Low-dose menaquinone-7 supplementation improved extra-hepatic vitamin K status, but had no effect on thrombin generation in healthy subjects
What this study found
MK-7 improved extra-hepatic vitamin K status and did not affect thrombin generation, supporting haemostatic safety in healthy adults. Across dose groups, uncarboxylated osteocalcin generally decreased and carboxylated osteocalcin increased; for example, at 360 mg/d ucOC changed from 1.9 to 0.7 and cOC from 4.5 to 6.7, while dp-ucMGP fell from 389 to 171. Thrombin generation showed no difference at baseline versus end for ETP (P=0.691) or PH (P=0.844). The findings suggest biologic activity on vitamin K-dependent proteins without adverse coagulation effects, although long-term clinical…
- Study & population
- Healthy adult men and women recruited from the Maastricht University community participated in a 12-week oral MK-7 dose-ranging intervention.
- Intervention
- MK-7 (menaquinone-7) capsules were taken orally once daily with breakfast or dinner for 12 weeks.
- Key limitation
- Very small active-arm sample sizes (N=6 per dose) limit precision and increase risk of chance findings.
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Open PDFOriginal abstract
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.