Can Vitamin K2 Reverse Arterial Calcification?

Wednesday, November 12, 2008
It certainly can in rats. In April 2007, Dr. Cees Vermeer and his group published a paper on the effect of vitamin K on arterial calcification (the accumulation of calcium in the arteries). As I mentioned two posts ago, arterial calcification is tightly associated with the risk of heart attack and death. Warfarin-treated rats are an established model of arterial calcification. Warfarin also causes calcification in humans. The drug is a "blood thinner" that inhibits vitamin K recycling, and inhibits the conversion of vitamin K1 (phylloquinone) to K2 MK-4 (menaquinone-4). This latter property turns out to be the critical one in the calcification process.

Rats are able to convert vitamin K1 to K2 MK-4, whereas humans don't seem to convert well. Conversion efficiency varies between species.
Dr. Vermeer's group treated rats with warfarin for 6 weeks, during which they developed extensive arterial calcification. They also received vitamin K1 to keep their blood clotting properly. At 6 weeks, the warfarin-treated rats were broken up into several groups:
  • One continued on the warfarin and K1 diet
  • One was placed on a diet containing a normal amount of K1 (no warfarin)
  • One was placed on a high K1 diet (no warfarin)
  • The last was placed on a high K2 MK-4 diet (no warfarin)
After 6 more weeks, the first two groups developed even more calcification, while the third and fourth groups lost about 40% of their arterial calcium. The high vitamin K groups also saw a decrease in cell death in the artery wall, a decrease in uncarboxylated (inactive) MGP, and an increase in arterial elasticity. They also measured the vitamin K content of aortas from each group. The group that received the 12-week warfarin treatment had a huge amount of K1 accumulation in the aorta, but no K2 MK-4. This is expected because warfarin inhibits the conversion of K1 to K2 MK-4. It's notable that when conversion to K2 was blocked, K1 alone was totally ineffective at activating MGP and preventing calcification.

In the group fed high K1 but no warfarin, there was about three times more K2 MK-4 in the aortas than K1, suggesting that they had converted it effectively and that vascular tissue selectively accumulates K2 MK-4. A high K1 intake was required for this effect, however, since the normal K1 diet did not reverse calcification. The rats fed high K2 MK-4 had only K2 MK-4 in their aortas, as expected.

What does this mean for us? K2 MK-4 appears to be the form of vitamin K that arteries prefer (although not enough is known about the longer menaquinones, such as MK-7, to rule out a possible effect). Humans don't seem to be very good at making the conversion from K1 to K2 MK-4 (at normal intakes; there are suggestions that at artificially large doses we can do it). That means we need to ensure an adequate K2 MK-4 intake to prevent or reverse arterial calcification; eating K1-rich greens won't cut it. It's worth noting that the amounts of K1 and K2 used in the paper were very large, far beyond what is obtainable through food. But the regression took only 6 weeks, so it's possible that a smaller amount of K2 MK-4 over a longer period could have the same effect in humans.

K2 MK-4 (and perhaps other menaquinones like MK-7) may turn out to be an effective treatment for arterial calcification and cardiovascular disease in general. It's
extremely effective at preventing osteoporosis-related fractures in humans. That's a highly significant fact. Osteoporosis and arterial calcification often come hand-in-hand. Thus, they are not a result of insufficient or excessive calcium, but of a failure to use the available calcium effectively. In the warfarin-treated rats described above, the serum (blood) calcium concentration was the same in all groups. Osteoporosis and arterial calcification are two sides of the same coin, and the fact that one can be addressed with K2 MK-4 means that the other may be as well.

Both osteoporosis and arterial calcification may turn out to be symptoms of vitamin K2 deficiency, resulting from the modern fear of animal fats and organs, and the deterioration of traditional animal husbandry practices. So eat your pastured dairy, organs, fish roe and shellfish! And if you have arterial calcification, as judged by a
heart scan, you may want to consider supplementing with additional K2 MK-4 (also called menaquinone-4 and menatetrenone).

The osteoporosis studies were done with 45 milligrams per day, which was well tolerated but seems excessive to me. Smaller doses were not tested. From the limited information available on the K2 content of foods, 1 milligram of K2 MK-4 per day seems like the upper limit of what you can get from food. That's about 40 times more than the average person eats. Anything more and you're outside your body's operating parameters. Make sure you're getting adequate vitamin D3 and A if you supplement with K2. Vitamin D3 in particular
increases the secretion of MGP, so the two work in concert.