Transport of Vitamin K to Bone in Humans

Abstract

Molecules with vitamin K activity are important for optimal bone health. The major compound of this group in bone is vitamin K1 (phylloquinone), which is derived exclusively from plant foods in the diet. Vitamin K1 is absorbed along with dietary fat from the small intestine and transported by chylomicrons in blood. In serum obtained after an overnight fast from healthy men more than half of the vitamin K1 was recovered from the density fraction that contains chylomicrons and chylomicron remnants (CR), and only a quarter was associated with the major lipoprotein in serum, low density lipoprotein. The concentration of vitamin K1 in serum is closely related to the triglyceride concentration. Another determinant of vitamin K1 concentration in serum is the presence of specific variants of apolipoprotein E (apoE). ApoE is a small protein through which the vitamin K-rich CR bind to lipoprotein receptors. The three most common variants of apoE promote CR clearance from circulation with very different efficiency, in the order E2>E3>E4. The variant that promotes CR clearance best is associated with low vitamin K1 concentration in serum and increased response to vitamin K antagonists. Vitamin K1 concentration in serum is linked to vitamin K status of bone. The bone protein osteocalcin tends to be less completely carboxylated in people with low vitamin K concentrations in serum. Many hemodialysis patients with a history of bone fractures have indications of poor vitamin K status. The same patients also appear to have a greatly increased prospective bone fracture risk.

Associations of apolipoprotein E gene with ischemic stroke and intracranial atherosclerosis

“…Chylomicron uptake and clearance are affected significantly by APOE genotype, 25 leading to marked fluctuations in plasma concentrations of vitamin K1. 26 Low vitamin K1 levels have been measured, especially in patients carrying the e4 allele 26 and are associated with a poor outcome in hemorrhagic stroke patients. 27 Thus, possible interactions between APOE variants and vitamin K1 metabolism might be related to the risk of IS independently of the development of atherosclerosis.…”

Pharmacogenetics of warfarin: current status and future challenges

“…60 Vitamin K 1 is absorbed from the small intestine along with dietary fat, transported by chylomicrons in the blood and subsequently cleared by the liver through an APOE receptorspecific uptake. [61][62][63] Uptake of chylomicrons and thus vitamin K 1 into the liver varies between different APOE alleles, the rank order being *E44*E34*E2. 61,64 Consistent with this, patients with the APOE*E2 allele, who allegedly have the least efficient uptake of vitamin K 1 , have an increased risk of warfarin-associated intracerebral haemorrhage.…”

“…[61][62][63] Uptake of chylomicrons and thus vitamin K 1 into the liver varies between different APOE alleles, the rank order being *E44*E34*E2. 61,64 Consistent with this, patients with the APOE*E2 allele, who allegedly have the least efficient uptake of vitamin K 1 , have an increased risk of warfarin-associated intracerebral haemorrhage. 65 In a Swedish cohort, it was shown that CYP2C9*1/ *1 individuals (extensive metabolizers) who were homozygous for APOE*E4 were given significantly higher warfarin doses than other CYP2C9 extensive metabolizers.…”

The Relations Between the Vitamins and Alzheimer Dementia

“…Allison AC (Allison, 2001) proposed a possible role of vitamin K deficiency in the pathogenesis of AD and in augmenting brain damage associated with cerebrovascular disease, based on the potential actions of vitamin K in the brain and through a link to the apolipoprotein E genotype. The apolipoprotein E4 allele, an established risk factor for AD (Mattson, 2004), strongly influences plasma vitamin K levels (Kohlmeier M, 1996;Saupe J, 1993). Thus, carriers of apolipoprotein E4 allele could also those with the lowest vitamin K concentrations, an association that has not yet been investigated.…”