Vitamin K2: Part Three – Rotterdam
In Vitamin K2: Part One and Vitamin K2: Part Two, I reported some weak associations suggesting that vitamin K2 (found in animals foods), but not vitamin K1 (found in plant foods), might play a role in protecting against heart disease.
Part Three is on yet another study from The Netherlands, this time a component of the The Rotterdam Study published in 2004 (1). Unlike the other other two studies, this one had much stronger results.
The study had a prospective component in which 4,807 men and women aged 55 years and older were followed for an average of 7.2 years. At baseline, all participants were given an ECG to determine if they had heart disease and were excluded if they did.
Vitamin K2 intake was positively associated with the intake of total fat, saturated fat, and calcium, as well as body mass index, and diabetes; it was inversely associated with intake of polyunsaturated fatty acids.
For vitamin K1, the results once again showed it not to be associated with a reduced risk of heart disease (nor mortality).
In model 1, that adjusted for age, gender, and total energy intake, when comparing the group with the highest daily intake (> 33 µg) of vitamin K2 to the lowest (< 22 µg), K2 was associated with a reduced risk of heart disease (.71, .51-1.00), death from heart disease (.59, .35-.99), and overall mortality (.81, .67-.98). These findings are borderline statistically significant.
However, in model 2 that adjusted for factors in model 1 and also body mass index, smoking status and history, diabetes, education, and intake of alcohol, saturated fat, polyunsaturated fat, flavonols (a group of antioxidants), and calcium, the associations became much stronger for heart disease (.59, .40-.86), death from heart disease (.43, .24-.77), and overall mortality (.74, .59-.92).
There was also a cross-sectional component of the study in which 4,473 people were given x-rays at baseline to determine if they had aortic artery calcification. Vitamin K2 intake was inversely associated with severe calcification in model 1 (.56, .39-.80) and model 2 (.48, .32-.71).
As for the possibility of reverse causation (in which people with poor health decided to eat fewer foods high in K2), the authors said, “In contrast to phylloquinone [K1], intake of menaquinone [K2] (mainly MK-4 from eggs and meat, and MK-8 and MK-9 from cheese), is not related to a healthy lifestyle or diet, which makes it unlikely that the observed reduction in coronary risk is due to confounding. Subjects with a history of MI were excluded from the analysis to avoid bias that may arise from intentional changes in diet.”
They also said, “We hypothesize that menaquinones in cheese (MK-8 and MK-9) could exert a beneficial effect in the cardiovascular system and that the high cheese consumption in France and the Mediterranean countries may possibly account for lower prevalences of [heart disease].”
Although the results from this one study are fairly strong, it takes a lot more than one cohort study to justify recommendations for preventing chronic disease. You could combine these results with those for the studies reviewed in Vitamin K2: Part One and Part Two, but those studies are not nearly as strong. Finally, all of these studies included only older people from The Netherlands; we need data from other regions.
In a relatively quick search of PubMed, I could not find any other studies looking at the association between vitamin K2 and heart disease in humans. In fairness to me, the search was quick because so few results were returned. But I will be looking around some more and also reviewing more studies on vitamin K2 and other diseases in the upcoming days.
At this point in time, I am not going out to get vitamin K2 supplements. However, I’m also not dismissing the idea that in a few weeks from now, I might be.
1. Geleijnse JM, Vermeer C, Grobbee DE, Schurgers LJ, Knapen MH, van der Meer IM, Hofman A, Witteman JC. Dietary intake of menaquinone is associated with a reduced risk of coronary heart disease: the Rotterdam Study. J Nutr. 2004 Nov;134(11):3100-5. | link