Key messages
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Taking an oral (by mouth) iron preparation may increase iron stores in the blood compared to not taking an oral iron preparation.
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The higher iron in the blood meant more people could donate that otherwise may have been deferred (stopped from donating because of low iron levels).
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More people taking iron tablets may experience unwanted effects like gut problems while taking the tablets, at least initially, compared to people not taking iron tablets.
What is iron supplementation, and how can it help with blood donation?
Low iron is a common cause of deferral (stopped from donating) in people wishing to donate blood. If iron removed from the body through blood donation is not replaced, then donors may become iron deficient. All donors are screened at each visit for low iron levels. Iron can usually be replenished through a healthy diet, but it may take a long time. Iron supplementation using tablets or injections may reduce this time and help donors return to being able to donate much sooner.
What did we want to find out?
We wanted to find out if giving iron tablets or an injection of iron to potential blood donors would improve the iron stores in their blood, and reduce the chance of them being deferred (stopped) from donating because they had too little iron in their blood.
What did we do?
We searched for studies that compared giving iron supplements (as tablets, an injection, or an infusion (into a vein)) with getting no iron supplementation, as well as comparing different types of iron and different doses of iron. We compared and summarised the results of the studies and rated our confidence in the evidence based on factors such as study methods and sizes.
What did we find?
We found 8 new studies, for a total of 38 studies (7475 people). Iron was most commonly given as daily tablets (orally), with only five studies looking at other methods (injections or infusions directly into the blood).
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Iron tablets may increase the iron stored in the blood when taken over a few weeks or months compared to not taking iron tablets. This probably allowed more people to donate at their next attempt (lower deferral rates) (7 studies, 1647 people for deferral).
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More people taking iron tablets experienced unwanted effects, mostly gut problems such as stomach pain, constipation (hard stools), and diarrhoea (loose watery stools), compared to those not taking iron tablets (8 studies, 2641 people).
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There was no difference in non-gut problems (like headaches) between people who took iron tablets and those who didn't, and those that took the iron tablets found they had less "weakness" than those not taking the tablets.
What are the limitations of the evidence?
Our confidence in the evidence ranged from high to very low. In cases where our confidence was limited, this was because some of the studies were very old or very small (not many people were studied), and sometimes the studies did not report on everyone they said they would, and it was possible that people in the studies knew which treatment they were getting. We wanted to look at how different types of iron or different doses worked differently, as well as the impact on men and women separately, and whether they already had low iron stores in their blood, but not all studies gave us this information, so the answers are not as clear as we would like.
How up-to-date is the evidence?
This review updates our previous review, last published in 2014. The evidence is current to January 2025.
Read the full abstract
Iron deficiency is a significant cause of deferral in people wishing to donate blood. If iron removed from the body through blood donation is not replaced, then donors may become iron deficient. All donors are screened at each visit for low haemoglobin (Hb) levels. However, some deferred blood donors do not return to donate. Deferred first-time donors are even less likely to return. Interventions that reduce the risk of provoking iron deficiency and anaemia in blood donors will therefore increase the number of blood donations. Currently, iron supplementation for blood donors is not a standard of care in many blood services. A systematic review is required to answer specific questions regarding the efficacy and safety of iron supplementation in blood donors.
Objectives
To assess the effectiveness and safety of iron supplementation to reduce deferral, iron deficiency and/or anaemia in blood donors.
Search strategy
We searched 10 electronic databases (including CENTRAL, MEDLINE, Embase, and Transfusion Evidence Library) and 4 ongoing trial registries on 28 January 2025. We did not restrict our search by language, date, or publication status.
Selection criteria
Randomised controlled trials (RCTs) comparing iron supplementation versus placebo or control, oral versus parenteral iron supplementation, iron supplementation versus iron-rich food supplements, and different doses, treatment durations and preparations of iron supplementation in healthy blood donors. Autologous blood donors were excluded.
Data collection and analysis
We combined data using random-effects meta-analyses. We evaluated heterogeneity using the I2 statistic; we explored considerable heterogeneity (I2 > 75%) in subgroup analyses. We carried out sensitivity analyses to assess the impact of trial quality on the results.
Main results
Thirty RCTs (4704 participants) met the eligibility criteria, including 19 comparisons of iron supplementation and placebo or control; one comparison of oral and parenteral iron supplementation; four comparisons of different doses of iron supplementation; one comparison of different treatment durations of iron supplementation; and 12 comparisons of different iron supplementation preparations.
Many studies were of low or uncertain methodological quality and therefore at high or uncertain risk of bias. We therefore rated the quality of the evidence for our outcomes as moderate. There was a statistically significant reduction in deferral due to low haemoglobin in donors who received iron supplementation compared with donors who received no iron supplementation, both at the first donation visit after commencement of iron supplementation (risk ratio (RR) 0.34; 95% confidence interval (CI) 0.21 to 0.55; four studies; 1194 participants; P value < 0.0001) and at subsequent donations (RR 0.25; 95% CI 0.15 to 0.41; three studies; 793 participants; P value < 0.00001). Supplementation also resulted in significantly higher haemoglobin levels (mean difference (MD) 2.36 g/L; 95% CI 0.06 to 4.66; eight studies; 847 participants, P value =0.04), and iron stores, including serum ferritin (MD 13.98 ng/mL; 95% CI 8.92 to 19.03; five studies; 640 participants; P value < 0.00001) and transferrin saturation (MD 3.91%; 95% CI 2.02 to 5.80; four studies; 344 participants; P value < 0.0001) prior to further donation. The differences were maintained after subsequent donation(s).
Adverse effects were widely reported and were more frequent in donors who received iron supplementation (RR 1.60; 95% CI 1.23 to 2.07; four studies; 1748 participants; P value = 0.0005). Adverse effects included constipation, diarrhoea, nausea, vomiting and taste disturbances, and some participants stopped treatment due to side effects.
Authors' conclusions
Iron supplementation may lead to improved blood indices and iron stores, but we are uncertain about the effect due to heterogeneity in the population and different methods and doses of iron supplementation.
Subgrouping (by sex, baseline iron stores, daily elemental iron dose, supplementation duration, and iron preparation) showed some 'low credibility' subgroup differences. Visual inspection of the data (forest plots) suggests more high-quality data may highlight potential differences further in some populations, to target those most in need.
Future studies should assess the impact of supplementation on potentially more vulnerable populations through the stratification of participants by both sex and baseline iron stores; investigate the impact of total and daily doses of iron; and conduct a longer-term assessment of adverse events associated with oral iron supplementation.
Funding
This review had no dedicated funding.
Registration
Protocol and previous versions available via DOIs: 10.1002/14651858.CD009532 and 10.1002/14651858.CD009532.pub2.
