Peer-reviewed article
Iron Deficiency and Human Brain Electrophysiology Across the Lifespan: A Systematic and Mechanistic Review of Resting EEG, Event-Related Potentials, and Treatment Responsiveness.
Chmiel J, Góral-Półrola J, Leśnicka P, Kopańska M ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This systematic review examined how iron deficiency affects brain electrical activity across all ages, from infants to adults. The researchers found that iron deficiency is linked to changes in brain wave patterns, including increased slow waves and reduced alpha activity, as well as delays in how the brain processes information. Iron supplementation improved some of these brain electrical markers, though recovery was variable and some changes persisted even after iron levels normalized. The review identified limitations in existing studies, including small sample sizes and inconsistent methods across different research groups.
Key points
- Iron deficiency was commonly associated with increased slow-wave activity and reduced alpha activity in the brain
- Sensory and cognitive processing was delayed, with prolonged P300 and N2 latencies observed
- Iron supplementation improved several brain electrical outcomes, but recovery was variable and some abnormalities persisted after hematological correction
- Findings suggest iron deficiency disrupts timing, synchronization, and maturation of neural activity through impaired energy metabolism and neurotransmission
- No specific electrophysiological biomarker can currently be established as a definitive indicator of iron deficiency
Limitations
The review was limited by heterogeneous diagnostic criteria across studies, small sample sizes, inconsistent EEG methods, residual confounding, variable risk of bias, and some non-independence of reports from overlapping cohorts. The contextual anemia evidence from non-iron-specific conditions could not be directly interpreted as showing iron-specific effects.
Abstract
Introduction Iron is essential for cerebral energy metabolism, neurotransmitter synthesis, myelination, and neural development. Iron deficiency may therefore impair brain function even before overt anemia develops. This systematic and mechanistic review synthesized EEG findings associated with iron deficiency across the lifespan and evaluated electrophysiological changes following iron treatment. Materials and methods PubMed/MEDLINE, Scopus, Web of Science, Embase, PsycINFO, and Google Scholar were searched from inception to July 2026. Human studies examining iron deficiency or iron-deficiency anemia using EEG, quantitative EEG, task-related oscillations, event-related potentials, or cortical-evoked potentials formed the core evidence base. Two additional studies of chronic kidney disease-related or mixed-etiology anemia were retained as contextual evidence to help distinguish iron-specific electrophysiological effects from abnormalities associated more generally with anemia severity and reduced oxygen-carrying capacity. Risk of bias was assessed using RoB 2 and ROBINS-I. Because of substantial heterogeneity, findings were synthesized narratively. Results Thirty reports were retained for narrative synthesis, covering participants from the neonatal period to adulthood. Twenty-eight formed the core iron-specific evidence base, whereas two were analyzed separately as contextual anemia evidence. Iron deficiency was commonly associated with increased slow-wave activity, reduced alpha activity, delayed sensory and cognitive processing, prolonged P300 and N2 latencies, altered frontal alpha asymmetry, and impaired differentiation between relevant and irrelevant stimuli. Reductions in P300 amplitude were less consistent but were observed in severe anemia, demanding cognitive tasks, and after infantile iron-deficiency anemia. Iron supplementation improved several spectral and ERP outcomes, although recovery was variable and some abnormalities persisted after hematological correction. Interpretation was limited by heterogeneous diagnostic criteria, small samples, inconsistent EEG methods, residual confounding, variable risk of bias, and the partial non-independence of reports arising from overlapping longitudinal cohorts or parent trials. Findings from the contextual anemia studies were not interpreted as direct evidence of an effect of iron deficiency. Conclusions Iron deficiency may disrupt the timing, synchronization, and maturation of neural activity through impaired energy metabolism, neurotransmission, myelination, and synaptic development. EEG may be useful for detecting functional brain alterations and monitoring treatment response, but no specific electrophysiological biomarker can currently be established.