Lactoferrin efficacy versus ferrous sulfate in curing iron deficiency and iron deficiency anemia in pregnant women
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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.
Keywords
Iron deficiency Iron deficiency anemia Lactoferrin Pregnant women InflammationNotes
Acknowledgment
This research has been granted by Microbo srl, Rome, Italy.
References
- Baker EN, Baker HM (2005) Molecular structure, binding properties and dynamics of lactoferrin. Cell Mol Life Sci 62:2531–2539CrossRefPubMedGoogle 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 134:532–543CrossRefPubMedGoogle 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 13:1575–1578PubMedGoogle Scholar
- Bothwell TH (2000) Iron requirements in pregnancy and strategies to meet them. Am J Clin Nutr 72:257–264Google 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–R894Google Scholar
- Cheng Y, Zak O, Aisen P, Harrison SC, Walz T (2004) Structure of the human transferrin receptor-transferrin complex. Cell 116:565–576CrossRefPubMedGoogle Scholar
- Collard KJ (2009) Iron homeostasis in the neonate. Pediatrics 123:1208–1221CrossRefPubMedGoogle Scholar
- De Domenico I, Ward DM, Langelier C (2007) The molecular mechanism of hepcidin-mediated ferroportin down-regulation. Mol Biol Cell 18:2569–2578CrossRefPubMedGoogle 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 9:72–81CrossRefPubMedGoogle Scholar
- Dejaco C, Gasche C (2002) Anemia in chronic inflammatory intestinal disease: an often underestimated problem. Dtsch Med Wochenschr 127:805–808CrossRefPubMedGoogle 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 106:3979–3984CrossRefPubMedGoogle 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 1:191–200CrossRefPubMedGoogle Scholar
- Frazer DM, Anderson GJ (2009) Hepcidin compared with prohepcidin: an absorbing story. Am J Clin Nutr 89:475–476CrossRefPubMedGoogle Scholar
- Ganz T (2005) Hepcidin regulator of intestinal iron absorption and iron recycling by macrophages. Best Pract Res Clin Haematol 18:171–182CrossRefPubMedGoogle Scholar
- Ganz T (2006) Hepcidin and its role in regulating systemic iron metabolism. Hematology 507:29–35CrossRefGoogle Scholar
- Ganz T, Olbina G, Girelli D, Nemeth E, Westerman M (2008) Immunoassay for human serum hepcidin. Blood 112:4292–4297CrossRefPubMedGoogle 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 388:482–488CrossRefPubMedGoogle Scholar
- Harris ED (1992) New insights into placental iron transport. Nutr Rev 50:329–331PubMedGoogle Scholar
- Kadiiska MB, Burkitt MJ, Xiang QH (1995) Iron supplementation generates hydroxyl radical in vivo. An ESR spin-trapping investigation. J Clin Invest 96:1653–1657CrossRefPubMedGoogle 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 480:147–150CrossRefPubMedGoogle 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 6:279–291CrossRefPubMedGoogle Scholar
- Ludwiczek S, Aigner E, Theurl I, Weiss G (2003) Cytokine-mediated regulation of iron transport in human monocytic cells. Blood 101:4148–4154CrossRefPubMedGoogle Scholar
- Mims MP, Prchal JT (2005) Divalent metal transporter 1. Hematology 10:339–345CrossRefPubMedGoogle Scholar
- Nemeth E, Ganz T (2006a) Regulation of iron metabolism by hepcidin. Annu Rev Nutr 26:323–342CrossRefPubMedGoogle Scholar
- Nemeth E, Ganz T (2006b) Hepcidin and iron-loading anemia’s. Haematologica 91:727–732PubMedGoogle 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 306:2090–2093CrossRefPubMedGoogle 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 113:1271–1276PubMedGoogle 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 110:1037–1044PubMedGoogle 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 30:505–510CrossRefPubMedGoogle 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 8:377–380CrossRefGoogle 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 3:1–6Google 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 91:44–51CrossRefPubMedGoogle 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)Google Scholar
- Park CH, Valore EV, Waring AJ, Ganz T (2001) A urinary antimicrobial peptide synthesized in the liver. J Biol Chem 276:7806–7810CrossRefPubMedGoogle 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 4:386–393CrossRefPubMedGoogle 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 45:394–397CrossRefPubMedGoogle Scholar
- Scholl TO (2005) Iron status during pregnancy: setting the stage for mother and infant. Am J Clin Nutr 81:1218S–1222SPubMedGoogle 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 21:147–168CrossRefGoogle 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 107:4142–4148CrossRefPubMedGoogle Scholar
- Valenti P, Antonini G (2005) Lactoferrin: an important host defense against microbial and viral attack. Cell Mol Life Sci 62:2576–2587CrossRefPubMedGoogle 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 17:783–790Google Scholar
- Weinberg ED (2009) Iron availability and infection. Biochim Biophys Acta 1790:600–605PubMedGoogle 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 100:3776–3781CrossRefPubMedGoogle 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 125:746–754CrossRefPubMedGoogle Scholar