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

Abstract

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. 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. 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. 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.