Skip to main content

Advertisement

SpringerLink
Log in

Lactoferrin efficacy versus ferrous sulfate in curing iron deficiency and iron deficiency anemia in pregnant women

  • Published:
BioMetals Aims and scope Submit manuscript

Abstract

Iron deficiency (ID) and iron deficiency anemia (IDA) are the most common iron disorders throughout the world. ID and IDA, particularly caused by increased iron requirements during pregnancy, represent a high risk for preterm delivery, fetal growth retardation, low birth weight, and inferior neonatal health. Oral administration of ferrous sulfate to cure ID and IDA in pregnancy often fails to increase hematological parameters, causes adverse effects and increases inflammation. Recently, we have demonstrated safety and efficacy of oral administration of 30% iron saturated bovine lactoferrin (bLf) in pregnant women suffering from ID and IDA. Oral administration of bLf significantly increases the number of red blood cells, hemoglobin, total serum iron and serum ferritin already after 30 days of the treatment. The increasing of hematological values by bLf is related to the decrease of serum IL-6 and the increase of serum hepcidin, detected as prohepcidin, whereas ferrous sulfate increases IL-6 and fails to increase hematological parameters and prohepcidin. bLf is a more effective and safer alternative than ferrous sulfate for treating ID and IDA in pregnant women.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Baker EN, Baker HM (2005) Molecular structure, binding properties and dynamics of lactoferrin. Cell Mol Life Sci 62:2531–2539

    Article  CAS  PubMed  Google Scholar 

  • Bastin J, Drakesmith H, Rees M, Sargent I, Townsend A (2006) Localisation of proteins of iron metabolism in the human placenta and liver. Br J Haematol 134:532–543

    Article  CAS  PubMed  Google Scholar 

  • Belluzzi A, Roda G, Tonon F, Soleti A, Caponi A, Tuci A, Roda A, Roda E (2007) A new iron free treatment with oral fish cartilage polysaccharide for iron deficiency chronic anemia in inflammatory bowel diseases: a pilot study. World J Gastroenterol 13:1575–1578

    CAS  PubMed  Google Scholar 

  • Bothwell TH (2000) Iron requirements in pregnancy and strategies to meet them. Am J Clin Nutr 72:257–264

    Google Scholar 

  • Bradley J, Leibold EA, Harris ZL, Wobken JD, Clarke S, Zumbrennen KB, Eisenstein RS, Georgieff MK (2004) Influence of gestational age and fetal iron status on IRP activity and iron transporter protein expression in third-trimester human placenta. Am J Physiol Regul Integr Comp Physiol 287:R01–R894

    Google Scholar 

  • Cheng Y, Zak O, Aisen P, Harrison SC, Walz T (2004) Structure of the human transferrin receptor-transferrin complex. Cell 116:565–576

    Article  CAS  PubMed  Google Scholar 

  • Collard KJ (2009) Iron homeostasis in the neonate. Pediatrics 123:1208–1221

    Article  PubMed  Google Scholar 

  • De Domenico I, Ward DM, Langelier C (2007) The molecular mechanism of hepcidin-mediated ferroportin down-regulation. Mol Biol Cell 18:2569–2578

    Article  PubMed  Google Scholar 

  • De Domenico I, Ward MD, Kaplan J (2008) Regulation of iron acquisition and storage: consequences for iron-linked disorders. Nat Rev Mol Cell Biol 9:72–81

    Article  PubMed  Google Scholar 

  • Dejaco C, Gasche C (2002) Anemia in chronic inflammatory intestinal disease: an often underestimated problem. Dtsch Med Wochenschr 127:805–808

    Article  CAS  PubMed  Google Scholar 

  • Delaby C, Pilard N, Goncalves AS, Beaumont C, Canonne-Hergaux F (2005) Presence of the iron exporter ferroportin at the plasma membrane of macrophages is enhanced by iron loading and down-regulated by hepcidin. Blood 106:3979–3984

    Article  CAS  PubMed  Google Scholar 

  • Donovan A, Lima CA, Pinkus JL, Pinkus GS, Zon LI, Robine S, Andrews NC (2005) The iron exporter ferroportin Slc40a1 is essential for iron homeostasis. Cell Metab 1:191–200

    Article  CAS  PubMed  Google Scholar 

  • Frazer DM, Anderson GJ (2009) Hepcidin compared with prohepcidin: an absorbing story. Am J Clin Nutr 89:475–476

    Article  CAS  PubMed  Google Scholar 

  • Ganz T (2005) Hepcidin regulator of intestinal iron absorption and iron recycling by macrophages. Best Pract Res Clin Haematol 18:171–182

    Article  CAS  PubMed  Google Scholar 

  • Ganz T (2006) Hepcidin and its role in regulating systemic iron metabolism. Hematology 507:29–35

    Article  Google Scholar 

  • Ganz T, Olbina G, Girelli D, Nemeth E, Westerman M (2008) Immunoassay for human serum hepcidin. Blood 112:4292–4297

    Article  CAS  PubMed  Google Scholar 

  • Gunshin H, Mackenzie B, Berger UV, Gunshin Y, Romero MF, Boron WF, Nussberger S, Gollan JL, Hediger MA (1997) Cloning and characterization of a mammalian proton-coupled metal-ion transporter. Nature 388:482–488

    Article  CAS  PubMed  Google Scholar 

  • Harris ED (1992) New insights into placental iron transport. Nutr Rev 50:329–331

    CAS  PubMed  Google Scholar 

  • Kadiiska MB, Burkitt MJ, Xiang QH (1995) Iron supplementation generates hydroxyl radical in vivo. An ESR spin-trapping investigation. J Clin Invest 96:1653–1657

    Article  CAS  PubMed  Google Scholar 

  • Krause A, Neitz S, Magert HJ, Schulz A, Forssmann WG, Schulz-Knappe P, Adermann K (2000) A novel highly disulfide bonded human peptide, exhibits antimicrobial activity. FEBS Lett 480:147–150

    Article  CAS  PubMed  Google Scholar 

  • Loreal O, Haziza-Pigeon C, Troadec MB, Detivaud L, Turlin B, Courselaud B, Ilyin G, Brissot P (2005) Hepcidin in iron metabolism. Curr Protein Pept Sci 6:279–291

    Article  CAS  PubMed  Google Scholar 

  • Ludwiczek S, Aigner E, Theurl I, Weiss G (2003) Cytokine-mediated regulation of iron transport in human monocytic cells. Blood 101:4148–4154

    Article  CAS  PubMed  Google Scholar 

  • Mims MP, Prchal JT (2005) Divalent metal transporter 1. Hematology 10:339–345

    Article  CAS  PubMed  Google Scholar 

  • Nemeth E, Ganz T (2006a) Regulation of iron metabolism by hepcidin. Annu Rev Nutr 26:323–342

    Article  CAS  PubMed  Google Scholar 

  • Nemeth E, Ganz T (2006b) Hepcidin and iron-loading anemia’s. Haematologica 91:727–732

    CAS  PubMed  Google Scholar 

  • Nemeth E, Tuttle MS, Powelson J, Vaughn MB, Donovan A, Ward DM, Ganz T, Kaplan J (2004a) Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306:2090–2093

    Article  CAS  PubMed  Google Scholar 

  • Nemeth E, Rivera S, Gabayan V (2004b) IL-6 mediates hypoferremia of inflammation by inducing the synthesis of the iron regulatory hormone hepcidin. J Clin Invest 113:1271–1276

    CAS  PubMed  Google Scholar 

  • Nicolas G, Chauvet C, Viatte L, Danan JL, Bigard X, Devaux I, Beaumont C, Kahn A, Vaulont S (2002) The gene encoding the iron regulatory peptide hepcidin is regulated by anemia, hypoxia, and inflammation. J Clin Invest 110:1037–1044

    CAS  PubMed  Google Scholar 

  • Oldenburg B, Van Berge Henegouwen GP, Rennick D (2000) Iron supplementation affects the production of pro-inflammatory cytokines in IL-10 deficient mice. Eur J Clin Invest 30:505–510

    Article  CAS  PubMed  Google Scholar 

  • Paesano R, Torcia F, Berlutti F, Pacifici E, Ebano V, Moscarini M, Valenti P (2006) Oral administration of lactoferrin increases hemoglobin and total serum iron in pregnant women. Biochem Cell Biol 8:377–380

    Article  Google Scholar 

  • Paesano R, Pacifici E, Ermini B, Pietropaoli M, Valenti P (2008) Ipoferremia e anemia da carenza di ferro in gravidanza. Evidenze cliniche della maggiore efficacia della lattoferrina, somministrata per os, rispetto al solfato ferroso. Il Ginecol Riv di Ostet e Ginecol 3:1–6

    Google Scholar 

  • Paesano R, Pietropaoli M, Gessani S, Valenti P (2009) The influence of lactoferrin, orally administered, on systemic iron homeostasis in pregnant women suffering of iron deficiency and iron deficiency anemia. Biochimie 91:44–51

    Article  CAS  PubMed  Google Scholar 

  • Paesano R, Berlutti F, Pietropaoli M, Goolsbee W, Pacifici E, Valenti P (2010) Lactoferrin efficacy versus ferrous sulfate in curing iron disorders in pregnant and non pregnant women. Int J Immunopathol Pharmacol (in press)

  • Park CH, Valore EV, Waring AJ, Ganz T (2001) A urinary antimicrobial peptide synthesized in the liver. J Biol Chem 276:7806–7810

    Article  CAS  PubMed  Google Scholar 

  • Provenzano R, Schiller B, Rao M, Coyne D, Brenner L, Pereira BJ (2009) Ferumoxytol as an intravenous iron replacement therapy in hemodialysis patients. Clin J Am Soc Nephrol 4:386–393

    Article  CAS  PubMed  Google Scholar 

  • Reifen R, Matas Z, Zeidel L, Berkovitch Z, Bujanover Y (2000) Iron supplementation may aggravate inflammatory status of colitis in a rat model. Dig Dis Sci 45:394–397

    Article  CAS  PubMed  Google Scholar 

  • Scholl TO (2005) Iron status during pregnancy: setting the stage for mother and infant. Am J Clin Nutr 81:1218S–1222S

    CAS  PubMed  Google Scholar 

  • Schümann K, Ettle T, Szegner B, Elsenhans B, Solomons NW (2007) On risks and benefits of iron supplementation recommendations for iron intake revisited. J Trace Elem Med Bio 21:147–168

    Article  Google Scholar 

  • Theurl I, Mattle V, Seifert M, Mariani M, Marth C, Weiss G (2006) Dysregulated monocyte iron homeostasis and erythropoietin formation in patients with anemia of chronic disease. Blood 107:4142–4148

    Article  CAS  PubMed  Google Scholar 

  • Valenti P, Antonini G (2005) Lactoferrin: an important host defense against microbial and viral attack. Cell Mol Life Sci 62:2576–2587

    Article  CAS  PubMed  Google Scholar 

  • Valenti P, Pacifici E, Pietropaoli M, Paesano R (2008) La Lattoferrina per os, un’importante alternativa priva di effetti indesiderati, nella prevenzione e trattamento dell’ipoferremia ed anemia da carenza di ferro in gravidanza. Riv It Ostet Ginecol 17:783–790

    Google Scholar 

  • Weinberg ED (2009) Iron availability and infection. Biochim Biophys Acta 1790:600–605

    CAS  PubMed  Google Scholar 

  • Weinstein DA, Roy CN, Fleming MD (2002) Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease. Blood 100:3776–3781

    Article  CAS  PubMed  Google Scholar 

  • Zoller H, Theurl I, Koch RO, McKie AT, Vogel W, Weiss G (2003) Duodenal cytochrome b and hephaestin expression in patients with iron deficiency and hemochromatosis. Gastroenterology 125:746–754

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgment

This research has been granted by Microbo srl, Rome, Italy.

Author information

Authors and Affiliations

  1. Department of Obstetrician and Gynaecology, Sapienza University of Rome, Rome, Italy

    Rosalba Paesano

  2. Clinica “Fabia Mater”, Rome, Italy

    Rosalba Paesano & Enrica Pacifici

  3. Department of Public Health Sciences, Sapienza University of Rome, Piazzale A. Moro 5, 00185, Rome, Italy

    Francesca Berlutti, Fabrizio Pantanella & Piera Valenti

  4. Microbo Srl, Biotechnology Company, Rome, Italy

    Miriam Pietropaoli

  5. BMG Pharma LLC, Carson, Nevada, USA

    William Goolsbee

Authors
  1. Rosalba Paesano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Francesca Berlutti
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Miriam Pietropaoli
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Fabrizio Pantanella
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Enrica Pacifici
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. William Goolsbee
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Piera Valenti
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Piera Valenti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Paesano, R., Berlutti, F., Pietropaoli, M. et al. Lactoferrin efficacy versus ferrous sulfate in curing iron deficiency and iron deficiency anemia in pregnant women. Biometals 23, 411–417 (2010). https://doi.org/10.1007/s10534-010-9335-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10534-010-9335-z

Keywords

Search

Navigation