Randomised study of cognitive effects of iron supplementation in non-anaemic iron-deficient adolescent girls

Lancet. 1996 Oct 12;348(9033):992-6. doi: 10.1016/S0140-6736(96)02341-0.


Background: Up to 25% of adolescent girls in the USA are iron deficient. This double-blind, placebo-controlled clinical trial assessed the effects of iron supplementation on cognitive function in adolescent girls with non-anaemic iron deficiency.

Methods: 716 girls who enrolled at four Baltimore high schools were screened for non-anaemic iron deficiency (serum ferritin < or = 12 micrograms/L with normal haemoglobin). 98 (13.7%) girls had non-anaemic iron deficiency of whom 81 were enrolled in the trial. Participants were randomly assigned oral ferrous sulphate (650 mg twice daily) or placebo for 8 weeks. The effect of iron treatment was assessed by questionnaires and haematological and cognitive tests, which were done before treatment started and repeated after the intervention. We used four tests of attention and memory to measure cognitive functioning. Intention-to-treat and per-protocol analyses were done.

Findings: Of the 81 enrolled girls with non-anaemic iron deficiency, 78 (96%) completed the study (39 in each group). Five girls (three control, two treatment) developed anaemia during the intervention and were excluded from the analyses. Thus, 73 girls were included in the per-protocol analysis. Ethnic distribution, mean age, serum ferritin concentrations, haemoglobin concentrations, and cognitive test scores of the groups did not differ significantly at baseline. Postintervention haematological measures of iron status were significantly improved in the treatment group (serum ferritin 27.3 vs 12.1 micrograms/L, p < 0.001). Regression analysis showed that girls who received iron performed better on a test of verbal learning and memory than girls in the control group (p < 0.02).

Interpretation: In this urban population of non-anaemic iron-deficient adolescent girls, iron supplementation improved verbal learning and memory.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Age Factors
  • Anemia, Iron-Deficiency / etiology
  • Attention / drug effects
  • Baltimore
  • Cognition / drug effects*
  • Double-Blind Method
  • Ethnicity
  • Female
  • Ferritins / blood
  • Ferrous Compounds / administration & dosage
  • Ferrous Compounds / therapeutic use*
  • Hemoglobins / analysis
  • Humans
  • Iron / blood
  • Iron Deficiencies*
  • Iron Metabolism Disorders / blood
  • Iron Metabolism Disorders / drug therapy*
  • Linear Models
  • Memory / drug effects
  • Placebos
  • Verbal Learning / drug effects


  • Ferrous Compounds
  • Hemoglobins
  • Placebos
  • ferrous sulfate
  • Ferritins
  • Iron