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

Laboratory of Human Nutrition, Institute of Food, Nutrition and Health, Swiss Federal Institute of Technology Zürich, Switzerland.
American Journal of Clinical Nutrition (Impact Factor: 6.5). 10/2012; 96(6). DOI: 10.3945/ajcn.112.041004
Source: PubMed

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. The trial was registered at as NCT01092377.

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    ABSTRACT: Background: Although iron supplementation in malaria-free areas mostly reduces infectious morbidity, it can sometimes increase morbidity from infections as a result of the dependence of pathogenic microorganisms on iron. Supplementation with n–3 (n-3) long chain polyunsaturated fatty acids (LCPUFAs) improved morbidity in several human studies. However, information on the combined effect of iron and n–3 LCPUFA supplementation on infectious morbidity is limited. Objective: We determined whether n–3 LCPUFAs and iron supplementation, alone or in combination, affected absenteeism and illness in iron-deficient schoolchildren with low fish intake. Design: A total of 321 South African children (aged 6–11 y) with iron deficiency (ID) were randomly divided into 4 groups to receive 1) iron plus placebo, 2) a mixture of docosahexaenoic acid and eicosapentaenoic acid (DHA/EPA) plus placebo, 3) iron plus DHA/EPA, or 4) placebo plus placebo as oral supplements 4 times/wk for 8.5 mo. Morbidity was recorded, and iron-status indexes were measured. The total phospholipid fatty acid composition of peripheral blood mononuclear cell membranes was analyzed in a subsample (n = 130). Results: Iron supplementation increased the number of days with illness when all symptoms were considered (B: 0.87; 95% CI: 0.71, 1.03) as well as illness that was specifically caused by respiratory symptoms (B: 1.45; 95% CI: 1.21, 1.70), whereas DHA/EPA reduced the number of days with illness at school (B: 20.96; 95% CI: 21.33, 20.59). The increases caused by iron were reduced to the levels seen in the placebo plus placebo group when iron was provided in combination with DHA/EPA as indicated by significant iron x DHA/EPA interactions (both P , 0.001). Conclusion: Iron supplementation increased morbidity (mostly respiratory) in iron-deficient South African schoolchildren with low DHA/EPA intake, but when iron was given in combination with DHA/EPA, this effect was prevented. This trial was registered at as NCT01092377.
    American Journal of Clinical Nutrition 03/2015; 101(3). DOI:10.3945/ajcn.113.081208 · 6.50 Impact Factor


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May 31, 2014