Study shows K1 is NOT Cardio-Protective

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Vitamin K2 supports heart health through impact on Matrix Gla Protein; K1 has no effect.

Vitamin K is not a single vitamin – it is a family of vitamins comprised of vitamins K1 (phylloquinone) and K2 (menaquinone). While multiple observational studies and small-scale intervention studies suggest that high K intake is associated with improved markers for cardiovascular health – namely increased Matrix Gla protein (MGP) activation – a recent study published in Clinical Nutrition investigated the causal relationship between genetically predicted K concentrations and the risk of coronary heart disease (CHD), and found that K1 had no impact on MGP, noting that Vitamin K2 has a positive impact on cardiovascular health.


The study, “Circulating phylloquinone, inactive Matrix Gla protein and coronary heart disease risk: A two-sample Mendelian Randomization study”, examined data from three studies: the European Prospective Investigation into Cancer and Nutrition (EPIC)-CVD case cohort study, CARDIOGRAMplusC4D and the UK Biobank, resulting in 103,097 CHD cases. Genetically predicted vitamin K concentrations were measured using circulating phylloquinone and dephosphorylated uncarboxylated MGP (dp-ucMGP).


The authors wrote: “Using the genetic score for circulating phylloquinone, we found that circulating phylloquinone was not causually related to CHD risk (RR 1.00 (95%CI: 0.98; 1.04)). Lower genetically predicted dp-ucMGP concentration was associated with lower CHD risk with a RR of 0/96 (95%CI: 0.93; 0.99) for every 10 μg/L decrease in dpucMGP.

“This inconsistent result may reflect the influence of menaquinones in the association with CHD,” the authors concluded.

Different ImpACTS between vitamins K1 and K2

The paper is significant because it articulates the difference in health impact between vitamins K1 and K2, and highlights that vitamin K2 must be obtained for a cardiovascular benefit.


“While it is true that ‘improving K status’ will impact cardiovascular health, this paper helps to emphasize that all K vitamins are not the same. Ex-NattoPharma’s research has shown that vitamin K2 supplementation can halt and even regress progression of arterial stiffness, and that is accomplished through the activation of MGP,” says Eric Anderson, NattoPharma Senior Vice President of Global Marketing and Business Development. Ex-“NattoPharma has been at the forefront of making the industry aware of the research around Vitamin K2 and K-dependent proteins. Our long-term mission is to elucidate Vitamin K2’s benefits beyond Vitamin K1, as this Clinical Nutrition paper has shown, with the ultimate goal of securing a K2-specific recommended daily intake (RDI).”


Zwakenberg SR, Burgess S, Sluijis I, Weiderpass E, Beulens JWJ, van der Schouw YT. Circulating phylloquinone, inactive Matrix Gla protein and coronary heart disease risk: A two-sample Mendelian Randomization study. Clin Nutr. 2019 May 7. pii: S0261-5614(19)30200-6.


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