Background: Epidemiologists have observed that blood donation is associated with decreased risk of type 2 diabetes and cardiovascular disease.

Methods: We investigated the relationship between iron stores and insulin sensitivity, after controlling for known confounding factors, and compared insulin sensitivity between blood donors and individuals who had never donated blood (nondonors). In 181 men, insulin sensitivity and insulin secretion were evaluated through frequently sampled intravenous glucose tolerance tests with minimal model analysis. Men who donated blood between 6 months and 5 years before inclusion (n = 21) were carefully matched with nondonors (n = 66) for age, body mass index, waist-to-hip ratio, and cardiovascular risk profile, including blood lipids, blood pressure, and smoking status.

Results: Frequent blood donors (2–10 donations) had increased insulin sensitivity [3.42 (1.03) vs 2.45 (1.2) × 10⁻⁴ · min⁻¹ · mIU/L; P = 0.04], decreased insulin secretion [186 (82) vs 401.7 (254) mIU/L · min; P <0.0001], and significantly lower iron stores [serum ferritin, 101.5 (74) vs 162 (100) μg/L; P = 0.017] than nondonors, but the 2 groups had similar blood hematocrits and blood hemoglobin concentrations.

Conclusions: Blood donation is simultaneously associated with increased insulin sensitivity and decreased iron stores. Stored iron seems to impact negatively on insulin action even in healthy people, and not just in classic pathologic conditions associated with iron overload (hemochromatosis and hemosiderosis). According to these observations, it is imperative that a definition of excessive iron stores in healthy people be formulated.