The Effect of menaquinone-7 Supplementation on Circulating Species of Matrix Gla Protein

Atherosclerosis. 2012 Dec;225(2):397-402. doi: 10.1016/j.atherosclerosis.2012.09.019. Epub 2012 Sep 25.

Abstract

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 μg/d, 360 μg/d of 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, 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 μg and 360 μg 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 μg (60%) and 360 μg (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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Biomarkers / blood
  • Calcium-Binding Proteins / blood*
  • Carboxylic Acids / blood
  • Dietary Supplements*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Down-Regulation
  • Enzyme-Linked Immunosorbent Assay
  • Extracellular Matrix Proteins / blood*
  • Female
  • Humans
  • Male
  • Medication Adherence
  • Middle Aged
  • Netherlands
  • Osteocalcin / blood
  • Phosphorylation
  • Time Factors
  • Vitamin K 2 / administration & dosage
  • Vitamin K 2 / analogs & derivatives*
  • Vitamins / administration & dosage*

Substances

  • Biomarkers
  • Calcium-Binding Proteins
  • Carboxylic Acids
  • Extracellular Matrix Proteins
  • Vitamins
  • matrix Gla protein
  • Osteocalcin
  • Vitamin K 2
  • vitamin MK 7