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 trial enrolling 692 frequent blood donors aged 18+ (men with ≥3 RBC-equivalent donations in prior 12 months; women with ≥2 RBC-equivalent donations). Eligibility required not taking supplemental iron and the ability to donate at least two (women) or three (men) RBC-equivalent donations per year during a 2-year follow-up. Ferritin, soluble transferrin receptor (sTfR), and complete blood count were measured at each donation; ferritin and sTfR assessed by immunoassay methods.

After each donation, one daily tablet of ferrous gluconate taken for 60 days with dosages of 38 mg elemental iron, 19 mg elemental iron, or 0 mg (placebo).

Among 393 completers, iron status improved in the iron-pill groups (19 mg and 38 mg) and in the iron-status information group, with end-of-study measures similar across the 19 mg, 38 mg, and iron-status-letter groups. Compared with controls (placebo or no-information letter), ferritin <26 ng/mL declined by >50% in the three interventional groups; ferritin rose by 10.3 ng/mL (iron-status letter), 18.3 ng/mL (19 mg), and 16.7 ng/mL (38 mg). log(sTfR/ferritin) decreased by 0.15, 0.32, and 0.25 in those groups. Hb rose by 0.3–0.4 g/dL in the iron groups; the iron-status letter group had little Hb change. In longitudinal analyses across all 692 participants, 19 mg and 38 mg iron pills improved iron status, while placebo and no-information worsened. Once-daily 19 mg iron was as effective as 38 mg; providing ferritin information was helpful but less effective than pills; donors who do not take action become more iron-deficient.

Only 57% of randomized participants completed the final visit; completion varied by arm with higher deenrollment in pill groups. Adverse events occurred in 21% of active pill enrollments and did not differ between iron and placebo; adverse events were not monitored in letter arms. Loss to follow-up may bias results; generalizability may be limited to the studied frequent-donor population.