If you follow cycling, then you no doubt know about the 4 year long battle of Roman Kreuziger. Now with his CAS case finally coming due, Roman is facing, what I would consider I near certain ban. I’ll get to why I’m near certain a little bit later. First, let’s recap the situation.
What goes down, apparently goes back up (at least when you dope)
Roman’s case is an interesting one mainly because his purported response to extended training and racing seems to parallel a handful of other notable athletes who have also demonstrated a spike in reticulocytes (new red blood cells) and Hb, or hematocrit (Hct). Probably the most famous of which was Il Elephantino, Marco Pantani, who also feigned innocence by claiming first dehydration, then that his Hct actually increased with training, something that run counter to known human physiology. Kreuziger’s case is a bit different, but also evolved during the height of the Giro. To recap:
Biological passport data taken from early April through late May 2012 — the period that Kreuziger prepared for, and competed in, the Giro d’Italia — shows a concurrent drop in hemoglobin and reticulocytes, followed by a spike in hemoglobin concurrent with a rise, and then dramatic drop, in reticulocytes.
During the final 10 days of the 2012 Giro d’Italia, Kreuziger’s hematocrit rose from 43.2 to 48.1, finishing higher than his pre-Giro value of 45.1 — an anomaly, as most athletes see a decrease of hematocrit/hemoglobin “after physical effort of sufficient duration and intensity due to plasma volume expansion,” as the UCI attests; i.e., during the final 10 days of a grand tour.
A rise in hemoglobin and a drop in reticulocytes, or immature blood cells, can be indicative of blood transfusions, as the body shuts down creation of its own red blood cells. A higher than expected hematocrit and elevated reticulocyte percentage can also be indicative of the use of EPO to artificially stimulate production of red blood cells.
Kreuziger argues that he has never exceeded the limit values in his biological passport; part of his defense is that his elevated reticulocyte level is due to the prescription drug L-Thyroxine, which he takes for hypothyroidism. He has never tested positive for doping. (Velo News, June 3, 2015)
To facilitate my discussion, I’ve bolded some key parts of the case, notably the red flags with Roman’s passport data, as well as his defense. The underlined portions merely highlight meaningless distractors athletes use; recall Lance Armstrong never officially tested positive either. However, let’s consider the claim that red cell count and Hct increased during the final days of one of the hardest 3-week races in the world. Simply stated, this one is DOA, in my opinion. It simply doesn’t happen in normal individuals; mild polycythemia can occur due to prolonged (2-wks+) of altitude exposure, while severe polycythemia is the result of certain diseases. Its safe to say, neither Roman, nor Pantani were suffering from anytime of disease-related polycythemia, so their Hct should decrease like everyone else (see footnote on 2015 Giro) due to a fairly large expansion (up to 15%) of plasma volume, the water portion of the blood. Contrary to what some think, increased plasma volume is a good thing for several reasons, including:
- improved thermoregulation/greater sweating capacity
- improved stroke volume
- reduced blood viscosity (i.e., blood flows better)
- 2 million years of evolution have developed the best sweaters on the planet
In other words, there is no plausible evidence to support the claim that Hct would increase in the latter stages of the Giro, let alone decrease then increase suddenly, except for cases of severe dehydration. Not surprisingly, this is typical initial go to response by riders, including Pantani. But a closer look at the numbers doesn’t support support this claim, and riders have yet to provide evidence themselves. From Pantani’s case:
His (Pantani) level of red blood cells was 52% – above the 50% level legally permitted by the UCI…Pantani’s Mercatone Uno team suggested that dehydration, and his victories on the last two mountain top stage finishes may have increased his hematocrite level…Pantani said he was well inside the legal limit when checked earlier in the race, “Pantani “I had the (leader’s) pink jersey, my hematocrite level was at 46% and I wake up to this surprise. I think there’s certainly something not quite right.”
Yes, there was something not quite right, and Marco’s math just was not adding up. First, he said his Hct was 46%, presumably form the night before, but the morning test said 52%. His team then claimed it was dehydration (the other excuses came later), but that argument just does not hold up. First, assuming his total blood volume (cells + plasma) was 5 L, a Hct of 46% after a very hard day of racing then rehydrating would have left him with about 2.3 L of red blood cells (RBC’s) and 2.7 L of plasma. Then, 8 hrs later, the blood checks reveal a Hct of 52%, which means that for the dehydration hypothesis to work, his RBC’s would remain at 2.3 L, but his total volume would have dropped to 4.4 L (2.3 / 0.52 = 4.4 L); in other words, Pantani lost about 600 ml of water overnight due to sweat losses, or about 1% of his body weight. This should not be confused with waking up in the morning and pissing out 600 ml (24 oz) in a massive pee. The body tightly regulates water and sodium reabsorption, to maintain plasma volume. Long story short, Pantani’s story is implausible at best. But what about Roman?
Well, Roman too, tried the dehydration story first, but then switched to blaming his thyroid medication, L-thyroxine. Is it possible that Levo-thyroxine (generic thyroid medication) caused an increase in reticulocytes? Sure. In fact, a quick search of the literature shows that it occurs in mice. But animal studies do not always translate well to humans. Data from the FDA indicates that the following:
- # Reporting any side effect of LEVOTHYROXINE : 6861
- # Reporting LEVOTHYROXINE caused INCREASED RETICULOCYTE COUNT: 1
- % Reporting INCREASED RETICULOCYTE COUNT INCREASED: 0.0146%
- FDA reports of any drug causing RETICULOCYTE COUNT INCREASED : 313
- Average percentage for all medicated patients where INCREASED RETICULOCYTE COUNT INCREASED was reported: 0.0020% (FactMed)
- 67,614 people reported side effects when taking Levothyroxine, 5 of which reported Increased have Reticulocyte Count.
So yes, it is possible, but the numbers just do not support Roman Kreuziger’s argument. Moreover, when asked about his defense, and whether his reticulocytes were elevated he had this response:
“Yes, of course, I have been taking it for 10 years. I increase the dosage every two years…It’s not something you can be without…I have been increasing the dosage every two years. I started with 50 micrograms per day, now 125 micrograms.”
As VeloNews noted, english is not his first language, so its possible he misinterpreted the emailed questions, but I find it hard to believe his lawyer missed this, as well. Moreover, my wife was diagnosed with hypothyroidism more than 10 years ago, and his increasing dose every 10 years seems odd. Taken as a whole, I just do not think any of the facts support Kreuziger’s case. Short of him clearly showing a (thyroxine) dose-(reticulocyte) response relationship, his arguments seem more hypotheticals. Not surprisingly, his argument held little sway with WADA, and I would expect CAS to uphold the original suspension. Either way, we should know by the end of June. Time will tell.
Footnote: A friend of mine works with a Pro Tour team and reported that during the recent Giro the riders’ Hcts dropped significantly throughout the race, including one rider who went from 42% at the start to 37% within the last week; exactly what we would expect.