In adolescents, iron-deficiency anemia is the leading cause of disability-adjusted life years lost. The World Health Organization recommends delivering iron supplementation through school-based platforms, requiring partnerships with the education sector. This anemia-reduction intervention is valued for the perceived benefits of improved learning and school performance. This article aims to systematically review the available evidence on the relationship between iron status and anemia and impacts of iron interventions on cognitive and academic performance in adolescents. Fifty studies were included: n = 26 cross-sectional and n = 24 iron-containing interventions. Our review suggests that iron status and anemia may be associated with academic performance in some contexts and that iron supplementation during adolescence may improve school performance, attention, and concentration. However, nearly all supplementation trials were judged to have moderate or high risk of bias. We did not find evidence suggesting that iron status and anemia influenced or were associated with attention, intelligence, nor memory in adolescents. Further, iron supplementation did not improve memory and recall or intelligence. Overall, more high-quality research is needed to guide programmers and policy makers to understand the relationships between anemia and educational performance and the potential impacts of iron interventions, which effectively reduce anemia, on adolescents’ learning and school performance.
Iron supplementation and fortification are used to treat iron deficiency, which is often associated with gastrointestinal conditions, such as inflammatory bowel disease and colorectal cancer. Within the gut, commensal bacteria contribute to maintaining systemic iron homeostasis. Disturbances that lead to excess iron promote the replication and virulence of enteric pathogens. Consequently, research has been interested in better understanding the effects of iron supplementation and fortification on gut bacterial composition and overall gut health. While animal and human trials have shown seemingly conflicting results, these studies emphasize how numerous factors influence gut microbial composition. Understanding how different iron formulations and doses impact specific bacteria will improve the outcomes of iron supplementation and fortification in humans. Furthermore, discerning the nuances of iron supplementation and fortification will benefit subpopulations that currently do not respond well to treatment.
IntroductionThe WHO recommends daily oral iron supplementation for 12 weeks in women and adolescents where anaemia prevalence is greater than 40%. However, if iron deficiency is not a major cause of anaemia, then, at best, untargeted iron supplementation is a waste of resources; at worst, it could cause harm. Further, different forms of iron with varying bioavailability may present greater risks of harm.Methods and analysisA 12-week three-arm, double-blind, randomised controlled supplementation trial was conducted in Cambodia to determine if there is potential harm associated with untargeted iron supplementation. We will recruit and randomise 480 non-pregnant women (ages 18–45 years) to receive one of three interventions: 60 mg elemental iron as ferrous sulfate (the standard, commonly used form), 18 mg ferrous bisglycinate (a highly bioavailable iron amino acid chelate) or placebo. We will measure ferritin concentrations (to evaluate non-inferiority between the two forms of iron), as well as markers of potential harm in blood and stool (faecal calprotectin, gut pathogen abundance and DNA damage) at baseline and 12 weeks. Mixed-effects generalised linear models will be used to assess the effect of iron on ferritin concentration and markers of potential harm at 12 weeks.Ethics and disseminationEthical approval was obtained from the University of British Columbia Clinical Research Ethics Board (H18-02610), the Children's and Women's Health Centre of British Columbia Research Ethics Board (H18-02610) and the National Ethics Committee for Health Research in Cambodia (273-NECHR). Findings will be published in peer-reviewed journals, presented to stakeholders and policymakers globally and shared within participants’ communities.Trial registration numberClinicalTrials.gov Registry (NCT04017598).
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