Vitamin K and vascular calcification

In 1929 a Danish Biochemist work on the cholesterol metabolism in chicken fed on a low-fat diet, free from sterols lead to the discovery of Vitamin K. He noticed subcutaneous and intramuscular hematomas in the chicken fed on a low-fat diet for 6 weeks or more. When he re-fed them fatty food the hemorrhagic effect was not reversed. Instead, he fed them Hempseed and the hemorrhagic effect got reversed. So, he called this antihemorrhagic factor. In German, it is known as Koagulation–vitamin. It has got its name Vitamin K from Koagulation. Vitamin K1 (phylloquinone) is from plant-based foods and Vitamin K2 (MK7 menaquinone) is from other sources. Henrik Dam and Edward Doisy received Nobel prize 1943 for their discovery of Vitamin K.

Vitamin K2 is linked with vascular calcification. Vascular smooth muscle cells produce Matrix Gla Protein (MGP). Vitamin K acts as a cofactor for gamma-carboxylation of MGP after which it inhibits the vascular calcification. When the MGP gene was deleted from the rats there was complete arterial calcification and they died in 6 weeks. Similarly, when rats were treated with Warfarin, they developed vascular calcification. Treating them with high doses of Vitamin K, it resulted in reversal of the calcification.

It was observed that high doses of Vitamin K will reduce the arterial stiffness and increase vascular elasticity. This mechanical effect will improve cardiovascular functions. In a recent paper published, M K Shea et al 2020 (nearly 4000 patients) observed a relation between the all-cause mortality and serum levels of Vitamin K. When serum levels were lower than 0.5 nmol/ L, the all-cause mortality was 19% higher than the patients with higher levels (> 1.0 nmol/ L) of serum vitamin K in 13 years follow up. But surprisingly there was no such association noted between cardiovascular disease and serum levels of vitamin K.

We need more studies to understand the reversal effect on vascular calcification and improvement of haemodynamic effects in the calcified vessels. Currently we are treating diabetic patients with tibial arterial disease with guidewires, balloons and stents in addition to the statins, antiplatelets, CE/ARBs and antidiabetics. Vitamin K2 (menaquinone) induced correction of vascular calcification is an additional benefit to the patients, but this needs to be proved in more number of robust trials.  

M Kyla Shea, Kathryn Barger, Sarah L Booth, Gregory Matuszek, Mary Cushman, Emelia J Benjamin, Stephen B Kritchevsky, Daniel E Weiner. Vitamin K status, cardiovascular disease, and all-cause mortality: a participant-level meta-analysis of 3 US cohorts. The American Journal of Clinical Nutrition, Volume 111, Issue 6, June 2020, Pages 1170–1177,