EPO is an erythropoiesis-stimulating agent (ESA) that is sold in recombinant form (rhEPO) for injection. It usually is packaged as a lyophilized (freeze dried) powder that is reconstituted with sterile water before injection. One popular form is called Epogen (r), and it is made for subcutaneous usage. A starting dosage is typically 20 i.u. per kilogram bodyweight, 3 times/week. After two to four weeks, a maintenance dose of 20 i.u. /kg BW can be taken once a week.
EPO use can be very dangerous if the user allows their hematocrit to creep too high. The ideal hematocrit for athletic performance is thought to be 55 (expressed in percent). Levels above this can result in "sludging" of the blood, which reduces microcirculation. This is counterproductive to oxygen transport. Additionally, at high hematocrit levels one is at greater risk for deadly vascular events such as stroke, especially if he/she becomes dehydrated during competition (which increases hematocrit even further).
In addition to increasing aerobic efficiency through greater oxygen transport in the blood, there is some evidence suggesting EPO may also have anabolic effects. EPO has been shown in rat studies to substantially increase weight gain and injury repair after surgery. Furthermore, EPO receptors are present on myoblasts (immature muscle cell progenitors) and may have a potential in muscle development and repair.
EPO, or its alternative erythropoetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production. It is a cytokine for erythrocyte (red blood cell) precursors in the bone marrow.
Also called hematopoietin or hemopoietin, it is produced by the peritubular capillary endothelial cells in the kidney, and is the hormone that regulates red blood cell production. It also has other known biological functions. For example, EPO plays an important role in the brain's response to neuronal injury. EPO is also involved in the wound healing process.
When exogenous EPO is used as a performance-enhancing drug, it is classified as an erythropoiesis-stimulating agent (ESA). Exogenous EPO can often be detected in blood, due to slight difference from the endogenous protein, for example in features of posttranslational modification.
Red blood cell production
The primary role of EPO is an essential hormone for red blood cell production. Without it, definitive erythropoiesis does not take place. Under hypoxic conditions, the kidney will produce and secrete EPO to increase the production of red blood cells by targeting CFU-E, proerythroblast and basophilic erythroblast subsets in the differentiation. EPO has its primary effect on red blood cell progenitors and precursors (which are found in the bone marrow in humans) by promoting their survival through protecting these cells from apoptosis.
EPO is the primary erythropoietic factor that cooperates with various other growth factors (e.g., IL-3, IL-6, glucocorticoids, and SCF) involved in the development of erythroidlineage from multipotent progenitors. The burst-forming unit-erythroid (BFU-E) cells start EPO receptor expression and are sensitive to EPO. Subsequent stage, the colony-forming unit-erythroid (CFU-E), expresses maximal EPO receptor density and is completely dependent on EPO for further differentiation. Precursors of red cells, the proerythroblasts and basophilic erythroblasts also express EPO receptor and are therefore affected by it.
Epo has a range of actions including vasoconstriction-dependent hypertension, stimulating angiogenesis, and inducing proliferation of smooth muscle fibers. It can increase iron absorption by suppressing the hormone hepcidin.
EPO levels of 100 times the baseline have been detected in brain tissue as a natural response to hypoxic damage. In rats, pretreatment with erythropietin was associated with neuronal protection during induced cerebral hypoxia. Trials in humans have not been reported.
Multiple studies have suggested that EPO improves memory. This effect is independent of its effect on hematocrit. Rather, it is associated with an increase in hippocampal response and effects on synaptic connectivity, neuronal plasticity, and memory-related neural networks. EPO may have effects on mood.
EPO available for use as therapeutic agents are produced by recombinant DNA technology in cell culture, and include Epogen/Procrit (epoetin alfa) and Aranesp (darbepoetin alfa); they are used in treating anemia resulting fromchronic kidney disease, inflammatory bowel disease (Crohn's disease and ulcer colitis) and myelodysplasia from the treatment of cancer (chemotherapy and radiation). The package inserts include boxed warnings of increased risk of death, myocardial infarction, stroke, venous thromboembolism, and tumor recurrence, particularly when used to increase the hemoglobin levels to more than 11 to 12 g/dl.