Iron deficiency-related symptoms in non-anemic whole blood donors

Introduction: Whole blood donors are at increased risk for iron deficiency (ID). ID anemia is associated with several symptoms, such as fatigue, cognitive dysfunction, pica, and restless leg syndrome (RLS). However, it is unclear if these symptoms also occur when a donor has developed ID without anemia. This study aims to determine whether non-anemic ID (NAID) is associated with the occurrence of ID-related symptoms. Study Designs and Methods: We combined data from three studies in whole blood donors (i.e., Donor Insight-III, FIND'EM, and FORTE) to create a substantial sample size (N = 12,143). The self-reported occurrence and severity of ID-related symptoms, such as physical and mental health, fatigue, cognitive functioning, pica, and RLS, was measured using validated questionnaires. Associations were studied using logistic regression modeling with ID-related symptoms derived from the questionnaires as the dependent variable and ferritin level group (0-15 mu g/L, 15-30 mu g/L, and >30 mu g/L) as explanatory variable. Results: After applying inclusion and exclusion criteria, 9829 donors were eligible for analysis. In the models corrected for age, body mass index, Hb level, and cohort, only fatigue was shown to be associated with ferritin levels in men, showing lower odds (OR 1.41, 95% CI 1.11-1.79) for fatigue with higher ferritin levels. Conclusion: In these studies, NAID was only associated with self-reported fatigue in male donors. Although selection bias may have led to underestimated associations, ferritin measurements in donors should be primarily considered as a measure to prevent anemia, rather than to prevent or mitigate NAID-related symptoms.