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Vitamin K2 Reverses Artery Hardening by 40%

A high-dose vitamin K supplement reduced calcium precipitates associated with hardening of the arteries by 37 percent in rats, scientists from The Netherlands have reported.

If the results can be reproduced in humans, high-dose vitamin K could have potential clinical implications for reducing arterial calcification, which is an important independent risk factor for the development of cardiovascular disease (CVD). “High vitamin K intake not only prevents calcification, but even regresses arterial calcifications,” lead researcher Leon Schurgers from Maastricht University said.

There are two main forms of vitamin K: phylloquinone, also known as phytonadione, (vitamin K1) which is found in green leafy vegetables such as lettuce, broccoli and spinach, and makes up about 90 percent of the vitamin K in a typical Western diet; and menaquinones (vitamins K2), which make up about 10 percent of Western vitamin K consumption and can be synthesized in the gut by microflora. Menaquinones (MK-n: with the n determined by the number of prenyl side chains) can also be found in the diet; MK-4 can be found in animal meat, MK-7, MK-8, and MK-9 are found in fermented food products like cheese, and natto is a rich source of MK-7.

The new study is said to be the first in rats to show that arterial calcification (calcium build-up that produces hardening) and the subsequent decreased elasticity of the blood vessels may be reversible by high vitamin K intake.

"The medical community used to believe that calcification passively occurred in the end stages of cardiovascular disease," said Schurgers. "However, in the last 10 years we have learned that Vitamin K-dependent proteins are directly involved in the inhibition of vascular calcification, and that Vitamin K2 is necessary to activate these proteins. This study demonstrates a significant potential role for Vitamin K2 in cardiovascular health."

In the new study, the researchers induced arterial hardening in rats by interfering with vitamin K-metabolism, by adding the vitamin K-antagonist warfarin to the diets. Vitamin K is reported to act on a protein called matrix Gla-Protein (MGP), said to be the strongest inhibitor of arterial calcification.

Initially, the rats were divided into two groups, a control group with vitamin K added to the diet, and a warfarin treated group to induce calcification. After six weeks of treatment with warfarin, the researchers report that the rats showed signs of significant arterial hardening.

The warfarin treated rats were then further divided into four groups and assigned to one of four intervention groups for a further six weeks: a standard diet plus warfarin, a standard diet plus vitamin K1 at normal dose (5 micrograms per gram of food, purchased from Sigma), a standard diet plus high-dose vitamin K1 (100 micrograms per gram of food), or the standard diet plus high-dose vitamin K2 (MK-4, 100 micrograms per gram of food, gifted from Eisai, Japan).

Schurgers and his co-workers report that during the second six week period, the calcifications in the warfarin-treated control group continued linearly, as did the calcification in the normal dose vitamin K1 group, indicating that dietary vitamin K1 intake had no effect.

However, in both high-dose groups (K1 and K2) no continued calcification occurred, but the existing hardening was found to be reversed by about 50 percent after six weeks of supplementation.

Interestingly, vitamin K2 concentration in the tissues of both groups were similar, which showed the vitamin K1 was converted into vitamin K2.

"The effect of K1 and the conversion rate of K1 to K2 was due to the extremely high dose of K vitamins used in this model,” said Schurgers. “This would be probably less in a normal diet, even with supplemental K1. In contrast, the Rotterdam study showed a significant protective benefit with Natural Vitamin K2 at just 45mcg per day, whereas K1 had no correlation at all."

The researchers also report that the reduced calcification was also accompanied by improved arterial elasticity in the high vitamin K groups to a similar level as in the control rats.

“In this study we provide evidence that warfarin-induced medial vascular calcification in rats is preventable or even reversible by high vitamin K intake, with a putative role for the vitamin K-dependent protein MGP,” wrote the researchers.

“Whether increased vitamin K intake could have such an effect in humans has to be investigated,” they concluded. “Obviously this is only possible in patients not receiving oral anticoagulant treatment.”


Arterial calcification (AC) is generally regarded as an independent risk factor for cardiovascular morbidity and mortality. Matrix Gla protein (MGP) is a potent inhibitor of AC, and its activity depends on vitamin K (VK). In rats, inactivation of MGP by treatment with the vitamin K antagonist warfarin leads to rapid calcification of the arteries. Here, we investigated whether preformed AC can be regressed by a VK-rich diet. Rats received a calcification-inducing diet containing both VK and warfarin (W&K). During a second 6-week period, animals were randomly assigned to receive either W&K (3.0 mg/g and 1.5 mg/g, subsequently), a diet containing a normal (5 microg/g) or high (100 microg/g) amount of VK (either K1 or K2). Increased aortic calcium concentration was observed in the group that continued to receive W&K and also in the group changed to the normal dose of VK and AC progressed. Both the VK-rich diets decreased the arterial calcium content by some 50%. In addition, arterial distensibility was restored by the VK-rich diet. Using MGP antibodies, local VK deficiency was demonstrated at sites of calcification. This is the first study in rats demonstrating that AC and the resulting decreased arterial distensibility are reversible by high-VK intake.


L.J. Schurgers, H.M.H. Spronk, B.A.M. Soute, P.M. Schiffers, J.G.R. DeMey, and C. Vermeer. Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats. Blood. 2007 Apr 1;109(7):2823-31.

Key concepts: Vitamin K2, artery hardening