High dietary menaquinone intake is associated with reduced coronary calcification



      Dietary vitamin K is thought to decrease risk of cardiovascular disease by reducing coronary calcification, but inconsistent results are reported. This may be due to different effects of vitamin K1 (phylloquinone) and vitamin K2 (menaquinone, MK), but few studies included both.


      We investigated the association of intake of phylloquinone and menaquinone, including its subtypes (MK4–MK10), with coronary calcification in a cross-sectional study among 564 post-menopausal women. Phylloquinone and menaquinone intake was estimated using a food-frequency questionnaire.


      Sixty-two percent (n = 360) of the women had coronary calcification based on 1.5-mm thick slices. Phylloquinone intake was not associated with coronary calcification with a relative risk (RR) of 1.17 (95%-confidence interval: 0.96–1.42; ptrend = 0.11) of the highest versus lowest quartile. Menaquinone intake was associated with decreased coronary calcification with an RR of 0.80 (95%-CI: 0.65–0.98; ptrend = 0.03).


      This study shows that high dietary menaquinone intake, but probably not phylloquinone, is associated with reduced coronary calcification. Adequate menaquinone intakes could therefore be important to prevent cardiovascular disease.


      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Bolton-Smith C.
        • Price R.J.
        • Fenton S.T.
        • Harrington D.J.
        • Shearer M.J.
        Compilation of a provisional UK database for the phylloquinone (vitamin K1) content of foods.
        Br J Nutr. 2000; 83: 389-399
        • Schurgers L.J.
        • Vermeer C.
        Determination of phylloquinone and menaquinones in food. Effect of food matrix on circulating vitamin K concentrations.
        Haemostasis. 2000; 30: 298-307
        • Furie B.
        • Bouchard B.A.
        • Furie B.C.
        Vitamin K-dependent biosynthesis of gamma-carboxyglutamic acid.
        Blood. 1999; 93: 1798-1808
        • Cranenburg E.C.
        • Schurgers L.J.
        • Vermeer C.
        Vitamin K: the coagulation vitamin that became omnipotent.
        Thromb Haemost. 2007; 98: 120-125
        • Shanahan C.M.
        • Proudfoot D.
        • Farzaneh-Far A.
        • Weissberg P.L.
        The role of Gla proteins in vascular calcification.
        Crit Rev Eukaryot Gene Expr. 1998; 8: 357-375
        • Greenland P.
        • Bonow R.O.
        • Brundage B.H.
        • et al.
        ACCF/AHA 2007 clinical expert consensus document on coronary artery calcium scoring by computed tomography in global cardiovascular risk assessment and in evaluation of patients with chest pain: a report of the American College of Cardiology Foundation Clinical Expert Consensus Task Force (ACCF/AHA Writing Committee to Update the 2000 Expert Consensus Document on Electron Beam Computed Tomography) developed in collaboration with the Society of Atherosclerosis Imaging and Prevention and the Society of Cardiovascular Computed Tomography.
        J Am Coll Cardiol. 2007; 49: 378-402
        • Abedin M.
        • Tintut Y.
        • Demer L.L.
        Vascular calcification: mechanisms and clinical ramifications.
        Arterioscler Thromb Vasc Biol. 2004; 24: 1161-1170
        • Saito E.
        • Wachi H.
        • Sato F.
        • Sugitani H.
        • Seyama Y.
        Treatment with vitamin K(2) combined with bisphosphonates synergistically inhibits calcification in cultured smooth muscle cells.
        J Atheroscler Thromb. 2007; 14: 317-324
        • Spronk H.M.
        • Soute B.A.
        • Schurgers L.J.
        • et al.
        Matrix Gla protein accumulates at the border of regions of calcification and normal tissue in the media of the arterial vessel wall.
        Biochem Biophys Res Commun. 2001; 289: 485-490
        • Luo G.
        • Ducy P.
        • McKee M.D.
        • et al.
        Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein.
        Nature. 1997; 386: 78-81
        • Koos R.
        • Mahnken A.H.
        • Muhlenbruch G.
        • et al.
        Relation of oral anticoagulation to cardiac valvular and coronary calcium assessed by multislice spiral computed tomography.
        Am J Cardiol. 2005; 96: 747-749
        • Schurgers L.J.
        • Aebert H.
        • Vermeer C.
        • Bultmann B.
        • Janzen J.
        Oral anticoagulant treatment: friend or foe in cardiovascular disease?.
        Blood. 2004; 104: 3231-3232
        • Spronk H.M.
        • Soute B.A.
        • Schurgers L.J.
        • Thijssen H.H.
        • De Mey J.G.
        • Vermeer C.
        Tissue-specific utilization of menaquinone-4 results in the prevention of arterial calcification in warfarin-treated rats.
        J Vasc Res. 2003; 40: 531-537
        • Erkkila A.T.
        • Booth S.L.
        • Hu F.B.
        • et al.
        Phylloquinone intake as a marker for coronary heart disease risk but not stroke in women.
        Eur J Clin Nutr. 2005; 59: 196-204
        • Erkkila A.T.
        • Booth S.L.
        • Hu F.B.
        • Jacques P.F.
        • Lichtenstein A.H.
        Phylloquinone intake and risk of cardiovascular diseases in men.
        Nutr Metab Cardiovasc Dis. 2007; 17: 58-62
        • Geleijnse J.M.
        • Vermeer C.
        • Grobbee D.E.
        • et al.
        Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study.
        J Nutr. 2004; 134: 3100-3105
        • Sabour S.
        • Franx A.
        • Rutten A.
        • et al.
        High blood pressure in pregnancy and coronary calcification.
        Hypertension. 2007; 49: 813-817
        • Ocke M.C.
        • Bueno-de-Mesquita H.B.
        • Goddijn H.E.
        • et al.
        The Dutch EPIC food frequency questionnaire. I. Description of the questionnaire, and relative validity and reproducibility for food groups.
        Int J Epidemiol. 1997; 26: S37-S48
        • Ocke M.C.
        • Bueno-de-Mesquita H.B.
        • Pols M.A.
        • Smit H.A.
        • Van Staveren W.A.
        • Kromhout D.
        The Dutch EPIC food frequency questionnaire. II. Relative validity and reproducibility for nutrients.
        Int J Epidemiol. 1997; 26: S49-S58
        • Suttie J.
        Vitamin K and human nutrition.
        J Am Diet Assoc. 1992; 92: 585-590
        • Shearer M.J.
        • Bach A.
        • Kohlmeier M.
        Chemistry, nutritional sources, tissue distribution and metabolism of vitamin K with special reference to bone health.
        J Nutr. 1996; 126: 1181S-1186S
        • Booth S.L.
        • Madabushi H.T.
        • Davidson K.W.
        • Sadowski J.A.
        Tea and coffee brews are not dietary sources of vitamin K-1 (phylloquinone).
        J Am Diet Assoc. 1995; 95: 82-83
        • Ferland G.
        • MacDonald D.L.
        • Sadowski J.A.
        Development of a diet low in vitamin K-1 (phylloquinone).
        J Am Diet Assoc. 1992; 92: 593-597
        • Booth S.L.
        • Sadowski J.A.
        • Weihrauch J.L.
        • Ferland G.
        Vitamin K-1 (phylloquinone) content of foods: a provisional table.
        J Food Comp Anal. 1993; 6: 109-120
        • Agatston A.S.
        • Janowitz W.R.
        • Hildner F.J.
        • Zusmer N.R.
        • Viamonte Jr., M.
        • Detrano R.
        Quantification of coronary artery calcium using ultrafast computed tomography.
        J Am Coll Cardiol. 1990; 15: 827-832
        • Sabour S.
        • Rutten A.
        • van der Schouw Y.T.
        • et al.
        Inter-scan reproducibility of coronary calcium measurement using multi detector-row computed tomography (MDCT).
        Eur J Epidemiol. 2007; 22: 235-243
        • Spiegelman D.
        • Hertzmark E.
        Easy SAS calculations for risk or prevalence ratios and differences.
        Am J Epidemiol. 2005; 162: 199-200
        • Rumberger J.A.
        • Simons D.B.
        • Fitzpatrick L.A.
        • Sheedy P.F.
        • Schwartz R.S.
        Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area. A histopathologic correlative study.
        Circulation. 1995; 92: 2157-2162
        • Reddy J.
        • Bilezikian J.P.
        • Smith S.J.
        • Mosca L.
        Reduced bone mineral density is associated with breast arterial calcification.
        J Clin Endocrinol Metab. 2008; 93: 208-211
      1. Gast GCM, de Roos NM, Sluijs I, et al. A high menaquinone but not phylloquinone intake reduces the incidence of coronary heart disease in women, unpublished.

        • Schurgers L.J.
        • Vermeer C.
        Differential lipoprotein transport pathways of K-vitamins in healthy subjects.
        Biochim Biophys Acta. 2002; 1570: 27-32
        • Berkner K.L.
        • Runge K.W.
        The physiology of vitamin K nutriture and vitamin K-dependent protein function in atherosclerosis.
        J Thromb Haemost. 2004; 2: 2118-2132
        • Thijssen H.H.
        • Drittij-Reijnders M.J.
        Vitamin K distribution in rat tissues: dietary phylloquinone is a source of tissue menaquinone-4.
        Br J Nutr. 1994; 72: 415-425
        • Schurgers L.J.
        • Teunissen K.J.
        • Hamulyak K.
        • Knapen M.H.
        • Vik H.
        • Vermeer C.
        Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7.
        Blood. 2007; 109: 3279-3283
        • Cockayne S.
        • Adamson J.
        • Lanham-New S.
        • Shearer M.J.
        • Gilbody S.
        • Torgerson D.J.
        Vitamin K and the prevention of fractures: systematic review and meta-analysis of randomized controlled trials.
        Arch Intern Med. 2006; 166: 1256-1261