Elsevier

Atherosclerosis

Volume 203, Issue 2, April 2009, Pages 489-493
Atherosclerosis

High dietary menaquinone intake is associated with reduced coronary calcification

https://doi.org/10.1016/j.atherosclerosis.2008.07.010Get rights and content

Abstract

Background

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.

Methods

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.

Results

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).

Conclusion

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.

Introduction

Vitamin K is a fat-soluble vitamin that occurs in two biologically active forms; vitamin K1 (phylloquinone) and vitamin K2 (menaquinone; MK-4 through MK-10). Phylloquinone, the most common form, is present in green, leafy vegetables and certain vegetable oils [1], while menaquinones mostly occur in animal products like meat, eggs, and cheese [2]. Vitamin K functions as a cofactor in the gamma-glutamyl carboxylation of certain glutamic acid (Gla) residues of vitamin K-dependent proteins for their activation [3]. Such Gla-proteins include coagulation factors prothrombin, Factor VII, IX, and X [3]. Phylloquinone is effectively cleared from the circulation by the liver, the main site for clotting factor synthesis and is therefore thought to be particularly important for blood coagulation [4].

Vitamin K also functions as a cofactor for activation of Gla-proteins in extrahepatic tissues such as bone (osteocalcin) and the vessel wall (matrix Gla-protein) (MGP). Matrix Gla-protein is a powerful inhibitor of vascular calcification [5]. Vascular vitamin K deficiency could therefore increase the amount of undercarboxylated, non-functional MGP and lead to increased calcium deposition. Coronary calcification is a strong, independent predictor of coronary events [6] and this is an actively regulated process [7] that could be regressed by vitamin K, carbonic anhydrase, and bisphosphonates [8]. Vitamin K deficiency could therefore lead to cardiovascular disease (CVD) [3], [9]. Indeed, MGP-knock out mice develop severe coronary calcification [10]. In addition, the drug warfarin, inhibiting Gla residue formation, was shown to increase coronary calcification in rats and humans [11], [12]. Studies showed that vitamin K rich diets could prevent these effects in warfarin-treated rats [13], but these effects on coronary calcification were particularly due to menaquinone and not phylloquinone [13].

Results from human, observational studies investigating relations between vitamin K intake and cardiovascular diseases are inconsistent. The Nurses’ Health Study showed a modest risk reduction of coronary heart disease (CHD) for high phylloquinone intakes [14], while no significant associations were observed in the Health Professionals Follow-up Study and the Rotterdam Study [15], [16]. On the other hand, in the Rotterdam Study a strong inverse association between menaquinone intake and coronary heart disease mortality and severe aortic calcification was observed [16]. These inconsistencies may relate to different effects of phylloquinone and menaquinone on coronary calcification. So far, only the Rotterdam Study investigated both phylloquinone and menaquinone intake, while relations of different menaquinone subtypes with coronary calcification have not been studied. We investigated the association between dietary intake of both phylloquinone and menaquinone, including its subtypes, with coronary calcification in a cross-sectional study of 564 Dutch women.

Section snippets

Study population

We used data from a cross-sectional study among 564 post-menopausal healthy women as has been detailed earlier [17]. In short, these women were selected from participants of the PROSPECT study, one of the two Dutch cohorts participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). In PROSPECT 17,357 healthy participants of a nationwide population-based breast-cancer screening programme, aged 49–70 years, living in Utrecht and surroundings were enrolled between

Results

Table 1 shows the baseline characteristics of our study population. Sixty-two percent of the women had coronary calcification based on 1.5-mm thick slices. Higher intake of menaquinone was associated with increasing educational attainment, prevalence of diabetes and energy-adjusted intakes of protein and calcium.

Table 2 shows associations of quartiles of phylloquinone and menaquinone with coronary calcification. Intake of phylloquinone was not associated (ptrend = 0.09) with increased coronary

Discussion

This study shows that high intakes of menaquinone are associated with decreased coronary calcification. Intake of phylloquinone, however, was not associated with coronary calcification.

Strengths of this study include the complete information on cardiovascular risk factors and measurement of coronary calcium data. Nevertheless, certain limitations should be addressed. The main limitation of this study is the relative validity of our FFQ to estimate intake of vitamin K. Relative validity of our

Conflict of interest

None declared.

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