Biocomparison Study

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

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.

Study Overview

• Status: Completed
• Conditions: Bone Health; Vascular Health
• Intervention / Treatment: Dietary supplement: Vitamin K1-capsules; Dietary supplement: Vitamin K2-capsules; Dietary supplement: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Maastricht, Netherlands
    • VitaK BV / Maastricht University Medicial Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center

Study record dates

Study Major Dates

• Study Start: March 1, 2011
• Primary Completion (Actual): June 1, 2011
• Study Completion (Actual): September 1, 2011

Study Registration Dates

• First Submitted: July 9, 2012
• First Submitted That Met QC Criteria: July 10, 2012
• First Posted (Estimate): July 11, 2012

Study Record Updates

• Last Update Posted (Estimate): July 11, 2012
• Last Update Submitted That Met QC Criteria: July 10, 2012
• Last Verified: July 1, 2012

More Information

Terms related to this study

• Keywords: efficacy; phylloquinone,; menaquinone-7; vitamin K-status
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Fibrin Modulating Agents; Micronutrients; Antifibrinolytic Agents; Hemostatics; Coagulants; Vitamin K; Vitamins; Vitamin K 1; Vitamin K 2
• Other Study ID Numbers: 10-3-018