Differences in circulating non-transferrin-bound iron after oral administration of ferrous sulfate, sodium iron EDTA, or iron polymaltose in women with marginal iron stores

Authors

  • K. Schümann Research Center for Nutrition and Food Science (ZIEL), Freising-Weihenstephan, Germany
  • N. W. Solomons Center for Studies of Sensory Impairment, Aging and Metabolism (CeSSIAM), Guatemala City, Guatemala
  • M. Orozco Center for Studies of Sensory Impairment, Aging and Metabolism (CeSSIAM), Guatemala City, Guatemala
  • M. E. Romero-Abal Center for Studies of Sensory Impairment, Aging and Metabolism (CeSSIAM), Guatemala City, Guatemala
  • G. Weiss Department of Internal Medicine I, Clinical Immunology and Infectious Diseases, Medical University of Innsbruck, Austria

DOI:

https://doi.org/10.18370/2309-4117.2017.37.89-96

Keywords:

anemia, malaria, oral iron supplementation, iron polymaltose, NaFeEDTA, FeSO4, non-transferrin-bound iron

Abstract

Background. The adverse interactions between iron supplements and malaria have driven the assessment of new therapeutic options for anemia prophylaxis in areas holoendemic for falciparum malaria.

Objective. To determine the responses of circulating non-transferrin-bound iron (NTBI) and plasma iron to three different oral iron compounds – ferrous sulfate, sodium iron ethylenediaminetetraacetate (NaFeEDTA), and iron polymaltose (IPM) – in women with marginal iron stores.

Methods. Serum samples from 10 Guatemalan women with marginal iron stores were collected every 90 minutes over a period of 270 minutes, after the individually randomized administration of 100 mg of iron from each of the three studied iron compounds or water alone. Serum iron concentration was quantified by the ferrozine method, and circulating NTBI concentration was determined with a fluorometric competitive binding assay. Kinetic responses and maximal cumulative changes in serum concentrations of iron and NTBI were compared between the four treatments. Comparison was made with data from the same protocol in iron-adequate men.

Conclusions. The administration of the two “slow-release” iron compounds, NaFeEDTA and IPM, resulted in a highly significant suppression of the appearance of NTBI in the circulation in the postsupplement period. These two bioavailable forms of iron supplement could represent a safe option for supplementation in malarial areas. The slope of the iron – NTBI relationship is steeper in men than in women.

References

  1. Beard, J.L. Iron. In: Present knowledge in nutrition, 9th ed. Ed. by B.A. Bowman. Washington, DC. ILSI Press (2006): 430–44.
  2. Schumann, K. “Safety aspects of iron in food.” Ann Nutr Metab 45 (2001): 91–101.
  3. Schumann, K., Ettle, T., Szegner, B., et al. “On risk and benefits of iron supplementation – recommendations for iron intake revisited.” J Trace Elem Med Biol 21 (2007): 147–68.
  4. Murray, M.J., Murray, A.B., Murray, M.B., Murray, C.J. “The adverse effect of iron repletion on the course of certain infections.” Br Med J 21 (1978):1113–5.
  5. Weinberg, E.D. “Iron loading and disease surveillance.” Emerg Infect Dis 5 (1995): 346–52.
  6. Schaible, U.E., Kaufmann, S.H. “Iron and microbial infection.” Nat Rev Microbiol 2 (2004): 946–53.
  7. Nairz, M., Schroll, A., Sonnweber, T., Weiss, G. “The struggle for iron – a metal at the host-pathogen interface.” Cell Microbiol 12 (2010):1691–702.
  8. Harvey, P.W., Heywood, P.F., Nesheim, M.C., et al. “The effect of iron therapy on malarial infection in Papua New Guinean schoolchildren.” Am J TropMed Hyg 40 (1989): 12–8.
  9. Smith, A.W., Hendrickse, R.G., Harrison, C., et al. “The effects on malaria of treatment of iron-deficiency anaemia with oral iron in Gambian children.” Ann Trop Paediatr 9 (1989): 17–23.
  10. van den Hombergh, J., Dalderop, E., Smit, Y. “Does iron therapy benefit children with severe malaria-associated anaemia? A clinical trial with 12 weeks supplementation of oral iron in young children from the Turiani Division, Tanzania.” J Trop Pediatr 42 (1996): 220–7.
  11. Berger, J., Dyck, J.L., Galan, P., et al. “Effect of daily iron supplementation on iron status, cell-mediated immunity, and incidence of infections in 6–36 month old Togolese children.” Eur J Clin Nutr 54 (2000): 29–35.
  12. Menendez, C., Kahigwa, E., Hirt, R., et al. “Randomized placebo-controlled trial of iron supplementation and malaria chemoprophylaxis for prevention of severe anaemia and malaria in Tanzanian infants.” Lancet 350 (1997): 844–50.
  13. Ojukwu, J.U., Okebe, J.U., Yahav, D., Paul, M. “Oral iron supplementation for preventing or treating anaemia among children in malariaendemic areas.” Cochrane Database Syst Rev 10 (2011): CD006589.
  14. Sazawal, S., Black, R.E., Ramsan, M., et al. “Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomized, placebo-controlled trial.” Lancet 367 (2006): 133–43.
  15. World Health Organization. Conclusions and recommendations of the WHO consultation on prevention and control of iron deficiency in infants and young children in malaria-endemic areas. Food Nutr Bull 28 (2007):S621–7.
  16. Schűmann, K., Christ, F.“Did the iron age end in Pemba?” Sight Life Mag 3 (2007): 6–13.
  17. Prentice, A.M.“Iron metabolism, malaria, and other infections: what is all the fuss about?” J Nutr 138 (2008):2537–41.
  18. Prentice, A.M., Ghattas, H., Doherty, C., Cox, S.E. “Iron metabolism and malaria.” Food Nutr Bull 28 (2007): S524–39.
  19. Sarkate, P., Patil, A., Parulekar, S., et al. “A randomised double-blind study comparing sodium feredetate with ferrous fumarate in anaemia in pregnancy.” J Indian Med Assoc 105 (2007): 278–84.
  20. Andango, P.E., Osendarp, S.J., Ayah, R., et al. “Efficacy of iron-fortified whole maize flour on iron status of schoolchildren in Kenya: a randomized controlled trial.” Lancet 369 (2007): 1799–806.
  21. Longfils, P., Monchy, D., Weinheimer, H., et al. “A comparative intervention trial on fish sauce fortified with NaFe-EDTA and FeSO4+citrate in iron deficiency anemic school children in Kampot, Cambodia.” Asia Pac J Clin Nutr 17 (2008):250–7.
  22. Reddy, P.S., Adsul, B.B., Gandewar, K., et al. “Evaluation of efficacy and safety of iron polymaltose complex and folic acid (Mumfer) vs iron formulation (ferrous fumarate) in female patients with anaemia.” J Indian Med Assoc 99 (2001):154–5.
  23. Saha, L., Pandhi, P., Gopalan, S., et al. “Comparison of efficacy, tolerability, and cost of iron polymaltose complex with ferrous sulphate in the treatment of iron deficiency anaemia in pregnant women.” Med Gen Med 9 (2007): 1.
  24. Haliotis, F.A., Papanastasiou, D.A. “Comparative study of tolerability and efficacy of iron protein succinylate versus iron hydroxide polymaltose complex in the treatment of iron deficiency in children.” Int J Clin Pharmacol Ther 36 (1998): 320–5.
  25. Geisser, P. “Safety and efficacy of iron(III)-hydroxide polymaltose complex/a review of over 25 yearsexperience.” Arzneimittelforschung 57 (2007): 439–52.
  26. Schumann, K., Solomons, N.W., Romero-Abal, M.-E., et al. “Oral administration of ferrous sulfate, but not of iron polymaltose and sodium iron EDTA, results in a substantial increase of non-transferrin-bound iron in healthy men.” Food Nutr Bull 33 (2012):128–36.
  27. Hentze, M.W., Muckenhalter, M.U., Gaby, B., Camaschella, C. “Two to tango: regulation of mammalian iron metabolism.” Cell 142 (2010): 24–38.
  28. Vanoaica, L., Darshan, D., Richman, L., et al. “Intestinal ferritin H is required for an accurate control of iron absorption.” Cell 12 (2010): 273–82.
  29. Breuer, W., Cabantchik, Z.I. “A fluorescence-based one step assay for serum non-transferrin-bound iron.” Anal Biochem 299(2001): 194–202.
  30. Hider, R.C. “Nature of non-transferrin-bound iron.” Eur J Clin Nutr 32 (2002): 50–4.
  31. Hutchinson, C., Al-Ashgar, W., Liu, D., et al. “Oral ferrous sulphate leads to a marked increase in pro-oxidant non-transferrin-bound iron.” Eur J Clin Invest 34 (2004): 782–4.
  32. Dresow, B., Petersen, D., Fischer, R., Nielsen, P. “Non-transferrin-bound iron in plasma followed administration of oral iron drugs.” Biometals 21 (2008): 273–6.
  33. Messner, D.J., Kowdley, K.V. “Neoplastic transformation of rat liver epithelial cells is enhanced by non-transferrin-bound iron.” BMC Gastroenterol 8 (2008): 2.
  34. Ozment, C.P., Turi, J.L. “Iron overload following red blood cell transfusion and its impact on disease severity.” Biochim Biophys Acta 1790 (2009): 694–701.
  35. Porter, J.B. “Pathophysiology of transfusional iron overload: contrasting patterns in thalassemia major and sickle cell disease.” Haemoglobin 33 (2009): S37–45.
  36. Hershko, C. “Pathogenesis and management of iron toxicity in thalassemia.” Ann N Y Acad Sci 1202 (2010):1–9.
  37. Kartikasari, A.E.R., Georgiou, N.A., Visseren, F.L., et al. “Endothelial activation and induction of monocyte adhesion by non-transferrin-bound iron present in human sera.” FASEB J 20 (2005): 353–5.
  38. Gray, C., McCormick, C., Turner, G., Craig, A. “ICAM-1 can play a major role in mediating P. falciparum adhesion to endothelium under flow.” Mol Biochem Parasitol 128 (2003): 187–93.
  39. DeValk, B., Addicks, M.A., Gosriwatana, I., et al. “Non-transferrin-bound iron is present in serum of hereditary haemochromatosis heterozygotes.” Eur J Clin Invest 30 (2000): 248–51.
  40. Rao, B.S., Vijayasarathy, C.ь “Fortification of common salt with iron: effect of chemical additives on stability and bioavailability.” Am J Clin Nutr 28 (1975): 1395–401.
  41. Rios, E., Hunter, R.E., Cook, J.D., et al. “The absorption of iron as supplements in infant cereal and infant formulas.” Pediatrics 55 (1975):686–93.
  42. Hoppe, M., Hulthen, L., Hallberg, L. “The validation of using serum iron increase to measure iron absorption in human subjects.” Br JNutr 92 (2004): 485–8.
  43. Hoppe, M., Hulthen, L., Hallberg, L.“The relative bioavailability in humans of elemental iron powders for use in food fortification.” Eur J Nutr 45 (2006): 37–44.
  44. Wallenburg, H.C., van Eijk, H.G. “Effect of oral iron supplementation during pregnancy on maternal and fetal iron status.” J Perinat Med 12 (1984): 7–12.
  45. Chwang, L.C., Soemantri, A.G., Pollitt, E. “Iron supplementation and physical growth of rural Indonesian children.” Am J Clin Nutr 47 (1988): 496–501.
  46. Katz, J., Khatry, S.K., Leclerq, S.C., et al. “Daily supplementation with iron plus folic acid, zinc, and their combination is not associated with younger age at first walking unassisted in malnourished preschool children from a deficient population in rural Nepal.” J Nutr 140 (2010): 1317–21.

Published

2017-10-30

How to Cite

Schümann, K., Solomons, N. W., Orozco, M., Romero-Abal, M. E., & Weiss, G. (2017). Differences in circulating non-transferrin-bound iron after oral administration of ferrous sulfate, sodium iron EDTA, or iron polymaltose in women with marginal iron stores. REPRODUCTIVE ENDOCRINOLOGY, (37), 89–96. https://doi.org/10.18370/2309-4117.2017.37.89-96

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Section

Science - practice