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
Free accessResearch articleFirst published online June, 2013
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
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.
Results
The serum iron and NTBI responses to ferrous sulfate were significantly greater than those to water and the other two iron compounds. Serum iron responses to IPM did not differ from those to water alone.
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.
SchümannK. Safety aspects of iron in food. Ann Nutr Metab2001;45:91–101.
3.
SchümannKEttleTSzegnerBElsenhansBSolomonsNW. On risk and benefits of iron supplementation—recommendations for iron intake revisited. J Trace Elem Med Biol2007;21:147–68.
4.
MurrayMJMurrayABMurrayMBMurrayCJ. The adverse effect of iron repletion on the course of certain infections. Br Med J1978;21:1113–5.
5.
WeinbergED. Iron loading and disease surveillance. Emerg Infect Dis1995;5:346–52.
6.
SchaibleUEKaufmannSH. Iron and microbial infection. Nat Rev Microbiol2004;2:946–53.
7.
NairzMSchrollASonnweberTWeissG. The struggle for iron—a metal at the host-pathogen interface. Cell Microbiol2010;12:1691–702.
8.
HarveyPWHeywoodPFNesheimMCGalmeKZegansMHabichtJPStephensonLSRadimerKLBrabinBForsythKAlpersMP. The effect of iron therapy on malarial infection in Papua New Guinean schoolchildren. Am J Trop Med Hyg1989;40:12–8.
9.
SmithAWHendrickseRGHarrisonCHayesRJGreenwoodBM. The effects on malaria of treatment of iron-deficiency anaemia with oral iron in Gambian children. Ann Trop Paediatr1989;9:17–23.
10.
van den HomberghJDalderopESmitY. 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 Pediatr1996;42:220–7.
11.
BergerJDyckJLGalanPAploganASchneiderDTraissacPHercbergS. 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 Nutr2000;54:29–35.
12.
MenendezCKahigwaEHirtRVounatsouPAponteJJFontFAcostaCJSchellenbergDMGalindoCMKimarioJUrassaHBrabinBSmithTAKituaAYTannerMAlonsoPL. Randomised placebo-controlled trial of iron supplementation and malaria chemoprophylaxis for prevention of severe anaemia and malaria in Tanzanian infants. Lancet1997;350:844–50.
13.
OjukwuJUOkebeJUYahavDPaulM. Oral iron supplementation for preventing or treating anaemia among children in malaria-endemic areas. Cochrane Database Syst Rev2011;(10):CD006589.
14.
SazawalSBlackRERamsanMChwayaHMStoltzfusRJDuttaADhingraUKaboleIDebSOthmanMKKaboleFM. 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, randomised, placebo-controlled trial. Lancet2006;367:133–43.
15.
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 Bull2007;28:S621–7.
16.
Sch&udblacmannKChristF. Did the iron age end in Pemba?Sight Life Mag2007;3:6–13.
17.
PrenticeAM. Iron metabolism, malaria, and other infections: what is all the fuss about?J Nutr2008;138:2537–41.
18.
PrenticeAMGhattasHDohertyCCoxSE. Iron metabolism and malaria. Food Nutr Bull2007;28:S524–39.
19.
SarkatePPatilAParulekarSRegeNNSamantBDLokhandeJGuptaAKulkarniK. A randomised double-blind study comparing sodium feredetate with ferrous fumarate in anaemia in pregnancy. J Indian Med Assoc2007;105:278, 280–1, 284.
20.
Andang'oPEOsendarpSJAyahRWestCEMwanikiDLDe WolfCAKraaijenhagenRKokFJVerhoefH. Efficacy of iron-fortified whole maize flour on iron status of schoolchildren in Kenya: a randomised controlled trial. Lancet2007;369:1799–806.
21.
LongfilsPMonchyDWeinheimerHChavasitVNakanishiYSchümannK. 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 Nutr2008;17:250–7.
22.
ReddyPSAdsulBBGandewarKKordeKMDesaiA. 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 Assoc2001;99:154–5.
23.
SahaLPandhiPGopalanSMalhotraSSahaPK. 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 Med2007;9:1.
24.
HaliotisFAPapanastasiouDA. 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 Ther1998;36:320–5.
25.
GeisserP. Safety and efficacy of iron(III)-hydroxide polymaltose complex/a review of over 25 years experience. Arzneimittelforschung2007;57:439–52.
26.
SchümannKSolomonsNWRomero-AbalM-EOrozcoMWeissGMarxJJ. Oral administration of ferrous sulfate, but not of iron polymaltose and sodium iron EDTA, results in a substantial increase of nontransferrin-bound iron in healthy men. Food Nutr Bull2012;33:128–36.
27.
HentzeMWMuckenhalterMUGabyBCamaschellaC. Two to tango: regulation of mammalian iron metabolism. Cell2010;142:24–38.
28.
VanoaicaLDarshanDRichmanLSchümannKKühnLC. Intestinal ferritin H is required for an accurate control of iron absorption. Cell2010;12:273–82.
29.
BreuerWCabantchikZI. A fluorescence-based one-step assay for serum non transferrin-bound iron. Anal Biochem2001;299:194–202.
30.
HiderRC. Nature of nontransferrin-bound iron. Eur J Clin Nutr2002;32:50–4.
31.
HutchinsonCAl-AshgarWLiuDHiderRCPowellJJGeisslerCA. Oral ferrous sulphate leads to a marked increase in pro-oxidant non-transferrin-bound iron. Eur J Clin Invest2004;34:782–4.
32.
DresowBPetersenDFischerRNielsenP. Non-transferrin-bound iron in plasma followed administration of oral iron drugs. Biometals2008;21:273–6.
33.
MessnerDJKowdleyKV. Neoplastic transformation of rat liver epithelial cells is enhanced by non-transferrin-bound iron. BMC Gastroenterol2008;8:2.
34.
OzmentCPTuriJL. Iron overload following red blood cell transfusion and its impact on disease severity. Biochim Biophys Acta2009;1790:694–701.
35.
PorterJB. Pathophysiology of transfusional iron overload: contrasting patterns in thalassemia major and sickle cell disease. Haemoglobin2009;33:S37–45.
36.
HershkoC. Pathogenesis and management of iron toxicity in thalassemia. Ann N Y Acad Sci2010;1202:1–9.
37.
KartikasariAERGeorgiouNAVisserenFLvan Kats-RenaudHvan AsbeckBSMarxJJ. Endothelial activation and induction of monocyte adhesion by non-transferrin-bound iron present in human sera. FASEB J2005;20:353–5.
38.
GrayCMcCormickCTurnerGCraigA. ICAM-1 can play a major role in mediating P. falciparum adhesion to endothelium under flow. Mol Biochem Parasitol2003;128:187–93.
39.
DeValkBAddicksMAGosriwatanaILuSHiderRCMarxJJ. Non-transferrin-bound iron is present in serum of hereditary haemochromatosis heterozygotes. Eur J Clin Invest2000;30:248–51.
40.
RaoBSVijayasarathyC. Fortification of common salt with iron: effect of chemical additives on stability and bioavailability. Am J Clin Nutr1975;28:1395–401.
41.
RiosEHunterRECookJDSmithNJFinchCA. The absorption of iron as supplements in infant cereal and infant formulas. Pediatrics1975;55:686–93.
42.
HoppeMHulthénLHallbergL. The validation of using serum iron increase to measure iron absorption in human subjects. Br J Nutr2004;92:485–8.
43.
HoppeMHulthénLHallbergL. The relative bioavailability in humans of elemental iron powders for use in food fortification. Eur J Nutr2006;45:37–44.
44.
WallenburgHCvan EijkHG. Effect of oral iron supplementation during pregnancy on maternal and fetal iron status. J Perinat Med1984;12:7–12.
45.
ChwangLCSoemantriAGPollittE. Iron supplementation and physical growth of rural Indonesian children. Am J Clin Nutr1988;47:496–501.
46.
KatzJKhatrySKLeclerqSCMullanyLCYanikELStoltzfusRJSiegelEHTielschJM. 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 Nutr2010;140:1317–21.
