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

18 studies (12 RCTs, 6 pre-post), 1,408 participants; of these only 204 were children and adolescents (mean age 13.9, 56% female); 1,176 were menstruating adults

NON-ANAEMIC children and adolescents aged 5-17 and menstruating adults. The point of the review is to test iron supplementation in people who are not anaemic - some iron-deficient without anaemia, some iron-replete.

PubMed and Scopus search for randomized placebo-controlled trials and pre-post studies of iron supplementation in non-anaemic populations. Random-effects pooling of like designs. Graded C because only 204 of 1,408 participants are children, pre-post studies are pooled alongside RCTs (and produce effects two to three times larger, a textbook demonstration of why uncontrolled designs inflate), and the child-specific estimates are thinly powered. The decisive analysis is the subgroup that EXCLUDES iron-deficient participants.

In RCTs, iron supplementation in non-anaemic participants 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 not attention or depression. Uncontrolled pre-post studies produced far larger estimates (depression d = 0.93, fatigue d = 1.01, overall psychiatric symptoms d = 1.13). Critically: subgroup analyses confirmed the results for iron-deficient-only groups, and SUPPLEMENTATION EFFECTS WERE ABSENT WHEN IRON-DEFICIENT PARTICIPANTS WERE EXCLUDED. Iron helps the iron-deficient. It does nothing for the replete.

None internally for the RCT arm. The pre-post arm is uncontrolled and its inflated estimates should be discarded, which the authors implicitly concede by reporting the two separately.