Abstract
Background:
Obesity increases the risk for iron deficiency, but the underlying mechanism is unclear. It is possible that overweight individuals may have lower dietary iron intake and/or bioavailability. Alternatively, obesity-related inflammation may increase hepcidin concentrations and reduce iron availability. Circulating hepcidin levels have not been compared in normal weight vs overweight individuals.
Objective:
The objective of this study was to compare iron status, dietary iron intake and bioavailability, as well as circulating levels of hepcidin, leptin and interleukin-6 (IL-6), in overweight vs normal weight children.
Design:
In 6–14-year-old normal and overweight children (n=121), we measured dietary iron intake, estimated iron bioavailability and determined body mass index s.d. scores (BMI-SDS). In all children (n=121), we measured fasting serum ferritin, soluble transferrin receptor (sTfR), C-reactive protein (CRP) and leptin; in a subsample, we measured IL-6 (n=68) and serum hepcidin (n=30).
Results:
There were no significant differences in dietary iron intake or bioavailability comparing normal and overweight children. The prevalence of iron-deficient erythropoiesis (an increased sTfR concentration) was significantly higher in the overweight than in the normal weight children (20 vs 6%, P=0.022, with sTfR concentrations of 4.40±0.77 and 3.94±0.88 mg l−1, respectively, P=0.010). Serum hepcidin levels were significantly higher in the overweight children (P=0.001). BMI-SDS significantly correlated with sTfR (P=0.009), serum hepcidin (P=0.005) and the three measures of subclinical inflammation, namely CRP (P<0.001), IL-6 (P<0.001) and leptin (P<0.001). In a multiple regression model, serum hepcidin was correlated with BMI-SDS (P=0.020) and body iron (P=0.029), but not with the inflammatory markers.
Conclusion:
Our findings indicate that there is reduced iron availability for erythropoiesis in overweight children and that this is unlikely due to low dietary iron supply but rather due to hepcidin-mediated reduced iron absorption and/or increased iron sequestration.
References
Seltzer CC, Mayer J . Serum iron and iron-binding capacity in adolescents.2. comparison of obese and nonobese subjects. Am J Clin Nutr 1963; 13: 354–361.
Scheer JC, Guthrie HA . Hemoglobin criteria with respect to obesity. Am J Clin Nutr 1981; 34: 2748–2751.
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.
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.
Wenzel BJ, Mayer J, Stults HB . Hypoferraemia in obese adolescents. Lancet 1962; 2: 327–328.
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.
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.
Lecube A, Carrera A, Losada E, Hernandez C, Simo R, Mesa J . Iron deficiency in obese postmenopausal women. Obesity (Silver Spring) 2006; 14: 1724–1730.
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 (Lond) 2007; 31: 1412–1419.
Bekri S, Gual P, Anty R, Luciani N, Dahman M, Ramesh B et al. Increased adipose tissue expression of hepcidin in severe obesity is independent from diabetes and NASH. Gastroenterology 2006; 131: 788–796.
Park CH, Valore EV, Waring AJ, Ganz T . Hepcidin, a urinary antimicrobial peptide synthesized in the liver. J Biol Chem 2001; 276: 7806–7810.
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.
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.
Laftah AH, Ramesh B, Simpson RJ, Solanky N, Bahram S, Schümann K et al. Effect of hepcidin on intestinal iron absorption in mice. Blood 2004; 103: 3940–3944.
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 Obes 2008; 32: 1098–1104.
Menzie CM, Yanoff LB, Denkinger BI, McHugh T, Sebring NG, Calis KA et al. Obesity-related hypoferremia is not explained by differences in reported intake of heme and nonheme, iron or intake of dietary factors that can affect iron absorption. J Am Diet Assoc 2008; 108: 145–148.
Aeberli I, Biebinger R, Lehmann R, L’Allemand D, Spinas GA, Zimmermann MB . Serum retinol-binding protein 4 concentration and its ratio to serum retinol are associated with obesity and metabolic syndrome components in children. J Clin Endocrinol Metab 2007; 92: 4359–4365.
Aeberli I, Molinari L, Spinas G, Lehmann R, L’Allemand D, Zimmermann MB . Dietary intakes of fat and antioxidant vitamins are predictors of subclinical inflammation in overweight Swiss children. Am J Clin Nutr 2006; 84: 748–755.
Aeberli I, Zimmermann MB, Molinari L, Lehmann R, l’Allemand D, Spinas GA et al. Fructose intake is a predictor of LDL particle size in overweight schoolchildren. Am J Clin Nutr 2007; 86: 1174–1178.
Aeberli I, Beljean N, Lehmann R, l’Allemand D, Spinas GA, Zimmermann MB . The increase of fatty acid-binding protein aP2 in overweight and obese children: interactions with dietary fat and impact on measures of subclinical inflammation. Int J Obes 2008; 32: 1513–1520.
Lytle LA, Nichaman MZ, Obarzanek E, Glovsky E, Montgomery D, Nicklas T et al. Validation of 24-h recalls assisted by food records in third-grade children. The CATCH Collaborative Group. J Am Diet Assoc 1993; 93: 1431–1436.
Infanger E Schweizer Nährwerttabelle: Schweizerische Gesellschaft für Ernährung, SGE, Bern, Bundesamt für Gesundheit, BAG, Bern, Eidgenössische Technische Hochschule, ETH, Zürich 2005.
Kongkachuichai R, Napatthalung P, Charoensiri R . Heme and nonheme iron content of animal products commonly consumed in Thailand. J Food Compost Anal 2002; 15: 389–398.
Tseng M, Chakraborty H, Robinson DT, Mendez M, Kohlmeier L . Adjustment of iron intake for dietary enhancers and inhibitors in population studies: bioavailable iron in rural and urban residing Russian women and children. J Nutr 1997; 127: 1456–1468.
Monsen ER, Balintfy JL . Calculating dietary iron bioavailability—refinement and computerization. J Am Diet Assoc 1982; 80: 307–311.
Bothwell TH, Charlton RW, Cook JD, Finch CA . Iron Metabolism in Man. Blackwell Scientific Publications: London, 1979.
Ogden CL, Kuczmarski RJ, Flegal KM, Mei Z, Guo S, Wei R et al. Centers for Disease Control and Prevention 2000 growth charts for the United States: improvements to the 1977 National Center for Health Statistics version. Pediatrics 2002; 109: 45–60.
Zimmermann MB, Gubeli C, Puntener C, Molinari L . Detection of overweight and obesity in a national sample of 6-12-y-old Swiss children: accuracy and validity of reference values for body mass index from the US Centers for Disease Control and Prevention and the International Obesity Task Force. Am J Clin Nutr 2004; 79: 838–843.
Kemna EHJM, Tjalsma H, Willems HL, Swinkels DW . Hepcidin: from discovery to differential diagnosis. Haematologica 2008; 93: 90–97.
WHO, UNICEF, UNU. Iron deficiency anaemia. Assessment, prevention and control. A guide for programme managers. Geneva 2001.
Pfeiffer CM, Cook JD, Mei ZG, Cogswell ME, Looker AC, Lacher DA . Evaluation of an automated soluble transferrin receptor (sTfR) assay on the Roche Hitachi analyzer and its comparison to two ELISA assays. Clin Chim Acta 2007; 382: 112–116.
Cook JD, Flowers CH, Skikne BS . The quantitative assessment of body iron. Blood 2003; 101: 3359–3364.
Zimmermann MB, Hurrell RF . Nutritional iron deficiency. Lancet 2007; 370: 511–520.
Aeberli I, Kaspar M, Zimmermann MB . Dietary intake and physical activity of normal weight and overweight 6 to 14 year old Swiss children. Swiss Med Wkly 2007; 137: 424–430.
Hallberg L . Pool concept in food iron-absorption and some of its implications. Proc Nutr Soc 1974; 33: 285–291.
Carpenter CE, Mahoney AW . Contributions of heme and nonheme iron to human-nutrition. Crit Rev Food Sci Nutr 1992; 31: 333–367.
Hallberg L, Hulthen L . Prediction of dietary iron absorption: an algorithm for calculating absorption and bioavailability of dietary iron. Am J Clin Nutr 2000; 71: 1147–1160.
Reddy MB, Hurrell RF, Cook JD . Estimation of nonheme-iron bioavailability from meal composition. Am J Clin Nutr 2000; 71: 937–943.
Bhargava A, Bouis HE, Scrimshaw NS . Dietary intakes and socioeconomic factors are associated with the hemoglobin concentration of Bangladeshi women. J Nutr 2001; 131: 758–764.
Du SF, Zhai FY, Wang YF, Popkin BM . Current methods for estimating dietary iron bioavailability do not work in China. J Nutr 2000; 130: 193–198.
Acknowledgements
We would like to thank all the children and families who participated in the study. We also thank Isabella Sciaroni, Nicole Beljean, Alexandra Uster and Evelyne Pflugi (ETH Zürich, Switzerland) who assisted with the study. Special thanks also go to Harold Tjalsma from http://www.hepcidinanalysis.com in Nijmegen for his assistance with the hepcidin measurements.
Each of the authors contributed to the study design and the statistical analysis of the data as well as the writing and editing of the paper. Data collection and laboratory analysis was done by IA.
This study was funded by the ETH Zurich.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Aeberli, I., Hurrell, R. & Zimmermann, M. Overweight children have higher circulating hepcidin concentrations and lower iron status but have dietary iron intakes and bioavailability comparable with normal weight children. Int J Obes 33, 1111–1117 (2009). https://doi.org/10.1038/ijo.2009.146
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/ijo.2009.146
- Springer Nature Limited