title: Bioavailability and Chemical/Functional Aspects of Synthetic MK-7 vs Fermentation-Derived MK-7 in Randomised Controlled Trials.
abstract: We investigated the bioavailability of a synthetic form of the vitamin K2 molecule menaquinone-7 (MK-7) in a randomised single-blinded two-way cross-over study. Healthy subjects (20 - 66 years of age) took a single 180 μg dose of synthetic MK-7 or fermentation-derived MK-7, and serum MK-7 concentrations were monitored for 72 hours to calculate AUC(0 - 72 h) and Cmax. We also compared the biological effects of placebo, fermentation-derived MK-7 (90 μg) and 3 doses of synthetic MK-7(45, 90 and 180 μg) in a randomised double-blinded parallel study. Healthy subjects (20 - 60 years of age) took one of the supplements daily for 43 days, and the fraction of carboxylated osteocalcin (OC) was compared between day 1 and day 43 as a marker for vitamin K activity. In the bioavailability study, the 90 % confidence interval for the ratio of the AUC(0-72 h) values for synthetic and fermentationderived MK-7 was 83 - 111, indicating bioequivalence. The 90 % confidence interval for the Cmax ratio was 83 - 131. The serum concentrations of carboxylated OC and undercarboxylated OC were increased (p = 0.01) and reduced (p = 0.02), respectively, after daily intake of 180 μg of synthetic MK-7 for 43 days, indicating increased vitamin K activity. Across both studies, only 1 participant reported an adverse event (dry mouth; 180 μg synthetic MK-7 group, functional study) that was considered possibly related to synthetic MK-7 supplementation. Our findings provide evidence that the tested synthetic form of MK-7 is bioequivalent to fermentation-derived MK-7, exhibits vitamin K activity and is well tolerated in healthy subjects.
authors.affiliation: 1 Kappa Bioscience AS, Oslo, Norway.
authors.forename: Mona
authors.initials: M
authors.lastname: Møller
authors.affiliation: 2 Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Ingrid M Fange
authors.initials: IMF
authors.lastname: Gjelstad
authors.affiliation: 3 Mericon AS, Skien, Norway.
authors.forename: Ingebjørg
authors.initials: I
authors.lastname: Baksaas
authors.affiliation: 3 Mericon AS, Skien, Norway.
authors.forename: Tone
authors.initials: T
authors.lastname: Grande
authors.affiliation: 4 Synthetica AS, Oslo, Norway.
authors.forename: Inger Reidun
authors.initials: IR
authors.lastname: Aukrust
authors.affiliation: 2 Department of Nutrition, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Christian A
authors.initials: CA
authors.lastname: Drevon
keywords: K2VITAL®; MK-7; Menaquinone-7; Vitamin K2; bioequivalence; equivalency; osetocalcin