Differences between vitamins K1 and K2
Almost 90% of all vitamin K in the human diet occurs in the form of K1, and modern technology has allowed its quantification in food for several decades. However, only 11 years ago it became possible to also accurately analyse foods for their K2 content. The data were published by Schurgers et al  and this table is still used worldwide to estimate human vitamin K2 intake in study cohorts.
The first study cohort in which vitamin K intake was differentiated into K1 and K2 was the Rotterdam Study, a group of 4,500 elderly men and women (> 55 years old) whose dietary habits were repeatedly analysed by taking food frequency questionnaires with health monitoring during a follow-up period of over 10 years. The results were stunning: whereas dietary vitamin K1 intake had no effect on cardiovascular health, there was a strong inverse association between K2 intake and the extent of aortic calcification, the occurrence of myocardial infarction, and cardiovascular mortality (50% lower in those consuming 45 µg/day of K2 or more). Also all-cause mortality was reduced by 25% in this group . By that time, the mechanism underlying these outcomes was not understood, and there was disbelief in the scientific community. Therefore, the study was repeated by a different research group, in an independent and much larger cohort known as the Prospect study. The total number of subjects was over 16,000 and again the observation period was 10 years or more. And – like in the Rotterdam Study – no effect on cardiovascular health of K1 was observed and a major effect of K2. By the much larger power than in the Rotterdam study, the researchers were even able to calculate that each extra intake of 10 µg/day of K2 resulted in a 9% decreased risk for cardiovascular mortality .
Differences between K1 and K2 did not remain restricted to cardiovascular disease prevention: in 2008 and 2009 two important papers were published showing that high dietary intake of K2 has a strong protective effect against prostate cancer  and all other major forms of cancer except breast cancer . Also in this case there was no effect of K1 and – like for cardiovascular disease – the effective dose of K2 was reported to be around 45 µg/day. Of course it is intriguing why K2, forming only 10% of our total dietary vitamin K intake, can have such dramatic effects. First, we have to realize that K1 is of plant origin, where it is tightly bound to the chloroplasts; hence dietary sources of K1 are green, leafy vegetables. Chloroplasts are poorly digested, however, so that only 5-10% of the ingested K1 enters the circulation and becomes available for the body. K2, on the other hand, is produced by bacteria and occurs in the fat fraction of foods like cheese, curd, eel, and flat fish. In eel and flat fish the K2 originates from their food: decaying organic material at the bottom of the sea. K2 is taken up from the digestive tract rapidly and completely . From these data it may be calculated that there is a comparable influx of K1 and K2 in our system.
A second difference between both K vitamins becomes clear when we look at the transport following intestinal absorption. Both are fat-soluble vitamins and need a transport vehicle that brings them from the gut to the liver. This is accomplished by the triacylglycerol-rich lipoproteins (for short: triglycerides). In a second step K2, being the most lipophylic of the K-vitamins, is incorporated into low density lipoproteins (LDL) which bring it to other tissues including bone, vessel wall, prostate, lungs, etc. K1, on the other hand, is hardly found in LDL (see figure) . The different transport mechanisms for K1 and K2 is the reason why in the extra-hepatic tissues health effects of K2 are much more prominent than those of K1. A third major difference between K1 and K2 is their half-life time in the circulation: whereas K1 has a half-life time of about 1.5 hour, that of the predominant dietary forms of K2 is 3 days or longer . This is probably related to the long half-life time of its carrier LDL, and means that K2 is much longer available for uptake by extra-hepatic tissues than K1.
Whereas large population-based studies have demonstrated significant health effect for K2 at intakes of 45 µg/day and higher, we also have to conclude that this intake level is not met by 75% of the healthy adult population. It must also be realised that in the western diet, K2 is almost inevitably found in the saturated fat fraction, which is regarded as unhealthy.
Therefore, I recommend daily consumption of the Japanese food natto, which is a low-fat product extremely rich in K2. In case this is not available or appreciated (natto has a very strong taste and smell), supplements or fortified foods containing extracts from natto food or from its K2 producing bacteria Bacillus subtilis natto are a healthy alternative.
Presently, a 3-year placebo-controlled clinical trial in healthy volunteers is in progress at VitaK, Maastricht University. In this trial we investigate potential health effects of MenaQ7, NattoPharma's brand name for K2. Clinical endpoints in this trial are bone health and vascular health. The outcomes are expected by the end of 2011.
- Schurgers, L.J., Vermeer, C. Determination of phylloquinone and menaquinones in food: effect of food matrix on circulating vitamin K concentrations. Haemostasis 30 (2000) 298-307.
- Geleijnse, J.M., Vermeer, C., Grobbee, D.E., Pols, H.A.P., Schurgers, L.J., Knapen, M.H.J., van der Meer, I.M., Hofman, A., Witteman, J.C.M. Dietary intake of vitamin K-2 reduces the risk of cardiac events and aortic atherosclerosis: The Rotterdam Study. J. Nutr. 134 (2004) 3100-3105.
- Gast, G.C.M., de Roos, N.M., Sluijs, I, Bots, M.L., Beulens, J.W.J., Geleijnse, J.M., Witteman, J.C., Grobbee, D.E., Peeters, P.H.M., van der Schouw, Y.T. A high menaquinone intake reduces the incidence of coronary heart disease. Nutr. Metab. Cardiovasc. Dis. 19 (2009) 504-510.
- Nimptsch, K., Rohrmann, S., Linseisen, J. Dietary intake of vitamin K and risk of prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg) Am. J. Clin. Nutr.87 ( 2008) 985–992.
- Nimptsch, K., Rohrmann, S., Linseisen, J. Dietary vitamin K intake in relation to cancer incidence and mortality: results from the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg). Am. J Clin. Nutr. 91 (2010) 1348–1358.
- Gijsbers, B.L.M.G., Jie, K.-S.G., Vermeer, C. Effect of food composition on vitamin K absorption in human volunteers. Brit. J. Nutr. 76 (1996) 223-229.
- Schurgers, L.J., Vermeer, C. Differential lipoprotein transport pathways of K-vitamins in healthy subjects. Biochim. Biophys. Acta 1570 (2002) 27-32.
- Schurgers, L.J., Teunissen, K.J.F., Hamulyák, K., Knapen, M.H.J., Vik, H., Vermeer, C. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood 109 (2007) 3279-3283.
|Postprandial vitamin K uptake in circulating trigliceride fraction||Postprandial vitamin K uptake in circulating LDL fraction|
Postprandial uptake of K vitamins in the circulation. Twelve volunteers received a single oral dose of synthetic K1, synthetic K2 (MK-4) and natural K2 (MK-7). MK-4 is structurally very similar to K1 and has comparable lipophylicity, whereas MK-7 has a much higher fat solubility. The three K vitamins were given as a mixture (1 mg of each) solubilized in sunflower seed oil. Blood was taken by venipuncture at the indicated time points and analysed for its vitamin K content. It is clear that within 8 hours most of the K1 and MK-4 had disappeared from the triglyceride-rich lipoproteins, and after 24 hours also little MK-7 was left in this fraction (left panel). The major difference in pharmacokinetic behaviour, however, was found at the level of LDL: whereas little K1 and MK-4 were found in this fraction during the first hours following intake, MK-7 was abundantly present in the LDL fraction with a half-life time of at least several days.