The function of vitamin K is to serve as a co-factor during the post-translational carboxylation of glutamate (Glu) residues into γ-carboxyglutamate (Gla) residues. The vital importance of the Gla-proteins essential for normal haemostasis is well recognized. During recent years, new Gla-containing proteins have been discovered and the vitamin K-dependent carboxylation is also essential for their function. It seems, however, that our dietary vitamin K intake is too low to support the carboxylation of at least some of these Gla-proteins. According to the triage theory, long-term vitamin K inadequacy is an independent, but modifiable risk factor for the development of degenerative diseases of ageing including osteoporosis and atherosclerosis.
BerknerKL. The vitamin K-dependent carboxylase. Annu Rev Nutr2005;25:127–49
2.
DucyP, DesboisC, BoyceB, Increased bone formation in osteocalcin-deficient mice. Nature1996;382:448–52
3.
LuoG, DucyP, McKeeMD, Spontaneous calcification of arteries and cartilage in mice lacking matrix GLA protein. Nature1997;386:78–81
4.
ViegasCS, CavacoS, NevesPL, Gla-rich protein is a novel vitamin K-dependent protein present in serum that accumulates at sites of pathological calcifications. Am J Pathol2009;175:2288–98
5.
SchurgersLJ, CranenburgECM, VermeerC. Matrix Gla-protein: the calcification inhibitor in need of vitamin K. Thromb Haemostas2008;100:593–603
6.
ShearerMJ, NewmanP. Metabolism and cell biology of vitamin K. Thromb Haemostas2008;100:530–47
7.
SchurgersLJ, VermeerC. Determination of phylloquinone and menaquinones in food: effect of food matrix on circulating vitamin K concentrations. Haemostasis2000;30:298–307
8.
McCannJC, AmesBN. Vitamin K, an example of triage theory: is micronutrient inadequacy linked to diseases of aging?Am J Clin Nutr2009;90:889–907
WallinR, SaneDC, HutsonSM. Vitamin K 2,3-epoxide reductase and the vitamin K-dependent gammacarboxylation system. Thromb Res2003;108:221–6
11.
FeskanichD, WeberP, WillettWC, RockettH, BoothS, ColditzGA. Vitamin K intake and hip fractures in women: a prospective study. Am J Clin Nutr1999;69:74–9
12.
BoothSL, BroeKE, GagnonDR, Vitamin K intake and bone mineral density in women and men. Am J Clin Nutr2003;77:512–6
13.
MacdonaldHM, McGuiganFE, Lanham-NewSA, FraserWD, RalstonSH, ReidDM. Vitamin K1 intake is associated with higher bone mineral density and reduced bone resorption in early postmenopausal Scottish women: no evidence of gene–nutrient interaction with apolipoprotein E polymorphisms. Am J Clin Nutr2008;87:1513–20
14.
HartJP, ShearerMJ, KlenermanL, Electrochemical detection of depressed circulating levels of vitamin K1 in osteoporosis. J Clin Endocrinol Metab1985;60:1268–9
15.
HodgesSJ, AkessonK, VergnaudP, ObrantK, DelmasPD. Circulating levels of vitamins K1 and K2 decreased in elderly women with hip fracture. J Bone Miner Res1993;8:1241–5
16.
TsugawaN, ShirakiM, SuharaY, Low plasma phylloquinone concentration is associated with high incidence of vertebral fracture in Japanese women. J Bone Miner Metab2008;26:79–85
17.
KnapenMHJ, Nieuwenhuijzen KrusemanAC, WoutersRSME, VermeerC. Correlation of serum osteocalcin fractions with bone mineral density in women during the first 10 years after menopause. Calcif Tissue Int1998;63:375–9
18.
SzulcP, ChapuyM-C, MeunierPJ, DelmasPD. Serum undercarboxylated osteocalcin is a marker of the risk of hip fracture in elderly women. J Clin Invest1993;91:1769–74
19.
SzulcP, ArlotM, ChapuyM-C, DuboeufF, MeunierPJ, DelmasPD. Serum undercarboxylated osteocalcin correlates with hip bone mineral density in elderly women. J Bone Miner Res1994;9:1591–5
20.
LuukinenH, KäkönenS-M, PettersonK, Strong prediction of fractures among older adults by the ratio of carboxylated to total serum osteocalcin. J Bone Miner Res2000;15:2473–8
21.
IwamotoJ, SatoY, TakedaT, MatsumotoH. High-dose vitamin K supplementation reduces fracture incidence in postmenopausal women: a review of the literature. Nutr Res2009;29:221–8
22.
BraamLAJLM, KnapenMHJ, GeusensP, Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age. Calcif Tissue Int2003;73:21–6
23.
Bolton-SmithC, McMurdoMET, PatersonCR, Two-year randomized controlled trial of vitamin K1 (phylloquinone) and vitamin D3 plus calcium on the bone health of older women. J Bone Miner Res2007;22:509–19
24.
NeogiT, BoothSL, ZhangYQ, Low vitamin K status is associated with osteoarthritis in the hand and knee. Arthritis Rheum2006;54:1255–61
25.
GeleijnseJM, VermeerC, GrobbeeDE, Dietary intake of vitamin K-2 reduces the risk of cardiac events and aortic atherosclerosis: The Rotterdam Study. J Nutr2004;134:3100–5
26.
GastGCM, de RoosNM, SluijsI, A high menaquinone intake reduces the incidence of coronary heart disease. Nutr Metab Cardiovasc Dis2009;19:504–10
27.
BeulensJWJ, BotsML, AtsmaF, High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis2009;203:489–93
28.
PricePA, FausSA, WilliamsonMK. Warfarin causes rapid calcification of the elastic lamellae in rat arteries and heart valves. Arterioscler Thromb Vasc Biol1998;18:1400–7
29.
SchurgersLJ, AebertH, VermeerC, BültmannB, JanzenJ. Oral anticoagulant treatment: friend or foe in cardiovascular disease?Blood2004;104:3231–2
30.
KoosR, MahnkenAH, MühlenbruchG, Relation of oral anticoagulation to cardiac valvular and coronary calcium assessed by multisliced spiral computed tomography. Am J Cardiol2005;96:747–9
31.
SchurgersLJ, BarretoDV, LiaboeufS, The circulating inactive form of matrix Gla protein is a surrogate marker for vascular calcification in chronic kidney disease: a preliminary report. Clin J Am Soc Nephrol2010;5:568–75
32.
ParkerBD, SchurgersLJ, BrandenburgVM, FGF-23, matrix Gla protein, fetuin-A and mortality in persons with coronary heart disease: The Heart and Soul Study. Ann Int Med2010;152:640–8
33.
UelandT, GullestadL, DahlCP, Undercarboxylated matrix gla protein is associated with development of heart failure in symptomatic aortic stenosis. J Int Med2010;268:483–92
34.
CranenburgECM, KoosR, SchurgersLJ, Characterization and potential diagnostic value of circulating matrix Gla protein (MGP) species. Thromb Haemostas2010;104:811–22
35.
VermeerC. Clinical trial on beneficial effects of long term menaquinone-7 (vitamin K2) intake by postmenopausal women. ClinicalTrials.Gov NCT00642551
36.
KroonA. The effects of vitamin K2 supplementation on the progression of coronary artery calcification. Clinical Trials. Gov NCT01002157
37.
NimptschK, RohrmannS, LinseisenJ. Dietary intake of vitamin K and risk of prostate cancer in the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg). Am J Clin Nutr2008;87:985–92
38.
NimptschK, RohrmannS, KaaksR, LinseisenJ. Dietary vitamin K intake in relation to cancer incidence and mortality: results from the Heidelberg cohort of the European Prospective Investigation into Cancer and Nutrition (EPIC-Heidelberg). Am J Clin Nutr2010;91:1348–58
39.
AllisonAC. The possible role of vitamin K deficiency in the pathogenesis of Alzheimer's disease and in augmenting brain damage associated with cardiovascular disease. Med Hypotheses2001;57:151–5
40.
SatoY, HondaY, HayashidaN, IwamotoJ, KanokoT, SatohK. Vitamin K deficiency and osteopenia in elderly women with Alzheimer's disease. Arch Phys Med Rehabil2005;86:576–81
41.
PresseN, ShatensteinB, KergoatMJ, FerlandG. Low vitamin K intakes in community-dwelling elders at an early stage of Alzheimer's disease. J Am Diet Assoc2008;108:2095–9
42.
YoshidaM, BoothSL, MeigsJB, SaltzmanE, JacquesPF. Phylloquinone intake, insulin sensitivity, and glycemic status in men and women. Am J Clin Nutr2008;88:210–5
43.
SheaMK, O'DonnellCJ, HoffmannU, Vitamin K supplementation and progression of coronary artery calcium in older men and women. Am J Clin Nutr2009;89:1799–807
44.
YoshidaM, JacquesPF, MeigsJB, Effect of vitamin K supplementation on insulin resistance in older men and women. Diabetes Care2008;31:2092–6
45.
BeulensJW, van derADL, GrobbeeDE, SluijsI, SpijkermanAM, van der SchouwYT. Dietary phylloquinone and menaquinones intakes and risk of type 2 diabetes. Diabetes Care2010;33:1699–705
