Effect of iron intake on iron status: A systematic review and meta-analysis of randomized controlled trials

Background: The response of status biomarkers to an increase in iron supply depends on several physiologic and environmental factors, which make it difficult to predict the outcome of an intervention. Objective: We assessed effects of baseline iron status, sex, menopausal status, duration of intervention, iron form, and daily dose on the change in iron status in response to iron supplementation. Design: A systematic review of randomized controlled trials (RCTs) of iron-supplementation and -fortification trials that assessed effects on hemoglobin, serum ferritin (SF), soluble transferrin receptor, or body iron was conducted. Subgrouping and straight-line and curved metaregression were used to describe the magnitude and dose-responsiveness of effect modifiers with respect to changes in status. Results: Forty-one RCTs were included; none of the RCTs were judged at low risk of bias. Random-effects meta-analyses showed that iron supplementation significantly improved iron status but with high levels of heterogeneity. Metaregression explained approximately one-quarter of between-study variance in effect size. There were clear effects on SF with study duration (increase in SF concentration/wk: 0.51 μg/L; 95% CI: 0.02, 1.00 μg/L; P = 0.04) and dose (increase in SF concentration/g Fe: 0.10 μg/L; 95% CI: 0.01, 0.20 μg/L; P = 0.036) and on hemoglobin concentrations with baseline iron status [-0.08 g/dL (95% CI: 0.15, 0.00 g/dL) per 10-μg/L increase in baseline SF concentration; P = 0.02]. Insufficient data were available to assess effects on body iron, sex, or menopausal status. Conclusion: Quantitative relations between baseline iron status, study duration, and iron dose on changes in iron-status biomarkers, which were generated from the meta-analyses, can be used to predict effects of trials of iron supplementation and fortification and to design iron-intervention programs.