I bumped into a post of captaindrudge again. He is the one who inspired me to write about caffeine. This time it is about famous EPO. I take up this issue because I realized in the many discussions I had with endurance athletes about doping that many of them don’t have a clue what hides behind the big letters E-P-O. It is medication and if put in the right place it can be very helpful. This needs to be underlined beforehand. Erythropoietin is a hormone that, if the genetically manufactured versions are 100% identical with the human one, cannot be directly detected in our body. This is the main concern for those who want to use it as dope. In medicine it is different. There halflife, efficacy and bioavailability are of much greater concern.

• Erythropoietin is an endogenous glycoprotein (protein with a bunch of sugars attached to it) hormone produced mostly by the kidney that stimulates erythropoiesis (production of red blood cells by the bone marrow)

• Darbepoetin alfa (Aranesp) is the synthetic form of recombinant* human erythropoietin (epoetin).

• Epoetin and darbepoetin are manufactured by inserting a gene encoding the protein (drug) into mammalian cells such that they begin to produce it, culturing the cells (growing the cells in a controlled artificial environment) in bioreactors, and then harvesting the drug from them.

In the case of epoetin, the gene is identical to that found in humans. The gene encoding darbepoetin has been tinkered with such that darbepoetin contains more sialic acid (a type of sugar) groups than epoetin. This modification increases its half-life (x3) and enhances its activity relative to epoetin.

Both derivatives are used to correct anemia (reduction in the amount of circulating red blood cells causing symptoms such as fatigue, shortness of breath, sleep disorders, and reduced cognitive function) associated with chronic kidney disease and cancer chemotherapy. Damage to the kidneys and bone marrow, respectively, blunts the normal response of the body to anemia (increased secretion of endogenous erythropoietin leading to increased red blood cell synthesis in the bone marrow).

• EPO has been abused by a number of athletes in endurance sports (blood doping - increasing the number of red blood cells in order to enhance performance - enables blood to carry more oxygen)… and is still in use…

• Since it contains no components of human blood, may be okayed for use by Jehovah’s Witnesses as a possible alternative to blood transfusion.

Excessive use can cause polycythemia (too many red blood cells to the point that they thicken the blood - increase its viscosity). The heart has to work harder to pump blood. The consequences may be heart failure and increased risk of thrombosis (heart attack and stroke), both of which can take a fatal course.

Just recently an immunoblot test method has become available to detect EPO in urine by using monoclonal antibodies. There is still an on-going discussion about the validity of this method developed by Françoise Lasne and Jaques de Ceaurriz.

*recombinant EPO (rEPO) is EPO produced by biotechniques using genetically modified cells. The gene coding for EPO is inserted into the cell of a hamster. Hamster cells are the preferably used cells for manufacturing erythropoietin.

Joy MS. Darbepoetin alfa: a novel erythropoiesis-stimulating protein. Ann Pharmacother. 2002 Jul-Aug;36(7-8):1183-92.