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

Systematic review and meta-analysis of 41 randomized controlled trials in healthy adults, reported in 43 articles. Participants were predominantly premenopausal women, often with iron deficiency or iron-deficiency anemia, with fewer studies in men, postmenopausal women, and mixed-sex populations.

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. Doses ranged from 6 mg/day to 120 mg/day, were given daily or 5 days/week, and lasted from 3 to 72 weeks.

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 concluded that higher dose and longer duration influence ferritin response, while data were insufficient to fully assess sex or menopausal-status effects.

Substantial heterogeneity was present for all major outcomes, and intervention regimens varied widely in dose, form, frequency, and duration. Evidence was limited for men, postmenopausal women, and body iron outcomes, and arm-level demographic detail was sparse. The review could not fully assess sex or menopausal-status effects because of the small number of relevant studies.