Effect of iron intake on iron status: a systematic review and meta-analysis of randomized controlled trials.
What this study found
Iron supplementation improved iron-status biomarkers overall, but effects were heterogeneous across trials. Pooled effects favored iron for hemoglobin (MD +0.51 g/dL; 95% CI 0.37, 0.65; P < 0.00001; I2 = 83%), serum ferritin (MD 9.19 mg/L; 95% CI 6.63, 11.75; P < 0.00001; I2 = 73%), soluble transferrin receptor (MD 20.46 mg/L; 95% CI 20.68, 20.23; P = 0.0001; I2 = 75%), and body iron (MD 1.89 mg/kg; 95% CI 1.04, 2.75; P = 0.0001; I2 = 60%). Baseline ferritin modified hemoglobin response, with a 0.08-g/dL increase in response per 10-mg/L higher baseline ferritin (P = 0.02). The review…
- Study & population
- Systematic review and meta-analysis of 41 randomized controlled trials in healthy adults, reported in 43 articles.
- Intervention
- Across 41 randomized controlled trials, active arms received supplemental iron in a wide range of formulations and delivery vehicles, including ferrous sulfate, ferrous fumarate, ferrous carbonate, heme iron, and iron-fortified foods or beverages.
- Key limitation
- Substantial heterogeneity was present for all major outcomes, and intervention regimens varied widely in dose, form, frequency, and duration.
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Open PDFOriginal abstract
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.