Erythropoietin (EPO) and Blood Doping in Sports

Erythropoietin is a glycoprotein hormone, and is also produced as a biomedicine. It is often referred to by a selection of different names, such as hemopoietin, hematopoietin, and erythropoetin. A short name for it is EPO. When the exogenous form is used as a performance enhancer, it is considered as an erythropoiesis-stimulating agent, or ESA for short.

The human body uses this material in a process called erythropoiesis, in which the production of red blood cells occurs. It is also used by the body in additional functions.

If you follow sports, you’ve undoubtedly heard about athletes who have been caught using performance-enhancing drugs (PEDs). Anabolic steroids are some of the more well-known PEDs, but erythropoietin (EPO)—a drug used to boost red blood cell counts in a practice called “blood doping”—falls under the same umbrella of forbidden substances. In fact, EPO has been a source of widespread abuse and controversy among professional cyclists since the 1980s.

This, however, does make sense when you understand that the kidney is basically in charge of the blood. The drug could also be a strong placebo; after all, sports are a test of the mind as well as the body. However, before reaching this point it is clear that we need to at least pay homage to the physiologists; after all the end result of the biochemistry must be to improve the body function so that a person can run faster or for longer. An autopsy did not specify the cause of death – he had been passed fit to ride by a doctor – but in a television interview afterwards, his widow said she hoped his fate would serve as a warning to other athletes who take the drug. Their lives are disrupted frequently, even if they never test positive. Since then blood doping has apparently taken a back seat to EPO, but more sensitive testing has revealed that it has not gone away.
A ball park figure for this would be 3-4 weeks. The estimated doping prevalences at Daegu and Moscow were compared using a Kolmogorov-Smirnov test, which assesses the largest vertical difference between the two curves, and a Cramér-von Mises test, which considers the sum of the differences. Cohen’s group is now analyzing mountains of data on EPO. 2003;37:190-1. The oft-quoted example here is Eero Mantyranta, a Finnish cross-country skier who won gold medals in the 1964 Winter Olympics; along with the rest of his family, Mantyranta was shown to have a mutation increasing the activity of his EPO receptor (EPO-R). Elizabeth Quinn. Many of the most popular new compounds are identical to natural chemicals made by the body – making sure detection difficult or impossible.
Med Sci Sports Exerc. Most of the efforts concern elite athletes with much less impact on amateur sports and the general public. Data is presented as percent change from baseline, with a line connecting means. Blood loading has a slightly different risk profile. Ancient Greek athletes used special diets and stimulating potions to improve performance, and 19th century endurance athletes indulged in strychnine, caffeine, cocaine and alcohol. “EPO (erythropoietin) doping in elite cycling: No evidence of benefit, but high risk of harm.” ScienceDaily. The third scenario would occur if two embryos fused together early in development, creating a single chimeric person (New Scientist print edition, 15 November). The low dose strategy is called micro-dosing and involves the athlete using high dosages of EPO initially to get his levels up, and then maintains them with low dosages.

The Biochemistry Of Drugs And Doping Methods Used To Enhance Aerobic Sport Performance

Blood doping is the practice of boosting the number of red blood cells in the bloodstream in order to enhance athletic performance. Autologous blood doping detection is done indirectly via CO rebreathing technique to measure the nonphysiologic increases in Hb mass. The principle of CO rebreathing method used currently requires an O2-CO gas mixture inhalation for about 10-15mins. 30 By measuring the difference in carboxyhemoglobin concentration (HbCO) before and after rebreathing, the volume of CO and the binding capacity of Hb for CO ( 1.39ml g-1), total Hb mass can be calculated. 30 This detection method is problematic for an athlete as it is not desirable to breathe in CO shortly before a competition, which may potentially affect their performances.

I’d agree that this was one of the most successful doping programs the sport has ever seen (up until now), but I’m not sure I agree that it was the most sophisticated and professionalised. To me, it seemed pretty amateur after reading Tyler Hamilton’s book, The Secret Race. USPS was flushing drugs down the toilet of a bus, keeping EPO in the kitchen fridge, hiding syringes in coke cans…the only surprising thing to me in all of this was how ridiculous it became was and that they got away with it for so long.

Epo mimetic peptides (EMPs) are synthetic cyclic peptides of about 20 amino acids. A potent pegylated EMP dimer (INN: peginesatide; Hematide) proved to stimulate erythropoiesis in experimental animals 49 and in healthy male volunteers. 50 Peginesatide is currently in phase 3 trials for the treatment of patients with chronic renal failure (CKD). Peginesatide can be detected by enzyme-linked immunoassay. 49 In a clinical trial on 14 patients with CKD, who had pure red cell aplasia because of anti-Epo antibodies and were treated with peginesatide for 28 months, neutralizing antibodies against the drug occurred in one of the patients. 51 This should further discourage athletes to use the medicine as a doping means.

What Is “Blood Doping?”

Blood doping refers to any attempt to improve athletic performance by artificially increasing your red blood cell count. Red blood cells are responsible for carrying oxygen molecules throughout the body. The more red blood cells you have, the greater your energy expenditure and the slower you will “burn out” during extreme physical activity.

Methods of blood doping include:

Transfusions of someone else’s blood
Re-infusion of one’s own red blood cells1
Administration of enhancement drugs such as EPO

Blood doping is in violation of standards set by the World Anti-Doping Agency (WADA) and is banned in professional sports.2 Even with rigorous testing among athletes, that hasn’t stopped some from doing it anyway.

EPO Controversies

EPO has been banned since the early 1990s, but the first tests did not become available until the 2000 Summer Olympics.3

Abuse of EPO made world headlines when Floyd Landis, the 2006 Tour de France winner, was stripped of his title after testing positive for doping. Having confessed to using PEDs for years, Floyd went even further by accusing 17 other cyclists of doping, including seven-time Tour de France titleholder Lance Armstrong.

In 2005, a year after his seventh Tour de France win, Lance Armstrong was accused of using EPO, a claim that was eventually confirmed in 2012. After publicly admitting to EPO use, Armstrong was stripped of all of his cycling titles.

Other cyclists caught in the crosshairs of the EPO controversy were champions Willy Voit, David Millar, Phillipe Gaumont, and Jesus Manzano.

Effect on Athletic Performance

EPO is a naturally occurring hormone that can be synthesized in the lab and injected directly into the skin or bloodstream. In terms of sports performance, it has been shown to increase the proliferation of red blood cells and increase the amount of oxygen carried to muscles.3

Increased availability of oxygen is believed to slow the progression of muscle fatigue and increased endurance during performance athletic events.4

The ability to exert force for longer periods of time is what makes blood doping so appealing for professional athletes. Doing so may help reduce the recovery time between workouts, increase muscle power, and maintain an edge during competitions.

With that being said, there is evidence that EPO injections may deliver fewer benefits than initially thought.

A 2017 study published in Lancet Hematology concluded that cyclists given a subcutaneous injection of EPO for eight weeks performed no better in exercise tests or road race performance than cyclists given a placebo.

Potential Dangers

EPO has been shown to induce hypertension (high blood pressure) by literally crowding plasma with excessive red blood cells.5 This serves to “thicken” the blood, increasing vascular constriction and the overall blood pressure. Greater blood viscosity puts a strain on the heart, increasing the risk of blood clots, heart attacks, and stroke.

Drug interactions may occur between EPO and medications used to treat hypotension (low blood pressure), including Astonin (fludrocortisone) and midodrine. Taking EPO with these drugs may amplify their effect, leading to drug-induced hypertension.

EPO can cause severe lung toxicity if taken with cancer drugs used to treat leukemia, lymphomas, and breast cancer, such as Cytoxan (cyclophosphamide).

Is It Worth It?

Blood doping is an illicit method of improving athletic performance by artificially boosting the blood ‘s ability to bring more oxygen to muscles. 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.

The paper outlines the different approaches and diagnostic tools that some federations have to identify and target sportspeople demonstrating abnormal blood profiles. Originally blood tests were introduced for medical reasons and for limiting misuse of recombinant human erythropoietin (rHuEPO). In this way it became possible to prevent athletes with haematocrit levels well above normal, and potentially dangerous for their health, competing in sport. Today, with nearly a decade of blood testing experience, sports authorities should be familiar with some of the limitations and specially the ability of blood tests performed prior to competitions to fight efficiently against the misuse of rHuEPO, blood transfusion, and artificial haemoglobin.

The IOC’s last Summer Games in Rio in 2016 were marred by the Russian doping scandal that led to the exclusion of many of the country’s athletes from competition. The outgoing WADA president Craig Reedie acknowledged that “Clearly there have been times when elements within the system have failed to live up to expectations,” and called the state-sponsored doping in “The worst case of system failure, certainly in my time as president, if not in the entire history of the anti-doping movement”.

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. However a new systemic review of existing research, published in the British Journal of Clinical Pharmacology, reveals that there is no scientific evidence that it does enhance performance, but there is evidence that using it in sport could place a user’s health and life at risk.

The practice of enhancing performance through artificial means is as old as competitive sport itself. The first time blood doping came to my attention was after the 1984 Olympics in Los Angeles. I thought I knew the basics of how doping worked after hearing about it for all these years but got a fascinating insight into this science after sitting down with haematologist and fellow cyclist (who prefers to remain anonymous) who explained as much as I could comprehend. I’ve decided to break this down into a few separate articles to make it more digestible. This first article which provides background on blood doping might be slightly basic for many of you, but there are some things you might not have known.

EPO and other banned PEDs are under constant scrutiny by sporting agencies. Athletes are regularly tested to detect their presence. Athletes who test positive for EPO face possible suspension, the withdrawal of competition titles, and even a lifetime ban from sports if the PED abuse is especially egregious.

Bottomline

Despite the temptation to use PEDs, the risks to your health and reputation far outweigh any possible benefit. If you feel that you are underperforming as an athlete, don’t let supplements be your first choice of treatment.

Instead, talk to your coach about safer options, such as nutrition, alternate forms of training, or the implementation of sports psychology techniques. If you need to increase your red blood cell count for medical reasons, consult with your doctor to develop a treatment plan that makes sense for you.

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