Skip to main content
SpringerLink
Log in

The Role of Zinc in the Etiology of Anemia

  • Chapter
  • First Online:
Nutritional Anemia

Part of the book series: Nutrition and Health ((NH))

  • 548 Accesses

Abstract

Zinc could play a causal role in the etiology of anemia because of its many required functions in iron metabolism and immune health. Zinc deficiency and anemia often coexist, especially in low-income settings, where there are low intakes of iron and zinc, high intakes of phytates, and increased risk of inflammation. Although it is unknown to what degree zinc deficiency can exacerbate or even independently cause anemia, there are several steps in which zinc is required in the regulation of hematopoiesis. Directly, decreased zinc availability could impair expression of iron transporters and other regulatory proteins important for iron homeostasis and erythroid development. Indirectly, decreased zinc availability could alter immune response and increase oxidative stress, both of which can interfere with hemoglobin production. However, zinc supplementation studies with cell lines, animals, and humans have not consistently shown an increase in hemoglobin concentrations. Therefore, the degree to which zinc affects anemia, if any, remains unclear and needs further investigation.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. King JC, Brown KH, Gibson RS, Krebs NF, Lowe NM, Siekmann JH, et al. Biomarkers of Nutrition for Development (BOND)-Zinc Review. J Nutr. 2015;146(4):858S–85S.

    Article  Google Scholar 

  2. International Zinc Nutrition Consultative Group (IZiNCG). International Zinc Nutrition Consultative Group (IZiNCG) website. https://www.izincg.org/riskzincdeficiency.

  3. World Health Organization (WHO). Micronutrient Database. https://www.who.int/vmnis/database/en/.

  4. Development Initiatives Poverty Research Ltd. 2020 global nutrition report: action on equity to end malnutrition. Bristol, UK: Development Initiatives; 2020. https://globalnutritionreport.org/reports/global-nutrition-report-2018/three-issues-critical-need-attention/.

    Google Scholar 

  5. World Health Organization (WHO). The global prevalence of anaemia in 2011. Geneva: World Health Organization (WHO); 2015. https://apps.who.int/iris/bitstream/handle/10665/177094/9789241564960_eng.pdf;jsessionid=78BE360BA88056636E540876AD4D2D37?sequence=1.

    Google Scholar 

  6. Wessells KR, Brown KH. Estimating the global prevalence of zinc deficiency: results based on zinc availability in national food supplies and the prevalence of stunting. PLoS One. 2012;7(11):e50568.

    Article  Google Scholar 

  7. Hess SY. National risk of zinc deficiency as estimated by national surveys. Food Nutr Bull. 2017;38(1):3–17.

    Article  Google Scholar 

  8. Gupta S, Brazier AKM, Lowe NM. Zinc deficiency in low- and middle-income countries: prevalence and approaches for mitigation. J Hum Nutr Diet. 2020;33(5):624–43.

    Article  CAS  Google Scholar 

  9. Harika R, Faber M, Samuel F, Mulugeta A, Kimiywe J, Eilander A. Are low intakes and deficiencies in iron, vitamin A, zinc, and iodine of public health concern in Ethiopian, Kenyan, Nigerian, and South African children and adolescents? Food Nutr Bull. 2017;38(3):405–27.

    Article  Google Scholar 

  10. Roos N, Ponce MC, Doak CM, Dijkhuizen M, Polman K, Chamnan C, et al. Micronutrient status of populations and preventive nutrition interventions in South East Asia. Matern Child Health J. 2019;23(S1):29–45.

    Article  CAS  Google Scholar 

  11. Wieringa F, Dahl M, Chamnan C, Poirot E, Kuong K, Sophonneary P, et al. The high prevalence of anemia in Cambodian children and women cannot be satisfactorily explained by nutritional deficiencies or hemoglobin disorders. Nutrients. 2016;8(6):348.

    Article  Google Scholar 

  12. Houghton LA, Parnell WR, Thomson CD, Green TJ, Gibson RS. Serum zinc is a major predictor of anemia and mediates the effect of selenium on hemoglobin in school-aged children in a nationally representative survey in New Zealand. J Nutr. 2016;146(9):1670–6.

    Article  CAS  Google Scholar 

  13. Gibson RS, Abebe Y, Stabler S, Allen RH, Westcott JE, Stoecker BJ, et al. Zinc, gravida, infection, and iron, but not vitamin B-12 or folate status, predict hemoglobin during pregnancy in Southern Ethiopia. J Nutr. 2008;138(3):581–6.

    Article  CAS  Google Scholar 

  14. Greffeuille V, Fortin S, Gibson R, Rohner F, Williams A, Young MF, et al. Associations between zinc and hemoglobin concentrations in preschool children and women of reproductive age: an analysis of representative survey data from the Biomarkers Reflecting Inflammation and Nutritional Determinants of Anemia (BRINDA) project. Pending.

    Google Scholar 

  15. Ece A, Uyanik BS, Işcan A, Ertan P, Yiğitoğlu MR. Increased serum copper and decreased serum zinc levels in children with iron deficiency anemia. Biol Trace Elem Res. 1997;59(1–3):31–9.

    Article  CAS  Google Scholar 

  16. Ma A-G, Chen X-C, Xu R-X, Zheng M-C, Wang Y, Li J-S. Comparison of serum levels of iron, zinc and copper in anaemic and non-anaemic pregnant women in China. Asia Pac J Clin Nutr. 2004;13(4):348–52.

    CAS  Google Scholar 

  17. Gebremedhin S, Enquselassie F, Umeta M. Prevalence of prenatal zinc deficiency and its association with socio-demographic, dietary and health care related factors in rural Sidama, Southern Ethiopia: a cross-sectional study. BMC Public Health. 2011;11:898.

    Article  CAS  Google Scholar 

  18. Kelkitli E, Ozturk N, Aslan NA, Kilic-Baygutalp N, Bayraktutan Z, Kurt N, et al. Serum zinc levels in patients with iron deficiency anemia and its association with symptoms of iron deficiency anemia. Ann Hematol. 2016;95(5):751–6.

    Article  CAS  Google Scholar 

  19. Palacios AM, Hurley KM, De-Ponce S, Alfonso V, Tilton N, Lambden KB, et al. Zinc deficiency associated with anaemia among young children in rural Guatemala. Matern Child Nutr. 2020;16(1):e12885.

    Article  Google Scholar 

  20. Atasoy HI, Bugdayci G. Zinc deficiency and its predictive capacity for anemia: unique model in school children. Pediatr Int. 2018;60(8):703–9.

    Article  CAS  Google Scholar 

  21. Shamim AA, Kabir A, Merrill RD, Ali H, Rashid M, Schulze K, et al. Plasma zinc, vitamin B(12) and α-tocopherol are positively and plasma γ-tocopherol is negatively associated with Hb concentration in early pregnancy in north-west Bangladesh. Public Health Nutr. 2013;16(8):1354–61.

    Article  Google Scholar 

  22. Ames BN. Low micronutrient intake may accelerate the degenerative diseases of aging through allocation of scarce micronutrients by triage. Proc Natl Acad Sci U S A. 2006;103(47):17589–94.

    Article  CAS  Google Scholar 

  23. Ferreira GC. Heme synthesis. In: Encyclopedia of biological chemistry. 2nd edn. 2013.

    Google Scholar 

  24. Information on EC 4.2.1.24—porphobilinogen synthase. BRENDA—the comprehensive enzyme information system. https://www.brenda-enzymes.org/enzyme.php?ecno=4.2.1.24.

  25. Information on EC 1.15.1.1—superoxide dismutase. BRENDA—the comprehensive enzyme information system. https://www.brenda-enzymes.org/enzyme.php?ecno=1.15.1.1&UniProtAcc=Q9YE27&OrganismID=171.

  26. Iuchi Y, Okada F, Onuma K, Onoda T, Asao H, Kobayashi M, et al. Elevated oxidative stress in erythrocytes due to a SOD1 deficiency causes anaemia and triggers autoantibody production. Biochem J. 2007;402(2):219–27.

    Article  CAS  Google Scholar 

  27. Sangkhae V, Nemeth E. Regulation of the Iron Homeostatic Hormone Hepcidin123. Adv Nutr. 2017;8(1):126–36.

    Article  CAS  Google Scholar 

  28. Ginzburg YZ. Hepcidin-Ferroportin axis in health and disease. In Vitamins and hormones. Elsevier; 2019. p. 17–45. https://linkinghub.elsevier.com/retrieve/pii/S0083672919300020.

  29. Knez M, Graham RD, Welch RM, Stangoulis JCR. New perspectives on the regulation of iron absorption via cellular zinc concentrations in humans. Crit Rev Food Sci Nutr. 2017;57(10):2128–43.

    Article  CAS  Google Scholar 

  30. Liu M-J, Bao S, Napolitano JR, Burris DL, Yu L, Tridandapani S, et al. Zinc regulates the acute phase response and serum amyloid A production in response to sepsis through JAK-STAT3 signaling. PLoS One. 2014;9(4):e94934.

    Article  Google Scholar 

  31. Kondaiah P, Yaduvanshi PS, Sharp PA, Pullakhandam R. Iron and zinc homeostasis and interactions: does enteric zinc excretion cross-talk with intestinal iron absorption? Nutrients. 2019;11(8)

    Google Scholar 

  32. Zhang Y, Wang L, Dey S, Alnaeeli M, Suresh S, Rogers H, et al. Erythropoietin action in stress response, tissue maintenance and metabolism. Int J Mol Sci. 2014;15(6):10296–333.

    Article  Google Scholar 

  33. Haase VH. Regulation of erythropoiesis by hypoxia-inducible factors. Blood Rev. 2013;27(1):41–53.

    Article  CAS  Google Scholar 

  34. Lee SR. Critical role of zinc as either an antioxidant or a prooxidant in cellular systems. Oxid Med Cell Longev. 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5884210/.

  35. Maret W. Zinc biochemistry: from a single zinc enzyme to a key element of life12. Adv Nutr. 2013;4(1):82–91.

    Article  CAS  Google Scholar 

  36. Liem RKH. Cytoskeletal integrators: the spectrin superfamily. Cold Spring Harb Perspect Biol. 2016;8(10):a018259.

    Article  Google Scholar 

  37. Paterson PG, Card RT. The effect of zinc deficiency on erythrocyte deformability in the rat. J Nutr Biochem. 1993;4(4):250–5.

    Article  CAS  Google Scholar 

  38. Maywald M, Wessels I, Rink L. Zinc signals and immunity. Int J Mol Sci. 2017;18(10). https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5666901/.

  39. Weiss G, Goodnough LT. Anemia of chronic disease. N Engl J Med. 2005;352(10):1011–23.

    Article  CAS  Google Scholar 

  40. Kassebaum NJ. The global burden of anemia. Hematol Clin. 2016;30(2):247–308.

    Google Scholar 

  41. World Health Organization (WHO). Nutritional anaemias: tools for effective prevention and control. 2017. 96p. https://www.who.int/publications/i/item/9789241513067.

  42. Chen Y-H, Shiu J-R, Ho C-L, Jeng S-S. Zinc as a signal to stimulate red blood cell formation in fish. Int J Mol Sci. 2017;18(1).

    Google Scholar 

  43. Chen Y-H, Feng H-L, Jeng S-S. Zinc supplementation stimulates red blood cell formation in rats. Int J Mol Sci. 2018;19(9).

    Google Scholar 

  44. Brown KH, Peerson JM, Baker SK, Hess SY. Preventive zinc supplementation among infants, preschoolers, and older prepubertal children. Food Nutr Bull. 2009;30(1 Suppl):S12–40.

    Article  Google Scholar 

  45. Dekker LH, Villamor E. Zinc supplementation in children is not associated with decreases in hemoglobin concentrations. J Nutr. 2010;140(5):1035–40.

    Article  CAS  Google Scholar 

  46. Mayo-Wilson E, Imdad A, Junior J, Dean S, Bhutta ZA. Preventive zinc supplementation for children, and the effect of additional iron: a systematic review and meta-analysis. BMJ Open. 2014;4(6):e004647.

    Article  Google Scholar 

  47. Petry N, Olofin I, Boy E, Donahue Angel M, Rohner F. The effect of low dose iron and zinc intake on child micronutrient status and development during the first 1000 days of life: a systematic review and meta-analysis. Nutrients. 2016;8(12).

    Google Scholar 

  48. Campos Ponce M, Polman K, Roos N, Wieringa FT, Berger J, Doak CM. What approaches are most effective at addressing micronutrient deficiency in children 0–5 years? A review of systematic reviews. Matern Child Health J. 2019;23(Suppl 1):4–17.

    Article  CAS  Google Scholar 

  49. Barffour MA, Hinnouho G-M, Kounnavong S, Wessells KR, Ratsavong K, Bounheuang B, et al. Effects of daily zinc, daily multiple micronutrient powder, or therapeutic zinc supplementation for diarrhea prevention on physical growth, anemia, and micronutrient status in rural Laotian children: a randomized controlled trial. J Pediatr. 2019;207:80–89.e2.

    Article  CAS  Google Scholar 

  50. Noor RA, Abioye AI, Darling AM, Hertzmark E, Aboud S, Premji Z, et al. Prenatal zinc and vitamin a reduce the benefit of iron on maternal hematologic and micronutrient status at delivery in Tanzania. J Nutr. 2020;150(2):240–8.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. UCSF Benioff Children’s Hospital Oakland, Oakland, CA, USA

    David W. Killilea

  2. Department of Biological Sciences, City College of San Francisco, San Francisco, CA, USA

    Jonathan H. Siekmann

Authors
  1. David W. Killilea
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jonathan H. Siekmann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Jonathan H. Siekmann .

Editor information

Editors and Affiliations

  1. Human Nutrition, The University of British Columbia, Vancouver, BC, Canada

    Crystal D. Karakochuk

  2. Institute of Food Nutrition and Health, ETH Zurich, Zürich, Zürich, Switzerland

    Michael B. Zimmermann

  3. Department of Health, University of Applied Sciences of South Switzerland (SUPSI) and Swiss Distance University of Applied Sciences (FFHS), Zürich, Zürich, Switzerland

    Diego Moretti

  4. International Health, Sight and Life Foundation and Johns Hopkins School of Public Health, Basel, Switzerland

    Klaus Kraemer

Ethics declarations

Neither of the authors declare a conflict of interest with regard to this manuscript. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of UCSF or City College of San Francisco.

Rights and permissions

Reprints and permissions

Copyright information

© 2022 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Killilea, D.W., Siekmann, J.H. (2022). The Role of Zinc in the Etiology of Anemia. In: Karakochuk, C.D., Zimmermann, M.B., Moretti, D., Kraemer, K. (eds) Nutritional Anemia. Nutrition and Health. Springer, Cham. https://doi.org/10.1007/978-3-031-14521-6_14

Download citation

  • DOI: https://doi.org/10.1007/978-3-031-14521-6_14

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-031-14520-9

  • Online ISBN: 978-3-031-14521-6

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation