Non-anaemic iron deficiency - a disease looking for recognition of diagnosis: a systematic review

Eur J Haematol. 2016 Jun;96(6):618-28. doi: 10.1111/ejh.12645. Epub 2015 Sep 17.


Objective: To capture all data meeting a rigid definition of non-anaemic iron deficiency (NAID) and determine whether it is associated with poor outcomes compared with normal iron status and whether iron supplementation improves outcomes in NAID.

Design: Systematic review.

Data sources: EMBASE, Medline, Web of Science,, International Clinical Trials Registry Platform (ICTRP) and Central from database inception to April 2014.

Eligibility criteria: Ferritin <16 μg/L (<12 μg/L if age <5 yr) in the absence of anaemia in observational studies or randomised trials. Where populations were deemed to be sufficiently similar, meta-analysis was undertaken.

Results: There were 21 studies included. NAID in pregnancy associated with reduction in birthweight (P = 0.028). Iron supplementation in NAID was associated with improvement in objective scores (P = 0.005) and self-rating (P = 0.03) of fatigue. Meta-analysis was limited and, where possible, was not statistically significant including the comparison of NAID with cardiovascular function in adults (VO2max P = 0.21, RERmax P = 0.68), educational attainment in children (P = 0.14), infant mental (P = 0.29) and psychomotor (P = 0.07) development, and iron supplementation in NAID with educational attainment in language (P = 0.31).

Conclusions: There is emerging evidence that NAID is a disease in its own right, deserving of further research in the development of strategies for detection and treatment.

Keywords: NAID; iron deficiency; non-anaemic iron deficiency.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Clinical Studies as Topic
  • Diagnosis, Differential*
  • Dietary Supplements
  • Female
  • Ferritins / blood
  • Humans
  • Iron / metabolism*
  • Iron Deficiencies*
  • Male
  • Phenotype*
  • Pregnancy


  • Ferritins
  • Iron