EPO The Endurance Athlete's Steroid

Read the sports section of any newspaper lately and you will no doubt see the headlines dealing with Lance Armstrong’s alleged use of EPO. Apparently, he is accused of testing positive for having used the substance to enhance his performance during several Tour de France cycle races. Actually, the use of EPO in endurance exercise is nothing new and it has been recognized as an ergogenic or performance enhancing substance for several years. This article aims to provide some basic information on EPO, its mechanism of operation and the dangers involved with its use by athletes.

What is EPO?

EPO is an abbreviation for erthropoetin. Contrary to many of the articles currently in the media, erythropoietin is not a drug – it is a peptide hormone produced naturally in the body, manufactured and released from the kidney. The role of EPO is to stimulate bone marrow to manufacture more erythrocytes (red blood cells). This has the effect of increasing the hematocrit - the percentage of blood by volume composed of erythrocytes. Special oxygen sensitive cells in the kidney are able to determine the concentration of oxygen in the blood, and this is the suspected mechanism for its release into the blood stream.

A good example of EPO’s working is the effect of increased altitude on blood oxygen concentration. As altitude progressively increases, atmospheric pressure decreases. Therefore the amount of air at altitude decreases, decreasing the available oxygen (nitrogen, carbon dioxide too) needed for respiration. The kidney cells detect this decrease in oxygen and release EPO into the bloodstream to stimulate the production of more erythrocytes. Erythrocytes contain a protein called hemoglobin, which via the blood circulatory system transports oxygen from the lungs to other parts of the body and to a lesser degree carries carbon dioxide back to the lungs where it is exhaled.

Why do athletes use EPO?

Actually, the main use of administrating exogenous sources (not produced within the body) of EPO in humans is to treat patients suffering from anemia, especially those with kidney failure and those undergoing chemotherapy for cancer. However, with the recent great increase in genetic engineering technology, synthetic or recombinant EPO (rEPO) has become readily available and has come to be abused by athletes – especially endurance athletes. The theoretical logic for its use as an ergogenic aid in athletes is this: if you increase the oxygen-carrying ability of the blood (erythrocytes) above normal levels, then it follows that the muscles will receive more oxygen and be able to perform better and generate more power for longer periods of time, thereby significantly improving performance.

This logic explains why some endurance athletes train at altitude or participate in the forbidden practice of “blood doping” as a means of boosting the number of erythrocytes. Blood doping involves drawing blood from an athlete to induce anemia, waiting a few weeks to allow erythropoietin to restore the hematocrit to normal levels (~ 45% men, ~ 42% women), and then reinfusing the athlete’s stored blood thereby boosting the erythrocyte density. Administration of rEPO is capable of producing performance benefits comparable to blood doping and significantly better results than several weeks or months of altitude training. An athlete may boost their hematocrit levels 3-4% within 4 weeks with rEPO use. As a result of this ergogenic effect, several athletic governing bodies have frowned upon blood doping and rEPO use, as they are essentially methods of cheating.

How do you test for EPO abuse in athletes?

Testing athletes suspected of rEPO abuse is complicated and may in large part explain athletes like Lance Armstrong’s predicament. Although there are some protocols for the detection of rEPO, unfortunately at this time it is difficult to perform these tests with a very high degree of accuracy. rEPO has very slight biochemical differences to EPO produced within the body and is detectable in urine, but its half-life is so short, it is usually undetectable within 12 hours of administration. Another method of detection is to measure the athlete’s pre-competition hematocrit and percentage blood composed of reticulocytes (immature erythrocytes). Sports governing bodies like the International Cycling Union have placed a ceiling on athlete pre-competition hematocrit values at 50% (that is 50% of the blood volume is erythrocytes) and reticulocyte values at 2.4%. Reticulocytes begin to appear in the blood immediately after a rEPO dose and then later mature into erythrocytes. The value of 50% is “theoretically” proposed as the maximal hematocrit that can be achieved though natural physical conditioning means.

This method of setting a ceiling value is somewhat flawed however, as it may discriminate against the very few exceptional athletes (Lance Armstrong included) having a naturally higher training-induced hematocrit. In other words, it may be difficult to discriminate between a superior athlete with a genetically higher hematocit that may have boosted their levels “naturally” by performing altitude training and one that received the unfair advantage from simply taking several doses of rEPO. In the future, it is likely that rEPO and anabolic steroid hormone manufacturers will be required to attach an identifying chemical “tag” to their products to assist with detection.

What are the dangers associated with uncontrolled EPO abuse?

As with most ergogenic substances, there is usually a downside associated with their use. Although its recent track record is relatively clean, the health risks associated with its uncontrolled rEPO use have in some instances proven deadly. There is a strong link between the deaths of several Dutch cyclists and their apparent use of rEPO in the early 1980’s. The explanation for the deaths is suspected as an excessive proliferation of erythrocytes, producing a condition known as polycythemia.

As the hematocrit increases, the other main component of blood called plasma decreases. Plasma is the liquid portion of blood, and under normal conditions forms about 55% per unit volume. In a condition such as polycythemia, the blood becomes thicker - almost sludgy, making it increasingly difficult for the heart to pump blood though the body. Again is unclear of the exact cause of the deaths but it is likely that heart attacks were responsible. The increased viscosity of the blood also increases blood pressure and the risk of a clotting incident like a stroke. Just as the temptation exists for the use of any performance-enhancing product, there is the associated temptation to experiment with ever increasing doses, so the risks associated with rEPO use by the inexperienced user are quite real.

In conclusion, this article has aimed to provide some basic information on EPO and it effects on exercise and sport performance. Although there are some disadvantages associated with its use, it is probably the most effective ergogenic substance available today for endurance events. The benefits of rEPO on endurance-type exercise are comparable to the effects of anabolic steroids in events that rely heavily on strength and power. The future usefulness of EPO remains to be seen; but as science and technology advance, it is likely that rEPO may be replaced by less detectable and more effective substances such as recombinant hemoglobin and possibly even injectable genes.