Effects of iron and n-3 fatty acid supplementation, alone and in combination, on cognition in school children: a randomized, double-blind, placebo-controlled intervention in South Africa

Am J Clin Nutr. 2012 Dec;96(6):1327-38. doi: 10.3945/ajcn.112.041004. Epub 2012 Oct 24.

Abstract

Background: Little is known about the combined effects of iron and n-3 (omega-3) fatty acid (FA) supplementation on cognitive performance. The provision of either DHA/EPA or iron alone in rats with combined iron and n-3 FA deficiency has been reported to exacerbate cognitive deficits associated with deficiency.

Objective: We investigated the effects of iron and DHA/EPA supplementation, alone and in combination, in children with poor iron and n-3 FA status.

Design: In a 2-by-2 factorial trial, children with iron deficiency (ID) (n = 321; aged 6-11 y) were allocated to receive 1) iron (50 mg) plus DHA/EPA (420/80 mg), 2) iron plus placebo, 3) placebo plus a mixture of DHA and EPA (DHA/EPA), or 4) placebo plus placebo as oral supplements (4/wk) for 8.5 mo. Cognition was assessed at baseline and endpoint by using the Hopkins Verbal Learning Test (HVLT) and subscales of the Kaufman Assessment Battery for Children.

Results: Both iron and DHA/EPA significantly increased weight-for-age z scores. Iron increased the number of words recalled at HVLT recall 2 (intervention effect: 0.90; 95% CI: 0.18, 1.62), and in anemic children, iron increased scores in the Atlantis Delayed test (1.51; 95% CI: 0.03, 2.99) and HVLT recall 2 (2.02; 95% CI: 0.55, 3.49). DHA/EPA showed no benefit in any of the cognitive tests but decreased Atlantis test scores (-2.48; 95% CI: -3.99, -0.96) in children who were anemic at baseline and decreased Atlantis delayed scores (-0.9; 95% CI: -1.45, -0.36) in girls with ID, whereas boys tended to perform better.

Conclusions: In children with poor iron and n-3 FA status, iron supplementation improved verbal and nonverbal learning and memory, particularly in children with anemia. In contrast, DHA/EPA supplementation had no benefits on cognition and impaired working memory in anemic children and long-term memory and retrieval in girls with ID.

Trial registration: ClinicalTrials.gov NCT01092377.

Publication types

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

MeSH terms

  • Anemia, Iron-Deficiency / blood
  • Anemia, Iron-Deficiency / diet therapy*
  • Anemia, Iron-Deficiency / physiopathology
  • Child
  • Child Development
  • Cognition Disorders / etiology
  • Cognition Disorders / prevention & control*
  • Dietary Supplements*
  • Double-Blind Method
  • Fatty Acids, Omega-3 / blood
  • Fatty Acids, Omega-3 / therapeutic use*
  • Female
  • Hemoglobins / analysis
  • Humans
  • Iron, Dietary / therapeutic use*
  • Learning Disabilities / etiology
  • Learning Disabilities / prevention & control
  • Male
  • Memory Disorders / etiology
  • Memory Disorders / prevention & control
  • Memory, Short-Term
  • Poverty Areas
  • Rural Health
  • Sex Characteristics
  • South Africa
  • Weight Gain

Substances

  • Fatty Acids, Omega-3
  • Hemoglobins
  • Iron, Dietary

Associated data

  • ClinicalTrials.gov/NCT01092377