Vitamin K as a Diet Supplement with Impact in Human Health: Current Evidence in Age-Related Diseases

Dina C Simes, Carla S B Viegas, Nuna Araújo, Catarina Marreiros, Dina C Simes, Carla S B Viegas, Nuna Araújo, Catarina Marreiros

Abstract

Vitamin K health benefits have been recently widely shown to extend beyond blood homeostasis and implicated in chronic low-grade inflammatory diseases such as cardiovascular disease, osteoarthritis, dementia, cognitive impairment, mobility disability, and frailty. Novel and more efficient nutritional and therapeutic options are urgently needed to lower the burden and the associated health care costs of these age-related diseases. Naturally occurring vitamin K comprise the phylloquinone (vitamin K1), and a series of menaquinones broadly designated as vitamin K2 that differ in source, absorption rates, tissue distribution, bioavailability, and target activity. Although vitamin K1 and K2 sources are mainly dietary, consumer preference for diet supplements is growing, especially when derived from marine resources. The aim of this review is to update the reader regarding the specific contribution and effect of each K1 and K2 vitamers in human health, identify potential methods for its sustainable and cost-efficient production, and novel natural sources of vitamin K and formulations to improve absorption and bioavailability. This new information will contribute to foster the use of vitamin K as a health-promoting supplement, which meets the increasing consumer demand. Simultaneously, relevant information on the clinical context and direct health consequences of vitamin K deficiency focusing in aging and age-related diseases will be discussed.

Keywords: age-related diseases; diet supplement; inflammation; pathological calcification; vitamin K; vitamin K-dependent proteins.

Conflict of interest statement

Dina Simes and Carla Viegas are cofounders of Genogla Diagnostics. The authors declare that there is no conflict of interest regarding the publication of this paper.

Figures

Figure 1
Figure 1
Chemical Structure of Vitamin K vitamers. Phylloquinone or vitamin K1 (A), menaquinone-n (MKn), or vitamin K2 (B) and menadione or vitamin K3 (C).

References

    1. Dam B.Y.H., Schnheyder F. The occurence and chemical nature of vitamin k. Biochem. J. 1936;30:897–901.
    1. Nelsestuen G.L., Suttie W. Mode of Action of Vitamin K. Calcium Binding Properties of Bovine Prothrombint. Biochem. J. 1972;11:4961–4964. doi: 10.1021/bi00776a013.
    1. Willems B.A.G., Vermeer C., Chris P., Reutelingsperger M., Schurgers L.J. The realm of vitamin K dependent proteins: Shifting from coagulation toward calcification. Mol. Nutr. Food Res. 2014;58:1620–1635. doi: 10.1002/mnfr.201300743.
    1. Cranenburg E.C.M., Schurgers L.J., Uiterwijk H.H., Beulens J.W.J., Dalmeijer G.W., Westerhuis R., Magdeleyns E.J., Herfs M., Vermeer C., Laverman G.D. Vitamin K intake and status are low in hemodialysis patients. Kidney Int. 2012;82:605–610. doi: 10.1038/ki.2012.191.
    1. Misra D., Booth S.L., Tolstykh I., Felson D.T., Nevitt M.C., Lewis C.E., Torner J., Neogi T. Vitamin K Deficiency Is Associated with Incident Knee Osteoarthritis. Am. J. Med. 2013;126:243–248. doi: 10.1016/j.amjmed.2012.10.011.
    1. Simes D.C., Viegas C.S.B., Araujo N., Marreiros C. Vitamin K as a Powerful Micronutrient in Aging and Age-Related Diseases: Pros and Cons from Clinical Studies. IJMS. 2019;20:4150. doi: 10.3390/ijms20174150.
    1. Lippi G., Favaloro E.J. Laboratory hemostasis: From biology to the bench. Clin. Chem. Lab. Med. 2018;56:1035–1045. doi: 10.1515/cclm-2017-1205.
    1. Dahlbäck B. Blood coagulation and its regulation by anticoagulant pathways: Genetic pathogenesis of bleeding and thrombotic diseases. J. Intern. Med. 2005;257:209–223. doi: 10.1111/j.1365-2796.2004.01444.x.
    1. Van De Wouwer M., Collen D., Conway E.M. Thrombomodulin-protein C-EPCR system integrated to regulate coagulation and inflammation. Arter. Thromb. Vasc. Biol. Biol. 2004;24:1374–1383. doi: 10.1161/01.ATV.0000134298.25489.92.
    1. Riewald M., Petrovan R.J., Donner A., Mueller B.M., Ruf W. Activation of endothelial cell protease activated receptor 1 by the protein C pathway. Science. 2002;296:1880–1882. doi: 10.1126/science.1071699.
    1. Maillard C., Berruyer M., Serre C., Dechavanne M., Delmas P. Protein-S, a vitamin K-dependent protein, is a bone matrix component synthesized and secreted by osteoblasts. Endocrinology. 1992;130:1599–1604.
    1. Rezende S.M., Simmonds R.E., Lane D.A. Coagulation, inflammation, and apoptosis: Different roles for protein S and the protein S-C4b binding protein complex. Blood. 2004;103:1192–1201. doi: 10.1182/blood-2003-05-1551.
    1. Vasse M. Protein Z, a protein seeking a pathology. Thromb. Haemost. 2008;100:548–556. doi: 10.1160/TH08-01-0024.
    1. Almawi W.Y., Al-Shaikh F.S., Melemedjian O.K., Almawi A.W. Protein Z, an anticoagulant protein with expanding role in reproductive biology. Reproduction. 2013;146:R73–R80. doi: 10.1530/REP-13-0072.
    1. Neve A., Corrado A., Cantatore F.P. Osteocalcin: Skeletal and extra-skeletal effects. J. Cell. Physiol. 2013;228:1149–1153. doi: 10.1002/jcp.24278.
    1. Zoch M.L., Clemens T.L., Riddle R.C. New Insights into the Biology of Osteocalcin. Bone. 2016;27:915–918. doi: 10.1016/j.bone.2015.05.046.
    1. Bjorklund G., Svanberg E., Dadar M., David J.C., Salvatore C., Dominic J.H., Jan A. The role of matrix Gla protein (MGP) in vascular calcification. Curr. Med. Chem. 2018 doi: 10.2174/0929867325666180716104159.
    1. Gheorghe S.R., Craciun A.M. Matrix Gla protein in tumoral pathology. Clujul Med. 2016;89:319–321. doi: 10.15386/cjmed-579.
    1. Boström K., Zebbondj A.F., Yao Y., Lin T.S., Torres A. Matrix GLA protein stimulates VEGF expression through increased transforming growth factor-β1 activity in endothelial cells. J. Biol. Chem. 2004;279:52904–52913. doi: 10.1074/jbc.M406868200.
    1. Fernández-Fernández L., Bellido-Martín L., De Frutos P.G. Growth arrest-specific gene 6 (GAS6): An outline of its role in haemostasis and inflammation. Thromb. Haemost. 2008;100:604–610. doi: 10.1160/TH08-04-0253.
    1. Cosemans J.M.E.M., Van Kruchten R., Olieslagers S., Schurgers L.J., Verheyen F.K., Munnix I.C.A., Waltenberger J., Angelillo-Scherrer A., Hoylaerts M.F., Carmeliet P., et al. Potentiating role of Gas6 and Tyro3, Axl and Mer (TAM) receptors in human and murine platelet activation and thrombus stabilization. J. Thromb. Haemost. 2010;8:1797–1808. doi: 10.1111/j.1538-7836.2010.03935.x.
    1. Hasanbasic I., Rajotte I., Blostein M. The role of γ-carboxylation in the anti-apoptotic function of gas6. J. Thromb. Haemost. 2005;3:2790–2797. doi: 10.1111/j.1538-7836.2005.01662.x.
    1. Viegas C.S.B., Costa R.M., Santos L., Videira P.A., Silva Z., Araújo N., Macedo A.L., Matos A.P., Vermeer C., Simes D.C. Gla-rich protein function as an anti-inflammatory agent in monocytes/macrophages: Implications for calcification-related chronic inflammatory diseases. PLoS ONE. 2017;12:e0177829. doi: 10.1371/journal.pone.0177829.
    1. Viegas C.S.B., Rafael M.S., Enriquez J.L., Teixeira A., Vitorino R., Luís I.M., Costa R.M., Santos S., Cavaco S., Neves J., et al. Gla-Rich Protein acts as a Calcification Inhibitor in the Human Cardiovascular System. Arter. Thromb. Vasc. Biol. 2015;35:399–408. doi: 10.1161/ATVBAHA.114.304823.
    1. Cavaco S., Viegas C.S.B., Rafael M.S., Ramos A., Magalhães J., Blanco F.J., Vermeer C., Simes D.C. Gla-rich protein is involved in the cross-talk between calcification and inflammation in osteoarthritis. Cell. Mol. Life Sci. 2016;73:1051–1065. doi: 10.1007/s00018-015-2033-9.
    1. Viegas C.S.B., Santos L., Macedo A.L., Matos A.A., Silva A.P., Neves P.L. Chronic Kidney Disease Circulating Calciprotein Particles and Extracellular Vesicles Promote Vascular Calcification: A Role for GRP (Gla-Rich Protein) Arter. Thromb. Vasc. Biol. 2018;38:575–587. doi: 10.1161/ATVBAHA.117.310578.
    1. Hamilton D.W. Functional role of periostin in development and wound repair: Implications for connective tissue disease. J. Cell Commun. Signal. 2008;2:9–17. doi: 10.1007/s12079-008-0023-5.
    1. Kim B.R., Kwon Y.W., Park G.T., Choi E.J., Seo J.K., Jang I.H., Kim S.C., Ko H.C., Lee S.C., Kim J.H. Identification of a novel angiogenic peptide from periostin. PLoS ONE. 2017;12:e0187464. doi: 10.1371/journal.pone.0187464.
    1. Kühn B., Del Monte F., Hajjar R.J., Chang Y.S., Lebeche D., Arab S., Keating M.T. Periostin induces proliferation of differentiated cardiomyocytes and promotes cardiac repair. Nat. Med. 2007;13:962–969. doi: 10.1038/nm1619.
    1. Kulman J.D., Harris J.E., Xie L., Davie E.W. Proline-rich Gla protein 2 is a cell-surface vitamin K-dependent protein that binds to the transcriptional coactivator Yes-associated protein. Proc. Natl. Acad. Sci. USA. 2007;104:8767–8772. doi: 10.1073/pnas.0703195104.
    1. Kulman J.D., Harris J.E., Haldeman B.A., Davie E.W. Primary structure and tissue distribution of two nove proline-rich γ-carboxyglutamic acid proteins. Proc. Natl. Acad. Sci. USA. 1997;94:9058–9062. doi: 10.1073/pnas.94.17.9058.
    1. Khazi F.R., Chu K.C., High K.A. Transmembrane Gla Protein 4 as a Novel Modulator of ERK2. Blood. 2006;108:544. doi: 10.1182/blood.V108.11.544.544.
    1. Presnell S.R., Stafford D.W. The Vitamin K-dependent Carboxylase. Thromb. Haemost. 2002;87:937–946. doi: 10.1055/s-0037-1613115.
    1. Shikdar S., Bhattacharya P.T. StatPearls [Internet] StatPearls Publishing; Treasure Island, FL, USA: 2019. [(accessed on 12 December 2019)]. International Normalized Ratio (INR) [Updated 2019 Mar 25] Available online:
    1. Conly J., Stein K., Worobetz L., Rutledge-Harding S. The contribution of vitamin K2 (menaquinones) produced by the intestinal microflora to human nutritional requirements for vitamin K. Am. J. Gastroenterol. 1994;89:915–923.
    1. Aziz F., Patil P. Role of Prophylactic Vitamin K in Preventing Antibiotic Induced Hypoprothrombinemia. Indian J. Pediatr. 2015;82:363–367. doi: 10.1007/s12098-014-1584-3.
    1. Shevcbuk Y.M., Conly J.M. Antibiotic-Associated Hypoprothrombinemia: A Review of Prospective Studies, 1966–1988. Rev. Infect. Dis. 1990;12:1109–1126. doi: 10.1093/clinids/12.6.1109.
    1. Cinaz S.Y., Tavi B., Sarı S., Cinaz P. Vitamin k deficiency because of ceftriaxone usage and prolonged diarrhoea. JPCH. 2011;47:314–315.
    1. Chen L., Hsiao F., Shen L., Wu F.L., Tsay W. Use of Hypoprothrombinemia-Inducing Cephalosporins and the Risk of Hemorrhagic Events: A Nationwide Nested Case-Control Study. PLoS ONE. 2016;27:e0158407. doi: 10.1371/journal.pone.0158407.
    1. Vroonhof K., Van Rijn H.J.M., Van Hattum J. Vitamin K deficiency and bleeding after long-term use of cholestyramine. Neth. J. Med. 2003;61:19–21.
    1. MacWalter R., Fraser H., Armstrong K. Orlistat Enhances Warfarin Effect. Ann. Pharmacother. 2003;37:510–512. doi: 10.1345/aph.1C122.
    1. Sutor A., von Kries R., Cornelissen E., McNinch A., Andrew M. Vitamin K deficiency bleeding (VKDB) in infancy. ISTH Pediatric/Perinatal Subcommittee. International Society on Thrombosis and Haemostasis. Thromb. Haemost. 1999;81:456–461.
    1. American Academy of Pediatrics Committee on Fetus and Newborn Controversies concerning vitamin K and the newborn. Pediatrics. 2003;112:191–192.
    1. Pichler E., Pichler L. The neonatal coagulation system and the vitamin K deficiency bleeding—A mini review. Wien. Med. Wochenschr. 2008;158:385–395. doi: 10.1007/s10354-008-0538-7.
    1. Schulte R., Jordan L.C., Morad A., Naftel R.P., Iii J.C.W., Sidonio R. Rise in Late Onset Vitamin K Defi ciency Bleeding in Young Infants Because of Omission or Refusal of Prophylaxis at Birth. Pediatr. Neurol. 2014;50:564–568. doi: 10.1016/j.pediatrneurol.2014.02.013.
    1. Wen L., Chen J., Duan L., Li S. Vitamin K-dependent proteins involved in bone and cardiovascular health. Mol. Med. Rep. 2018;18:3–15. doi: 10.3892/mmr.2018.8940.
    1. Alisi L., Cao R., De Angelis C., Cafolla A., Caramia F., Cartocci G., Librando A., Fiorelli M. The Relationships Between Vitamin K and Cognition: A Review of Current Evidence. Front. Neurol. 2019;10:239. doi: 10.3389/fneur.2019.00239.
    1. Shea M.K., Kritchevsky S.B., Hsu F., Nevitt M., Booth S.L., Kwoh C.K., Mcalindon T.E., Drummen N., Harris T.B., Womack C., et al. The association between vitamin K status and knee osteoarthritis features in older adults: The Health, Aging and Body Composition Study. Osteoarthr. Cartil. 2016;23:370–378. doi: 10.1016/j.joca.2014.12.008.
    1. Shea M.K., Booth S.L., Weiner D.E., Brinkley T.E., Kanaya A.M., Murphy R.A., Simonsick E.M., Wassel C.L., Vermeer C., Kritchevsky S.B. Circulating Vitamin K Is Inversely Associated with Incident Cardiovascular Disease Risk among Those Treated for Hypertension in the Health, Aging, and Body Composition Study (Health ABC) 1–3. J. Nutr. 2017;147:888–895. doi: 10.3945/jn.117.249375.
    1. Zhang S., Guo L., Bu C. Vitamin K status and cardiovascular events or mortality: A meta-analysis. Eur. J. Prev. Cardiol. 2019;26:549–553. doi: 10.1177/2047487318808066.
    1. Ferland G. Vitamin K, an emerging nutrient in brain function. Biofactors. 2012;38:151–157. doi: 10.1002/biof.1004.
    1. Chatrou M.L., Winckers K., Hackeng T.M., Reutelingsperger C.P., Schurgers L.J. Vascular calcification: The price to pay for anticoagulation therapy with vitamin K-antagonists. Blood Rev. 2012;26:155–166. doi: 10.1016/j.blre.2012.03.002.
    1. Dinicolantonio J.J., Bhutani J., Keefe J.H.O. The health benefits of vitamin K. Open Heart. 2015;2:e000300. doi: 10.1136/openhrt-2015-000300.
    1. Namba S., Yamaoka-tojo M., Hashikata T., Ikeda Y., Kitasato L., Hashimoto T., Shimohama T., Tojo T., Takahira N., Masuda T., et al. Long-term warfarin therapy and biomarkers for osteoporosis and atherosclerosis. BBA Clin. 2015;12:76–80. doi: 10.1016/j.bbacli.2015.08.002.
    1. Van Gorp R.H., Schurgers L.J. New Insights into the Pros and Cons of the Clinical Use of Vitamin K Antagonists (VKAs) Versus Direct Oral Anticoagulants (DOACs) Nutrients. 2015;7:9538–9557. doi: 10.3390/nu7115479.
    1. Schurgers L.J., Uitto J., Reutelingsperger C.P. Vitamin K-dependent carboxylation of matrix Gla-protein: A crucial switch to control ectopic mineralization. Trends Mol. Med. 2013;19:217–226. doi: 10.1016/j.molmed.2012.12.008.
    1. Schurgers L.J., Spronk H.M.H., Soute B.A.M., Schiffers P.M., Demey J.G.R., Vermeer C. Regression of warfarin-induced medial elastocalcinosis by high intake of vitamin K in rats. Blood. 2007;109:2823–2831. doi: 10.1182/blood-2006-07-035345.
    1. Lerner R.G., Aronow W.S., Sekhri A., Palaniswamy C., Ahn C., Singh T., Sandhu R. Warfarin use and the risk of valvular calcification. J. Thromb. Haemost. 2009;7:2023–2027. doi: 10.1111/j.1538-7836.2009.03630.x.
    1. Rennenberg R.J.M.W., Van Varik B.J., Schurgers L.J., Hamulyak K., Cate H., Leiner T., Vermeer C., De Leeuw P.W., Kroon A.A. Chronic coumarin treatment is associated with increased extracoronary arterial calcification in humans. Blood. 2010;115:5121–5123. doi: 10.1182/blood-2010-01-264598.
    1. Han K.H., O’Neill W.C. Increased Peripheral Arterial Calcification in Patients Receiving Warfarin. J. Am. Heart Assoc. 2016;5:e002665. doi: 10.1161/JAHA.115.002665.
    1. Schurgers L.J., Joosen I.A., Laufer E.M., Chatrou M.L.L., Herfs M., Winkens M.H.M., Westenfeld R., Veulemans V., Krueger T., Shanahan C.M., et al. Vitamin K-Antagonists Accelerate Atherosclerotic Calcification and Induce a Vulnerable Plaque Phenotype. PLoS ONE. 2012;7:e43229. doi: 10.1371/journal.pone.0043229.
    1. Koos R., Mahnken A.H., Mühlenbruch G., Brandenburg V., Pflueger B., Wildberger J.E., Kühl H.P. Relation of Oral Anticoagulation to Cardiac Valvular and Coronary Calcium Assessed by Multislice Spiral Computed Tomography. Am. J. Cardiol. 2005;96:747–749. doi: 10.1016/j.amjcard.2005.05.014.
    1. Weijs B., Blaauw Y., Rennenberg R., Schurgers L., Timmermans C., Pison L., Nieuwlaat R., Hofstra L., Kroon A., Wildberger J., et al. Patients using vitamin K antagonists show increased levels of coronary calcification: An observational study in low-risk atrial fibrillation patients. Eur. Heart J. 2011;32:2555–2562. doi: 10.1093/eurheartj/ehr226.
    1. Villines T.C., Malley P.G.O., Feuerstein I.M., Thomas S., Taylor A.J. Does Prolonged Warfarin Exposure Potentiate Coronary Calcification in Humans? Results of the Warfarin and Coronary Calcification Study. Calcif. Tissue Int. 2009;85:494–500. doi: 10.1007/s00223-009-9300-4.
    1. Mac-Way F., Poulin A., Utescu M.S., De Serres S.A., Marquis K., Douville P., Desmeules S., Larivière R., Lebel M., Agharazii M. The impact of warfarin on the rate of progression of aortic stiffness in hemodialysis patients: A longitudinal study. Nephrol. Dial. Transpl. 2014;29:2113–2120. doi: 10.1093/ndt/gfu224.
    1. Verdalles Guzmán Ú., De La Cueva P., Verde E., De Vinuesa S.G., Goicoechea M., Mosse A., López Gómez J.M., Luño J. Calciphylaxis: Fatal complication of cardiometabolic syndrome in patients with end stage kidney disease. Nefrologia. 2008;28:32–36.
    1. Eggebrecht L., Prochaska H., Schulz A., Arnold N., Junger C., Gobel S., Laubert-reh D., Binder H., Beutel M.E., Pfeiffer N., et al. Intake of Vitamin K Antagonists and Worsening of Cardiac and Vascular Disease: Results From the Population-Based Gutenberg Study. J. Am. Heart Assoc. 2018;7:e008650. doi: 10.1161/JAHA.118.008650.
    1. Andrews J., Psaltis P.J., Bayturan O., Shao M., Stegman B., Elshazly M., Kapadia S.R., Tuzcu E.M., Nissen S.E., Nicholls S.J., et al. Warfarin Use Is Associated With Progressive Coronary Arterial Calcification: Insights From Serial Intravascular Ultrasound. JACC Cardiovasc. Imaging. 2018;11:1315–1323. doi: 10.1016/j.jcmg.2017.04.010.
    1. Peeters F., Dudink E., Kimenai D., Weijs B., Altintas S., Heckman L., Mihl C., Schurgers L., Wildberger J., Meex S., et al. Vitamin K Antagonists, Non-Vitamin K Antagonist Oral Anticoagulants, and Vascular Calcification in Patients with Atrial Fibrillation. TH Open. 2018;2:e391–e398. doi: 10.1055/s-0038-1675578.
    1. Schwarb H., Tsakiris D.A. New Direct Oral Anticoagulants (DOAC) and Their Use Today. Dent. J. 2016;4:5. doi: 10.3390/dj4010005.
    1. Shearer M., Newman P. Metabolism and cell biology of vitamin K. Thromb. Haemost. 2008;100:530–547.
    1. Shearer M.J., Newman P. Recent trends in the metabolism and cell biology of vitamin K with special reference to vitamin K cycling and MK-4 biosynthesis. J. Lipid Res. 2014;55:345–362. doi: 10.1194/jlr.R045559.
    1. Booth S.L. Vitamin K: Food composition and dietary intakes. Food Nutr. Res. 2012;1:1–5. doi: 10.3402/fnr.v56i0.5505.
    1. Nakagawa K., Hirota Y., Sawada N., Yuge N., Watanabe M., Uchino Y., Okuda N., Shimomura Y., Suhara Y., Okano T. Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. Nature. 2010;468:117–121. doi: 10.1038/nature09464.
    1. Tie J., Stafford D. Structural and functional insights into enzymes of the vitamin K cycle. J. Thromb. Haemost. 2016;14:236–247. doi: 10.1111/jth.13217.
    1. Stafford D.W. The vitamin K cycle. J. Thromb. Haemost. 2005;3:1873–1878. doi: 10.1111/j.1538-7836.2005.01419.x.
    1. Rishavy M.A., Berkner K.L. Vitamin K Oxygenation, Glutamate Carboxylation, and Processivity: Defining the Three Critical Facets of Catalysis by the Vitamin K-Dependent Carboxylase. Adv. Nutr. 2012;3:135–148. doi: 10.3945/an.111.001719.
    1. Shearer M.J., Fu X., Booth S.L. Vitamin K Nutrition, Metabolism, and Requirements: UBIAD and Future Research. Adv. Nutr. 2012;3:182–195. doi: 10.3945/an.111.001800.
    1. Buitenhuis H., Soute B., Vermeer C. Comparison of the vitamins K1, K2 and K3 as cofactors for the hepatic vitamin K-dependent carboxylase. Biochim. Biophys. Acta. 1990;1034:170–175. doi: 10.1016/0304-4165(90)90072-5.
    1. Ohsaki Y., Shirakawa H., Hiwatashi K., Furukawa Y., Mizutani T., Komai M. Vitamin K Suppresses Lipopolysaccharide-Induced Inflammation in the Rat. Biosci. Biotechnol. Biochem. 2006;70:926–932. doi: 10.1271/bbb.70.926.
    1. Ohsaki Y., Shirakawa H., Miura A., Giriwono P.E., Sato S., Ohashi A., Iribe M., Goto T., Komai M. Vitamin K suppresses the lipopolysaccharide-induced expression of inflammatory cytokines in cultured macrophage-like cells via the inhibition of the activation of nuclear factor κB through the repression of IKKα/β phosphorylation. J. Nutr. Biochem. 2010;21:1120–1126. doi: 10.1016/j.jnutbio.2009.09.011.
    1. Fujii S., Shimizu A., Takeda N., Oguchi K., Katsurai T. Systematic synthesis and anti-inflammatory activity of x-carboxylated menaquinone derivatives. Investigations on identified and putative vitamin K2 metabolites. Bioorg. Med. Chem. 2015;23:2344–2352. doi: 10.1016/j.bmc.2015.03.070.
    1. Mukai K., Shingo I., Morimoto H. Stopped-flow Kinetic Study of Vitamin E Regeneration Reaction with Biological Hydroquinones (Reduced Forms of Ubiquinone, Vitamin K and Tocopherolquinone) in Solution. Biol. Chem. 1992;267:22277–22281.
    1. Vervoort L.M.T., Ronden J.E., Thijssen H.H.W. The Potent Antioxidant Activity of the Vitamin K Cycle in Microsomal Lipid Peroxidation. Biochem. Pharmacol. 1997;54:871–876. doi: 10.1016/S0006-2952(97)00254-2.
    1. Westhofen P., Watzka M., Marinova M., Hass M., Kirfel G., Mu J., Bevans C.G., Mu C.R., Oldenburg J. Human Vitamin K 2,3-Epoxide Reductase Complex Subunit 1-like 1 (VKORC1L1) Mediates Vitamin K-dependent Intracellular Antioxidant Function. Biol. Chem. 2011;286:15085–15094. doi: 10.1074/jbc.M110.210971.
    1. Li J., Lin J.C., Wang H., Peterson J.W., Furie B.C., Furie B., Booth S.L., Volpe J.J., Rosenberg P.A. Novel Role of Vitamin K in Preventing Oxidative Injury to Developing Oligodendrocytes and Neurons. J. Neurosci. 2003;23:5816–5826. doi: 10.1523/JNEUROSCI.23-13-05816.2003.
    1. Li J., Wang H., Rosenberg P.A. Vitamin K Prevents Oxidative Cell Death by Inhibiting Activation of 12-Lipoxygenase in Developing Oligodendrocytes. J. Neurosci. Res. 2009;87:1997–2005. doi: 10.1002/jnr.22029.
    1. Ambrożewicz E., Muszyńska M., Tokajuk G., Grynkiewicz G., Žarković N., Skrzydlewska E. Beneficial Effects of Vitamins K and D3 on Redox Balance of Human Osteoblasts Cultured with Hydroxypatite-Based Biomaterials. Cells. 2019;8:325. doi: 10.3390/cells8040325.
    1. Cutler R.G., Kelly J., Storie K., Pedersen W.A., Tammara A., Hatanpaa K., Troncoso J.C., Mattson M.P. Involvement of oxidative stress-induced abnormalities in ceramide and cholesterol metabolism in brain aging and Alzheimer’s disease. Proc. Natl. Acad. Sci. USA. 2004;101:2070–2075. doi: 10.1073/pnas.0305799101.
    1. Jana A., Hogan E.L., Pahan K. Ceramide and neurodegeneration: Susceptibility of neurons and oligodendrocytes to cell damage and death. J. Neurol. Sci. 2009;278:5–15. doi: 10.1016/j.jns.2008.12.010.
    1. De Chaves E.P., Sipione S. Sphingolipids and gangliosides of the nervous system in membrane function and dysfunction. FEBS Lett. 2010;584:1748–1759. doi: 10.1016/j.febslet.2009.12.010.
    1. Lev M., Milford A. The 3-Ketodihydrosphingosine melaninogenicus: Synthetase of Bacteroides melaninogenicus: Induction by Vitamin K. Arch. Biochem. Biophys. 1973;157:500–508. doi: 10.1016/0003-9861(73)90668-1.
    1. Sundaram K.S., Lev M. Regulation of sulfotransferase activity by vitamin k in mouse brain. Arch. Biochem. Biophys. 1990;277:109–113. doi: 10.1016/0003-9861(90)90557-F.
    1. Sundaram K.S., Lev M. Warfarin administration reduces synthesis of sulfatides and other sphingolipids in mouse brain. J. Lipid Res. 1988;29:1475–1479.
    1. Thijssen H., Drittij-Reijnders M. Vitamin K status in human tissues: Tissue-specific accumulation of phylloquinone and menaquinone-4. Br. J. Nutr. 1996;75:121–127. doi: 10.1079/BJN19960115.
    1. Carrie I., Portoukalian J., Vicaretti R., Rochford J., Potvin S., Ferland G. Menaquinone-4 Concentration Is Correlated with Sphingolipid Concentrations in Rat Brain. J. Nutr. 2004;134:167–172. doi: 10.1093/jn/134.1.167.
    1. Sundaram K.S., Engelke J.A., Foley A.L., Suttie J., Lev M. Vitamin K Status Influences Brain Sulfatide Metabolism in Young Mice and Rats. J. Nutr. 1996;126:2746–2751.
    1. Okano T., Shimomura Y., Yamane M., Suhara Y., Kamao M., Sugiura M., Nakagawa K. 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;25:11270–11279. doi: 10.1074/jbc.M702971200.
    1. Presse N., Shatenstein B., Kergoat M.J., Ferland G. Low Vitamin K Intakes in Community-Dwelling Elders at an Early Stage of Alzheimer’s Disease. J. Am. Diet. Assoc. 2008;108:2095–2099. doi: 10.1016/j.jada.2008.09.013.
    1. Presse N., Belleville S., Gaudreau P., Greenwood C.E., Kergoat M., Morais J.A., Payette H., Shatenstein B., Ferland G. Vitamin K status and cognitive function in healthy older adults. Neurobiol. Aging. 2013;34:2777–2783. doi: 10.1016/j.neurobiolaging.2013.05.031.
    1. Xv F., Chen J., Duan L., Li S. Research progress on the anticancer effects of vitamin K2. Oncol. Lett. 2018;15:8926–8934. doi: 10.3892/ol.2018.8502.
    1. Hitomi M., Yokoyama F., Nonomura T., Masaki T., Yosiji H., Inoeu H., Kinekawa F., Kurokohchi K., Uchida N., Watanabe S., et al. Antitumor effects of vitamins K1, K2 and K3 on hepatocellular carcinoma in vitro and in vivo. Int. J. Oncol. 2005;26:713–720. doi: 10.3892/ijo.26.3.713.
    1. Dasari S., Ali S.M., Zheng G., Chen A., Dontaraju V.S., Bosland M.C., Kajdacsy-balla A., Gnanasekar M. Vitamin K and its analogs: Potential avenues for prostate cancer management. Oncotarget. 2017;8:57782–57799. doi: 10.18632/oncotarget.17997.
    1. Schurgers L.J., Vermeer C. Determination of Phylloquinone and Menaquinones in Food. Effect of Food Matrix on Circulating Vitamin K Concentrations. Haemostasis. 2000;30:298–307.
    1. Schurgers L.J., Teunissen K.J.F., Hamulya K., Knapen M.H.J., Vik H., Vermeer C. Vitamin K- containing dietary supplements: Comparison of synthetic vitamin K1 and natto-derived menaquinone-7. Blood. 2007;109:3279–3283. doi: 10.1182/blood-2006-08-040709.
    1. Schurgers L.J., Vermeer C. Differential lipoprotein transport pathways of K-vitamins in healthy subjects. Biochim. Biophys. Acta. 2002;1570:27–32. doi: 10.1016/S0304-4165(02)00147-2.
    1. Hirota Y., Tsugawa N., Nakagawa K., Suhara Y., Tanaka K., Uchino Y., Takeuchi A., Sawada N., Kamao M., Wada A., et al. Menadione (Vitamin K3) Is a Catabolic Product of Oral Phylloquinone (Vitamin K1) in the Intestine and a Circulating Precursor of Tissue Menaquinone-4 (Vitamin K2) in Rats. J. Biol. Chem. 2013;288:33071–33080. doi: 10.1074/jbc.M113.477356.
    1. Tsugawa N., Shiraki M., Suhara Y., Kamao M., Tanaka K., Okano T. Vitamin K status of healthy Japanese women: Age-related vitamin K requirement for gamma-carboxylation of osteocalcin. Am. J. Clin. Nutr. 2006;83:380–386. doi: 10.1093/ajcn/83.2.380.
    1. Geleijnse J.M., Vermeer C., Grobbee D.E., Schurgers L.J., Knapen M.H.J., Van Der Meer I.M., Hofman A., Witteman J.C.M. Dietary Intake of Menaquinone Is Associated with a Reduced Risk of Coronary Heart Disease: The Rotterdam Study. J. Nutr. 2004;134:3100–3105. doi: 10.1093/jn/134.11.3100.
    1. Gast G.C., de Roos N.M., Sluijs I., Bots M.L., Beulens J.W., Geleijnse J.M., Witteman J.C., Grobbee D.E., Peeters P.H., van der Schouw Y.T. A high menaquinone intake reduces the incidence of coronary heart disease. Nutr. Metab. Cardiovasc. Dis. 2009;19:504–510. doi: 10.1016/j.numecd.2008.10.004.
    1. Shea M.K., Booth S.L., Miller M.E., Burke G., Chen H., Cushman M., Tracy R.P., Kritchevsky S.B. Associations between circulating vitamin K1 and coronary calcium progression in community-dwelling adults: the Multi-Etcnic Study of Atherosclerosis. Am. J. Clin. Nutr. 2013;98:197–208. doi: 10.3945/ajcn.112.056101.
    1. Usui Y., Tanimura H., Nishimura N., Kobayashi N., Okanou T., Zawa K. Vitamin K concentrations in the plasma and liver of surgical patients. Am. J. Clin. Nutr. 1990;51:846–852. doi: 10.1093/ajcn/51.5.846.
    1. Walther B., Karl J.P., Booth S.L., Boyaval P. Menaquinones, Bacteria, and the Food Supply: The Relevance of Dairy and Fermented Food Products to Vitamin K Requirements. Adv. Nutr. 2013;4:463–473. doi: 10.3945/an.113.003855.
    1. Shearer M.J., Bolton-Smith C. The UK food data-base for vitamin K and why we need it. Food Chem. 2000;68:213–218. doi: 10.1016/S0308-8146(99)00157-0.
    1. Bolton-smith C., Price R.J.G., Fenton S.T., Harrington D.J., Shearer M.J. Compilation of a provisional UK database for the phylloquinone (vitamin K1) content of foods. Br. J. Nutr. 2000;83:389–399.
    1. Ben-shem A., Frolow F., Nelson N. Crystal structure of plant photosystem I. Nature. 2003;426:630–635. doi: 10.1038/nature02200.
    1. Gross J., Cho W.K., Lezhneva L., Falk J., Krupinska K., Shinozaki K., Seki M., Herrmann R.G., Meurer J. A Plant Locus Essential for Phylloquinone (Vitamin K1) Biosynthesis Originated from a Fusion of Four Eubacterial Genes. J. Biol. Chem. 2006;281:17189–17196. doi: 10.1074/jbc.M601754200.
    1. Piironen V., Koivu T., Tammisalo O., Mattila P. Determination of phylloquinone in oils, margarines and butter by high-performance liquid chromatography with electrochemical detection. Food Chem. 1997;59:473–480. doi: 10.1016/S0308-8146(96)00288-9.
    1. Peterson J.W., Muzzey K.L., Haytowitz D., Exler J., Lemar L., Booth S.L. Phylloquinone (vitamin K1) and Dihydrophylloquinone Content of Fats and Oils. JAOCS. 2002;79:641–646. doi: 10.1007/s11746-002-0537-z.
    1. Elder S.J., Haytowitz D.B., Howe J., Peterson J.W., Booth S.L. Vitamin K Contents of Meat, Dairy, and Fast Food in the U.S. Diet. J. Agric. Food Chem. 2006;54:463–467. doi: 10.1021/jf052400h.
    1. Kamao M., Yoshitomo S., Tsuwaga N., Uwano M., Yamaguchi N., Uenishi K., Ishida H., Sasaki S., Okano T. Vitamin K Content of Foods and Dietary Vitamin K Intake in Japanese Young Women. J. Nutr. Sci. Vitaminol. 2007;53:464–470. doi: 10.3177/jnsv.53.464.
    1. Bito T., Teng F., Watanabe F. Bioactive Compounds of Edible Purple Laver Porphyra sp. (Nori) J. Agric. Food Chem. Agric. Food Chem. 2017;65:10685–10692. doi: 10.1021/acs.jafc.7b04688.
    1. Suttie J. The importance of menaquinones in human nutrition. Ann. Rev. Nutr. 1995;15:399–417. doi: 10.1146/annurev.nu.15.070195.002151.
    1. Collins M.D., Jones D. Distribution of isoprenoid quinone structural types in bacteria and their taxonomic implications. Microbiol. Rev. 1981;45:316–354.
    1. Fernandez F., Collins M.D. Vitamin K composition of anaerobic gut bacteria. FEMS Microbiol. Lett. 1987;41:175–180. doi: 10.1111/j.1574-6968.1987.tb02191.x.
    1. Conly J., Stein K. Quantitative and qualitative measurements of K vitamins in human. Am. J. Gastroenterol. 1992;87:311–316.
    1. Conly J., Stein K. The production of menaquinones (vitamin K2) by intestinal bacteria and their role in maintaining coagulation homeostasis. Prog. Food Nutr. Sci. 1992;16:307–343.
    1. Bourdichon F., Casaregola S., Farrokh C., Frisvad J.C., Gerds M.L., Hammes W.P., Harnett J., Huys G., Laulund S., Ouwehand A., et al. Food fermentations: Microorganisms with technological beneficial use. Int. J. Food Microbiol. 2012;154:87–97. doi: 10.1016/j.ijfoodmicro.2011.12.030.
    1. Morishita T., Tamura N., Makino T., Kudo S. Production of Menaquinones by Lactic Acid Bacteria. J. Dairy Sci. 1999;82:1897–1903. doi: 10.3168/jds.S0022-0302(99)75424-X.
    1. Manoury E., Jourdon K., Boyaval P., Fourcassié P. Quantitative measurement of vitamin K2 (menaquinones) in various fermented dairy products using a reliable high-performance liquid chromatography method. J. Dairy Sci. 2013;96:1335–1346. doi: 10.3168/jds.2012-5494.
    1. Vermeer C., Raes J., Van Hoofd C., Knapen M.H.J., Xanthoulea S. Menaquinone Content of Cheese. Nutrients. 2018;10:446. doi: 10.3390/nu10040446.
    1. Hojo K., Watanabe R., Mori T., Taketomo N. Quantitative measurement of tetrahydromenaquinone-9 in cheese fermented by propionibacteria. J. Dairy Sci. 2007;90:4078–4083. doi: 10.3168/jds.2006-892.
    1. Kaneki M., Hedges S.J., Hosoi T., Fujiwara S., Lyons A., Crean S.J., Ishida N., Nakagawa M., Takechi M., Sano Y., 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;4:315–321. doi: 10.1016/S0899-9007(00)00554-2.
    1. Villa J.K., Diaz M.A., Pizziolo V.R., Martino H.S. Effect of vitamin K in bone metabolism and vascular calcification: A review of mechanisms of action and evidences. Crit. Rev. Food Sci. Nutr. 2017;57:3959–3970. doi: 10.1080/10408398.2016.1211616.
    1. Sakane R., Kimura K., Hirota Y., Ishizawa M., Takagi Y., Akimori W., Shigefumi K., Makoto M., Suhara Y. Synthesis of novel vitamin K derivatives with alkylated phenyl groups introduced at the ω-terminal side chain and evaluation of their neural differentiation activities. Bioorg. Med. Chem. 2017;27:4881–4884. doi: 10.1016/j.bmcl.2017.09.038.
    1. Kimura K., Hirota Y., Kuwahara S., Takeuchi A., Tode C., Wada A., Osakabe N., Suhara Y. Synthesis of Novel Synthetic Vitamin K Analogues Prepared by Introduction of a Heteroatom and a Phenyl Group That Induce Highly Selective Neuronal Differentiation of Neuronal Progenitor Cells. J. Med. Chem. 2017;60:2591–2596. doi: 10.1021/acs.jmedchem.6b01717.
    1. Fujii S., Kagechika H. Medicinal Chemistry of Vitamin K Derivatives and Metabolites. Vital Health Wellbeing. 2017:239–255. doi: 10.5772/63511.
    1. Isler O., Doebel K., Hoffman-La Roche Inc. Synthesis of Vitamin K1 Using Boron Trifluoride Catalysts. 2,683,176. U.S. Patent. 1954 Jul 6;
    1. Fieser L.F. Synthesis of Vitamin K1. J. Am. Chem. Soc. 1939;61:3467–3475. doi: 10.1021/ja01267a072.
    1. Afanasjeva J. Administration of Injectable Vitamin K Orally. Hosp. Pharm. 2017;52:645–649. doi: 10.1177/0018578717729663.
    1. Daines A.M., Payne R.J., Humphries M.E., Abell A.D. The Synthesis of Naturally Occurring Vitamin K and Vitamin K Analogues. Org. Chem. 2003;7:1–15. doi: 10.2174/1385272033486279.
    1. Coman S.M., Parvulescu V.I., Wuttke S., Kemnitz E. Synthesis of Vitamin K1 and K1-Chromanol by Friedel–Crafts Alkylation in Heterogeneous Catalysis. ChemCatChem. 2010;2:92–97. doi: 10.1002/cctc.200900205.
    1. European Commission . Opinion on Vitamin K1 (Phytonadione) Scientific Committee on Consumer Safety; Brussels, Belgium: 2007. pp. 1–31. SCCP/1105/07.
    1. Tien J.-H., Pang C.-Y., Hsu N.-H., Sunny Pharmatec Inc. Method of Making Vitamin K1. Application WO2016060670A1. U.S. Patent. 2016 Apr 21;
    1. EFSA FEEDAP Panel (EFSA Panel on Additives and Products or Substances used in Animal Feed) Scientific Opinion on the safety and efficacy of vitamin K3 (menadione sodium bisulphite and menadione nicotinamide bisulphite) as a feed additive for all animal species. EFSA J. 2014;12:3532.
    1. Tarento T.D.C., Mcclure D.D., Talbot A.M., Regtop H.L., Biffin J.R., Valtchev P., Dehghani F., Kavanagh J.M., Tarento T.D.C., Mcclure D.D., et al. A potential biotechnological process for the sustainable production of vitamin K1. Crit. Rev. Biotechnol. 2019;39:1–19. doi: 10.1080/07388551.2018.1474168.
    1. Snyder C.D., Rapoport H. Synthesis of Menaquinones. J. Am. Chem. Soc. 1974;96:8046–8054. doi: 10.1021/ja00833a035.
    1. Baj A., Wa P., Kutner A., Morzycki J.W., Witkowski S. Convergent synthesis of menaquinone-7 (MK-7) Org. Process Res. Dev. 2016;20:1026–1033. doi: 10.1021/acs.oprd.6b00037.
    1. Suhara Y., Watanabe M., Motoyoshi S., Nakagawa K., Wada A., Takeda K., Takahashi K., Tokiwa H., Okano T. Synthesis of new vitamin K analogues as steroid and xenobiotic receptor (SXR) agonists: Insights into the biological role of the side chain part of vitamin K. J. Med. Chem. 2011;54:4918–4922. doi: 10.1021/jm200201k.
    1. Suhara Y., Hanada N., Okitsu T., Sakai M., Watanabe M., Nakagawa K., Wada A., Takeda K., Takahashi K., Tokiwa H., et al. Structure-activity relationship of novel menaquinone-4 analogues: Modification of the side chain affects their biological activities. J. Med. Chem. 2012;55:1553–1558. doi: 10.1021/jm2013166.
    1. Vermeer C., van’t Hoofd C., Knapen M.H.J., Xanthoulea S. Synthesis of 2-methyl-1,4-naphthoquinones with higher gamma-glutamyl carboxylase activity than MK-4 both in vitro and in vivo. Bioorg. Med. Chem. 2017;27:208–211. doi: 10.1016/j.bmcl.2016.11.073.
    1. Mahanama R., Berenjian A., Valtchev P., Talbot A., Biffin R., Regtop H., Dehghani F., Kavanagh J.M. Enhanced production of menaquinone 7 via solid substrate fermentation from Bacillus subtilis. Int. J. Food Eng. 2011;7 doi: 10.2202/1556-3758.2314.
    1. Berenjian A., Mahanama R., Talbot A., Regtop H., Kavanagh J., Dehghani F. Advances in menaquinone-7 production by bacillus subtilis natto: Fed-batch glycerol addition. Am. J. Biochem. Biotechnol. 2012;8:105–110.
    1. Singh R., Puri A., Panda B.P. Development of menaquinone-7 enriched nutraceutical: Inside into medium engineering and process modeling. J. Food Sci. Technol. 2015;52:5212–5219. doi: 10.1007/s13197-014-1600-7.
    1. Berenjian A., Mahanama R., Kavanagh J., Dehghani F., Berenjian A., Mahanama R., Kavanagh J., Dehghani F. Critical Reviews in Biotechnology Vitamin K series: Current status and future prospects. Crit. Rev. Biotechnol. 2015;35:199–208. doi: 10.3109/07388551.2013.832142.
    1. Schallmey M., Singh A., Ward O.P. Developments in the use of Bacillus species for industrial production. Can. J. Microbiol. 2004;50:1–17. doi: 10.1139/w03-076.
    1. Sato T., Yamada Y., Ohtani Y., Mitsui N., Murasawa H., Araki S. Production of menaquinone (vitamin K2)-7 by Bacillus subtilis. J. Biosci. Bioeng. 2001;91:16–20. doi: 10.1016/S1389-1723(01)80104-3.
    1. Song J., Liu H., Wang L., Dai J., Liu Y., Liu H., Zhao G., Wang P., Zheng Z. Enhanced Production of Vitamin K2 from Bacillus subtilis (natto) by Mutation and Optimization of the Fermentation Medium. Braz. Arch. Biol. Technol. 2014;57:606–612.
    1. Berenjian A., Chan N.L.C., Mahanama R., Talbot A., Regtop H., Kavanagh J., Dehghani F. Effect of biofilm formation by Bacillus subtilis natto on menaquinone-7 biosynthesis. Mol. Biotechnol. 2013;54:371–378. doi: 10.1007/s12033-012-9576-x.
    1. Sato T., Yamada Y., Ohtani Y., Mitsui N., Murasawa H., Araki S. Efficient production of menaquinone (vitamin K2) by a menadione-resistant mutant of Bacillus subtilis. J. Ind. Microbiol. Biotechnol. 2001;26:115–120. doi: 10.1038/sj.jim.7000089.
    1. Tsukamoto Y., Kasai M., Kakuda H. Construction of a Bacillus subtilis (natto) with High Productivity of Vitamin K2 (Menaquinone-7) by Analog Resistance. Biosci. Biotechnol. BioChem. 2001;65:2007–2015. doi: 10.1271/bbb.65.2007.
    1. Nishito Y., Osana Y., Hachiya T., Popendorf K., Toyoda A., Fujiyama A., Itaya M., Sakakibara Y. Whole genome assembly of a natto production strain Bacillus subtilis natto from very short read data. BMC Genom. 2010;11:243. doi: 10.1186/1471-2164-11-243.
    1. Ma Y., McClure D.D., Somerville M.V., Proschogo N.W., Dehghani F., Kavanagh J.M., Coleman N.V. Metabolic Engineering of the MEP Pathway in Bacillus subtilis for Increased Biosynthesis of Menaquinone-7. ACS Synth. Biol. 2019;8:1620–1630. doi: 10.1021/acssynbio.9b00077.
    1. Yang S., Cao Y., Sun L., Li C., Lin X., Cai Z., Zhang G., Song H. Modular Pathway Engineering of Bacillus subtilis to Promote de Novo Biosynthesis of Menaquinone-7. ACS Synth. Biol. 2019;8:70–81. doi: 10.1021/acssynbio.8b00258.
    1. Sanghvi A., Lo Y. Present and potential industrial applications of macro- and microalgae. Recent Pat. Food Nutr. Agric. 2010;2:187–194. doi: 10.2174/1876142911002030187.
    1. Collins K.G., Fitzgerald G.F., Stanton C., Ross R.P. Looking beyond the terrestrial: The potential of seaweed derived bioactives to treat non-communicable diseases. Mar. Drugs. 2016;14:60. doi: 10.3390/md14030060.
    1. Romano G., Costantini M., Sansone C., Lauritano C., Ruocco N., Ianora A. Marine microorganisms as a promising and sustainable source of bioactive molecules. Mar. Environ. Res. 2017;128:58–69. doi: 10.1016/j.marenvres.2016.05.002.
    1. Stengel D.B., Connan S. Marine Algae: A Source of Biomass for Biotechnological Applications. Methods Mol. Biol. 2015;1308:1–37.
    1. De Roeck-holtzhauer Y., Quere I., Claire C. Vitamin analysis of five planktonic microalgae and one macroalga. J. Appl. Phycol. 1991;3:259–264. doi: 10.1007/BF00003584.
    1. Tarento T.D.C., Mcclure D.D., Vasiljevski E., Schindeler A., Dehghani F., Kavanagh J.M. Microalgae as a source of vitamin K1. Algal Res. 2018;36:77–87. doi: 10.1016/j.algal.2018.10.008.
    1. Johnson T.W., Shen G., Zybailov B., Kolling D., Reategui R., Beauparlant S., Vassiliev I.R., Bryant D.A., Jones A.D., Golbeck J.H., et al. Recruitment of a foreign quinone into the A1 site of photosystem I. I. Genetic and physiological characterization of phylloquinone biosynthetic pathway mutants in Synechocystis sp. PCC 6803. J. Biol. Chem. 2000;275:8523–8530. doi: 10.1074/jbc.275.12.8523.
    1. Mimuro M., Tsuchiya T., Inoue H., Sakuragi Y., Itoh Y., Gotoh T., Miyashita H., Bryant D.A., Kobayashi M. The secondary electron acceptor of photosystem I in Gloeobacter violaceus PCC 7421 is menaquinone-4 that is synthesized by a unique but unknown pathway. FEBS Lett. 2005;579:3493–3496. doi: 10.1016/j.febslet.2005.05.029.
    1. Sakuragi Y., Zybailov B., Shen G., Bryant D.A., Golbeck J.H., Diner B.A., Karygina I., Pushkar Y., Stehlik D. Recruitment of a foreign quinone into the A1 site of photosystem I: Characterization of a menB rubA double deletion mutant in Synechococcus sp. PCC 7002 devoid of FX, FA, and FB and containing plastoquinone or exchanged 9,10-anthraquinone. J. Biol. Chem. 2005;280:12371–12381. doi: 10.1074/jbc.M412943200.
    1. Ikeda Y., Komura M., Watanabe M., Minami C., Koike H., Itoh S., Kashino Y., Satoh K. Photosystem I complexes associated with fucoxanthin-chlorophyll-binding proteins from a marine centric diatom, Chaetoceros gracilis. Biochim. Biophys. Acta. 2008;1777:351–361. doi: 10.1016/j.bbabio.2008.01.011.
    1. Yoshida E., Nakamura A., Watanabe T. Reversed-phase HPLC determination of chlorophyll a′ and naphthoquinones in photosystem I of red algae: Existence of two menaquinone-4 molecules in photosystem I of Cyanidium caldarium. Anal. Sci. 2003;19:1001–1005. doi: 10.2116/analsci.19.1001.
    1. Koivu T.J., Piironen V.I., Henttonen S.K., Mattila P.H. Determination of Phylloquinone in Vegetables, Fruits, and Berries by High-Performance Liquid Chromatography with Electrochemical Detection. J. Agric. Food Chem. Food Chem. 1997;45:4644–4649. doi: 10.1021/jf970357v.
    1. Booth S.L., Sadowski J.A., Penningtont J.A.T. Phylloquinone (Vitamin K1) Content of Foods in the US. Food and Drug Administration’s Total Diet Study. J. Agric. Food Chem. Food Chem. 1995;43:1574–1579. doi: 10.1021/jf00054a030.
    1. Salvaterra T., Green D.S., Crowe T.P., O’Gorman E.J. Impacts of the invasive alga Sargassum muticum on ecosystem functioning and food web structure. Biol. Invasions. 2013;15:2563–2576. doi: 10.1007/s10530-013-0473-4.
    1. Epstein G., Smale D.A. Undaria pinnatifida: A case study to highlight challenges in marine invasion ecology and management. Ecol. Evol. 2017;7:8624–8642. doi: 10.1002/ece3.3430.
    1. von Kries R., Hachmeister A., Gobel U. Oral mixed micellar vitamin K for prevention of late vitamin K deficiency bleeding. Arch. Dis Child. Fetal Neonatal Ed. 2003;88:109–112. doi: 10.1136/fn.88.2.F109.
    1. Hasselt P.M., Van Janssens G.E.P.J., Slot T.K., Van Der Ham M., Minderhoud T.C., Talelli M., Akkermans L.M., Rijcken C.J.F., Van Nostrum C.F. The influence of bile acids on the oral bioavailability of vitamin K encapsulated in polymeric micelles. J. Control. Release. 2009;133:161–168. doi: 10.1016/j.jconrel.2008.09.089.
    1. Leiro V., Moreno P., Sarmento B., Durão J., Gales L., Pêgo A., Barrias C. 1-Design and preparation of biomimetic and bioinspired materials. In: Rodrigues L., Mota M., editors. Bioinspired Materials for Medical Applications. Woodhead Publishing; Cambridge, UK: 2017. pp. 1–44.
    1. Sun F., Ye C., Thanki K., Leng D., Van Hasselt P.M., Hennink W.E., van Nostrum C.F. Mixed micellar system stabilized with saponins for oral delivery of vitamin K. Colloids Surf. B Biointerfaces. 2018;170:521–528. doi: 10.1016/j.colsurfb.2018.06.049.
    1. Hamrick H.J., Gable K., Freeman H., Dunn L., Zimmerman P., Rusin M.M., Linthavong R., Wright E., Moss A., Skinner C. Reasons for Refusal of Newborn Vitamin K Prophylaxis: Implications for Management and Education. Hosp. Pediatr. 2019;6:15–21. doi: 10.1542/hpeds.2015-0095.
    1. Gomaa Y.A., Garland M.J., Mcinnes F., El-khordagui L.K., Wilson C., Donnelly R.F. Laser-engineered dissolving microneedles for active transdermal delivery of nadroparin calcium. Eur. J. Pharm. Biopharm. 2012;82:299–307. doi: 10.1016/j.ejpb.2012.07.008.
    1. Quinn H.L., Bonham L., Hughes C.M., Donnelly R.F. Design of a Dissolving Microneedle Platform for Transdermal Delivery of a Fixed-Dose Combination of Cardiovascular Drugs. J. Pharm. Sci. 2015;104:3490–3500. doi: 10.1002/jps.24563.
    1. Sullivan S.P., Koutsonanos D.G., Martin P., Lee J., Zarnitsyn V., Murthy N., Compans R.W., Skountzou I., Prausnitz R. Dissolving Polymer Microneedle Patches for Influenza Vaccination. Nat. Med. 2010;16:915–920. doi: 10.1038/nm.2182.
    1. González-vázquez P., Larrañeta E., Mccrudden M.T.C., Jarrahian C., Rein-weston A., Quintanar-solares M., Zehrung D., Mccarthy H., Courtenay A.J., Donnelly R.F. Transdermal delivery of gentamicin using dissolving microneedle arrays for potential treatment of neonatal sepsis. J. Control. Release. 2017;265:30–40. doi: 10.1016/j.jconrel.2017.07.032.
    1. Hutton A.R.J., Quinn H.L., Mccague P.J., Jarrahian C., Rein-weston A., Co P.S., Gerth-guyette E., Zehrung D., Larrañeta E., Donnelly R.F. Transdermal delivery of vitamin K using dissolving microneedles for the prevention of vitamin K deficiency bleeding. Int. J. Pharm. 2018;541:56–63. doi: 10.1016/j.ijpharm.2018.02.031.
    1. Kidd P.M. Vitamins D and K as pleiotropic nutrients: Clinical importance to the skeletal and cardiovascular systems and preliminary evidence for synergy. Altern. Med. Rev. 2010;15:199–222.
    1. Van Ballegooijen A.J., Pilz S., Tomaschitz A., Grübler M.R., Verheyen N. The Synergistic Interplay between Vitamins D and K for Bone and Cardiovascular Health: A Narrative Review. Int. J. Endocrinol. 2017;2017:7454376. doi: 10.1155/2017/7454376.
    1. Viegas C., Araújo N., Marreiros C., Simes D. The interplay between mineral metabolism, vascular calcification and inflammation in Chronic Kidney Disease (CKD): Challenging old concepts with new facts. Aging. 2019;11:4274–4299. doi: 10.18632/aging.102046.
    1. Theuwissen E., Cranenburg E.C., Knapen M.H., Magdeleyns E.J., Teunissen K.J., Schurgers L.J., Smit E., Vermeer C. Low-dose menaquinone-7 supplementation improved extra-hepatic vitamin K status, but had no effect on thrombin generation in healthy subjects. Br. J. Nutr. 2012;108:1652–1657. doi: 10.1017/S0007114511007185.
    1. Schulman S., Furie B. How I treat poisoning with vitamin K antagonists. Blood. 2015;125:438–442. doi: 10.1182/blood-2014-08-597781.
    1. Spahr J.E., Maul J.S., Rodgers G.M. Superwarfarin Poisoning: A Report of Two Cases and Review of the Literature. Am. J. Hematol. 2007;82:656–660. doi: 10.1002/ajh.20784.

Source: PubMed

스폰서 및 공동 작업자

건강 상태

약물 개입

3
구독하다