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Principles of Sports Medicine & Exercise Science

Erythropoietin

by Janine Ungvarsky, Michael A. Buratovich

Category: Treatment

Specialties and related fields: Hematology, oncology

Definition: a glycoprotein cytokine secreted by the kidneys that increases the rate of production of red blood cells in response to falling levels of oxygen in the tissues

KEY TERMS

anemia: a condition in which the blood doesn’t have enough healthy red blood cells

bone marrow: the soft, spongy tissue with many blood vessels found in the center of most bones

cytokine: a broad category of small, secreted proteins and glycoproteins, such as interferon, interleukin, and growth factors, secreted by certain cells of the immune system and other tissues that influence other cells

drug doping: the use of prohibited medications, drugs, or treatments by athletes to improve athletic performance

INTRODUCTION

Erythropoietin, also known as EPO, is a cytokine manufactured in the kidneys and can also be produced synthetically. It helps to stimulate the bone marrow to grow red blood cells, which help carry oxygen throughout the body. Erythropoietin is important in several ways. Measuring the level of erythropoietin in the body can help diagnose some illnesses. Erythropoietin can be administered to help increase the number of red blood cells a person’s body produces. Erythropoietin treatment can help treat anemia, or low red blood cell levels, resulting from several causes. While EPO is used for many important and life-sustaining reasons, some athletes have inappropriately used it to improve their performance.

BACKGROUND

About 40 percent of the blood volume in the human body is made up of red blood cells, also called “erythrocytes.” Red blood cells carry oxygen from the lungs to the rest of the body and transport waste products, including carbon dioxide, away from cells and tissue in the body. When there are not enough red blood cells, the body is deprived of its oxygen to generate energy. As a result, the person often becomes tired, pale, and possibly short of breath. This condition is known as “anemia.”

Anemia is caused in one of two ways. First, anemia may result if the body does not produce enough erythrocytes. Certain medications, such as those used for chemotherapy, can impair the body’s ability to make red blood cells. Illnesses or insufficient dietary iron or vitamin B12 can cause anemia since both are needed to produce red blood cells. The second cause is the loss or damage of blood cells. Prolonged bleeding, such as from an injury or illnesses such as infections, cancer, or kidney disease, can secondarily cause anemia.

Red blood cells generally live for about one hundred twenty days before they need to be replaced. The body is continuously replenishing its supply. Some cells located in healthy kidneys can detect the reduction in oxygen in the blood as the red blood cell level drops and release erythropoietin to trigger the bone marrow to produce new cells. The kidneys produce about 90 percent of the erythropoietin the body needs; the remainder comes from the liver.

In 1906, French physician Paul Carnot and his assistant, C. Deflandre, discovered that if they took blood from an anemic rabbit and injected it into a healthy rabbit, it made more red blood cells. They deduced that something in the anemic blood triggered the production of new cells. When it proved difficult to replicate their results, some doubted their hypothesis. However, in the middle of the twentieth century, researchers were finally able to confirm the results of Carnot and Deflandre. Additional experiments that connected the circulatory systems of two living rats determined that if one was exposed to low oxygen conditions, both developed new red blood cells. This experiment confirmed the existence of erythropoietin. Between 1964 and 1977, American biochemist Eugene Goldwasser was able to isolate and purify erythropoietin. Goldwasser’s landmark discovery was followed in 1983 by the development of a synthetic or manufactured version of erythropoietin.

OVERVIEW

For many years, frequent blood transfusions and the addition of iron and B₁₂-rich foods to the diet were the only practical ways physicians treated anemia. The discovery of erythropoietin and the production of synthetic versions radically improved anemia treatment. It also made it possible to improve treatments for those undergoing treatment for serious diseases that deplete red blood cells, such as cancer, acquired immune deficiency syndrome (AIDS), and human immunodeficiency virus (HIV).

Patients who need treatment with erythropoietin receive it by injection into a vein (intravenously) or under the skin (subcutaneously). The drug requires a physician’s order. The three forms are erythropoietin alfa, sold under the brand names Procrit, Epogen, and Retacrit, and darbepoetin alfa, sold under the brand name Aranesp. Darbepoetin alfa requires less frequent administration but has a mode of action identical to erythropoietin alfa. The third, very long-acting form of epoetin beta (Mircera) has methoxy polyethylene glycol (PEG) butanoic acid groups attached to erythropoietin. These attached groups decrease the molecule’s elimination from the body and its activation of erythropoietin receptors. Consequently, patients only need one Mircera injection every two to four weeks.

Blood tests determine the effectiveness of erythropoietin. Since it takes several weeks for new red cells to form, these tests will be done two to four weeks after starting therapy with erythropoietin and may be repeated. A physician may adjust the dosages of the drug based on the results of the blood tests.

While these drugs can significantly improve anemia and help prevent it in patients with other conditions that lead to anemia, erythropoietin does have potentially serious side effects. It can cause blood clots, particularly in patients prone to them, who are idle because of prolonged bed rest, who have had surgery, or who are taking certain other medications, including several chemotherapy drugs. Patients at a higher risk of developing clots may take blood thinners while on erythropoietin to minimize the chance of clot formation. Cancer patients may experience increased progression of their cancers while on erythropoietin. For these reasons, erythropoietin products carry “Black Box Warnings” from the US Food and Drug Administration for these adverse effects. Erythropoietin formulations increase blood volume and can significantly raise blood pressure.

MISUSE

For decades, athletes have known that increasing the body’s ability to use oxygen can improve athletic performance. For this reason, athletes do wind sprints and similar exercises to build the lungs’ capacity to provide as much oxygen as possible. When erythropoietin became readily available in the late 1980s, professional athletes were quick to see its potential to artificially boost their oxygen capacity by building an abundance of oxygen-carrying red blood cells.

The use of “bootleg” synthetic erythropoietin led to “blood doping,” in which athletes take drugs as a shortcut to improving their performance. Many professional sports leagues and associations banned the use of erythropoietin beginning in the 1990s. Erythropoietin was one of several performance-enhancing drugs used by cyclist Lance Armstrong. The revelation that he was using these drugs led to Armstrong being stripped of seven Tour de France titles and an Olympic medal in 2012. Other athletes also faced penalties after being caught misusing erythropoietin.

Citation Types

Type

Format

MLA 9th

Ungvarsky, Janine, and Michael A. Buratovich. "Erythropoietin." Principles of Sports Medicine & Exercise Science, edited by Michael A. Buratovich, Salem Press, 2022. Salem Online, online.salempress.com/articleDetails.do?articleName=POSpKin_0142.

APA 7th

Ungvarsky, J., & Buratovich, M. A. (2022). Erythropoietin. In M. A. Buratovich (Ed.), Principles of Sports Medicine & Exercise Science. Salem Press. online.salempress.com.

CMOS 17th

Ungvarsky, Janine and Buratovich, Michael A. "Erythropoietin." Edited by Michael A. Buratovich. Principles of Sports Medicine & Exercise Science. Hackensack: Salem Press, 2022. Accessed September 16, 2025. online.salempress.com.

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