Blood Doping 101

The World Anti-Doping Agency (WADA) defines blood doping as “The misuse of certain techniques and/or substances to increase one’s red blood cell mass, which allows the body to transport more O2 to muscles and therefore increase stamina and performance.”

At the heart of doping in endurance sports such as cycling, the drug you’ve probably heard most about is EPO. Formally known as erythropoietin, EPO is a hormone that controls red blood cell production. Hemoglobin mass is a key factor for maximal exercise capacity. When EPO is injected into an athlete and used as a performance-enhancing drug, it is classified as an erythropoiesis (red blood cell production) stimulating agent.

Francesco Conconi (left) is regarded as the father of modern blood doping. He headed up the Centro Studi Biomedici Applicati allo Sport research centre at the University of Ferrara where he optimised performance-enhancement through legal and illegal means for Italian athletes in the 1980s. His prize student was Michele Ferrari (right) and they were both keen cyclists. They’d set out on rides together to explore each of their own thresholds to investigate performance factors like haematocrit and lung capacity. With access to various substances, they’d experiment on themselves to see the effect firsthand. Conconi’s break-through moment was when he, Ferrari, and assistants helped Francesco Moser break the one hour record in 1984, aided by blood transfusions (not illegal at the time). It was Conconi who taught notorious doctors like Ferrari and Cecchini the fine art of blood doping. You have to remember however, the mindset at the time was that they were making a scientific contribution to the sport. Unfortunately their mindsets did not change as time went on and young athletes were dying at alarming rates.

But time did go on and so did the systematic doping. The chickens came home to roost on October 10, 2012 when the USADA’s Reasoned Decision was released on the Lance Armstrong/USPS doping conspiracy which said:

‘The evidence shows beyond any doubt that the US Postal Service Pro Cycling Team ran the most sophisticated, professionalised and successful doping program that sport has ever seen.”

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.

But as well soon see, the science behind doping is both a sophisticated and fascinating topic of human physiology.

The Fick Equation

For those of you who took sports physiology 101 you might remember the Fick Equation, which is basically the measurement of cardiac output.

The Fick equation determines the rate at which a person uses oxygen in their body – which is also known as VO2 (the volume of oxygen uptake).

O2max = Qmax X a-vO2max.

This states that the maximum rate of oxygen uptake is (O2max) is the product of a high cardiac output (Q) and a wide difference for arterial-venous oxygen (a-vO2) (the oxygen content in the arterial and venous blood)

At the heart of success in endurance sport is aerobic capacity (excuse the pun). Improvements in aerobic capacity are relative to how much blood the heart pumps out to the working skeletal muscles with every beat.

Aerobic Capacity is also referred to as VO2Max. Someone like Greg Lemond has a massive stroke volume and VO2max of 92.5 ml/kg/min. The 2012 junior time trial world champion Oskar Svendsen is reported to have the highest VO2 Max ever recorded in a human at 97.5ml/kg/min. The highest recorded VO2 max for Lance Armstrong is 84 ml/kg/min and Cadel Evans 88 ml/kg/min. A high VO2 max doesn’t guarantee success, but is often used as a key indicator. If the stories about Mark Cavendish are true, his VO2 Max and lactate threshold scores and were so low that he was told that he’d never have a career in pro cycling.

VO₂ max is often expressed as a relative rate in millilitres of oxygen per kilogram of bodyweight per minute (ml/kg/min). The only variables in VO2max that you can manipulate to improve it is by reducing your bodyweight, or increasing your haemoglobin mass.

The Cheating Equation

In aerobic sports such as cycling, the main factors determining performance are the high delivery of oxygen to the exercising muscles and its use.

The two systems on the right (max Cardiac Output and max O2 extraction) are what you’re born with and are difficult, perhaps impossible, to manipulate to higher values during competition. With cardiac output, our maximum achievable heart rate goes down as we all age. Your stroke volume is what you’re born with and this cannot be manipulated past a certain point. On the right, the arterial oxygen extraction is operating at approximately 90% at maximal exercise and is difficult to change. Mitochondrial respiratory capacity is inherited from your mother. When an athlete dopes, these things aren’t changed. The only variable that remains open for manipulations with regards to increasing performance is the hemoglobin concentration and blood volume (the left side of the diagram). This is the basis of blood doping.

Methods

Athletes can either cheat by injecting EPO or transfuse red blood cells to elevate the haemoglobin mass. Both will achieve the same endpoint. Tyler Hamilton described some slight differences in his book however. He explained what Bjarne Riis taught him, “Unlike the slow rise in hematocrit created by EPO, transfusions provided an instant boost of around 3 points.” He also described the sensation as being different. “The key to riding with a BB [blood transfusion] is that you have to push past all the warning signs, past all the usual walls. You get to that place beyond your edge, the pace where you’ve fallen a thousand times, and all of a sudden you can hang in there. You’re not just surviving; you’re competing, making moves, dictating the race.”

Altitude training is another way to increase the body’s production of red blood cells, but the body has natural checks and balances so that adaptations are done slowly and safely. Altitude training is legal in most countries but banned by in Italian. Many professional cyclists have no problem admitting that they use altitude tents and I personally don’t feel that this training technique steps into a grey area.

EPO

The performance enhancing effect of recombinant human erythropoietin (we’ll just call it EPO from now on) in sports was investigated shortly after its introduction in clinical use. It soon became clear that administration of EPO at doses of X to Y U/kg body weight (this information is out there, but it would be irresponsible to print here) per week for 4 to 6 weeks increases O2max and the time to exhaustion substantially. If you can get your hands on it, it’s cheap and it’s effective.

To provide the most efficient red blood cell production, EPO should be kept at a steady level of approximately x to y mU/mL above baseline levels. Higher levels lead to EPO wastage, and lower levels cause inefficient red blood cell production.

There are a couple different strategies when taking EPO. There is the high dosage (X UI per kilogramo of body weight 3 times per week) strategy which athletes use to elevate blood levels but is much more easily detected. 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. Recent studies in which EPO was applied to test subjects in lower dosages showed that O2 max is increased by 6%-12% when the hematocrit is increased to approximately 0.50 but also demonstrated that time to exhaustion (in the lab) at a given level of O2 max is increased by up to 50% (more info and references to studies here).

(Image photoshopped)

There are two types of blood transfusions: Autologous and homologous. Autologous is where the patient takes his or her own blood, and homologous is when the patient receives a donor’s blood.

In receiving someone else’s blood you need to make sure that it is compatible. If not, your body will react to it as foreign substance and destroy it. You read about Tyler Hamilton urinating blood in his book. This is one of those reactions. This most likely because blood bags got mixed up and he received blood that wasn’t intended for him. In its worst form, you can die from this incompatible reaction. You can dope this way and match the major similarities in blood. If they match, you are unlikely to have any problems. Homologous transfusion can be detected by testing for minor incompatibilities. Even if you get all the major similarities right, there are other complications that can arise that will create a reaction.

You might ask why somebody would risk a homologous transfusion when his own blood could be used. There are a couple reasons. First, there is a negative dip in performance initially after taking blood out. Second, there have been stories about how athletes would transfuse the blood of a donor who was being administered EPO at the appropriate time before a race. I cannot confirm that this has happened, but it would be an effective doping strategy and would likely help avoid detection.

Summary

As we can see there are many physiological inputs to optimising anaerobic capacity, but only a few systems can be manipulated beyond what you were born with. There are two ways to blood dope, each having the same physiological effect. From the athlete’s side, the doping is the easy part. Not getting caught it more difficult. From the drug testers side, proving that an athlete was doping is the challenge where numerous markers and clinical scenarios need to be considered to understand the full picture.

Upcoming articles in series:

- How testers detect EPO and transfusions and how athletes beat the tests
- Short term and long term risks of Blood Doping
- The Future of Blood Doping – Gene Therapy