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 fermentation-derived 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.