• VITAMIN K
• NUTRITION
• BLOOD COAGULATION
• BONE METABOLISM
• VASCULAR BIOLOGY
• K1 vs K2

 

With the generation of the MGP knock-out mouse, which exhibits extensive and lethal calcification and cartilaginous metaplasia of the media of all elastic arteries, the role of vitamin K and vitamin K-dependent proteins in vascular calcification has gained substantial attention. Several Gla-proteins have been isolated from the calcified atherosclerotic plaques. The finding of different proteins containing Gla in bone and ectopic calcification including hardened plaque suggests that certain calcium-binding proteins containing this amino acid may be of importance in the mineralization process. Indeed, on a level of gene expression, MGP was found to be up-regulated in vivo and in vitro in association with calcification. The role of vitamin K in atherosclerosis was recently investigated. In these studies the authors screened for the occurrence of calcifications in the abdominal aorta in more then hundred of apparently healthy volunteers between 60 and 80 years of age. They also recorded the nutritional habits and preferences with the aid of food frequency questionnaires. The subjects were classified into four categories according to the degree of aortic calcification, ranging from no visible calcification to severe calcifications. It turned out that subjects with severe atherosclerotic calcifications had a significantly lower long-term vitamin K intake, a higher amount of undercarboxylated bone Gla-protein (osteocalcin), and lower bone mass. These data suggest that a biochemical vitamin K-deficiency is common in atherosclerotic subjects.
On the basis of these data we propose to re-define vitamin K-deficiency as follows. Mild vitamin K deficiency is a condition in which the circulating osteocalcin is significantly undercarboxylated, whereas the blood coagulation factor prothrombin still contains a functional Gla domain. Severe vitamin K deficiency may than be regarded as a condition in which descarboxyprothrombin is detectable in the circulation.

In hypercholesterolemic rabbits it has been shown that high doses of vitamin K2 decrease the circulating cholesterol concentrations, and suppress the progression of atherosclerotic plaques, intima thickening and pulmonary atherosclerosis. Moreover, data from our group showed that in a rat model for arterial calcification vitamin K2 completely prevented calcification, whereas vitamin K1 had little effect. In a human cross sectional study called the Rotterdam study, the vitamin K1 and vitamin K2 intake was measured and subjects were subdivided in tertiles according to their vitamin K dietary intake. It was shown that people in the tertile with the highest intake of K2 had a 50% reduced risk on developing arterial calcifications and a 50% reduced risk of dying from heart disease. This effect was not found for K-1.

Figure: Vitamin K2 intake and cardiovascular disease.

Despite these promising data only one vitamin K intervention trial has been published in which the vascular condition was used as a clinical endpoint. The 3-year study was performed among 188 postmenopausal women, a group known to be at risk for rapid decay of the vascular condition. The elastic properties of the common carotid artery were recorded during the study using an ultrasound technique. It was demonstrated that a supplement providing 1 mg/day of vitamin K1 completely abolished age related arterial stiffening, whereas in the placebo group the elastic properties had decreased by 13% during the study period.

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