Biocomparison Study

Study Overview
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Brief Summary
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The effects of two vitamin K-forms on carboxylation of the vitamin K-dependent proteins osteocalcin and matrix-gla protein will be compared after supplementing these vitamins in a nutritional dose range. The investigators hypothesized that MK-7 is more effective than K1 at a dose comparable to the RDA of vitamin K.

Detailed Description
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Vitamin K is a group name for the naturally occurring phylloquinone (K1) and menaquinones (MK-n; K2). The latter can be subdivided into the short-chain (e.g. MK-4) and the long-chain (e.g. MK-7, MK-8, and MK-9) menaquinones. Earlier studies have shown that high vitamin K intake leads to improved bone and vascular health by increased carboxylation of vitamin K-dependent proteins in these tissues. In the dietary range, MK-7 has been suggested to be the most effective cofactor for the carboxylation of Gla-proteins, such as osteocalcin (OC) and matrix-Gla protein (MGP).Until now, no randomized controlled trial has compared the efficacy of K1 versus MK-7 in a nutritional dose range. The investigators are therefore interested to compare the effects of K1 and MK-7 on OC and MGP carboxylation after supplementing these vitamins at a dose not exceeding the RDA.

Official Title
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Comparison of Effects of Nutritional Doses Vitamin K1 and K2 on Carboxylation

Conditions
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Bone Health, Vascular Health

Intervention / Treatment
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* Dietary Supplement: Placebo
* Dietary Supplement: Vitamin K1-capsules
* Dietary Supplement: Vitamin K2-capsules


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men and women, aged between 20-80 years Normal body weight and height (18.5 kg/m2 < BMI < 30 kg/m2) Stable body weight (weight gain or loss < 3 kg in past 3 mo) Written consent to take part in the study Agreement to adhere to dietary restrictions required by the protocol Exclusion Criteria: Abuse of drugs and/or alcohol Use of vitamin supplements containing vitamin K Pregnancy (a history of) metabolic or gastrointestinal diseases, e.g. hepatic or renal disorders, osteoporosis Chronic degenerative and/or inflammatory diseases, e.g. diabetes mellitus, cancer, cardiovascular disease Use of oral anticoagulants, drugs or hormones that influence bone metabolism Corticoid treatment Subjects with anaemia or subjects who recently donated blood or plasma Systemic treatment or topical treatment likely to interfere with coagulation metabolism (salicylates, antibiotics)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: vitamin K1 capsules<br>27 participants received for three months 1 vitamin K1-capsule per day containing 52 µg of K1 | Dietary Supplement: Vitamin K1-capsules<br>* 27 participants received for 3 months 1 vitamin K1-capsule per day containing 52 µg of K1/day<br>|
| Active Comparator: Vitamin K2-capsules<br>27 participants received for three months 1 vitamin K2-capsule per day containing 75 µg of MK-7. | Dietary Supplement: Vitamin K2-capsules<br>* 27 participants received for 3 months 1 vitamin K2-capsule per day containing 75 µg of MK-7.<br>|
| Placebo Comparator: Placebo capsules<br>27 participants received for 3 months 1 placebo capsule per day | Dietary Supplement: Placebo<br>* 27 participants received for three months 1 placebo capsule per day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| carboxylation of osteocalcin | The primary objective of the study is to compare the effects of K1 and MK-7 on circulating ucOC levels after supplementing these vitamins at a nutritional dose. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| carboxylation of matrix-gla protein | The secondary objective of the study is to compare the effects of K1 and MK-7 on circulating ucMGP, which is emerging as a biomarker of arterial calcification. | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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phylloquinone,, menaquinone-7, vitamin K-status, efficacy