Study suggests EPO not a PEDA

[PillarofBalance]

Background
Substances that potentially enhance performance (eg, recombinant human erythropoietin [rHuEPO]) are considered doping and are therefore forbidden in sports; however, the scientific evidence behind doping is frequently weak. We aimed to determine the effects of rHuEPO treatment in well trained cyclists on maximal, submaximal, and race performance and on safety, and to present a model clinical study for doping research on other substances.

Methods
We did this double-blind, randomised, placebo-controlled trial at the Centre for Human Drug Research in Leiden (Netherlands). We enrolled healthy, well trained but non-professional male cyclists aged 18–50 years and randomly allocated (1:1) them to receive abdominal subcutaneous injections of rHuEPO (epoetin β; mean dose 6000 IU per week) or placebo (0·9% NaCl) for 8 weeks. Randomisation was stratified by age groups (18–34 years and 35–50 years), with a code generated by a statistician who was not masked to the study. The primary outcome was exercise performance, measured as maximal power output (Pmax), maximal oxygen consumption VO2 max, and gross efficiency in maximal exercise tests with 25 W increments per 5 min, as lactate threshold and ventilatory threshold 1 (VT1) and 2 (VT2) at submaximal levels during the maximal exercise test, and as mean power, VO2, and heart rate in the submaximal exercise tests at the highest mean power output for 45 min in a laboratory setting and in a race to the Mont Ventoux (France) summit, using intention-to-treat analyses. The trial is registered with the Dutch Trial Registry (Nederlands Trial Register), number NTR5643.

Findings
Between March 7, 2016, and April 13, 2016, we randomly assigned 48 participants to the rHuEPO group (n=24) or the placebo group (n=24). Mean haemoglobin concentration (9·6 mmol/L vs 9·0 mmol/L [estimated difference 0·6, 95% CI 0·4 to 0·8]) and maximal power output (351·55 W vs 341·23 W [10·32, 3·47 to 17·17]), and VO2 max (60·121 mL/min per kg vs 57·415 mL/min per kg [2·707, 0·911 to 4·503]) in a maximal exercise test were higher in the rHuEPO group compared with the placebo group. Submaximal exercise test parameters mean power output (283·18 W vs 277·28 W [5·90, −0·87 to 12·67]) and VO2 (50·288 mL/min per kg vs 49·642 mL/min per kg [0·646, −1·307 to 2·600]) at day 46, and Mont Ventoux race times (1 h 40 min 32 s vs 1 h 40 min 15 s [0·3%, −8·3 to 9·6]) did not differ between groups. All adverse events were grade 1–2 and were similar between both groups. No events of grade 3 or worse were observed.

Interpretation
Although rHuEPO treatment improved a laboratory test of maximal exercise, the more clinically relevant submaximal exercise test performance and road race performance were not affected. This study shows that clinical studies with doping substances can be done adequately and safely and are relevant in determining effects of alleged performance-enhancing drugs.

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

 

[PillarofBalance]

This actually looks like a decent quality study design albeit small with only 48 participants.

Results essentially show a minute difference in times for trained cyclists.

 

[BigSwolePump]

Been a long time since I have seen EPO around.

 

[Bro Bundy]

its big in mma and any endurance sports...great way to get a stroke imo

 

[MrRippedZilla]

This actually looks like a decent quality study design albeit small with only 48 participants.
Results essentially show a minute difference in times for trained cyclists.

Honestly, the first thing that came into my mind when I saw the paper was the time when scientists did their best to bullshit people into believing that AAS weren't PEDs either. That's until they tapped out in the mid 90s, decades after everyone (athletes, coaches, etc) knew what was up.

I think the fact that the results completely contradict reality is enough to warrant some skepticism here. At least until they're replicated. These comments from the authors, suggesting that everything Lance Armstrong took (EPO, test, GH, etc) probably didn't work and it was all just placebo, further heightens my skepticism. I smell bullshit on many, many levels.

 

[PillarofBalance]

Honestly, the first thing that came into my mind when I saw the paper was the time when scientists did their best to bullshit people into believing that AAS weren't PEDs either. That's until they tapped out in the mid 90s, decades after everyone (athletes, coaches, etc) knew what was up.

I think the fact that the results completely contradict reality is enough to warrant some skepticism here. At least until they're replicated. These comments from the authors, suggesting that everything Lance Armstrong took (EPO, test, GH, etc) probably didn't work and it was all just placebo, further heightens my skepticism. I smell bullshit on many, many levels.

That's precisely what I was thinking, back when they tried to say test won't improve performance.

But I am curious where they fudged the numbers

 

[DieYoungStrong]

A minute difference to an elite cyclist is one hell of a difference. Stages can come down to seconds.

So first there's that. A minute gap in an elite race is like a 200lb total difference between 2 elite plers in the same class.

Last, calling bullshit. Cycling is the dirtiest sport out there. They wouldn't be doing it all these years if it wasn't working.

 

[Flyingdragon]

I met DYS at the park, he was on his bike........

 

[BRICKS]

A minute difference to an elite cyclist is one hell of a difference. Stages can come down to seconds.

So first there's that. A minute gap in an elite race is like a 200lb total difference between 2 elite plers in the same class.

Last, calling bullshit. Cycling is the dirtiest sport out there. They wouldn't be doing it all these years if it wasn't working.

I work with a doc that was a professional cycles. He sais everybody in that sport is on something.

 

[MrRippedZilla]

That's precisely what I was thinking, back when they tried to say test won't improve performance.
But I am curious where they fudged the numbers

Finally got my hands on the full paper. Also had to do some background reading since EPO, endurance and all that jazz really isn't in my domain of interest.
So the data actually looks fine. It's the abstract, discussion and everything else involving the authors giving their opinions that requires a lot of filtering - not exactly an uncommon flaw nor a surprise if you read their comments in the link I gave in my previous post (claims of test, gh, epo, etc providing only a placebo benefit, lots of bullshit along those lines).

The EPO group, literally, beat the placebo group in every single marker that was measured. Max oxygen consumption, max power output, lactate threshold, ventilatory threshold, etc, etc. The surprising part is that this stuff didn't translate to a real improvement when it came to an actual road cycle race or the submax testing.
My endurance bunnies tell me that EPO is rarely used for any kind of submaximal stuff with the real edge coming from the fact that it allows you to attack harder for longer (during breakaways, bridging gaps, etc). This raises the possibility that the reason for the lack of significant difference between the groups was down to the testing methods. The authors admit that when looking at maximum performance (time to exhaustion type stuff) EPO provides a massive edge - we're talking a 22-70% increase - so this kind of validates what my bunnies were saying. Basically, the submax testing results mean nothing.

As to the actual race results, flaws related to training and (possibly) EPO dosing need to be taken into account.
It is pretty common for high levels of endurance training to cause lower levels of RBC, HCT, etc and that is why EPO use in the off season is a good idea. It allows those values to stay at baseline = can train harder for longer = better race performance. This also helps maintain the high training volume (20hrs+, 700km+ per week) that pro cyclists have. Well, in this study we had amateurs who trained "substantially less" (no numbers given) and a study length of only 8 weeks. Therefore, it shouldn't be too surprising that the results here do not reflect the results in real life. Is this enough to explain the lack of difference when it came to race performance? Maybe. Maybe not.

Finally, we have to consider the impact of the actual EPO dosing.
Too much EPO, or just a shitty protocol in general, may actually hinder performance by increasing perceived exertion. This is related to thicker blood = harder to maintain a higher heart rate. It's finicky stuff and I can certainly understand why the pros consult with a bunch of doping experts before messing around with it. You hear about micro dosing and a bunch of other protocols that indicate that its not as simple as inject a bunch of EPO and you're good to go - higher doses may not be better. The dosing within the data varies from 4,000-26,000ius per week so its not exactly easy to figure out what may be "optimal" depending on the race conditions.

So yes, the reason for the surprising results appears to be related to the testing, dosing, and training (or lack thereof). The data itself is good, and a useful addition to what we already have, but it doesn't say what the authors and media seem to think it says