Erythropoietic effects of low-dose cobalt application.

Cobaltous ions (Co2+) stabilize HIF alpha, increase endogenous erythropoietin (EPO) production, and may, therefore, be used as a performance-enhancing substance. To date, the dosage necessary to stimulate erythropoiesis is unknown. The aim of this study was, therefore, to determine the minimum dosage necessary to increase erythropoietic processes. In a first double-blind placebo-controlled study (n = 5), single oral Co2+ dosages of 5 mg (n = 6) and 10 mg (n = 7) were administered to healthy young men. Cubital venous blood and urine samples were collected before and up to 24 hours after Co2+ administration. In a second study, the same daily Co2+ dosages were administered for five days (placebo: n = 5, 5 mg: n = 9, 10 mg: n = 7). Blood and urine samples were taken the day before administration and at day 3 and day 5. Plasma [EPO] was elevated by 20.5 +/- 16.9% at 5 hours after the single 5-mg administration (p < 0.05) and by 52.8 +/- 23.5% up to 7 hours following the 10-mg Co2+ administration (p < 0.001). Urine [Co2+] transiently increased, with maximum values 3-5 hours after Co2+ ingestion (5 mg: from 0.8 +/- 1.1 to 153.6 +/- 109.4 ng/mL, 10 mg: from 1.3 +/- 1.7 to 338.0 +/- 231,5 ng/mL). During the five days of Co2+ application, 5 mg showed a strong tendency to increase [EPO], while the 10-mg application significantly increased [EPO] at day 5 by 27.2 +/- 26.4% (p < 0.05) and the immature reticulocyte fraction by 49.9 +/- 21.7% (p < 0.01). [Ferritin] was decreased by 12.4 +/- 10.4 ng/mL (p < 0.05). An oral Co2+ dosage of 10 mg/day exerts clear erythropoietic effects, and 5 mg/day tended to increase plasma EPO concentration.