Genomes and Genes
vitamin k 2
Summary: A group of substances similar to VITAMIN K 1 which contains a ring of 2-methyl-1,4-naphthoquinione and an isoprenoid side chain of varying number of isoprene units. In vitamin K 2, each isoprene unit contains a double bond. They are produced by bacteria including the normal intestinal flora.
- Sato Y, Honda Y, Kuno H, Oizumi K. Menatetrenone ameliorates osteopenia in disuse-affected limbs of vitamin D- and K-deficient stroke patients. Bone. 1998;23:291-6 pubmed
- Kitagawa J, Hara T, Tsurumi H, Ninomiya S, Ogawa K, Adachi S, et al. Synergistic growth inhibition in HL-60 cells by the combination of acyclic retinoid and vitamin K2. J Cancer Res Clin Oncol. 2011;137:779-87 pubmed publisher..Moreover, ACR and VK(2) induced increases in G0/G1 phase HL-60 cells, alone and synergistically in combination. The synergistic effects of ACR and VK(2) on HL-60 cells may provide a novel strategy for treating leukemia. ..
- Iwamoto J, Takeda T, Ichimura S. Combined treatment with vitamin k2 and bisphosphonate in postmenopausal women with osteoporosis. Yonsei Med J. 2003;44:751-6 pubmed..It is proposed that the role of vitamin K2 should be emphasized, when used in combination with bisphosphonates, especially in patients with vitamin K deficiency. ..
- Saffarini D, Blumerman S, Mansoorabadi K. Role of menaquinones in Fe(III) reduction by membrane fractions of Shewanella putrefaciens. J Bacteriol. 2002;184:846-8 pubmed..These results indicate that menaquinones are essential components for the reduction of Fe(III) by both whole cells and purified membrane fractions when formate or lactate is used as the electron donor...
- Ma M, Qu X, Mu G, Chen M, Cheng Y, Kokudo N, et al. Vitamin K2 inhibits the growth of hepatocellular carcinoma via decrease of des-gamma-carboxy prothrombin. Chemotherapy. 2009;55:28-35 pubmed publisher..Vitamin K(2) might suppress the growth and invasion of HCC cells via decrease of DCP. ..
- Lu X, Zhou R, Sharma I, Li X, Kumar G, Swaminathan S, et al. Stable analogues of OSB-AMP: potent inhibitors of MenE, the o-succinylbenzoate-CoA synthetase from bacterial menaquinone biosynthesis. Chembiochem. 2012;13:129-36 pubmed publisher..A pH-dependent interconversion of the free keto acid and lactol forms of the inhibitors is also described, along with implications for inhibitor design. ..
- Bruge F, Bacchetti T, Principi F, Littarru G, Tiano L. Olive oil supplemented with menaquinone-7 significantly affects osteocalcin carboxylation. Br J Nutr. 2011;106:1058-62 pubmed publisher..We conclude that regular consumption of MK-7-enriched olive oil may constitute a valid approach in order to preserve some key biochemical mechanisms controlling bone mineralisation. ..
- Matsumoto K, Okano J, Nagahara T, Murawaki Y. Apoptosis of liver cancer cells by vitamin K2 and enhancement by MEK inhibition. Int J Oncol. 2006;29:1501-8 pubmed..These data demonstrated that VK2 induced apoptosis and activated the MEK/ERK1/2 signaling pathway in a cell-type specific manner, and a MEK inhibitor could augment the cell death in these cells. ..
- Lamson D, Plaza S. The anticancer effects of vitamin K. Altern Med Rev. 2003;8:303-18 pubmed..Tyrosine kinases associated with cyclins have also been shown to be affected by vitamin K, which can lead to cell cycle arrest and cell death. ..
- Ozaki I, Zhang H, Mizuta T, Ide Y, Eguchi Y, Yasutake T, et al. Menatetrenone, a vitamin K2 analogue, inhibits hepatocellular carcinoma cell growth by suppressing cyclin D1 expression through inhibition of nuclear factor kappaB activation. Clin Cancer Res. 2007;13:2236-45 pubmed..Vitamin K2 inhibits the growth of HCC cells via suppression of cyclin D1 expression through the IKK/IkappaB/NF-kappaB pathway and might therefore be useful for treatment of HCC. ..
- Yamamoto T, Nakamura H, Liu W, Cao K, Yoshikawa S, Enomoto H, et al. Involvement of hepatoma-derived growth factor in the growth inhibition of hepatocellular carcinoma cells by vitamin K(2). J Gastroenterol. 2009;44:228-35 pubmed publisher..These findings suggested that regulation of the HDGF gene expression is one of the crucial mechanisms of vitamin K(2)-induced cell growth suppression for HCC. ..
- Iwamoto J, Yeh J, Takeda T. Effect of vitamin K2 on cortical and cancellous bones in orchidectomized and/or sciatic neurectomized rats. J Bone Miner Res. 2003;18:776-83 pubmed..The present study provides evidence indicating that vitamin K2 has the potential to suppress bone resorption or bone turnover and/or stimulate bone formation in vivo in ORX and/or NX rats. ..
- Li L, Qi Z, Qian J, Bi F, Lv J, Xu L, et al. Induction of apoptosis in hepatocellular carcinoma Smmc-7721 cells by vitamin K(2) is associated with p53 and independent of the intrinsic apoptotic pathway. Mol Cell Biochem. 2010;342:125-31 pubmed publisher..In summary, these data suggested that VK(2) can inhibit the growth of Smmc-7721 cells by induction of apoptosis involving caspase 8 activation and p53. This apoptotic process was not mediated by the intrinsic apoptotic pathway. ..
- Gast G, de Roos N, Sluijs I, Bots M, Beulens J, Geleijnse J, et al. A high menaquinone intake reduces the incidence of coronary heart disease. Nutr Metab Cardiovasc Dis. 2009;19:504-10 pubmed publisher..A high intake of menoquinones, especially MK-7, MK-8 and MK-9, could protect against CHD. However, more research is necessary to define optimal intake levels of vitamin K intake for the prevention of CHD. ..
- Kobayashi M, Hara K, Akiyama Y. Effects of vitamin K2 (menatetrenone) on calcium balance in ovariectomized rats. Jpn J Pharmacol. 2002;88:55-61 pubmed..These findings suggest that the poor Ca balance observed in ovariectomized rats may be improved by vitamin K2; vitamin K2 may be involved in preventing bone loss in vivo. ..
- Fu Q, Boonchayaanant B, Tang W, Trost B, Criddle C. Simple menaquinones reduce carbon tetrachloride and iron (III). Biodegradation. 2009;20:109-16 pubmed publisher..The results indicate that molecules within the menaquinone family may contribute to both the extracellular and cell-associated reduction of carbon tetrachloride and iron (III). ..
- Iwasaki Y, Yamato H, Murayama H, Sato M, Takahashi T, Ezawa I, et al. Combination use of vitamin K(2) further increases bone volume and ameliorates extremely low turnover bone induced by bisphosphonate therapy in tail-suspension rats. J Bone Miner Metab. 2003;21:154-60 pubmed..These data suggested that concomitant use of vitamin K(2) with bisphosphonate excessively ameliorates too much suppression of bone turnover while more efficiently preventing bone volume loss. ..
- Ichikawa T, Horie Inoue K, Ikeda K, Blumberg B, Inoue S. Vitamin K2 induces phosphorylation of protein kinase A and expression of novel target genes in osteoblastic cells. J Mol Endocrinol. 2007;39:239-47 pubmed..These results suggest that vitamin K(2) modulates its target gene expression in osteoblastic cells through the PKA-dependent mechanism, which may be distinct from the previously known vitamin K signaling pathways. ..
- Ishizuka M, Kubota K, Shimoda M, Kita J, Kato M, Park K, et al. Effect of menatetrenone, a vitamin k2 analog, on recurrence of hepatocellular carcinoma after surgical resection: a prospective randomized controlled trial. Anticancer Res. 2012;32:5415-20 pubmed..3%, 58.1%, and 31.0%, respectively (p=0.060). MNT has a moderately suppressive effect on HCC recurrence after hepatectomy, especially in patients with a normal preoperative DCP level. ..
- Zhang H, Ozaki I, Hamajima H, Iwane S, Takahashi H, Kawaguchi Y, et al. Vitamin K2 augments 5-fluorouracil-induced growth inhibition of human hepatocellular carcinoma cells by inhibiting NF-?B activation. Oncol Rep. 2011;25:159-66 pubmed..VK2 inhibited 5-FU-induced NF-?B activation and cyclin D1 expression. Therefore, combination of VK2 and 5-FU might represent a new therapeutic strategy for patients with HCC. ..
- Baik K, Kim M, Park S, Lee D, Lee S, Ka J, et al. Spirosoma rigui sp. nov., isolated from fresh water. Int J Syst Evol Microbiol. 2007;57:2870-3 pubmed..Strain WPCB118(T) represents a novel species of the genus Spirosoma, for which the name Spirosoma rigui sp. nov. is proposed. The type strain is WPCB118(T) (=KCTC 12531(T)=NBRC 101117(T)). ..
- Knapen M, Schurgers L, Vermeer C. Vitamin K2 supplementation improves hip bone geometry and bone strength indices in postmenopausal women. Osteoporos Int. 2007;18:963-72 pubmed..Vitamin K(2) helps maintaining bone strength at the site of the femoral neck in postmenopausal women by improving BMC and FNW, whereas it has little effect on DXA-BMD. ..
- Kakizaki S, Sohara N, Sato K, Suzuki H, Yanagisawa M, Nakajima H, et al. Preventive effects of vitamin K on recurrent disease in patients with hepatocellular carcinoma arising from hepatitis C viral infection. J Gastroenterol Hepatol. 2007;22:518-22 pubmed..However, there was no significant difference in the survival rates. The chemopreventive effects of vitamin K2 are not sufficient. The development of a further regimen such as combination therapy is required. ..
- Dairi T. Menaquinone biosyntheses in microorganisms. Methods Enzymol. 2012;515:107-22 pubmed publisher..In the case of the former two strains, AFL was converted to FL by deaminases then to DHFL. In contrast, AFL was directly converted to DHFL in H. pylori. ..
- Hiratsuka T, Furihata K, Ishikawa J, Yamashita H, Itoh N, Seto H, et al. An alternative menaquinone biosynthetic pathway operating in microorganisms. Science. 2008;321:1670-3 pubmed publisher..As humans and commensal intestinal bacteria, including lactobacilli, lack this pathway, it represents an attractive target for the development of chemotherapeutics...
- Takeuchi Y, Suzawa M, Fukumoto S, Fujita T. Vitamin K(2) inhibits adipogenesis, osteoclastogenesis, and ODF/RANK ligand expression in murine bone marrow cell cultures. Bone. 2000;27:769-76 pubmed..Therefore, MK4 may favor bone metabolism to spare bone mass as a compound that modulates cellular differentiation and functions in bone marrow in addition to as a nutrient factor. ..
- Tsang C, Kamei Y. Novel effect of vitamin K(1) (phylloquinone) and vitamin K(2) (menaquinone) on promoting nerve growth factor-mediated neurite outgrowth from PC12D cells. Neurosci Lett. 2002;323:9-12 pubmed..These results suggest that the K vitamins enhance neurite outgrowth via the activation of PKA and MAPK-mediated signaling pathways in PC12D cells. ..
- Iwasaki Y, Yamato H, Murayama H, Sato M, Takahashi T, Ezawa I, et al. Maintenance of trabecular structure and bone volume by vitamin K(2) in mature rats with long-term tail suspension. J Bone Miner Metab. 2002;20:216-22 pubmed
- Nakagawa K, Hirota Y, Sawada N, Yuge N, Watanabe M, Uchino Y, et al. Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. Nature. 2010;468:117-21 pubmed publisher..Our results show that UBIAD1 is a human MK-4 biosynthetic enzyme; this identification will permit more effective decisions to be made about vitamin?K intake and bone health. ..
- Habu D, Shiomi S, Tamori A, Takeda T, Tanaka T, Kubo S, et al. Role of vitamin K2 in the development of hepatocellular carcinoma in women with viral cirrhosis of the liver. JAMA. 2004;292:358-61 pubmed..13 (95% CI, 0.02-0.99; P =.05). There is a possible role for vitamin K2 in the prevention of hepatocellular carcinoma in women with viral cirrhosis. ..
- Otsuka M, Kato N, Shao R, Hoshida Y, Ijichi H, Koike Y, et al. Vitamin K2 inhibits the growth and invasiveness of hepatocellular carcinoma cells via protein kinase A activation. Hepatology. 2004;40:243-51 pubmed..In conclusion, similar to an acyclic retinoid--which was previously reported to prevent the recurrence of HCC--vitamin K(2), another lipid-soluble vitamin, may be a promising therapeutic means for the management of HCC. ..
- Spronk H, Soute B, Schurgers L, Thijssen H, De Mey J, Vermeer C. Tissue-specific utilization of menaquinone-4 results in the prevention of arterial calcification in warfarin-treated rats. J Vasc Res. 2003;40:531-7 pubmed
- Mizuta T, Ozaki I. Hepatocellular carcinoma and vitamin K. Vitam Horm. 2008;78:435-42 pubmed publisher..Our laboratory findings revealed that the inhibitory effect of vitamin K2 against HCC cell growth was generated by suppressing cyclin D1 expression through inhibition of NF-kappaB activation. ..
- Thijssen H, Vervoort L, Schurgers L, Shearer M. Menadione is a metabolite of oral vitamin K. Br J Nutr. 2006;95:260-6 pubmed..The observations make it likely that part of the menaquinone-4 in tissues results from uptake and prenylation of circulating menadione. ..
- Ito A, Shirakawa H, Takumi N, Minegishi Y, Ohashi A, Howlader Z, et al. Menaquinone-4 enhances testosterone production in rats and testis-derived tumor cells. Lipids Health Dis. 2011;10:158 pubmed publisher..MK-4 may be involved in steroidogenesis in the testis, and its supplementation could reverse the downregulation of testosterone production in elders. ..
- Georgellis D, Kwon O, Lin E. Quinones as the redox signal for the arc two-component system of bacteria. Science. 2001;292:2314-6 pubmed..Thus, the Arc signal transduction system provides a link between the electron transport chain and gene expression. ..
- Yoshida H, Shiratori Y, Kudo M, Shiina S, Mizuta T, Kojiro M, et al. Effect of vitamin K2 on the recurrence of hepatocellular carcinoma. Hepatology. 2011;54:532-40 pubmed publisher..811) between the placebo and combined active-drug groups, and the study was discontinued in March 2007. Efficacy of vitamin K2 in suppressing HCC recurrence was not confirmed in this double-blind, randomized, placebo-controlled study. ..
- Jiang M, Chen M, Cao Y, Yang Y, Sze K, Chen X, et al. Determination of the stereochemistry of 2-succinyl-5-enolpyruvyl-6-hydroxy-3- cyclohexene-1-carboxylate, a key intermediate in menaquinone biosynthesis. Org Lett. 2007;9:4765-7 pubmed..Structural determination of this key intermediate represents a critical step to complete elucidation of the biosynthetic pathway. ..
- Inoue T, Sugiyama T, Matsubara T, Kawai S, Furukawa S. Inverse correlation between the changes of lumbar bone mineral density and serum undercarboxylated osteocalcin after vitamin K2 (menatetrenone) treatment in children treated with glucocorticoid and alfacalcidol. Endocr J. 2001;48:11-8 pubmed..Randomized double-blind controlled trials are needed to confirm our findings. ..
- Iwamoto J, Takeda T, Sato Y, Shen C, Yeh J. Beneficial effect of pretreatment and treatment continuation with risedronate and vitamin K2 on cancellous bone loss after ovariectomy in rats: a bone histomorphometry study. J Nutr Sci Vitaminol (Tokyo). 2006;52:307-15 pubmed..Moreover, even though the dosing frequency of the drugs was reduced after OVX, treatment continuation appeared to be more beneficial than pretreatment for increasing the cancellous bone mass. ..
- Schurgers L, Teunissen K, Hamulyak K, Knapen M, Vik H, Vermeer C. Vitamin K-containing dietary supplements: comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood. 2007;109:3279-83 pubmed..MK-7 induced more complete carboxylation of osteocalcin, and hematologists should be aware that preparations supplying 50 mug/d or more of MK-7 may interfere with oral anticoagulant treatment in a clinically relevant way. ..
- Beulens J, Bots M, Atsma F, Bartelink M, Prokop M, Geleijnse J, et al. High dietary menaquinone intake is associated with reduced coronary calcification. Atherosclerosis. 2009;203:489-93 pubmed publisher..03). This study shows that high dietary menaquinone intake, but probably not phylloquinone, is associated with reduced coronary calcification. Adequate menaquinone intakes could therefore be important to prevent cardiovascular disease. ..
- Azuma K, Urano T, Ouchi Y, Inoue S. Vitamin K2 suppresses proliferation and motility of hepatocellular carcinoma cells by activating steroid and xenobiotic receptor. Endocr J. 2009;56:843-9 pubmed..These results suggest that the activation of SXR could contribute to tumor suppressive effects of vitamin K2 on HCC cells. ..
- Lee P, Hsu A, Ha H, Clarke C. A C-methyltransferase involved in both ubiquinone and menaquinone biosynthesis: isolation and identification of the Escherichia coli ubiE gene. J Bacteriol. 1997;179:1748-54 pubmed..The data presented identify the E. coli UbiE polypeptide and provide evidence that it is required for the C methylation reactions in both ubiquinone and menaquinone biosynthesis. ..
- Ding L, Hirose T, Yokota A. Four novel Arthrobacter species isolated from filtration substrate. Int J Syst Evol Microbiol. 2009;59:856-62 pubmed publisher..nov. (type strain LC10(T)=IAM 15385(T)=CCTCC AB 206017(T)) and Arthrobacter albidus sp. nov. (type strain LC13(T)=IAM 15386(T)=CCTCC AB 206018(T)) are proposed...
- Dairi T. An alternative menaquinone biosynthetic pathway operating in microorganisms: an attractive target for drug discovery to pathogenic Helicobacter and Chlamydia strains. J Antibiot (Tokyo). 2009;62:347-52 pubmed publisher..As humans and some useful intestinal bacteria, such as lactobacilli, lack the alternative pathway, it would be an attractive target for the development of chemotherapeutics. ..
- Kojima K, Tamano M, Akima T, Hashimoto T, Kuniyoshi T, Maeda C, et al. Effect of vitamin K2 on the development of hepatocellular carcinoma in type C cirrhosis. Hepatogastroenterology. 2010;57:1264-7 pubmed..Consequently, to further validate its benefits, we believe that menatetrenone should be actively administered to patients with intractable (interferon-resistant) cirrhosis. ..
- Shibayama Imazu T, Aiuchi T, Nakaya K. Vitamin K2-mediated apoptosis in cancer cells: role of mitochondrial transmembrane potential. Vitam Horm. 2008;78:211-26 pubmed publisher..However, other pathways may be involved since cyclosporin A failed to completely inhibit vitamin K2-induced apoptosis. ..
- Iwamoto J, Takeda T, Sato Y. Effects of vitamin K2 on osteoporosis. Curr Pharm Des. 2004;10:2557-76 pubmed..No randomized well-controlled prospective studies conducted on a sufficiently large number of patients have been reported yet, therefore, further studies are needed to confirm the efficacy of vitamin K2 in the treatment of osteoporosis. ..
- Kato S, Mano T, Kobayashi T, Yamazaki N, Himeno Y, Yamamoto K, et al. A calcium-deficient diet caused decreased bone mineral density and secondary elevation of estrogen in aged male rats-effect of menatetrenone and elcatonin. Metabolism. 2002;51:1230-4 pubmed..These data suggest that the change in testicular aromatase expression might be, in part, a compensatory mechanism for the bone mineral deficiency induced by the Ca-deficient diet in aged male rats. ..
- Shiomi S, Nishiguchi S, Kubo S, Tamori A, Habu D, Takeda T, et al. Vitamin K2 (menatetrenone) for bone loss in patients with cirrhosis of the liver. Am J Gastroenterol. 2002;97:978-81 pubmed..017). No adverse effects of vitamin K2 were noted. Vitamin K2 can prevent bone loss and may therefore be useful in the management of bone disease in women with cirrhosis of the liver. ..
- Okano T, Shimomura Y, Yamane M, Suhara Y, Kamao M, Sugiura M, et al. Conversion of phylloquinone (Vitamin K1) into menaquinone-4 (Vitamin K2) in mice: two possible routes for menaquinone-4 accumulation in cerebra of mice. J Biol Chem. 2008;283:11270-9 pubmed
- ..Furthermore, I will shortly discuss the interaction with vitamin D and the paradox in relation to warfarin treatment. ..
- Iwamoto J, Takeda T, Ichimura S. Effect of menatetrenone on bone mineral density and incidence of vertebral fractures in postmenopausal women with osteoporosis: a comparison with the effect of etidronate. J Orthop Sci. 2001;6:487-92 pubmed
- Dawson A, Fyfe P, Hunter W. Specificity and reactivity in menaquinone biosynthesis: the structure of Escherichia coli MenD (2-succinyl-5-enolpyruvyl-6-hydroxy-3-cyclohexadiene-1-carboxylate synthase). J Mol Biol. 2008;384:1353-68 pubmed publisher..This, in addition to structural and sequence comparisons with putative MenD orthologues, provides insight into the specificity and reactivity of MenD and allows a two-stage reaction mechanism to be proposed. ..
- Sato T, Ohtani Y, Yamada Y, Saitoh S, Harada H. Difference in the metabolism of vitamin K between liver and bone in vitamin K-deficient rats. Br J Nutr. 2002;87:307-14 pubmed..Furthermore, the counteracting effect of MK-7 on prolonged PT in vitamin K-deficient rats was found to be higher than phylloquinone or MK-4. ..
- Maklashina E, Hellwig P, Rothery R, Kotlyar V, Sher Y, Weiner J, et al. Differences in protonation of ubiquinone and menaquinone in fumarate reductase from Escherichia coli. J Biol Chem. 2006;281:26655-64 pubmed..These findings represent an example of how enzymes that are designed to accommodate either UQ or MQ at a single Q binding site may nevertheless develop sufficient plasticity at the binding pocket to react differently with MQ and UQ. ..
- Ichikawa T, Horie Inoue K, Ikeda K, Blumberg B, Inoue S. Steroid and xenobiotic receptor SXR mediates vitamin K2-activated transcription of extracellular matrix-related genes and collagen accumulation in osteoblastic cells. J Biol Chem. 2006;281:16927-34 pubmed..Our results suggest a new function for vitamin K2 in bone formation as a transcriptional regulator of extracellular matrix-related genes, that are involved in the collagen assembly. ..
- Carpentier W, De Smet L, Van Beeumen J, Brigé A. Respiration and growth of Shewanella oneidensis MR-1 using vanadate as the sole electron acceptor. J Bacteriol. 2005;187:3293-301 pubmed..Analysis of an mtrB-deficient mutant confirmed the results of a previous paper indicating that OmcB may function as a vanadate reductase or may be part of a vanadate reductase complex. ..
- Sasaki N, Kusano E, Takahashi H, Ando Y, Yano K, Tsuda E, et al. Vitamin K2 inhibits glucocorticoid-induced bone loss partly by preventing the reduction of osteoprotegerin (OPG). J Bone Miner Metab. 2005;23:41-7 pubmed..The present study demonstrated that the inhibition exerted by vitamin K2 of the reduction in OPG induced by GC may, at least in part, play a role in the prevention and treatment of GC-induced bone loss. ..
- Kobayashi M, Hara K, Akiyama Y. Effects of vitamin K2 (menatetrenone) and alendronate on bone mineral density and bone strength in rats fed a low-magnesium diet. Bone. 2004;35:1136-43 pubmed..Our results from this model suggest that MK-4 and ALN affect bone mechanical properties by different mechanisms. ..
- Xin F, Takemitsu M, Atsuta Y. Effect of vitamin K(2) on lumbar vertebral bone: histomorphometric analyses in experimental osteoporotic rats. J Orthop Sci. 2001;6:535-9 pubmed..In conclusion, vitamin K(2) is thought to be beneficial for the properties of bone microarchitecture in the condition of osteoporosis. ..
- Kaneki M, Hodges S, Hedges S, Hosoi T, Fujiwara S, Lyons A, et al. Japanese fermented soybean food as the major determinant of the large geographic difference in circulating levels of vitamin K2: possible implications for hip-fracture risk. Nutrition. 2001;17:315-21 pubmed
- Hara K, Kobayashi M, Akiyama Y. Vitamin K2 (menatetrenone) inhibits bone loss induced by prednisolone partly through enhancement of bone formation in rats. Bone. 2002;31:575-81 pubmed..K(2) treatment also inhibited the decrease in MS/BS and BFR/BS induced by 30 mg/kg pred. These results suggest that K(2) prevents bone loss partly through the enhancement of bone formation. ..
- Sato Y, Honda Y, Kunoh H, Oizumi K. Long-term oral anticoagulation reduces bone mass in patients with previous hemispheric infarction and nonrheumatic atrial fibrillation. Stroke. 1997;28:2390-4 pubmed..Both warfarin-induced reduction in vitamin K function and lowered vitamin K1 concentrations are probable causes of this osteopenia. ..
- Otomo H, Sakai A, Ikeda S, Tanaka S, Ito M, Phipps R, et al. Regulation of mineral-to-matrix ratio of lumbar trabecular bone in ovariectomized rats treated with risedronate in combination with or without vitamin K2. J Bone Miner Metab. 2004;22:404-14 pubmed..Different effects among different drugs on material properties, including mineral-to-matrix ratio, may reflect differences in the relative rate and magnitude of osteoclastic bone resorption and osteoblastic primary bone mineralization. ..
- Nowicka B, Kruk J. Occurrence, biosynthesis and function of isoprenoid quinones. Biochim Biophys Acta. 2010;1797:1587-605 pubmed publisher..Biosynthetic pathway of isoprenoid quinones has been described, as well as their additional, recently recognized, diverse functions in bacterial, plant and animal metabolism. ..
- Iwasaki Ishizuka Y, Yamato H, Murayama H, Ezawa I, Kurokawa K, Fukagawa M. Menatetrenone rescues bone loss by improving osteoblast dysfunction in rats immobilized by sciatic neurectomy. Life Sci. 2005;76:1721-34 pubmed..These results indicated that MK-4 rescued bone volume by improving osteoblast dysfunction and accelerating gamma carboxylation of osteocalcin. MK-4 may be useful for treating disuse osteopenia. ..
- van Summeren M, Braam L, Lilien M, Schurgers L, Kuis W, Vermeer C. The effect of menaquinone-7 (vitamin K2) supplementation on osteocalcin carboxylation in healthy prepubertal children. Br J Nutr. 2009;102:1171-8 pubmed publisher..These findings demonstrate that in healthy, prepubertal children, modest supplementation with MK-7 increases circulating concentrations of MK-7 and increases osteocalcin carboxylation. ..
- Kolappan S, Zwahlen J, Zhou R, Truglio J, Tonge P, Kisker C. Lysine 190 is the catalytic base in MenF, the menaquinone-specific isochorismate synthase from Escherichia coli: implications for an enzyme family. Biochemistry. 2007;46:946-53 pubmed..The studies reported here extend the mechanism recently proposed for this enzyme family by He et al.: He, Z., Stigers Lavoie, K. D., Bartlett, P. A., and Toney, M. D. (2004) J. Am. Chem. Soc. 126, 2378-85. ..
- Kanamori T, Shimizu M, Okuno M, Matsushima Nishiwaki R, Tsurumi H, Kojima S, et al. Synergistic growth inhibition by acyclic retinoid and vitamin K2 in human hepatocellular carcinoma cells. Cancer Sci. 2007;98:431-7 pubmed..This combination might therefore be effective for the chemoprevention and chemotherapy of HCC. ..
- Nimptsch K, Nieters A, Hailer S, Wolfram G, Linseisen J. The association between dietary vitamin K intake and serum undercarboxylated osteocalcin is modulated by vitamin K epoxide reductase genotype. Br J Nutr. 2009;101:1812-20 pubmed publisher..Thus, the results show that the inverse association between dietary vitamin K intake and serum ucOC depends on a functionally relevant allelic variant of the VKORC1 gene. ..
- Hotta N, Ayada M, Sato K, Ishikawa T, Okumura A, Matsumoto E, et al. Effect of vitamin K2 on the recurrence in patients with hepatocellular carcinoma. Hepatogastroenterology. 2007;54:2073-7 pubmed..These findings suggest that VK2 does not appear to prevent recurrence of HCC after curative treatment. Our study is preliminary and large-scale trials are needed to determine whether VK2 is of benefit to decrease the recurrence of HCC. ..
- Cheung A, Tile L, Lee Y, Tomlinson G, Hawker G, Scher J, et al. Vitamin K supplementation in postmenopausal women with osteopenia (ECKO trial): a randomized controlled trial. PLoS Med. 2008;5:e196 pubmed publisher..More studies are needed to further examine the effect of vitamin K on fractures and cancers. ClinicalTrials.gov (#NCT00150969) and Current Controlled Trials (#ISRCTN61708241). ..