Healthy
Conditions
Keywords
vitamin K2, oral anticoagulation, interference, level of anticoagulation, carboxylation level of osteocalcin and matrix-gla protein
Brief summary
Oral anticoagulants that are widely used for the treatment of thrombo-embolic disease exert their effect by blocking the recycling of vitamin K. Vitamin K acts as a co-factor in the posttranslational carboxylation of vitamin K-dependent proteins such as osteocalcin and matrix-gla protein. It is important to quantify the dose-response relationship of the interaction between vitamin K and oral anticoagulants and to investigate at what dosage vitamin K will interfere with oral anticoagulants in a clinically relevant way.
Detailed description
From all K-vitamins, menaquinone-7 has been identified as the most effective cofactor for the carboxylation reaction of Gla-proteins. In this respect it is important to quantify the dose-response relationship of the interaction between oral anticoagulants and menaquinone-7. The primary objective of the study is to demonstrate at what menaquinone-7 intake the vitamin will interfere with oral anticoagulants in a clinically relevant way. Clinically relevant is defined as a decrease in level of anticoagulation that would require a change in oral anticoagulant treatment in order to stay within target levels. Secondary objective of the study is to investigate changes in carboxylation level of osteocalcin and matrix-gla protein after menaquinone-7 supplementation during the oral anticoagulation treatment period. This will demonstrate whether during oral anticoagulation menaquinone-7 will be transported preferentially to the liver or to other target tissues.
Interventions
DRUGacenocoumarol
max 5 mg per day during 10 weeks
DIETARY_SUPPLEMENTmenaquinone-7
In successive weeks (6 weeks) the dosage is increased over the range 10 µg to 20 µg increasing to 45 µg MK-7 for the final week.
Sponsors
Maastricht University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Healthy male and female adults between 18 and 45 years of age. * Subjects of normal body weight and height according to BMI \< 30 * Subject has given written consent to take part in the study
Exclusion criteria
* Subjects with (a history of) of coagulation disorders * Subjects with (a history of) metabolic or gastrointestinal disease * Subjects using (multi)-vitamin supplements containing vitamin K * Subjects presenting chronic inflammatory diseases * Subjects using any medication 3 months prior to the study (e.g. corticoϊd treatment, oral anticoagulants) * Subjects using oral anticonception * Subject with (a history of) soy allergy
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| changes in level anticoagulation | 10 weeks |
Secondary
| Measure | Time frame |
|---|---|
| changes in carboxylation level of osteocalcin and matrix-gla protein | 10 weeks |
Countries
Netherlands
Outcome results
None listed