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Pharmacokinetics of Menaquinone-7 (Vitamin K2) in Healthy Volunteers

Knapen MHJ, Vermeer C, Braam LAJLM and Theuwissen E

Objective: Because of the wide-spread use of menaquinone-7 (MK-7, a form of vitamin K2) supplements, we have investigated its pharmacokinetics following a single intake from various formulations.
Methods: Different formulations were compared in four human intervention studies with healthy volunteers. Participants received either capsules (filling material: linseed oil; MK-7 carrier material: sunflower oil) or tablets (filling material: dicalcium phosphate dehydrate (DCPD) and cellulose; MK-7 carriers: casein, Arabic gum, or sunflower oil). MK-7-absorption profiles (24 h area-under-the-curves, 24 h AUCs) were used to compare intestinal absorption. Special attention was given to intra- and inter-subject variability.
Results: The absorption (time-to-peak) of MK-7 from tablets was slower than from capsules, 6 h as compared to 2 h-4 h, respectively. Probably, the oily matrix of the capsules released the lipophilic MK-7 more rapidly than the powder matrix of the tablets. We further found a dose response relationship for MK-7 at 24 h after the single-dose intakes (at group level). As compared to baseline, circulating MK-7 levels were still elevated at 24 h after intake, confirming the relatively long half-life of MK-7. The different MK-7 carrier materials showed similar 24 h-absorption profiles, indicating that the carrier was not influencing MK-7 absorption. Next to high intra-subject variability, high inter-subject variability
was seen in the different studies. This was found for both, peak height and for total absorption (measured as 24 h-AUC). While some subjects showed a linear dose-response relation, other subjects had similar 24 h-AUCs after intake of MK-7 at different dosages
Conclusions: We have demonstrated that on a group level the bioavailability (24 h absorption) of MK-7 was similar for capsules and tablets, and also for the different MK-7 carriers. MK-7 absorption from the various formulations showed high intra- and inter-individual differences.