Drug dilemma
Meldonium is banned despite a lack of evidence showing it is a performance enhancer,
Maria Sharapova is the most noteworthy athlete to have failed a drug test for meldonium. But in the month since the tennis star revealed her use of a drug she contends is for medical reasons, a slew of other top athletes have been implicated.
They include fellow Russians Yuliya Efimova, a four-time breaststroke world champion, and Nikolai Kuksenkov, the country’s best male gymnast. In all, 140 athletes have tested positive for meldonium in the three months after it was banned Jan. 1, according to a World Anti-Doping Agency spokesman.
But as the tally of failed tests is increasing, critics are raising questions about whether meldonium enhances performance and how WADA could ban the drug with what they say is relatively little scientific evidence.
“There’s really no evidence that there’s any performance enhancement from meldonium. Zero,” said Don Catlin, a longtime anti-doping expert and the scientific director of the Banned Substances Control Group.
Those supporting meldonium’s ban point to its potential to enhance performance and measures of its use by athletes, both before and since the ban.
Those questions highlight a difficult position for WADA. With scant existing research, how does it know meldonium enhances performance? Does it need to ban a drug such as meldonium before it understands its benefits and potential harms because it sees athletes using the drug? And if it’s not enhancing performance, why are a large number of seemingly healthy athletes taking a drug used to treat patients with heart problems?
WHY DRUG WAS BANNED
Meldonium’s journey to WADA’s prohibited substances list began in March 2014 when the U.S. Anti-Doping Agency received a confidential tip that Eastern European athletes were using the drug to enhance performance.
By October of that year, meldonium, which also goes by the brand name Mildronate, was on WADA’s monitoring list. In February 2015, scientists completed a study of global athlete usage of the drug.
In reviewing 8,320 urine samples, the study, which was funded by the Partnership for Clean Competition, found that 182 samples contained meldonium. At 2.2% of the sample, it was more than double the rate for any other drug on the list.
Results from the European Games in Baku, Azerbaijan, in June seemed to support concealed use of the drug. That research, published in the British Journal of Sports Medicine, showed positive tests for meldonium in 66 of 762 urine samples but said only 23 of the 662 athletes tested had declared their use of the drug.
Of the 662 doping-control forms the study reviewed, 525 declared the use of a medication or nutritional supplement. Use of meldonium was found in 15 of 21 sports, and the total count included 13 medalists.
While acknowledging evidence of meldonium’s performanceenhancing effects was limited, the study concluded that, because it was not being used primarily for therapeutic reasons, “(It was) evidently being used with the intention to either improve recovery or enhance performance.”
To be considered for WADA’s prohibited list, a substance must meet two of three criteria: It enhances or has the potential to enhance performance, it presents an actual or potential health risk or it violates the spirit of sport.
Once meldonium was up for consideration, WADA’s expert group could consider public discussion on the drug, information from medical literature and the availability of a test for the drug, among other factors.
WADA decided in September to ban the drug, and that went into effect Jan. 1. In its explanatory note, WADA wrote that it was banned because of evidence of use with the intention of enhancing performance.
Andrew Pipe, medical and scientific adviser to the Canadian Centre for Ethics in Sport, acknowledged there was little English-language literature available on meldonium, which was created in Latvia in the 1970s.
But Pipe defended its addition to the list, saying that, while he was not speaking for WADA, the committee did follow WADA’s process. In a statement, a WADA spokesman similarly noted that the agency followed its process in banning meldonium.
“If you have a substance that has a purported mechanism that is capable of enhancing performance, you have evidence it is being used by large numbers of athletes and you have evidence that it is used by a large number of athletes concealed, then I think you come to the conclusion that this is a substance that should be placed on the prohibited list,” said Pipe, who was chairman of the expert group at the time.
SEEKING EVIDENCE
Catlin and others question whether meldonium meets the basic criteria to be considered for the list. It’s not that it doesn’t enhance performance, Catlin said, it’s that there’s not research to show that.
“They have to try to show that it enhances performance, but by banning it they’ve already said it enhances performance, and that will make people turn to it,” Catlin said. “You can find that it has effects, but it’s difficult to link those to performance enhancement. I’ve tried and tried to figure out why so many athletes seem to be taking it.”
The drug works by shifting cells’ metabolism from fatty acids to carbohydrates for energy, a process that requires less oxygen.
A 2002 paper from researchers at Tbilisi State Medical University in Georgia found the drug had a positive effect on the physical working capacity of judokas, concluding it did not have side effects. Research presented in 2012 at the Baltic Sport Science Conference found much the same, noting it was not on the doping list.
Grindeks, the company that manufactures Mildronate, says it is not a performance-enhancing drug because it prevents the death of ischemic cells and does not increase performance of normal cells.
WADA does not have to prove a substance’s performance-enhancing effects, and athletes are not able to challenge a drug ’s inclusion on the prohibited list.
Catlin contends WADA incorrectly used evidence of use as a criterion. While few question whether use of the drug violates the spirit of sport, the broadest of the three criteria, some question how much it meets the first two.
“If you take those criteria seriously, then you would think that substances need to be innocent before proven guilty,” said Roger Pielke Jr., a University of Colorado professor whose book The Edge: The War against Cheating and Corruption in the Cutthroat
World of Elite Sports is due out this year. “You can just say here’s a substance, athletes are taking it, therefore we have suspicion that it has performance-enhancing effects. Your anti-doping list would expand very rapidly if any substance that is out there and you just add it to the list.
“If evidence is to matter, then the meldonium ban was put into place before that evidence became readily available.”
So what can be concluded from the high number of athletes using meldonium?
Catlin found little reason behind Sharapova’s explanations, which included a magnesium deficiency and a family history of diabetes, and suggested there was little to infer from the number of failed tests other than that many athletes used meldonium.
But others accept the conclusion from WADA — that its use is at least with the intent to enhance performance.
Victor Conte, founder of the Bay Area Laboratory Co- Operative (BALCO), said athletes’ use of meldonium was an endorsement of its performance-enhancing effects.
“They know when it works. When you take drugs, you know when you’re stronger, faster, have more endurance,” he said.
“Of course it works. Now is there a double-blind, placebocontrolled, crossover clinical trial with a sufficient total of subjects involved to be published in a credible scientific journal? No. But is there rampant use of it in Olympic sports? Yes.”