Biology for Nursing Practice
(Location of the University)
INTRODUCTION
The earliest recorded use of performance-enhancing substances dates back to the era of the Olympians in Greece, specifically 776 BC (Bowers 1998). ‘Doping’—an overused term in the field of sports—originates from the Dutch word “doop”, a viscous opium juice which was once a favorite of the ancient Greeks.
Nonetheless, it is a common knowledge of today that the use of performance-enhancing drugs is banned because of the unfair advantage it gives to sportsmen. Cunning as it may seem, athletes in the 1990s have found ways to improve their performance sans the use of mainstream drugs that could be easily detected through tests. These include blood doping, erythropoietin stimulating agent (ESA) use and erythropoietin (EPO) administration. The former involves classic blood transfusions—either autologous or homologous—to increase one’s red blood cell count, hematocrit and haemoglobin (Power and Howley 2001).
But with the drawbacks brought about by blood doping such as transfusion-related infections and storage issues, the popularity of ESA and EPO use has soared.
Epogen was initially approved by the Food and Drug Administration (FDA) in 1989 for its clinical uses in hematologic disorders e.g. anemia related to kidney failure. Erythropoietin injections were aimed at naturally increasing the red blood cells of the body. Exogenous EPO was thought to augment maximal oxygen uptake (VO2 max); that is, the maximal oxygen uptake that can be utilized at the cellular level for the entire body (Baechle and Earle 2000).
Because ESAs and EPO do not require risky transfusions, many endurance athletes in the 1990s were believed to have abused such medications in order to increase their hemoglobin and hematocrit levels (Truong and Ip 2012). The ultimate goal indeed was to improve sports performance through enhanced oxygen transport to the muscles, bones, brain and other body organs.
Along with the ethical considerations, abusing EPO has brought about numerous medical complications (Birchard 2000). Adverse effects include polycythemia, congestive heart failure, stroke, myocardial infarction and death. Numerous serious cases due to EPO abuse have been documented.
ERYTHROPOIETIN: WHAT IT IS AND WHAT IT DOES TO THE BODY
Red blood cell production—otherwise known as erythropoiesis—is controlled by a glycoprotein hormone called erythropoietin (EPO). EPO is a protein signaling molecule (cytokine) for RBC precursors in the bone marrow. Also known as hematopoietin, EPO is produced by the kidney’s interstitial fibroblasts in association with the tubular epithelial tubule and the peritubular capillary (Jacobson, Goldwasser, Fried and Plzak 1957). During the fetal and perinatal period, however, EPO is largely produced by the perisinusoidal cells of the liver. It is only during adulthood that renal production of EPO is predominant.
EPO production is primarily stimulated under hypoxic conditions—that is, when the body is short of oxygen supply (Beleslin-Cokic, Cokic, Yu, Weksler, Schechter and Noguchi 2004). EPO levels in the body can increase up to a thousand-fold during hypoxic stress.
Aside from erythropoiesis, endogenous EPO is responsible for various bodily mechanisms such as vasoconstriction, angiogenesis (a physiological process through which new vessels form from pre-existing ones), proliferation of smooth muscle fibers and iron absorption (Ashby et. al 2010). Several studies also suggest that EPO can boost memory. This is associated with an increase in hippocampal response plus the effects on synaptic connectivity (Adamcio et. al 2008).
THE BIRTH OF EXOGENOUS ERYTHROPOIETIN
Scientists before 1980s have long struggled in coming up with treatment modalities to cure anemia, a hematologic condition characterized by deficiency of red blood cells and/or hemoglobin.
It was only through the efforts of the following people on separate occasions that a cutting-edge treatment came to existence: Paul Carnot (a French professor in 1905 who proposed the idea that hormones regulate RBC production); Eva Bonsdroff, Eeva Jalavisto, K.R. Reissman and Allan Erslev (who studied the hemopoietic substance “erythropoietin”); John Adamson and Joseph Eschbach (who isolated various forms of renal failure and the role of EPO in erythropoiesis). The result was a purified EPO that later on evolved into its synthetic (Epogen) and genetically-engineered (RhEPO) counterparts.
CLINICAL APPLICATIONS OF EPO
John, Jaison, Jain, Kakkar and Jacob (2012) support that the recombinant human erythropoietin is arguably the best therapeutic application of recombinant DNA technology to date. It has successfully resolved cases of erythropoiesis-related anemia secondary to renal failure, HIV and myelodysplasia.
Many kinds of RhEPO are commercially available today. Its efficacy is dose dependent. The dosing is tailored according to the patient’s clinical presentation as well.
BLOOD DOSING—AND ITS DARKEST SIDE
Administration of EPO increases the body’s maximum oxygen consumption capacity. As a result, a person’s endurance is heightened and his physique improves. Such findings have led to its misuse in the field of sports (Gaudard, Varlet-Marie, Bresolle and Audran 2003).
Despite the known benefits, EPO use has its share of risks. Misuse can lead to various complications.
It has been observed that the incidences of adverse effects in anemic patients occur as the hemoglobin levels increase above 13.0 g/dL (Birchard 2000). Singbartl (1994) concluded in his study that the adverse effects of long-term EPO administration include arterial hypertension, cerebral convulsion, thrombo-embolism, iron deficiency and influenza-like syndrome.
The effects of misuse in endurance athletes cannot be overlooked as well. Lage et.al (2002) reported about the case of a 26-year old professional cyclist who admitted using RhEPO and was later diagnosed with cerebral sinus thrombosis. The patient presented a 2-month history of headaches and his MRI scans revealed occlusion of the right transverse sinuses and superior sagittal regions. In another research developed by Fisher (1991), he stated that 18 European cyclists have died possibly because of EPO abuse.
ERYTHROPOIETIN AND THROMBOSIS
Such striking events brought about by EPO administration could be linked to the combination of increased hematocrit, thicker blood viscosity and dehydration; thus, making the blood sludgy and prone to thrombus-formation (Begg and Hearns 1966).
In a study conducted by Besarab et.al (1998), it has been said that the relative risk of death in the high hematocrit group in dialysis patients was contributed by increased doses of erythropoietin. Also, a rapid rise in hemoglobin levels has been associated by series of adverse cardiovascular events such as vascular access thrombosis, myocardial infarction and cerebrovascular accident (Abramowicz 2001).
MORE ABOUT EPO IN COMPETITIVE SPORTS
According to John et.al (2012), the most common recombinant EPOs and analogues misused by athletes are RhEPO, Darbepoetin alpha and CERA.
Because of the hazards brought about by EPO abuse, the International Olympic Committee in 1990 prohibited its use in sports. However, EPO’s availability in the market makes it more challenging for the sports and ethics organizations plus law enforcement agencies to detect misuse cases. For one, differentiation between endogenous and exogenous erythropoietin is difficult. EPO has a relatively short half-life in serum (Fukuda, Sasaki and Lopez 1989) and is undetectable in urine after 3-4 days of administration.
CONCLUSION
Numerous attempts at detection have been carried out in the past few years. Blood doping is still prevalent as athletes continue to develop new techniques to counter the system. Exercise studies of RhEPO use has shown to heighten levels of hemoglobin, hematocrit, VO2 max other markers—some of which are highly correlated with performance enhancement. That being said, temptation to misuse EPO is likely in the world of sports. There is certainly a need for reinforcement and awareness to athletes, coaches, sports organizations and even medical practitioners about the potential dangers that EPO abuse could bring.
REFERENCES
- Abramowicz, M., 2001. Darbepoetin (Aranesp)—A long-acting erythropoietin. Med Lett 43:109-110.
- Adamcio, B., Sargin, D., Stradomska, A., Medrihan, L., Gertler, C., Theis, F., Zhang, M., Müller, M., Hassouna, I., Hannke, K., Sperling, S., Radyushkin, K., El-Kordi, A., Schulze, L., Ronnenberg, A., Wolf, F., Brose, N., Rhee, J.S., Zhang, W., Ehrenreich, H., 2008. Erythropoietin enhances hippocampal long-term potentiation and memory. BMC Biology 6: 37.
- Ashby, D.R., Gale, D.P., Busbridge, M., Murphy, K.G., Duncan, N.D., Cairns, T.D., Taube, D.H., Bloom, S.R., Tam, F.W., Chapman, R., Maxwell, P.H., Choi, P., 2010. Erythropoietin administration in humans causes a marked and prolonged reduction in circulating hepcidin. Haematologica 95 (3): 505–8.
- Baechle, T.R. and Earle, R.W., 2000. Essentials of strength training and conditioning. Human Kinetics (2nd edn). Champaign, USA.
- Begg, T.B., Hearns, J.B., 1966. Components in blood viscosity. The relative contribution of haematocrit, plasma fibrinogen and other proteins. Clin Sci [online] 31:87-93. Available at: <http://www.ncbi.nlm.nih.gov/pubmed/5912708?dopt=Abstract> [Accessed 26 May 2014].
- Beleslin-Cokic, B.B., Cokic, V.P., Yu, X., Weksler, B.B., Schechter, A.N. and Noguchi, C.T., 2004. Erythropoietin and hypoxia stimulate erythropoietin receptor and nitric oxide production by endothelial cells. Blood, 104(7):2073-80
- Besarab, A., Bolton, W.K., Browne, J.K., et al., 1998. The effects of normal as compared with low hematocrit values in patients with cardiac disease who are receiving hemodialysis and epoetin. The New England Journal of Medicine [online] 339(9):584-90. Available at: <http://www.ncbi.nlm.nih.gov/pubmed/9718377?dopt=Abstract> [Accessed 26 May 2014].
- Birchard, K., 2000. Past, present, and future of drug abuse at the olympics. Lancet 356: 1008.
- Bowers, L., 1998. Athletic Drug Testing. Clinics in Sports Medicine 17:299-318.
- Fukuda, M.N., Sasaki, H., Lopez, L. and Fukuda, M., 1989. Survival of recombinant erythropoietin in the circulation: The role of carbohydrates. Blood 73:84–9.
- Gaudard, A., Varlet-Marie, E., Bressolle, F. and Audran, M., 2003. Drugs for increasing oxygen and their potential use in doping: a review. Sports Med 33(3):187-212.
- Jacobson, L.O., Goldwasser, E., Fried, W., Plzak, L., 1957. Role of the kidney in erythropoiesis. Nature [online] 179 (4560): 633–4. Available at: <http://www.nature.com/nature/journal/v179/n4560/abs/179633a0.html> [Accessed 26 May 2014].
- John, M.J., Jaison, V., Jain, K., Kakkar and Jacob, J.J., 2012. Erythropoietin use and abuse. Indian J Endocrinol Metab [online] 16(2):220-227. Available at: <http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3313739/> [Accessed 26 May 2014].
- Lage, J.M., Panizo, C., Masdeu, J. and Rocha, E., 2002. Cyclist’s doping associated with cerebral sinus thrombosis. Neurology 58: 665.
- Power, S.K. and Howley, E.T., 2001. Exercise physiology. McGraw-Hill, New York.
- Singbartl, G., 1994. Adverse events of erythropoietin in long-term and in acute/short-term treatment. Clin Investig [online] 72(6 Suppl):S36-43. Available at: http://www.ncbi.nlm.nih.gov/pubmed/7950171 [Accessed 26 May 2014].
- Truong, H.B. and Ip, E.J., 2012. A Review of Erythropoietin Abuse: An Analysis of Effectiveness and Safety in Exercise. Sports Med Doping Stud [online] 2:2. Available at: http://omicsonline.org/a-review-of-erythropoietin-abuse-an-analysis-of-effectiveness-and-safety-in-exercise-2161-0673.1000106.pdf [Accessed 26 May 2014].
