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Mechanistic insights into the treatment of iron-deficiency anemia and arthritis in humans with dietary molybdenum


In the last few decades, there has been a resurgence in interest in the use of dietary supplements to treat diseases in humans and molybdenum has the potential to be used therapeutically. In humans, dietary molybdenum has been shown to treat iron-deficiency anemia and it may treat joint pain in arthritis. It has been proposed that the anti-anemic and tentative anti-arthritic properties of molybdenum are because it is increasing the activity of one or more mammalian molybdoenzymes. Molybdenum forms part of the active site of these enzymes. Despite this, it is unlikely that a molybdenum deficiency can develop in humans that are on an oral diet and not exposed to unsafe levels of a molybdenum antagonist. Therefore, the underlying mechanism by which dietary molybdenum treats or may treat these diseases is currently not known. This minireview examines three possible underlying mechanisms. It investigates the possibility that molybdenum: increases the quantity of active mammalian molybdoenzymes, restores or partially restores activity to malfunctioning mammalian molybdoenzymes, or blocks nuclear receptors, in cells. The examination of these mechanisms has provided an impression of the mechanism by which molybdenum treats iron-deficiency anemia and may treat arthritis; and hypothesize uses of molybdenum for other human diseases.

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  1. 1.

    Hille R, Hall J, Basu P. The mononuclear molybdenum enzymes. Chem Rev. 2014;114:3963–4038.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  2. 2.

    Mendel RR, Kruse T. Cell biology of molybdenum in plants and humans. Biochim Biophys Acta. 2012;1823:1568–79.

    CAS  PubMed  Article  Google Scholar 

  3. 3.

    Novotny JA, Peterson CA. Molybdenum. Adv Nutr. 2018;9:272–3.

    PubMed  PubMed Central  Article  Google Scholar 

  4. 4.

    National Health and Medical Research Council, New Zealand Ministry of Health. Nutrient references values for Australia and New Zealand. Canberra, Australia: National Health and Medical Research Council, Australian Government Department of Health; 2017. pp189-192.

  5. 5.

    Biego GH, Joyeux M, Hartemann P, Debry G. Daily intake of essential minerals and metallic micropollutants from foods in France. Sci Total Environ. 1998;217:27–36.

    CAS  PubMed  Article  Google Scholar 

  6. 6.

    Novotny JA. Molybdenum nutriture in humans. J Evid Based Complementary Alter Med. 2011;16:164–8.

    CAS  Article  Google Scholar 

  7. 7.

    Novotny JA, Turnlund JR. Molybdenum intake influences molybdenum kinetics in men. J Nutr. 2007;137:37–42.

    CAS  PubMed  Article  Google Scholar 

  8. 8.

    Turnlund JR, Keyes WR, Peiffer GL, Chiang G. Molybdenum absorption, excretion, and retention studied with stable isotopes in young men during depletion and repletion. Am J Clin Nutr. 1995;61:1102–9.

    CAS  PubMed  Article  Google Scholar 

  9. 9.

    Li WJ, Chen C, You ZF, Yang RM, Wang XP. Current drug managements of wilson’s disease: from west to east. Curr Neuropharmacol. 2016;14:322–5.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  10. 10.

    Gartner EM, Griffith KA, Pan Q, Brewer GJ, Henja GF, Merajver SD, et al. A pilot trial of the anti-angiogenic copper lowering agent tetrathiomolybdate in combination with irinotecan, 5-flurouracil, and leucovorin for metastatic colorectal cancer. Invest New Drugs. 2009;27:159–65.

    CAS  PubMed  Article  Google Scholar 

  11. 11.

    Sardesai VM. Molybdenum: an essential trace element. Nutr Clin Pract. 1993;8:277–81.

    CAS  PubMed  Article  Google Scholar 

  12. 12.

    Mortensen JA .The relationship of molybdenum to iron status in pregnancy and anemia in rats and humans. All Graduate Theses and Dissertations. 5189. Utah, USA: Utah State University; 1977.

  13. 13.

    Moss M. Effects of molybdenum on pain and general health: a pilot study. J Nut Environ Med. 1995;5:55–61.

    CAS  Article  Google Scholar 

  14. 14.

    Camaschella C. Iron-deficiency anemia. N Engl J Med. 2015;372:1832–4183.

    PubMed  Article  Google Scholar 

  15. 15.

    GBD 2015 Disease and Injury Incidence and Prevalence Collaborators. Global, regional, and national incidence, prevalence, and years lived with disability for 310 diseases and injuries, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016;388:545–1602.

    Article  Google Scholar 

  16. 16.

    National Institute of Arthritis and Musculoskeletal and Skin Diseases. Arthritis and rheumatic diseases. Bethesda: United States of America; 2014.

  17. 17.

    Mouratoff GJ, Batterman RC. Serum iron absorption tests of a sustained-release form of oral iron. J New Drugs. 1961;1:157–9.

    CAS  PubMed  Article  Google Scholar 

  18. 18.

    Posner LB, Wilson F. An evaluation of sustained-release molybdenized ferrous sulfate in iron-deficiency anemia of pregnancy. J New Drugs. 1963;3:155–60.

    CAS  PubMed  Article  Google Scholar 

  19. 19.

    Topham R, Goger M, Pearce K, Schultz P. The mobilization of ferritin iron by liver cytosol. A comparison of xanthine and NADH as reducing substrates. Biochem J. 1989;261:137–43.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  20. 20.

    Bolann BJ, Ulvik RJ. Release of iron from ferritin by xanthine oxidase. Role superoxide Radic Biochem J. 1987;243:55–59.

    CAS  Google Scholar 

  21. 21.

    McCubbin MD, Hou G, Abrams GD, Dick R, Zhang Z, Brewer GJ. Tetrathiomolybdate is effective in a mouse model of arthritis. J Rheumatol. 2006;33:2501–6.

    CAS  PubMed  Google Scholar 

  22. 22.

    Omoto A, Kawahito Y, Prudovsky I, Tubouchi Y, Kimura M, Ishino H, et al. Copper chelation with tetrathiomolybdate suppresses adjuvant-induced arthritis and inflammation-associated cachexia in rats. Arthritis Res Ther. 2005;7:R1174–1182.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  23. 23.

    Wang X, Oberleas D, Yang MT, Yang SP. Molybdenum requirement of female rats. J Nutr. 1992;122:1036–1041.

    CAS  PubMed  Article  Google Scholar 

  24. 24.

    Komada H, Kise Y, Nakagawa M, Yamamura M, Hioki K, Yamamoto M. Effect of dietary molybdenum on esophageal carcinogenesis in rats induced by N-methyl-N-benzylnitrosamine. Cancer Res. 1990;50:2418–22.

    CAS  PubMed  Google Scholar 

  25. 25.

    American Institute of Nutrition. Report of the American Institute of Nurtition Ad Hoc Committee on Standards for Nutritional Studies. J Nutr. 1977;107:1340–8.

    Article  Google Scholar 

  26. 26.

    Luo XM, Wei HJ, Yang SP. Inhibitory effects of molybdenum on esophageal and forestomach carcinogenesis in rats. J Natl Cancer Inst. 1983;71:75–80.

    CAS  PubMed  Google Scholar 

  27. 27.

    Wei HJ, Luo XM, Yang SP. Effects of molybdenum and tungsten on mammary carcinogenesis in SD rats. J Natl Cancer Inst. 1985;74:469–73.

    CAS  PubMed  Google Scholar 

  28. 28.

    Seaborn CD, Yang SP. Effect of molybdenum supplementation on N-nitroso-N-methylurea-induced mammary carcinogenesis and molybdenum excretion in rats. Biol Trace Elem Res. 1993;39:245–56.

    CAS  PubMed  Article  Google Scholar 

  29. 29.

    Tricker AR. N-nitroso compounds and man: sources of exposure, endogenous formation and occurrence in body fluids. Eur J Cancer Prev. 1997;6:226–68.

    CAS  PubMed  Article  Google Scholar 

  30. 30.

    Koizumi T, Tajima K, Emi N, Hara A, Suzuki KT. Suppressive effect of molybdenum on hepatotoxicity of N-nitrosodiethylamine in rats. Biol Pharm Bull. 1995;18:460–2.

    CAS  PubMed  Article  Google Scholar 

  31. 31.

    Veena S, Rashmi S. A review on mechanism of nitrosamine formation, metabolism and toxicity in in vivo. Int J Toxicol Pharm Res. 2014;6:86–96.

    Google Scholar 

  32. 32.

    Viles K, Mathai C, Jourd’heuil FL, Jourd’heuil D. Xanthine oxidase-mediated denitrosation of N-nitroso-tryptophan by superoxide and uric acid. Nitric Oxide. 2013;28:57–64.

    CAS  PubMed  Article  Google Scholar 

  33. 33.

    Linder N. Expression and regulation of human xanthine oxidoreductase doctoral thesis. Helsinki, Finland: University of Helsinki; 2005.

  34. 34.

    Heck IS, Schrag JD, Sloan J, Millar LJ, Kanan G, Kinghorn JR, et al. Mutational analysis of the gephyrin-related molybdenum cofactor biosynthetic gene cnxE from the lower eukaryote aspergillus nidulans. Genetics. 2002;161:623–32.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  35. 35.

    Falciani F, Terao M, Goldwurm S, Ronchi A, Gatti A, Minoia C, et al. Molybdenum(VI) salts convert the xanthine oxidoreductase apoprotein into the active enzyme in mouse L929 fibroblastic cells. Biochem J. 1994;298:69–77.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  36. 36.

    Mendel R, Alikulov Z, Lvov N, Muller A. Presence of the molybdenum-cofactor in nitrate reductase-deficient mutant cell lines of nicotiana tabacum. Mol Gen Genet. 1981;181:395–9.

    CAS  Article  Google Scholar 

  37. 37.

    Tan WH, Eichler FS, Hoda S, Lee MS, Baris H, Hanley CA, et al. Isolated sulfite oxidase deficiency: a case report with a novel mutation and review of the literature. Pediatrics. 2005;116:757–66.

    PubMed  Article  Google Scholar 

  38. 38.

    Abumrad NN, Schneider AJ, Steel D, Rogers LS. Amino acid intolerance during prolonged total parenteral nutrition reversed by molybdate therapy. Am J Clin Nutr. 1981;34:2551–9.

    CAS  PubMed  Article  Google Scholar 

  39. 39.

    Ikegami T, Natsumeda Y, Weber G. Decreased concentration of xanthine dehydrogenase (EC in rat hepatomas. Cancer Res. 1986;46:3838–41.

    CAS  PubMed  Google Scholar 

  40. 40.

    Prajda N, Morris HP, Weber G. Imbalance of purine metabolism in hepatomas of different growth rates as expressed in behavior of xanthine oxidase (EC Cancer Res. 1976;36:4639–4466.

    CAS  PubMed  Google Scholar 

  41. 41.

    Saha T, Makar S, Swetha R, Gutti G, Singh SK. Estrogen signaling: an emanating therapeutic target for breast cancer treatment. Eur J Med Chem. 2019;177:116–43.

    CAS  PubMed  Article  Google Scholar 

  42. 42.

    Shyamala G, Leonard L. Inhibition of uterine estrogen receptor transformation by sodium molybdate. J Biol Chem. 1980;255:6028–31.

    CAS  PubMed  Article  Google Scholar 

  43. 43.

    Olefsky JM. Nuclear receptor minireview series. J Biol Chem. 2001;276:36863–4.

    CAS  PubMed  Article  Google Scholar 

  44. 44.

    Kliewer SA. The nuclear pregnane X receptor regulates xenobiotic detoxification. J Nutr. 2003;133:2444S–2447S.

    CAS  PubMed  Article  Google Scholar 

  45. 45.

    Yoshida A, Taniguchi S, Mitani Y, Ueda Y, Urabe K, Adachi T, et al. In vivo effects of molybdate on activation of rat liver cytosol glucocorticoid receptor. Horm Metab Res. 1988;20:566–9.

    CAS  PubMed  Article  Google Scholar 

  46. 46.

    Jakszyn P, Gonzalez CA. Nitrosamine and related food intake and gastric and oesophageal cancer risk: a systematic review of the epidemiological evidence. World J Gastroenterol. 2006;12:4296–303.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  47. 47.

    Song P, Wu L, Guan W. Dietary nitrates, nitrites, and nitrosamines intake and the risk of gastric cancer: a meta-analysis. Nutrients. 2015;7:9872–95.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  48. 48.

    Wang H, Venkatesh M, Li H, Goetz R, Mukherjee S, Biswas A, et al. Pregnane X receptor activation induces FGF19-dependent tumor aggressiveness in humans and mice. J Clin Invest. 2011;121:3220–32.

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  49. 49.

    Klocke R, Mani AR, Moore KP, Morris CJ, Blake DR, Mapp PI. Inactivation of xanthine oxidoreductase is associated with increased joint swelling and nitrotyrosine formation in acute antigen-induced arthritis. Clin Exp Rheumatol. 2005;23:345–50.

    CAS  PubMed  Google Scholar 

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I thank the University of Queensland Library, University of Queensland, Brisbane, Australia; for assistance with obtaining copies of research and review papers.

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Correspondence to Brian James Grech.

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BJG has filed a patent describing a Mo treatment paradigm.

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Grech, B.J. Mechanistic insights into the treatment of iron-deficiency anemia and arthritis in humans with dietary molybdenum. Eur J Clin Nutr 75, 1170–1175 (2021).

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