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Earlier studies have shown that high vitamin K-intake leads to improved bone and vascular health by increased carboxylation of Gla-proteins in these tissues. From all K-vitamins, Menaquinone-7 (MK7) has been identified as the most effective cofactor for the carboxylation reaction of Gla-proteins such as osteocalcin and matrix-gla protein. The question remains which dosage of MK7 leads to optimal carboxylation levels of these proteins.
The primary objective of this double-blind randomized intervention study is to establish the optimal dose of MK7 for carboxylation of the vitamin K-dependent proteins osteocalcin in bone and matrix-gla protein in the vessel wall. The optimal dose will be the concentration at which osteocalcin and matrix-gla protein are > 90% in the active (=carboxylated) form.
This study is a double-blind randomized intervention study. In total 42 healthy volunteers (men and women) between 18 and 45 years will be recruited among the Maastricht University community (coworkers/students) and randomized into one of the following groups:
Placebo, 10 mcg MK7, 20 mcg MK7, 45 mcg MK7, 90 mcg MK7, 180 mcg MK7, 360 mcg MK7.
Each group will consist of 6 volunteers with approximately equal numbers of men and women (3 men / 3 women). A double-blind design of the study is chosen to avoid the occurrence of bias during the study. The randomization procedure will be performed by an investigator who is not involved in the coordination of the study and will generate specific randomization codes for each subject. After randomization, the volunteers consume the indicated amount of capsules once daily with either breakfast of dinner during a period of 12 weeks.
During the first week, blood samples of the volunteers will be collected at day 0, 1, 3 and 7 to study immediate effects on carboxylation of OC and MGP. After the first week, blood samples will be drawn every first day of week 2, 4, 6, 8, 10, and 12.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| PLACEBO | Placebo Comparator | MK7 dosage 0 mcg, 4 capsules, orally, daily for 12 weeks. |
|
| MK7_10 | Active Comparator | MK7 dosage 10 mcg, 1 capsule of 10 mcg and 3 placebo-capsules, orally, daily for 12 weeks. |
|
| MK7_20 | Active Comparator | MK7 dosage 20 mcg, 2 capsules of 10 mcg and 2 placebo-capsules, orally, daily for 12 weeks. |
|
| MK7_45 | Active Comparator | MK7 dosage 45 mcg, 1 capsules of 45 mcg and 3 placebo-capsules, orally, daily for 12 weeks. |
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| MK7_90 | Active Comparator | MK7 dosage 90 mcg, 2 capsules of 45 mcg and 2 placebo-capsules, orally, daily for 12 weeks. |
|
| MK7_180 | Active Comparator |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo | Dietary Supplement |
| ||
| MK7 |
| Measure | Description | Time Frame |
|---|---|---|
| undercarboxylated osteocalcin (ucOC) | UcOC will be assessed by making use of a sandwich ELISA (in ng/ml) | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| carboxylated osteocalcin (cOC) | cOC will be assessed by making use of a sandwich ELISA (in ng/ml) | 12 weeks |
| undercarboxylated matrix-gla protein (ucMGP) | ucMGP will be assessed by making use of a sandwich ELISA (in pM) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Cees Vermeer, PhD | Maastricht University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| VitaK BV / University of Maastricht | Maastricht | PO Box 616 | 6200 MD | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22289649 | Derived | Theuwissen E, Cranenburg EC, Knapen MH, Magdeleyns EJ, Teunissen KJ, Schurgers LJ, Smit E, Vermeer C. Low-dose menaquinone-7 supplementation improved extra-hepatic vitamin K status, but had no effect on thrombin generation in healthy subjects. Br J Nutr. 2012 Nov 14;108(9):1652-7. doi: 10.1017/S0007114511007185. Epub 2012 Jan 31. | |
| 22136751 |
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| ID | Term |
|---|---|
| C062629 | menaquinone 7 |
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MK7 dosage 180 mcg, 4 capsules of 45 mcg, orally, daily for 12 weeks.
|
| MK7_360 | Active Comparator | MK7 dosage 360 mcg, 1 capsule of 360 mcg and 3 placebo-capsules, orally, daily for 12 weeks. |
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| 12 weeks |
| Knapen MH, Schurgers LJ, Shearer MJ, Newman P, Theuwissen E, Vermeer C. Association of vitamin K status with adiponectin and body composition in healthy subjects: uncarboxylated osteocalcin is not associated with fat mass and body weight. Br J Nutr. 2012 Sep 28;108(6):1017-24. doi: 10.1017/S000711451100626X. Epub 2011 Dec 5. |