Saturday, March 7, 2009

Latest Study on Vitamin K and Coronary Heart Disease

A Dutch group led by Dr. Yvonne T. van der Schouw recently published a paper examining the link between vitamin K intake and heart attack (thanks Robert). They followed 16,057 women ages 49-70 years for an average of 8.1 years, collecting data on their diet and incidence of heart attack.

They found no relationship between K1 intake and heart attack incidence. K1 is the form found in leafy greens and other plant foods. They found that each 10 microgram increase in daily vitamin K2 consumption was associated with a 9% lower incidence of heart attack. Participants consumed an average of 29 micrograms K2 per day, with a range of 0.9 to 128 micrograms. That means that participants with the highest intake had a very much reduced incidence of heart attack on average. Vitamin K2 comes from animal foods (especially organs and pastured dairy)and fermented foods such as cheese, sauerkraut, miso and natto. Vitamin K is fat-soluble, so low-fat animal foods contain less of it. Animal foods contain the MK-4 subtype while fermentation produces longer menaquinones, MK-5 through MK-14.

There's quite a bit of evidence to support the idea that vitamin K2 inhibits and possibly reverses arterial calcification, which is possibly the best overall measure of heart attack risk. It began with the observations of Dr. Weston Price, who noticed an inverse relationship between the K2 MK-4 content of butter and deaths from coronary heart disease and pneumonia in several regions of the U.S. You can find those graphs in Nutrition and Physical Degeneration.

The 25% of participants eating the most vitamin K2 (and with the lowest heart attack risk) also had the highest saturated fat, cholesterol, protein and calcium intake. They were much less likely to have elevated cholesterol, but were more likely to be diabetic.

Here's where the paper gets strange. They analyzed the different K2 subtypes individually (MK-4 through MK-9). MK-7 and MK-6 had the strongest association with reduced heart attack risk per microgram consumed, while MK-4 had no significant relationship. MK-8 and MK-9 had a weak but significant protective relationship.

There are a few things that make me skeptical about this result. First of all, the studies showing prevention/reversal of arterial calcification in rats were done with MK-4. MK-4 inhibits vascular calcification in rats whereas I don't believe the longer menaquinones have been tested. Furthermore, they attribute a protective effect to MK-7 in this study, but the average daily intake was only 0.4 micrograms! You could get that amount of K2 if a Japanese person who had eaten natto last week sneezed on your food. I can't imagine that amount of MK-7 is biologically significant. That, among other things, makes me skeptical of what they're really observing.

I'm not convinced of their ability to parse the effect into the different K2 subtypes. They mentioned in the methods section that their diet survey wasn't very accurate at estimating the individual K2 subtypes. Combine that with the fact that the K2 content of foods varies quite a bit by animal husbandry practice and type of cheese, and you have a lot of variability in your data. Add to that the well-recognized variability inherent in these food questionnaires, and you have even more variabiltiy.

I'm open to the idea that longer menaquinones (K2 MK-5 and longer, including MK-7) play a role in preventing cardiovascular disease, but I don't find the evidence sufficient yet. MK-4 is the form of K2 that's made by animals, for animals. Mammals produce it in their breast milk and other animals produce it in eggs all the way down to invertebrates. I think we can assume they make MK-4, and not the longer menaquinones, for a reason.

MK-4 is able to play all the roles of vitamin K in the body, including activating blood clotting factors, a role traditionally assigned to vitamin K1. This is obvious because K2 MK-4 is the only significant source of vitamin K in the diet of infants before weaning. No one knows whether the longer menaquinones are able to perform all the functions of MK-4; it hasn't been tested and I don't know how you could ever be sure. MK-7 is capable of performing at least some of these functions, such as activating osteocalcin and clotting factors.

I do think it's worth noting that the livers of certain animals contain longer menaquinones, including MK-7. So it is possible that we're adapted to eating some of the longer menaquinones. Many cultures also have a tradition of fermented food (probably a relatively recent addition to the human diet), which could further increase the intake of longer menaquinones. The true "optimum", if there is one, may be to eat a combination of forms of K2, including MK-4 and the longer forms. But babies and healthy traditional cultures such as the Masai seem to do quite well on a diet heavily weighted toward MK-4, so the longer forms probably aren't strictly necessary. If you haven't already seen it, check out my post on 20th century butter consumption and coronary heart disease risk in the United States.

Well if you've made it this far, you're a hero (or a nerd)! Now for some humor. From the paper:
The concept of proposing beneficial effects to vitamin K2 seems to have different basis as for vitamin K1. Vitamin K1 has been associated with a heart-healthy dietary pattern in the earlier work in the USA and this attenuated their associations with CHD. Vitamin K2 has different sources and relate to different dietary patterns than vitamin K1. This suggests that the risk reduction with vitamin K2 is not driven by dietary patterns, but through biological effects.
If that reads like gobledygook, it's because it is. They're trying to justify the fact that participants in the highest K2 intake group ate the most saturated fat and cholesterol (since K2 came mostly from cheese, milk and meat), yet had the lowest heart attack incidence and the lowest serum cholesterol. Look at them squirm! Could this "paradox" be the reason the paper was published in an obscure journal? Here's more:
Thus, although our findings may have important practical implications on CVD prevention, it is important to mention that in order to increase the intake of vitamin K2, increasing the portion vitamin K2 rich foods in daily life might not be a good idea. Vitamin K2 might be, for instance more relevant in the form of a supplement or in low-fat dairy. More research into this is necessary.
Translation: "People who ate the most cheese, milk and meat had the lowest heart attack rate, but be careful not to eat those things because they might give you a heart attack. Get your K2 from low-fat dairy (barely contains any) and supplements (same way your ancestors got it). Gimme more money."

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