Low doses of recombinant human erythropoietin does not affect C-terminal FGF23 in healthy men

Recombinant human erythropoietin (rhEpo) can improve human performance, but misuse remains difficult to detect. C-terminal fibroblast growth factor 23 (cFGF23) was recently demonstrated to increase following injection of a single high dose rhEpo, but the effect of more frequent low doses is unknown. Using a randomized double-blind placebo-controlled design, we investigated whether 2 weeks of subcutaneous injections three times a week of 50 IU/kg Eprex (low-dose) or 20 IU/kg Eprex (micro-dose) increase cFGF23 levels compared with saline (placebo) injections in 24 healthy males. Venous blood was sampled at day -3, 0, 1, 3, 11, 14, 18, and 25 of the treatment and analyzed for cFGF23 and erythropoietin concentration ([EPO]). The level of cFGF23 was similar at days -3, 0, 1, 3, 11, 14, 18, and 25 with the low-dose (23 +/- 4, 26 +/- 5, 23 +/- 7, 27 +/- 6, 25 +/- 8, 24 +/- 10, 22 +/- 5, and 24 +/- 7 RU/mL, respectively), micro-dose (23 +/- 6, 25 +/- 5, 23 +/- 8, 28 +/- 9, 27 +/- 7, 25 +/- 9, 25 +/- 5, and 23 +/- 6 RU/mL, respectively) and placebo (23 +/- 6, 24 +/- 6, 26 +/- 7, 26 +/- 6, 31 +/- 6, 31 +/- 7, 24 +/- 4, and 27 +/- 8 RU/mL, respectively) treatment. The correlation coefficient between plasma [EPO] and plasma cFGF23 levels was R-2= 0.01 and insignificant. The results demonstrate that cFGF23 is not sensitive to low doses of subcutaneous rhEpo injections in healthy males.