title: Vitamin K2 supplementation in haemodialysis patients: a randomized dose-finding study.
abstract: BACKGROUND
  Haemodialysis patients suffer from accelerated vascular calcification. The vitamin K-dependent matrix Gla protein (MGP) is one of the most powerful inhibitors of vascular calcification. Haemodialysis patients have high levels of the inactive form of MGP (desphosphorylated-uncarboxylated-MGP, dp-uc-MGP) and may benefit from pharmacological doses of vitamin K2 (menaquinone) to improve the calcification inhibitory activity of MGP.
  
  
  METHODS
  To determine the optimal dose of menaquinone-7 (MK-7) for MGP activation, 200 chronic haemodialysis patients were recruited to randomly receive 360, 720 or 1080 µg of MK-7 thrice weekly for 8 weeks. Dp-uc-MGP was measured at baseline and after 8 weeks. Dietary intake of vitamin K1 (phylloquinone) and menaquinone was estimated based on a detailed questionnaire.
  
  
  RESULTS
  At baseline, dp-uc-MGP was not associated with phylloquinone intake (P = 0.92), but correlated inversely with menaquinone intake (P = 0.023). MK-7 supplementation dose dependently reduced dp-uc-MGP. The levels decreased by 17, 33 and 46% in the respective groups. Drop-outs were mainly due to gastrointestinal side-effects related to the unpleasant smell of the tablets.
  
  
  CONCLUSIONS
  Chronic haemodialysis patients have high levels of inactive MGP, possibly related to a low dietary vitamin K intake. Pharmacological doses of MK-7 dose-dependently reduce dp-uc-MGP. Menaquinone supplementation may be a novel approach to prevent vascular calcifications in chronic haemodialysis patients.
authors.affiliation: Division of Nephrology, OLV Hospital, Aalst, Belgium.
authors.forename: Rogier
authors.initials: R
authors.lastname: Caluwé
authors.affiliation: Division of Nephrology and Infectious Diseases, AZ St.-Jan Hospital, Brugge, Belgium.
authors.forename: Stefaan
authors.initials: S
authors.lastname: Vandecasteele
authors.affiliation: Division of Nephrology, OLV Hospital, Aalst, Belgium.
authors.forename: Bruno
authors.initials: B
authors.lastname: Van Vlem
authors.affiliation: VitaK, Maastricht University, EV Maastricht, the Netherlands.
authors.forename: Cees
authors.initials: C
authors.lastname: Vermeer
authors.affiliation: Division of Nephrology and Infectious Diseases, AZ St.-Jan Hospital, Brugge, Belgium.
authors.forename: An S
authors.initials: AS
authors.lastname: De Vriese
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002135:Calcium-Binding Proteins / Q000097:blood*; D019587:Dietary Supplements; D004305:Dose-Response Relationship, Drug; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D006490:Hemostatics / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D006435:Renal Dialysis; D016037:Single-Blind Method; D011795:Surveys and Questionnaires; D061205:Vascular Calcification / Q000517:prevention & control; D010837:Vitamin K 1 / Q000008:administration & dosage; D024482:Vitamin K 2 / Q000008:administration & dosage / Q000031:analogs & derivatives*; D014815:Vitamins / Q000008:administration & dosage; D055815:Young Adult; D000097568:Matrix Gla Protein
chemical_list: D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D006490:Hemostatics; D010837:Vitamin K 1; D024482:Vitamin K 2; D014815:Vitamins; D000097568:Matrix Gla Protein; C062629:menaquinone 7
keywords: haemodialysis; menaquinone; vascular calcification