{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:14:06Z","timestamp":1792815246790,"version":"4.5.0"},"reference-count":222,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T00:00:00Z","timestamp":1655164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Vitamin K2-7, also known as menaquinone-7 (MK-7) is a form of vitamin K that has health-beneficial effects in osteoporosis, cardiovascular disease, inflammation, cancer, Alzheimer\u2019s disease, diabetes and peripheral neuropathy. Compared to vitamin K1 (phylloquinone), K2-7 is absorbed more readily and is more bioavailable. Clinical studies have unequivocally demonstrated the utility of vitamin K2-7 supplementation in ameliorating peripheral neuropathy, reducing bone fracture risk and improving cardiovascular health. We examine how undercarboxylated osteocalcin (ucOC) and matrix Gla protein (ucMGP) are converted to carboxylated forms (cOC and cMGP respectively) by K2-7 acting as a cofactor, thus facilitating the deposition of calcium in bones and preventing vascular calcification. K2-7 is beneficial in managing bone loss because it upregulates osteoprotegerin which is a decoy receptor for RANK ligand (RANKL) thus inhibiting bone resorption. We also review the evidence for the health-beneficial outcomes of K2-7 in diabetes, peripheral neuropathy and Alzheimer\u2019s disease. In addition, we discuss the K2-7-mediated suppression of growth in cancer cells\n                    <jats:italic>via<\/jats:italic>\n                    cell-cycle arrest, autophagy and apoptosis. The mechanistic basis for the disease-modulating effects of K2-7 is mediated through various signal transduction pathways such as PI3K\/AKT, MAP Kinase, JAK\/STAT, NF-\u03baB,\n                    <jats:italic>etc<\/jats:italic>\n                    . Interestingly, K2-7 is also responsible for suppression of proinflammatory mediators such as IL-1\u03b1, IL-1\u03b2 and TNF-\u03b1. We elucidate various genes modulated by K2-7 as well as the clinical pharmacometrics of vitamin K2-7 including K2-7-mediated pharmacokinetics\/pharmacodynamics (PK\/PD). Further, we discuss the current status of clinical trials on K2-7 that shed light on dosing strategies for maximum health benefits. Taken together, this is a synthetic review that delineates the health-beneficial effects of K2-7 in a clinical setting, highlights the molecular basis for these effects, elucidates the clinical pharmacokinetics of K2-7, and underscores the need for K2-7 supplementation in the global diet.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2022.896920","type":"journal-article","created":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T03:23:22Z","timestamp":1655177002000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":87,"title":["Molecular Pathways and Roles for Vitamin K2-7 as a Health-Beneficial Nutraceutical: Challenges and Opportunities"],"prefix":"10.3389","volume":"13","author":[{"given":"Nikita","family":"Jadhav","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saiprasad","family":"Ajgaonkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Praful","family":"Saha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranay","family":"Gurav","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amitkumar","family":"Pandey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivek","family":"Basudkar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yash","family":"Gada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangita","family":"Panda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shashank","family":"Jadhav","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dilip","family":"Mehta","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sujit","family":"Nair","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1016\/j.ejphar.2015.06.014","article-title":"Menaquinone-7 as a Novel Pharmacological Therapy in the Treatment of Rheumatoid Arthritis: A Clinical Study","volume":"761","author":"Abdel-Rahman","year":"2015","journal-title":"Eur. J. Pharmacol."},{"key":"B2","unstructured":"Effect of Vitamin K2 Supplementation on Vascular Calcification in Hemodialysis Patients: a Controlled Randomized Trial\n            Ab\u00fadR. P.\n          2020"},{"key":"B3","unstructured":"Anzctr2021"},{"key":"B4","unstructured":"Anzctr2020"},{"key":"B5","doi-asserted-by":"publisher","first-page":"582","DOI":"10.1016\/j.sjbs.2014.03.002","article-title":"Molecular Mechanisms of Leptin and Pro-apoptotic Signals Induced by Menadione in HepG2 Cells","volume":"21","author":"Al-Suhaimi","year":"2014","journal-title":"Saudi J. Biol. Sci."},{"key":"B6","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1007\/s11154-019-09517-9","article-title":"Endocrine Roles of Vitamin K-dependent- Osteocalcin in the Relation between Bone Metabolism and Metabolic Disorders","volume":"21","author":"Al-Suhaimi","year":"2020","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"B7","unstructured":"Alzheimer\u2019s Foundation of America2022"},{"key":"B8","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1186\/s12882-017-0609-3","article-title":"High Dephosphorylated-Uncarboxylated MGP in Hemodialysis Patients: Risk Factors and Response to Vitamin K2, A Pre-post Intervention Clinical Trial","volume":"18","author":"Aoun","year":"2017","journal-title":"BMC Nephrol."},{"key":"B9","unstructured":"Risk Factors for Vascular Calcifications in Hemodialysis Patients: to what Extent Is Vitamin K2 Deficiency Involved?\n            AounM.\n          2016"},{"key":"B10","first-page":"2","article-title":"Evolving Story of Bone Health and the Nutritional Support","author":"Badmaev","year":"2011","journal-title":"NutraCos"},{"key":"B11","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1128\/mr.46.3.241-280.1982","article-title":"Biosynthesis of Vitamin K (Menaquinone) in Bacteria","volume":"46","author":"Bentley","year":"1982","journal-title":"Microbiol. Rev."},{"key":"B221","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1007\/s12033-012-9576-x","article-title":"Effect of Biofilm Formation by Bacillus subtilis natto on Menaquinone-7 Biosynthesis","volume":"54","author":"Berenjian","year":"2013","journal-title":"Mol. Biotechnol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1146\/annurev.nutr.25.050304.092713","article-title":"The Vitamin K-dependent Carboxylase","volume":"25","author":"Berkner","year":"2005","journal-title":"Annu. Rev. Nutr."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1357","DOI":"10.1017\/S0007114513001013","article-title":"The Role of Menaquinones (Vitamin K\u2082) in Human Health","volume":"110","author":"Beulens","year":"2013","journal-title":"Br. J. Nutr."},{"key":"B14","first-page":"1","article-title":"Determinants of Vitamin K Status in Humans","volume-title":"Vitamins & Hormones","author":"Booth","year":"2008"},{"key":"B15","unstructured":"Assess Tolerability and Availability of a Multi-Target Dietary Supplement in an Aging Population\n            BorehamD.\n          2021"},{"key":"B16","unstructured":"The Impact of Vitamin K2 and Inactive Vitamin D Supplementation on Vascular Calcification in Pediatric Patients on Regular Hemodialysis\n            BorolossyR. M. A. E. K. E.\n          2019"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1800","DOI":"10.1172\/JCI116391","article-title":"Bone Morphogenetic Protein Expression in Human Atherosclerotic Lesions","volume":"91","author":"Bostr\u00f6m","year":"1993","journal-title":"J. Clin. Invest"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1017\/S0007114511001425","article-title":"Olive Oil Supplemented with Menaquinone-7 Significantly Affects Osteocalcin Carboxylation","volume":"106","author":"Brug\u00e8","year":"2011","journal-title":"Br. J. Nutr."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1093\/ndt\/gft464","article-title":"Vitamin K2 Supplementation in Haemodialysis Patients: a Randomized Dose-Finding Study","volume":"29","author":"Caluw\u00e9","year":"2014","journal-title":"Nephrol. Dial. Transpl."},{"key":"B20","unstructured":"Randomized Prospective Open Interventional Multi-Centre Study on Finding the Optimal Dose of Vitamin K2 Supplements for Hemodialysis Patients\n            CaluweR.\n          2012"},{"key":"B21","unstructured":"Safety and Efficacy of Vitamin K Antagonists versus Rivaroxaban in Hemodialysis Patients with Atrial Fibrillation: a Multicenter Randomized Controlled Trial\n            CaluweR.\n          2020"},{"key":"B22","unstructured":"The Effect of Replacement of Vitamin K Antagonist by Rivaroxaban with or without Vitamin K2 Supplementation on Vascular Calcifications in Chronic Hemodialysis Patients: A Randomized Controlled Trial\n            CaluweR.\n          2019"},{"key":"B23","unstructured":"Clinical Trials Register 2019-004906-882019"},{"key":"B24","first-page":"307","article-title":"The Production of Menaquinones (Vitamin K2) by Intestinal Bacteria and Their Role in Maintaining Coagulation Homeostasis","volume":"16","author":"Conly","year":"1992","journal-title":"Prog. Food Nutr. Sci."},{"key":"B25","unstructured":"Clinicaltrials2017"},{"key":"B26","unstructured":"Clinicaltrials2021"},{"key":"B27","unstructured":"Clinicaltrials2017"},{"key":"B28","unstructured":"Clinicaltrials2017"},{"key":"B29","unstructured":"Clinicaltrials2017"},{"key":"B30","unstructured":"Clinicaltrials2021"},{"key":"B31","unstructured":"Clinicaltrials2019"},{"key":"B32","unstructured":"Clinicaltrials2020"},{"key":"B33","unstructured":"Clinicaltrials2021"},{"key":"B34","doi-asserted-by":"publisher","first-page":"397","DOI":"10.1016\/j.atherosclerosis.2012.09.019","article-title":"The Effect of Menaquinone-7 Supplementation on Circulating Species of Matrix Gla Protein","volume":"225","author":"Dalmeijer","year":"2012","journal-title":"Atherosclerosis"},{"key":"B35","unstructured":"Study of the Effect of Food Vitamin K2 Intake in Association with a Fermented Dairy Product on Patients Treated with Vitamin K Antagonist (VKA)2014"},{"key":"B36","unstructured":"Dementia2021"},{"key":"B37","unstructured":"The Effects of Menaquinone-7 Supplementation in Patients with Aortic Valves Calcification\n            DiederichsenA.\n          2021"},{"key":"B38","unstructured":"A Phase 2, Double Blind, Randomized, Placebo-Controlled Clinical Trial to Investigate the Safety and Effects of Oral Vitamin K2 Supplementation in COVID-19\n            DofferhoffT.\n          2021"},{"key":"B39","unstructured":"Transdermal Delivery of Fat-Soluble Vitamins in Liposomes: a Randomized Study2018"},{"key":"B40","unstructured":"Phase 1 Study of Combination Strontium, Melatonin and Nutritional Co-factors on Bone Health and Quality of Life in Postmenopausal Women with Osteopenia2018"},{"key":"B41","unstructured":"A Randomized, Placebo-Controlled, Phase II\/III Clinical Study on Inhibitory Effects of E0167 on Recurrence of Hepatocellular Carcinoma2008"},{"key":"B42","unstructured":"Short-Term Menatetrenone Therapy Increases Gamma-Carboxylation of Osteocalcin with A Moderate Increase of Bone Turnover in Postmenopausal Osteoporosis: A Randomized Prospective Study2018"},{"key":"B43","doi-asserted-by":"publisher","first-page":"172","DOI":"10.5001\/omj.2014.44","article-title":"Vitamin K Dependent Proteins and the Role of Vitamin K2 in the Modulation of Vascular Calcification: a Review","volume":"29","author":"El Asmar","year":"2014","journal-title":"Oman Med. J."},{"key":"B44","doi-asserted-by":"publisher","first-page":"15985","DOI":"10.1074\/jbc.275.21.15985","article-title":"SOCS-3 Is an Insulin-Induced Negative Regulator of Insulin Signaling","volume":"275","author":"Emanuelli","year":"2000","journal-title":"J. Biol. Chem."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1007\/s00198-009-1126-4","article-title":"Vitamin K2 Supplementation Does Not Influence Bone Loss in Early Menopausal Women: a Randomised Double-Blind Placebo-Controlled Trial","volume":"21","author":"Emaus","year":"2010","journal-title":"Osteoporos. Int."},{"key":"B46","unstructured":"Comparative Study Evaluating the Effect of the Administration of Vitamin K1 versus Vitamin K2 on Vascular Calcification in Dialysis Patients\n            FaridS.\n          2021"},{"key":"B47","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1186\/s12885-021-08138-3","article-title":"PIVKA-II Serves as a Potential Biomarker that Complements AFP for the Diagnosis of Hepatocellular Carcinoma","volume":"21","author":"Feng","year":"2021","journal-title":"BMC Cancer"},{"key":"B48","volume-title":"Cheese: Chemistry, Physics and Microbiology","author":"Fox","year":"2004"},{"key":"B49","unstructured":"Decalcification of the Aortic Valve by Vitamin K2 (Menaquinone-7)\n            FrangiR.\n          2019"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2021.778014","article-title":"New Vistas in microRNA Regulatory Interactome in Neuropathic Pain","volume":"12","author":"Gada","year":"2022","journal-title":"Front. Pharmacol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"756","DOI":"10.1021\/acssynbio.0c00568","article-title":"Highly Efficient Production of Menaquinone-7 from Glucose by Metabolically Engineered Escherichia coli","volume":"10","author":"Gao","year":"2021","journal-title":"ACS Synth. Biol."},{"key":"B52","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1007\/s11274-020-02880-9","article-title":"Menaquinone-7 Production in Engineered Escherichia coli","volume":"36","author":"Gao","year":"2020","journal-title":"World J. Microbiol. Biotechnol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1002\/term.1627","article-title":"Vitamin MK-7 Enhances Vitamin D3-Induced Osteogenesis in hMSCs: Modulation of Key Effectors in Mineralization and Vascularization","volume":"9","author":"Gigante","year":"2015","journal-title":"J. Tissue Eng. Regen. Med."},{"key":"B54","unstructured":"Effects of Vitamin K2 on Recovery from Muscle Damaging Exercise in Young and Older Adults\n            GrayS.\n          2021"},{"key":"B55","doi-asserted-by":"publisher","first-page":"5785","DOI":"10.1128\/MCB.19.8.5785","article-title":"NF-kappaB Controls Cell Growth and Differentiation through Transcriptional Regulation of Cyclin D1","volume":"19","author":"Guttridge","year":"1999","journal-title":"Mol. Cell Biol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"343","DOI":"10.1080\/1028415X.2018.1504428","article-title":"Vitamin K2 Protects PC12 Cells against A\u03b2 (1-42) and H2O2-Induced Apoptosis via P38 MAP Kinase Pathway","volume":"23","author":"Hadipour","year":"2020","journal-title":"Nutr. Neurosci."},{"key":"B57","doi-asserted-by":"publisher","first-page":"896","DOI":"10.3390\/ijms20040896","article-title":"Vitamin K: Double Bonds beyond Coagulation Insights into Differences between Vitamin K1 and K2 in Health and Disease","volume":"20","author":"Halder","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B58","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/s0065-230x(08)60352-8","article-title":"Genetic Alterations of Cyclins, Cyclin-dependent Kinases, and Cdk Inhibitors in Human Cancer","volume":"68","author":"Hall","year":"1996","journal-title":"Adv. Cancer Res."},{"key":"B59","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1254\/fpj.113.185","article-title":"Interaction of Warfarin and Vitamin K2 on Arterial Thrombotic Tendency Using a Rat Aorta Loop Model","volume":"113","author":"Hara","year":"1999","journal-title":"Nihon Yakurigaku Zasshi"},{"key":"B60","doi-asserted-by":"publisher","first-page":"990","DOI":"10.1152\/physrev.1989.69.3.990","article-title":"Osteocalcin and Matrix Gla Protein: Vitamin K-dependent Proteins in Bone","volume":"69","author":"Hauschka","year":"1989","journal-title":"Physiol. Rev."},{"key":"B61","first-page":"294","article-title":"Peripheral Neuropathy: Pathogenic Mechanisms and Alternative Therapies","volume":"11","author":"Head","year":"2006","journal-title":"Altern. Med. Rev."},{"key":"B62","unstructured":"Relation between Plasma Vitamin K2 and Glycemic Control and Metabolic Parameters in Type 2 Diabetic Patients\n            HelmyM. Y.\n          2021"},{"key":"B63","doi-asserted-by":"publisher","first-page":"462","DOI":"10.1038\/nrrheum.2015.48","article-title":"A Look behind the Scenes: the Risk and Pathogenesis of Primary Osteoporosis","volume":"11","author":"Hendrickx","year":"2015","journal-title":"Nat. Rev. Rheumatol."},{"key":"B64","doi-asserted-by":"publisher","first-page":"713","DOI":"10.3892\/ijo.26.3.713","article-title":"Antitumor Effects of Vitamins K1, K2 and K3 on Hepatocellular Carcinoma In Vitro and In Vivo","volume":"26","author":"Hitomi","year":"2005","journal-title":"Int. J. Oncol."},{"key":"B65","doi-asserted-by":"publisher","first-page":"977","DOI":"10.1038\/nature02079","article-title":"Bone Recognition Mechanism of Porcine Osteocalcin from Crystal Structure","volume":"425","author":"Hoang","year":"2003","journal-title":"Nature"},{"key":"B66","doi-asserted-by":"publisher","first-page":"423","DOI":"10.3390\/biom11030423","article-title":"Molecular Mechanism of Vitamin K2 Protection against Amyloid-\u03b2-Induced Cytotoxicity","volume":"11","author":"Huang","year":"2021","journal-title":"Biomolecules"},{"key":"B67","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/j.nut.2017.09.016","article-title":"Vitamin K2 Alleviates Type 2 Diabetes in Rats by Induction of Osteocalcin Gene Expression","volume":"47","author":"Hussein","year":"2018","journal-title":"Nutrition"},{"key":"B68","doi-asserted-by":"publisher","first-page":"2960","DOI":"10.1016\/j.bbagen.2012.12.026","article-title":"In Silico and In Vitro Characterization of Anti-amyloidogenic Activity of Vitamin K3 Analogues for Alzheimer's Disease","volume":"1830","author":"Huy","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"B69","doi-asserted-by":"publisher","first-page":"471","DOI":"10.3177\/jnsv.61.471","article-title":"Low-Dose Daily Intake of Vitamin K(2) (Menaquinone-7) Improves Osteocalcin \u03b3-Carboxylation: A Double-Blind, Randomized Controlled Trials","volume":"61","author":"Inaba","year":"2015","journal-title":"J. Nutr. Sci. Vitaminol. (Tokyo)"},{"key":"B70","unstructured":"Effect of Menaquinone (MK-7) Supplementation on Metabolic, Nutritional, Inflammatory Status and Matrix \u03b3- Carboxyglutamate Protein in DMII"},{"key":"B71","unstructured":"Effect of Menaquinone Supplementation on Insulin Resistance, Lipid Profile, Anthropometric Measurments, Endocrine Markers and Oxidative Stress in Patients with Polycystic Ovary Syndrome Who Will Be Referred to Health Centers of Shiraz University of Medical Sciences13962022"},{"key":"B72","unstructured":"Effect of Menaquinone(MK-7) Supplementation on Deppression Status, Fasting Blood Sugar and Serum Vitamin K Level in Patients with Polycystic Ovary Syndrome2021"},{"key":"B73","unstructured":"Effects of Calcium, Vitamins D and K Co-supplementation on Insulin Resistance, Inflammatory Factors and Biomarkers of Oxidative Stress in Coronary Heart Disease"},{"key":"B74","unstructured":"Effects of Vitamin K2 (MK-7) Oral Supplementation on Glycemic Control and Lipid Profile in Individuals with Type 2 Diabetes: A Double-Blind Randomized2020"},{"key":"B75","unstructured":"The Effect of Combined Vitamins D, K and Calcium Supplementation on Metabolic Profiles in Women with Polycystic Ovary Syndrome2018"},{"key":"B76","doi-asserted-by":"publisher","article-title":"Using Vitamin K to Improve Strength and Balance in Older People","year":"2018","DOI":"10.1186\/ISRCTN18436190"},{"key":"B77","doi-asserted-by":"publisher","article-title":"Vitamin K Therapy to Improve Vascular Health in Patients with Chronic Kidney Disease","year":"2015","DOI":"10.1186\/ISRCTN21444964"},{"key":"B78","doi-asserted-by":"publisher","article-title":"Vitamin K to Improve Markers of Vascular Health and Physical Function in Older People with Vascular Disease","year":"2012","DOI":"10.1186\/ISRCTN93213492"},{"key":"B79","doi-asserted-by":"publisher","first-page":"87","DOI":"10.2174\/157488606775252629","article-title":"Role of Vitamin K2 in the Treatment of Postmenopausal Osteoporosis","volume":"1","author":"Iwamoto","year":"2006","journal-title":"Curr. Drug Saf."},{"key":"B80","doi-asserted-by":"publisher","first-page":"1971","DOI":"10.3390\/nu6051971","article-title":"Vitamin K2 Therapy for Postmenopausal Osteoporosis","volume":"6","author":"Iwamoto","year":"2014","journal-title":"Nutrients"},{"key":"B81","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/s1359-6101(00)00018-6","article-title":"NF-kappaB and Cell-Cycle Regulation: the Cyclin Connection","volume":"12","author":"Joyce","year":"2001","journal-title":"Cytokine Growth Factor Rev."},{"key":"B82","unstructured":"JPRN2019"},{"key":"B83","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1111\/j.1349-7006.2006.00384.x","article-title":"Synergistic Growth Inhibition by Acyclic Retinoid and Vitamin K2 in Human Hepatocellular Carcinoma Cells","volume":"98","author":"Kanamori","year":"2007","journal-title":"Cancer Sci."},{"key":"B84","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1016\/S0899-9007(00)00554-2","article-title":"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","volume":"17","author":"Kaneki","year":"2001","journal-title":"Nutrition"},{"key":"B85","doi-asserted-by":"publisher","first-page":"279","DOI":"10.3892\/ijmm.19.2.279","article-title":"Menaquinone-7 Regulates Gene Expression in Osteoblastic MC3T3E1 Cells","volume":"19","author":"Katsuyama","year":"2007","journal-title":"Int. J. Mol. Med."},{"key":"B86","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1007\/s10787-019-00580-x","article-title":"Activation of Microglia and Astrocytes: a Roadway to Neuroinflammation and Alzheimer's Disease","volume":"27","author":"Kaur","year":"2019","journal-title":"Inflammopharmacology"},{"key":"B87","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1038\/ejcn.2016.3","article-title":"Steady-state Vitamin K2 (Menaquinone-7) Plasma Concentrations after Intake of Dairy Products and Soft Gel Capsules","volume":"70","author":"Knapen","year":"2016","journal-title":"Eur. J. Clin. Nutr."},{"key":"B88","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1038\/ejcn.2017.146","article-title":"Vitamin K-Induced Effects on Body Fat and Weight: Results from a 3-year Vitamin K2 Intervention Study","volume":"72","author":"Knapen","year":"2018","journal-title":"Eur. J. Clin. Nutr."},{"key":"B89","unstructured":"Intervention Study on the Effect of Vitamin K2 (Menaquinone-7) Supplementation on the Vascular Stiffness in Subjects with Poor Vitamin K-Status\n            KnapenM.\n          2018"},{"key":"B90","doi-asserted-by":"publisher","first-page":"19","DOI":"10.22159\/ajpcr.2017.v10i5.17014","article-title":"ADVERSE EFFECTS AND SIDE EFFECTS ON VITAMIN THERAPY: A REVIEW","volume":"10","author":"Korah","year":"2017","journal-title":"Asian J. Pharm. Clin. Res."},{"key":"B91","unstructured":"De-escalation of the Daily Jarlsberg Cheese-Dose Related to the Osteocalcin Level in Healthy Women: Estimation of a Maintaining Daily Jarlsberg Cheese-Dose\n            LarsenP. S."},{"key":"B92","unstructured":"Effect of Jarlsberg Cheese Compared to Cheese without Vitamin K2 Regarding Increased Osteocalcin Level in Healthy Women\n            LarsenP. S."},{"key":"B93","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1016\/j.tcm.2014.10.021","article-title":"Vascular Calcification: Mechanisms of Vascular Smooth Muscle Cell Calcification","volume":"25","author":"Leopold","year":"2015","journal-title":"Trends Cardiovasc Med."},{"key":"B94","doi-asserted-by":"publisher","first-page":"3709","DOI":"10.19540\/j.cnki.cjcmm.20170907.004","article-title":"Effect of Proinflammatory Factors TNF-\u03b1,IL-1\u03b2, IL-6 on Neuropathic Pain","volume":"42","author":"Li","year":"","journal-title":"Zhongguo Zhong Yao Za Zhi"},{"key":"B95","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/j.diabres.2017.11.020","article-title":"Effect of Vitamin K2 on Type 2 Diabetes Mellitus: A Review","volume":"136","author":"Li","year":"2018","journal-title":"Diabetes Res. Clin. Pract."},{"key":"B96","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1007\/s10295-017-1931-2","article-title":"Biotransformation of Menadione to its Prenylated Derivative MK-3 Using Recombinant Pichia pastoris","volume":"44","author":"Li","year":"","journal-title":"J. Ind. Microbiol. Biotechnol."},{"key":"B97","unstructured":"Placebo Controlled Pilot Trial to Determine the Effect of Metabolic RheostatTM and Butyrate Ultra on Hemoglobin A1C and Blood Glucose Levels in Patients with Pre-diabetes\n            LiZ.\n          2021"},{"key":"B98","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/nature21029","article-title":"Neurotoxic Reactive Astrocytes Are Induced by Activated Microglia","volume":"541","author":"Liddelow","year":"2017","journal-title":"Nature"},{"key":"B99","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1111\/j.1467-789X.2005.00159.x","article-title":"Adiponectin: Action, Regulation and Association to Insulin Sensitivity","volume":"6","author":"Lihn","year":"2005","journal-title":"Obes. Rev."},{"key":"B100","doi-asserted-by":"publisher","first-page":"847","DOI":"10.3390\/nu10070847","article-title":"Undercarboxylated Osteocalcin: Experimental and Human Evidence for a Role in Glucose Homeostasis and Muscle Regulation of Insulin Sensitivity","volume":"10","author":"Lin","year":"2018","journal-title":"Nutrients"},{"key":"B101","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.757603","article-title":"Vitamin K2 Inhibits Hepatocellular Carcinoma Cell Proliferation by Binding to 17\u03b2-Hydroxysteroid Dehydrogenase 4","volume":"11","author":"Lu","year":"2021","journal-title":"Front. Oncol."},{"key":"B102","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.neures.2013.10.004","article-title":"Neuroinflammation: the Role and Consequences","volume":"79","author":"Lyman","year":"2014","journal-title":"Neurosci. Res."},{"key":"B220","doi-asserted-by":"publisher","first-page":"1620","DOI":"10.1021\/acssynbio.9b00077","article-title":"Metabolic Engineering of the MEP Pathway in Bacillus subtilis for Increased Biosynthesis of Menaquinone-7","volume":"8","author":"Ma","year":"2019","journal-title":"ACS Synth. Biol."},{"key":"B103","unstructured":"Absorption of Different Forms of Vitamin K from Dairy Products\n            Maastricht University Medical Center"},{"key":"B104","unstructured":"Bicuspid Aortic Valve Stenosis and the Effect of vItamin K2 on Calciummetabolism on 18F-NaF PET\/MRI (BASIK2): a Pilot Study\n            Maastricht University Medical Center"},{"key":"B105","unstructured":"Clinical Trial on Beneficial Effects of Long Term Menaquinone-7 (Vitamin K2) Intake by Postmenopausal Women\n            Maastricht University Medical Center"},{"key":"B106","unstructured":"Comparative Study of Three Delivery Systems of Menaquinone-7\n            Maastricht University Medical Center\n          2013"},{"key":"B107","unstructured":"Comparison of Absorption and Efficacy of 3 Different Menaquinone-7 Delivery Systems; Casein Powder, Arabic Gum Powder, or Linseed Oil\n            Maastricht University Medical Center"},{"key":"B108","unstructured":"Comparison of Absorption of Vitamin K2 Human Study Gelpell\n            Maastricht University Medical Center"},{"key":"B109","unstructured":"Comparison of Bioavailability of Three Different Vitamin K2 Formulations\n            Maastricht University Medical Center"},{"key":"B110","unstructured":"Comparison of Effects of Nutritional Doses Vitamin K1 and K2 on Carboxylation\n            Maastricht University Medical Center"},{"key":"B111","unstructured":"Comparison of Efficacy of Different Dosages Vitamin K2\n            Maastricht University Medical Center"},{"key":"B112","unstructured":"Dose-finding Study for Vitamin K2 in Human Volunteers\n            Maastricht University Medical Center"},{"key":"B113","unstructured":"The Effects of Vitamin K2 Supplementation on the Progression of Coronary Artery Calcification\n            Maastricht University Medical Center"},{"key":"B114","unstructured":"Safety Study of Vitamin K2 during Anticoagulation in Human Volunteers2008"},{"key":"B115","doi-asserted-by":"publisher","DOI":"10.2202\/1556-3758.2314","article-title":"Enhanced Production of Menaquinone 7 via Solid Substrate Fermentation from Bacillus Subtilis","volume":"7","author":"Mahanama","year":"2011","journal-title":"Int. J. Food Eng."},{"key":"B116","doi-asserted-by":"publisher","first-page":"5583","DOI":"10.1007\/s00253-019-09913-w","article-title":"Biofilm Reactors as a Promising Method for Vitamin K (Menaquinone-7) Production","volume":"103","author":"Mahdinia","year":"2019","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"B117","doi-asserted-by":"publisher","first-page":"195","DOI":"10.1007\/s00449-017-1857-0","article-title":"Optimization of Bacillus Subtilis Natto Growth Parameters in Glycerol-Based Medium for Vitamin K (Menaquinone-7) Production in Biofilm Reactors","volume":"41","author":"Mahdinia","year":"2018","journal-title":"Bioprocess Biosyst. Eng."},{"key":"B118","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1007\/s11274-016-2169-2","article-title":"Production and Application of Menaquinone-7 (Vitamin K2): a New Perspective","volume":"33","author":"Mahdinia","year":"2017","journal-title":"World J. Microbiol. Biotechnol."},{"key":"B119","doi-asserted-by":"publisher","first-page":"399","DOI":"10.5114\/ceji.2017.72806","article-title":"Butyrophilins: an Important New Element of Resistance","volume":"42","author":"Malinowska","year":"2017","journal-title":"Cent. Eur. J. Immunol."},{"key":"B120","doi-asserted-by":"publisher","first-page":"1222","DOI":"10.3390\/nu13041222","article-title":"The Dual Role of Vitamin K2 in \"Bone-Vascular Crosstalk\": Opposite Effects on Bone Loss and Vascular Calcification","volume":"13","author":"Mandatori","year":"2021","journal-title":"Nutrients"},{"key":"B121","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1093\/nutrit\/nux022","article-title":"US Pharmacopeial Convention Safety Evaluation of Menaquinone-7, a Form of Vitamin K","volume":"75","author":"Marles","year":"2017","journal-title":"Nutr. Rev."},{"key":"B122","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1053\/jhep.2003.50112","article-title":"Cyclins and Cyclin-dependent Kinases: Comparative Study of Hepatocellular Carcinoma versus Cirrhosis","volume":"37","author":"Masaki","year":"2003","journal-title":"Hepatology"},{"key":"B123","unstructured":"Evaluation of Factors II, VII, IX, X, and Proteins C and S, Following High-Dose Vitamin K Supplementation\n            MdS. M.\n          2012"},{"key":"B124","unstructured":"Rationale and Design of the Vitamin K2 and Vitamin D3 Intervention Trial in Children and Adolescents with the Low-Energy Bone Fractures2021"},{"key":"B125","unstructured":"Influence of Vitamin K2 Administration on Vessel Calcification Markers in Patients with Chronic Kidney Disease2010"},{"key":"B126","first-page":"20","article-title":"The Potential Protective Role of Vitamin K in Diabetic Neuropathy","author":"Mehta","year":"2017","journal-title":"NutraCos"},{"key":"B127","doi-asserted-by":"publisher","DOI":"10.4172\/2167-0870.1000160","article-title":"Pharmacokinetics of Menaquinone-7 (Vitamin K2) in Healthy Volunteers","volume":"4","author":"Mhj","year":"2014","journal-title":"J. Clin. Trials"},{"key":"B128","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.1016\/S0032-9592(00)00157-6","article-title":"New Developments in Solid-State Fermentation","volume":"35","author":"Mitchell","year":"2000","journal-title":"Process Biochem."},{"key":"B129","unstructured":"The Clinical Effect of Vitamin K Administration in Type 2 Diabetic Patients\n            MohamedA.\n          2020"},{"key":"B130","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1024\/0300-9831\/a000258","article-title":"Bioavailability and Chemical\/Functional Aspects of Synthetic MK-7 vs Fermentation-Derived MK-7 in Randomised Controlled Trials","volume":"87","author":"M\u00f8ller","year":"2017","journal-title":"Int. J. Vitam. Nutr. Res."},{"key":"B131","doi-asserted-by":"publisher","first-page":"1397","DOI":"10.1038\/sj.emboj.7600615","article-title":"Biglycan Is a New Extracellular Component of the Chordin-BMP4 Signaling Pathway","volume":"24","author":"Moreno","year":"2005","journal-title":"EMBO J."},{"key":"B132","doi-asserted-by":"publisher","first-page":"1897","DOI":"10.3168\/jds.S0022-0302(99)75424-X","article-title":"Production of Menaquinones by Lactic Acid Bacteria","volume":"82","author":"Morishita","year":"1999","journal-title":"J. Dairy Sci."},{"key":"B133","unstructured":"Effects of Vitamin K2 and D3 Supplementation on 18F-NaF PET\/MRI in Patients with Carotid and Coronary Artery Disease\n            MottaghyF.\n          2021"},{"key":"B134","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1369\/0022155412456380","article-title":"Biglycan: a Multivalent Proteoglycan Providing Structure and Signals","volume":"60","author":"Nastase","year":"2012","journal-title":"J. Histochem Cytochem"},{"key":"B135","unstructured":"Underlying Causes of Low Vitamin K Status in Hemodialysis Patients - Full Text View2019"},{"key":"B136","unstructured":"Netherlands Trial Register2009"},{"key":"B137","unstructured":"Netherlands Trial Register2011"},{"key":"B138","unstructured":"Netherlands Trial Register2016"},{"key":"B139","unstructured":"Netherlands Trial Register2020"},{"key":"B140","unstructured":"Netherlands Trial Register2021"},{"key":"B141","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.molmed.2004.01.007","article-title":"p38 MAP Kinase: a Convergence Point in Cancer Therapy","volume":"10","author":"Olson","year":"2004","journal-title":"Trends Mol. Med."},{"key":"B142","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1016\/j.cellsig.2014.12.018","article-title":"Signaling Pathway for Adiponectin Expression in Adipocytes by Osteocalcin","volume":"27","author":"Otani","year":"2015","journal-title":"Cell Signal"},{"key":"B143","doi-asserted-by":"publisher","first-page":"2236","DOI":"10.1158\/1078-0432.CCR-06-2308","article-title":"Menatetrenone, a Vitamin K2 Analogue, Inhibits Hepatocellular Carcinoma Cell Growth by Suppressing Cyclin D1 Expression through Inhibition of Nuclear Factor kappaB Activation","volume":"13","author":"Ozaki","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"B144","doi-asserted-by":"publisher","first-page":"623","DOI":"10.1097\/MPH.0000000000000040","article-title":"The Efficacy of Vitamin K2 and Calcitriol Combination on Thalassemic Osteopathy","volume":"35","author":"Ozdemir","year":"2013","journal-title":"J. Pediatr. Hematol. Oncol."},{"key":"B145","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1089\/jmf.2016.0030","article-title":"Inhibition of TNF-\u03b1, IL-1\u03b1, and IL-1\u03b2 by Pretreatment of Human Monocyte-Derived Macrophages with Menaquinone-7 and Cell Activation with TLR Agonists In Vitro","volume":"19","author":"Pan","year":"2016","journal-title":"J. Med. Food"},{"key":"B146","volume-title":"New Vistas in Noncoding RNA Regulatory Interactome in the Pathogenesis of Diabetes","author":"Pandey","year":"2022"},{"key":"B147","unstructured":"Treatment to Reduce Vascular Calcification in Hemodialysis Patients Using Vitamin K (Trevasc-HDK): A Study Protocol for a Randomized Controlled Trial\n            PeixinS. H. W.\n          2020"},{"key":"B148","unstructured":"Vitamin K2 Supplementation and Effect on Arterial Stiffness Progression in the Renal Transplant Population\n            Ph.DS. A. B. M. D.\n          2017"},{"key":"B149","unstructured":"Pharmacokinetics of Omega-3 Fatty Acids Esterified in Monoglycerides, Ethyl Esters, or Triglycerides in Humans\n            PlourdeM.\n          2020"},{"key":"B150","unstructured":"Vitamin K and Glucose Metabolism in Adults at Risk for Diabetes\n            PollockN."},{"key":"B151","unstructured":"Vitamin K and Glucose Metabolism in Children at Risk for Diabetes\n            PollockN."},{"key":"B152","unstructured":"Vitamin K to Slow Progression of Cardiovascular Disease Risk in Hemodialysis Patients (Vita-K \u201cN\u201d CKD Study)\n            PollockN."},{"key":"B153","unstructured":"Vitamin K to Slow Progression of Dyslipidemia and Diabetes Risk\n            PollockN."},{"key":"B154","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1186\/s12906-021-03304-3","article-title":"Effects of Vitamin K2 Supplementation on Atherogenic Status of Individuals with Type 2 Diabetes: a Randomized Controlled Trial","volume":"21","author":"Rahimi Sakak","year":"2021","journal-title":"BMC Complement. Med. Ther."},{"key":"B155","doi-asserted-by":"publisher","first-page":"232","DOI":"10.2174\/1389201019666180515115534","article-title":"High Level of Menaquinone-7 Production by Milking Menaquinone-7 with Biocompatible Organic Solvents","volume":"19","author":"Ranmadugala","year":"2018","journal-title":"Curr. Pharm. Biotechnol."},{"key":"B156","doi-asserted-by":"publisher","first-page":"e26221","DOI":"10.1097\/MD.0000000000026221","article-title":"Vitamin K2 (Menaquinone-7) Supplementation Does Not Affect Vitamin K-dependent Coagulation Factors Activity in Healthy Individuals","volume":"100","author":"Ren","year":"2021","journal-title":"Med. Baltim."},{"key":"B157","doi-asserted-by":"publisher","first-page":"9977","DOI":"10.1523\/JNEUROSCI.0336-15.2015","article-title":"Elimination of Microglia Improves Functional Outcomes Following Extensive Neuronal Loss in the Hippocampus","volume":"35","author":"Rice","year":"2015","journal-title":"J. Neurosci."},{"key":"B158","doi-asserted-by":"publisher","first-page":"628","DOI":"10.3390\/ijms20030628","article-title":"Association of the Inactive Circulating Matrix Gla Protein with Vitamin K Intake, Calcification, Mortality, and Cardiovascular Disease: A Review","volume":"20","author":"Roumeliotis","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B159","doi-asserted-by":"publisher","first-page":"154","DOI":"10.3389\/fmed.2020.00154","article-title":"Vascular Calcification in Chronic Kidney Disease: The Role of Vitamin K- Dependent Matrix Gla Protein","volume":"7","author":"Roumeliotis","year":"2020","journal-title":"Front. Med. (Lausanne)"},{"key":"B160","unstructured":"Effect of Supplementation with Vitamins D3 and K2 in Non-carboxyled Osteocalcine and Insulin Serum Levels in Patients with Diabetes Mellitus Type 2\n            RuizJ. I. A.\n          2019"},{"key":"B161","unstructured":"Food Supplementation with Vitamin K2 to Activate MGP as an Endogenous Inhibitor of Vascular Calcification in Hemodialysis Patients2011"},{"key":"B162","unstructured":"Cognitive Dissonance Based Intervention to Promote Multivitamin Adherence on Bariatric Patients\n            SanchezD. L. G.\n          2021"},{"key":"B163","doi-asserted-by":"publisher","first-page":"8751","DOI":"10.3390\/ijms21228751","article-title":"Can We Treat Neuroinflammation in Alzheimer's Disease?","volume":"21","author":"S\u00e1nchez-Saras\u00faa","year":"2020","journal-title":"Ijms"},{"key":"B164","doi-asserted-by":"publisher","first-page":"2317","DOI":"10.3390\/ijms20092317","article-title":"Menaquinone-4 Suppresses Lipopolysaccharide-Induced Inflammation in MG6 Mouse Microglia-Derived Cells by Inhibiting the NF-\u039ab Signaling Pathway","volume":"20","author":"Saputra","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B165","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1186\/1475-2891-11-93","article-title":"Comparison of Menaquinone-4 and Menaquinone-7 Bioavailability in Healthy Women","volume":"11","author":"Sato","year":"2012","journal-title":"Nutr. J."},{"key":"B166","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1093\/ndt\/gfv111","article-title":"Vascular Calcification in Chronic Kidney Disease: an Update","volume":"31","author":"Schlieper","year":"2016","journal-title":"Nephrol. Dial. Transpl."},{"key":"B167","unstructured":"A Randomized, Placebo-Controlled, Double Blind Trial to Investigate whether Vitamin K2 Can Influence Arterial Calcification in Patients with Type 2 Diabetes\n            SchouwY. T. V. D.\n          2019"},{"key":"B168","doi-asserted-by":"publisher","first-page":"3279","DOI":"10.1182\/blood-2006-08-040709","article-title":"Vitamin K-Containing Dietary Supplements: Comparison of Synthetic Vitamin K1 and Natto-Derived Menaquinone-7","volume":"109","author":"Schurgers","year":"2007","journal-title":"Blood"},{"key":"B169","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/s0304-4165(02)00147-2","article-title":"Differential Lipoprotein Transport Pathways of K-Vitamins in Healthy Subjects","volume":"1570","author":"Schurgers","year":"2002","journal-title":"Biochim. Biophys. Acta"},{"key":"B170","doi-asserted-by":"publisher","first-page":"146","DOI":"10.5414\/cnp63146","article-title":"Mechanisms of Vascular Calcification in Renal Disease","volume":"63","author":"Shanahan","year":"2005","journal-title":"Clin. Nephrol."},{"key":"B171","doi-asserted-by":"publisher","first-page":"8","DOI":"10.3390\/nu8010008","article-title":"Concepts and Controversies in Evaluating Vitamin K Status in Population-Based Studies","volume":"8","author":"Shea","year":"2016","journal-title":"Nutrients"},{"key":"B172","doi-asserted-by":"publisher","first-page":"182","DOI":"10.3945\/an.111.001800","article-title":"Vitamin K Nutrition, Metabolism, and Requirements: Current Concepts and Future Research","volume":"3","author":"Shearer","year":"2012","journal-title":"Adv. Nutr."},{"key":"B173","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1111\/j.1440-1746.2009.06085.x","article-title":"Naturally Occurring K Vitamins Inhibit Pancreatic Cancer Cell Survival through a Caspase-dependent Pathway","volume":"25","author":"Showalter","year":"2010","journal-title":"J. Gastroenterol. Hepatol."},{"key":"B174","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1007\/s00432-007-0349-z","article-title":"Induction of Apoptosis in PA-1 Ovarian Cancer Cells by Vitamin K2 Is Associated with an Increase in the Level of TR3\/Nur77 and its Accumulation in Mitochondria and Nuclei","volume":"134","author":"Sibayama-Imazu","year":"2008","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"B175","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.1093\/brain\/aww016","article-title":"Eliminating Microglia in Alzheimer's Mice Prevents Neuronal Loss without Modulating Amyloid-\u03b2 Pathology","volume":"139","author":"Spangenberg","year":"2016","journal-title":"Brain"},{"key":"B176","unstructured":"The Efficacy of Vitamin K2 on Human Osteoporosis, Blood-Vessel Calcification and Sclerosis\n            SuS.-L.\n          2013"},{"key":"B177","doi-asserted-by":"publisher","first-page":"12969","DOI":"10.1073\/pnas.0405259101","article-title":"The Immune Regulatory Protein B7-H3 Promotes Osteoblast Differentiation and Bone Mineralization","volume":"101","author":"Suh","year":"2004","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B178","unstructured":"The Effect of Intraperitoneal Administration of Vitamin K2 on Thermal and Chemical Pain Following Global Cerebral Ischemia in Male Wistar Rats\n            Talaei FirozjaeiS.\n            FereidoniM.\n            Farhadi MoghaddamB.\n            RamandiD.\n          2018"},{"key":"B179","unstructured":"Dietary Supplements to Reduce Symptom Severity and Duration in People with SARS-CoV-2: A Randomized, Double Blind, Placebo Controlled Clinical Trial2021"},{"key":"B180","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.1017\/S0007114511007185","article-title":"Low-dose Menaquinone-7 Supplementation Improved Extra-hepatic Vitamin K Status, but Had No Effect on Thrombin Generation in Healthy Subjects","volume":"108","author":"Theuwissen","year":"2012","journal-title":"Br. J. Nutr."},{"key":"B181","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1111\/jth.12203","article-title":"Effect of Low-Dose Supplements of Menaquinone-7 (Vitamin K2 ) on the Stability of Oral Anticoagulant Treatment: Dose-Response Relationship in Healthy Volunteers","volume":"11","author":"Theuwissen","year":"2013","journal-title":"J. Thromb. Haemost."},{"key":"B182","unstructured":"Inhibition of Aortic Valve Calcification through the Carboxylation Mechanism of Matrix Gla Protein (MGP), Following Administration of Vitamin K2 (Menaquinone-7). Correlation with Mitral Annulus and Ascending Aorta Calcification\n            ToutouzasK.\n          2021"},{"key":"B183","unstructured":"Role of Vitamin K2 in the Reduction of the Calcium Content at the Level of the Carotid Bifurcation in Patients with Subcritical Lesions\n            TshombaY.\n          2019"},{"key":"B184","first-page":"613","article-title":"The Mechanisms of Vitamin K2-Induced Apoptosis of Myeloma Cells","volume":"91","author":"Tsujioka","year":"2006","journal-title":"Haematologica"},{"key":"B185","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1016\/s0009-8981(99)00152-7","article-title":"Process of Carboxylation of Glutamic Acid Residues in the Gla Domain of Human Des-Gamma-Carboxyprothrombin","volume":"289","author":"Uehara","year":"1999","journal-title":"Clin. Chim. Acta"},{"key":"B186","unstructured":"The VITAKIDS-Study: The Effect of Vitamin K Supplementation on Osteocalcin Carboxylation in Healthy Children2008"},{"key":"B187","unstructured":"2018"},{"key":"B188","unstructured":"2018"},{"key":"B189","unstructured":"Phase II Study of Natto Supplementation to Prevent Loss of Bone Mass in Women Immediately after Menopause: a Randomised Double Blind Placebo-Controlled Trial2008"},{"key":"B190","unstructured":"Intestinal Microbiota and Vitamin K Levels in PXE Patients (IMPROVE Study)2019"},{"key":"B191","unstructured":"Investigations of the Effect of MK-7 on Bone and Glucose Metabolism and Arterial Calcification2016"},{"key":"B192","unstructured":"Absorption of Transdermal Vitamins in Post Bariatric Surgery Patients2021"},{"key":"B193","unstructured":"Osteocalcin in Bone Metabolism and Aging: Effect of Vitamin K Supplementation on Circulating Levels of Osteocalcin, on Glucose and Energy Metabolism and on Muscle Mass and Function2020"},{"key":"B194","doi-asserted-by":"publisher","first-page":"e31941","DOI":"10.2196\/31941","article-title":"Vitamin K Insufficiency in the Indian Population: Pilot Observational Epidemiology Study","volume":"8","author":"Vaidya","year":"","journal-title":"JMIR Public Health Surveill."},{"key":"B195","first-page":"33679","article-title":"An Intrinsic Need for K2-7 Supplementation: A Narrative Review of K2-7 and Peripheral Neuropathy. Communicated","volume":"42","author":"Vaidya","year":"","journal-title":"Biomed. J. Sci. Tech. Res."},{"key":"B196","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1017\/S0007114509382100","article-title":"The Effect of Menaquinone-7 (Vitamin K2) Supplementation on Osteocalcin Carboxylation in Healthy Prepubertal Children","volume":"102","author":"van Summeren","year":"2009","journal-title":"Br. J. Nutr."},{"key":"B197","unstructured":"Vitamin K in PEritonial DIAlysis (VIKIPEDIA)\n            VasileiosV.\n          2021"},{"key":"B198","unstructured":"Phase 2 Study Randomized Placebo Controlled with Vitamin K2 in Asymptomatic Calcified Carotid Stenosis\n            VidaleS.\n          2014"},{"key":"B199","doi-asserted-by":"publisher","first-page":"3959","DOI":"10.1080\/10408398.2016.1211616","article-title":"Effect of Vitamin K in Bone Metabolism and Vascular Calcification: A Review of Mechanisms of Action and Evidences","volume":"57","author":"Villa","year":"2017","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"B200","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1055\/s-0037-1614168","article-title":"Modulation of the Binding of Matrix Gla Protein (MGP) to Bone Morphogenetic Protein-2 (BMP-2)","volume":"84","author":"Wallin","year":"2000","journal-title":"Thromb. Haemost."},{"key":"B201","doi-asserted-by":"publisher","first-page":"463","DOI":"10.3945\/an.113.003855","article-title":"Menaquinones, Bacteria, and the Food Supply: the Relevance of Dairy and Fermented Food Products to Vitamin K Requirements","volume":"4","author":"Walther","year":"2013","journal-title":"Adv. Nutr."},{"key":"B202","doi-asserted-by":"publisher","first-page":"136","DOI":"10.3978\/j.issn.2305-5839.2015.03.49","article-title":"Role of Pro-inflammatory Cytokines Released from Microglia in Alzheimer's Disease","volume":"3","author":"Wang","year":"2015","journal-title":"Ann. Transl. Med."},{"key":"B203","doi-asserted-by":"publisher","first-page":"116","DOI":"10.3389\/fncel.2019.00116","article-title":"Emerging Role of Schwann Cells in Neuropathic Pain: Receptors, Glial Mediators and Myelination","volume":"13","author":"Wei","year":"2019","journal-title":"Front. Cell Neurosci."},{"key":"B204","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1053\/j.ajkd.2011.10.041","article-title":"Effect of Vitamin K2 Supplementation on Functional Vitamin K Deficiency in Hemodialysis Patients: A Randomized Trial","volume":"59","author":"Westenfeld","year":"2012","journal-title":"Am. J. Kidney Dis."},{"key":"B205","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1210\/jcem.86.5.7463","article-title":"Hypoadiponectinemia in Obesity and Type 2 Diabetes: Close Association with Insulin Resistance and Hyperinsulinemia","volume":"86","author":"Weyer","year":"2001","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"B206","doi-asserted-by":"publisher","first-page":"110540","DOI":"10.1016\/j.fct.2019.05.048","article-title":"A Comparatively Study of Menaquinone-7 Isolated from Cheonggukjang with Vitamin K1 and Menaquinone-4 on Osteoblastic Cells Differentiation and Mineralization","volume":"131","author":"Wu","year":"2019","journal-title":"Food Chem. Toxicol."},{"key":"B207","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.1016\/j.jnutbio.2011.11.010","article-title":"The Role of PKC Isoforms in the Inhibition of NF-\u039ab Activation by Vitamin K2 in Human Hepatocellular Carcinoma Cells","volume":"23","author":"Xia","year":"2012","journal-title":"J. Nutr. Biochem."},{"key":"B208","doi-asserted-by":"publisher","first-page":"8926","DOI":"10.3892\/ol.2018.8502","article-title":"Research Progress on the Anticancer Effects of Vitamin K2","volume":"15","author":"Xv","year":"2018","journal-title":"Oncol. Lett."},{"key":"B209","doi-asserted-by":"publisher","DOI":"10.15761\/IMM.1000101","article-title":"Role of Nutritional Factor Menaquinone-7 in Bone Homeostasis and Osteoporosis Prevention","volume":"1","author":"Yamaguchi","year":"2014","journal-title":"Integr. Mol. Med."},{"key":"B210","doi-asserted-by":"publisher","first-page":"762","DOI":"10.1038\/nature01705","article-title":"Cloning of Adiponectin Receptors that Mediate Antidiabetic Metabolic Effects","volume":"423","author":"Yamauchi","year":"2003","journal-title":"Nature"},{"key":"B211","doi-asserted-by":"publisher","DOI":"10.1002\/aic.16754","article-title":"Metabolic Engineering ofBacillus Subtilisfor High\u2010titer Production of Menaquinone\u20107","volume":"66","author":"Yang","year":"2020","journal-title":"AIChE J."},{"key":"B212","doi-asserted-by":"publisher","first-page":"726213","DOI":"10.3389\/fonc.2021.726213","article-title":"Progression of Prothrombin Induced by Vitamin K Absence-II in Hepatocellular Carcinoma","volume":"11","author":"Yang","year":"2021","journal-title":"Front. Oncol."},{"key":"B213","doi-asserted-by":"publisher","first-page":"629","DOI":"10.4161\/auto.5941","article-title":"Vitamin K2 Induces Autophagy and Apoptosis Simultaneously in Leukemia Cells","volume":"4","author":"Yokoyama","year":"2008","journal-title":"Autophagy"},{"key":"B214","doi-asserted-by":"publisher","first-page":"6047","DOI":"10.3390\/ijms20236047","article-title":"Bone Pain in Cancer Patients: Mechanisms and Current Treatment","volume":"20","author":"Zaj\u0105czkowska","year":"2019","journal-title":"Ijms"},{"key":"B215","unstructured":"Effect of Vitamin K2 (MK7) on Cardiovascular and Bone Disease in Dialysis Patients: A Prospective, Randomized Placebo-Controlled Double Blind Trial2020"},{"key":"B216","doi-asserted-by":"publisher","first-page":"24719","DOI":"10.18632\/oncotarget.15791","article-title":"Lactobacillus Casei Zhang and Vitamin K2 Prevent Intestinal Tumorigenesis in Mice via Adiponectin-Elevated Different Signaling Pathways","volume":"8","author":"Zhang","year":"2017","journal-title":"Oncotarget"},{"key":"B222","doi-asserted-by":"publisher","first-page":"1093","DOI":"10.6061\/clinics\/2012(09)18","article-title":"Synergistic Growth Inhibition by Sorafenib and Vitamin K2 in Human Hepatocellular Carcinoma Cells","volume":"67","author":"Zhang","year":"2012","journal-title":"Clinics (Sao Paulo)"},{"key":"B217","doi-asserted-by":"publisher","first-page":"1010","DOI":"10.1006\/bbrc.1993.2350","article-title":"Amplification and Overexpression of Cyclin D1 in Human Hepatocellular Carcinoma","volume":"196","author":"Zhang","year":"1993","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B218","doi-asserted-by":"publisher","first-page":"624","DOI":"10.1002\/kjm2.12373","article-title":"Statins, Vascular Calcification, and Vitamin K\u2010dependent Proteins: Is There a Relation?","volume":"37","author":"Zhelyazkova\u2010Savova","year":"2021","journal-title":"Kaohsiung J. Med. Sci."},{"key":"B219","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1093\/ajcn\/nqz147","article-title":"The Effect of Menaquinone-7 Supplementation on Vascular Calcification in Patients with Diabetes: a Randomized, Double-Blind, Placebo-Controlled Trial","volume":"110","author":"Zwakenberg","year":"2019","journal-title":"Am. J. Clin. Nutr."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.896920\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,14]],"date-time":"2022-06-14T03:23:56Z","timestamp":1655177036000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.896920\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,14]]},"references-count":222,"alternative-id":["10.3389\/fphar.2022.896920"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.896920","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,14]]},"article-number":"896920"}}