Low-dose menaquinone-7 supplementation improved extra-hepatic vitamin K status, but had no effect on thrombin generation in healthy subjects

• Published in: British journal of nutrition Vol. 108; no. 9; pp. 1652 - 1657
• Main Authors: Theuwissen, Elke, Cranenburg, Ellen C., Knapen, Marjo H., Magdeleyns, Elke J., Teunissen, Kirsten J., Schurgers, Leon J., Smit, Egbert, Vermeer, Cees
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 14.11.2012
• Subjects: Adult; adverse effects; Algorithms; Biological and medical sciences; Blood Coagulation; Blood Coagulation Tests; carboxylation; Coagulation; Decarboxylation; Dietary supplements; Dietary Supplements - adverse effects; dose response; Dose-response effects; Double-Blind Method; enzyme-linked immunosorbent assay; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; Hemostatics - administration & dosage; Hemostatics - adverse effects; Hemostatics - pharmacokinetics; Hemostatics - therapeutic use; Human and Clinical Nutrition; Humans; Liver; Male; men; menaquinones; Middle Aged; Netherlands; Nutrition research; Nutritional Status; osteocalcin; Osteocalcin - blood; Osteocalcin - metabolism; Pilot Projects; placebos; Proteins; Public health; thrombin; tissues; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Vitamin K - blood; Vitamin K 2 - administration & dosage; Vitamin K 2 - adverse effects; Vitamin K 2 - analogs & derivatives; Vitamin K 2 - pharmacokinetics; Vitamin K 2 - therapeutic use; Vitamin K Deficiency - blood; Vitamin K Deficiency - diet therapy; Vitamin K Deficiency - metabolism; vitamin status; Vitamins; women; Young Adult; Netherlands; Osteocalcin; Menaquinone-7; Endogenous thrombin potential; Matrix Gla-protein; Healthy subject; Digestive system; Low dose; Liver; Menaquinone; Protein; Vertebrata; Generation; Endogenous; Mammalia; Supplementation; Vitamin K
• ISSN: 0007-1145; 1475-2662; 1475-2662
• DOI: 10.1017/S0007114511007185

Vitamin K is required for the carboxylation of Gla-proteins in the liver (coagulation factors) and extra-hepatic tissues, such as bone (osteocalcin, OC), and arterial wall (matrix Gla-protein, MGP). Although the coagulation factors are essentially fully carboxylated under normal conditions, 10–40 % of OC and MGP remains undercarboxylated. We were therefore interested to study the dose–response effects of extra intake of menaquinones on the carboxylation of the extra-hepatic Gla-proteins. A total of forty-two healthy Dutch men and women aged between 18 and 45 years were randomised into seven groups to receive: placebo capsules or menaquinone-7 (MK-7) capsules at a daily dose of 10, 20, 45, 90, 180 or 360 μg. Circulating uncarboxylated OC (ucOC), carboxylated OC (cOC) and desphospho-uncarboxylated MGP were measured by ELISA. The ucOC:cOC ratio was calculated from circulating ucOC and cOC values. Endogenous thrombin potential and peak height were determined by calibrated automated thrombography. To increase the statistical power, we collapsed the treatment groups into three dosage groups: placebo, low-dose supplementation (doses below RDA, Commission Directive 2008/100/EC), and high-dose supplementation (doses around RDA, Commission Directive 2008/100/EC). MK-7 supplementation at doses in the order of the RDA (Commission Directive 2008/100/EC) increased the carboxylation of circulating OC and MGP. No adverse effects on thrombin generation were observed. Extra MK-7 intake at nutritional doses around the RDA (Commission Directive 2008/100/EC) improved the carboxylation of the extra-hepatic vitamin K-dependent proteins. Whether this improvement contributes to public health, i.e. increasing the protection against age-related diseases needs further investigation in specifically designed intervention trials.