Psychiatric and cognitive outcomes of iron supplementation in non-anemic children, adolescents, and menstruating adults: A meta-analysis and systematic review.
Level 1 - systematic review of randomized trials
Systematic review and meta-analysis of randomized controlled trials (alongside pre-post studies)
PubMed 40945632 · doi:10.1016/j.neubiorev.2025.106372
What was done
A systematic review and random-effects meta-analysis evaluated the effects of iron supplementation on psychiatric and cognitive outcomes in non-anemic individuals. Searches of PubMed and Scopus identified randomized placebo-controlled trials (RCTs) and pre-post intervention studies in children/adolescents (ages 5–17) and menstruating adults. The review included 18 studies (12 RCTs, 6 pre-post studies) comprising 1,408 participants (1,176 menstruating adults, mean age 34.6 ± 9.5 years; 204 youth, mean age 13.9 ± 1.4 years, 56% female). Sixteen studies were included in quantitative meta-analyses.
What was found
In RCTs, iron supplementation significantly improved anxiety (d = 0.34), fatigue (d = 0.34), physical well-being (d = 0.42), cognitive intelligence (d = 0.46), and short-term memory (d = 0.53), but showed no improvement for attention or depression. In uncontrolled pre-post studies, improvements were reported for depression (d = 0.93), fatigue (d = 1.01), and overall psychiatric symptoms (d = 1.13). Subgroup analyses showed effects were consistent in iron-deficient groups, youth, and menstruating adults, but supplementation effects were completely absent when excluding participants with baseline iron deficiency.
Why it matters
Iron deficiency appears to compromise cognitive function, fatigue, and anxiety before anemia even develops. This suggests clinical value in screening for and treating tissue-level iron deficiency in at-risk populations even when hemoglobin levels remain normal.
Limits
Six of the 18 included studies were uncontrolled pre-post designs with substantially larger effect sizes than RCTs. The pediatric/adolescent sample size was relatively small (n = 204 across all youth studies). The abstract reports point estimates without confidence intervals, p-values, or measures of between-study heterogeneity, and does not report specific iron formulations, doses, treatment durations, or biochemical thresholds used to define iron deficiency.
Cited by
- supports Nutrient deficiencies such as iron deficiency, vitamin D deficiency, and low omega-3 status drive or exacerbate anxiety and depression.