Iron and a mixture of DHA and EPA supplementation, alone and in combination, affect bioactive lipid signalling and morbidity of iron deficient South African school children in a two-by-two randomised controlled trial.

We recently reported that iron supplementation increased respiratory morbidity in iron deficient South African children. This increase, however, was attenuated when iron was provided in combination with a mixture of DHA/EPA. To explore potential underlying mechanisms, we examined the effects of iron and DHA/EPA, alone and in combination, on plasma lipid-derived immune modulator concentrations and related gene expression in peripheral blood mononuclear cells (PBMC). DHA/EPA decreased inflammatory 12-hydroxyeicosatetraenoic acid and tended to increase anti-inflammatory and pro-resolving 17-hydroxydocosahexaenoic acid (17-HDHA), while iron decreased 17-HDHA. However, in combination with iron, the anti-inflammatory effect of DHA/EPA was maintained. These biochemical changes may explain the prevention of iron-induced respiratory morbidity that we observed when iron was supplemented in combination with DHA/EPA during the 8.5 month randomised controlled trial and might lead to a safer approach of delivering iron supplementation. The study was registered at clinicaltrials.gov as NCT01092377.