American Heart Association (0515605T).

⁴ Address correspondence to SL Booth, USDA Human Nutrition Research Center on Aging, Tufts University, 711 Washington Street, Boston, MA 02111. E-mail: sarah.booth@tufts.edu .

Background: Coronary artery calcification (CAC) is an independent predictor of cardiovascular disease. A preventive role for vitamin K in CAC progression has been proposed on the basis of the properties of matrix Gla protein (MGP) as a vitamin K–dependent calcification inhibitor.

Objective: The objective was to determine the effect of phylloquinone (vitamin K1) supplementation on CAC progression in older men and women.

Design: CAC was measured at baseline and after 3 y of follow-up in 388 healthy men and postmenopausal women; 200 received a multivitamin with 500 µg phylloquinone/d (treatment), and 188 received a multivitamin alone (control).

Results: In an intention-to-treat analysis, there was no difference in CAC progression between the phylloquinone group and the control group; the mean (±SEM) changes in Agatston scores were 27 ± 6 and 37 ± 7, respectively. In a subgroup analysis of participants who were 85% adherent to supplementation (n = 367), there was less CAC progression in the phylloquinone group than in the control group (P = 0.03). Of those with preexisting CAC (Agatston score > 10), those who received phylloquinone supplements had 6% less progression than did those who received the multivitamin alone (P = 0.04). Phylloquinone-associated decreases in CAC progression were independent of changes in serum MGP. MGP carboxylation status was not determined.

Conclusions: Phylloquinone supplementation slows the progression of CAC in healthy older adults with preexisting CAC, independent of its effect on total MGP concentrations. Because our data are hypothesis-generating, further studies are warranted to clarify this mechanism.