Related Terms

• Aranesp®, blood doping, colony-stimulating factor, cytokine, EPO, Epogen®, erythropoiesis-stimulating agent, erythropoietin, ESA, hematopoietin, hemopoietin, peptide hormone, performance enhancers, Procrit®.

Background

• Erythropoietin (EPO) is a hormone that is produced naturally by the kidneys in response to a low concentration of oxygen in the blood. While EPO is produced by the liver in the fetus, by adulthood the kidneys have taken over most EPO production.

• EPO promotes the formation of red blood cells in the bone marrow. The production of more red blood cells results in the ability to carry more oxygen to body tissue.

• In the 1980s, genetically engineered EPO was produced by biotechnology companies for clinical use. Currently, EPO is available for medical treatments under various trade names, such as Epogen®, Procrit®, and Aranesp®.

• EPO is used therapeutically in the treatment of anemia (a low amount of red blood cells) related to kidney disease, chemotherapy or radiation, HIV therapy, or heart failure. It is also being investigated for the treatment of sickle cell anemia.

• Athletes benefit from injections of EPO, a form of blood doping, because more oxygen is delivered to the cells of the body by red blood cells. EPO has been used illegally by athletes to increase performance.

• In 1985, the International Olympic Committee banned any artificial means of altering one's blood chemistry, thus banning EPO usage. The World Anti-Doping Agency, which unifies antidoping policies among sports federations worldwide, has placed EPO on its prohibited list.

• An entire cycling team was banned from the 1998 Tour de France for the use of EPO as a performance enhancer.

• Until recently, it has been difficult to detect EPO in the bloodstream or urine of athletes, as the levels do not remain high enough to identify for long. More reliable tests for the illegal usage of EPO by athletes have recently been developed.

• In 2000, scientists developed a urine test that distinguishes between naturally produced EPO and synthetic EPO. This test has been widely applied among endurance athletes, but the accuracy of it remains controversial. One criticism of the test is that it may not be able to clearly distinguish between pharmaceutical EPO and other proteins produced by an athlete's body after strenuous exercise. Scientists are working on a way to interpret these tests that can better discriminate between pharmaceutical EPO and other proteins produced in the body.

• It is necessary for these urine tests to distinguish between naturally produced EPO and manufactured EPO, because high levels of EPO produced in the body can be caused by other variables, such as altitude training.

• Belgian triathlete Rutger Beke successfully overturned an EPO doping conviction against him following a positive urine test in 2004. Beke argued that the positive test result was due to bacterial contamination (which is not uncommon, due to the presence of normal bacteria on the external urethra), causing degraded protein. He claimed the degraded protein in his urine was indistinguishable from EPO, and that the test had produced a false positive.

Technique

• General: The synthetic version of the hormone erythropoietin (EPO) is active only when injected.

• Synthetic EPO is available as a liquid in single- or multidose vials and is stored under refrigeration. The liquid should not be frozen or shaken. It can be injected into the vein (intravenously), under the skin (subcutaneously), or into the muscle (intramuscularly).

• Intravenous injections of EPO result in a rapid increase of EPO concentration in the blood; the elimination half-life, or time it takes to lose half its activity, is 4-13 hours. Subcutaneous injections result in a peak blood concentration of EPO of about 12-18 hours after administration. There is little information about how the body absorbs and breaks down intramuscular EPO injections, as it is normally given intravenously or subcutaneously.

• Medical uses: When used medically, a typical starting dose of EPO is 50 international units per kilogram of body weight injected three times weekly.

• Dosage adjustments are based on monitoring the hemoglobin levels of the patient. The suggested target hemoglobin range is between 10 and 12 grams per deciliter of blood. The dose should be reduced by 25% if the hemoglobin is 12 grams per deciliter of blood or has increased by 1 gram per deciliter of blood in a two-week period. Doses are increased by 25% if the hemoglobin does not increase by 2 grams per deciliter of blood after eight weeks of therapy. Dosage increases should not occur more frequently than every four weeks.

• Athletic performance enhancement: Athletes use EPO by injecting a synthetic version. It is often injected throughout the training for a particular event, 2-3 times weekly.

• The onset of action for EPO after injection is several days, with peak effects reached after 2-3 weeks.

• Some athletes have reported injecting 1,000 units of EPO daily for the weeks preceding a competition.

• Many athletes supplement EPO injections with either oral or injectable iron. Iron supplementation makes EPO injections more effective.

• Athletes have found that by reducing the amount of EPO injected, they are less likely to be caught by current detection methods.

• The benefits of the additional red blood cells produced by EPO injections last for several weeks to months after the injections are discontinued, while the EPO itself only remains in the system very briefly, usually a few days to a week after the last injection.

Theory/Evidence

• Synthetic erythropoietin (EPO) works in the same way as that produced by the kidneys. It causes the release of premature red blood cells from the bone marrow into the blood stream.

• Once in the bloodstream, these red blood cells mature, raising hemoglobin and hematocrit levels. This increases the oxygen-carrying capacity of the blood and results in increased oxygen concentration to body tissue. This is important to athletes, because if the muscles are not receiving enough oxygen, they fatigue rapidly.

• EPO use by athletes may increase their aerobic endurance by up to 10-15% by increasing the concentration of oxygen available to body tissue. Because maximal use of oxygen appears to be the major limiting factor in endurance sports, this may give an athlete an advantage over competitors.

• Australian studies have shown that increases in an athlete's performance produced by EPO use of more than four weeks are similar to increases expected over several years without the use of the hormone.

Safety

• Experts suggest consulting a qualified healthcare provider before making decisions about therapies or health conditions.

• Excess erythropoietin (EPO) may result in too many red blood cells. This may lead to blood clots, strokes, heart attack, seizures, high blood pressure, and other cardiovascular risks.

• Those who supplement EPO with iron are also at risk of iron overload. Side effects of iron usage include constipation, stomach irritation, nausea, vomiting, and heartburn. Iron overdose may cause damage to gastrointestinal linings, kidney and liver impairment, coma, and acidosis.

• The deaths of some athletes have been attributed to the use of EPO as a performance enhancer. Deaths associated with EPO use are often caused by sudden cardiac arrest and have happened often while the athlete was sleeping.

• People with high blood pressure or a history of heart disease or seizures are at an increased risk of complications from EPO.

• The injection of synthetic EPO may cause the body to produce antibodies against the foreign substance. These antibodies may destroy red blood cells, resulting in anemia. This means that people who inject EPO may experience a dangerous immune reaction, resulting in a low level of red blood cells.

• Other reported side effects that may be associated with EPO use include cough, respiratory congestion, shortness of breath, fever, dizziness, headache, itchiness, and joint aches.

• Injection site reactions such as irritation, swelling, redness, bruising, and pain may occur.

Author Information

• This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

Natural Standard developed the above evidence-based information based on a thorough systematic review of the available scientific articles. For comprehensive information about alternative and complementary therapies on the professional level, go to www.naturalstandard.com. Selected references are listed below.

1. Diamanti-Kandarakis E, Konstantinopoulos PA, Papailiou J, et al. Erythropoietin abuse and erythropoietin gene doping: detection strategies in the genomic era. Sports Med. 2005;35(10):831-40.View Abstract

2. Gaudard A, Varlet-Marie E, Bressolle F, et al. Drugs for increasing oxygen and their potential use in doping: a review. Sports Med. 2003;33(3):187-212.View Abstract

3. National Institutes of Health Office of Science Education. http://.science.education.nih.gov

4. Natural Standard: The Authority on Integrative Medicine. www.naturalstandard.com

5. Schumacher YO, Schmid A, Dinkelmann S, et al. Artificial oxygen carriers--the new doping threat in endurance sport? Int J Sports Med. 2001 Nov;22(8):566-71. View Abstract

6. Scott J, Phillips GC. Erythropoietin in sports: a new look at an old problem. Curr Sports Med Rep. 2005 Aug;4(4):224-6. View Abstract

7. World Anti-Doping Agency. www.wada-ama.org