A randomized, blinded, placebo‐controlled trial of education and iron supplementation for mitigation of iron deficiency in regular blood donors

Randomized, blinded, placebo-controlled multicenter study of frequent adult blood donors in the United States who were not taking iron supplements. Participants were assigned in a 1:1:1:1:1 ratio to five equal-sized arms and followed from June 2011 to April 2012 with final visits over a two-year period.

Five-arm randomized trial: two active oral iron regimens used ferrous gluconate tablets providing 38 mg or 19 mg elemental iron taken after each blood donation, compared with a placebo tablet arm. Two additional active management arms used ferritin-based iron-status letters or no-information letters instead of tablets.

Daily oral iron supplementation with 19 mg or 38 mg elemental iron, and ferritin-based iron-status letters, were effective and largely equivalent for mitigating donation-related iron deficiency; no intervention led to worsening iron status. Ferritin increased by 16.7 and 18.3 in the 38 mg and 19 mg iron groups, compared with 0.3 in the no-information letter group and 0.8 in placebo, and ferritin <26 ng/mL declined by 50% in the iron-status letter, 19 mg, and 38 mg groups. Ferritin <12 ng/mL fell by 70%+ in those same groups, while control arms were unchanged; log(sTfR/ferritin) <2.07 decreased by 30%-50% in the intervention groups (p=0.003 for all). Mean hemoglobin at end of study was 0.3-0.4 g/dL higher in the iron and iron-status letter groups than in placebo or no-information groups, and adverse events did not differ between iron and placebo arms.

Completed sample sizes were smaller than randomized sample sizes in several arms, especially placebo and the 19 mg group, which increases imprecision. Baseline ferritin and related iron measures differed across arms at enrollment, and the educational letter arms make the comparison less purely supplement-specific. Dietary intake and physical activity were not reported, and some donors in the letter arm did not act on their low-ferritin information.