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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{at}tufts.edu.
ABSTRACT
Background: Coronary artery calcification (CAC) is an independent predictor of cardiovascular disease. A preventive role for vitamin K in CAC progression has been proposed based on 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/d phylloquinone (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. This trial was registered at clinicaltrials.gov as NCT00183001.
Received for publication December 10, 2008. Accepted for publication March 20, 2009.
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J. C McCann and B. N Ames Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging? Am. J. Clinical Nutrition, October 1, 2009; 90(4): 889 - 907. [Abstract] [Full Text] [PDF]
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