A new publication by Schurgers et al., titled Matrix Gla-protein: The calcification inhibitor in need of vitamin K elucidates the pivotal importance of vitamin K in the activation of Matrix Gla Protein (MGP), the most potent inhibitor of vascular calcification known.
The Role of MGP inhibiting Vascular Calcification
This new paper, authored by researchers at VitaK, the largest institute dedicated to vitamin K research and part of the University of Maastricht, discusses the recent discoveries associated with MGP and its involvement in the regulation of calcium accumulation. MGP functions to keep the arteries free from calcifications, thereby keeping them flexible and elastic.
“MGP’s pivotal importance for vascular health is demonstrated by the fact that there seems to be no effective alternative mechanism for calcification inhibition in the vasculature,” explained Dr Schurgers. “Importantly, what we have seen in population studies is that the form of vitamin K indicated for a decrease in calcification is natural vitamin K2, the menaquinones, and particularly the longer menaquinones called MK-7, 8 and 9.”
To perform its inhibitory function MGP has to be activated by vitamin K during a so-called carboxylation reaction. In the absence of vitamin K the biological function of MGP is impaired and species remain “undercarboxylated”( i.e. inactive). Impairment of MGP will cause arterial calcifications, which is currently regarded as the strongest predictor of cardiovascular events.
Evidence for the importance of carboxylation of the glutamic acid residues to become gamma-carboxy glutamic acid for optimal MGP function was provided by Murshed et al., who used mice to demonstrate that only carboxylated MGP exhibits anti-mineralization properties. Further research showed that high vitamin K intake resulted in improved MGP carboxylation and regression of calcification. Therefore, an optimal vitamin K intake is important to maintain the risk and rate of calcification as low as possible.
MGP as A Marker for Cardio Vascular Disease
Calcification is now regarded as an actively regulated process, and there is general consensus that the inhibitors of calcification such as MGP play an important role. Our body is supersaturated with calcium and phosphate, still we do not calcify all over the place. The balance between the calcium and phosphate product and the inhibitors is tightly balanced.
The measurement of MGP as biomarker to reflect early signs of vascular disease could be of great importance. Both cardiovascular calcification and MGP activity are directly correlated with vitamin K2 intake. A new blood test to measure the amount of inactive MGP in the circulation is currently under development. The fraction of MGP circulating in the bloodstream mirrors MGP produced in the tissues, and the measurement of undercarboxylated MGP seems to be a promising biomarker for cardiovascular calcification detection.
Chronic kidney disease (CKD) patients and the risk of CVD
Calcification is widespread in the apparently healthy elderly population, but also in patients suffering from CKD, diabetes and atherosclerosis. CKD patients have the highest rate of arterial calcification, and cardiovascular mortality is 20-fold higher when compared to the healthy population. Additionally, moderate to severe vascular calcifications are found in 60-80% of patients on hemodialysis, while it was shown that vitamin K-status in CKD patients is low, with 30% of the haemodialysis patients having sub-clinical vitamin K-deficiency. Therefore the possibility of vitamin K supplementation to reduce the risk for cardiovascular events should be considered.
Anticoagulation therapy with Vitamin K antagonists such as warfarin are regularly prescribed in patients with cardiovascular disease. Warfarin is used to treat atrial fibrillation or venous thrombosis but the downside is that it further reduces the already low vitamin K-status in these patients. Together with the known high levels of undercarboxylated MGP present in calcified areas, these data are suggestive for high vitamin K intake as a treatment option for people suffering from cardiovascular calcification. Initial clinical studies in dialysis patients are in progress.
Forms of K vitamins
Two naturally-occurring forms of vitamin K have been identified, and these are designated as vitamin K1 and K2. Because of the difference in their structure, various K1 and K2 have different bioactivity, efficacy and bioavailability.
Vitamin K1 is found in green leafy vegetables, such as broccoli, spinach and kale. Vitamin K1 is poorly absorbed as it is tighly bound to the chloroplast membrane. Vitamin K2 is from bacterial origin, and its absorption is nearly complete. Moreover, due to its lipophilicity it has a very long half life in the circulation, giving the body 24 hours supply of vitamin K2. Natural Vitamin K2 is the source of vitamin K preferred by all tissues including bone, cartilage and soft tissues. Vitamin K2 prevents arterial calcium accumulation that has been found contributory to the development of cardiovascular disorders. Vitamin K2 plays an important role in maintaining health of bones and vessels.
A study published in the “Journal of Nutrition” called the “Rotterdam Study” (in 2004) found increased intake of Vitamin K2 from dietary sources significantly reducing the incidence of arterial calcification and the risk of Cardiovascular heart disease mortality by 50% as compared to low dietary vitamin K2 intake. In this study, vitamin K1 had no effect at all.
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