Ferritin-guided iron supplementation as an alternative or complement to prolonged blood donation intervals (FORTE): a...

Regular blood donation is associated with an increased risk of iron deficiency and anaemia. Oral iron supplementation is known to shorten post-donation iron recovery time and could serve as an alternative to extended donation intervals. We aimed to evaluate the effect of different iron supplementation protocols on ferritin and haemoglobin levels, gastrointestinal side-effects, iron deficiency-related symptoms, and donor return compared with placebo supplementation.

In this double-blind, randomised, placebo-controlled trial conducted at seven of Sanquin's blood donation centres in The Netherlands, donors aged 18-80 years with ferritin levels equal to or less than 30 μg/L were randomly allocated to one of six study groups, using block randomisation in equal numbers by sex and age. Donors were instructed to adhere to a ferrous bisglycinate supplementation protocol for 56 days, taking capsules containing 0 mg (placebo), 30 mg, or 60 mg of elemental iron, either daily or on alternate days. The primary outcomes were presence of iron deficiency (<15 μg/L), low ferritin (15-30 μg/L), and low haemoglobin (≤135 g/L for male donors and ≤125 g/L for female donors) at 56 days' follow-up. Analyses were conducted using an intention-to-treat approach. This trial is registered in the Dutch trial registry (NL7328.018.20) and is complete.

Between Aug 1, 2021, and Jan 15, 2023, 830 donors (464 [56%] female donors and 366 [44%] male donors; 789 [95%] of Dutch origin and 26 [3%] of non-Dutch origin) had low ferritin and were included in the trial. At 56 days, 55 (51%) of 108 participants in the placebo daily group, 58 (49%) of 119 participants in the placebo alternate day group, 11 (10%) of 107 participants in the 30 mg daily group, eight (7%) of 112 participants in the 30 mg alternate day group, one (1%) of 114 participants in the 60 mg daily group, and four (4%) of 110 participants in the 60 mg alternate day group presented with iron deficiency. Compared with daily placebo, all iron supplementation groups exhibited similar significantly lower odds of iron deficiency at 56 days, with odds ratios (ORs) of 0·62 (95% CI 0·56-0·68) for 30 mg daily, 0·63 (0·57-0·70) for 30 mg alternative days, 0·60 (0·55-0·66) for 60 mg daily, and 0·65 (0·59-0·72) for 60 mg on alternative days. For low ferritin, 0·70 (0·63-0·78) for 30 mg daily, 0·82 (0·74-0·91) for 30 mg on alternative days, 0·52 (0·47-0·57) for 60 mg daily, and 0·61 (0·55-0·68) for 60 mg on alternate days. For low haemoglobin, the ORs were 0·78 (0·67-0·91) for 30 mg daily, 0·80 (0·68-0·93) for 30 mg on alternative days, 0·75 (0·64-0·86) for 60 mg daily, and 0·77 (0·66-0·90) for 60 mg alternative days. Adverse events were reported in two participants-one event, an increase in migraines, was considered potentially related to the study intervention, but the other (a death) was deemed unrelated.

In regular donors with low ferritin, iron supplementation-60 mg taken daily, in particular-effectively mitigates iron deficiency, low ferritin, and low haemoglobin. Iron supplementation is an effective alternative or supplement to extended donation intervals for whole-blood donors with low ferritin levels.

Sanquin Blood Supply Foundation.

For the Dutch translation of the abstract see Supplementary Materials section.