Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Nutrition in acute and chronic diseases

Non-anemic iron deficiency: correlations between symptoms and iron status parameters

European Journal of Clinical Nutrition volume 76, pages 835–840 (2022)Cite this article

Subjects

Abstract

Objectives

To register all symptoms reported by non-anemic menstruating women, and examine the links between these symptoms and iron status parameters available including serum ferritin (SF) in primary care.

Subjects and methods

In this cross-sectional study, we collected clinical and biological data from 780 French menstruating women aged 18–50 years. The data included an anonymous questionnaire (biometric information, physical and cognitive symptoms, reduction in physical performance, current quality of life with SF-36 questionnaire) and seven biological parameters available in primary care. We excluded women with anemia (hemoglobin < 12 g/dl) or chronic disease. Correlations were studied for 554 participants in bivariate analysis (BVA) and multivariate analysis (MVA), with adjusted odds ratio (OR). Receiver operating characteristic (ROC) curves were established for significant correlations in MVA (p < 0.05).

Results

Among these 554 non-anemic women included, 304 (54.9%) had SF level below 50 µg/l, 103 (18.6%) had SF level below 20 µg/l, and 60 (10.8%) had SF level below 15 µg/l. Iron deficiency was significantly correlated with recent hair loss for SF ≤ 15 µg/l (OR = 2.19 with p = 0.02 in MVA) and SF ≤ 20 µg/l (OR = 2.26 with p < 0.01 in MVA). SF ≤ 20 µg/l was also correlated with limitations due to emotional problems according to SF-36 questionnaire (p = 0.01 in MVA). SF ≤ 50 µg/l was significantly correlated with restless legs syndrome (OR = 2.82 with p = 0.01 in MVA). Only one ROC curve for restless legs syndrome could suggest an optimal SF cut-off point at 39 µg/l (sensitivity 73%, specificity 61%).

Conclusion

We identified two symptoms significantly more reported by non-anemic iron-deficient menstruating women: recent hair loss for serum ferritin (SF) ≤ 20 µg/l and restless legs syndrome for SF ≤ 50 µg/l. Non-anemic iron deficiency may also impact their quality of life, but further investigation is needed. If one of these symptoms is reported in primary care, the possibility of a symptomatic iron deficiency cannot be ruled out, and iron supplementation should be considered.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. ACC/SCN. Fourth report on the world nutrition situation. Washington, DC: ASS/SCN; 2000.

  2. Galan P, Yoon HC, Preziosi P, Viteri F, Valeix P, Fieux B, et al. Determining factors in the iron status of adult women in the SU.VI.MAX study. Supplementation en vitamines et minéraux antioxydants. Eur J Clin Nutr. 1998;52:383–8.

    Article  CAS  Google Scholar 

  3. Hinton PS, Giordano C, Brownlie T, Haas JD. Iron supplementation improves endurance after training in iron-depleted, nonanemic women. J Appl Physiol. 2000;88:1103–11.

    Article  CAS  Google Scholar 

  4. Brutsaert TD, Hernandez-Cordero S, Rivera J, Viola T, Hughes G, Haas JD. Iron supplementation improves progressive fatigue resistance during dynamic knee extensor exercise in iron-depleted, nonanemic women. Am J Clin Nutr. 2003;77:441–8.

    Article  CAS  Google Scholar 

  5. Crouter SE, DellaValle DM, Haas JD. Relationship between physical activity, physical performance, and iron status in adult women. Appl Physiol Nutr Metab. 2012;37:697–705.

    Article  CAS  Google Scholar 

  6. Bruner AB, Joffe A, Duggan AK, Casella JF, Brandt J. Randomised study of cognitive effects of iron supplementation in non-anaemic iron-deficient adolescent girls. Lancet. 1996;348:992–6.

    Article  CAS  Google Scholar 

  7. Murray-Kolb LE, Beard JL. Iron treatment normalizes cognitive functioning in young women. Am J Clin Nutr. 2007;85:778–87.

    Article  CAS  Google Scholar 

  8. Grondin MA, Ruivard M, Perrève A, Derumeaux-Burel H, Perthus I, Roblin J, et al. Prevalence of iron deficiency and health-related quality of life among female students. J Am Coll Nutr. 2008;27:337–41.

    Article  Google Scholar 

  9. Verdon F, Burnand B, Stubi CL, Bonard C, Graff M, Michaud A, et al. Iron supplementation for unexplained fatigue in non-anaemic women: double blind randomised placebo controlled trial. BMJ. 2003;326:1124.

    Article  CAS  Google Scholar 

  10. Vaucher P, Druais PL, Waldvogel S, Favrat B. Effect of iron supplementation on fatigue in nonanemic menstruating women with low ferritin: a randomized controlled trial. CMAJ. 2012;184:1247–54.

    Article  Google Scholar 

  11. Favrat B, Balck K, Breymann C, Hedenus M, Keller T, Mezzacasa A, et al. One 1000 mg iron dose of ferric carboxymaltose improved fatigue in iron-deficient, non-anaemic women in the randomised placebo-controlled study PREFER. BJOG. 2012;119:232–3.

    Google Scholar 

  12. Krayenbuehl PA, Battegay E, Breymann C, Furrer J, Schulthess G. Intravenous iron for the treatment of fatigue in nonanemic, premenopausal women with low serum ferritin concentration. Blood. 2011;118:3222–7.

    Article  CAS  Google Scholar 

  13. Sharma R, Stanek J, Koch T, Grooms L, O’Brien S. Intravenous iron therapy in non-anemic iron-deficient menstruating adolescent females with fatigue. Am J Hematol. 2016;91:973–7.

    Article  CAS  Google Scholar 

  14. Tison F, Crochard A, Leger D, Boue´e S, Lainey E, El, et al. Epidemiology of restless legs syndrome in French adults: A nationwide survey: The INSTANT Study. Neurology. 2005;65:239–46. 26

    Article  CAS  Google Scholar 

  15. O′Keeffe ST, Gavin K, Lavan JN. Iron status and restless legs syndrome in the elderly. Age Ageing. 1994;23:200–2.

    Article  Google Scholar 

  16. Trenkwalder C, Allen R, Hogl B, Paulus W, Winkelmann J. Restless legs syndrome associated with major diseases: a systematic review and new concept. Neurology. 2016;86:1336–43.

    Article  CAS  Google Scholar 

  17. Allen RP, Adler CH, Du W, Butcher A, Bregman DB, Earley CJ. Clinical efficacy and safety of IV ferric carboxymaltose (FCM) treatment of RLS: a multi-centred, placebo-controlled preliminary clinical trial. Sleep Med. 2011;12:906–13.

    Article  Google Scholar 

  18. Trenkwalder C, Winkelmann J, Oertel W, Virgin G, Roubert B, Mezzacasa. Ferric carboxymaltose in patients with restless legs syndrome and nonanemic iron deficiency: a randomized trial. Mov Disord. 2017;32:1478–82.

    Article  CAS  Google Scholar 

  19. Vignatelli L, Billiard M, Clarenbach P, Garcia-Borreguero D, Kaynak D, Liesiene V, et al. EFNS guidelines on management of restless legs syndrome and periodic limb movement disorder in sleep. Eur J Neurol. 2006;13:1049–65.

    Article  CAS  Google Scholar 

  20. Rushton DH. Nutritional factors and hair loss. Clin Exp Dermatol. 2002;27:396–404.

    Article  CAS  Google Scholar 

  21. Trost LB, Bergfeld WF, Calogeras E. The diagnosis and treatment of iron deficiency and its potential relationship to hair loss. J Am Acad Dermatol. 2006;54:824–44.

    Article  Google Scholar 

  22. Camaschella C. Iron-deficiency anemia. N Engl J Med. 2015;372:1832–43.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Service Médecine Interne, CHU Estaing, Clermont-Ferrand, France

    Julien Beatrix & Marc Ruivard

  2. Service Hématologie, Gen-Bio, Clermont-Ferrand, France

    Claire Piales & Eric Marchiset

  3. Service Santé Publique, CHU Gabriel Montpied, Clermont-Ferrand, France

    Pauline Berland & Laurent Gerbaud

  4. UMR 6602 UCA/CNRS/SIGMA - T.G.I., Université Clermont Auvergne, Clermont-Ferrand, France

    Laurent Gerbaud & Marc Ruivard

Authors
  1. Julien Beatrix
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Claire Piales
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pauline Berland
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eric Marchiset
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Laurent Gerbaud
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Marc Ruivard
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JB and MR were responsible for designing the study. JB, CP, and EM were responsible for data collection and management. PB and LG were responsible for statistical analysis. JB and MR were responsible for writing and editing the manuscript.

Corresponding author

Correspondence to Julien Beatrix.

Ethics declarations

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Beatrix, J., Piales, C., Berland, P. et al. Non-anemic iron deficiency: correlations between symptoms and iron status parameters. Eur J Clin Nutr 76, 835–840 (2022). https://doi.org/10.1038/s41430-021-01047-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41430-021-01047-5

Search

Advanced search

Quick links