Psychiatric and cognitive outcomes of iron supplementation in non-anemic children, adolescents, and menstruating adults: A meta-analysis and systematic review

Iron plays a key role in brain functions like energy metabolism and neurotransmitter synthesis. Yet, iron deficiency (ID) is the most common nutritional deficiency worldwide. Children, adolescents, and menstruating adults are particularly at risk. Even in the absence of anemia, ID can be associated with fatigue, reduced quality of life, and worsened symptoms of depression, anxiety, and ADHD. This systematic review and meta-analysis examined the impact of iron supplementation on psychiatric and cognitive outcomes in non-anemic children, adolescents, and menstruating adults. PubMed and Scopus searches identified randomized placebo-controlled trials (RCTs) and pre-post studies involving iron supplementation in non-anemic children and adolescents (ages 5–17 years) and menstruating adults. Studies of similar designs and outcomes were pooled for random-effects meta-analyses. Eighteen studies (12 RCTs, six pre-post) involving 1408 participants, including 1176 menstruating adults (mean age 34.6 ± 9.5 years) and 204 children and adolescents (mean age 13.9 ± 1.4 years, 56 % female), were identified, and sixteen were meta-analyzed. In RCTs, supplementation improved symptoms of 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 not attention or depression. Pre-post studies showed improvements in depression (d = 0.93), fatigue (d = 1.01), and overall psychiatric symptoms (d = 1.13). Subgroup analyses confirmed consistent results for ID-only groups, youth, and menstruating adults, though supplementation effects were absent when excluding ID participants. This suggests that, before anemia emerges, ID may impact brain function, potentially requiring identification and treatment.