Vitamin K status has been linked to fat and glucose metabolism by several authors, but whether high vitamin K intake influences body weight or composition has remained unclear. Here we tested the hypothesis that increased vitamin K intake decreases body fat or fat distribution.
In a randomized placebo-controlled human intervention trial, 214 postmenopausal women, 55–65 years of age, received either 180 mcg/day of vitamin K2 (menaquinone-7, MK-7) or placebo for 3 years. Osteocalcin (OC) carboxylation was used as a marker for vitamin K status, and fat distribution was assessed by dual-energy X-ray absorptiometry total body scan.
In the total cohort, MK-7 supplementation increased circulating carboxylated OC (cOC) but had no effect on body composition. In those with an above-median response in OC carboxylation (‘good responders’), MK-7 treatment resulted in a significant increase in total and human molecular weight adiponectin and a decrease in abdominal fat mass and in the estimated visceral adipose tissue area compared with the placebo group and the poor responders.
The fact that changes in body composition measures or markers for fat or glucose metabolism were not associated with changes in uncarboxylated OC (ucOC) does not support the assumption that ucOC stimulates fat metabolism in humans. Instead, high vitamin K2 intake may support reducing body weight, abdominal and visceral fat, notably in subjects showing a strong increase in cOC. A causal relation between the changes in cOC and body fat or distribution cannot be concluded from these data.
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Lee NK, Karsenty G . Reciprocal regulation of bone and energy metabolism. Trends Endocrinol Metab 2008; 19: 161–166.
Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, Confavreux C et al. Endocrine regulation of energy metabolism by the skeleton. Cell 2007; 130: 456–469.
Shiba S, Ikeda K, Azuma K, Hasegawa T, Amizuka N, Horie-Inoue K et al. γ-Glutamyl carboxylase in osteoblasts regulates glucose metabolism in mice. Biochem Biophys Res Commun 2014; 453: 350–355.
Ferron M, Lacombe J, Germain A, Oury F, Karsenty G . GGCX and VKORC1 inhibit osteocalcin endocrine functions. J Cell Biol 2015; 208: 761–776.
Ferron M, Hinoi E, Karsenty G, Ducy P . Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci USA 2008; 105: 5266–5270.
Ferron M, McKee MD, Levine RL, Ducy P, Karsenty G . Intermittent injections of osteocalcin improve glucose metabolism and prevent type 2 diabetes in mice. Bone 2012; 50: 568–575.
Sogabe N, Maruyama R, Baba O, Hosoi T, Goseki-Sone M . Effects of long-term vitamin K(1) (phylloquinone) or vitamin K(2) (menaquinone-4) supplementation on body composition and serum parameters in rats. Bone 2011; 48: 1036–1042.
Booth SL, Centi A, Smith SR, Gundberg CM . The role of osteocalcin in human glucose metabolism: marker or mediator? Nat Rev Endocrinol 2013; 9: 43–55.
Juanola-Falgarona M, Salas-Salvado J, Estruch R, Portillo MP, Casas R, Miranda J et al. Association between dietary phylloquinone intake and peripheral metabolic risk markers related to insulin resistance and diabetes in elderly subjects at high cardiovascular risk. Cardiovasc Diabetol 2013; 12: 7.
Shea MK, Booth SL, Gundberg CM, Peterson JW, Waddell C, Dawson-Hughes B et al. Adulthood obesity is positively associated with adipose tissue concentrations of vitamin K and inversely associated with circulating indicators of vitamin K status in men and women. J Nutr 2010; 140: 1029–1034.
Knapen MHJ, Schurgers LJ, Shearer MJ, Newman P, Theuwissen E, Vermeer C . Association of vitamin K status with adiponectin and body composition in healthy subjects: uncarboxylated osteocalcin is not associated with fat mass and body weight. Br J Nutr 2012; 108: 1017–1024.
Tamura T, Yoneda M, Yamane K, Nakanishi S, Nakashima R, Okubo M et al. Serum leptin and adiponectin are positively associated with bone mineral density at the distal radius in patients with type 2 diabetes mellitus. Metabolism 2007; 56: 623–628.
Kanazawa I, Yamaguchi T, Yamauchi M, Yamamoto M, Kurioka S, Yano S et al. Serum undercarboxylated osteocalcin was inversely associated with plasma glucose level and fat mass in type 2 diabetes mellitus. Osteoporos Int 2011; 22: 187–194.
Pittas AG, Harris SS, Eliades M, Stark P, Dawson-Hughes B . Association between serum osteocalcin and markers of metabolic phenotype. J Clin Endocrinol Metab 2009; 94: 827–832.
Fernandez-Real JM, Izquierdo M, Ortega F, Gorostiaga E, Gómez-Ambrosi J, Moreno-Navarrete JM et al. The relationship of serum osteocalcin concentration to insulin secretion, sensitivity, and disposal with hypocaloric diet and resistance training. J Clin Endocrinol Metab 2009; 94: 237–245.
Kindblom JM, Ohlsson C, Ljunggren O, Karlsson MK, Tivesten A, Smith U et al. Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men. J Bone Miner Res 2009; 24: 785–791.
Im JA, Yu BP, Jeon JY, Kim SH . Relationship between osteocalcin and glucose metabolism in postmenopausal women. Clin Chim Acta 2008; 396: 66–69.
Yeap BB, Chubb SA, Flicker L, McCaul KA, Ebeling PR, Beilby JP et al. Reduced serum total osteocalcin is associated with metabolic syndrome in older men via waist circumference, hyperglycemia, and triglyceride levels. Eur J Endocrinol 2010; 163: 265–272.
Centi AJ, Booth SL, Gundberg CM, Saltzman E, Nicklas B, Shea MK . Osteocalcin carboxylation is not associated with body weight or percent fat changes during weight loss in post-menopausal women. Endocrine 2015; 50: 627–632.
Hwang YC, Jeong IK, Ahn KJ, Chung HY . The uncarboxylated form of osteocalcin is associated with improved glucose tolerance and enhanced beta-cell function in middle-aged male subjects. Diabetes Metab Res Rev 2009; 25: 768–772.
Ibarrola-Jurado N, Salas-Salvado J, Martinez-Gonzalez MA, Bulló M . Dietary phylloquinone intake and risk of type 2 diabetes in elderly subjects at high risk of cardiovascular disease. Am J Clin Nutr 2012; 96: 1113–1118.
Yoshida M, Booth SL, Meigs JB, Saltzman E, Jacques PF . Phylloquinone intake, insulin sensitivity, and glycemic status in men and women. Am J Clin Nutr 2008; 88: 210–215.
Kumar R, Binkley N, Vella A . Effect of phylloquinone supplementation on glucose homeostasis in humans. Am J Clin Nutr 2010; 92: 1528–1532.
Yoshida M, Jacques PF, Meigs JB, Saltzman E, Shea MK, Gundberg CM et al. Effect of vitamin K supplementation on insulin resistance in older men and women. Diabetes Care 2008; 31: 2092–2096.
Choi HJ, Yu J, Choi H, An JH, Kim SW, Park KS et al. Vitamin K2 supplementation improves insulin sensitivity via osteocalcin metabolism: a placebo-controlled trial. Diabetes Care 2011; 34: e147.
Shea MK, Dawson-Hughes B, Gundberg CM, Booth SL . Reducing undercarboxylated osteocalcin with vitamin K supplementation does not promote lean tissue loss or fat gain over 3 years in older women and men: a randomized controlled trial. J Bone Miner Res 2017; 32: 243–249.
Knapen MHJ, Drummen NE, Smit E, Vermeer C, Theuwissen E . Three-year low-dose menaquinone-7 supplementation helps decrease bone loss in healthy postmenopausal women. Osteoporos Int 2013; 24: 2499–2507.
Braam LAJLM, Knapen MHJ, Geusens P, Brouns F, Hamulyák K, Gerichhausen MJ et al. Vitamin K1 supplementation retards bone loss in postmenopausal women between 50 and 60 years of age. Calcif Tissue Int 2003; 73: 21–26.
Knapen MHJ, Schurgers LJ, Vermeer C . Vitamin K2 supplementation improves bone geometry and bone strength indices in postmenopausal women. Osteoporos Int 2007; 18: 963–972.
Rasekhi H, Karandish M, Jalali MT, Mohammad-shahi M, Zarei M, Saki A et al. The effect of vitamin K1 supplementation on sensitivity and insulin resistance via osteocalcin in prediabetic women: a double-blind randomized controlled clinical trial. Eur J Clin Nutr 2015; 69: 891–895.
Hotamisligil GS . Inflammation and metabolic disorders. Nature 2006; 444: 860–867.
This work was supported by NattoPharma (Høvik, Norway). The sponsor had no role in the design, analysis or writing of this article.
CV contributed to the design of the study and was involved in the interpretation of the findings and preparation of the manuscript; MHJK was involved in the conduct of the study and performed the statistical analyses. MHJK and KMJ contributed to the interpretation of the findings and to the preparation of the manuscript. All authors read and approved the final manuscript.
The authors declare no conflict of interest.
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Knapen, M., Jardon, K. & Vermeer, C. Vitamin K-induced effects on body fat and weight: results from a 3-year vitamin K2 intervention study. Eur J Clin Nutr 72, 136–141 (2018) doi:10.1038/ejcn.2017.146
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