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Am J Clin Nutr. 2015 Mar;101(3):668-79. doi: 10.3945/ajcn.113.081208. Epub 2014 Dec 31.

n-3 Long-chain PUFAs reduce respiratory morbidity caused by iron supplementation in iron-deficient South African schoolchildren: a randomized, double-blind, placebo-controlled intervention.

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From the Centre of Excellence for Nutrition, North-West University, Potchefstroom, South Africa (LM, CMS, and JB); the Human Development and Health Academic Unit, Faculty of Medicine, University of Southampton, Southampton, United Kingdom (PCC), the National Institute for Health Research Biomedical Research Centre in Nutrition, Southampton University Hospital National Health Service Foundation Trust and University of Southampton, Southampton, United Kingdom (PCC); the Department of Biological Sciences, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia (PCC); and the Laboratory of Human Nutrition, Institute of Food, Nutrition and Health, Eidgenössische Technische Hochschule Zürich, Switzerland (MBZ).



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 (ω-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.


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.


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).


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: -0.96; 95% CI: -1.33, -0.59). 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 × DHA/EPA interactions (both P < 0.001).


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.



iron; morbidity; n–3 long-chain polyunsaturated fatty acids; randomized controlled trial; schoolchildren; supplementation

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