Drug Test Anal. 2018 Aug 15. doi: 10.1002/dta.2478. [Epub ahead of print]

Erythropoietic effects of low-dose cobalt application.

Hoffmeister T, Schwenke D, Wachsmuth N, Krug O, Thevis M, Byrnes W, Schmidt W.


Abstract

Cobaltous ions (Co2+ ) stabilize HIFα, increase endogenous erythropoietin (EPO) production, and may, therefore, be used as 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 h after Co2+ administration. In a second study, the same daily Co2+ dosages were administered for 5 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 h after the single 5 mg administration (p<0.05) and by 52.8±23.5% up to 7 h following the 10 mg Co2+ administration (p<0.001). Urine [Co2+ ] transiently increased, with maximum values 3 h - 5 h 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 5 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.