Abstract P071: The Effect of Menaquinone -7 Supplementation on Circulating Species of Matrix-Gla Protein

Background: Menaquinones intake is associated with a reduced risk of coronary calcification and coronary heart disease. This association may be explained by increased carboxylation of matrix-Gla protein (MGP) by menaquinones. However, the effect of menaquinone supplementation on MGP carboxylation has not been investigated to date. Objective: To investigate if 180 µg/day and 360 µg/day menaquinone supplementation may increase carboxylation of MGP. Design: A randomized, double-blind, placebo-controlled trial was performed. Sixty subjects aged 40–65 years were randomly allocated to supplementation of 180 μg/d, 360 μg/d of menaquinone-7 (MK-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, uncarboxylated osteocalcin (ucOC), carboxylated osteocalcin (cOC) and various cardiovascular risk factors were measured. The ratio of ucOC to cOC was used as proxy of vitamin K status. Results: Dp-ucMGP, decreased significantly and dose-dependently in the 180 μg and 360 mg MK-7 supplementation groups ( P time*treatment <0.001) by 31% (400 pM to 276 pM) and 46% (391 pM to 210 pM) respectively after 12 weeks, while dp-ucMGP circulation levels remained unchanged after placebo treatment. The osteocalcin ratio also decreased significantly and dose-dependently in the 180 μg and 360 mg MK-7 treatment ( P time*treatment <0.001) by 57% (0.44 to 0.19) and 74% (0.42 to 0.11) respectively after 12 weeks, while osteocalcin ratio remained unchanged after placebo treatment, showing improved vitamin K status and indicating 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. Also the prothrombin time did not differ between treatments arms ( P time*treatment=0.92). Furthermore, changes over time in other risk factors of cardiovascular disease like blood lipid profile or blood pressure did not differ between treatments. Conclusions: Supplementation with MK-7 decreased dp-ucMGP with 31% to 46%. Like the osteocalcin ratio, dp-ucMGP can be used as a sensitive marker of vitamin K status. MK-7 supplementation has no effect on dp-cMGP and t-ucMGP concentrations.