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Effectiveness of intermittent iron and high-dose vitamin A supplementation on hemoglobin, iron and vitamin A status of schoolchildren in southern Ethiopia: a randomized placebo controlled trial

European Journal of Clinical Nutrition (2025)Cite this article

Subjects

Abstract

Objective

We assessed the effectiveness of weekly iron and semestrial high-dose vitamin A supplementation on hemoglobin (Hb) concentration, and iron and vitamin A status of schoolchildren in rural Ethiopia.

Method

Using a 2 × 2 factorial design, 504 schoolchildren aged 7–10 years were randomly assigned to one of the four arms: control placebo; high-dose vitamin A; iron; or iron and high-dose vitamin A. Semestrial 200,000 IU vitamin A and weekly 42 mg of iron supplement were provided for 11 months. At baseline and at endline, Hb and serum concentrations of ferritin (sF), soluble transferrin receptor (sTfR), and retinol-binding protein (RBP) were measured. Serum indicators were adjusted for inflammation indicators, while Hb was adjusted for village altitude. Total body iron was calculated from sTfR and sF concentrations using an established formula.

Result

At baseline, prevalence of anemia (Hb < 11.0 g/dL), iron deficiency (sTfR > 8.3 mg/L or sF < 15 μg/L), iron-deficiency anemia, and vitamin A deficiency (RBP < 0.7 μmol/L) were 27.8%, 21.7%, 6.3% and 12.2%, respectively. Both iron and vitamin A supplementation had no significant effect on Hb, sTfR, and RBP concentrations. Supplementing iron weekly significantly increased sF (6.86 μg/L, 95%CI: 1.67, 12.05) and total body iron (0.45 mg/Kg, 95%CI: 0.17, 0.74), while semestrial vitamin A supplementation had no significant effect on both sF and total body iron.

Conclusion

Intermittent iron and vitamin A supplementation had no significant detectable effects on Hb, sTfR, and RBP concentrations of schoolchildren. Weekly iron supplementation improved sF concentrations. These findings suggest that providing iron and vitamin A supplements to populations where the extent of the deficiencies is not a major public health problem may not be beneficial.

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Fig. 1: Participants flowchart.
Fig. 2: Effects of intermittent iron supplementation and periodic high-dose vitamin A on iron and vitamin A biomarkers of schoolchildren, by intervention arm.

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Data availability

Data used in this analysis are available at https://osf.io/nwh7f.

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Acknowledgements

We would like to thank the children who participated in this study, their parents/guardians, school teachers, health extension workers of the village, district health and education offices, and the research team who made this study possible.

Funding

This work was conducted under the PhD studies of BTG, whose scholarship was partially funded by the Flemish Interuniversity Council (VLIR-UOS) in the context of the Institutional University Cooperation Program (IUC) with Arba Minch University https://www.vliruos.be/en/projects/project/22?pid=3604. Iron and iron-placebo supplements were produced and donated by Metagenics (Belgium, https://www.metagenics.eu/en_EU/). Vitamin A supplements and RDT kits were obtained from the Arba Minch town and Arba Minch Zuria district health offices. The funders had no role in the study design, data collection and analysis, decision to publish, or the preparation of the manuscript.

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Authors and Affiliations

  1. School of Public Health, College of Medicine and Health Sciences, Arba Minch University, Arba Minch, Ethiopia

    Befikadu Tariku Gutema, Muluken Bekele Sorrie, Eshetu Zerihun Tariku & Wanzahun Godana Boynito

  2. Department of Public Health and Primary Care, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium

    Muluken Bekele Sorrie, Eshetu Zerihun Tariku, Wanzahun Godana Boynito, Stefaan De Henauw & Souheila Abbeddou

  3. Department of Medical laboratory, College of Medicine and Health Sciences, Arba Minch University, Arba Minch, Ethiopia

    Sifray Batire Belayneh & Tsegaye Yohanes

  4. School of Medicine, College of Medicine and Health Sciences, Arba Minch University, Arba Minch, Ethiopia

    Tadiwos Hailu Zewdie

  5. Department of Translational Physiology, Infectiology and Public Health, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium

    Bruno Levecke

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  1. Befikadu Tariku Gutema
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Contributions

The authors’ contributions were as follows—SA, SDH, and BTG were responsible for the design of the study. BL trained the staff at Arba Minch University on the Kato Katz technique. BTG, MBS, SBB, EZT, WGB, THZ, and TY conducted the research and SA, BL, and BTG supervised data collection. BTG completed the statistical analyses and drafted the manuscript. SA contributed to the writing of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Befikadu Tariku Gutema.

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Competing interests

The authors declare no competing interests.

Ethics approval

The study was conducted in accordance with the Declaration of Helsinki, and all procedures were approved by the Commission on Medical Ethics of Ghent University Hospital, Ghent, Belgium (EC/2019/1289) and by the National Research Ethics Review Committee of the Ministry of Science and Higher Education, Ethiopia (P.S.M/14.1/505/20). The study is registered on clinicaltrials.gov with the reference number NCT04137354 (https://clinicaltrials.gov/study/NCT04137354). Letters of permission were written for district administrations, district health and education offices, kebele leaders, and school directors. Following contact with school directors, a sensitization workshop was organized for directors, teachers, and parents. Informed written consent for the children’s participation was obtained from their parents, and assent was obtained from the children.

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41430_2025_1678_MOESM1_ESM.docx

Supplemental tables for subgroup analysis using baseline characteristics of the study participants to investigate the effectiveness of the supplementation intervention on outcomes

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Gutema, B.T., Sorrie, M.B., Belayneh, S.B. et al. Effectiveness of intermittent iron and high-dose vitamin A supplementation on hemoglobin, iron and vitamin A status of schoolchildren in southern Ethiopia: a randomized placebo controlled trial. Eur J Clin Nutr (2025). https://doi.org/10.1038/s41430-025-01678-y

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