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.


METHODS
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.
Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX Utrecht, The Netherlands. G.W.Dalmeijer@umcutrecht.nl
G W
GW
Dalmeijer
Y T
YT
van der Schouw
E
E
Magdeleyns
N
N
Ahmed
C
C
Vermeer
J W J
JW
Beulens
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D002135:Calcium-Binding Proteins / Q000097:blood*; D002264:Carboxylic Acids / Q000097:blood; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D015536:Down-Regulation; D004797:Enzyme-Linked Immunosorbent Assay; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D009426:Netherlands; D015675:Osteocalcin / Q000097:blood; D010766:Phosphorylation; D013997:Time Factors; D024482:Vitamin K 2 / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014815:Vitamins / Q000008:administration & dosage*; D000097568:Matrix Gla Protein
D015415:Biomarkers; D002135:Calcium-Binding Proteins; D002264:Carboxylic Acids; D016326:Extracellular Matrix Proteins; D015675:Osteocalcin; D024482:Vitamin K 2; D014815:Vitamins; D000097568:Matrix Gla Protein; C062629:menaquinone 7