All donors are screened at each donation for hemoglobin (Hb) levels, and low Hb is the most common reason for blood donors to be deferred, affecting up to 15% of female and 5% of male donors in Europe. Deferred donors are also less likely to return to donate blood. While iron supplementation is not currently the standard of care, some blood centers encourage donors to take some form of iron supplements, though the effectiveness is unclear. The Cochrane Library performed a meta-analysis through January 2025 of all randomized controlled trials (RCTs) in healthy blood donors that compared iron supplementation to either no iron or iron in different forms (oral or IV) or doses. A total of 38 RCTs were identified with a total of 7475 blood donors representing 15 different countries (53% from Europe and 26% from the USA). Oral iron supplementation after first whole blood donation versus no iron reduces the deferral rate due to low Hb at subsequent donations (risk ratio (RR) 0.39; 95% C.I., 0.20 to 0.76; 7 studies, 1647 donors; moderate certainty evidence), but donors may experience more adverse events (8 studies, 2641 donors; low certainty evidence). While deferral rates were not reported by the three RCTs (n=558) that compared intravenous (IV) iron to no iron, Hb levels were higher in returning donors who received IV iron at first donation compared to those who did not (mean difference 8.02; 95% C.I., 3.22 to 12.83 g/L higher; moderate certainty evidence). Further studies are needed to elucidate the most effective forms of iron, dosing regimens, iron formulations, and donor subgroups that will benefit the most.
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