What are the benefits of erythropoietin?
Artificially increasing your erythropoietin levels produces more haemoglobin and red blood cells and therefore improves the amount of oxygen that can be delivered to tissues, particularly muscles. This can improve performance, although this type of doping practice is banned by most professional sport committees.
What does it mean when your Erythropoietin is high?
Increased levels of erythropoietin might be due to a condition called polycythaemia (too many red blood cells) or it could be evidence of a kidney tumour. Raised levels of Erythropoietin in athletes indicate erythropoietin abuse (doping).
Does erythropoietin enhance whole body lipid oxidation during prolonged exercise?
Erythropoietin enhances whole body lipid oxidation during prolonged exercise in humans. J Physiol Biochem 2015;71:9–16. doi:10.1007/s13105-014-0374-8 . Modelling the transfers of training effects on performance in elite triathletes. Int J Sports Med 2002;23:55–63. doi:10.1055/s-2002-19276 .
Does recombinant human erythropoietin increase aerobic capacity?
. Prolonged administration of recombinant human erythropoietin increases submaximal performance more than maximal aerobic capacity. Eur J Appl Physiol 2007;101:481–6. doi:10.1007/s00421-007-0522-8
How much does EPO increase performance?
Improves 3-K time by 6%; effects last at least four weeks. A new and nicely designed study of EPO's effect on distance runners has shown that four weeks of every-other-day injections improves 3000-meter running time by an average of 6%.
How does EPO increase endurance capacity?
EPO doping in Athletes Raised levels of Erythropoietin in athletes indicate erythropoietin abuse (doping). EPO doping can boost the number of red blood cells and there by increased availability of oxygen to the muscles. This can help the athlete with increased performance ability and endurance.
Does EPO increase stamina?
Like steroids, this hormone actually occurs naturally, being produced by the cells in your kidneys to regulate the production of red blood cells spewing from your bone marrow. These red blood cells carry more oxygen in your blood so the EPO increases your oxygen absorption, reduces fatigue and increases endurance.
Can athletes improve their performance by taking recombinant human erythropoietin?
Recombinant human erythropoietin (rHuEPO) is used clinically to improve circulating erythrocyte levels. The literature is inconsistent regarding the performance-enhancing effects of erythropoietin; some studies suggest it is ergogenic, while other studies suggest there is no evidence to support the claim.
How do athletes use erythropoietin?
By injecting EPO, athletes aim to increase the number of red blood cells and, consequently, their aerobic capacity. If EPO levels are too high the body will produce too many red blood cells which can thicken the blood, leading to clotting, heart attack and stroke.
What is the action of erythropoietin?
Erythropoietin acts by binding to its cell surface receptor which is expressed at the highest level on erythroid progenitor cells to promote cell survival, proliferation, and differentiation in production of mature red blood cells.
Why is erythropoietin banned in sport?
The drug erythropoietin, often called EPO, is banned from sports because it is believed to enhance an athlete's performance and give people who use it an unfair advantage over unenhanced competitors.
Does EPO work immediately?
When epoetin begins to work, usually in about 6 weeks, most people start to feel better. Some people are able to be more active. However, epoetin only corrects anemia. It has no effect on kidney disease, cancer, or any other medical problem that needs regular medical attention.
Does EPO increase VO2 max?
Heuberger and colleagues found that EPO significantly increased haemoglobin levels and increased VO2 max.
What is one way for athletes to increase their red blood cell count?
The easiest and legal way for athletes to increase the volume of red blood cells in their body is to train at altitude. When the body is exposed to the lower oxygen of the high altitude the kidneys produce EPO and the cell counts increase.
Why did Lance Armstrong EPO?
Gizmodo notes the irony that Armstrong was "likely given EPO when he was recovering from cancer under a doctor's treatment." Aside from the apparent endurance boost provided by EPO, Swiss researchers found that EPO also has a performance-enhancing effect in the brain, increasing motivation.
How much can EPO increase VO2 max?
EPO treatment significantly increased VO2,max by approximately 5% in both the HR and C lines, with no dosexline type interaction.
Does EPO increase VO2 max?
Heuberger and colleagues found that EPO significantly increased haemoglobin levels and increased VO2 max.
Do marathon runners use EPO?
There are two popular methods athletes use to increase their red blood cell count: blood transfusions and medications, like EPO. While preparing naturally for a marathon takes months of incremental training, blood transfusions and EPO are respectively effective within hours to weeks.
What type of fitness training can affect the hormone erythropoietin EPO?
In the classical LH-TH method, which is the first concept of altitude training, the athletes live and train at moderate altitudes (2,000–3,000 m) to stimulate erythropoiesis, which increases erythrocyte volume, thus enhancing sea-level endurance performance.
How to increase EPO?
Although some herbs may help boost natural production of EPO, exercise is the most effective way to do so. However, it also matters which kind of exercise you preform. The more intense exercise, the greater the stimulus. Although jogging can increase the levels of EPO, it is not the most effective.
Why is EPO used in the cardiovascular system?
This prevents excessive accumulation unlike when using performance enhancing drugs or PEDs. EPO is primarily used to treat anemia, especially in people with kidney failure but it can also be used to treat anemia in people with congestive heart failure . However, EPO receptors are present throughout the cardiovascular system because ...
What herbs increase stem cell production?
While there are a couple of herbs which can increase natural production of this powerful hormone, two of them stand out. This includes Echinacea and Astragalus, a well known adaptogen. These two act on bone marrow causing it to increase production of stem cells.
What is EPO in sports?
Erythropoietin herbal boosters: Its effect on the heart muscle and athletic performance. EPO or erythropoietin is a hormone responsible for red blood cell production. It is produced primarily by the kidneys. Liver also produces it but in much smaller amounts.
What is EPO used for?
Since EPO significantly increases aerobic abilities, especially endurance, it is often abused by endurance athletes such as marathon runners and cyclists. It was one of the main PEDs used by Lance Armstrong and several other top cyclists which competed in Tour de France, at the time.
What does it mean when you have more EPO?
So, more EPO means more stem cells and red blood cells, higher hemoglobin levels and oxygen levels in the blood.
Why do athletes work out at night?
Athletes that abuse EPO may start working out in the middle of the night, in order to prevent formation of blood clots which may lead to heart attack or heart failure. On the other hand, erythropoietin produced by your own body can help reduce the risk of heart disease since its levels are regulated by the endocrine system.
What is EPO hormone?
EPO is a naturally produced glycoprotein hormone that induces erythropoiesis, and maturation and proliferation of oxygen-delivering erythrocytes . 3 The body uses EPO to control the number of circulating erythrocytes, thus maintaining tissue oxygen delivery levels within a narrow range. 3 Recombinant human erythropoietin (rHuEPO) has also been developed in the laboratory and successfully administered to patients with late-stage renal failure to improve circulating erythrocyte levels. 4
What is rHuepo used for?
Recombinant human erythropoietin (rHuEPO) is used clinically to improve circulating erythrocyte levels. The literature is inconsistent regarding the performance-enhancing effects of erythropoietin; some studies suggest it is ergogenic, while other studies suggest there is no evidence to support the claim.
What is rHuepo in psychology?
rHuEPO was the sole substance administered to participants at a given time. Studies that looked at other substances were included if participants were not administered both substances simultaneously or if we were able to separate the effects of these substances to analyse the effects of the intervention. The presence of a placebo group and reported between-group differences were also necessary for inclusion to allow for comparisons.
How were outcomes stratified?
Outcomes were stratified by treatment periods and dosages. Only differences between intervention and placebo groups were included for analysis to control for the placebo effect. Where appropriate, quantitative analysis was performed for outcomes with two or more studies and with low heterogeneity using a random-effects analysis model. Review Manager V.5.3 was used to calculate the I² statistics for heterogeneity, overall effect and standard mean difference (SMD), as well as to construct forest plots. Effect sizes were measured using SMDs with 95% CIs to allow for standardisation of different unit measurements per outcome. A priori sensitivity analyses for baseline participant training status (untrained vs prior training) would be carried out for analyses with moderate heterogeneity as per the Cochrane interpretation guide (40%<I²<60%). 11 When quantitative analysis was not performed (eg, substantial heterogeneity with I² >60%), 11 a qualitative analysis for combining evidence was performed. At least two independent reviewers analysed the data. Disagreements were resolved by repeated review and consensus.
When did rHuepo become available?
Introduction Athletes have attempted to glean the ergogenic benefits of recombinant human erythropoietin (rHuEPO) since it became available in the 1980s. However, there is limited consensus in the literature regarding its true performance-enhancing effects.
Does rHuepo increase RPE?
One study reported no significant difference in RPE between the placebo group and the groups that received low, medium or high doses of rHuEPO under both testing conditions. 13 In contrast, another study reported that a high dose of rHuEPO increased RPE compared with the placebo group (p<0.05). 22
Is rHuepo better than placebo?
There is low-to-moderate quality evidence suggesting that, independent of dosage, rHuEPO may be more beneficial than placebo in enhancing haematological, pulmonary measures, maximal power output and time to exhaustion.
What is the function of erythropoietin?
It stimulates the survival, proliferation, and differentiation of erythroblasts ( Jelkmann, 2011 ). The molecule exerts its effects by binding to its receptor (EPOR), which triggers its activation, followed by the activation of different kinases and intracellular signaling pathways such as the Janus kinase (JAK)-2 and signal transducer and activator of transcription (STAT)-5 pathways ( Debeljak and Sytkowski, 2012 ). Besides its hematopoietic effects, EPO-EPOR signaling functions in several tissues and systems, including the central nervous system, heart, kidney, gastrointestinal system, reproductive tract, and endothelium ( Ogunshola and Bogdanova, 2013, Arcasoy, 2008 ). Moreover, the pleiotropic effects of erythropoietin (EPO) are not only mediated by an endocrine, but also by autocrine and paracrine mechanisms ( Sytkowski, 2007 ).
What is erythropoietin in sports?
Abstract. Erythropoietin (EPO) is the main hormone regulating red blood cell (RBC) production. The large-scale production of a recombinant human erythropoietin (rHuEPO) by biotechnological methods has made possible its widespread therapeutic use as well as its misuse in sports. Since the marketing of the first epoetin in 1989, ...
What was the impact of oxygen transport on athletes?
During the Mexico City 1968 Olympics, it became evident that the oxygen transport capacity of exercising muscles was the limiting factor for aerobic performances ( Jokl et al., 1969 ). The performances were significantly affected by altitude-impaired oxygen delivery. Consistent with this phenomenon, Ekblom et al. reported that an increase in the hemoglobin (Hb) concentration can ameliorate the maximal oxygen uptake (VO2max) and consequently athletic performance ( Ekblom et al., 1972 ). Shortly thereafter, athletes started to experiment with blood transfusions to increase Hb for improved performance. However, this practice requires a sophisticated methodology and carries the risk of adverse effects. Following its global commercialization between 1987 and 1989, recombinant human erythropoietin (rHuEPO) use surged in the 1990s/2000s due to its easy access and its significant impact on performance. The drug was readily placed on the International Olympic Committee (IOC) list of banned substances in 1990, although no validated detection method was available. A decade later, a direct test to effectively differentiate between endogenous and recombinant EPO based on isoelectric focusing (IEF) was developed by Lasne and de Ceaurriz ( Lasne and de Ceaurriz, 2000 ). Concurrently, the indirect detection of rHuEPO via blood markers of erythropoiesis was also established ( Parisotto et al., 2000 ). In accordance with the indirect detection of blood doping, the Athlete Biological Passport (ABP) was developed and implemented in 2008 ( Sottas et al., 2011 ). The hematological module of the ABP aims to assess the effects of blood manipulators, such as erythropoiesis-stimulating agents (ESAs), on selected biological parameters. The implementation of this tool provoked a trending change of cheating athletes that now use microdoses of rHuEPO to avoid large fluctuations in the levels of blood markers in the ABP and to reduce the detection window for classic direct detection ( Ashenden et al., 2011 ). These microdoses are hardly detectable with classical hematological parameters, and new markers need to be developed to increase the sensitivity of the diagnostic tool. Recently, the pharmaceutical industry has developed new ESAs, which provide good candidates for doping. Alarmingly, some athletes have tested positive for some of these agents, although many are still in clinical trials. Consequently, anti-doping laboratories have to prepare for this situation and to develop new methods for the detection of ESAs. Omics technologies, such as transcriptomics and ironomics, offer promising candidates for the refinement of the hematological module. Although the microdosing trend has decreased the occurrence of death related to ESAs, their long-term misuse associates with significant adverse effects that can be irreversible. Therefore, anti-doping authorities play a crucial role in educating athletes about these risks.
How is HUEPo produced?
Endogenous HuEPO production is mainly regulated by hypoxia and this regulation occurs at the transcriptional level ( Jelkmann, 2011 ). When the oxygen supply of the human body decreases, transcriptional factors defined as hypoxia-inducible factors (HIFs) are activated, inducing the expression of several genes that include the Epo gene. Under normoxic conditions, GATA-2 and NF-κB suppress the Epo promoter, and HIF prolyl hydroxylases (HIF-PH) degrade the HIFα subunit ( La Ferla et al., 2002 ). Under hypoxic conditions, on the other hand, the oxygen-dependent activity of HIF-PH shuts down, which stabilizes HIFα and triggers its dimerization with HIFβ and Epo transcription.
Why do people use ESA?
The public often forgets that ESAs are first intended to ameliorate the quality of life in patients suffering from a particular syndrome. Molecules designed to increase erythropoiesis are mainly used to treat anemia in patients with CKD or undergoing chemotherapy. Under normoxic physiological conditions, Hb levels are endogenously regulated by the blood oxygen level via the HIF system. ESA injections shock the system, and increase the erythrocyte number and the transport capacity of oxygen, which increases blood viscosity and the probability of thromboembolic events. Although professional athletes gravitate toward microdosing regimens that require medical supervision, amateur athletes may use high doses of these compounds and often according to anecdotal information. Besides increasing blood viscosity, long-term use of ESAs can result in various side effects such as red cell aplasia and heart failure ( Tsitsimpikou et al., 2011, Locatelli and Del Vecchio, 2003 ). In individuals with an iron deficiency, epoetin can elevate thrombocyte counts and increase the risk of cardiovascular problems, including cardiac arrest, seizures, arrhythmia, hypertension, congestive heart failure, vascular thrombosis, myocardial infarction, and edema ( Franz, 2009, Tsitsimpikou et al., 2011, Streja et al., 2008 ). Moreover, EPO is also involved in angiogenesis ( Hardee et al., 2007 ), and EPO withdrawal may lead to neocytolysis ( Trial et al., 2001 ). Furthermore, the combination microdoses of rHuEPO with other substances, such as testosterone or transfused blood, can have harmful consequences for the individual. The administration of ESAs to subjects with naturally high endogenous levels of EPO can also cause serious adverse effects. Finally, endogenous EPO is depleted upon the administration of rHuEPO through a negative feedback mechanism and this inhibition can be irreversible after long-term treatment ( Tsitsimpikou et al., 2011 ).
What is a rHuepo?
The third -generation rHuEPO continuous erythropoietin receptor activator (CERA) was launched on the European market in 2007 ( Jelkmann, 2012 ). The drug consists of CHO cell-produced epoetin beta linked to methoxy polyethylene glycol (PEG). Pegylation results in a molecular size of approximately 60 kDa, leading to a lower affinity for the EPO receptor, hindering its glomerular filtration by the kidneys, and increasing its serum half-life ( Macdougall, 2005 ). The exceptional stability of CERA in the blood results in a mean serum half-life of 70–122 h, which decreases its administration to once monthly or less frequently ( Macdougall et al., 2006 ). Because of its wider detection window, CERA is less likely to be used for doping purposes ( Fig. 1 ). The manufacturer (Roche) developed a CERA-specific ELISA for pharmacokinetic studies and provided it to the World Anti-Doping Agency (WADA) before the marketing of the drug.
What is epoetin alfa used for?
CHO cell-produced epoetin alfa was subsequently approved by the United States Food and Drug Administration (FDA) for the treatment of anemic patients with chronic kidney disease (CKD). It was then approved for the treatment of anemia associated with chemotherapy in cancer patients or with antiviral treatment in HIV patients and for the preparation of autologous blood donation prior to surgery. The treatment decreases the risks of recurrent blood transfusions and iron overload, and improves the quality of life ( Bonomini et al., 2016 ). The serum half-life of epoetin alfa is approximately 8 and 24 h when the product is administered intravenously or subcutaneously, respectively ( Franz, 2009 ). The bioavailability of epoetin alfa is low, and up to three injections per week are needed to attain therapeutic effects ( Macdougall et al., 1991 ). For doping uses, the short elimination time is advantageous, because the detection window is narrowed, whereas the effect is sustained ( Fig. 1 ).
Why is EPO important for athletes?
This is useful for athletes, since red blood cells shuttle oxygen to the cells, including muscle cells, enabling them to operate more effectively . EPO is a peptide hormone and can be produced synthetically using recombinant DNA technology.
What happens if you inject EPO?
If EPO levels are too high the body will produce too many red blood cells which can thicken the blood, leading to clotting, heart attack and stroke.
What is EPO produced by?
Produced naturally by the kidneys, EPO is also available as a pharmaceutical. EPO stimulates the production of red blood cells in bone marrow and regulates the concentration of red blood cells and haemoglobin in the blood.
What sports did Lance Armstrong use EPO for?
Other sports associated with EPO use include boxing (Shane Mosley, 2003), 50km walk (Alex Schwazer, 2012) and athletics (Rashid Jacobs, 2008).
What is the purpose of EPO?
Erythropoietin—more commonly known as EPO—is a type of blood doping that can help improve an athlete's endurance.
When was the first EPO test done?
An approved test for EPO was first introduced at the Sydney 2000 Olympic Games. The test used a combination of urine testing, which would identify the presence of EPO (direct test) and blood testing, which would show the residual ‘footprints’ of EPO drug use over time (indirect test). This was the first time blood was used for drug testing.
Can you use EPO without detection?
In essence the new test will look for genetic expressions which prove that EPO has been used. If the new test proves accurate and viable, it will be almost impossible to use EPO without detection.
What are the conditions that reduce erythropoietin production?
The production of erythropoietin is reduced in certain conditions such as kidney failure, chronic diseases like HIV /AIDS, and certain cancers and in chronic inflammatory diseases like rheumatoid arthritis.
What is erythropoietin?
Erythropoietin (EPO) is a hormone that is produced predominantly by specialised cells called interstitial cells in the kidney. Once it is made, it acts on red blood cells to protect them against destruction. At the same time it stimulates stem cells of the bone marrow to increase the production of red blood cells.
What causes high erythropoietin levels?
It causes a condition known as polycythaemia which means high red blood cell count. In many people, polycythaemia does not cause any symptoms.
Why is erythropoietin used in kidney disease?
If you have too little erythropoietin, which is usually caused by chronic kidney disease, there will be fewer red blood cells and you will have anaemia. Erythropoietin has been made synthetically for the treatment of anaemia that results from chronic kidney failure. It is also given to patients with some rarer types of cancer.
What happens to erythropoietin when oxygen levels go down?
When there is sufficient oxygen in the blood circulation, the production of erythropoietin is reduced , but when oxygen levels go down, the production of erythropoietin goes up. This is an adaptive mechanism because it facilitates the production of more red blood cells to transport more oxygen around the body, thus raising oxygen levels in ...
What hormone is used to detect hypoxaemia?
Blood sample being tested for the presence of the performance-enhancing hormone erythropoeitin. Although the precise mechanisms that control the production of erythropoietin are poorly understood, it is well known that specialised cells in the kidney are capable of detecting and responding to low levels of oxygen (hypoxaemia) ...
Does EPO doping increase red blood cells?
Raised levels of Erythropoietin in athletes indicate erythropoietin abuse (doping). EPO doping can boost the number of red blood cells and there by increased availability of oxygen to the muscles. This can help the athlete with increased performance ability and endurance.
Why would a marker be introduced in the athlete biopassport?
Markers originating from transcriptomics or ironomics could be introduced in the Athlete Biological Passport to ameliorate ESAs detection.
Can cheating athletes use erythropoiesis stimulators?
Cheating athletes now use microdoses of erythropoiesis-stimulating agents that are difficult to detect with current validated methods.
Is rHuepo expensive?
However, the production of rHuEPO is costly, and the frequent administration of an injectable formula is not optimal for compliance of therapeutic patients. Hence, pharmaceutical industries are currently developing alternative approaches to stimulate erythropoiesis, which might offer new candidates for doping purposes.
How long did the EPO study take?
The testing involved an 13-week period, where the 16 athletes were split into two groups. The control group received placebo injection, whereas the 8 cyclists in the EPO group received a dosage of EPO on a schedule worked out over the 13-week period. One potential problem with the study was that the EPO group could not be blinded that they were receiving EPO, for ethical reasons. What this means is that everyone receiving EPO KNEW that they were, and there’s good reason to believe that simply knowing you’re receiving a drug improves performance as well! The control subjects were blinded, so they did not know whether they were on EPO or not, which does partly offset this problem.
What journal published the EPO study?
This great study, published in the European Journal of Applied Physiology earlier this year, evaluated the effects of EPO use on performance during cycling. We’ll try to break the study down as simply and clearly as possible:
How long is the EPO trial?
At the intensity of cycling tested in this study, the improvement in time before exhaustion was roughly 11 minutes on a 22 minute trial. Of course, there are some (including us) who would debate the merits of a “ride to exhaustion” as a measure of performance. Normally, we prefer to see a Time-trial as a measure of performance, because the concept of riding to fatigue is not really an accurate or repeatable measure of performance.
Does EPO work?
This study clearly shows that EPO works. I’d extend that to say that any practice that increases the body’s ability to carry O2 will work – so the same goes for blood doping. If they work, and work by the sort of margins we seem to be talking here – tens of percent, then can one gifted, unique individual dominate the sport? I think not.
Do steroids help with recovery?
There are benefits to using steroids, for sure, in that they will assist in recovery. There is ample evidence of how testosterone levels fall progressively during a period of hard training or racing and so the correct use of steroids will improve recovery and thus performance in the longer races.
Can you be blinded by EPO?
One potential problem with the study was that the EPO group could not be blinded that they were receiving EPO, for ethical reasons. What this means is that everyone receiving EPO KNEW that they were, and there’s good reason to believe that simply knowing you’re receiving a drug improves performance as well!
Does Marco Pantani have a hematocrit graph?
There is plenty of evidence that shows indirect benefits, including Marco Pantani’s remarkble hematocrit graph, which correlated precisely with his performance over the course of three seasons. But it’s direct evidence we’re after, and that’s where we turn to a study published in August this year.
