Vanadium. Its Role for Humans

  • Dieter Rehder
Part of the Metal Ions in Life Sciences book series (MILS, volume 13)


Vanadium is the 21st most abundant element in the Earth’s crust and the 2nd-to-most abundant transition metal in sea water. The element is ubiquitous also in freshwater and nutrients. The average body load of a human individual amounts to 1 mg. The omnipresence of vanadium hampers checks directed towards its essentiality. However, since vanadate can be considered a close blueprint of phosphate with respect to its built-up, vanadate likely takes over a regulatory function in metabolic processes depending on phosphate. At common concentrations, vanadium is non-toxic. The main source for potentially toxic effects caused by vanadium is exposure to high loads of vanadium oxides in the breathing air of vanadium processing industrial enterprises. Vanadium can enter the body via the lungs or, more commonly, the stomach. Most of the dietary vanadium is excreted. The amount of vanadium resorbed in the gastrointestinal tract is a function of its oxidation state (VV or VIV) and the coordination environment. Vanadium compounds that enter the blood stream are subjected to speciation. The predominant vanadium species in blood are vanadate and vanadyl bound to transferrin. From the blood stream, vanadium becomes distributed to the body tissues and bones. Bones act as storage pool for vanadate. The aqueous chemistry of vanadium(V) at concentration <10 μM is dominated by vanadate. At higher concentrations, oligovanadates come in, decavanadate in particular, which is thermodynamically stable in the pH range 2.3–6.3, and can further be stabilized at higher pH by interaction with proteins.

The similarity between vanadate and phosphate accounts for the interplay between vanadate and phosphate-dependent enzymes: phosphatases can be inhibited, kinases activated. As far as medicinal applications of vanadium compounds are concerned, vanadium’s mode of action appears to be related to the phosphate-vanadate antagonism, to the direct interaction of vanadium compounds or fragments thereof with DNA, and to vanadium’s contribution to a balanced tissue level of reactive oxygen species. So far vanadium compounds have not yet found approval for medicinal applications. The antidiabetic (insulin-enhancing) effect, however, of a singular vanadium complex, bis(ethylmaltolato)oxidovanadium(IV) (BEOV), has revealed encouraging results in phase IIa clinical tests. In addition, in vitro studies with cell cultures and parasites, as well as in vivo studies with animals, have revealed a broad potential spectrum for the application of vanadium coordination compounds in the treatment of cardiac and neuronal disorders, malignant tumors, viral and bacterial infections (such as influenza, HIV, and tuberculosis), and tropical diseases caused by parasites, e.g., Chagas’ disease, leishmaniasis, and amoebiasis.


antiparasitic vanadium compounds antiviral potential cardiovascular effects essentiality of vanadium insulin-enhancing action vanadate-phosphate antagonism 


  1. 1.
    (a) D. Rehder, Future Med. Chem. 2012, 4, 1823–1837. (b) D. Rehder, in Detoxification of Heavy Metals, Eds I. Sherameti, A. Varma, Soil Biology 2011, 30, ch. 11.Google Scholar
  2. 2.
    T. Shimizu, K. Ichikawa, M. Masayuki, Y. Shijo, Bunseki Kagaku 1989, 38, 201–203.CrossRefGoogle Scholar
  3. 3.
    T. L. Gerke, K. G. Scheckel, M. R Schock, Environ. Sci. Technol. 2009, 43, 4412–4418.PubMedCrossRefGoogle Scholar
  4. 4.
    G. Giuli, G. Pratesi, S. G. Eeckhout, E. Paris, 68th Ann. Meteoritic. Soc. Meeting, Zurich 2006, p. 5148.Google Scholar
  5. 5.
    D. Rehder, Bioinorganic Vanadium Chemistry, John Wiley & Sons, Chichester, 2008, pp 87–155.CrossRefGoogle Scholar
  6. 6.
    D. G. Barcelaux, J. Toxicol. Clinic. Toxicol. 1999, 37, 265–278.CrossRefGoogle Scholar
  7. 7.
    M. D. Cohen, ACS Symposium Series 2007, 974, 217–239. (b) T. Scior, A. Guevara-García, P. Bernard, Q.-T. Do, D. Domeyer, S. Laufer, Mini Rev. Med. Chem. 2005, 5, 995–1008.Google Scholar
  8. 8.
    J. O. Olopade, J. R. Condor, Curr. Topics Toxicol. 2011, 7, 33–39.Google Scholar
  9. 9.
    G. Heinemann, B. Fichti, W. Vogt, Clin. Pharmacol. 2003, 55, 241–245.CrossRefGoogle Scholar
  10. 10.
    A. Gorzsás, I. Andersson, L. Pettersson, Eur. J. Inorg. Chem. 2006, 3559–3565.Google Scholar
  11. 11.
    D. Sanna, P. Buglyó, G. Micera, E. Garribba, J. Biol. Inorg. Chem. 2010, 15, 825–839.PubMedCrossRefGoogle Scholar
  12. 12.
    (a) D. Sanna, L. Bíro, P. Buglyó, G. Micera, E. Garribba, J. Inorg. Biochem. 2012, 115, 87–99. (b) G. C. Justino, E. Garribba, S. Mehtab, J. Costa Pessoa, J. Biol. Inorg. Chem. 2013, 18, 803–813.Google Scholar
  13. 13.
    K. H. Thomson, J. Lichter, C. LeBel, M. C. Scaife, J. H. McNeill, C. Orvig, J. Inorg. Biochem. 2009, 103, 554–558.CrossRefGoogle Scholar
  14. 14.
    T. C. Delgado, A. I. Tomaz, I. Corriera, J. Costa Pessoa, J. G. Jones, C. F. G. C. Geraldes, M. M. C. A. Castro, J. Inorg. Biochem. 2005, 99, 2328–2339.PubMedCrossRefGoogle Scholar
  15. 15.
    J. Priestley, Phil. Trans. Roy. Soc. London 1876, 166, 495–556.CrossRefGoogle Scholar
  16. 16.
    V. A. Ehrlich, A. K. Nersesyan, K. Alefie, C. Hoelzl, F. Ferk, J. Bichler, E. Valic, A. Schaffer, R. Schulte-Herrmann, M. Fenech, K.-H. Wagner, S. Knasmüller, Environ. Health Perspect. 2008, 116, 1689–1693.PubMedCentralPubMedCrossRefGoogle Scholar
  17. 17.
    H. P. Monteiro, C. C. Winterburn, A. Stern, Free Radic. Res. Commun. 1991, 12–13, 125–129.PubMedCrossRefGoogle Scholar
  18. 18.
    N. Gao, M. Ding, J. Z. Zheng, Z. Zhang, S. S. Leonard, K. J. Liu, X. Shi, B.-H. Jiang, J. Biol. Chem. 2002, 277, 31963–31971.PubMedCrossRefGoogle Scholar
  19. 19.
    H. Kelm, H.-J. Krüger, Angew. Chem. Int. Ed. 2001, 40, 2344–2348.CrossRefGoogle Scholar
  20. 20.
    E. J. Baran, Chem. Biodivers. 2008, 5, 1475–1484.PubMedCrossRefGoogle Scholar
  21. 21.
    (a) J. R. Treberg, J. E. Stacey, W. R. Driedzic, Comp. Biochem. Physiol. B 2012, 161, 323–330. (b) H. Michibata,T. Ueki, Biomol. Concepts 2010, 1, 97–107.Google Scholar
  22. 22.
    J. Krakowiak, D. Lundberg, I. Persson, Inorg. Chem. 2012, 51, 9598–9609.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    M. Kaliva, E. Kyriakakis, A. Salifoglou, Inorg. Chem. 2002, 41, 7015–7023.PubMedCrossRefGoogle Scholar
  24. 24.
    H. Schmidt, I. Andersson, D. Rehder, L. Pettersson, Chem. Eur. J. 2001, 7, 251–257.PubMedCrossRefGoogle Scholar
  25. 25.
    J. Schemberg, K. Schneider, U. Demmer, E. Warkentin, A. Müller, U. Ermler, Angew. Chem. Int. Ed. 2007, 46, 2409–2413.CrossRefGoogle Scholar
  26. 26.
    (a) L. Wittenkeller, A. Abraha, R. Ramasamy, D. Mota de Freitas, L. A. Theisen, D. C. Crans, J. Am. Chem. Soc. 1991, 113, 7872–7881. (b) N. Steens, A. M. Ramadan, T. N. Parac-Vogt, Chem. Commun. 2009, 965–967.Google Scholar
  27. 27.
    S. Lobert, N. Isern, B. S. Hennington, J. J. Correia, Biochemistry 1994, 33, 6244–6252.PubMedCrossRefGoogle Scholar
  28. 28.
    M. Aureliano, Dalton Trans. 2009, 9093–9100.Google Scholar
  29. 29.
    S. S. Soares, C. Gutiérrez-Merino, M. Aureliano, J. Inorg. Biochem. 2007, 101, 789–796.PubMedCrossRefGoogle Scholar
  30. 30.
    (a) N. E. Levinger, L. C. Rubenstrunk, B. Baruah, D. C. Crans, J. Am. Chem. Soc., 2011, 133, 7205–7214. (b) D. C. Crans, N. E. Levinger, Acc. Chem. Res., 2012, 45, 1637–1645.Google Scholar
  31. 31.
    (a) M. Weyand, H.-J. Hecht, M. Kieß, M.-F. Liaud, H. Vilter, D. Schomburg, J. Mol. Biol. 1999, 293, 595–611. (b) L. Kaysser, P. Bernhardt, S.-J. Nam, S. Loesgen, J. G. Ruby, P. Skewes-Cox, P. R. Jensen, W. Fenical, B. S. Moore, J. Am. Chem. Soc. 2012, 134, 11988–11991.Google Scholar
  32. 32.
    (a) Y. Lindquist, G. Schneider, P. Vihko, Eur. J. Biochem. 1994, 221, 139–142. (b) M. Z. Mehdi, A. K. Srivastava, Arch. Biochem. Biophys. 2005, 440, 158–164. (c) M. Zhang, M. Zhou, R. L. Van Etten, C. V. Stauffacher, Biochemistry 1997, 36, 15–23.Google Scholar
  33. 33.
    N. Tanaka, V. Dumay, Q. Liao, A. J. Lange, R. Wever, Eur. J. Biochem. 2002, 269, 2162–2167.PubMedCrossRefGoogle Scholar
  34. 34.
    R. Renirie, W. Hemrika, R. Wever, J. Biol. Chem. 2000, 16, 11650–11667.CrossRefGoogle Scholar
  35. 35.
    C. C. McLauchlan, J. D. Hooker, M. A. Jones, Z. Dymon, E. A. Backhus, B. A. Greiner, N. A. Dorner, M. A. Youkhana, L. M. Manus, J. Inorg. Biochem. 2010, 104, 274–281.PubMedCrossRefGoogle Scholar
  36. 36.
    B. Akabayov, A. W. Kulczyk, S. R. Akabayov, C. Theile, L. W. McLaughlin, B. Beauchamp, A. M. van Oijen, C. C. Richardson, J. Biol. Chem., 2011, 286, 29146–29157.PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    M. J. Gresser, A. S. Tracey, K. M. Parkinson, J. Am. Chem. Soc. 1986, 108, 6229–62343.CrossRefGoogle Scholar
  38. 38.
    T. Kiss, E. Kiss, G. Micera, D. Sanna, Inorg. Chim. Acta 1998, 283, 202–210.CrossRefGoogle Scholar
  39. 39.
    I. Andersson, A. Gorzsás, C. Kerezsi, I. Tóth, L. Pettersson, Dalton Trans. 2005, 3658–3666.Google Scholar
  40. 40.
    I. Andersson, S. Angus-Dunge, O. W. Howarth, L. Pettersson, J. Inorg. Biochem. 2000, 80, 51–58.PubMedCrossRefGoogle Scholar
  41. 41.
    (a) A. S. Tracey, M. J. Gresser, Proc. Natl. Acad. Sci. USA 1986, 83, 609–613. (b) A. S. Tracey, M. J. Gresser, Can. J. Chem. 1988, 66, 2570–2574.Google Scholar
  42. 42.
    (a) T. Scully, Nature 2012, 485, S2–S3. (b) L. Chen, D. J. Magliano, P. L. Zimmer, Nat. Rev. Endocrinol. 2012, 8, 228–236.Google Scholar
  43. 43.
    C. Talchai, S. Xuan, H. V. Lin, L. Sussel, D. Accili, Cell 2012, 150, 1223–1234.PubMedCentralPubMedCrossRefGoogle Scholar
  44. 44.
    M. F. Dunn, Biometals 2005, 18, 295–303.PubMedCrossRefGoogle Scholar
  45. 45.
    M. Hiromura, Y. Adachi, M. Machida, M. Hattori, H. Sakurai, Metallomics 2009, 1, 92–100.CrossRefGoogle Scholar
  46. 46.
    G. R. Willsky, L.-H. Chi, M. Godzala III, P. J. Kostyniak, J. J. Smee, A. M. Trujillo, J. A. Alfano, W. Ding, Z. Hu, D. C. Crans, Coord. Chem. Rev. 2011, 255, 2258–2269.PubMedCentralPubMedCrossRefGoogle Scholar
  47. 47.
    J. Gätjens, B. Meier, Y. Adachi, H. Sakurai, D. Rehder, Eur. J. Inorg. Chem. 2006, 3575–3585.Google Scholar
  48. 48.
    J. Nilsson, A. A. Shteinman, E. Degerman, E. A. Enyedy, T. Kiss, U. Behrens, D. Rehder, E. Nordlander, J. Inorg. Biochem. 2011, 105, 1795–1800.PubMedCrossRefGoogle Scholar
  49. 49.
    H. Ou, L. Yan, D. Mustafi, M. W. Makinen, M. J. Brady, J. Biol. Inorg. Chem. 2005, 10, 874–886.PubMedCrossRefGoogle Scholar
  50. 50.
    S. Karmaker, T. K. Saha, Y. Yoshikawa, H. Sakurai, ChemMedChem 2007, 2, 1607–1612.PubMedCrossRefGoogle Scholar
  51. 51.
    R. Mukherjee, E. G. Donnay, M. A. Radomski, C. Miller, D. A. Redfern, A. Gericke, D. S. Damron, N. E. Brasch, Chem. Commun. 2008, 3783–3785.Google Scholar
  52. 52.
    T. A. Clark, C. E. Heylinger, M. Kopilas, A. L. Edel, A. Junaid, F. Aguilar, D. D. Smyth, J. A. Thliveris, M. Merchant, H. K. Kim, G. N. Pierce, Metabolism 2012, 61, 742–753.PubMedCrossRefGoogle Scholar
  53. 53.
    K. G. Peters, M. G. Davis, B. W. Howard, M. Pokross, V. Rastogi, C. Diven, K. D. Greis, E. Eby-Wilkens, M. Maier, A. Evdokimov, S. Soper, F. Genbauffe, J. Inorg. Biochem. 2003, 96. 321–330.PubMedCrossRefGoogle Scholar
  54. 54.
    A. Bishayee, A. Waghray, M. P. Patel, M. Chatterjee, Cancer Lett. 2010, 294, 1–12.PubMedCrossRefGoogle Scholar
  55. 55.
    M. M. Evangelou, Oncol. Hematol. 2002, 42, 249–265.Google Scholar
  56. 56.
    H. Faneca, V. A. Figueiredo, I. Tomaz, G. Gonçalves, F. Avecilla, M. C. Pedroso de Lima, C. F. G. C. Geraldes, J. Costa Pessoa, M. M. C. A. Castro, J. Inorg. Biochem. 2009, 103, 601–608.PubMedCrossRefGoogle Scholar
  57. 57.
    I. Fichtner, J. Claffey, A. Deally, B. Gleeson, M. Hogan, M. R. Markelova, H. Müller-Bunz, H. Weber, M. Tacke, J. Organomet. Chem. 2010, 695, 1175–1181.CrossRefGoogle Scholar
  58. 58.
    O. J. D’Cruz, F. M. Uckun, Expert Opin. Investig. Drugs 2002, 11, 1829–1836.PubMedCrossRefGoogle Scholar
  59. 59.
    N. A. Lewis, F. Liu, L. Seymour, A. Magnuse, T. R. Erves, J. Faye Arca, F. A. Beckford, R. Venkatraman, A. Gonzáles-Sarrías, F. R. Fronczkek, D. G. VanDerveer, N. P. Seeram, A. Liu, W. L. Jarrett, A. A. Holder, Eur. J. Inorg. Chem. 2012, 664–677.Google Scholar
  60. 60.
    P. Köpf-Maier, H. Köpf, Drugs Future 1986, 11, 297–319.Google Scholar
  61. 61.
    (a) Q. Wang, T.-T. Liu, Y. Fu, K. Wang, X.-G. Yang, J. Biol. Inorg. Chem. 2010, 15, 1087–1097. (b) T.-T. Liu, Y.-J. Liu, Q. Wang, X.-G. Yang, K. Wang, J. Biol. Inorg. Chem. 2012, 17, 311–320.Google Scholar
  62. 62.
    J. O. Olopade, A. B. Madhan Kumar, A. Das, X. Liu, B. Todorich, J. L. Liang, B. Slagle-Webb, J. R. Connor, Proc. Am. Ass. Cancer Res. 2009, 50, 1344 (#5575).Google Scholar
  63. 63.
    (a) Md. S. Bhuiyan, K. Fukunaga, J. Pharmacol. Sci. 2009, 110, 1–13. (b) K. Fukunaga, Yakugaku Zasshi 2012, 132, 279–284.Google Scholar
  64. 64.
    D. A. Liem, C. C. Gho, B. C. Gho, S. Kazim, O. C. Manintveld, P. D. Verdouw, D. J. Duncker, J. Pharmacol. Exp. Therapeut. 2004, 309, 1256–1262.CrossRefGoogle Scholar
  65. 65.
    C. L. Walker, M. J. Walker, N.-K. Liu, E. C. Risberg, X. Gao, J. Chen, X,-M. Xu, PLoS ONE 2012, 7, e30012.Google Scholar
  66. 66.
    K. T. Keyes, J. Xu, B. Long, C. Zhang, Z. Hu, Y. Ye, Am. J. Phys. Heart Circ. Physiol. 2010, 298, H1198–H1208.CrossRefGoogle Scholar
  67. 67.
    (a) S. Shigeta, S. Mori, T. Yamase, N. Yamamoto, N. Yamamoto, Biomed. Pharmacother. 2006, 60, 211–219. (b) T. Yamase, E. Ishikawa, K. Fukaya, H. Nojiri, T. Taniguchi, T. Atake, Inorg. Chem. 2004, 43, 8150–8157.Google Scholar
  68. 68.
    S.-Y. Wong, R. W.-Y. Sun, N. P.-Y. Chung, C.-L. Lin, C.-M. Che, Chem. Commun. 2005, 3544–3546.Google Scholar
  69. 69.
    A. Ross, D. C. Soares, D. Covelli, C. Pannecouque, L. Budd, A. Collins, N. Robertson, S. Parsons, E. De Clercq, P. Kennepohl, P. J. Sadler, Inorg. Chem. 2010, 49, 1122–1132.PubMedCentralPubMedCrossRefGoogle Scholar
  70. 70.
    R. Renirie, A. Dewilde, C. Pierlot, R. Wever, D. Hober, J.-M. Aubry, J. Appl. Microbiol. 2008, 105, 264–270.PubMedCrossRefGoogle Scholar
  71. 71.
    P. I. da S. Maia, F. R. Pavan, C. Q. F. Leite, S. S. Lemos, G. F. de Sousa, A. A. Batista, O. R. Nascimento, J. Ellena, E. E. Castellano, E. Niquet, V. M. Deflon, Polyhedron 2009, 28, 398–406.Google Scholar
  72. 72.
    D. Gambino, Coord. Chem. Rev. 2011, 255, 2193–2203.CrossRefGoogle Scholar
  73. 73.
    M. R. Maurya, A. A. Khan, A. Azam, S. Ranjan, N. Mondal, A. Kumar, F. Avecilla, J. Costa Pessoa, Dalton Trans. 2010, 39, 1345–1360.PubMedCrossRefGoogle Scholar
  74. 74.
    J. Benítez, L. Becco, I. Correira, S. M. Leal, H. Guiset, J. Costa Pessoa, J. Lorenzo, S. Tanco, P. Escobar, V. Moreno, B. Garat, D. Gambino, J. Inorg. Biochem. 2011, 105, 303–312.PubMedCrossRefGoogle Scholar
  75. 75.
    J. Benítez, L. Guggeri, I. Tomaz, G. Arrambide, M. Navarro, J. Costa Pessoa, B. Garat, D. Gambino, J. Inorg. Biochem. 2009, 103, 609–616.PubMedCrossRefGoogle Scholar
  76. 76.
    G. R. Noleto, A. L. R. Mercê, M. Iacomini, P. A. J. Gorin, V. T. Soccol, M. B. M. Oloveira, Molec. Cellul. Biochem. 2002, 233, 73–83.CrossRefGoogle Scholar
  77. 77.
    A. K. Haldar, S. Banerjee, K. Naskar, D. Kalita, N. S. Islam, S. Roy, Experim. Parasitol. 2009, 122, 145–154.CrossRefGoogle Scholar
  78. 78.
    T. L. Turner, V. H. Nguyen, C. C. McLauchlan, Z. Dymon, B. M. Dorsey, J. D. Hooker, M. A. Jones, J. Inorg. Biochem. 2012, 108, 96–104.PubMedCrossRefGoogle Scholar
  79. 79.
    H. E. Roscoe, Phil. Trans. Roy. Soc. A 1870, 160, 317–331.CrossRefGoogle Scholar
  80. 80.
    Y. J. Kim, A. C. Marschilok, K. J. Takeuchi, E. S. Takeuchi, J. Power Sources 2011, 196, 6781–6787.PubMedCentralPubMedCrossRefGoogle Scholar
  81. 81.
    E. O. von Lippmann, Ber. Dtsch. Chem. Ges. 1888, 21, 3492–3493.CrossRefGoogle Scholar
  82. 82.
    H. Vilter, K.-W. Glombitza, A. Grawe, Bot. Mar. 1983, 26, 331–340.Google Scholar
  83. 83.
    B. Lyonnet, X. Martz, E. Martin, La Presse Médicale 1899, 32, 191–192.Google Scholar
  84. 84.
    L. C. Cantley, Jr., L. Josephson, R. Warner, M. Yanagisawa, C. Lechene, G. Guidotti, J. Biol. Chem. 1977, 252, 7421–7423.PubMedGoogle Scholar
  85. 85.
    D. C. Crans, A. M. Trujillo, P. S. Pharazyn, M. D. Cohen, Coord. Chem. Rev. 2011, 255, 2178–2192.CrossRefGoogle Scholar
  86. 86.
    L. Nordquist, M. Johansson, Vasc. Health Risk Manag. 2008, 4, 1283–1288.PubMedCentralPubMedGoogle Scholar
  87. 87.
    H. E. Roscoe, Philos. Mag. 1870, 39, 146–150.Google Scholar

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© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Chemistry DepartmentUniversity of HamburgHamburgGermany

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