The relationship between vitamin K and peripheral arterial disease (Vissers LE et al.)

Results of a long-term observational study that explored the interdependence of high dietary intake of phylloquinone (Vitamin K1) and menaquinones (Vitamin K2) and the reduced risk of peripheral arterial disease (PAD) have recently been published in Atherosclerosis.

The methodology applied to this study depended on investigating the association between intake of Vitamin K1 and Vitamin K2 with PAD in a prospective cohort with 36,629 participants. The researchers examined this association in general population of men and women, and explored effect modification through cardiovascular risk factors such as sex, hypertension, and diabetes. Occurrence of PAD was obtained by linkage to national registries. Baseline intake of K1 and K2  was estimated using a validated food-­frequency questionnaire. Multivariate Cox regression was used to estimate adjusted hazard ratio’s for the association. During 12.1 years of follow-up, the researchers documented 489 incident cases of PAD.

This study showed that menaquinones intake was associated with a reduced risk of PAD with a hazard ratio (HR) of 0.71, 95% CI; 0.53­0.95 for the highest versus lowest quartile. The researchers observed a stronger association (p interaction 0.0001) in participants with hypertension (HR 0.59; 95% CI 0.39­0.87) or diabetes (HR 0.56; 95% CI 0.18­1.91), though confidence intervals were wide in the small (n = 530) diabetes stratum. Phylloquinone intake was not associated with PAD risk.

The authors explained that: “The different associations observed for phylloquinone and menaquinones may be explained by differences in bioavailability or metabolism. Phylloquinone predominantly serves as a cofactor for coagulation factors, because the triacylglycerol-rich lipoprotein fraction that carries phylloquinone is mainly cleared by the liver. Menaquinones, on the other hand, are not only transported by triacylglycol-rich lipoprotein, but also by low-density lipoprotein which transports it to extra-hepatic tissues such as the vascular wall. Once in the vessel wall, menaquinones also have a longer half-time than phylloquinone, thus leading to a larger extrahepatic efficacy of menaquinones.”

“The results of this study clearly showed that a high intake of Vitamin K2 was significantly associated with a reduced risk of PAD, at least in hypertensive participants,” says Dr. Katarzyna Maresz, president of the International Science and Health Foundation. “A high menaquinone dietary intake may be associated with a reduced risk of PAD in participants with diabetes as well, though no statistically significant results were observed. Whereas high phylloquinone intake does not seem associated with PAD risk.”


Vissers LET, Dalmeijer GW, Boer JMA, Verschuren WMM, van der Schouw YT, Beulens JWJ. The relationship between vitamin K and peripheral arterial disease. Atherosclerosis 252 (2016) 15-20. DOI:

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