Vitamin K may reverse arterial calcification - study

Atherosclerosis, known as hardening or furring of the arteries is a key risk factor for cardiovascular disease, the cause of over 50 per cent of deaths in Europe and the US and estimated to cost the economy … "Given that arterial calcifications are predictive of cardiovascular events, regression of arterial calcification may help reduce to reduce the risk of death in people with chronic kidney disease and coronary artery disease," wrote lead author Leon Schurgers from VitaK at Maastricht University.

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 per cent of the vitamin K in a typical Western diet; and menaquinones (vitamins K2), which make up about 10 per cent of Western vitamin K consumption and can be synthesised 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.

MK-4 is distinct from other MKs because it is not a major constituent of the spectrum of MKs produced by gut microflora, but can be derived from K1 in vivo .

A synthetic form of vitamin K, known as K3, does exist but is not recommended for human consumption.

Writing in the current issue of the journal Blood , Schurgers and co-workers report the findings of their experiments using 10-week old male Wistar Kyoto rats.

The animals were fed a diet containing the blood thinner warfarin (3 mg/g food) and low-dose vitamin K1 (1.5 mg/g food) to induce calcium build-up in the blood vessels for six weeks.

Warfarin is known to promote calcium accumulations in the arteries by inactivating a protein called matrix Gla protein (MGP), a regulator of calcium crystal formation in the circulatory system.

MGP is a vitamin K-dependent protein - meaning vitamin K is required to activate this important protein Subsequently, the animals were divided into four groups, the first to continue the warfarin plus K1 diet, while the other three stopped warfarin intake.

These three warfarin-free groups consumed the control diet supplemented with normal dose K1 (0.5 micrograms/g food), high-dose K1 (100 micrograms/g food) or vitamin K2 in the form of menaquinone-4 (100 micrograms/g food) for another six weeks.

The researchers report that, during the initial six-weeks of warfarin plus K1 supplementation, all animals showed a significant increase in their arterial calcium levels, and this was found to continue for the normal dose K1 group after warfarin administration had stopped.

"In contrast," the researcher state "high-vitamin K intake (both K1 and K2) not only blocked the progress of further calcium accumulation but also lead to a greater than 37 per cent reduction of previously accumulated arterial calcium precipitates within six weeks."

Moreover, MGP was found to be present as the inactive form in the normal dose K1 group, while significant levels of the active from were observed for both high-dose K1 and K2 supplemented groups.

"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," stated the researchers.

"Although it is well known that MGP is important in the prevention of calcification, its contribution to regression of arterial calcification is a novel finding."

Schurgers stated that the effects of increased vitamin K intake needed to be investigated in humans.

"Our study shows that in an animal model vitamin K can actually regress preformed calcifications.

The health implications for humans are significant, and we have previously published research showing that the highest vitamin K2 intake from dietary sources has been linked to significant reductions in vascular calcification compared to those with the lowest K2 intake," he said.

Source: Blood 1 April 2007, Volume 109, Number 7, Pages 2823-2831 "Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats" Authors: L.J. Schurgers, H.M.H. Spronk, B.A.M. Soute, P.M. Schiffers, J.G.R. DeMey, C. Vermeer