Background: Iron deficiency (ID) and iron deficiency anemia (IDA) are highly-prevalent nutrient deficiencies and have been shown to have a range of negative effects on cognition and brain function. Human intervention studies including measures at three levels—blood, brain, and behavior—are rare and our objective was to model the relationships among measures at these three levels in school-going Indian adolescents.
Methods: Male and female adolescents in rural India were screened for ID/IDA. Subjects consumed 2 meals/day for 6 months; half were randomly assigned to consume meals made from a standard grain (pearl millet) and half consumed meals made from an iron biofortified pearl millet (BPM). Prior to and then at the conclusion of the feeding trial, they completed a set of cognitive tests with concurrent electroencephalography (EEG).
Results: Consumption of the BPM resulted in significantly larger improvements (relative to the comparison pearl millet) in the iron biomarkers (mean partial η2 for treatment condition = 0.07), the behavioral variables (mean partial η2 = 0.18), and the EEG variables (mean partial η2 = 0.21). Critically, the best model for the relationship between iron status and cognition had brain measures as a mediating factor, with both serum ferritin as a primary predictor and hemoglobin as a moderator.
Conclusions: A dietary intervention involving a biofortified staple grain was shown to be effective in improving blood iron biomarkers, behavioral measures of cognition, and EEG measures of brain function. Modeling the relationships among these variables strongly suggests multiple mechanisms by which blood iron level affects brain function and cognition.
Trial registration: Registered at ClinicalTrials.gov: NCT02152150, 02 June 2014.