All About Salbutamol

[brownbobby]

Re:

John is probably right about the gaming, but let's play along here. What kind of evidence could support Froome’s claim? There are tests for kidney function, but not for after the fact. His claim seems to be he had acute kidney malfunction, but that the kidneys returned to normal by stage 18. So tests for kidney function on him now are unlikely to help.

So what could help? His urine samples prior to stage 18 now become extremely important. If his kidneys were not excreting substances properly—let’s say his kidney malfunction occurred during part or maybe all of the Vuelta—then his salbutamol levels for these earlier stages should have been really low, probably < 100 or even 50 ng/ml. If they were much lower than his levels after stage 18, and perhaps also lower than at other times in his career, say, at the TDF, that would be suggestive. But how good these levels would be as evidence would depend on how much salbutamol Froome was taking then, and of course he can’t prove how much he was taking. Unless there was a really sharp drop-off—say, from 300-600 ng/ml to < 100 ng/ml—this evidence would not be compelling. And there’s no reason to think his kidney malfunction would occur suddenly, unless it was triggered by some event, such as acute dehydration. I guess that’s possible.

So they would probably also look at other substances in the urine, such as creatinine. But this is complicated, too, because during the intense exercise of a GT, his creatinine blood levels will be much higher than at rest, and this will affect urine levels even if the kidney is not fully efficient. I would think even in a rider with normal functioning kidneys there would be huge variations in creatinine in the urine during a GT, and these variations will tend to obscure any consistent effect that kidney malfunction might have. They might want to compare creatinine levels in his Vuelta samples with those in earlier samples, e.g., from the TDF, to try to establish some kind of baseline.

But this is not the way one normally looks for kidney problems. One would want to measure serum creatinine levels, and urinary levels I think are only used if urine can be collected over a set period of time, not just in one sample given at the end of a stage. So Froome will not only be trying to prove that he had kidney problems after-the-fact, but with limited samples available. He might have given a blood sample during the Vuelta, which could be helpful, but one sample in isolation would be of limited value.

Translation of the L'equipe article on another website I've come across says that Froome's 'team of experts have come up with this defence based on abnormally low levels of salbutamol in his tests the day before and after the fateful stage 18 test.

So as you say all of his previous tests will be crucial here. If they do demonstrate the AAF being sandwiched by a couple of 'freak' (specifically for Froome) readings then maybe the defence has some legs....

 

[gillan1969]

Re: Re:

John is probably right about the gaming, but let's play along here. What kind of evidence could support Froome’s claim? There are tests for kidney function, but not for after the fact. His claim seems to be he had acute kidney malfunction, but that the kidneys returned to normal by stage 18. So tests for kidney function on him now are unlikely to help.

So what could help? His urine samples prior to stage 18 now become extremely important. If his kidneys were not excreting substances properly—let’s say his kidney malfunction occurred during part or maybe all of the Vuelta—then his salbutamol levels for these earlier stages should have been really low, probably < 100 or even 50 ng/ml. If they were much lower than his levels after stage 18, and perhaps also lower than at other times in his career, say, at the TDF, that would be suggestive. But how good these levels would be as evidence would depend on how much salbutamol Froome was taking then, and of course he can’t prove how much he was taking. Unless there was a really sharp drop-off—say, from 300-600 ng/ml to < 100 ng/ml—this evidence would not be compelling. And there’s no reason to think his kidney malfunction would occur suddenly, unless it was triggered by some event, such as acute dehydration. I guess that’s possible.

So they would probably also look at other substances in the urine, such as creatinine. But this is complicated, too, because during the intense exercise of a GT, his creatinine blood levels will be much higher than at rest, and this will affect urine levels even if the kidney is not fully efficient. I would think even in a rider with normal functioning kidneys there would be huge variations in creatinine in the urine during a GT, and these variations will tend to obscure any consistent effect that kidney malfunction might have. They might want to compare creatinine levels in his Vuelta samples with those in earlier samples, e.g., from the TDF, to try to establish some kind of baseline.

But this is not the way one normally looks for kidney problems. One would want to measure serum creatinine levels, and urinary levels I think are only used if urine can be collected over a set period of time, not just in one sample given at the end of a stage. So Froome will not only be trying to prove that he had kidney problems after-the-fact, but with limited samples available. He might have given a blood sample during the Vuelta, which could be helpful, but one sample in isolation would be of limited value.

Translation of the L'equipe article on another website I've come across says that Froome's 'team of experts have come up with this defence based on abnormally low levels of salbutamol in his tests the day before and after the fateful stage 18 test.

So as you say all of his previous tests will be crucial here. If they do demonstrate the AAF being sandwiched by a couple of 'freak' (specifically for Froome) readings then maybe the defence has some legs....

but presumably all days will be with self-reported dosages...so only knowing one side of the equation can't be a defence....or at least for the scientists...this may be one for public opinion and damage limitation on comeback....media led rather than science led ( a bit like when Swart was deployed)

 

[ScienceIsCool]

Re: Re:

Translation of the L'equipe article on another website I've come across says that Froome's 'team of experts have come up with this defence based on abnormally low levels of salbutamol in his tests the day before and after the fateful stage 18 test.

So as you say all of his previous tests will be crucial here. If they do demonstrate the AAF being sandwiched by a couple of 'freak' (specifically for Froome) readings then maybe the defence has some legs....

I love the hand-waving portion of the defense.

See, it's technically possible that the data supports the unlikely notion of a freak occurrence of temporary renal dysfunction, and well...

<waves hands frantically>

Is there any evidence that this actually happened?

<waves hands even faster>

It's a ballsy strategy, I'll give you that.

John Swanson

 

[ScienceIsCool]

I should have added that maybe.... Just maybe. Low readings fro Salbutamol would have been due to him not using his inhaler! After all, it's not a preventative that you take daily. It's taken when you need it, and sparingly. I hope for his sake that they rigorously documented his usage. And even then they'll need to have some sort of evidence that this freak, out of nowhere, lasts for a couple of days kidney problem actually happened.

John Swanson

 

[gillan1969]

Re:

I should have added that maybe.... Just maybe. Low readings fro Salbutamol would have been due to him not using his inhaler! After all, it's not a preventative that you take daily. It's taken when you need it, and sparingly. I hope for his sake that they rigorously documented his usage. And even then they'll need to have some sort of evidence that this freak, out of nowhere, lasts for a couple of days kidney problem actually happened.

John Swanson

they might document his usage, but then he goes to his room and..............................

 

[Summoned]

Re:

I should have added that maybe.... Just maybe. Low readings fro Salbutamol would have been due to him not using his inhaler! After all, it's not a preventative that you take daily. It's taken when you need it, and sparingly. I hope for his sake that they rigorously documented his usage. And even then they'll need to have some sort of evidence that this freak, out of nowhere, lasts for a couple of days kidney problem actually happened.

John Swanson

Fortunately, Sky has a sterling record of being able to document what medications were administered to their riders and for what reason.

 

[Wiggo's Package]

Re: Re:

snipped...

Also from the CW article:

'L’Equipe says that Froome and Sky – who deny exceeding the permitted dosages for salbutamol – have yet to pass their dossier containing their defence to the scientific experts at the UCI’s Legal Anti-Doping Services (LADS), but that the LADS has already brought in its own kidney specialist with this in mind.

Sky still haven't patched up that leak ? ... The L'Equipe source (presumably the same source that leaked the +ve test result) not only appears to know what defense Team Froome is planning to run but is also happy to pass that on to UCI so that they can get a head start on countering it

I suspect this leak to L'Equipe has come from the UCI side of the fence

And depending on the backwards and forwards of the legal proceedings to date Froome's lawyer could have made the UCI aware in outline that renal malfunction will form the basis of the defence without having yet handed over a "dossier" of supporting documents

 

[Robert5091]

Let me guess, the doc had it all documented on his laptop and ...

 

[movingtarget]

Re: Re:

I should have added that maybe.... Just maybe. Low readings fro Salbutamol would have been due to him not using his inhaler! After all, it's not a preventative that you take daily. It's taken when you need it, and sparingly. I hope for his sake that they rigorously documented his usage. And even then they'll need to have some sort of evidence that this freak, out of nowhere, lasts for a couple of days kidney problem actually happened.

John Swanson

Fortunately, Sky has a sterling record of being able to document what medications were administered to their riders and for what reason.

Urgh what package..........

 

[Merckx index]

Translation of the L'equipe article on another website I've come across says that Froome's 'team of experts have come up with this defence based on abnormally low levels of salbutamol in his tests the day before and after the fateful stage 18 test.

Thanks for this info. As soon as I heard of this defense, I thought of two possible scenarios leading to it. The first, more likely, is that Froome just told the scientists, come up with something, anything that will explain this high level. They saw this as a possibility, and looked over his previous levels to see how consistent they might be with this story. IOW, come up with a theory, then try to fit the facts to it. This is what dopers usually do in their defense; not real science, of course.

The second possibility is that a scientist was just looking over the previous levels, and this pattern jumped out at him/her: one or more days with very low levels compared to the rest. This is science; the facts first, the theory is suggested by them. In this case, the argument, as you say, is stronger.

But a single day of an abnormally low level is not very strong evidence (and why should the level be low the day after? the high level is supposed to result from return to normal function). For one thing, as noted before, what constitutes a low level depends on how much salbutamol he was taking, and there’s no way to prove what it was, unless Froome actually records this in some notebook after every stage, which I doubt. Second, though I’m not an authority on renal function, it sounds improbable that his kidneys would shut down for just a day or so. I would expect this to be a problem that would persist over a longer period of time (which of course raises other issues, such as why didn’t he notice this).

Third, if this did happen, why has it never happened before? Since Froome has been tested so often, the odds are pretty good that if it did happen before, he would have had another AAF. One could argue that maybe he did, but it was taken care of without ever becoming public. But if this kind of thing happens to Froome, it would probably happen to other athletes. AFAIK, no athlete has ever used this defense, at least not successfully. And it’s not because no one else ever thought about it. If you look at Petacchi’s CAS case, e.g., you see that his team raised a very similar notion, that there was some problem with metabolism. That’s not quite the same thing, but it’s close enough to indicate that his scientists probably considered temporary renal failure. Logically, you would consider every possible way a high level could result.

In any case, I think there are two main lines of evidence Froome’s team will use. First, as discussed, previous urine samples, to document that levels of substances in his urine were below what was expected. And second, studies showing that individuals can suffer temporary dysfunction, resulting from some cause that could apply to Froome, probably dehydration.

Here’s an article that may be of some help:

http://sci-hub.la/https://www.nature.com/articles/ncpneph0218

Acute renal failure (ARF) is defined as a rapid (i.e. over hours to weeks) and usually reversible decline in glomerular filtration rate (GFR) that can occur either in the setting of previously normal renal function (‘classic’ ARF) or in a patient with pre-existing chronic renal disease (‘acute-on-chronic’ renal failure).1–3

After exclusion of those who suffered chronic renal failure, ARF (defined as a serum creatinine level >5.6 mg/dl [495.0 μmol/l]) developed in 172 adults per million people (pmp) per year in an unselected population.5 Incidence ranged between 17 pmp/year and 949 pmp/year for adults less than 50 years of age and those aged between 80 years and 89 years, respectively.

Seventeen out of a million, or about one in 60,000.

The article notes that ARF can be classified as oliguric, presenting as low urine output, or non-oliguric, diagnosed as high serum levels of creatinine. The mildest form, defined as “Risk”, would presumably be what Froome is proposed to have had, and the article mentions it can appear over a period of 1-7 days.

And here’s an article evaluating renal function in ultramarathon cyclists:

https://www.researchgate.net/profile/Guenther_Neumayr/publication/8086952_Renal_Function_and_Plasma_Volume_Following_Ultramarathon_Cycling/links/54cf20ba0cf24601c092e1c7.pdf

The authors concluded there was little effect. Serum creatinine levels did rise about 30% right after the race, but had returned to normal 24 hr later.

The study affirms that in world class cyclists the enormous strains of ultramarathon cycling influence renal function only on a minimal scale.

 

[Merckx index]

Re: Re:

Supposedly the sabutamol level was: low-high-low in the samples from Stages 16-17-18, respectively. So as you said, that pattern stands out, and could be the starting-point for some kind of defense.

But let me emphasize a point I made only parenthetically in my previous post: I don't see how a low level following stage 18 helps. The theory is that his function was impaired so that salbutamol accumulated in the blood, then suddenly function returned to normal, so a much higher than normal concentration appeared in the urine. But if his kidney function was normal at that point, his salbutamol levels on succeeding stages should also have been normal, whatever that was. I wonder if the article misunderstood what the researcher told the reporters.

But the whole argument seems easily dismantled, because these urine samples will also contain all the ordinary biomarkers of normal renal function, and those will presumably be at fairly consistent, normal levels on all of the days tested.

Yes, if that's the case. I would think after all this time they would have tested the samples for other substances like creatinine, so they would know if that backed them up. But maybe not yet. Maybe they just recently came up with the possibility of kidney malfunction, and haven't had time to follow that up with further testing.

Some of the news articles about this claim: that Froome's lawyers already abandoned the dehydration concept, meaning they probably know his USG was too low to support such an approach

That's not what I mean. He apparently wasn't dehydrated on stage 18, not enough to raise his USG to the level needed to make a large correction in the allowed DL. But what I was referring to is the possibility that on a previous stage he suffered from dehydration, which temporarily affected his kidneys. This is possible. Renal function could have been affected as a result of the shock of dehydration, so that even after rehydrating, he still wasn't passing substances normally.

Making the whole thing a high-stakes game based on a claim difficult to prove. They can't seek to (re)create conditions of acute renal failure

Gives new meaning to the term DQ: double or quits, or as we say in America, double or nothing. And that in itself has a double meaning. It can refer to gambling that he can skate, at the risk of doubling his penalty if his strategy fails. It can also refer to the fact that he wants to ride the Giro/TDF double, and will risk not being able to ride either (if he loses the hearing) rather than one (if he accepted a shorter suspension).

I've been trying to understand Froome's thought process here. Is the Vuelta title so important to him that he's willing to risk the Giro/TDF this year, and maybe next year as well? Even if, say, a short suspension following admitting he made a mistake prevented him from riding either the Giro or the Tour, he could at least ride the Vuelta again, getting back that title he lost. Then go for the double, or at least one of those GTs next year. Whereas if his strategy fails, he probably won't be able to ride a GT till 2020, and considering his age at the time, and the long layoff, his prospects of winning another GT would seem to be pretty dim.

I just wonder if what Froome is doing is the result of careful calculation of the potential consequences, or if he just become so worried about losing the Vuelta, after all his unsuccessful attempts to win it, that he's thrown caution to the wind.

 

[Poursuivant]

Re: Re:

Supposedly the sabutamol level was: low-high-low in the samples from Stages 16-17-18, respectively. So as you said, that pattern stands out, and could be the starting-point for some kind of defense.

But let me emphasize a point I made only parenthetically in my previous post: I don't see how a low level following stage 18 helps. The theory is that his function was impaired so that salbutamol accumulated in the blood, then suddenly function returned to normal, so a much higher than normal concentration appeared in the urine. But if his kidney function was normal at that point, his salbutamol levels on succeeding stages should also have been normal, whatever that was. I wonder if the article misunderstood what the researcher told the reporters.

But the whole argument seems easily dismantled, because these urine samples will also contain all the ordinary biomarkers of normal renal function, and those will presumably be at fairly consistent, normal levels on all of the days tested.

Yes, if that's the case. I would think after all this time they would have tested the samples for other substances like creatinine, so they would know if that backed them up. But maybe not yet. Maybe they just recently came up with the possibility of kidney malfunction, and haven't had time to follow that up with further testing.

Some of the news articles about this claim: that Froome's lawyers already abandoned the dehydration concept, meaning they probably know his USG was too low to support such an approach

That's not what I mean. He apparently wasn't dehydrated on stage 18, not enough to raise his USG to the level needed to make a large correction in the allowed DL. But what I was referring to is the possibility that on a previous stage he suffered from dehydration, which temporarily affected his kidneys. This is possible. Renal function could have been affected as a result of the shock of dehydration, so that even after rehydrating, he still wasn't passing substances normally.

Making the whole thing a high-stakes game based on a claim difficult to prove. They can't seek to (re)create conditions of acute renal failure

Gives new meaning to the term DQ: double or quits, or as we say in America, double or nothing. And that in itself has a double meaning. It can refer to gambling that he can skate, at the risk of doubling his penalty if his strategy fails. It can also refer to the fact that he wants to ride the Giro/TDF double, and will risk not being able to ride either (if he loses the hearing) rather than one (if he accepted a shorter suspension).

I've been trying to understand Froome's thought process here. Is the Vuelta title so important to him that he's willing to risk the Giro/TDF this year, and maybe next year as well? Even if, say, a short suspension following admitting he made a mistake prevented him from riding either the Giro or the Tour, he could at least ride the Vuelta again, getting back that title he lost. Then go for the double, or at least one of those GTs next year. Whereas if his strategy fails, he probably won't be able to ride a GT till 2020, and considering his age at the time, and the long layoff, his prospects of winning another GT would seem to be pretty dim.

I just wonder if what Froome is doing is the result of careful calculation of the potential consequences, or if he just become so worried about losing the Vuelta, after all his unsuccessful attempts to win it, that he's thrown caution to the wind.

Would it really be doubled? I thought Petacchi never admitted wrongdoing as well, for his 9 months ban?

 

[Wiggo's Package]

Re: Re:

I've been trying to understand Froome's thought process here. Is the Vuelta title so important to him that he's willing to risk the Giro/TDF this year, and maybe next year as well? Even if, say, a short suspension following admitting he made a mistake prevented him from riding either the Giro or the Tour, he could at least ride the Vuelta again, getting back that title he lost. Then go for the double, or at least one of those GTs next year. Whereas if his strategy fails, he probably won't be able to ride a GT till 2020, and considering his age at the time, and the long layoff, his prospects of winning another GT would seem to be pretty dim.

I just wonder if what Froome is doing is the result of careful calculation of the potential consequences, or if he just become so worried about losing the Vuelta, after all his unsuccessful attempts to win it, that he's thrown caution to the wind.

An alternative view on Froome's thought process:-

- Accepting responsibility for the AAF and taking a short ban so he can race this year is not a viable option. Froome has spouted too much sanctimonious crap ("This is one yellow jersey which will stand the test of time...") and backed himself into a corner. And Brailsfraud won't let him take a pragmatic approach because the team would implode

- But Froome's expensive legal and scientific team haven't been able to help much. There is no easy way out especially now Uncle Brian's departure has taken the "file in the bin" option off the table. So he's gone for the obscure renal malfunction option that is potentially hard to prove either way and creates enough doubt for the UCI to hang their hat on if so inclined

- Importantly the obscure renal malfunction option is, as you say, double or quits. Either Froome gets a free pass or he gets a 2yr ban. This puts added pressure on the UCI because ending the career of the sport's 33yr old top rider would be terrible PR. In that context the UCI might just decide to do the usual sports administrator thing and prioritise reputation over anti-doping. Froome's lawyer has in a calculating way offered the UCI a classic fudge

However, the big problem with the double or quits approach is that there's now a Frenchman and not a Brit in charge at the UCI. The correlation between Froome's GT wins and a Brit being in charge of the UCI is quite striking. Next up - a high correlation between Bardet winning GTs and a Frenchman being in charge of the UCI? Who knows, but Bardet winning the TdF more likely to happen with Froome out the picture

 

[Alpe73]

Re: Re:

I've been trying to understand Froome's thought process here. Is the Vuelta title so important to him that he's willing to risk the Giro/TDF this year, and maybe next year as well? Even if, say, a short suspension following admitting he made a mistake prevented him from riding either the Giro or the Tour, he could at least ride the Vuelta again, getting back that title he lost. Then go for the double, or at least one of those GTs next year. Whereas if his strategy fails, he probably won't be able to ride a GT till 2020, and considering his age at the time, and the long layoff, his prospects of winning another GT would seem to be pretty dim.

I just wonder if what Froome is doing is the result of careful calculation of the potential consequences, or if he just become so worried about losing the Vuelta, after all his unsuccessful attempts to win it, that he's thrown caution to the wind.

An alternative view on Froome's thought process:-

- Accepting responsibility for the AAF and taking a short ban so he can race this year is not a viable option. Froome has spouted too much sanctimonious crap ("This is one yellow jersey which will stand the test of time...") and backed himself into a corner. And Brailsfraud won't let him take a pragmatic approach because the team would implode

- But Froome's expensive legal and scientific team haven't been able to help much. There is no easy way out especially now Uncle Brian's departure has taken the "file in the bin" option off the table. So he's gone for the obscure renal malfunction option that is potentially hard to prove either way and creates enough doubt for the UCI to hang their hat on if so inclined

- Importantly the obscure renal malfunction option is, as you say, double or quits. Either Froome gets a free pass or he gets a 2yr ban. This puts added pressure on the UCI because ending the career of the sport's 33yr old top rider would be terrible PR. In that context the UCI might just decide to do the usual sports administrator thing and prioritise reputation over anti-doping. Froome's lawyer has in a calculating way offered the UCI a classic fudge

However, the big problem with the double or quits approach is that there's now a Frenchman and not a Brit in charge at the UCI. The correlation between Froome's GT wins and a Brit being in charge of the UCI is quite striking. Next up - a high correlation between Bardet winning GTs and a Frenchman being in charge of the UCI? Who knows, but Bardet winning the TdF more likely to happen with Froome out the picture

New "New Journalism"

 

[gillan1969]

Re: Re:

I've been trying to understand Froome's thought process here. Is the Vuelta title so important to him that he's willing to risk the Giro/TDF this year, and maybe next year as well? Even if, say, a short suspension following admitting he made a mistake prevented him from riding either the Giro or the Tour, he could at least ride the Vuelta again, getting back that title he lost. Then go for the double, or at least one of those GTs next year. Whereas if his strategy fails, he probably won't be able to ride a GT till 2020, and considering his age at the time, and the long layoff, his prospects of winning another GT would seem to be pretty dim.

I just wonder if what Froome is doing is the result of careful calculation of the potential consequences, or if he just become so worried about losing the Vuelta, after all his unsuccessful attempts to win it, that he's thrown caution to the wind.

An alternative view on Froome's thought process:-

- Accepting responsibility for the AAF and taking a short ban so he can race this year is not a viable option. Froome has spouted too much sanctimonious crap ("This is one yellow jersey which will stand the test of time...") and backed himself into a corner. And Brailsfraud won't let him take a pragmatic approach because the team would implode

- But Froome's expensive legal and scientific team haven't been able to help much. There is no easy way out especially now Uncle Brian's departure has taken the "file in the bin" option off the table. So he's gone for the obscure renal malfunction option that is potentially hard to prove either way and creates enough doubt for the UCI to hang their hat on if so inclined

- Importantly the obscure renal malfunction option is, as you say, double or quits. Either Froome gets a free pass or he gets a 2yr ban. This puts added pressure on the UCI because ending the career of the sport's 33yr old top rider would be terrible PR. In that context the UCI might just decide to do the usual sports administrator thing and prioritise reputation over anti-doping. Froome's lawyer has in a calculating way offered the UCI a classic fudge

However, the big problem with the double or quits approach is that there's now a Frenchman and not a Brit in charge at the UCI. The correlation between Froome's GT wins and a Brit being in charge of the UCI is quite striking. Next up - a high correlation between Bardet winning GTs and a Frenchman being in charge of the UCI? Who knows, but Bardet winning the TdF more likely to happen with Froome out the picture

all this speculation is, to be fair, far more exciting than any of froome's GT wins....the mountain ranges have changed to science, as have the competitors to bureaus, and indeed the teamates to laweyrs and renal specialists......but this unfolding comic-drama should keep us going (in the absence of a competitive cyclo cross season) until the spring one-day classics... good work team sky (bafta/emmy awards surely)

 

[Merckx index]

More speculation...Let’s say Froome really was suffering from acute renal failure to some degree. What could cause it to reverse, restoring normal kidney function, and resulting in rapid excretion of the built-up levels of salbutamol in the blood? A lot of recent research suggests that EPO exerts both nephroprotective and nephorestorative effects. That is, in animal models in which acute renal failure is induced by temporary restriction of blood flow to the kidneys, giving EPO before, during or after the operation results in significant improvement (maybe not surprising, given that most EPO is synthesized in the kidney). There appear to be direct effects of EPO on the kidney, independent of increasing the hematocrit, and some studies have shown that EPO also acts on brain centers that regulate kidney function.

So in this scenario, Froome suffers from renal impairment, with salbutamol levels building up in his blood until he takes EPO. The EPO helps restore normal renal function, with the high serum levels of the drug becoming converted into high levels in the urine.

This is obviously highly speculative, and I wouldn’t take it too seriously just yet (the required EPO doses are quite high, and of course, the entire renal impairment scenario seems to be a fantasy), but now we have a potential way of explaining why Froome’s salbutamol level was so high on just one day, an explanation moreover that leads back to blood doping. Wouldn’t it be ironic if Froome, in attempting to provide an innocent explanation for his salbutamol positive, actually showed how it could be the result of a blood transfusion after all (for note that blood transfusions are often accompanied by EPO, in order to reverse the inhibition of reticulocyte synthesis)?

https://www.ncbi.nlm.nih.gov/pubmed/25682558
http://sci-hub.la/10.1080/10641963.2016.1246565
http://sci-hub.la/10.1016/j.semnephrol.2006.05.010
https://www.ncbi.nlm.nih.gov/pubmed/27634442

But there’s another possibility in which one doesn’t have to postulate renal impairment from an unknown cause. As is the case with so many physiological relationships, EPO may have both beneficial and deleterious effects on the kidneys, depending on how much of it is present. So while this is again speculative, EPO might conceivably cause or at least exacerbate renal impairment. In this scenario, the problem would begin by taking EPO, leading to serum build-up of salbutamol levels. EPO, however, is mostly metabolized in the liver, so even with kidney function below normal, it would be cleared from the blood fairly quickly. At this point, kidney function would be restored.

This mechanism could conceivably explain not only Froome’s positive, but those of other riders like Ulissi and Petacchi. They took EPO, which caused a temporary renal impairment, resulting in an accumulation of salbutamol in the blood, and higher than normal urinary levels when kidney function recovered. Recovery would also be hastened at this point by the elevated hematocrit, which of course persists long after the EPO is metabolized.

https://www.ncbi.nlm.nih.gov/pubmed/29187371

 

[gillan1969]

More speculation...Let’s say Froome really was suffering from acute renal failure to some degree. What could cause it to reverse, restoring normal kidney function, and resulting in rapid excretion of the built-up levels of salbutamol in the blood? A lot of recent research suggests that EPO exerts both nephroprotective and nephorestorative effects. That is, in animal models in which acute renal failure is induced by temporary restriction of blood flow to the kidneys, giving EPO before, during or after the operation results in significant improvement (maybe not surprising, given that most EPO is synthesized in the kidney). There appear to be direct effects of EPO on the kidney, independent of increasing the hematocrit, and some studies have shown that EPO also acts on brain centers that regulate kidney function.

So in this scenario, Froome suffers from renal impairment, with salbutamol levels building up in his blood until he takes EPO. The EPO helps restore normal renal function, with the high serum levels of the drug becoming converted into high levels in the urine.

This is obviously highly speculative, and I wouldn’t take it too seriously just yet (the required EPO doses are quite high, and of course, the entire renal impairment scenario seems to be a fantasy), but now we have a potential way of explaining why Froome’s salbutamol level was so high on just one day, an explanation moreover that leads back to blood doping. Wouldn’t it be ironic if Froome, in attempting to provide an innocent explanation for his salbutamol positive, actually showed how it could be the result of a blood transfusion after all (for note that blood transfusions are often accompanied by EPO, in order to reverse the inhibition of reticulocyte synthesis)?

https://www.ncbi.nlm.nih.gov/pubmed/25682558
http://sci-hub.la/10.1080/10641963.2016.1246565
http://sci-hub.la/10.1016/j.semnephrol.2006.05.010
https://www.ncbi.nlm.nih.gov/pubmed/27634442

But there’s another possibility in which one doesn’t have to postulate renal impairment from an unknown cause. As is the case with so many physiological relationships, EPO may have both beneficial and deleterious effects on the kidneys, depending on how much of it is present. So while this is again speculative, EPO might conceivably cause or at least exacerbate renal impairment. In this scenario, the problem would begin by taking EPO, leading to serum build-up of salbutamol levels. EPO, however, is mostly metabolized in the liver, so even with kidney function below normal, it would be cleared from the blood fairly quickly. At this point, kidney function would be restored.

This mechanism could conceivably explain not only Froome’s positive, but those of other riders like Ulissi and Petacchi. They took EPO, which caused a temporary renal impairment, resulting in an accumulation of salbutamol in the blood, and higher than normal urinary levels when kidney function recovered.

https://www.ncbi.nlm.nih.gov/pubmed/29187371

to be fair, if Carlsberg did speculation......

some blood passport style data would be useful at this point, or far more usefully a blood profile across the Vuelta......unfortunately the only 'scientist looking at the physiology of multiple a GT winner chose to study him on only one day

 

[brownbobby]

More speculation...Let’s say Froome really was suffering from acute renal failure to some degree. What could cause it to reverse, restoring normal kidney function, and resulting in rapid excretion of the built-up levels of salbutamol in the blood? A lot of recent research suggests that EPO exerts both nephroprotective and nephorestorative effects. That is, in animal models in which acute renal failure is induced by temporary restriction of blood flow to the kidneys, giving EPO before, during or after the operation results in significant improvement (maybe not surprising, given that most EPO is synthesized in the kidney). There appear to be direct effects of EPO on the kidney, independent of increasing the hematocrit, and some studies have shown that EPO also acts on brain centers that regulate kidney function.

So in this scenario, Froome suffers from renal impairment, with salbutamol levels building up in his blood until he takes EPO. The EPO helps restore normal renal function, with the high serum levels of the drug becoming converted into high levels in the urine.

This is obviously highly speculative, and I wouldn’t take it too seriously just yet (the required EPO doses are quite high, and of course, the entire renal impairment scenario seems to be a fantasy), but now we have a potential way of explaining why Froome’s salbutamol level was so high on just one day, an explanation moreover that leads back to blood doping. Wouldn’t it be ironic if Froome, in attempting to provide an innocent explanation for his salbutamol positive, actually showed how it could be the result of a blood transfusion after all (for note that blood transfusions are often accompanied by EPO, in order to reverse the inhibition of reticulocyte synthesis)?

https://www.ncbi.nlm.nih.gov/pubmed/25682558
http://sci-hub.la/10.1080/10641963.2016.1246565
http://sci-hub.la/10.1016/j.semnephrol.2006.05.010
https://www.ncbi.nlm.nih.gov/pubmed/27634442

But there’s another possibility in which one doesn’t have to postulate renal impairment from an unknown cause. As is the case with so many physiological relationships, EPO may have both beneficial and deleterious effects on the kidneys, depending on how much of it is present. So while this is again speculative, EPO might conceivably cause or at least exacerbate renal impairment. In this scenario, the problem would begin by taking EPO, leading to serum build-up of salbutamol levels. EPO, however, is mostly metabolized in the liver, so even with kidney function below normal, it would be cleared from the blood fairly quickly. At this point, kidney function would be restored.

This mechanism could conceivably explain not only Froome’s positive, but those of other riders like Ulissi and Petacchi. They took EPO, which caused a temporary renal impairment, resulting in an accumulation of salbutamol in the blood, and higher than normal urinary levels when kidney function recovered. Recovery would also be hastened at this point by the elevated hematocrit, which of course persists long after the EPO is metabolized.

https://www.ncbi.nlm.nih.gov/pubmed/29187371

Highly speculative yes, but very interesting...

 

[Merckx index]

From Velonews:

Since day one of this mess, cyclists and cycling fans have asked me what is the Occam’s Razor for the Froome case. So over the past few weeks, I have posed the question to experts in the realm of medicine and sports science. Doctors, researchers, and so on. You have likely read about some of these experts on our site in recent weeks.

My questions: What’s the simplest explanation in the Froome case? What is Occam’s Razor here, given the facts of the case?
…
To a person, these doctors and researchers have provided a similar answer to the Occam’s Razor question: Froome either took an oral dose of salbutamol, or he used a salbutamol nebulizer. Both methods are forbidden by WADA code.

It was the final week of the 2017 Vuelta a España, and Chris Froome had a cold. And the cold inflamed his asthma. Note: many asthmatics (myself included) are familiar with this pattern. Even a basic head cold eventually ends up in our lungs, causing wheezing, tightness, and endless fits of phlegmy coughing.

Froome battled the coughs with his salbutamol inhaler. When a respiratory infection meets asthma, however, the coughing and wheezing can get bad. Using the puffer is akin to squirting a garden hose on a five-alarm fire.

Froome needed a firehose. And in this situation, the firehose was either a salbutamol tablet or a salbutamol nebulizer. Those are the methods that can deliver a big enough dose to douse the flames.

But there’s a problem: Oral salbutamol is banned, and nebulizers require a TUE. And the dose that both of these methods deliver is almost guaranteed to surpass the legal threshold.

Froome faced a tough choice. He could quit; he could continue, and risk his health, or he could gamble with the banned method.

The Occam’s Razor explanation is that Froome and Sky chose to gamble. Perhaps their calculus was that he could over-hydrate the next day and dilute his urine enough to avoid a positive test. Or that Sky’s political relationships within the sport would override what would surely be a minor infraction.

A nebulizer would be much more efficient (more relief per mg) than an oral dose, so between those two, I'd go with that. The only problem I have with this explanation is I would have thought that if this was the situation, Froome would have confessed and gone for the short suspension. He has been so adamant that he didn't take more than the allowed dose, which is something I would expect him to say only if a) it was true; or b) he was covering up intentional doping. But I have to say that if that's the worst criticism of this explanation, it looks pretty good compared to the others, which as we've seen, all have problems of their own. I still think intentional oral dosing is plausible, but one does have to account for why his levels went way up only on one day, and for that matter, why he was using the drug during a GT.

If this author's account is what happened, Froome has gambled twice. First, that he could get away with taking a supramaximal dose; he clearly lost that gamble. And second, that he could insist he didn't, and get off without any sanction. If he loses that, he will not only fairly likely be finished as a GT winner, but will take a massive PR hit, and face being fired from Sky. Whereas if he had confessed, Sky probably would not fire him, and he could present himself as someone who at least broke the rules purely for health reasons, rather than to gain a performance advantage.

And of course now it's too late for Froome to reverse himself, and confess to using a nebulizer. Many people would not believe him, and those who did would have to acknowledge that not only did he intentionally break the rules, but he lied about it until it appeared to his advantage to tell the truth. So even if this is actually what happened, Froome would come out of this looking just as bad as if he had intentionally used salbutamol for performance enhancement.

 

[movingtarget]

From Velonews:

It was the final week of the 2017 Vuelta a España, and Chris Froome had a cold. And the cold inflamed his asthma. Note: many asthmatics (myself included) are familiar with this pattern. Even a basic head cold eventually ends up in our lungs, causing wheezing, tightness, and endless fits of phlegmy coughing.
Froome battled the coughs with his salbutamol inhaler. When a respiratory infection meets asthma, however, the coughing and wheezing can get bad. Using the puffer is akin to squirting a garden hose on a five-alarm fire.
Froome needed a firehose.

This would be a straightforward explanation if it were true. Froome isn't sick, wheezing, phlegmatic, or battling coughs during any of the post-race interviews. All of the videos can be seen online. Froome didn't have a respiratory infection during the Vuelta. The Velonews author fabricated that part as if it would justify the doping with a legitimate medical concern. The "Occam's Razor" having been too dull for this purpose, the simplest explanation was not the truth. So I wonder if the article is half-joking

Yes for someone with moderate to severe asthma, such an infection does not disappear during the day or even overnight, it's a few days at best and in endurance sports such an illness combined with asthma would mean withdrawal from the event. Ventolin is not a magic potion in that regard. Only rest and additional drugs will help, not five hour bike rides over mountains in the Spanish summer. If he was playing in a snooker tournament or playing ten pin bowls he probably could have continued and the Ventolin would have been in his pocket even then.

 

[Merckx index]

At his Science of Sport website, Ross Tucker has a 7 minute video discussing the kidney malfunction theory. He provides one piece of new information: he says that back in December, right after the leak of the AAF, he heard several sources close to the investigation report that this was going to be part of Froome’s defense. IOW, this isn’t necessarily a last resort, something Froome turned to because there was no other way of explaining the positive.

That doesn’t necessarily mean, of course, that the theory will work. I would think one of the first things a science advisor would do in this situation is consider all the possible explanations for the positive, even before trying to replicate the positive in a lab test. We don’t know if they focused on this possibility as the most likely at that time. But Tucker adds that they wanted to see all the earlier tests--again, something I would expect any scientist would do--and if there was a suggestive pattern, they may have noticed it at the time.

Meanwhile, acute renal impairment is a known side effect of NSAIDs (non-steroidal anti-inflammatory drugs), which include aspirin and ibuprofen. Though paracetamol is technically not considered a NSAID, it also has this side effect, which is related to prostaglandin release and blood flow in the kidneys. I don't know how common this is; these drugs, of course, are very widely used. Adverse effects would be expected to occur more often in older people. On the other hand, I guess it's conceivable one might experience a temporary renal impairment without noticing it. This is all a stretch, but I'm trying to anticipate the case they're going to make.

Finally, something that just occurred to me. If salbutamol excretion was inhibited, it would remain in the blood for a relatively long time. This means it would pass through the liver and be metabolized, mainly sulfated. This would affect the enantiomer test, which depends on differential rates of sulfation for the two stereoisomers. In short, even inhaled salbutamol would probably test as oral under these conditions.

So this is a double-edged sword. On the one hand, assuming Froome's sample doesn't pass the enantiomer test, as I suspect has already been established, the renal impairment theory could explain this. OTOH, unless they have other solid evidence for this theory, like a string of very low levels preceding stage 18, some of the most important evidence won't help them. It can be interpreted as indicating intentional doping.

 

[70kmph]

Bad day for Team Froome as noose tightens:

A) Brailsford advised to provisionally ban his rider
B) Not all defenses will be acceptable to LADS
C) Case will take a year because of the high resistance

 

[thehog]

Re:

Bad day for Team Froome as noose tightens:

A) Brailsford advised to provisionally ban his rider
B) Not all defenses will be acceptable to LADS
C) Case will take a year because of the high resistance

I sense Brailsford might be stuck in “Cookson mode”, thinking he can do what he wants, when he wants and have his rider back on the team. Not sure he’s going to get the Henao privilege on this one.

 

[macbindle]

Cant find the Tucker vid. Could somebody post a link please?

 

[poupou]

Should be that : https://www.youtube.com/watch?v=HRoE_WjX-7E