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Nutritional Epidemiology

Dietary Intake of Menaquinone Is Associated with a Reduced Risk of Coronary Heart Disease: The Rotterdam Study¹

Johanna M. Geleijnse^*,, Cees Vermeer^**, Diederick E. Grobbee, Leon J. Schurgers^**, Marjo H. J. Knapen^**, Irene M. van der Meer^*, Albert Hofman^* and Jacqueline C. M. Witteman^*,2

^* Department of Epidemiology & Biostatistics, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands; Division of Human Nutrition, Wageningen University, Wageningen, The Netherlands; ^** Department of Biochemistry, Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands; and Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands

²To whom correspondence should be addressed. E-mail: j.witteman{at}erasmusmc.nl.

Vitamin K–dependent proteins, including matrix Gla-protein, have been shown to inhibit vascular calcification. Activation of these proteins via carboxylation depends on the availability of vitamin K. We examined whether dietary intake of phylloquinone (vitamin K-1) and menaquinone (vitamin K-2) were related to aortic calcification and coronary heart disease (CHD) in the population-based Rotterdam Study. The analysis included 4807 subjects with dietary data and no history of myocardial infarction at baseline (1990–1993) who were followed until January 1, 2000. The risk of incident CHD, all-cause mortality, and aortic atherosclerosis was studied in tertiles of energy-adjusted vitamin K intake after adjustment for age, gender, BMI, smoking, diabetes, education, and dietary factors. The relative risk (RR) of CHD mortality was reduced in the mid and upper tertiles of dietary menaquinone compared to the lower tertile [RR = 0.73 (95% CI: 0.45, 1.17) and 0.43 (0.24, 0.77), respectively]. Intake of menaquinone was also inversely related to all-cause mortality [RR = 0.91 (0.75, 1.09) and 0.74 (0.59, 0.92), respectively] and severe aortic calcification [odds ratio of 0.71 (0.50, 1.00) and 0.48 (0.32, 0.71), respectively]. Phylloquinone intake was not related to any of the outcomes. These findings suggest that an adequate intake of menaquinone could be important for CHD prevention.

KEY WORDS: • phylloquinone • menaquinone • vitamin K • coronary heart disease • population-based study

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