All About Salbutamol

[Merckx index]

Re:

I was thinking of this interview with Olivier Rabin, science director at WADA:

https://translate.google.com/translate?sl=auto&tl=en&js=y&prev=_t&hl=en&ie=UTF-8&u=http%3A%2F%2Fwww.lemonde.fr%2Fcyclisme%2Farticle%2F2017%2F12%2F14%2Faffaire-froome-la-charge-de-la-preuve-revient-a-l-athlete_5229768_1616656.html&edit-text=&act=url

Very interesting, thanks for the link. Since 1600 ug/24 hr is permitted, the rider would have to be allowed to have some salbutamol in his urine at the start of the test. If Rabin is serious about duplicating the conditions as they actually occurred, though, Froome would have to document taking some of the substance beginning after testing the previous day's stage, and it would be essentially impossible for him to make the case that he didn't urinate between then and 24 hr later. So this does seem to raise the bar even higher.

Some other interesting points made in the interview:

Has there been an overdose? It happens, even fairly frequently.

I note he's vague about the possibility of another substance affecting the excretion rate of salbutamol. If WADA knew about some substance, surely they would be studying it, but AFAIK, they aren't.

Note also that at the end, in response to a question about oral vs. inhaled, he says, "We have no element of certainty." As I thought, there is no approved test for this, because the tests that may exist aren't good enough (i.e., too many false positives and/or false negatives).

Not sure how fair that is. I guess you can do one test for WADA and if that doesn't get you off, still have another one for CAS.

I believe he can do it however he wants for CAS, though of course the closer it follows what actually happened on the road, the more convincing it will be.

Here’s a more recent study (2015) in which 1600 ug were inhaled all at once. It was mentioned by a scientist interviewed by VN, as a possible indication that super-threshold levels could occur while staying within the WADA rules. There were 13 subjects, and three protocols were run: rest, exercise and exercise/dehydration (water intake restricted). Urine samples were taken at 1.5, 4 and 6 hr. So a total of 117 samples were taken. Of these, 33 or 28% exhibited uncorrected levels > 1000 ng/ml; when urine was corrected for specific gravity, there were still 23 or 20% of the samples above the threshold.

However, keep in mind, again, that 1600 ug is not permitted in a short period of time. Also, even under these extreme conditions, only 5/117 samples exceeded 2000 ng/ml.

What someone really should test is 800 ug, followed by another 800 ug 12 hr later, then urine tests. That would set the ceiling on what is theoretically possible while following WADA rules. There has been a study, discussed above, in which 800 ug was taken at once, followed by urine tests. Only 1/64 samples exceeded 1000 ng/ml and was still below the 1200 ng/ml decision limit. However, from the two studies by the Elers group, I see that 12 hr after an 800 ug dose, there could be as much as 200-250 ug/nl if the subject doesn't pee. Most of this would be added to the amount excreted by the new 800 ug dose, if urine were collected soon after.

The other study I would like to see is of variability of one individual. Test the individual multiple times, not varying conditions, to see how much the urine levels vary. That would provide a baseline of variability, which would be increased if conditions such as exercise and dehydration varied.

http://sci-hub.la/10.1002/dta.1828

So this would be Froome's strategy:

a) He's already claimed he had three puffs after finishing the stage. If he could demonstrate he had five other puffs late in the stage, so the entire 800 ug dose was taken within two hours of testing, that would maximize his urine level.

b) If he's like one of the outlier subjects in published studies, he might conceivably have a level of 1000 ng/ml at that point

c) Most of the kinetic studies have first analyzed urine after four hours, but other studies show that the concentrations peak sooner, within an hour or so. They probably don't fall off too much, but somewhat. So that 1000 ng/ml level could possibly be pushed up to 1200-13000 ng/ml if the urine were assayed sooner.

d) If he took 800 ug in the previous 12 hr period, this would add some salbutamol to the total, if he were an outlier, maybe as much as 400-500 ng/ml. Now he's not far from 2000 ng/ml. and we still haven't considered dehydration.

e) At this point, though, the question would be raised, why wasn't such a high level ever realized before? Froome would have to establish that he never took more than 2-3 puffs total in any 12 hr period prior to this stage.

A very unlikely scenario, but I think that's what it would take. However, if he were willing to confess accidentally taking more than 800 ug, then it becomes a little more plausible. Not as much as oral dosing, but maybe enough to convince CAS.

 

[Random Direction]

Mercx - the alternate hypothesis is, of course far more likely. This does raise an interesting point - the conditional test potentially could be gamed to maximize the salbutamol concentration, to a far higher level than would occur in real world conditions. One would hope that the test requirements be set per the circumstances of the race stage and be monitored by a CAS staff member.

Too much potential for Sky to pull a Volkswagen otherwise.

Indeed they are probably running experiments now on how to maximize test scores for when froome actually has to be tested.

 

[sittingbison]

Re:

...indeed they are certainly running experiments now on how to maximize test scores for when froome actually has to be tested.

Fixed it for you. No charge

 

[sittingbison]

Re: Re:

...
e) At this point, though, the question would be raised, why wasn't such a high level ever realized before? Froome would have to establish that he never took more than 2-3 puffs total in any 12 hr period prior to this stage...

MI, a doctor working at a testing lab in one of the previous links said he had tested something like 50,000 samples for salbutamol. And there have been what, 21 positives over the past 20 years? And Dawg at 2000 is the World Champion? I think Dawgs fancy lawyer has an uphill battle convincing CAS that Dawg is alien enough to discount such a volume of anecdotal evidence....including Dawgs own prior hundreds of tests and specifically stage 17 and stage 19

 

[samhocking]

Obviously, a high dose of Salbutamol indicates severe breathing problems. We can all see the footage, and the end result compared to a peloton of athletes in their prime. Used to enhance his performance, and probably miscalculated the max -possibly because of a blood transfusion. I'm eager to find out, but it doesn't matter all that much. He had an unfair advantage, that's what counts.

I don't know when Sky left the mpcc exactly, but it's only the fourth scandal since. You had the rider who came forward about painkiller abuse within the team, the mysterious medical package delivery,TUEs during TDF wins, and now this. Add UCI's reluctance to do their job properly when it involves 35 million, and basicly nothings changed since the US Postal scam.

Were they ever part of the MPCC?

No.

My bad,they rejected to join because ofits medical rules.

Brailsford once said that Sky’s internal rules were more stringent than MPCC hence their reason for not joining :lol:

Brailsford said they would only join MPCC when they don't allow riders and staff banned for doping to be members.

 

[Blanco]

Hillarious! :lol:

You mean guys like Mick Rogers, Leinders, Zabriskie, De Jongh, Barry and others..? :lol:

Or maybe it had something to do with corticosteroids and other "marginal gains"

 

[Wiggo's Package]

Re:

Hillarious! :lol:

You mean guys like Mick Rogers, Leinders, Zabriskie, De Jongh, Barry and others..? :lol:

Or maybe it had something to do with corticosteroids and other "marginal gains"

That Brailsfraud is economical with the truth is the craziest conspiracy theory of the lot...

 

[movingtarget]

Re: Re:

...
e) At this point, though, the question would be raised, why wasn't such a high level ever realized before? Froome would have to establish that he never took more than 2-3 puffs total in any 12 hr period prior to this stage...

MI, a doctor working at a testing lab in one of the previous links said he had tested something like 50,000 samples for salbutamol. And there have been what, 21 positives over the past 20 years? And Dawg at 2000 is the World Champion? I think Dawgs fancy lawyer has an uphill battle convincing CAS that Dawg is alien enough to discount such a volume of anecdotal evidence....including Dawgs own prior hundreds of tests and specifically stage 17 and stage 19

The Alien defense. Froome is not human so his tolerance is higher. Born in an African laboratory. Hence the unusual riding style.

 

[70kmph]

Can we tell the difference between a general intake, which is strictly prohibited, and an inhaled intake?

We have no element of certainty. By combining certain indicators with other elements of outcome information and the environment described by the athlete, this may, however, lead to a relatively high level of certainty.

Olivier Rabin, science director at WADA

http://www.lemonde.fr/cyclisme/arti...euve-revient-a-l-athlete_5229768_1616656.html

 

[70kmph]

Re: Re:

There are ways that a sophisticated lab could differentiate between oral/injected salbutamol and inhaled. But are those methods part of the ordinary lab work-up on positive samples? Can WADA request any kind of testing they want in order to prove a point in a contested doping case? It is not so much technical as procedural, so that would be a good topic for someone to look into. They can prove it, but are they allowed to use the logical approach to do that?

See the Petacchi case from 10 years ago, they sent his sample to a Barcelona lab for this specific testing

In his witness statement, Prof. Segura, the Director of the Barcelona Laboratory, stated his
opinion that, “The results of the sample coded A926245, which I have been told belongs to Mr. Petacchi, are not compatible with an “accidental” swallowing of a portion of the product in the course of a therapeutic use of Salbutamol by inhalation, i.e within the dosage indicated above. Possible explanations of the results of the test obtained through the enantiomers method indicate that such results have been caused by a direct oral administration of Salbutamol or the “accidental” swallowing of a part of the product administered by inhalation at a supra therapeutic dose, i.e. a dose, which clearly exceeds the dosage indicated above”.

 

[Merckx index]

There are ways that a sophisticated lab could differentiate between oral/injected salbutamol and inhaled. But are those methods part of the ordinary lab work-up on positive samples? Can WADA request any kind of testing they want in order to prove a point in a contested doping case? It is not so much technical as procedural, so that would be a good topic for someone to look into. They can prove it, but are they allowed to use the logical approach to do that?

To repeat, there is apparently no approved test. If there were, WADA would use it and not have to be concerned with threshold levels. An unapproved test can certainly be submitted as evidence at CAS, but as noted in the Petacchi case, they didn't attempt to discriminate between an oral dose and an inhaled dose that was partially swallowed. The furthest they were willing to go, at least at that time, was to say that if he had inhaled no more than the allowed amount, the amount he could have swallowed would not have been enough to account for the results.

In any case, I don't know how you can stop a rider from claiming he swallowed some of the dose. In fact, according to ScienceisCool, typically only about 40 ug—at best--of a 100 ug dose is inhaled,and I would think it would be worse during the heat of a race. I assume the rest is swallowed. If it doesn't get into the system at all, then we have a real problem in overestimating how much a rider is taking. As SiC goes on to point out, studies using inhalers probably take care to make sure that all the dose is inhaled, because if it weren’t, it would be difficult to draw any conclusions in comparisons to oral doses. Yet checking some of the studies that have been linked in this thread, I find no mention of this in most cases. One article mentions the use of a spacer, which I understand helps ensure that more of the drug gets into your lungs. Is that sufficient to get all of it in? * You would think if it were a serious problem--and SiC linked an article indicating it is--that some mention of it would be made in the Methods section.

M. Olivier also raises two points which have not really been addressed by this salbutamol thread - could other substances which compete for the same cytochrome prolong the metabolism of the drug? And "at the renal level" he says some other substances could interfere with excretion of the salbutamol.

Without saying which drugs those may be, and whether those are also implicated in doping practices. But he says it's hard "to imagine ... all possible cases", so there are too many possibilities, to easily sort out

As I noted before, there doesn't seem to be any evidence of inhibitors that affect detoxification of salbutamol, nor of substances that affect renal clearance. When Olivier says "all possible cases", I think he's just referring to the fact that there could be such substances, but unless Froome's team can point to specific research, that doesn't help him. Petacchi’s team brought this issue up, but couldn’t back it up with any evidence. And of course, even if Froome did come up with some relevant evidence, he'd have to explain why this was only a problem on this one stage. This would also be the case if he had some more general disorder. E.g., if he had some problem with his liver or kidneys, that might affect clearance of the drug, but then one would expect to see the problem on preceding and/or succeeding stages.

One class of drugs that might be a problem would be b-blockers, or antagonists, but I assume Froome would not be taking any of those. I assume they're probably banned, in any case. They would not necessarily affect clearance of salbutamol, but by interfering with its interaction with its receptors, so more of the drug would be required to get a given effect. But even if he were taking a b-blocker, it certainly wouldn't be by inhalation, and I'm not sure how much of it would get into the lungs in that case.

By the way, just for the record, Froome has worn the leader's jersey in the TDF 59 times, per Wiki, and 20 times in the Vuelta. I haven't bothered to check, but he probably won a few stages in those Tours when he wasn't the leader, and would be tested then, too. When you add random OOC tests, he probably has been tested for salbutamol close to one hundred times.

*Here’s a recent study comparing a measured dose inhaler (MDI), which is generally what is used in the pharmacokinetic studies, with other means of inhaling salbutamol:

http://sci-hub.la/10.1016/j.pupt.2017.06.004

Subjects inhaled 800 ug of salbutamol, then provided a urine sample 30 min later. Using the MDI, 35% of the 800 ug dose was found in the urine. The study also used a filter which was placed over the subject’s throat; apparently previous studies showed that it would trap all of the substance that would otherwise go to the lungs. Analysis of the filter revealed that 65% of the inhaled dose was trapped on it. So a lot of the dose, but certainly not all of it.

The first result doesn’t make sense to me, it's way too much. However, other articles by the same group reported far lower values.

But another study noted that: "Even when MDIs are used correctly, approximately 10% of the drug is deposited in the lungs, whereas nearly 80% is deposited in the oropharynx." This study found no effect of using a spacer, as determined by an FEV1 test for effect on asthma. A study cited in the Discussion reported a slight increase in deposition in the lungs with the use of a spacer, and a major reduction in deposition in the throat. When I looked at that study, I found that the main effect of the spacer was to reduce by more than 50% the amount of drug getting into the body at all. The spacer was effective in reducing the amount of drug swallowed, but only because most of the drug never got into the body.

At this point I have no idea how studies of inhaled salbutamol can be carried out with any confidence that the amount nominally present in the puff gets in the lungs, or maybe even in the body.

http://www.scielo.br/scielo.php?script=sci_arttext&pid=S1806-37132011000600008&lng=en&nrm=iso&tlng=en

Here’s a study of the effect of a polymorphism (mutation) in a gene for a salbutamol-metabolizing enzyme. No differences between polymorphic and wild-type (normal) subjects were found. This is an example of research into the issue, though:

https://www.ncbi.nlm.nih.gov/pubmed/24692077

 

[Armchair Cyclist]

So motive for Salbutamol in larger doses, beyond relief of asthma symptoms, is weight loss while maintaining body mass: clearly desirable for a GT cyclist.

But would such somatological change not be a long term objective, attained by long term medication, rather than by sudden large doses? This goal seems compatible with all year round oral dosages, probably scaled back during competition. Even if Froome's response to a (relatively) poor day on stage 17 had been to eat incredibly unhealthily, no amount of Salbutamol will restore the desired weight/power ratio within 24 hours.

If we have accepted that dilution issues mean that blood bags are only a small contributor to the Salbutamol excretion levels recorded, what would be the motivation for such a huge Salbutamol intake on that particular day? The daily variances of asthma accounts for 3 extra puffs: what gain does Salbutamol give that quickly that comes even close to running the risk?

Is this a purely irrational panic response (in the pattern of running up Ventoux) of throwing anything and everything at a perceived problem? Or am I missing something about speed of weight loss, and some belief in the team that he was overweight on the morning of 7th Sept, and expected lots of Salbutamol to resolve the issue by mid afternoon?

 

[veganrob]

Didn't Froome claim he had actually gained weight during a TdF. Was it this year?

 

[yaco]

Froome claimed he weighed more at the Vuelta then at the TDF.

 

[hazaran]

What's the weight loss effect of Salbutamol supposed to be anyway? From what I read it makes you slightly tachycardic, so maybe extra base load from the elevated HR? That doesn't sound terribly effective at all.

 

[cnc-it]

Re:

So motive for Salbutamol in larger doses, beyond relief of asthma symptoms, is weight loss while maintaining body mass: clearly desirable for a GT cyclist.

But would such somatological change not be a long term objective, attained by long term medication, rather than by sudden large doses? This goal seems compatible with all year round oral dosages, probably scaled back during competition. Even if Froome's response to a (relatively) poor day on stage 17 had been to eat incredibly unhealthily, no amount of Salbutamol will restore the desired weight/power ratio within 24 hours.

If we have accepted that dilution issues mean that blood bags are only a small contributor to the Salbutamol excretion levels recorded, what would be the motivation for such a huge Salbutamol intake on that particular day? The daily variances of asthma accounts for 3 extra puffs: what gain does Salbutamol give that quickly that comes even close to running the risk?

Is this a purely irrational panic response (in the pattern of running up Ventoux) of throwing anything and everything at a perceived problem? Or am I missing something about speed of weight loss, and some belief in the team that he was overweight on the morning of 7th Sept, and expected lots of Salbutamol to resolve the issue by mid afternoon?

Doesn't salbutamol have a similar effect to cortisone when injected into the blood stream?..anti inflammatory..presumably if used in a much higher dose it would boost performance significantly then there may be a way of flushing it out of the body before the dope control? Maybe having a bad day previously caused his levels to go out of wack unexpectedly..?

 

[Red Rick]

Re: Re:

I was thinking of this interview with Olivier Rabin, science director at WADA:

https://translate.google.com/translate?sl=auto&tl=en&js=y&prev=_t&hl=en&ie=UTF-8&u=http%3A%2F%2Fwww.lemonde.fr%2Fcyclisme%2Farticle%2F2017%2F12%2F14%2Faffaire-froome-la-charge-de-la-preuve-revient-a-l-athlete_5229768_1616656.html&edit-text=&act=url

Very interesting, thanks for the link. Since 1600 ug/24 hr is permitted, the rider would have to be allowed to have some salbutamol in his urine at the start of the test. If Rabin is serious about duplicating the conditions as they actually occurred, though, Froome would have to document taking some of the substance beginning after testing the previous day's stage, and it would be essentially impossible for him to make the case that he didn't urinate between then and 24 hr later. So this does seem to raise the bar even higher.

Some other interesting points made in the interview:

Has there been an overdose? It happens, even fairly frequently.

I note he's vague about the possibility of another substance affecting the excretion rate of salbutamol. If WADA knew about some substance, surely they would be studying it, but AFAIK, they aren't.

Note also that at the end, in response to a question about oral vs. inhaled, he says, "We have no element of certainty." As I thought, there is no approved test for this, because the tests that may exist aren't good enough (i.e., too many false positives and/or false negatives).

Not sure how fair that is. I guess you can do one test for WADA and if that doesn't get you off, still have another one for CAS.

I believe he can do it however he wants for CAS, though of course the closer it follows what actually happened on the road, the more convincing it will be.

Here’s a more recent study (2015) in which 1600 ug were inhaled all at once. It was mentioned by a scientist interviewed by VN, as a possible indication that super-threshold levels could occur while staying within the WADA rules. There were 13 subjects, and three protocols were run: rest, exercise and exercise/dehydration (water intake restricted). Urine samples were taken at 1.5, 4 and 6 hr. So a total of 117 samples were taken. Of these, 33 or 28% exhibited uncorrected levels > 1000 ng/ml; when urine was corrected for specific gravity, there were still 23 or 20% of the samples above the threshold.

However, keep in mind, again, that 1600 ug is not permitted in a short period of time. Also, even under these extreme conditions, only 5/117 samples exceeded 2000 ng/ml.

What someone really should test is 800 ug, followed by another 800 ug 12 hr later, then urine tests. That would set the ceiling on what is theoretically possible while following WADA rules. There has been a study, discussed above, in which 800 ug was taken at once, followed by urine tests. Only 1/64 samples exceeded 1000 ng/ml and was still below the 1200 ng/ml decision limit. However, from the two studies by the Elers group, I see that 12 hr after an 800 ug dose, there could be as much as 200-250 ug/nl if the subject doesn't pee. Most of this would be added to the amount excreted by the new 800 ug dose, if urine were collected soon after.

The other study I would like to see is of variability of one individual. Test the individual multiple times, not varying conditions, to see how much the urine levels vary. That would provide a baseline of variability, which would be increased if conditions such as exercise and dehydration varied.

http://sci-hub.la/10.1002/dta.1828

So this would be Froome's strategy:

a) He's already claimed he had three puffs after finishing the stage. If he could demonstrate he had five other puffs late in the stage, so the entire 800 ug dose was taken within two hours of testing, that would maximize his urine level.

b) If he's like one of the outlier subjects in published studies, he might conceivably have a level of 1000 ng/ml at that point

c) Most of the kinetic studies have first analyzed urine after four hours, but other studies show that the concentrations peak sooner, within an hour or so. They probably don't fall off too much, but somewhat. So that 1000 ng/ml level could possibly be pushed up to 1200-13000 ng/ml if the urine were assayed sooner.

d) If he took 800 ug in the previous 12 hr period, this would add some salbutamol to the total, if he were an outlier, maybe as much as 400-500 ng/ml. Now he's not far from 2000 ng/ml. and we still haven't considered dehydration.

e) At this point, though, the question would be raised, why wasn't such a high level ever realized before? Froome would have to establish that he never took more than 2-3 puffs total in any 12 hr period prior to this stage.

A very unlikely scenario, but I think that's what it would take. However, if he were willing to confess accidentally taking more than 800 ug, then it becomes a little more plausible. Not as much as oral dosing, but maybe enough to convince CAS.

So they don't distinguish between oral vs inhaled. If there's any way to sneak in those pills in a capsule beforehand, it's easy.

So Froome's goals is gonna be to test as high as possible under 'legal' conditions. Is there anyway to verify all the things they're saying they did or do they no burden of proof for that?

Also, does he need to prove he gets over 1200, or does he need to prove he gets near 2000?

 

[veganrob]

Re:

What's the weight loss effect of Salbutamol supposed to be anyway? From what I read it makes you slightly tachycardic, so maybe extra base load from the elevated HR? That doesn't sound terribly effective at all.

The weight loss effects have been talked about several times in this thread.
Tachycardia can be minimized through long term use enabling higher doses. Also talked about

 

[hazaran]

Re: Re:

What's the weight loss effect of Salbutamol supposed to be anyway? From what I read it makes you slightly tachycardic, so maybe extra base load from the elevated HR? That doesn't sound terribly effective at all.

The weight loss effects have been talked about several times in this thread.
Tachycardia can be minimized through long term use enabling higher doses. Also talked about

Yes, I've seen lots of talk on weight loss. The point is I haven't seen what the purported mechanism is supposed to be *by which* salbumatol causes weight loss. Because last I checked it's not actually a magic diet pill.

 

[Merckx index]

Re: Re:

Yes, I've seen lots of talk on weight loss. The point is I haven't seen what the purported mechanism is supposed to be *by which* salbumatol causes weight loss. Because last I checked it's not actually a magic diet pill.

There have been a number of studies reporting increased metabolic rate and lipolysis (fat loss), e.g.:

https://www.ncbi.nlm.nih.gov/pubmed/26239482

Note this passage from the Introduction:

A possible substitute for ephedrine is albuterol, a common and accessible bronchodilator used to treat asthma and a selective β2 adrenergic agonist. It was previously shown to increase metabolic rate (oxygen consumption) and lipolysis when given by inhalation at four times the therapeutic dose of 200 μg (8, 9). Unfortunately, albuterol given at this dose in the aerosolized form invariably causes tachycardia. However, the swallowed fraction does not cause this side effect, and thus an orally given pill form of albuterol seems to be a safer form of administration (10).

This was also discussed at the bodybuilder's site linked by that South Bay blog that was discussed upthread.

Keep in mind that salbutamol acts at the same receptors clenbuterol does, though it's shorter acting and I believe has a lower affinity for these receptors. Could be described as a poor man's clenbuterol. It may not be much better than caffeine, but I don't think it has to be very effective to be attractive to riders, given that they can use it with impunity if they stay below the threshold.

But as you yourself have pointed out, he wouldn't be taking it for weight loss during a GT. I think it would have to be for recovery. There are studies suggesting it can promote muscle growth in animals, which is consistent with aiding recovery, though as I said before, I don't think this has been directly addressed:

https://www.ncbi.nlm.nih.gov/pubmed/7916118

In fact, I've seen several papers reporting new methods for assaying salbutamol in meat, specifically because it can be used to increase lean muscle in livestock, but is forbidden because of effects on consumers:

https://www.ncbi.nlm.nih.gov/pubmed/28278125
https://www.ncbi.nlm.nih.gov/pubmed/28911579

 

[hazaran]

Well, the rats certainly ended up *gaining weight* with the salbutamol treatment (hence why theres so much research on its effects on livestock) Sure, it was muscle mass, but then lipolysis & metabolic rate increase might not be so much effects in their own right but simply side effects of the muscle hypertrophy it induces, to grow muscles after all requires these things.

The doses they are using (8-16mg oral) also mean you would be "glowing", so really only suitable for the WADA protected night time - and then you better pee in the morning before they come. Doesn't make it impossible, but it's another stake into the heart of the transfusion thing.

 

[meat puppet]

Re:

Well, the rats certainly ended up *gaining weight* with the salbutamol treatment (hence why theres so much research on its effects on livestock) Sure, it was muscle mass, but then lipolysis & metabolic rate increase might not be so much effects in their own right but simply side effects of the muscle hypertrophy it induces, to grow muscles after all requires these things.

The doses they are using (8-16mg oral) also mean you would be "glowing", so really only suitable for the WADA protected night time - and then you better pee in the morning before they come. Doesn't make it impossible, but it's another stake into the heart of the transfusion thing.

Riding 5-7h a day will counterbalance the hyperthropic effect for sure.

Would not be too surprised if the purported use is recovery, as MI has said. Maybe the anabolic effect under a GT type endurance environment is speeded fixing of micro lesions in muscles etc instead of hypertrophy per se.

 

[Merckx index]

A little good news and a little bad news, perhaps, for Froome. The good news:

In the past, Wada has not adjusted the salbutamol threshold in test results to account for "high urine density", which can increase when you are dehydrated.

But that is changing from 1 March 2018, and a Wada spokesperson told BBC Sport that for any case currently being adjudicated, "the most beneficial rule to the athlete would apply".

http://www.bbc.com/sport/cycling/42417297

As I pointed out upthread, he would still have to be severely dehydrated (commonly defined as urine SG > 1.030) for the correction to lower his salbutamol level below the threshold, and my understanding is that if his urine were that concentrated, the sample would not have been approved for assay. In fact, his USG would have to be 1.040 to lower his level to the threshold of 1000 ng/ml, or 1.033 to reach the decision level of 1200 ng/ml. So I wanted to get an idea of how often riders are dehydrated to that extent.

The first two studies are by the same group (led by one L.E. Armstrong, no less), and involved an analysis of men and women riders in a 164 km ride, not race, under intense heat, 35 – 39o C (it's called the Hotter N' Hell Hundred). In the first study, they pooled data from three years. There were 88 men, with a mean USG of 1.019 +/.007 before the ride, and 1.024 +/- .007 after the ride. Based on these values, there would be about 16% with values > 1.030, and about 2% > 1.040.

http://sci-hub.la/10.1123/ijsnem.2015-0188

This is roughly consistent with another study by the same group of 42 men from that ride, reporting that 11 had USG > 1.030, and none > 1.040.

http://sci-hub.la/10.1519/JSC.0b013e318240f677

In another study by a different group, 11 males performed 90 minutes at 50% V02 max, followed by a self-paced 20 km TT at 35o C. Various hydrated or dehydrated states were tested. The USG values were all relatively low, generally about 1.010 at start and 1.015-1.020 at end, with SDs ranging from .002 - .008.

http://sci-hub.la/10.1111/sms.12343

Still another study analyzed 37 male mountain bikers over a 120 km Swiss Masters race. USG pre-race was 1.010 +/- .007, post-race was 1.014 +/- 0.007. They found that intake of 700 ml of fluid per hour was enough to prevent dehydration. However, temperatures were relatively cool, ranging from 5 – 11o C, the lowest temperature at altitude, > 2000 m.

http://sci-hub.la/10.1097/JSM.0b013e3181b47c93

Another study examined 18 mountain bikers in a 3 stage race. The highest mean value of USG was after stage 3, 1.025 +/ .001. Temperatures ranged from 9 – 22o C.

http://sci-hub.la/10.1136/bjsm.2008.049551

So overall, at moderate temperatures, dehydration does not seem to be a problem, while at very high temperatures it could be. I'm not sure how hot it was for Stage 18 in the Vuelta? In any case, the studies at high heat on the road were of amateur riders, who may not have been as careful about hydration as pro racers would be, though the men did take in an average of 5-6 l. of water over the entire ride, about 9 hours.

And a little bit of bad news, if Froome thought that he could get off without showing that 2000 ng/ml is possible under some conditions. I finally tracked down some information on Piepoli, who tested positive for salbutamol in the same Giro (I believe the same stage) that Petacchi did. His urine level was 1800 ng/ml., higher than Petacchi’s. Both riders got off initially through decisions by their national federations, but the Italian Olympic Committee (CONI) appealed Petacchi’s decision to CAS, where he lost (I discussed this CAS decision upthread). Piepoli held a license in Monaco, and his decision was not subject to appeal. He also claimed he had a medical certificate that allowed him to take doses of the drug that could result in urine levels > 1000 ng/ml. I’m not sure if that’s the same as a TUE, which at that time was needed just to be allowed to have levels up to 1000 ng/ml, but apparently it was good enough for Monaco. A Barcelona lab attempted to determine if his salbutamol was inhaled or taken systemically, but couldn’t reach a definitive conclusion.

AFAIK, Piepoli is the only rider in the past decade who tested for salbutamol > 1000 ng/ml. and wasn’t sanctioned, but it’s pretty clear from his case that he had no better argument than any of the riders who were sanctioned. If his case had gone to CAS, he almost definitely would have lost just as Petacchi did. Though the panel might have accepted that he took too much by mistake, as they did with Petacchi, as asthmatics have commented on this thread, taking doses of the required amounts by inhalation would be extremely unlikely. Also, about a year after the salbutamol positives, Piepoli tested positive for CERA. So I don’t think his case has much relevance for Froome’s. If Froome can't show that taking salbutamol within the allowed amounts can result in the high level reported, either as a result of dehydration or some other factor, there is no precedent that should allow him to avoid a suspension, and I would think of at least nine months.

http://www.cyclingnews.com/news/innocently-guilty-the-petacchi-case/
http://autobus.cyclingnews.com/news.php?id=news/2007/aug07/aug06news2
http://autobus.cyclingnews.com/news.php?id=news/2007/jun07/jun13news2

 

[bigcog]

But that is changing from 1 March 2018, and a Wada spokesperson told BBC Sport that for any case currently being adjudicated, "the most beneficial rule to the athlete would apply".

Why is that changing ? Is it due to lack of certainty in the test results ( doesn't appear to be case) or thinking it has no or minimal beneficial effect in terms of performance enhancement or to avoid lengthy and costly legal cases ?

 

[hazaran]

Well the WADA guidelines say they should only collect urine that is within a narrow range of specific gravity, but I think in practice they either don't have a good portable instrument to accurately measure SG, or sample collectors routinely ignore the guidelines (it can make their job easier). I stumbled on these lists of samples released as part of the investigation into Russian government doping and the SG shown is all over the place:

https://www.ipevidencedisclosurepackage.net/documents/EDP0650_T.pdf (samples from 1.003 to 1.035)
https://www.ipevidencedisclosurepackage.net/documents/EDP0757_T.pdf (samples from 1.003 to 1.034)

They certainly don't seem to be thrown out afterwards, either. No need to fake steroid profiles to coverup doping when you could simply declare a sample invalid.

Re: rule change, it's certainly bad timing for them if they inevitably get pulled into lengthy expert discussions on the validity of the test and test criteria. Particularly after *their* experts already argued in the Petacchi case the adjustment was unnecessary. Not a good look in a panel of judges. Quote from CAS decision, which the CAS panel readily accepted:

In response to Mr. Petacchi's argument that the concentration of Salbutamol found in
his urine should be adjusted to take into account the high specific gravity of hls uiine
that day, WADA pointed out that the practice of adjusting results to take into account
variations in specific gravity is only used by it in relation to endogenous substances.
Salbutamol is not an endogenous substance. There is no WADA technical document
or other guidance which recommends this practice in relation to it. Dr Rabin stated
that WADA does not apply a correction for specific gravity because the 1000 ng/ml
threshold is considered high enough generally to take into account all the variables
mentioned by Mr. Petacchi, including urine specific gravity.