Clinical trial NCT00483431: Dose-finding Study for Vitamin K2 in Human Volunteers
Official title: Dose-finding Study for Vitamin K2 in Human Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Vitamin K-status
Keywords: vitamin K2
dosis-response
osteocalcin
matrix-gla protein
Lead sponsor: Maastricht University Medical Center
Sponsor class: OTHER
First posted: 2007-06-07
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: undercarboxylated osteocalcin (ucOC)
timeFrame: 12 weeks
Secondary outcomes:
measure: carboxylated osteocalcin (cOC)
timeFrame: 12 weeks
measure: undercarboxylated matrix-gla protein (ucMGP)
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Maastricht
country: Netherlands
facility: VitaK BV / University of Maastricht
state: PO Box 616
Study officials:
affiliation: Maastricht University
name: Cees Vermeer, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.