Dose-finding Study for Vitamin K2 in Human Volunteers
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.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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PO Box 616
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Maastricht, PO Box 616, Netherlands, 6200 MD
- VitaK BV / University of Maastricht
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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) metabolic or gastrointestinal disease
- Subject with (a history of) soy allergy
- Subjects using vitamin supplements containing vitamin K
- Subjects presenting chronic inflammatory diseases
- Subjects receiving systemic treatment or topical treatment likely to interfere with evaluation of the study parameters
- Subjects receiving corticoϊd treatment
- Subjects using oral anticoagulants
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Placebo Comparator: PLACEBO
MK7 dosage 0 mcg, 4 capsules, orally, daily for 12 weeks.
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Active Comparator: MK7_10
MK7 dosage 10 mcg, 1 capsule of 10 mcg and 3 placebo-capsules, orally, daily for 12 weeks.
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Other Names:
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Active Comparator: MK7_20
MK7 dosage 20 mcg, 2 capsules of 10 mcg and 2 placebo-capsules, orally, daily for 12 weeks.
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Other Names:
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Active Comparator: MK7_45
MK7 dosage 45 mcg, 1 capsules of 45 mcg and 3 placebo-capsules, orally, daily for 12 weeks.
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Other Names:
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Active Comparator: MK7_90
MK7 dosage 90 mcg, 2 capsules of 45 mcg and 2 placebo-capsules, orally, daily for 12 weeks.
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Other Names:
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Active Comparator: MK7_180
MK7 dosage 180 mcg, 4 capsules of 45 mcg, orally, daily for 12 weeks.
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Other Names:
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Active Comparator: MK7_360
MK7 dosage 360 mcg, 1 capsule of 360 mcg and 3 placebo-capsules, orally, daily for 12 weeks.
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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undercarboxylated osteocalcin (ucOC)
Time Frame: 12 weeks
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UcOC will be assessed by making use of a sandwich ELISA (in ng/ml)
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12 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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carboxylated osteocalcin (cOC)
Time Frame: 12 weeks
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cOC will be assessed by making use of a sandwich ELISA (in ng/ml)
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12 weeks
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undercarboxylated matrix-gla protein (ucMGP)
Time Frame: 12 weeks
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ucMGP will be assessed by making use of a sandwich ELISA (in pM)
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12 weeks
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Collaborators and Investigators
Publications and helpful links
General Publications
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- MEC 07-3-014
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