Differential lipoprotein transport pathways of K-vitamins in healthy subjects.

Vitamin K is a group name for K1 (phylloquinone) and K2 (menaquinones). Both forms contribute to the tissue vitamin K status. Following intestinal absorption, the serum transport of these lipophilic compounds to their target tissues takes place via lipoproteins. In previous studies we have found that K1 is preferentially accumulated in the liver, whereas menaquinones have a more widespread distribution pattern. Here we have tested whether these differences may be explained by the different liposolubility of the various K-vitamers, resulting in their association with different lipoprotein particles. Six healthy male volunteers received a mixture containing 2 micromol of each of three K vitamers (K1, MK-4, and MK-9) dissolved in corn oil. Blood was obtained at baseline and at different time intervals after intake for the measurement of vitamin K in serum and in the lipoprotein fractions. During the first 4 h after intake all K-vitamins were found to be associated predominantly with the triacylglycerol-rich lipoprotein (TGRLP) fraction. Since the TGRLP fraction is mainly cleared by the liver, this suggests that initially most of the K-vitamins are transported to the liver. In contrast to K1, however, both menaquinones investigated were also found in TGRLP and low-density lipoprotein, whereas MK-4 was even present in high-density lipoprotein. This explains why menaquinones may have a different distribution profile and suggests a relatively large impact of menaquinones on extra-hepatic vitamin K status than generally assumed. Moreover, the very long half-life time of MK-9 in the circulation indicates that it may form a more constant source of vitamin K than are either K1 or MK-4.