Vitamin K2 supplementation in haemodialysis patients: a randomized dose-finding study

Nephrol Dial Transplant. 2014 Jul;29(7):1385-90. doi: 10.1093/ndt/gft464. Epub 2013 Nov 26.

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.

Keywords: haemodialysis; menaquinone; vascular calcification.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Administration, Oral
  • Adult
  • Aged
  • Aged, 80 and over
  • Calcium-Binding Proteins / blood*
  • Dietary Supplements*
  • Dose-Response Relationship, Drug
  • Extracellular Matrix Proteins / blood*
  • Female
  • Follow-Up Studies
  • Hemostatics / administration & dosage*
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Prospective Studies
  • Renal Dialysis*
  • Single-Blind Method
  • Surveys and Questionnaires
  • Vascular Calcification / prevention & control
  • Vitamin K 1 / administration & dosage
  • Vitamin K 2 / administration & dosage
  • Vitamin K 2 / analogs & derivatives*
  • Vitamins / administration & dosage
  • Young Adult

Substances

  • Calcium-Binding Proteins
  • Extracellular Matrix Proteins
  • Hemostatics
  • Vitamins
  • matrix Gla protein
  • Vitamin K 2
  • Vitamin K 1
  • vitamin MK 7