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Obesity, iron deficiency and anaemia: a complex relationship

Published online by Cambridge University Press:  29 April 2020

Ana C Cepeda-Lopez
Affiliation:
Health Sciences Division, University of Monterrey (UDEM), Monterrey, Mexico Email: ana.cepeda@udem.edu
Kaleab Baye
Affiliation:
Center for Food Science and Nutrition, Addis Ababa University, Addis Ababa, Ethiopia
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Abstract

Type
Invited Commentary
Copyright
© The Authors 2020

Low- and middle-income countries are facing complex, overlapping and interconnected burdens of malnutrition. Those different forms of malnutrition can co-exist within the same individual, households and populations, and across the life course and can even paradoxically be linked(1). Obesity (OB) and Fe deficiency (ID) are two of the commonest nutritional disorders in the world. A growing number of studies are showing that ID is common in individuals with overweight and OB (OW/OB)(Reference Cepeda-Lopez, Aeberli and Zimmermann2). In this issue of Public Health Nutrition, Zheng et al. contribute to this growing body of evidence by showing that ID, anaemia and OB are all public health concerns among schoolchildren in Guangzhou, China. They showed that ID anaemia contributed to <10 % of the overall anaemia prevalence and that OB is associated with ID, but not with anaemia or ID anaemia.

OB, characterised by chronic low-grade inflammation, increases hepcidin, reduces Fe absorption and eventually leads to systemic ID and/or Fe-restricted erythropoiesis(Reference Cepeda-Lopez, Melse-Boonstra and Zimmermann3Reference Nemeth, Tuttle and Powelson5). This reduction in Fe absorption in OW/OB subjects is paradoxical as it happens in spite of increased Fe requirements, partly due to increased blood volume(Reference Cepeda-Lopez, Zimmermann and Wussler6). Also striking is the finding that the enhancement of Fe absorption by ascorbic acid in OW/OB is one-half that in normal-weight women as illustrated in a recent stable isotope study in Switzerland(Reference Cepeda-Lopez, Melse-Boonstra and Zimmermann3). Further confirmation of the OB–ID relationship comes from studies that have shown lower circulating hepcidin and increased Fe absorption after laparoscopic sleeve-gastrectomy(Reference Cepeda-Lopez, Allende-Labastida and Melse-Boonstra7).

Several studies have consistently found an association with the features of anaemia of inflammation, specifically, elevated serum ferritin and low serum Fe. However, contrary to anaemia of inflammation, Hb concentration is usually not lower in individuals with OW/OB compared with normal-weight persons(Reference Ausk and Ioannou8). This is consistent with the findings by Zheng et al. where OB was associated with ID, but not with anaemia, which may initially appear paradoxical. Only 8·9 % of the anaemia was related to ID, which is unsurprisingly given the complex aetiology of anaemia. This finding echoes findings from a more recent systematic analysis of national surveys that suggests that the proportion of anaemia associated with ID is much lower than the assumed 50 % and that other causes including hereditary blood disorders and infections such as hookworm and malaria may be important contributors(Reference Petry, Olofin and Hurrell9).

While OB can contribute to ID, ID can in turn participate in OB-related pathogenesis. Given the intricate link between Fe status, O2 transport and physical performance(Reference Abbaspour, Hurrell and Kelishadi10), ID in the OW/OB can exacerbate the already low physical performance, hence, aggravating OB. Over secretion of hepcidin can also lead to Fe sequestration in cells of the reticuloendothelial system, which could induce oxidative stress, endoplasmic reticulum stress, inflammation and adipose tissue endocrine dysfunction(Reference Abbaspour, Hurrell and Kelishadi10,Reference Suchdev, Williams and Mei11) . Increased intracellular Fe stores in subjects with OW/OB could also result in tissue damage (e.g. liver), increasing the risk for hepatic cancer(Reference Chen and Chloupková12,Reference Moreno-Navarrete, Moreno and Puig13) , as well as neurodegenerative disorders(Reference Blasco, Puig and Daunis-i-Estadella14). For children, the combination of ID and OB can have dire consequences including impaired immune functions, poor cognitive and physical performance, as well as increased risk for non-communicable diseases in later life(Reference Ross15). Consequently, ID monitoring, prevention and treatment programmes should not only be confined to settings where high levels are expected because of high prevalence of undernutrition as is often the case in low- and middle-income countries but also target areas where OW/OB is a concern.

A key challenge that needs to be addressed is the complexity of Fe status assessment in individuals with OW/OB(Reference Yanoff, Menzie and Denkinger16). Commonly used biochemical markers are often affected by dilution or inflammation(17). For example, increased blood volume in the OW/OB can dilute serum Fe leading to an overestimation of hypoferraemia(Reference Cepeda-Lopez, Zimmermann and Wussler6). Inflammation can also confound serum ferritin, transferrin saturation and transferrin receptor measures(Reference Cepeda-Lopez, Allende-Labastida and Melse-Boonstra7,Reference Suchdev, Williams and Mei11,Reference Yanoff, Menzie and Denkinger16) . Zheng et al. were able to assess several Fe metabolism biomarkers, but did not measure inflammation markers like C-reactive protein and α1-acid glycoprotein which are essential to apply correction to serum ferritin values(Reference Yanoff, Menzie and Denkinger16,Reference Thurnham, Northrop-Clewes and Knowles18) . Measurement of soluble transferrin receptor could have allowed calculation of total body Fe using the log ratio of soluble transferrin receptor:serum ferritin. Moreover, the regression-correction approach is one method to ameliorate inflammation-confounded estimates of population-level ID(Reference Suchdev, Williams and Mei11). More research is needed to determine the validity of inflammation-corrected estimates in OW/OB populations.

The ever-growing risk of the co-occurrence of OB and ID and the urgency for effective double-duty actions to address it call for more studies like that of Zheng et al. However, future studies should consider, whenever possible, a combination of Fe status biomarkers including measuring serum hepcidin and inflammatory markers like C-reactive protein and α1-acid glycoprotein to allow a more accurate interpretation. The definition of ID and interpretation of Fe status biomarkers in populations with high rates of OB are more complex and warrant further investigation. Commonly used strategies to control ID (e.g. Fe supplementation and fortification) may also need to be re-evaluated as they might not be effective in populations with high OW/OB prevalence.

Acknowledgements

Financial support: This manuscript received no specific grant from any funding agency, commercial or not-for-profit sectors. Conflict of interest: The author declared no conflicts of interest. Authorship: All authors contributed to the writing and editing of the paper. A.C.C.L. drafted the manuscript. All authors read and approved the final manuscript and shared primary responsibility for the final content. Ethics of human subject participation: This work was conducted according to the guidelines laid down in the Declaration of Helsinki.

References

World Health Organization (2017) The double burden of malnutrition. Policy brief. WHO.Google Scholar
Cepeda-Lopez, AC, Aeberli, I & Zimmermann, MB (2010) Does obesity increase risk for iron deficiency? A review of the literature and the potential mechanisms. Int J Vitam Nutr Res 80, 263270.CrossRefGoogle ScholarPubMed
Cepeda-Lopez, AC, Melse-Boonstra, A, Zimmermann, MBet al. (2015) In overweight and obese women, dietary iron absorption is reduced and the enhancement of iron absorption by ascorbic acid is one-half that in normal-weight women. Am J Clin Nutr 102, 13891397.CrossRefGoogle ScholarPubMed
Mujica-Coopman, MF, Brito, A, Lopez de Romana, Det al. (2015) Body mass index, iron absorption and iron status in childbearing age women. J Trace Elem Med Biol 30, 215219.CrossRefGoogle ScholarPubMed
Nemeth, E, Tuttle, MS, Powelson, Jet al. (2004) Hepcidin regulates cellular iron efflux by binding to ferroportin and inducing its internalization. Science 306, 20902093.CrossRefGoogle ScholarPubMed
Cepeda-Lopez, AC, Zimmermann, MB, Wussler, Set al. (2019) Greater blood volume and Hb mass in obese women quantified by the carbon monoxide-rebreathing method affects interpretation of iron biomarkers and iron requirements. Int J Obes 43, 9991008.10.1038/s41366-018-0127-9CrossRefGoogle ScholarPubMed
Cepeda-Lopez, AC, Allende-Labastida, J, Melse-Boonstra, Aet al. (2016) The effects of fat loss after bariatric surgery on inflammation, serum hepcidin, and iron absorption: a prospective 6-mo iron stable isotope study. Am J Clin Nutr 104, 10301038.CrossRefGoogle ScholarPubMed
Ausk, KJ & Ioannou, GN (2008) Is obesity associated with anemia of chronic disease? A population-based study. Obesity 16, 23562361.CrossRefGoogle ScholarPubMed
Petry, N, Olofin, I, Hurrell, RFet al. (2016) The proportion of anemia associated with iron deficiency in low, medium, and high human development index countries: a systematic analysis of national surveys. Nutrients 8, 693.CrossRefGoogle ScholarPubMed
Abbaspour, N, Hurrell, R & Kelishadi, R (2014) Review on iron and its importance for human health. J Res Med Sci 19, 164174.Google ScholarPubMed
Suchdev, PS, Williams, AM, Mei, Zet al. (2017) Assessment of iron status in settings of inflammation: challenges and potential approaches. Am J Clin Nutr 106, 1626S1633S.CrossRefGoogle ScholarPubMed
Chen, J & Chloupková, M (2009) Abnormal iron uptake and liver cancer. Cancer Biol Ther 8, 16991708.CrossRefGoogle ScholarPubMed
Moreno-Navarrete, JM, Moreno, M, Puig, Jet al. (2017) Hepatic iron content is independently associated with serum hepcidin levels in subjects with obesity. Clin Nutr 36, 14341439.CrossRefGoogle ScholarPubMed
Blasco, G, Puig, J, Daunis-i-Estadella, Jet al. (2014) Brain iron overload, insulin resistance, and cognitive performance in obese subjects: a preliminary MRI case–control study. Diabetes Care 37, 3076.CrossRefGoogle ScholarPubMed
Ross, AC (2017) Impact of chronic and acute inflammation on extra- and intracellular iron homeostasis. Am J Clin Nutr 106, 1581s1587s.CrossRefGoogle ScholarPubMed
Yanoff, LB, Menzie, CM, Denkinger, Bet al. (2007) Inflammation and iron deficiency in the hypoferremia of obesity. Int J Obes 31, 14121419.CrossRefGoogle ScholarPubMed
World Health Organization/Centers for Disease Control and Prevention (2005) Assessing the Iron Status of Populations. Report of a Joint World Health Organization/Centers for Disease Control and Prevention Technical Consultation on the Assessment of Iron Status at the Population Level. Geneva: WHO.Google Scholar
Thurnham, DI, Northrop-Clewes, CA & Knowles, J (2015) The use of adjustment factors to address the impact of inflammation on vitamin a and iron status in humans. J Nutr 145, 1137S1143S.CrossRefGoogle ScholarPubMed