The effect of menaquinone-7 supplementation on circulating species of matrix Gla protein

Objective: To investigate whether menaquinone-7 (MK-7) supplementation increases carboxylation of MGP. Design: A randomized, double-blind, placebo-controlled trial was performed. Sixty participants (40-65 y) were randomly allocated to supplementation of 180 mu g/d, 360 mu g/d of K-7 or placebo during 12 weeks. At baseline, after 4 and 12 weeks, desphospho-uncarboxylated MGP (dp-ucMGP), desphospho-carboxylated MGP (dp-cMGP) and total uncarboxylated MGP (t-ucMGP) were measured by ELISA techniques. Furthermore, the ratio of uncarboxylated osteocalcin (ucOC) to carboxylated osteocalcin (cOC) was used as proxy of vitamin K status and various cardiovascular risk factors were measured. Results: Dp-ucMGP decreased significantly and dose-dependently in the 180 mu g and 360 mu g MK-7 supplementation groups (P time*treatment <0.001) after 12 weeks, by 31% and 46% respectively, while dp-ucMGP levels remained unchanged after placebo treatment. The osteocalcin ratio also decreased significantly after 12-week supplementation with 180 mu g (60%) and 360 mu g (74%) MK-7 (P time*treatment <0.001), while levels remained unchanged after placebo treatment. These results indicate improved vitamin K status and good compliance to the study treatment. Changes over time of dp-cMGP (p = 0.42) and t-ucMGP (p = 0.23) levels did not differ between treatment arms. Other cardiovascular risk factors did not differ between treatments arms. Conclusions: Menaquinone supplementation dose-dependently decreases dp-ucMGP concentrations, but does not affect other MGP species. Dp-ucMGP may serve as a non-invasive marker of vitamin K status.