Erythropoietin Essay Essay, Research Paper


Erythropoietin is a glycoprotein that is produced primarily in the kidneys in adults and, to a lesser extent, in the liver. It behaves like a hormone, regulating the level of erythropoiesis, and keeping the RBC count within a narrow range

It is used widely in medicine as a treatment for a number of serious illnesses, ranging from types of anaemia, to the treatment of certain types of cancer, and also in the battle against AIDS. Unfortunately certain athletes, who will do anything to win, have realised its ergogenic benefits, and also the severity of its misuse.

Regulation of Erythropoietin Production.

In the kidneys, erythropoietin is produced in fibroblastoid interstitial cells in the inner renal cortex, while in the liver, the hormone is produced by both hepatocytes and interstitial fibroblastoid cells. Although a variety of growth factors influence erythroid progenitor cell proliferation, erythropoietin is the most important, and erythropoiesis cannot continue in its absence.

Among the haematopoietic growth factors, erythropoietin is one of few that behaves like a hormone. It is unique because its production, under normal circumstances, is controlled solely at the level of its gene, by tissue hypoxia and not by the absolute number of circulating erythrocytes.

Hypoxia is the sole physiologic stimulus for erythropoietin production, and an excess of oxygen suppresses its production but never completely.

Some facts about EPO. (Birchard K, Lancet 1998; 352: 42.)

? Neither age nor gender influences the plasma erythropoietin level,

? Plasma erythropoietin is constant in a given individual,

? Erythropoietin production is regulated at the level of its gene,

? Hypoxia is the only physiologic stimulus for erythropoietin production,

? There are no pre-formed stores of erythropoietin,

? There is only one form of circulating erythropoietin

Following production in the kidneys and liver, erythropoietin travels to the bone marrow to interact with specific haematopoietic progenitor cells where it maintains RBC production.

What evidence is there that people take erythropoietin?

There are two current tests for EPO abuse. Prior to these however was a Haematocrit count. If the count was too high then the athlete in question would not be allowed to compete, but there would be no ban, as the test didn’t actually prove that they were taking an illegal substance. The first of the current tests is to check the urine for recombinant EPO (an artificial type made by drug companies). This can easily be overcome by stopping the administration of EPO two or three weeks prior to competition. This way, the high levels of EPO will be out of the system, yet the large benefits of it will last for a number of months.

The other test is a blood test. EPO injections produce high quantities of immature RBC’s in the blood, but again this can be over come by knowing how long it takes the immature cells to mature and stopping the injections enough in advance of the competition.

The way around this is obviously random testing out with the events, but this is not always viable.

What is the rationale that leads people to take it?

Athletes use erythropoietin to stimulate erythropoiesis, Until now, detection was a problem because erythropoietin is normally found in urine, and blood-sample analyses indicate only that erythropoiesis had been stimulated, not that drug use is to blame. EPO regulates erythropoiesis, keeping the packed-cell volume within a narrow range. Muscles of elite athletes need a lot of oxygen. A higher packed-cell volume can be achieved by injecting EPO. A higher packed-cell volume increases delivery of oxygen to tissues and enhances performance during competitions that require stamina, such as long-distance cycling and cross-country skiing.

Theoretically, a person could continue indefinitely to increase his/her work rate and remain in an aerobic state as long as the blood can continue to supply sufficient oxygen to the increasingly worked muscles.

A greater blood volume increases the amount of blood returning to the heart and therefore will allow a greater amount to be pumped out each heart beat, allowing the heart to pump more blood without increasing the heart rate. This is known as the Frank-Starling mechanism.

Red blood cells are an important acid buffer as well. With more blood cells you should be able to buffer more lactic acid. This means that EPO use may boost both the aerobic and anaerobic energy systems.

With EPO use, you could raise your haematocrit to about 55%, thereby increasing your blood’s haemoglobin content to 17.7 grams per 100 ml. Compare this to a normal haematocrit of about 45% and a haemoglobin content of 15 grams per 100ml, an 18% increase. This would mean a delivery of an additional 3.6 ml of oxygen per 100 ml of blood to active muscle – a serious advantage!

What advice would you give to someone who asked you if they should take it?


Erythropoietin use in fit young adults could have severe consequences. By boosting haematocrit levels above 50%, they are replicating polycythaemia, a disease that makes blood viscous. The athlete may go into cardiac arrest, have a pulmonary embolism, develop clots in any small vessel in the body, and experience seizures with hypertensive encephalopathy (inflammation of the brain causing disorientation, drowsiness, delirium, and possibly coma) that could be fatal.

One of the greatest risks is the combined use of EPO and steroids. If both drugs were used simultaneously, a stacking effect would occur, but it is more serious than that. When administering testosterone and erythropoietin in combination, it was found that the increase in erythropoiesis was much greater than the additive effect of both agents

Steps to reduce the risks may be to create a hyperhydrated state within the body and thus “diluting” the blood, or to take aspirin, intravenous heparin, vitamin E, and fatty fish oil to reduce clotting factors and allow RBCs to be more flexible and malleable. However, these proposed preventative measures have not been proven to work with EPO and such activities are discouraged.



It was suspected, but not proven, that the deaths of 18 Belgium and Dutch world-class cyclists may have been linked to erythropoietin-induced RBC growth.

Clearly EPO use can boost performance but the risk to the user is just too great. Any method that can safely dissuade athletes away from this hazardous avenue of performance enhancement should be considered.


M, Larkin. The Lancet, Issue: June 10, 2000

J. J. M. Marx. The Lancet, Issue: August 8, 1998

Audran, M., et all., Effects of Erythropoietin Administration in Training Athletes and Possible Indirect Detection in Doping Control. 1999 Medicine and Science in Sports and Exercise, 195: 639-645

Birchard K. Why doctors should worry about doping in sport. Lancet 1998; 352: 42. 9703/AIS blood. Html.

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