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Cyclists on erythropoietin were no faster than those on placebos in a race up Mont Ventoux last month.


Popular doping drug may not actually help cyclists

Tomorrow, on Bastille Day, stage 12 of the Tour de France will culminate in one of cycling’s legendary ascents: the ride to the barren summit of Mont Ventoux, a 22-kilometer path of pain, heroism, defeat, and death. Not far from the finish, riders will pass a memorial to Tom Simpson, the famous U.K. rider who collapsed and died there in 1967. An autopsy revealed that Simpson had taken amphetamines and alcohol to boost his performance, which may have contributed to sudden heart failure.

This year’s edition of the Tour de France has been remarkably free of doping scandals so far. But less than a month ago, in another race up the same windy slope, fully half the cyclists had a banned substance coursing through their veins. It wasn’t a sports event, but a scientific study: the largest ever trial to test whether erythropoietin (EPO), a drug that has marred the Tour for decades, really enhances athletic performance as 
users claim.

The scientists who organized the study have yet to analyze the full results, but they have already shared a key outcome with the press: Riders on EPO, which stimulates the body to make extra oxygen-carrying red blood cells, were no faster than those who took a placebo. The finding flies in the face of previous, smaller studies and cycling lore, and some are incredulous. “Based on what we know so far about EPO, I would be very surprised if that’s true,” says Don 
Catlin, the CEO of Anti-Doping Research, a lab in Los Angeles, California.

But Catlin and other doping researchers applaud the team for subjecting EPO to a rigorous trial. Such studies are rare; critics have argued that the ever-growing list of banned substances in sports—and the international testing industry that enforces it—have no firm basis in science.

For the World Anti-Doping Agency (WADA) to ban a substance, it must meet two of three criteria: It enhances performance, poses a threat to athlete health, or “violates the spirit of sport”—a criterion that helped put recreational drugs like cannabis on the list. Proof isn’t needed for any of the criteria, and evidence of performance enhancement is lacking in all but a handful of instances, such as the use of anabolic steroids in some strength-based sports.

Good studies are hard to do. Industry has no interest in footing the bill, and athletes would risk their careers if they participated. So a team led by Adam Cohen, the head of the Centre for Human Drug Research (CHDR) in Leiden, the Netherlands, turned to amateurs. They enlisted 48 well-trained male amateur cyclists for a randomized, controlled, double-blind study—the gold standard in medicine—“as if we were testing a treatment for a disease called cycling slowly,” says Jules Heuberger, a Ph.D. student at CHDR and a cycling aficionado. Cyclists from around the world offered to take part, he says. “EPO has this almost mythical status. People thought it would make them fly like a rocket.”

Participants were injected with EPO or a placebo for 8 weeks, during which they completed seven endurance tests in the lab. The final challenge was a 130-kilometer ride ending in the race up Mont Ventoux on 
19 June, a miserably cold day with an icy mistral blowing down the moonlike landscape. The winner, a lawyer, took an hour and 12 minutes to reach the summit. On average, riders on EPO were 38 seconds slower than the control group, a non
significant difference. And the EPO users hardly felt like they were running on rocket fuel; 62% guessed they were on a placebo.

But could EPO, the drug that allegedly helped Lance Armstrong rack up seven Tour victories, really be useless? It’s conceivable, Cohen says. Riders may only remember winning with EPO and forget the losses, he notes. The drug could also be a strong placebo; after all, sports are a test of the mind as well as the body.

It’s indisputable that the new red blood cells spawned by EPO increase the body’s maximum oxygen uptake (VO2max). But such an increase may not boost cycling performance, Cohen says. In long-distance races like the Tour, riders rarely perform at maximum uptake. Yet in a review of 13 previous EPO studies, the CHDR scientists found that all focused on VO2max instead of performance. Some weren’t controlled, only two had more than 20 participants, and none left the lab for a real-world race. “It’s not what you would normally consider clear evidence,” Cohen says.

Others are reserving judgment until the publication is in, but say they find it hard to believe EPO does nothing. There are biological reasons to suggest that increasing VO2max has an effect, says Bengt Kayser, a doping expert at the University of Lausanne in Switzerland. Transfusions with a rider’s own blood have been shown to boost VO2max and performance, he says. And he notes that the body has EPO receptors in many places, including the brain, which might provide alternative mechanisms for the drug to have an effect.

Although testimonials from athletes themselves may not amount to hard evidence, they can’t be dismissed, says Olivier de Hon, a scientist at the Anti-Doping Authority of the Netherlands in Capelle aan den IJssel, which advised on the study. Sports is full of fads that quickly fade—beet juice, rich in nitrates, is one recent example—but De Hon finds it hard to believe that cyclists would stick with a useless drug for decades. He says the scientists’ time and money would have been better spent studying doping substances about which less is known, such as human growth hormone, insulin-like growth factor 1, and cocaine.

Cohen’s group is now analyzing mountains of data on EPO. Among other things, they plan to look at its effects on blood clotting and muscle recovery. They will also send 300 urine samples from both groups to a WADA-accredited doping lab in Belgium to put EPO testing itself to the test. It’s still possible that the EPO group performed better in the lab rides but, for some reason, failed to prevail on the mountain, Heuberger says. But he would not be surprised to find no difference at all.

Even if the negative finding holds up, EPO may stay on WADA’s list. The agency tends to err on the side of prohibition, and politics plays into the process as well. Some have argued that it’s fine to keep ineffective but potentially harmful substances on the list to deter athletes from using them. Cohen, 
on the other hand, believes delisting a drug will make it less attractive to athletes. If nothing else, he hopes last month’s sprint up Mont Ventoux will show that a science-based approach to the issue is possible.