Erythropoietin

updated Feb 2005
Pharmacological cheating in sports is not a new phenomenon. Unfortunately, the modern era has witnessed explosive growth in new and different ways to achieve false victory. Advances in biochemistry, medicine, and other fields have benefited humanity in countless ways. Sadly, however, some have abused these advances for, “pursuit of victory at all cost”. A recent article by Dr. Timothy Noakes (1) highlights the breadth and depth of the problem. He discusses several “cheating venues”, but for this article I wish to focus on one, erythropoietin.

Erythropoietin (pronounced, ah-rith-ro-poy-tin, and abbreviated, EPO) is a relatively recent entry into the deceitful pursuit of glory. EPO is a protein hormone produced by the kidney. After being released into the blood stream it binds with receptors in the bone marrow, where it stimulates the production of red blood cells (erythrocytes). Medically, EPO is used to treat certain forms of anemia (e.g., due to chronic kidney failure). Logically, since EPO accelerates erythrocyte production it also increases oxygen carrying capacity. This fact did not long escape notice of the athletic community.

Blood doping is the process of artificially increasing the amount of red blood cells in the body in an attempt to improve athletic performance. In the past this was accomplished by transfusion. The athlete would “donate” a unit of blood into storage and then 3 weeks later, after the body had completely replaced the blood loss, transfuse the unit back into the body. This would occur just before a big race, effectively giving the athlete an “extra” unit of blood. This enables performance improvements in endurance sports because of the extra oxygen carrying capacity. The practice has been outlawed. Not just because it is unfair but because of the dangers involved.

EPO has put a whole new spin on blood doping. No need for messy transfusions, just shoot up with EPO to increase your circulating erythrocyte mass. Until recently accurate testing has been difficult because the recombinant human EPO made in the lab is virtually identical to the naturally occurring form and there are no firmly established normal ranges for EPO in the body. The only previously available route to curtail cheating for sports governing bodies was to ban an athlete if the hematocrit (see side bar) level was too high (e.g., above 50%). Thus, over the past 10 – 15 years some athletes chose to cheat because, as long as they kept their hematocrit levels below 50%, there seemed little risk of getting caught. Of course the other way to get caught was highlighted in the disastrous 1998 Tour de France. Several team doctors and personnel from several teams were caught red-handed with thousands of doses of EPO and other banned substances. Ultimately about 50% of the teams withdrew from the race – either for cheating or in protest.

Fortunately, testing technology has now caught up and promises to stem the tide of abuse. There is now an accurate urine test that can detect the differences between normal and synthetic EPO. This test is now the standard and was the sole means to detect for EPO use in the 2004 Athens Olympic Games. The reliability of this test helps explain the cascade of athletes who have been caught and, subsequently, banned from competition. This surge in positive tests will likely decline as the “word” gets out and EPO use declines -- at least until someone figures out a work-around. Of course, there is always the next great pharmacologic or genetic cheat just lurking around the corner to consider.

Ref(1) – Tainted Glory – Doping and Athletic Performance. Noakes, TD. NEJM. 351:9. Aug.26. 2004

Why is EPO dangerous?
The reason that EPO, and transfusion blood doping, is dangerous is because of increased blood viscosity. Basically, whole blood consists of red blood cells and plasma (water, proteins, etc.). The percentage of whole blood that is occupied by the red blood cells is referred to as, the hematocrit. A low hematocrit means dilute (thin) blood, and a high hematocrit mean concentrated (thick) blood. Above a certain hematocrit level whole blood can sludge and clog capillaries. If this happens in the brain it results in a stroke. In the heart, a heart attack. Unfortunately, this has happened to several elite athletes who have used EPO.

EPO use is especially dangerous to athletes who exercise over prolonged periods. A well-conditioned endurance athlete is more dehydration resistant than a sedentary individual. The body accomplishes this by several methods, but one key component is to “hold on” to more water at rest. Circulating whole blood is one location in which this occurs and, thus, can function as a water reservoir. During demanding exercise, as fluid losses mount, water is shifted out of the blood stream (hematocrit rises). If one is already starting with an artificially elevated hematocrit then you can begin to see the problem -- it is a short trip to the critical “sludge zone”.

Additional dangers of EPO include sudden death during sleep, which has killed approximately 18 pro cyclists in the past fifteen years, and the development of antibodies directed against EPO. In this later circumstance the individual develops anemia as a result of the body’s reaction against repeated EPO injections.
COPYRIGHT©2005 Mark Jenkins
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