EPO is apparently useless

[The Hitch]

Does this mean Lance might get his TdF's titles reinstated because EPO doesn't work? Lol.

If 50 other studies show the 50 other drugs he was loading his body with also have no effect on performance.

 

[DFA123]

“It’s just tragic to lose your career for something that doesn’t work, to lose seven yellow jerseys for a drug that has no effect,” said Jules Heuberger, who led the research at the Centre for Human Drug Research in The Netherlands.

Absolutely scandalous for a 'scientist' to make such an authoratative statement based on one study looking at a couple of dozen amateurs climbing one mountain. As if that one study comes anywhere near replicating the dosages used, training schedules, recovery schedules, interaction with other drugs, and general physiological responses of pro racers.

Jules Heuberger may have got his 5 minutes of fame, but at the cost of his reputation as a serious scientist, by making absurd generalisations like that.

 

[LaFlorecita]

Re: Re:

Here we go again!!!

The study actually showed that while EPO is a benefit when used in shorter events such as the 4 or 800 meters after a 130km plus bike ride the riders that received EPO were on average seventeen seconds slower than those who didn't.

And there is no reason to believe EPO would ever slow someone down. This smells like a confounding factor, maybe those that got EPO did not prepare as well.

 

[MatParker117]

Re: Re:

Here we go again!!!

The study actually showed that while EPO is a benefit when used in shorter events such as the 4 or 800 meters after a 130km plus bike ride the riders that received EPO were on average seventeen seconds slower than those who didn't.

And there is no reason to believe EPO would ever slow someone down. This smells like a confounding factor, maybe those that got EPO did not prepare as well.

It was essentially a Blind trial no cyclist involved knew if they got EPO or the placebo.

 

[King Boonen]

Re: Re:

This has already been discussed in The Clinic when the studies first results came out last year http://forum.cyclingnews.com/viewtopic.php?f=20&t=31030&hilit=epo maybe we could merge the thread?

I do have to ask that if EPO has no effect then why were the climbing times EPO era so much faster?

Yes, I made some criticisms of the study in the last post in that thread. They were based on the following article, which is still the only one by these authors that I can find:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690100/

The latest article is described as a study of two dozen cyclists on EPO vs. two dozen controls. They were not pro cyclists, ironic because one of the main criticisms made by researchers who believe EPO has no PE is that no studies have been done on pros. Beyond that, demonstrating that there was no difference in climbing times between the two groups prior to EPO would be critical, but how this was assured is not mentioned in the media reports. I assume all the riders climbed ADH before any EPO administration, and then were divided into two groups such that the average climbing time of each group was the same. But if that was the case, there could still be individual differences in response to EPO that would be significant even if the overall average was unchanged. This kind of effect, e.g., was reported in some of the studies with beetroot juice. Some riders experienced a highly significant decrease in time in a standard time trial, while others did not improve at all.

Also, I recall seeing some studies indicating that some individuals get more of a physiological enhancement from EPO than others, so it would be quite possible for major differences in performance enhancement to exist as well. Perhaps the authors did look at effects on individual riders, but without seeing the actual study, I can't comment on that.

Also note that another Dutch group has been trying to support a revisionist line on EPO:

http://www.scirp.org/journal/PaperInformation.aspx?paperID=64812

This was discussed in the Clinic before, too.

There is a new article, it's in the most recent edition of the Lancet Haematology:

link-to-paper

Currently online first so maybe not yet in pubmed. I've tried to download the PDF but it just takes me back to the summary.

 

[TourOfSardinia]

https://issuu.com/newshourbd/docs/epo

 

[King Boonen]

Re:

https://issuu.com/newshourbd/docs/epo

Thanks

I signed up for a free account and got access. Fairly surprised I don't have institutional access to be honest.

 

[sniper]

Re: Re:

...
Pantani, Riis, Armstrong, Virenque. All of them were wrong!!!

The latter three riders were likely using motorized bikes (and possibly the first rider, too) at various points in their carreer, so unfortunately they are not the best examples for measuring/analyzing the impact of EPO.

 

[sniper]

To add to the above:
I'm going to say that 1996 (tentatively) is a cut-off point.
From that year on, there is no way of telling who was and who wasn't using a motor at the top end.
So most if not all top-performances post-dating 1996 are possibly 'contaminated' and should not be used for analyzing the impact of EPO.

 

[ppanther92]

The study is laughable. If you want to measure things like this, you can't just make two groups and given one Epo and jump to a conlusion. What if the Epo group would have been 1 minute slower without Epo.

What is even the point in doing this study without baseline data?

 

[Benotti69]

Sky are obviously using EPO cos it doesn't work and Matt is getting in ahead of revelations

 

[sniper]

EPO is not only useless.
It's counterproductive.

"Ryder Hesjedal says he stopped doping in 2004. He was going backward on mountain biking's World Cup circuit, finishing worse than when he rode clean."
http://www.timescolonist.com/news/local/victoria-pro-cyclist-ryder-hesjedal-comes-clean-on-past-doping-1.1326391

 

[Merckx index]

The link provided earlier and also by KB did not work for me, it went to an error page. Another link provided in this thread went to the full article, but I couldn’t get it in a form large enough to read. I tried going to Lancet Hematology, but the article was not listed in the most recent issue (July). But I finally got the summary page here:

http://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(17)30105-9/fulltext?elsca1=tlpr

It says the free article can be obtained just by registering, which is free. I haven’t done that, but just from looking at the summary, I was surprised to learn that there was no pre-EPO trial; the researchers just randomized a group of forty-eight riders, apparently assuming that was a large enough number so that there would be no significant difference between the two groups in average climbing time.

There were the expected physiological effects, but they weren’t exceptionally large: about a 7% increase in Hb, a 5% increase in V02 max, and a 3% increase in maximal power. To put that in perspective, JV claimed he could raise his HT about 8%, and his power (presumably max) 4-6%. See the discussion last year in this thread:

viewtopic.php?f=20&t=31030&hilit=epo&start=20

Also want to point out that a previous study of EPO discussed by Ross Tucker at his web page reported that the really big benefit of EPO was in time to exhaustion (> 50%). This was not determined in this study, though they do report a non-significant 2% increase in submaximal power. I’ll have to read the full article to see how that was carried out.

 

[fmk_RoI]

Question for those who know these things: Michel Audran's 1999 study, Effects of erythropoietin administration in training athletes and possible indirect detection in doping control:

RESULTS: Significant changes in reticulocytes, hemoglobin (Hb) concentration, hematocrit (Hct), sTfr, and sTfr/serum proteins were observed during and after rHuEpo treatment. The maximal heart rate of 177 beats x min(-1) at the beginning of the study was significantly higher than the value of 168 beats x min(-1) after 26 d of rHuEpo administration. Compared with the values measured at baseline, the VT measured after rHuEpo administration occurred at a statistically significant high level of oxygen uptake.

CONCLUSIONS: When oxygen uptake measured at the VT was expressed as a percentage of V02 max, the values obtained were also significantly higher. The increased values of Tfr and sTfr/serum proteins, respectively, above 10 microg x mL(-1) and 153, indicated the probable intake of rHuEpo.

Why is this irrelevant and being ignored by the new authors who claim to have completed the first study of its kind?

 

[carton]

Well, the times up Ventoux were around 1:40 for both groups. So that's about 3.5 W/Kg. Or about 57% of Pantani. On that alone, we're running into some problems. That's about 725/5000 on Strava (depending on the segment), though, so hard to ask for that much more from the researchers on that front. It's just an issue of not dealing with professionals.

But more significantly a 5% increase in lactate threshold power versus a marginal decrease for the placebo group ain't nothing. Centering the study on the performance up Ventoux, while fun, adds unnecessary noise, particularly as four (nearly 10% of) participants didn't do the event. And most importantly: focusing on the absolute times up a hill is misleading, not least as the EPO group had a slightly lower baseline. Additionally, the fact that the placebo group lost 2kg on average during the test while the EPO group lost virtually nothing might, directly as well as potentially indirectly (signalling perhaps better training /diet) also help explain their marginally superior performance uphill at the end of the test.

It is definitely an interesting study. But I find it very, very hard to agree with their conclusions based on the evidence they are presenting.

“It’s just tragic to lose your career for something that doesn’t work, to lose seven yellow jerseys for a drug that has no effect,” said Jules Heuberger, who led the research at the Centre for Human Drug Research in The Netherlands.

Good God. What a serious, knowledgeable, objective statement by a clearly unbiased scientist.

PS: Thanks ToS for the link.

 

[Merckx index]

I’ve looked over the full article now. Here's a key passage from the discussion:

Results of other studies17–19found remarkable increases in reported submaximal tests, namely constant-load time-to-exhaustion tests, of 22–70%. These trials used short (between 3 min and 20 min) tests that, similar to the maximal exercise test, lead to exhaustion and therefore are less representative of real-life cycling. Our submaximal test was designed to closely mimic a road time trial of 45 min and in line with that was not intended to lead to exhaustion.

The goal of using rHuEPO in professional sports is to improve performance during road races, not in maximal exercise tests. Participants therefore took part in a race designed to mimic a professional road race at Mont Ventoux about 12 days after the last dose of the treatment period, which also tested the validity of our laboratory exercise tests as biomarkers of real cycling performance. The two treatment groups did not differ in race time or mean power output, thereby raising doubt about the predictive value of the increase in maximal
exercise test parameters by rHuEPO for performance in a road race. This outcome is further supported by the fact that rHuEPO treatment did not show an appreciable effect on a submaximal exercise test in the laboratory.

In claiming that their tests more closely mimic actual race conditions, the authors are assuming the riders pace themselves up climbs, aiming to ride at the maximum possible power short of exhaustion. As the authors themselves put it, the submaximal test (carried out in the laboratory prior to the climb, and used to support the latter results) was designed to mimic a time trial: “Participants were instructed to produce the highest mean power output during a 45-min period, attempting to mimic competitive cycling time trials.”

But of course climbs usually are not ridden in this manner. Often the leaders ride at a level below max until the last few km, when they go all out. Other times there will be attacks, when riders put out power that isn’t sustainable for more than a few seconds. Not to mention escapes earlier in the stage. So I don’t think that one can dismiss the effects on maximum power as irrelevant to a race. At best, one might argue—based just on this study, and not on others—that EPO should not improve time trialing.

I'm also wondering: since apparently all the subjects climbed MV at the same time, could there have been a pacing effect? Suppose the EPO group was slightly stronger, and the controls just drafted behind them? At that speed, there wouldn't be much air resistance, but one might speculate that the controls pushed themselves just slightly more to stay up with the EPO group, who didn't have anyone to pace them? Since there was apparently a considerable spread in times, this couldn't have affected every rider all the way up, but could it have had some effect?

Some other points.

1) There appears to be an error in Table 1. It lists the EPO group’s average baseline (before treatment) maximum power as 4.19 watts/kg, significantly lower than the 4.36 value for the controls. But in Table 2, the EPO value is 4.37. Other values in Table 1 are the same as the corresponding values in Table 2.

2) Table 2 lists the values of various parameters measured during the study. EPO was given weekly for eight weeks, and measurements of parameters were made at 2, 4, 6 and 8 weeks (days 11, 25, 39 and 53 in Table 2). The values at those various time periods were averaged to give a mean value at the end of the study, and this is the value used to determine if there was a significant difference between the two groups.

This is valid if the baseline values are the same, but sometimes they aren’t. E.g., the LT and LT power values are less at the baseline for the EPO group than for the controls. The difference is presumably not significant, but it means that the difference in the other direction at the end of the study is greater. Thus the LT for the EPO group increases by about 6%, compared to less than 2% for the controls. As carton says, that's not nothing. Moreover, while the EPO group starts out lower, it’s higher at every time period measured. So I would be cautious in concluding that EPO had no effect on the LT values, as the authors do (p-values in Table 2 insignificant).

3) A curious thing about Table 2 is that in virtually every case, the highest value is at day 39, not at day 53. If this were just for the EPO group, one might conclude that EPO’s maximum effects were achieved at six weeks, and after that there was actually a slight decline, perhaps due to endogenous feedback mechanisms. But the control group also exhibits peak values at day 39. So there was some systematic bias in the measurements at this time.

fmk: The authors do cite the Audran study. But based on what you posted, that just determined physiological effects, and is not inconsistent with anything reported by the current study.

 

[klintE]

EPO should be legal

 

[fmk_RoI]

fmk: The authors do cite the Audran study. But based on what you posted, that just determined physiological effects, and is not inconsistent with anything reported by the current study.

Cheers.

 

[Alex Simmons/RST]

3) A curious thing about Table 2 is that in virtually every case, the highest value is at day 39, not at day 53. If this were just for the EPO group, one might conclude that EPO’s maximum effects were achieved at six weeks, and after that there was actually a slight decline, perhaps due to endogenous feedback mechanisms. But the control group also exhibits peak values at day 39. So there was some systematic bias in the measurements at this time.

6 weeks huh? That's a pretty normal time period for regular aerobic training impacts to really start to show up in your performance data and for maximal aerobic/HIT work to begin to show a performance plateau and eventual decline. Perhaps there is a training bias?

I've not read it, don't think I need to since (i) it's clearly just plain silly and (ii) it's of no value to me as an ethical coach.

 

[Red Rick]

Anyone got a link in sci-hub?

What's the dosage?

Training? All that stuff?

 

[King Boonen]

Re:

Anyone got a link in sci-hub?

What's the dosage?

Training? All that stuff?

I edited my post on the first page, it should work with the parser now.

 

[86TDFWinner]

Re:

I'm fairly certain this has been discussed here before. However, if anyone believes EPO is worthless, I own a bridge in Brooklyn I will sell you for $5.

http://forum.cyclingnews.com/viewtopic.php?f=20&t=31030&hilit=epo

:lol: :lol: I wonder if he's on Wonderboys payroll? We all know he'll try to use this(as ALL cyclists going forward will as well), to try to get his lifetime ban lifted.

 

[Tonton]

Re: Dutch Study: "EPO little to no effect on trained cyclist

How do you say BS in Dutch?

 

[Strange Loop]

To access the article's full text (either HTML or PDF) you need to register an account for the Lancet's website. Registration is free and will grant you access to the article (free access). Obviously Elsevier wants a bit of personal information (job etc.) and tries to subscribe you to a newsletter, but you don't have to comply with that. You don't even have to use a valid email address.

I've read just read the paper, but as I can't really keep my eyes open, commenting on it has to wait until tomorrow. What I can say is that the general design seems fine and that they've more-or-less performed the statistical analyses I expected them to perform. (I don't know a lot about performance tests, so I can't comment on the ones they've used.)

 

[Merckx index]

6 weeks huh? That's a pretty normal time period for regular aerobic training impacts to really start to show up in your performance data and for maximal aerobic/HIT work to begin to show a performance plateau and eventual decline. Perhaps there is a training bias?

“Participants were instructed to maintain their usual training programme throughout the study.”

There should have been no benefit of training to either group, though differences in training would add to the heterogeneity of the groups, and I would think make comparing the groups just by averaging the results from the two dozen or so subjects even more complicated. The authors say all the subjects used a bike with a power meter, that recorded all their training rides, and that the average amount of training was roughly similar for the two groups. But If I were going to do a study like this, I would want all the subjects to undergo a similar training program, to minimize the effect of that variable. I would also want to record a climbing time prior to treatment, so the climbing time after treatment could be compared to a baseline, for each rider as well as for the group.

At least the maximal and submaximal power tests all were carried out before treatment as well as at one time (submaximal) or multiple times (maximal) after the treatment was begun, but the data are not broken down for individuals in the article per se. They may be included in an Appendix referred to by the authors—I’m sure they have the data somewhere--but unfortunately, the Appendix is not included in the free access to the article following registration.

I also noticed for the first time that four of the subjects did not finish the climb, and the authors factored this in, rather than discard these subjects. Also of note, about 60% of the riders treated with EPO thought/guessed they were receiving placebo treatment. I remember when Floyd confessed, he mentioned that he never thought his doping helped that much. OTOH, I believe Tyler Hamilton was quite explicit in saying he felt a major difference. I think there are probably substantial individual differences in not only the effects of EPO on performance, but in the perception of individuals of the effect.

I've not read it, don't think I need to since (i) it's clearly just plain silly and (ii) it's of no value to me as an ethical coach.

Though I think it's way over the top to conclude that EPO has no effect, if this study plants doubt in the minds of some riders who are tempted, that could be beneficial. A rider is already facing the possibility of testing positive and being suspended, and thus must weigh the potential PE vs. the risk. Any study that claims there is no enhancement, I suppose, will increase the likelihood that fear of risk will carry the day.