Abstract
Background and Aims
Vitamin K insufficiency is common and linked to an increased risk of cardiovascular disease and osteoporotic fractures. The aim of this study was to examine whether daily supplementation with oral vitamin K could improve vascular health and physical function in older people with established vascular disease.
Methods and results
A double blind, randomised, placebo-controlled trial. Participants aged ≤ 70 years with a history of vascular disease were randomised to receive 6 months of daily oral 100mcg vitamin K2 (MK7 subtype) or matching placebo with outcomes measured at 0, 3 and 6 months. The primary outcome was between-group difference in endothelial function assessed using flow-mediated dilatation of the brachial artery at 6 months. Secondary outcomes included carotid-radial pulse wave velocity, augmentation index, blood pressure, carotid intima-media thickness, C-reactive protein, B-type natriuretic peptide, cholesterol and desphospho-uncarboxylated matrix Gla protein levels. Handgrip strength and the Short Physical Performance Battery assessed physical function, while postural sway was measured using a 3-dimensional force platform.
Results
80 participants were randomised, mean age 77 (SD 5) years; 44/80 were male. Vitamin K levels rose in the intervention arm compared to placebo (+48 pg/ml vs −6 pg/ml, p=0.03) at 6 months. Desphospho-uncarboxylated Matrix Gla protein levels fell in the intervention group compared to placebo at 6 months (−130 [SD 117] pmol/L vs +13 [SD 180] pmol/L, p<0.001). No change was seen in endothelial function (between group difference −0.3% [95%CI −1.3 to 0.8], p=0.62). A modest, non-significant improvement in pulse wave velocity was seen in the vitamin K group (−0.8m/s [95%CI −1.8 to 0.3], p=0.15) while all other vascular and physical function outcomes unchanged.
Conclusions
Six months of vitamin K2 supplementation did not improve markers of vascular health or physical function in older patients with vascular disease.
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Abbreviations
- BNP:
-
B-type natriuretic peptide
- CRP:
-
C-reactive protein
- Dp-ucMGP:
-
Desphospho-uncarboxylated Matrix Gla Protein
- ECG:
-
Electrocardiogram
- FMD:
-
Flow mediated dilatation
- HPLC:
-
High performance liquid chromatography
- IMT:
-
intima-media thickness
- MGP:
-
Matrix Gla Protein
- PWV:
-
Pulse wave velocity
- RDI:
-
Recommended daily intake
- SBP:
-
Systolic blood pressure
- SPPB:
-
Short physical performance battery
References
Thane CW, Bates CJ, Shearer MJ, Unadkat N, Harrington DJ, Paul AA, Prentice A, Bolton-Smith C. Plasma phylloquinone (vitamin K1) concentration and its relationship to intake in a national sample of British elderly people. Br J Nutr 2002;876:615–22.
Gast GCM, de Roos NM, Sluijs I, Bots ML, Beulens JWJ, Geleijnse JM, Witteman JC, Grobbee DE, Peeters PH, van der Schouw YT. A high menaquinone intake reduces the incidence of coronary heart disease. Nutr Metab Cardiovasc Dis 2009;197:504–10.
Shea MK, Booth SL, Massaro JM, Jacques PF, D’Agostino RB, Sr., Dawson-Hughes B, Ordovas JM, O’Donnell CJ, Kathiresan S, Keaney JF Jr, et al. Vitamin K and vitamin D status: associations with inflammatory markers in the Framingham Offspring Study. Am J Epidemiol 2008;1673:313–20.
van den Heuvel EGHM, van Schoor NM, Lips P, Magdeleyns EJP, Deeg DJH, Vermeer C, den Heijer M. Circulating uncarboxylated matrix Gla protein, a marker of vitamin K status, as a risk of cardiovascular disease. Maturitas 2014;772:137–41.
Dalmeijer GW, van der Schouw YT, Magdeleyns EJ, Vermeer C, Verschuren WMM, Boer JMA, Beulens JWJ. Matrix Gla protein species and risk of cardiovascular events in type 2 diabetic patients. Diabetes Care 2013;3611:3766–71.
Schlieper G, Westenfeld R, Krüger T, Cranenburg EC, Magdeleyns EJ, Brandenburg VM, Djuric Z, Damjanovic T, Ketteler M, Vermeer C, et al. Circulating Nonphosphorylated Carboxylated Matrix Gla Protein Predicts Survival in ESRD. J Am Soc Nephrol 2011:22(2);387–95.
Kaesler N, Schettgen T, Mutucumarana VP, Brandenburg V, Jahnen-Dechent W, Schurgers LJ, Kruger T. A fluorescent method to determine vitamin K-dependent gamma-glutamyl carboxylase activity. Anal Biochem 2012;4212:411–6.
Braam LAJLM, Hoeks APG, Brouns F, Hamulyak K, Gerichhausen MJW, Vermeer C. Beneficial effects of vitamins D and K on the elastic properties of the vessel wall in postmenopausal women: a follow-up study. Thromb Haemost 2004;2:372–80.
Kamper AM, Stott DJ, Hyland M, Murray HM, Ford I. Predictors of functional decline in elderly people with vascular risk factors or disease. Age Ageing 2005;34:450–5.
Cheung AM, Tile L, Lee Y, Tomlinson G, Hawker G, Scher J, Hu H, Vieth R, Thompson R, Jamal S, et al. Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial. PLoS Med 2008;5(10):e196.
Dalmeijer GW, van der Schouw YT, Magdeleyns E, Ahmed N, Vermeer C, Beulens JW. The effect of menaquinone-7 supplementation on circulating species of matrix Gla protein. Atherosclerosis 2012;225:397–402.
Westenfeld R, Krueger T, Schlieper G, Cranenburg ECM, Magdeleyns EJ, Heidenreich S, Holzmann S, Vermeer C, Jahnen-Dechent W, Ketteler M, et al. Effect of vitamin K2 supplementation on functional vitamin K deficiency in haemodialysis patients: a randomised controlled trial. Am J Kidney Dis 2012;592:186–95.
Corretti MC, Anderson TJ, Benjamin EJ, Celermajer DS, Charbonneau F, Creager MA, Deanfield J, Drexler H, Gerhard-Herman M, Herrington D, et al. Guidelines for the ultrasound Assessment of Endothelial-Dependent Vasodilation of the Brachial Artery. J Am Coll Cardiol 2002;2:257–65.
Naka KN, Papathanassiou K, Bechlioulis A, Kazakos N, Pappas K, Tigas S, Makriyiannis D, Tsatsoulis A, Michalis LK. Determinants of vascular function in patients with type 2 diabetes. Cardiovasc Diabetol 2012; 11:127.
Perticone F, Ceravolo R, Pujia A, Ventura G, Iacopino S, Scozzafava A, Ferraro A, Chello M, Mastroroberto P, Verdecchia P, et al. Prognostic Significance of Endothelial Dysfunction in Hypertensive Patients. Circulation 2001;104:191–6.
Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, Lloyd JK, Deanfield JE. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992;340:1111–5.
Cranenburg ECM, Koos R, Schurgers LJ, Magdeleyns EJ, Schoonbrood THM, Landewe RB, Brandenburg VM, Bekers O, Vermeer C. Characterization and potential diagnostic value of circulating matrix Gla protein (MGP) species. Thromb Haemostas 2010;104:811–22.
Gawel J, Vengrow D, Collins J, Brown S, Buchanan A, Cook C. The short performance battery as a predictor for long term disability or institutionalization in the community dwelling population aged 65 years old or older. Phys Ther Rev 2012;171:37–44.
Decker LM, Ramdani S, Tallon G, Jaussent A, Picot MC, Bernard PL, et al. Physical function decline and degradation of postural sway dynamics in asymptomatic sedentary postmenopausal women. J Nutr Health Aging. 2015;193:348–55.
Pavol, MJ. Detecting and Understanding Differences in Postural Sway. Focus on A New Interpretation of Spontaneous Sway Measures Based on a Simple Model of Human Postural Control. J Neurophysiol 2005;93:20–1.
Moriguch, J, Itoh, H, Harada, S, Takeda, K, Hatta, T, Nakata, T, Sasaki, S. Low Frequency Regular Exercise Improves Flow-Mediated Dilatation of Subjects with Mild Hypertension. Hypertens Res 2005;28:315–21.
Dogra, GK, Watts GF, Herrmann, S, Thomas MAB, Irish AB. Statin therapy improves brachial artery endothelial function in nephrotic syndrome. Kidney Int 2002;62:550–7.
Kaesler N, Magdeleyns E, Herfs M, Schettgen T, Brandenburg V, Fliser D et al. Impaired vitamin K recycling in uremia is rescued by vitamin K supplementation. Kidney Int. 2014;86:286–93.
Health & Consumer Protection Directorate General. European Commission. Discussion Paper on the setting of maximum and minimum amounts for vitamins and minerals in foodstuffs. June 2006; 1–27.
Blankenhorn DH, Kramsch DM, Azen SP, Mack WJ, Cashin-Hemphill L, Hodis HN, De Boer LW, Mahrer PR, Masteller MJ, Vailas LI, et al. Coronary Angiographic Changes with Lovastatin Therapy: The Monitored Artherosclerosis Regression study (MARS). Ann Intern Med 1993;119:969–76.
George J, Carr E, Davis J, Belch JJF, Struthers AD. High dose allopurinol improves endothelial function by profoundly reducing vascular oxidative stress and not by lowering uric acid. Circulation 2006;114:2508–16.
Sugden JA, Davies JI, Witham MD, Morris AD, Struthers AD. Vitamin D improves endothelial function in patients with type 2 diabetes mellitus and low vitamin D levels. Diabet Med 2008;253:320–5.
Buurman BM, van Munster BC, Korevaar JC, Abu-Hanna A, Levi M, de Rooij SE. Prognostication in acutely admitted older patients by nurses and physicians. J Gen Int Med 2008;23:1883–9.
Dorner TE, Luger E, Tschinderle J, Stein KV, Haider S, Kapan A, et al. Association between nutritional status (MNA(R)-SF) and frailty (SHARE-FI) in acute hospitalised elderly patients. J Nutr, Health Aging 2014;18:264–9.
Matzen LE, Jepsen DB, Ryg J, Masud T. Functional level at admission is a predictor of survival in older patients admitted to an acute geriatric unit. BMC geriatrics 2012;12:32.
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Fulton, R.L., McMurdo, M.E.T., Hill, A. et al. Effect of vitamin K on vascular health and physical function in older people with vascular disease–a randomised controlled trial. J Nutr Health Aging 20, 325–333 (2016). https://doi.org/10.1007/s12603-015-0619-4
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DOI: https://doi.org/10.1007/s12603-015-0619-4