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.

Vitamin K is a cofactor in the production of blood coagulation factors (in the liver), osteocalcin (in bone), and matrix Gla protein (cartilage and vessel wall). Accumulating evidence suggests that for optimal bone and vascular health, relatively high intakes of vitamin K are required. The synthetic short-chain vitamin K 1 is commonly used in food supplements, but recently the natural long-chain menaquinone-7 (MK-7) has also become available as an over-the-counter (OTC) supplement. The purpose of this paper was to compare in healthy volunteers the absorption and efficacy of K 1 and MK-7. Serum vitamin K species were used as a marker for absorption and osteocalcin carboxylation as a marker for activity. Both K 1 and MK-7 were absorbed well, with peak serum concentrations at 4 hours after intake. A major difference between the 2 vitamin K species is the very long half-life time of MK-7, resulting in much more stable serum levels, and accumulation of MK-7 to higher levels (7-to 8-fold) during prolonged intake. MK-7 induced more complete carboxylation of osteocalcin, and hematologists should be aware that preparations supplying 50 g/d or more of MK-7 may interfere with oral anticoagulant treatment in a clinically relevant way.

Objective-Matrix ␥-carboxyglutamic acid (Gla) protein (MGP), a vitamin K-dependent protein, is a potent in vivo inhibitor of arterial calcification. We hypothesized that low endogenous production of MGP and impaired carboxylation of MGP may contribute to the development or the progression of vascular disease. Methods and Results-Novel conformation-specific antibodies against MGP were used for immunohistochemistry of healthy and sclerotic arteries. In healthy arteries, MGP was mainly displayed around the elastin fibers in the tunica media. The staining colocalized with that for carboxylated MGP, whereas undercarboxylated MGP (ucMGP) was not detected. In atherosclerotic arteries, ucMGP was found in the intima, where it was associated with vesicular structures. In Mönckeberg's sclerosis of the media, ucMGP was localized around all areas of calcification. The results indicate that ucMGP is strongly associated with vascular calcification of different etiologies. In a separate study, serum MGP concentrations in a cohort of 172 subjects who had undergone percutaneous coronary intervention were significantly reduced compared with an apparently healthy population. Key Words: matrix Gla protein (MGP) Ⅲ vitamin K Ⅲ calcification Ⅲ atherosclerosis T he extracellular fluids in the human body contain calcium and phosphate in high concentrations, even exceeding the solubility product for spontaneous precipitation. 1 However, physiological calcification is restricted to bone and teeth, whereas soft tissue calcification is regarded as pathological. Vascular calcification can occur at 3 anatomic sites: the intima where it is associated with atherosclerosis, the tunica media, and the heart valves. Huang et al showed that coronary artery calcification does not significantly affect stability of atheroma, 2 and the involvement of calcium salt accretion on cardiovascular disease is not known yet. However, overall vascular calcification is regarded as one of the major complications of cardiovascular disease and is an independent risk factor for myocardial infarction (MI) and cardiac death. [3][4][5][6] Therefore, prevention of vascular calcification is a prerequisite for human health. Inhibition of calcification is regarded presently as an active process in which a variety of proteins are involved throughout the body. 7 In the vasculature, a major calcification inhibitory factor is matrix ␥-carboxyglutamic acid (Gla) protein (MGP), a vitamin K-dependent protein synthesized by vascular smooth muscle cells (VSMCs). 8,9 Its 5 Gla residues are formed in a post-translational carboxylation reaction in which vitamin K functions as an essential cofactor. 10,11 MGP in its carboxylated form will be designated here as GlaMGP. The presence of the Gla residues is critical for MGP function, and undercarboxylated, inactive species of MGP (designated as GluMGP) are formed during inadequate vitamin K status or as a result of vitamin K antagonists. In animal models, it was demonstrated that impaired MGP synthesis 12,13 as well as treatment with vitamin ...

Summary Vitamin K mediates the synthesis of proteins regulating bone metabolism. We have tested whether high vitamin K 2 intake promotes bone mineral density and bone strength. Results showed that K 2 improved BMC and femoral neck width, but not DXA-BMD. Hence high vitamin K 2 intake may contribute to preventing postmenopausal bone loss. Introduction Vitamin K is involved in the synthesis of several proteins in bone. The importance of K vitamins for optimal bone health has been suggested by populationbased studies, but intervention studies with DXA-BMD as a clinical endpoint have shown contradicting results. Unlike BMC, DXA-BMD does not take into account the geometry (size, thickness) of bone, which has an independent contribution to bone strength and fracture risk. Here we have tested whether BMC and femoral neck width are affected by high vitamin K intake. Methods A randomized clinical intervention study among 325 postmenopausal women receiving either placebo or 45 mg/day of vitamin K 2 (MK-4, menatetrenone) during three years. BMC and hip geometry were assessed by DXA. Bone strength indices were calculated from DXA-BMD, femoral neck width (FNW) and hip axis length (HAL).Results K 2 did not affect the DXA-BMD, but BMC and the FNW had increased relative to placebo. In the K 2 -treated group hip bone strength remained unchanged during the 3-year intervention period, whereas in the placebo group bone strength decreased significantly. Conclusions Vitamin K 2 helps maintaining bone strength at the site of the femoral neck in postmenopausal women by improving BMC and FNW, whereas it has little effect on DXA-BMD.