Abstract
Background:
Many countries in the nutrition transition have high rates of iron deficiency (ID) and overweight (OW). ID is more common in OW children; this may be due to adiposity-related inflammation reducing iron absorption.
Objective:
We investigated whether weight status predicts response to oral iron supplementation in ID South African children.
Design:
A placebo-controlled trial of oral iron supplementation (50 mg, 4 × weeks for 8.5 months) was done in ID 6- to 11-year-old children (n=321); 28% were OW or obese. BMI-for-age z-scores (BAZ), hepcidin (in a sub-sample), hemoglobin, serum ferritin (SF), transferrin receptor (TfR), zinc protoporphyrin (ZnPP) and C-reactive protein (CRP) were measured; body iron was calculated from the SF to TfR ratio.
Results:
At baseline, BAZ correlated with CRP (r=0.201, P<0.001) and CRP correlated with hepcidin (r=0.384, P<0.001). Normal weight children supplemented with iron had significantly lower TfR concentrations at endpoint than the OW children supplemented with iron and the children receiving placebo. Higher BAZ predicted higher TfR (β=0.232, P<0.001) and lower body iron (β=−0.090, P=0.016) at endpoint, and increased the odds ratio (OR) for remaining ID at endpoint in both the iron and placebo groups (iron: OR 2.31, 95% CI: 1.13, 4.73; placebo: OR 1.78, 95% CI: 1.09, 2.91). In the children supplemented with iron, baseline hepcidin and BAZ were significant predictors of endpoint TfR, with a trend towards a hepcidin × BAZ interaction (P=0.058).
Conclusion:
South African children with high BAZ have a two-fold higher risk of remaining ID after iron supplementation. This may be due to their higher hepcidin concentrations reducing iron absorption. Thus, the current surge in OW in rapidly developing countries may undercut efforts to control anemia in vulnerable groups. The trial is registered at clinicaltrials.gov as NCT01092377.
This is a preview of subscription content, access via your institution
Access options
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
Similar content being viewed by others
References
WHO. 10 Facts on obesity. World Health Organisation: Geneva, 2010.
Srihari G, Eilander A, Muthayya S, Kurpad AV, Seshadri S . Nutritional status of affluent Indian school children: what and how much do we know? Indian Pediatr 2007; 44: 204–213.
Zimmermann MB, Winichagoon P, Gowachirapant S, Hess SY, Harrington M, Chavasit V et al. Comparison of the efficacy of wheat-based snacks fortified with ferrous sulfate, electrolytic iron, or hydrogen-reduced elemental iron: randomized, double-blind, controlled trial in Thai women. Am J Clin Nutr 2005; 82: 1276–1282.
Aeberli I, Hurrell RF, Zimmermann MB . Overweight children have higher circulating hepcidin concentrations and lower iron status but have dietary iron intakes and bioavailability comparable to normal weight children. Int J Obesity 2009; 33: 1111–1117.
Brotanek JM, Gosz J, Weitzman M, Flores G . Iron deficiency in early childhood in the United States: risk factors and racial/ethnic disparities. Pediatrics 2007; 120: 568–575.
Nead KG, Halterman JS, Kaczorowski JM, Auinger P, Weitzman M . Overweight children and adolescents: a risk group for iron deficiency. Pediatrics 2004; 114: 104–108.
Pinhas-Hamiel O, Newfield RS, Koren I, Agmon A, Lilos P, Phillip M . Greater prevalence of iron deficiency in overweight and obese children and adolescents. Int J Obes 2003; 27: 416–418.
Cepeda-Lopez AC, Osendarp SJM, Melse-Boonstra A, Aeberli I, Gonzalez-Salazar F, Feskens E et al. Sharply higher rates of iron deficiency in obese Mexican women and children are predicted by obesity-related inflammation rather than by differences in dietary iron intake. Am J Clin Nutr 2011; 93: 975–983.
Viatte L, S. Vaulont . Hepcidin, the iron watcher. Biochimie 2009; 91: 1223–1228.
Zimmermann MB, Zeder C, Muthayya S, Winichagoon P, Chaouki N, Aeberli I et al. Adiposity in women and children from transition countries predicts decreased iron absorption, iron deficiency and a reduced response to iron fortification. Int J Obesity 2008; 32: 1098–1104.
Tussing-Humphreys LM, Liang H, Nemeth E, Freels S, Braunschweig CA . Excess adiposity, inflammation, and iron-deficiency in female adolescents. J Am Diet Assoc 2009; 109: 297–302.
Tussing-Humphreys LM, Nemeth E, Fantuzzi G, Freels S, Holtermann AL, Galvani C et al. Decreased serum hepcidin and improved functional iron status 6 months after restrictive bariatric surgery. Obesity 2010; 18: 2010–2016.
Cepeda-Lopez AC, Aeberli I, Zimmermann MB . Does obesity increase risk for iron deficiency? A review of the literature and the potential mechanisms. Int J Vitam Nutr Res 2011; 80: 263–270.
Amato A, Santoro N, Calabro P, Grandone A, Swinkels DW, Perrone L et al. Effect of body mass index reduction on serum hepcidin levels and iron status in obese children. Int J Obes 2010; 34: 1772–1774.
Bourne LT, Lambert EV, Steyn K . Where does the black population of South Africa stand on the nutrition transition? Public Health Nutr 2002; 5: 157–162.
Armstrong MEG, Lambert MI, Lambert EV . Secular trends in the prevalence of stunting, overweight and obesity among South African children (1994-2004). Eur J Clin Nutr 2011; 65: 835–840.
Li YF, Dai Q, Jackson JC, Zhang J . Overweight is associated with decreased cognitive functioning among school-age children and adolescents. Obesity 2008; 16: 1809–1815.
Elias MF, Elias PK, Sullivan LM, Wolf PA, D'Agostino RB . Lower cognitive function in the presence of obesity and hypertension: the Framingham heart study. Int J Obesity 2003; 27: 260–268.
McCann JC, Ames BN . An overview of evidence for a causal relation between iron deficiency during development and deficits in cognitive or behavioral function. Am J Clin Nutr 2007; 85: 931–945.
Cook JD, Flowers CH, Skikne BS . The quantitative assessment of body iron. Blood 2003; 101: 3359–3364.
Metzgeroth G, Adelberger V, Dorn-Beineke A, Kuhn C, Schatz M, Maywald O et al. Soluble transferrin receptor and zinc protoporphyrin—competitors or efficient partners? Eur J Haematol 2005; 75: 309–317.
Zimmermann MB . Methods to assess iron and iodine status. Br J Nutr 2008; 99 (Suppl 3): S2–S9.
World Health Organisation, United Nations Children's Fund United Nations University. Iron deficiency anaemia. Assessment, prevention and control. World Health Organisation: Geneva, Switzerland, 2001.
Swinkels DW, Girelli D, Laarakkers C, Kroot J, Campostrini N, Kemna EHJM et al. Advances in quantitative hepcidin measurements by time-of-flight mass spectrometry. Plos One 2008; 3: 7.
Kroot JJ, Laarakkers CM, Geurts-Moespot AJ, Grebenchtchikov N, Pickkers P, van Ede AE et al. Immunochemical and mass-spectrometry-based serum hepcidin assays for iron metabolism disorders. Clin Chem 2010; 56: 1570–1579.
Krueger HS, Swart R, Labadarios D, Dannhauser A, Nel JH . Anthropometric status. In: Labadarios D, (ed). Consumption Survey, Fortification Baseline. Stellenbosch: South Africa, 2005, pp 121–160.
Micozzi MS, Albanes D, Stevens RG . Relation of Body Size and Composition to Clinical Biochemical and Hematologic Indexes in United-States Men and Women. Am J Clin Nutr 1989; 50: 1276–1281.
Wenzel BJ, Mayer J, Stults HB . Hypoferraemia in obese adolescents. Lancet 1962; 2: 327–328.
Yanoff LB, Menzie CM, Denkinger B, Sebring NG, McHugh T, Remaley AT et al. Inflammation and iron deficiency in the hypoferremia of obesity. Int J Obes 2007; 31: 1412–1419.
Zimmermann MB, Hurrell RF . Nutritional iron deficiency. Lancet 2007; 370: 511–520.
Rossi E, Bulsara MK, Olynyk JK, Cullen DJ, Summerville L, Powell LW . Effect of hemochromatosis genotype and lifestyle factors on iron and red cell indices in a community population. Clin Chem 2001; 47: 202–208.
Whitfield JB, Treloar S, Zhu G, Powell LW, Martin NG . Relative importance of female-specific and non-female-specific effects on variation in iron stores between women. Br J Haematol 2003; 120: 860–866.
Failla ML, Kennedy ML, Chen ML . Iron metabolism in genetically obese (ob/ob) mice. J Nutr 1988; 118: 46–51.
Anonymous. Iron. In: Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. National Academy Press: Washington, DC, 2001. pp 290–293.
Chung B, Matak P, McKie AT, Sharp P . Leptin increases the expression of the iron regulatory hormone hepcidin in HuH7 human hepatoma cells. J Nutr 2007; 137: 2366–2370.
Falzacappa MVV, Spasic MV, Kessler R, Stolte J, Hentze MW, Muckenthaler MU . STAT3 mediates hepatic hepcidin expression and its inflammatory stimulation. Blood 2007; 109: 353–358.
Wrighting DM, Andrews NC . Interleukin-6 induces hepcidin expression through STAT3. Blood 2006; 108: 3204–3209.
Tussing-Humphreys LM, Nemeth E, Fantuzzi G, Freels S, Guzman G, Holterman AX et al. Elevated systemic hepcidin and iron depletion in obese premenopausal females. Obesity 2009; 18: 1449–1456.
del Giudice EM, Santoro N, Amato A, Brienza C, Calabro P, Wiegerinck ET et al. Hepcidin in obese children as a potential mediator of the association between obesity and iron deficiency. J Clin Endocrinol Metab 2009; 94: 5102–5107.
Acknowledgements
We thank all the fieldworkers, teachers and principals of the schools for their support of the study, the children and parents for their participation in the trial, MRC and NWU colleagues and students, especially J Greeff, for their assistance during field and laboratory work, Anja Fleisch for doing preliminary data analyses and interpretation within her Bachelor’s thesis, and PL Jooste, and JC Jerling for acting as the Safety Monitoring Board. We thank Paul Lohmann GmbH (Lomapharm, Emmertal, Germany) for supplying the iron tablets used in the trial, and ET Wiegerinck (Hepcidinanalysis.com, Nijmegen, The Netherlands) for technical assistance. Financial support for the study was provided by Unilever Research and Development (Vlaardingen, The Netherlands) and The Medicor Foundation (Vaduz, Principality of Liechtenstein).
Author contributions
MZ, CMS, JB and LM designed and conducted the study; JB and IA analyzed the data and performed the statistical analyses; HT conducted the hepcidin analyses; JB, IA and MZ wrote the first draft of the manuscript; and all authors read and edited the manuscript. All authors had full access to all the data and JB had the responsibility for the final content of the paper and the decision to submit for publication.
The trial is registered at clinicaltrials.gov as NCT01092377.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Competing interests
The authors declare no conflict of interest.
Rights and permissions
About this article
Cite this article
Baumgartner, J., Smuts, C., Aeberli, I. et al. Overweight impairs efficacy of iron supplementation in iron-deficient South African children: a randomized controlled intervention. Int J Obes 37, 24–30 (2013). https://doi.org/10.1038/ijo.2012.145
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ijo.2012.145
Keywords
This article is cited by
-
Early childhood body mass index trajectory and overweight/obesity risk differed by maternal weight status
European Journal of Clinical Nutrition (2022)
-
Multiple micronutrient supplementation improves micronutrient status in primary school children in Hai Phong City, Vietnam: a randomised controlled trial
Scientific Reports (2021)
-
Prevalence, incidence, and trends of childhood overweight/obesity in Sub-Saharan Africa: a systematic scoping review
Archives of Public Health (2020)
-
Risk factors and morbidities associated with childhood obesity in sub-Saharan Africa: a systematic scoping review
BMC Nutrition (2020)
-
The effect of central obesity on inflammation, hepcidin, and iron metabolism in young women
International Journal of Obesity (2020)