K Deficiency Linked to Increased CVD Risk

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AHA publishes 11-year study drawing a clear line between K deficiency and increase risk of CHD.

Arteriosclerosis, Thrombosis, and Vascular Biology, the journal for the American Heart Association, just published an 11-year study that draws a clear line between vitamin K deficiency and an increased risk of coronary heart disease.[1]

To date, 19 Vitamin K–dependent proteins (VKDPs) have been described, with important roles in coagulation, platelet function, and vascular biology. Produced in an inactive form, all VKDPs obtain biological activity through the conversion of a glutamic acid residue into glutamate, a complex process requiring vitamin K.


“Western populations are not afflicted with blood diseases because of a vitamin K1 deficiency. Clearly we get enough vitamin K in our diets to effectively coagulate blood; however, our total K status outside the liver – particularly Vitamin K2 status – plays an important role in maintaining and supporting our heart and bone health,” says Dr. Hogne Vik, chief medical officer with ex-NattoPharma, world leader in vitamin K2 research and development and exclusive global supplier of MenaQ7® Vitamin K2 as MK-7.


The authors investigated whether VKDP activity was associated with cardiovascular disease in a random sample of 709 multi-ethnic adults free of cardiovascular disease drawn from the Multi-Ethnic Study of Atherosclerosis (MESA), who were followed up with for 11 years. The circulating des-γ-carboxy prothrombin (DCP) concentrations were measured to indicate lower VKDP activity. [Note: des-γ-carboxy prothrombin (DCP) is also known as protein induced by vitamin K absence/antagonist-II (PIVKA-II).]

Correlation between VKDP and cardiovascular survival risk

The results showed that ischemic cardiovascular disease incidence rates were higher with greater concentration of DCP. Further, that subjects with the lowest activity of VKDP revealed two-times higher risk of cardiovascular events than people with the highest activity of VKDP.


“The study showed that a total of 84% of the cohort participants had a DCP >2 ng/mL (considered the threshold for VKDP inactivity), so the majority of participants were vitamin K subdeficient. Moreover, it has been shown that participants with higher DCP concentrations (i.e., lower VKDP activity) tended to be older,” continues Dr. Vik, adding that a similar finding was shown by E. Theuwissen et al. (2014)[2]: that adults above 40 years showed the largest tissue-specific vitamin deficiency after children.


Further, there are other studies where VKDP correlates with cardiovascular survival risk:
• Schlieper et al. 2011[3] showed that lower levels of circulating dp-cMGP may serve a s predictor of mortality in dialysis patients.
• Mayer et al. 2016[4] concluded that concomitant abnormality of uncarboxylated MGP leads to about a two-fold increase of the relative mortality risk in chronic patients with vascular disease.
• Liu et al. 2015[5] showed that higher dp-ucMGP predicts total non-cancer and cardiovascular mortality, but lower coronary risk.


“Researchers have identified populations that consume large amounts of Vitamins K1 and K2 have better heart and bone health outcomes. Intervention studies have also demonstrated that adding vitamin K reduces cardiovascular risk factors,” concludes Dr. Vik. “This is yet another important study showing that a lack of K vitamins, particularly vitamin K2, results in increased cardiovascular risk. This finding should raise awareness of this important class of proteins as a potential contributor to cardiovascular disease protection.”


1 Danzinger J, Young RL, Shea MK, Tracy RP, Ix JH, Jenny NS, Mukamal KJ. Vitmain K-Dependent Protein Activity and Incident Ischemic Cardiovascular Disease: The Multi-Ethnic Study of Atherosclerosis. Athero, Thrombo, and Vasc Bio. 2016;36:1037–1042.
2 Theuwissen et al. Vitamin K status in healthy volunteers. Food & Function. 2014;5(2):229-34.
3 Schlieper et al. Circulating Nonphosphorylated Carboxylated Matrix Gla Protein Predicts Survival in ESRD . J Am Soc Nephrol 2011; 22: 387–395.
4 Mayer et al. The abnormal status of uncarboxylated matrix Gla protein species represents an additional mortality risk in heart failure patients with vascular disease. International Journal of Cardiology 203 (2016) 916–922.
5Liu YP et al. Inactive matrix Gla protein is causally related to adverse health outcomes: a Mendelian randomization study in a Flemish population. Hypertension. 2015 Feb;65(2):463-70.


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