Iron Status in Attention-Deficit/Hyperactivity Disorder: A Systematic Review and Meta-Analysis

PLoS One. 2017 Jan 3;12(1):e0169145. doi: 10.1371/journal.pone.0169145. eCollection 2017.


Background: Attention-deficit/hyperactivity disorder (ADHD) is one of the most common psychiatric disorders in children. However, the pathogenesis of ADHD remains unclear. Iron, an important trace element, is implicated in brain function and dopaminergic activity. Recent studies have investigated the association between iron deficiency and ADHD, but the results are inconsistent.

Methods: A systemic search of MEDLINE, EMBASE, Web of Science and Cochrane Library databases was supplemented by manual searches of references of key retrieved articles. Study quality was evaluated using the Newcastle-Ottawa Scale. The standardised mean difference (SMD) and 95% confidence intervals (CIs) were calculated using a random-effects model. H2 and I2 were used to evaluate the heterogeneity, and sensitivity, subgroup and meta-regression analyses were conducted to explore the reason of heterogeneity.

Results: The search yielded 11 studies published before July 25, 2016. Of these, 10 studies, comprising 2191 participants and 1196 ADHD cases, reported serum ferritin levels, and six studies, comprising 617 participants and 369 ADHD cases, reported serum iron levels. Serum ferritin levels were lower in ADHD cases (SMD = -0.40, 95% CI = -0.66 to -0.14). However, we found no correlation between serum iron levels and ADHD (SMD = -0.026, 95% CI = -0.29 to 0.24). Meta-regression analysis indicated that publication year, age, gender, sample size, and Hb levels did not significantly influence the pooled estimates of serum ferritin.

Conclusion: Lower serum ferritin rather than serum iron is associated with ADHD in children.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Attention Deficit Disorder with Hyperactivity / blood*
  • Brain / physiology
  • Child
  • Dopamine / metabolism
  • Female
  • Ferritins / blood
  • Humans
  • Iron / blood*
  • Male
  • Sample Size


  • Ferritins
  • Iron
  • Dopamine

Grant support

This work was supported by the National Science Foundation of China (No. 81330016, 81630038 and 81270724), the Major State Basic Research Development Program (2013CB967404 and 2012BAl04B00), grants from the Ministry of Education of China (IRT0935), a grant from the Science and Technology Bureau of Sichuan province (2014SZ0149 and 2016TD0002), and a grant from the clinical discipline program (neonatology) from the Ministry of Health of China (1311200003303).