The Effect of Daily Iron Supplementation with 60 mg Ferrous Sulfate for 12 Weeks on Non-Transferrin Bound Iron Concentrations in Women with a High Prevalence of Hemoglobinopathies
Abstract
:1. Introduction
2. Experimental Section
2.1. Study Design and Population
2.2. Ethical Approval
2.3. Blood Collection and Analysis
2.4. Statistical Analyses
3. Results
3.1. Baseline Characteristics
3.2. Indicators of Hematological and Nutritional Status at Baseline and 12 Weeks
3.3. Proportion of Women with an Elevated Serum NTBI Concentrations at 12 Weeks
3.4. Factors Associated with Elevated Serum NTBI Concentrations at 12 Weeks
4. Discussion
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
- Guideline: Daily Iron Supplementation in Adult Women and Adolescent Girls; World Health Organization: Geneva, Switzerland, 2016.
- Schümann, K.; Ettle, T.; Szegner, B.; Elsenhans, B.; Solomons, N.W. On risks and benefits of iron supplementation recommendations for iron intake revisited. J. Trace Elem. Med. Biol. 2007, 21, 147–168. [Google Scholar] [CrossRef] [PubMed]
- Karakochuk, C.D. Iron supplementation in predominantly iron-replete populations: Is there an emerging concern? Sight Life Mag. 2016, 30, 44–51. [Google Scholar]
- Zimmermann, M.B.; Fucharoen, S.; Winichagoon, P.; Sirankapracha, P.; Zeder, C.; Gowachirapant, S.; Judprasong, K.; Tanno, T.; Miller, J.L.; Hurrell, R.F. Iron metabolism in heterozygotes for hemoglobin E (HbE), alpha-thalassemia 1, or beta-thalassemia and in compound heterozygotes for HbE/beta-thalassemia. Am. J. Clin. Nutr. 2008, 88, 1026–1031. [Google Scholar] [CrossRef] [PubMed]
- Bain, B.J. Haemoglobinopathy Diagnosis, 2nd ed.; Blackwell Publishing Ltd.: Oxford, UK, 2006. [Google Scholar]
- Greer, J.P.; Foerster, J.; Rodgers, G.M.; Paraskevas, F. Wintrobe’s Clinical Hematology, 12th ed.; Lippincott Williams & Wilkins: Baltimore, MD, USA, 2009. [Google Scholar]
- Karakochuk, C.D.; Whitfield, K.C.; Barr, S.I.; Lamers, Y.; Devlin, A.M.; Vercauteren, S.M.; Kroeun, H.; Talukder, A.; McLean, J.; Green, T.J. Genetic hemoglobin disorders rather than iron deficiency are a major predictor of hemoglobin concentration in women of reproductive age in rural Prey Veng, Cambodia. J. Nutr. 2015, 145, 134–142. [Google Scholar] [CrossRef]
- Weatherall, D.J.; Clegg, J.B. Inherited haemoglobin disorders: An increasing global health problem. Public Health Rev. 2001, 79, 704–712. [Google Scholar]
- Piel, F.B.; Patil, A.P.; Howes, R.E.; Nyangiri, O.A.; Gething, P.W.; Williams, T.N.; Weatherall, D.J.; Hay, S.I. Global distribution of the sickle cell gene and geographical confirmation of the malaria hypothesis. Nat. Commun. 2010, 1, 104. [Google Scholar] [CrossRef] [Green Version]
- Kattamis, A.; Papassotiriou, I.; Palaiologou, D.; Apostolakou, F.; Galani, A.; Ladis, V.; Sakellaropoulos, N.; Papanikolaou, G. The effects of erythropoetic activity and iron burden on hepcidin expression in patients with thalassemia major. Haematologica 2006, 91, 809–812. [Google Scholar] [PubMed]
- Frazer, D.M.; Anderson, G.J. The regulation of iron transport. BioFactors 2014, 40, 206–214. [Google Scholar] [CrossRef] [PubMed]
- Hutchinson, C.; Liu, D.Y.; Hider, R.C.; Powell, J.J.; Geissler, C.A. Oral ferrous sulphate leads to a marked increase in pro-oxidant nontransferrin-bound iron. Eur. J. Clin. Investig. 2004, 34, 782–784. [Google Scholar] [CrossRef] [PubMed]
- Hod, E.A.; Brittenham, G.M.; Billote, G.B.; Francis, R.O.; Ginzburg, Y.Z.; Hendrickson, J.E.; Jhang, J.; Schwartz, J.; Sharma, S.; Sheth, S.; et al. Transfusion of human volunteers with older, stored red blood cells produces extravascular hemolysis and circulating non-transferrin-bound iron. Blood 2011, 118, 6675–6682. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Brissot, P.; Ropert, M.; Le Lan, C.; Loréal, O. Non-transferrin bound iron: A key role in iron overload and iron toxicity. Biochim. Biophys. Acta 2012, 1820, 403–410. [Google Scholar] [CrossRef] [PubMed]
- Brittenham, G.M.; Andersson, M.; Egli, I.; Foman, J.T.; Zeder, C.; Westerman, M.E.; Hurrell, R.F. Circulating non-transferrin-bound iron after oral administration of supplemental and fortification doses of iron to healthy women: A randomized study. Am. J. Clin. Nutr. 2014, 100, 813–820. [Google Scholar] [CrossRef] [PubMed]
- Karakochuk, C.D.; Barker, M.K.; Whitfield, K.C.; Barr, S.I.; Vercauteren, S.M.; Devlin, A.M.; Hutcheon, J.A.; Houghton, L.A.; Prak, S.; Hou, K.; et al. The effect of oral iron with or without multiple micronutrients on hemoglobin concentration and hemoglobin response among non-pregnant Cambodian women of reproductive age: A 2 × 2 double-blind randomized controlled supplementation trial. Am. J. Clin. Nutr. 2017, 106, 233–244. [Google Scholar] [CrossRef] [PubMed]
- Jacobs, E.M.G.; Hendriks, J.C.M.; Van Tits, B.L.J.H.; Evans, P.J.; Breuer, W.; Ding, Y.L.; Jansen, E.H.J.M.; Jauhiainen, K.; Sturm, B.; Porter, J.B.; et al. Results of an international round robin for the quantification of serum non-transferrin-bound iron: Need for defining standardization and a clinically relevant isoform. Anal. Biochem. 2005, 341, 241–250. [Google Scholar] [CrossRef] [PubMed]
- Thurnham, D.I.; McCabe, L.D.; Haldar, S.; Wieringa, F.T.; Northrop-Clewes, C.A.; McCabe, G.P. Adjusting plasma ferritin concentrations to remove the effects of subclinical inflammation in the assessment of iron deficiency: A meta-analysis. Am. J. Clin. Nutr. 2010, 92, 546–555. [Google Scholar] [CrossRef] [PubMed]
- Petry, N.; Egli, I.; Zeder, C.; Walczyk, T.; Hurrell, R. Polyphenols and phytic acid contribute to the low iron bioavailability from common beans in young women. J. Nutr. 2010, 140, 1977–1982. [Google Scholar] [CrossRef] [PubMed]
- Gibson, R.S.; Raboy, V.; King, J.C. Implications of phytate in plant-based foods for iron and zinc bioavailability, setting dietary requirements, and formulating programs and policies. Nutr. Rev. 2018, 76, 793–804. [Google Scholar] [CrossRef] [PubMed]
- Schümann, K.; Kroll, S.; Romero-Abal, M.E.; Georgiou, N.A.; Marx, J.J.M.; Weiss, G.; Solomons, N.W. Impact of oral iron challenges on circulating non-transferrin-bound iron in healthy guatemalan males. Ann. Nutr. Metab. 2012, 60, 98–107. [Google Scholar] [CrossRef] [PubMed]
- World Health Organization. Model List of Essential Medicines, 20th ed.; World Health Organization (WHO): Geneva, Switzerland, 2017. [Google Scholar]
- Schümann, K.; Solomons, N.W.; Orozco, M.; Romero-Abal, M.E.; Weiss, G. 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. Food Nutr. Bull. 2013, 34, 185–193. [Google Scholar] [CrossRef] [PubMed]
- Milman, N.; Jønsson, L.; Dyre, P.; Pedersen, P.L.; Larsen, L.G. Ferrous bisglycinate 25 mg iron is as effective as ferrous sulfate 50 mg iron in the prophylaxis of iron deficiency and anemia during pregnancy in a randomized trial. J. Perinat. Med. 2014, 42, 197–206. [Google Scholar] [CrossRef] [PubMed]
Fe | Placebo | p Value | |
---|---|---|---|
Total n (%) | 50 (50%) | 50 (50%) | |
Age, years, mean ± SD | 30.4 ± 7.3 | 31.2 ± 8.6 | 0.62 |
Parity, n of children born, median (IQR) | 1.5 (0, 3.0) | 1.0 (0, 3.0) | 0.73 |
Household size, n, mean ± SD | 4.5 ± 1.6 | 4.6 ± 1.3 | 0.63 |
Hemoglobin concentration, g/L, median (IQR) | 125 (117, 121) | 121 (115, 127) | 0.37 |
Ferritin concentration, 2 µg/L, median (IQR) | 46.4 (18.9, 80.6) | 38.3 (23.8, 58.6) | 0.59 |
Transferrin saturation, %, median (IQR) | 23.7 (14.6, 31.5) | 21.2 (12.5, 27.0) | 0.39 |
Prevalence of a hemoglobinopathy, 3 n (%) | 36/50 (72%) | 31/50 (62%) | 0.29 |
Fe | Placebo | p Value | |
---|---|---|---|
Total n (%) | 50 (50%) | 50 (50%) | |
Anemia (hemoglobin <120 g/L), n (%) | |||
At baseline | 20/50 (40%) | 19/50 (38%) | 0.84 |
At 12 weeks | 14/50 (28%) | 26/50 (52%) | 0.01 |
Iron deficiency (ferritin <15 µg/L), 2 n (%) | |||
At baseline | 8/50 (16%) | 10/50 (20%) | 0.60 |
At 12 weeks | 1/50 (2%) | 10/50 (20%) | 0.01 |
Transferrin saturation, %, median (IQR) | |||
At baseline | 23.7 (14.6, 31.5) | 21.3 (12.5, 27.0) | 0.39 |
At 12 weeks | 26.6 (20.9, 32.2) | 19.5 (11.0, 27.6) | 0.001 |
Elevated serum NTBI (≥0.1 µmol/L), n (%) | |||
At 12 weeks 3 | 9/50 (18%) | 8/50 (16%) | 0.79 |
Factor | OR (95% CI) | SE | p Value |
---|---|---|---|
Age, years | 0.98 (0.91, 1.05) | 0.036 | 0.55 |
Transferrin saturation, % | 1.04 (0.99, 1.09) | 0.024 | 0.12 |
Presence of a homozygous Hb EE disorder | 0.95 (0.09, 9.58) | 1.121 | 0.97 |
Iron supplementation (60 mg for 12 weeks) | 0.92 (0.30, 2.85) | 0.531 | 0.89 |
Constant | 0.16 (0.01, 2.02) | 0.207 | 0.16 |
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Steele, S.L.; Kroeun, H.; Karakochuk, C.D. The Effect of Daily Iron Supplementation with 60 mg Ferrous Sulfate for 12 Weeks on Non-Transferrin Bound Iron Concentrations in Women with a High Prevalence of Hemoglobinopathies. J. Clin. Med. 2019, 8, 180. https://doi.org/10.3390/jcm8020180
Steele SL, Kroeun H, Karakochuk CD. The Effect of Daily Iron Supplementation with 60 mg Ferrous Sulfate for 12 Weeks on Non-Transferrin Bound Iron Concentrations in Women with a High Prevalence of Hemoglobinopathies. Journal of Clinical Medicine. 2019; 8(2):180. https://doi.org/10.3390/jcm8020180
Chicago/Turabian StyleSteele, Shannon L., Hou Kroeun, and Crystal D. Karakochuk. 2019. "The Effect of Daily Iron Supplementation with 60 mg Ferrous Sulfate for 12 Weeks on Non-Transferrin Bound Iron Concentrations in Women with a High Prevalence of Hemoglobinopathies" Journal of Clinical Medicine 8, no. 2: 180. https://doi.org/10.3390/jcm8020180