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Iron incorporation in red blood cells of pediatric sickle cell anemia: a stable isotope pilot investigation

European Journal of Clinical Nutrition volume 78, pages 801–807 (2024)Cite this article

Subjects

Abstract

Background/Objectives

Sickle cell anemia (SCA) is marked by hypoxia, inflammation, and secondary iron overload (IO), which potentially modulate hepcidin, the pivotal hormone governing iron homeostasis. The aim was to evaluate the iron incorporation in red blood cells (RBC) in SCA pediatric patients, considering the presence or absence of IO.

Subjects/Methods

SCA children (n = 12; SCAtotal) ingested an oral stable iron isotope (57Fe) and iron incorporation in RBC was measured after 14 days. Patients with ≥1000 ng/mL serum ferritin were considered to present IO (SCAio+; n = 4) while the others were classified as being without IO (SCAio−; n = 8). Liver iron concentration (LIC) was determined by Magnetic Resonance Imaging (MRI) T2* method.

Results

The SCAio+ group had lower iron incorporation (mean ± SD: 0.166 ± 0.04 mg; 3.33 ± 0.757%) than SCAio− patients (0.746 ± 0.303 mg; 14.9 ± 6.05%) (p = 0.024). Hepcidin was not different between groups. Iron incorporation was inversely associated with serum ferritin level (SCAtotal group: r = −0.775, p = 0.041; SCAio− group: r = −0.982; p = 0.018) and sickle hemoglobin (HbS) presented positive correlation with iron incorporation (r = 0.991; p = 0.009) in SCAio− group. LIC was positively associated with ferritin (SCAtotal: r = 0.921; p = 0.026) and C reactive protein (SCAio+: r = 0.999; p = 0.020).

Conclusion

SCAio+ group had lower iron incorporation in RBC than SCAio− group, suggesting that they may not need to reduce their intake of iron-rich food, as usually recommended. Conversely, a high percentage of HbS may indirectly exacerbate hypoxia and seems to increase iron incorporation in RBC.

Trial Registration

This trial was registered at www.ensaiosclinicos.gov.br. Identifier RBR-4b7v8pt.

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Fig. 1: Flowchart of participant’s enrollment.
Fig. 2: Comparison of iron homeostasis markers between SCAio− and SCAio+ groups.
Fig. 3: Correlations of iron incorporation in RBC with ferritin and HbS and correlations of LIC with ferritin and CRP.

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Data availability

Data analyzed in this study are available from the corresponding author on reasonable request.

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Acknowledgements

We would like to thank all the volunteers who participated in this study and the excellent technical assistance provided by Isis Rodrigues, Viviane F. Meneses, Clarice M. Carvalho, Valdilene L. Souza, Elizabeth Pereira and Verônica Barbosa.

Funding

This study was funded by the Ministry of Health (Grant no. 777022/2012); Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) (Grant no. 408401/2017-6); Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) (Finance Code 001); Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (Grant no. E-26-010.100930/2018 and E-26/200.963/2022).

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Author notes

  1. These authors contributed equally: Juliana Omena, Vanessa Monteiro Voll.

Authors and Affiliations

  1. Nutrition Institute, Rio de Janeiro State University, Rio de Janeiro, Brazil

    Juliana Omena, Vanessa Monteiro Voll, Flávia Fioruci Bezerra, Cláudia dos Santos Cople Rodrigues & Marta Citelli

  2. Institute of Chemistry, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil

    Bernardo Ferreira Braz & Ricardo Erthal Santelli

  3. National Institute of Science & Technology of Bioanalytics (INCTBio), Campinas, Brazil

    Bernardo Ferreira Braz & Ricardo Erthal Santelli

  4. School of Nutrition, University of the Republic, Montevideo, Uruguay

    Carmen Marino Donangelo

  5. Radiology Department, Pedro Ernesto University Hospital, Rio de Janeiro, Brazil

    Gustavo Federico Jauregui

  6. Hematology Department, Pedro Ernesto University Hospital, Rio de Janeiro, Brazil

    Andrea Soares Ribeiro

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Contributions

MC, JO, FFB, and CSCR designed the study; CMD contributed to the design of the work; MC and CSCR were responsible for obtaining funding; JO, MC, and VMV conducted the research; JO, VMV, MC, BFB and RES conducted the laboratory analysis; FFB and CMD helped to interpret the data and provided critical suggestions and comments; GFJ and ASR conducted the MRI procedures; JO, VMV, FFB, and MC performed the statistical analysis; JO, VMV, and MC wrote the manuscript, and had primary responsibility for the final content. All authors read, contributed and approved the final manuscript.

Corresponding authors

Correspondence to Juliana Omena or Marta Citelli.

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The authors declare no competing interests.

Ethical approval

This research was performed in accordance with the Declaration of Helsinki and was approved by the Clinical Research Ethics Committee of State Institute of Hematology Arthur de Siqueira Cavalcanti (419/17; 2.788.659) and Pedro Ernesto University Hospital (2.695.418). The study was conducted only on children whose parents or guardians agreed to their participation and signed a free and informed consent form. The study was registered at www.ensaiosclinicos.gov.br (Identifier RBR-4b7v8pt).

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Omena, J., Voll, V.M., Bezerra, F.F. et al. Iron incorporation in red blood cells of pediatric sickle cell anemia: a stable isotope pilot investigation. Eur J Clin Nutr 78, 801–807 (2024). https://doi.org/10.1038/s41430-024-01465-1

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