title: Menaquinone-7 supplementation improves arterial stiffness in healthy postmenopausal women. A double-blind randomised clinical trial.
abstract: Observational data suggest a link between menaquinone (MK, vitamin K2) intake and cardiovascular (CV) health. However, MK intervention trials with vascular endpoints are lacking. We investigated long-term effects of MK-7 (180 µg MenaQ7/day) supplementation on arterial stiffness in a double-blind, placebo-controlled trial. Healthy postmenopausal women (n=244) received either placebo (n=124) or MK-7 (n=120) for three years. Indices of local carotid stiffness (intima-media thickness IMT, Diameter end-diastole and Distension) were measured by echotracking. Regional aortic stiffness (carotid-femoral and carotid-radial Pulse Wave Velocity, cfPWV and crPWV, respectively) was measured using mechanotransducers. Circulating desphospho-uncarboxylated matrix Gla-protein (dp-ucMGP) as well as acute phase markers Interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP), tumour necrosis factor-α (TNF-α) and markers for endothelial dysfunction Vascular Cell Adhesion Molecule (VCAM), E-selectin, and Advanced Glycation Endproducts (AGEs) were measured. At baseline dp-ucMGP was associated with IMT, Diameter, cfPWV and with the mean z-scores of acute phase markers (APMscore) and of markers for endothelial dysfunction (EDFscore). After three year MK-7 supplementation cfPWV and the Stiffness Index βsignificantly decreased in the total group, whereas distension, compliance, distensibility, Young's Modulus, and the local carotid PWV (cPWV) improved in women having a baseline Stiffness Index β above the median of 10.8. MK-7 decreased dp-ucMGP by 50 % compared to placebo, but did not influence the markers for acute phase and endothelial dysfunction. In conclusion, long-term use of MK-7 supplements improves arterial stiffness in healthy postmenopausal women, especially in women having a high arterial stiffness.
authors.forename: Marjo H J
authors.initials: MH
authors.lastname: Knapen
authors.forename: Lavienja A J L M
authors.initials: LA
authors.lastname: Braam
authors.forename: Nadja E
authors.initials: NE
authors.lastname: Drummen
authors.forename: Otto
authors.initials: O
authors.lastname: Bekers
authors.forename: Arnold P G
authors.initials: AP
authors.lastname: Hoeks
authors.affiliation: Cees Vermeer, PhD, VitaK, Maastricht University, Biopartner Center Maastricht, Oxfordlaan 70, 6229 EV Maastricht, The Netherlands, Tel: +31 43 388 5865, Fax: +31 43 388 5889, E-mail: c.vermeer@vitak.com.
authors.forename: Cees
authors.initials: C
authors.lastname: Vermeer
mesh_terms: D000368:Aged; D002097:C-Reactive Protein / Q000378:metabolism; D002339:Carotid Arteries / Q000473:pathology; D059168:Carotid Intima-Media Thickness; D019587:Dietary Supplements; D004311:Double-Blind Method; D019040:E-Selectin / Q000097:blood; D005260:Female; D005263:Femoral Artery / Q000473:pathology; D017127:Glycation End Products, Advanced / Q000097:blood; D064368:Healthy Volunteers; D006490:Hemostatics / Q000627:therapeutic use*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008875:Middle Aged; D017698:Postmenopause; D063177:Pulse Wave Analysis; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D019010:Vascular Cell Adhesion Molecule-1 / Q000097:blood; D059289:Vascular Stiffness / Q000187:drug effects*; D024482:Vitamin K 2 / Q000031:analogs & derivatives* / Q000627:therapeutic use
chemical_list: D019040:E-Selectin; D017127:Glycation End Products, Advanced; D006490:Hemostatics; C508600:IL6 protein, human; D015850:Interleukin-6; C546936:SELE protein, human; C439524:TNF protein, human; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D024482:Vitamin K 2; C062629:menaquinone 7; D002097:C-Reactive Protein
keywords: Arterial stiffness; Stiffness Index β; carotid intima-media thickness; menaquinone-7; pulse wave velocity