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Why Tenerife?

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Re: Re:

28 Dec 2016 11:39

thehog wrote:Because EPO at altitude or just prior to altitude, rather than using it as a pure performance enhancer, stimulates & speeds the natural effects and altitude acclimatisation for an increase in RBCs. The EPO test does not look for levels of EPO rather than recumbent EPO - smaller cell size etc. due to synthetic use rather than natural occurring. The test simply can't yield a result. Addtionally the legal aspect, its way too open for legal challenge making the already flakey test redundant.

People oft forget that the medical use of EPO is to stimulate the natural production of EPO rather than supplement a patient with EPO. A patient generally would receive a blood transfusion followed by a course of EPO.


No, that's a muddled and inaccurate explanation. Like many biological processes there's a long and complex pathway, but for now let's just worry about two bits: EPO and the EPO receptor. This is your standard lock and key model: EPO fits into the EPO receptor, which in response kicks off a cascade of signalling that results in more red blood cells.

That's the natural EPO that your body produces, so what's the artificial EPO that athletes take? It's recombinant human EPO, so it's the same sequence of amino acids as human EPO (other animals will have their own EPOs with very slightly different sequences), but made in a lab instead of the ribosomes of your cells. A protein is made as a 2D string, same as it's stored in DNA, but after the string is made, it's folded into the shape it needs to be to do its job, often with the help of special chaperone proteins. It may also have parts of the ends of the string chopped off, and can have sugars attached at certain places (this is called glycosylation and can help folding or tag a protein for immune system reasons etc.).

So even if recombinant EPO was made from the same DNA/amino acid sequence, it will end up looking different, because it was made with different biological machinery, inside bacteria or another non-human cell in a lab instead of your own cells. Also some manufacturers change the sequence slightly (e.g. Amgen's darbopoeitin alpha) to make the resulting EPO more stable etc. But these changes are still small enough that the key still fits in the lock.

So how does the EPO test work? Because of the different glycosylation, electrical charge is distributed differently around the artificial EPO. If we put a mix of natural and recombinant EPO in a gel and apply an electric current (electrophoresis) they will separate out. https://gbiomed.kuleuven.be/english/research/50000618/50753339/files/revepo.pdf

But back to the original point: there is nothing that would cause the test to not work on athletes who were at altitude. They may have produced more natural EPO due to hypoxia, but if they've taken artificial EPO it'll still separate out. It'll be more difficult to indirectly detect EPO usage via HgB/reticulocytes etc., but that's not the EPO test, that's the biological passport.

There's also the wider class of continuous erythropoietin receptor activators (CERAs) like Mircera of Ricky Ricco fame that are often based on the basic EPO protein, but modified enough that they need their own test to detect. You can also design drugs that target other earlier or later steps of the hypoxia pathway, like HIF-1 (hypoxia-inducible factor) that the Russians found was boosted by xenon. It's inaccurate to call any of those other substances EPO though.

thehog wrote:As an aside; Wiggins most likely took a EPO shot in the back of the bus; he was just drugged tested and about to be in transit for 6 hours and overnight (testing stops), so no chance he'd be tested again in the short window for the microdose to leave the body. Perfect opportunity to use EPO prior of going to altitude and minimising any chance of being tested.


Yep EPO or similar is the most obvious answer to "what drug would a professional cyclist get couriered several hundred miles and not want to talk about it?".
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Re: Why Tenerife?

28 Dec 2016 16:26

It wasn't a muddied explanation, it was a good reason why testing for EPO at altitude would not yield a positive test. The user will always (as they are not stupid enough to use at altitude) to microdose with EPO just prior to going to altitude and just as they return. The passport is designed to reduce its sensitivity before, during and after altitude and the EPO test would not detect synthetic EPO at any stage in the process as long as there around 6-10 hours clear after injection.

I also agree that all EPO is not equal and there are several variants.
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29 Dec 2016 10:06

We need to realise blood passports have their limitations - You have issues with athletes living in high altitude whose blood values can be out of the normal range - You had the Kreuzeger case which was thrown out - I have serious reservations with the science around blood passports.
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Re: Why Tenerife?

29 Dec 2016 11:50

thehog wrote:It wasn't a muddied explanation, it was a good reason why testing for EPO at altitude would not yield a positive test. The user will always (as they are not stupid enough to use at altitude) to microdose with EPO just prior to going to altitude and just as they return. The passport is designed to reduce its sensitivity before, during and after altitude and the EPO test would not detect synthetic EPO at any stage in the process as long as there around 6-10 hours clear after injection.


Well I was being charitable - it was a wrong explanation. You haven't explained why being at altitude would interfere with the EPO test (which is completely separate to the biological passport) to the point that it no longer works. Have you a source or sources for this theory? There doesn't seem to be much online but the 2002 paper "The effects of factors such as exercise and disease on the distribution of urinary erythropoietin isoforms" from the Australian Sports Drug Testing Laboratory cautiously says "some data has been obtained showing that the distribution of urinary EPO isoforms is not significantly affected by external factors such as altitude". Here's a 2011 review on natural EPO levels: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3082088/ - "On ascent to altitude, Epo levels reach peak values after 1–2 days and then fall to a new plateau at about twice that present at sea-level".

Note also that when we're talking about cyclists training at altitude we're talking about pretty modest heights - the Mt Teide hotel is only at 2200 metres, while when doctors in general are talking about altitude they're talking about places like the Bolivian capital La Paz (over 3500m), Tibet, the Altiplano etc., where someone coming from sea level is likely to need an acclimatisation period.

Any problems with detecting EPO microdosing shouldn't be significantly different to at sea level. The real problem is access. If the Spanish ADA put a tester full time in the hotel on Mt Teide for the whole time teams were there, I think they'd get results.
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29 Dec 2016 13:07

Back to the general issue though, yes, the bio passport in its current form isn't fit for purpose. The allowable range is way too wide, and it doesn't take into account the expected drop of values during a Grand Tour. So IMO the best way to catch people is direct testing for substances.

The EPO test is more sensitive than it used to be by the way. Remember Di Luca in 2013: http://www.cyclingnews.com/news/di-luca-reveals-details-of-his-doping-in-hard-hitting-autobiography/

Di Luca admits he simply got it wrong when he was tested for EPO in an out-of-competition test a few days before leaving for the 2013 Giro d'Italia. He reveals he injected himself with a micro-dose of the latest generation of EPO before going to bed but then was awoken by anti-doping inspectors at 7:30 the next morning. He made sure he urinated before giving the test to pass any traces of the EPO but was caught by a new, refined test that can detect EPO for 24 hours, rather the 6-8 hours most riders believed.


Santambrogio was caught at the same time, and then the Iglinskys, but we haven't had any high profile EPO cases since then. So I think riders are a lot more cautious about EPO use right now. Here's my conjecture about what the likes of, say, Astana are currently up to: go to altitude camp, take EPO if there are no testers around, or some legal erythropoeisis-stimulating substances, as well as take advantage of increase in natural EPO production to withdraw blood, freeze blood if necessary, or do the old two units out one unit in etc as detailed by Tyler. Then during a GT, transfer a couple of small bags. But how do they deal with the drop in reticulocytes post transfusion? I think even microdosing EPO during a GT is now pretty dangerous, but maybe there's a technically legal drug (fluimucil?) that boosts retics enough to not fall foul of the passport. It doesn't have to be powerful enough to actually give a performance gain, just to mask a small transfusion. Certainly looking at Astana in the last two Giros you get the impression that transfusions are the main engine.
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29 Dec 2016 13:21

IMO the best way to catch people is direct testing for substances.
agreed.
The means are there (see e.g. Brazilian cyclist caught for 14 substances pre-Rio), but (imo deliberately) not being exploited by UCI and the ADAs.

Interesting point about retics and flumicil.

Iinm, oldschool steroids boost hematocrit, too. I wonder if this means riders who use steroids during the season have to take steroids in the off-season too, so as not to trigger the passport.

As for riders being more careful with EPO, don't forget that according to some there are literally dozens of undetectable EPO variants on the market.
http://www.reuters.com/article/doping-epo-idUSL4E8EF70520120315
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Re: Why Tenerife?

21 Jun 2017 19:54

This link does not really tell us anything new, but it contains some interesting quotes. Annemiek van Vleuten comments to the Dutch news on winning the national ITT championship for the second time in a row.

"That I won the ITT is a good sign. I lost some weight, so I can be faster uphill, even though I didn't lose any power."

"I've been in a hotel with several riders preparing for the Tour de France, Alberto Contador, Chris Froome and the Astana men."
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Re: Why Tenerife?

05 Sep 2018 22:32

La Orotava, where did I hear this name before.... Tenerife! Kosta was tested on Tenerife on April 3rd https://www.instagram.com/p/BnV218CAPdX/?taken-by=kosta.siutsou

#notestingonTenerife ;)
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06 Sep 2018 11:40

Has it ever been about "no testing"? Isn't it rather that testing is more complicated, having a bit more notice of when you're being tested? Combined with being a great place to train, awash with PEDs and being able to play the altitude card for your ABP make it an ideal location but I guess insubstantially different in those regards to say Granada, Andorra or St. Moritz.

But you're welcome to post in the other thread which suggests there is an issue with OoC testing generally, or continue to smirk along here.
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