Trimetazidine Russian Doping Affair in Beijing has Olympic Movement Doing a Twizzle

Is the World’s Best Figure Skater another Example of Russian Doping or an Innocent Victim of Contamination?

By Oliver Catlin

Halfway through and the 2022 Beijing Olympics are spinning thanks to the latest Russian doping affair surrounding the world’s best figure skater. The future of the Olympic movement now hangs in the balance. This is the last thing the Olympic movement needed after the worst doping scandal ever perpetrated during the 2014 Sochi Olympics. It is easy to have a knee jerk reaction to the current case, where 15-year old figure skating sensation, Kamila Valieva, tested positive for the drug trimetazidine on a Christmas Day drug test that was finally reported on February 7. Now the entire Olympics awaits a decision to be made this weekend after the Court of Arbitration for Sport (CAS) was called in to sort out the matter. Most people probably think she is a doper given the scandalous history in Russia, but as we have learned over our years in anti-doping the answer may not be that straight forward in the end.

Let’s start with what trimetazidine is so we can get a foundation. Trimetazidine (TMZ) is a heart medication that has been used in medical practice to treat angina or stroke. It is not approved for use in the U.S. One paper describes that as an “orally administered antianginal agent trimetazidine increases cell tolerance to ischaemia by maintaining cellular homeostasis.” In simple terms TMZ can increase blood flow and stabilize blood pressure and can have endurance benefits. In 2012 the European Medicines Agency, “recommended restricting the use of trimetazidine-containing medicines in the treatment of patients with angina pectoris to second-line, add-on therapy.” It is banned in sport as a metabolic modulator in category S4.4 alongside another now infamous doping agent meldonium, also an anti-ischemic agent. Overall, the WADA system reported 57 trimetazidine findings from 2014 when it was first banned to 2020.

To most people it would seem unlikely that Valieva has a heart condition at age 15 that would justify medical use of TMZ. It is now recommended only as a second line therapy perhaps making legitimate treatment even less likely. Even if there was a medical need if she didn’t get a therapeutic use exemption (TUE) and disclose the use of TMZ in advance that would be a violation in itself.

The Valieva situation is framed by several trimetazidine cases. Sun Yang, the Chinese swimmer now notorious for a string of doping concerns, tested positive for trimetazidine in 2014. Yang claimed he had been prescribed it for chest pains but he did not declare it on his collection form. Yang received a three-month ban, his Chinese doctor was banned for a year. Valieva joins fellow Russian bobsledder Nadezhda Sergeeva who tested positive for trimetazidine two days prior to her race and was banned from competition at the 2018 Pyeongchang Olympics. Sergeeva served an eight-month ban after it was considered that she had used a contaminated supplement.

A third case in 2018 also points to the concern of supplement contamination. U.S. swimmer Madisyn Cox was positive for trimetazidine and originally thought it had come from water contamination. Cox eventually had her sanction reduced to six-months after testing discovered TMZ as a contaminant in a supplement. At BSCG our business revolves around protecting athletes from nutritional supplement contamination through our industry leading Certified Drug Free program, which verifies supplements are free of banned substances. These cases illustrate how important it is for athletes to protect themselves from the risks of supplement contamination.

Sergeeva’s is an illustrative case when it comes to the timeframe of action as she was banned from the Olympics two days after testing positive. Yet we still have no answer on Valieva? It is now five days past the result being announced, 49 days since the sample was taken, and we still don’t have an answer? This stinks of politicking to us, and surely many others.

Why did six weeks pass before a final result was issued? The laboratory in Sweden that did the testing explained the confirmation of the result was delayed due to COVID issues, something we can sympathize with and understand. We don’t believe anything nefarious happened at the lab. This isn’t a lab issue unlike the debacle in Sochi.

In a powerful article, Yahoo Sports reported that the Russian Anti-Doping Agency (RUSADA) evaluated the Valieva situation and decided on February 8 to issue a provisional suspension. Then in classic fashion RUSADA turned around the next day and overturned it with no reason provided, clearly heightening suspicion. The Russian Olympic Committee released a statement Friday saying she had “passed numerous doping tests” before and after Christmas Day.

Travis Tygart, head of the U.S. Anti-Doping Agency (USADA) is not happy. Surely there is another Russian doping fiasco afoot. In the Yahoo Sports article Tygart called the excuse, “classic diversion by the Russians.” Tygart goes on to say, “This drug doesn’t just show up in your water somehow, my guess is … there is likely someone else behind how she got this drug. Again, I don’t know the facts. But clearly you have enough to ask those kinds of questions and demand answers to them.”

We don’t know the facts either but the theories are flying. Could a rogue doctor or trainer have been responsible for giving her something? The Russians are investigating and I don’t think anyone would want to be one of the targets of that investigation. Looking for a scapegoat perhaps? There have certainly been cases where support personnel have doped athletes, both purposefully and accidentally.

Tygart’s comments to Yahoo Sports are quite interesting as they allude to another possible reason Valieva, or any other athlete for that matter, could test positive for trimetazidine or other drugs. That is contamination of food, prescription drugs, and yes maybe even water.

The research has actually proven that water, and even crops, could be contaminated with drugs banned in sport, even trimetazidine. A 2021 summary by Polish researchers explored the concern that pharmaceuticals may appear in water and pointed to 826.7 ng/L of trimetazidine that was found in raw wastewater in Poland with 457.8 ng/L in treated wastewater. Other banned substance categories like stimulants, hormones, diuretics and beta-blockers were also found in variety of water samples. A U.S. Environmental Protection Agency poster presentation demonstrated how drugs banned in sport could infiltrate crops irrigated with treated wastewater. This highlights the unfortunate reality that not all drug residues are removed during water treatment and that irrigation with treated wastewater can result in contamination of crops.

I wrote an article on, “Differentiating adulteration from natural or environmental presence in dietary supplements,” for Natural Product Insider in late 2020. The article noted the many challenges we face with compounds banned in sport that surround us every day in items like whey protein, deer antler, plant extracts, or sometimes our water and food.

The possibility of contamination causing positive drug tests is well noted both in World Anti-Doping Agency (WADA) regulations and also in prior doping cases that have established a precedent for innocent sources like meat to be considered a likely source of a positive. WADA has now accounted for meat contamination in a technical letter outlining, “Minimum Reporting Level for Certain Substances Known to be Potential Meat Contaminants.” The document explains special thresholds to avoid innocent positives from clenbuterol, ractopamine, zeranol and zilpaterol. But are those the only potential meat contaminants?

A patent application filed in 2016 for ‘Extended Release Formulation of Trimetazidine’ describes in the abstract that, “The present invention relates to a dry ready to use modified release dosage formulation for Trimetazidine dosage forms and its salts and derivatives thereof,… also use thereof as additive to animal feeds, foods and food supplements and also cosmetic and pharmaceutical compositions.” With use in animal feeds outlined this would seem to establish a possibility that trimetazidine could not only show up as a water contaminant in the environment but also as a possible meat contaminant.

Trenbolone is a commonly used anabolic steroid implant used in the livestock industry today and yet there are no thresholds to account for it as a possible meat contaminant. This was a primary concern in the case of Alex Wilson, a Swiss sprinter who tested positive in March of 2021 for epitrenbolone, a metabolite of trenbolone.

The Sports Integrity Initiative suggested a review of meat contamination was needed after the Swiss Olympic Federation was rebuked by WADA and the Athletics Integrity Unit of CAS for considering meat contamination in Wilson’s case and voiding a provisional sanction. The sanction was reinstated by CAS and it kept him out of the Tokyo Olympics. The article notes, “when trace amounts of known meat contaminants are involved and a proffered explanation has already been accepted as likely, it seems a little perverse for anti-doping to celebrate ending an athlete’s Olympic dream.”

Meanwhile, Carl Grove, a 90-year old American cyclist, set a world record in his age group in the Masters Track National Championships in 2018 only to test positive for the same drug epitrenbolone. USADA investigated and in their statement relieving him of any sanctions they noted, “Grove provided USADA with information which established that the source of his positive test was more likely than not caused by contaminated meat consumed the evening before competing on July 11, 2018. Prior to consuming the meat, Grove had tested negative for prohibited substances during an in-competition test on July 10, 2018.” Grove was allowed to keep his result and world record.

This crazy case prompted The New York Times to delve deeper in a 2019 review that included an interview with USADA’s Tygart. “Cases like this make us bang our head against the wall,” said Travis Tygart, the agency’s chief executive. “They’re not right.” He goes on, “I don’t think the meat industry has changed significantly,” Tygart said. “The issue is now that the labs can see so much farther down that the likelihood of capturing something increases.” In conclusion the article notes, “Tygart and Usada are pushing for changes when the World Anti-Doping Agency revises its rules in November. Tygart said he backed putting in minimums for some substances that don’t have them to help ensure that tests were not merely finding environmental contamination. He also said he believed that “no fault” cases, like when tainted food, water or medicine is ingested accidentally, should not be a violation or be publicly announced.” “It absolutely breaks my heart to see a case like this with Carl,” Tygart said.

The article notes a key fact, that any amount of a substance that has no thresholds, like epitrenbolone and trimetazidine, is a violation. “Usada is confident the positive test occurred because of the meat. Sophisticated modern testing methods showed that Grove had less than 500 picograms of trenbolone, “an extremely low level,” Tygart said. But there is no established legal minimum level of trenbolone; any amount is considered a positive.”

It appears that USADA made an exception to the rules in Grove’s case based on their investigation of the circumstances and the conclusion that the most likely reason Grove tested positive was innocent consumption of contaminated meat. Similar to what the Swiss Olympic Committee considered in Wilson’s case. Could similar reasoning be the reason why RUSADA overturned their initial provisional suspension of Valieva? Likely not since the RUSADA investigation appears to have only taken one day, but it is possible.

The case also highlights one of the challenges we face with the advancement of anti-doping testing capabilities. Today we can detect down to a fraction of a picogram (part per trillion) whereas a decade ago we were only able to see down to the low nanogram (parts per billion) level. With a thousand fold increase in the sensitivity of drug tests the timeframe of detection has drastically expanded. However, this also increases the possibility of finding miniscule amounts of substances that result from inadvertent and in many cases unavoidable ingestion of contaminated supplements or food.

Shelby Houlihan, one of America’s premier distance runners, tested positive for nandrolone metabolites before trials for the 2020 Tokyo Olympics and is now serving a four year ban. Her case put the meat contamination concern in the spotlight in The Washington Post as she blamed the finding on a pork burrito she got from an Oregon food truck. The contention was rejected by CAS, hence the ban, despite research from the WADA community in 2020 that actually demonstrated the possibility that eating pork from random sources in Germany had a 16.7% chance of making a clean person test positive for up to 24 hours for nandrolone metabolites according to current WADA thresholds. That explanation was simply not believed in Houlihan’s case.

In 2019 The Athletic reviewed several low level positive drug tests in the UFC for Nate Diaz and Neil Magny noting that we live in a ‘contaminated world.’ Both Diaz and Magny had tested positive for tiny amounts of Selective Androgen Receptor Modulators (SARMs) in the double digit picogram realm. When we say tiny we mean tiny, as in an amount equivalent to a grain of salt sliced into 50 million pieces then chopped in half. Both tested positive as a result of supplement contamination and they were relieved of any sanctions after investigation of the circumstances. Article excerpts below note some fascinating considerations that could be relevant in the Valieva case.

“Over-the-counter medicine and prescription medicine may have been contaminated for a long time, but we’re now picking them up,” said Dr. Daniel Eichner, head of the World Anti-Doping Agency (WADA) accredited Sports Medicine Research and Testing Laboratory (SMRTL) in Salt Lake City.

Jeff Novitzky, the UFC’s senior vice president of athlete health and performance who works hand in glove with the promotion’s anti-doping program that is administered by the United States Anti-Doping Agency, believes the problem of contaminants is “getting worse and worse.” This is one reason the UFC’s anti-doping program will fully enact significant changes in the coming weeks.

Novitzky said in Los Angeles during a stakeholder meeting held by the California State Athletic Commission on Oct. 15 to address “common sense” disciplinary guidelines and minimum thresholds pertaining to certain prohibited substances. “But we have seen more and more commonly what I would call benign supplements being positive for prohibited substances. We’ve seen a couple of occasions where a women’s multivitamin having a SARM — ostarine — in it. We’ve seen creatine have prohibited substances. We’ve seen pure protein powder have prohibited substances. We’ve seen prescription medication from legitimate pharmacies be contaminated with prohibited substances. And we’ve seen contaminants at compounding pharmacies, both here in the U.S. and abroad where they’re mixing their own drugs and other drugs they’re mixing getting into a different drug.”

Of the approximately 13,000 individual tests that have been administered under the auspices of the UFC Anti-Doping Program since it began 2015, USADA and the UFC have announced sanctions on 100 athletes. A little fewer than half of them have come with “either definitive evidence or evidence tending to show that those positive tests were results of contaminants and not purposeful doping,” Novitzky told the California commission.

The UFC experience mirrors others with multi-vitamins, creatine, protein, medicine and other benign products often resulting in inadvertent positives. In nearly 50% of UFC doping cases investigations unearth an inadvertent source of the drug in question. This statistic was supported by John Ruger, U.S. Olympic Committee Athlete Ombudsman, who said, “between 40% to 60% of positive test doping results were inadvertent (non-deliberate) cases,” as quoted in a swimmingworldmagazine.com article in 2014. Imagine if that holds true across the spectrum of sport drug testing. So, did Valieva really dope or is it contamination? Flip your coin.

In a progressive move, the UFC now has reporting thresholds for SARMs set at 100 picograms and epitrenbolone set at 200 picograms. As of now, these thresholds only apply in the UFC anti-doping program and have not been adopted in the Olympic movement. There are no reporting thresholds for trimetazidine in the Olympic movement or elsewhere and any amount found is still a positive despite potential sources of contamination existing as noted herein.

Things are not always as simple as they may appear in the doping or anti-doping realms. There are many innocent and inadvertent reasons why an athlete could test positive. The problem is those same reasons also give accused athletes who really doped many excuses to point to other than cheating. Sadly, testing alone can’t distinguish between purposeful use that has faded away to miniscule levels over time and accidental use of something that could have been eaten or consumed yesterday.

Nonetheless, sprinter Sha’Carri Richardson tested positive for marijuana at the U.S. Olympic Trials just before Tokyo and lost her chance to compete at the Games while serving her one-month ban. Shouldn’t something like that have happened to Valieva? We are now at 49 days and counting since the positive sample was collected and Valieva is still on the ice with a possible gold medal in hand and likely more to come if she is allowed to continue in individual competition that starts Tuesday. That is simply outrageous regardless of whether she is the next poster child of Russian doping or an innocent victim of contamination called out by advancements in testing capabilities. Purposeful, accidental, or a mistake not declaring therapeutic use, all deserve some kind of sanction.

Sadly we may never know the real reason Valieva tested positive but we will all be witness to how the Olympic movement handles the case, and so far it is not looking good. The CAS decision is due Monday morning Beijing time. The world will be watching.

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Russian Doping of a Different Sort: Russian and Eastern European Drugs Hiding in Plain Sight as Alternative Doping Agents

Russian doping has been at the forefront of people’s minds as the 2020 Tokyo Olympic Games fade in our memories and we prepare for the 2022 Beijing Olympics to begin in February. The state-sponsored doping that culminated at the 2014 Sochi Olympics continues to cast shade over Russian sport–excuse me, the Russian Olympic Committee (ROC)–and indeed global competition, as the ensuing discussion and veiled accusations mar the Olympic spirit. But perhaps people should also be concerned about Russian doping of a different sort, one that is not often considered but should be. History has shown that athletes use Russian and Eastern European drugs as doping agents and yet few are prohibited today.

The World Anti-Doping Agency (WADA) Prohibited List outlines the substances that are banned in international competition including the Olympics. The 2021 WADA Prohibited List consists of 333 compounds listed by name, but the inclusion of catch-all language also prohibits related substances in many product categories. To be found, however, drugs have to rise to a level of concern and be targeted first and the WADA list primarily focuses on drugs of Western origin. Only four drugs of Russian or Eastern European origin appear to be included. Certainly there are others out there that would be attractive as doping agents.

Let’s take a look at the four drugs on the WADA Prohibited List that are of Russian or Eastern European origin and explore alternatives that athletes may be using today.

The story starts with bromantan, which was developed in the 1980s at the Russian Academy of Medical Sciences in Moscow. It can be found under the brand name Ladasten and is technically an actoprotector. Research out of Korea in 2012 explored bromantan in The Pharmacology of Actoprotectors: Practical Application for Improvement of Mental and Physical Performance. The writers described actoprotectors as “synthetic adaptogens with a significant capacity to improve physical performance.” The literature noted, “Bromantan was first found in an athlete sample at the 1996 Atlanta Olympics and was officially banned in 1997 as a stimulant.” There have been 11 adverse findings for bromantan in the WADA system since 2006.

Perhaps this is not surprising as a perfect alternative, bemitil, also known as metaprot, is described in the literature above and remains widely available online today, often at sites that offer Russian medicines or nootropics. The paper above explains that “nowadays, bemitil is manufactured in Ukraine (commercial name: Antihot) and is widely used in preparing Ukrainian national sport teams for international competitions.” It also notes, “Bemitil was successfully employed in preparing the athletes of the USSR’s national team for the 1980 Olympic Games held in Moscow.”

“Bemitil was successfully employed in preparing the athletes of the USSR’s national team for the 1980 Olympic Games held in Moscow.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3762282/

Bemitil was added to the WADA monitoring program list in 2018, 38 years after the Moscow Olympics you will note, but is not yet prohibited. If it does get prohibited, fear not there are alternatives for it, too. A site that sells Eastern European drugs like bemitil, MOSPharma.com, suggests four related products including noopept (see below) and trekrezan “from Russian pharmaceutical company Usolye-Siberian CPP,” with activity that “increases endurance during physical and mental stress.”

Next on the list of Russian doping agents is mescocarb, a central nervous system (CNS) stimulant and a dopamine reuptake inhibitor patented originally in Russia in 1970 by Vni Khim Farmatsevtichesky. Also known as Armesocarb, it is currently in clinical trials as an antiparkinsonian drug from Melior Pharmaceuticals. It has been sold under the brand name Sydnocarb with a nod to the technical chemical category in which it fits, mesoionic sydnone imine. Mesocarb does not appear to be widely available today online. It has been prohibited in sport since at least 1996 based on references to it at that time, but it has only been responsible for two adverse analytical findings since 2006.

There are also Russian alternatives to CNS stimulants with semax as one option. A poster on black market products with suspiciously doping relevant ingredients – annual report from the 2016 Manfred Donike Workshop discussed that semax “acts as a nootropic agent on the central nervous system and regulates dopamine and serotonine levels.” MOSPharma.com describes semax as “100% original from the Russian CJSC INPC Peptogen,” and notes it is used “to stimulate the central nervous system and enhance memory, focus, mental and physical performance, analytical skills.”

Carphedon, otherwise known as phenylpiracetam, is the next on our list and one of a family called racetams that are generally considered nootropic drugs. In 2019, researchers from the Czech Republic considered Carphedon at the Crossroads: A Dangerous  Drug or a Promising Psychopharmaceutical? They explain this substance was “developed in Russia as a stimulant to keep astronauts awake on long missions, and occasionally used in Russia as a nootropic prescription for various types of neurological disease.” Carphedon “was synthesized in 1990 by Russian chemists as a combination of two drugs, nootropic piracetam and amphetamine stimulant.” A 2012 review of Piracetam and Piracetam-Like Drugs describes them as “modulators of cerebral functions,” used for, “various therapeutic interventions relating to the CNS, including (i) cognition/memory; (ii) epilepsy and seizure; (iii) neurodegenerative diseases; (iv) stroke/ischaemia; and (v) stress and anxiety.”

Handwritten notes from 1997 show carphedon was considered by my father, sports drug-testing guru Dr. Don H. Catlin, and colleagues at the IOC Medical Commission for addition to the prohibited list at the time. The notes describe carphedon as, “adaptogenic, registered in 1994 in Russian pharmacopeia that might help with space travel and improve workload.” The drug has caused 122 adverse analytical findings since 2006.

If you peruse the piracetam review highlighted above, you will find nine other racetam options that may be considered as doping agents. None is listed by WADA today. Neither is noopept, otherwise known as omberacetam, which has become one of the most popular nootropic agents on the market today. The National Institutes of Health (NIH) National Center for Advancing Translational Sciences (NCATS) notes that “noopept was patented by Russian-based pharmaceutical company JSC LEKKO Pharmaceuticals in 1996.” The information cites that the “research shows Noopept has similar effects, but works differently than other nootropics in the racetam-family.” A number of sites compare the effects of phenylpiracetam to noopept with nootriment.com, suggesting that “both are purported to have benefits for memory, concentration, mood and alertness.”

From a banned substance standpoint, phenylpiracetam is on the WADA Prohibited List while noopept is not listed nor is it targeted. A synthetic drug, noopept, is widely available in supplement form despite it not qualifying as a dietary supplement ingredient according to the Dietary Supplement Health and Education Act of 1994 (DSHEA), which defines legal supplement ingredients in the U.S. It shows up in 32 dietary supplement products in the NIH Office of Dietary Supplements Dietary Supplement Label Database. In 2016 a BSCG blog post I wrote considered noopept could be the next big doping agent hiding in plain sight. That still remains the case today.

Last but not least of the four Russian doping agents is meldonium, otherwise known as mildronate. One will remember the maelstrom that ensued when meldonium was added to the WADA Prohibited List in 2016. There were 515 positive drug tests for meldonium in 2016, making it the most common substance found that year in Olympic sport. Tennis star Maria Sharapova was among them. There were 269 more positives from 2017 to 2019 for a total of 784. Meldonium is included on the WADA Prohibited List as a metabolic modulator in category S4.

Scientists from the University of Latvia and the Latvian Institute of Organic Synthesis that created meldonium, described it as “an anti-ischemic drug.” Its performance-enhancing potential has been the subject of much debate likely because it is a complex substance that has a variety of effects. An excerpt from a 2005 paper written by the aforementioned scientists, Mildronate: An Antiischemic Drug for Neurological Indications, describes it as follows.

“Mildronate was designed to inhibit carnitine biosynthesis in order to prevent accumulation of cytotoxic intermediate products of fatty acid oxidation in ischemic tissues and to block this highly oxygen-consuming process. Mildronate is efficient in the treatment of heart ischemia and its consequences. Extensive evaluation of pharmacological activities of mildronate revealed its beneficial effect on cerebral circulation disorders and central nervous system (CNS) functions. The drug is used in neurological clinics for the treatment of brain circulation disorders. It appears to improve patients’ mood; they become more active, their motor dysfunction decreases, and asthenia, dizziness and nausea become less pronounced.”

The meldonium saga more than demonstrated athletes around the world had recognized an obscure anti-ischemia agent as a doping option and had started to use it. When it was prohibited, Russian scientists boasted they already had alternatives. As reported in USA Today from Moscow, “Federal Medical-Biological Agency head Vladimir Uiba says Russia has found ‘several drugs which are not banned and work significantly better than meldonium.’”

You don’t have to look far. Mexidol is broadly available on sites that cater to Russian medicine as well as on a site called DrDoping.com; very subtle. It is also available on Amazon from Pharmasoft at $21 for 50 tablets with a label that suggests it be used for “Anxiety Relief, Anti-Stress, and Ischemic Condition.” Mexidol, an anti-oxidant, was patented in 2002 in Russia with the patent describing the “invention relates to preparations used for prophylaxis and treatment of different forms of cardiac ischemia disease, atherosclerosis and acute circulation disturbances, cerebral insults.” With indications for ischemic conditions, it certainly appears similar to meldonium.

In a 2007 paper, Mexidol effects in extreme conditions, T.A. Varonina with the Institute of Pharmacology, Russian Academy of Medical Sciences notes, “Mexidol can be prescribed to humans to maintain efficiency in all kinds of extreme situations.” Could hundreds of Olympic athletes be using mexidol as an alternative to meldonium today?

A 2019 review from Russia of Pharmacoeconomic analysis of the neuroprotective medicines in the treatment of ischemic stroke compares mexidol to actovegin, which gained some notoriety as a potential doping agent around 2009 as explored in the Daily News. Actovegin, which DrDoping.com carries in pill form, is an extract from calf blood and is not on the WADA Prohibited List. In the article Olivier Rabin, WADA’s science director, suggests, “Actovegin could be used as a component of sophisticated blood doping methods, in which athletes withdraw, manipulate, and re-inject their blood to boost their endurance, or in conjunction with the use of erythropoietin, or EPO.”

When we ran independent drug-testing programs for several leading cycling teams in the peloton years ago, a key member of a team said to me after an event, “You know, Oliver, we aren’t doing anything that is over the line but we are doing everything we can up to the line.” That simple philosophy likely rings true across sport today.

People often ask if the Olympics or sport in general is clean today. To answer that simply, the system is very good at finding drugs that are currently defined as prohibited substances. None of the Russian or Eastern European drugs we note here–bemitil, trekrezan, semax, noopept and other racetams, actovegin, or mexidol–is on the WADA Prohibited List today. These Russian or Eastern European drugs certainly seem to be potential alternatives to prohibited drugs, but if they are not yet defined as such then using them is not yet considered doping. If sites like DrDoping.com has found them, who else might have them?

Oliver Catlin is the longtime president and co-founder of BSCG (Banned Substances Control Group), an international third-party certification and testing provider. With a background in sports anti-doping, he is widely regarded as a thought-leader in the field of sports nutrition and dietary supplements.

The Rio Olympics, the Russian Doping Scandal, Dietary Supplements and Banned Substances in Sport

A Discussion with Dr. Don H. Catlin and Oliver Catlin

Don H. Catlin, M.D., a renowned longtime sports anti-doping researcher, is considered a father of drug testing in sport. He founded the UCLA Olympic Analytical Laboratory prior to the 1984 Los Angeles Summer Olympics and served as its director for 25 years, growing it into the world’s largest lab testing for performance-enhancing drugs. Today, among other things, he is Chief Science Officer at BSCG (Banned Substances Control Group), a leading provider of analytical testing and certification programs for dietary supplements, natural products, ingredient suppliers and manufacturing facilities.

Oliver Catlin is president of BSCG. A well-respected executive, he has been working in the arenas of sports anti-doping and dietary supplements for more than a decade.

Dr. Don Catlin, left, and Oliver Catlin

In the interview that follows, Dr. Catlin and Mr. Catlin discuss the upcoming summer Olympic Games in Rio, the Russian doping scandal and dietary supplement issues related to drugs in sport.

 

Q. Dr. Catlin, as a former longtime member of the IOC (International Olympic Committee) Medical Commission, how do you feel about the IOC’s recent decision not to ban all Russian athletes at the Rio Olympics?

Dr. Catlin: I was not happy to wake up a few days ago to the news that the IOC did not ban Russian athletes from competing at the Summer Olympic Games in Rio. I was hoping to see a serious statement made against the practice of state-sponsored doping. Instead the IOC turned the decision over to International Federations and an IOC executive committee. Several high-level recent reports (McLaren, WADA report 1C, German television ARD) established that the state of Russia was clearly involved with directing doping activities in an operation that included,Russian lab director Dr. Grigory Rodchenkov, the state ministry of sport, and the FSB security forces (renamed from the KGB). The extent of the activities warranted a ban in my view. This decision presented an opportunity for the IOC to show its dedication to anti-doping ideals and make a serious statement in support of clean sport, but sadly they failed to make that statement

Mr. Catlin: If we don’t stand up for anti-doping in this instance, when will we? I think that perhaps the consideration of a complete ban was challenged by a lack of precedence for banning an entire country as a result of anti-doping as well as liability concerns. Clean athletes were going to be harmed whether a total ban was enacted or not; arguably more clean athletes are impacted by not proceeding with a ban. Although I don’t believe there is a precedent for keeping an entire country out of the Games due to systemic doping, there is perhaps a precedent for systemic doping factoring into whether a sport is allowed to remain an Olympic sport. It was not long ago that the status of baseball and softball as Olympic sports were affected in large part due to concerns over systemic doping in baseball. Surely a number of clean athletes were affected by the decision to remove these sports, and for a longer period of time than the Russian ban was being considered. Liability is also perhaps a concern. With gold medals being worth upwards of $10 million or more, the risk of Russian athletes suing for damages may have been a factor in the IOC’s decision.

 

Q. What do you make of Sochi Olympics lab director Dr. Rodchenkov’s claims that he helped to oversee the systematic doping of Russian Olympic athletes at the behest of the Russian government?

Dr. Catlin: I was deeply disappointed to learn that Grigory Rodchenkov, someone I had called a friend and a colleague, had become a central figure in the Russian doping scandal that has spanned many years. In an in-depth interview with the New York Times in May, Dr. Rodchenkov revealed his role in doping Russian athletes. He did this by providing cocktails of drugs that were designed to clear the system quickly, aiding Russian agencies in a scheme to cover up positive test results, and in the case of Sochi testing he participated in an elaborate sample switching scheme enabled by the FSB. Dr. Rodchenkov remained in the lab from midnight to dawn. He knew which samples were positive. He passed those through a hole in the wall to an FSB agent, who used a new technique to open the tamper proof bottles and replace the positive urine with a clean sample. The bottles were closed and passed back to the lab for testing. It is hard for me to stomach that kind of deceit from someone I had known for many years. Thankfully, most of the lab directors in the WADA system are dedicated and ethical scientists who work hard to defend anti-doping and clean sport.

Mr. Catlin: I think most observers of the Russian doping scandal realize that Russia presents a very different environment. There is often no option other than to follow state directives. Ramifications of challenging the state can be severe. The recent McLaren report noted that the Russian laboratory personnel did not have a choice in whether to be involved in the state-directed system; their employment required participation. We are focused on the current scandal but I think it is fair to say that this is not the first occasion that my father, or the larger anti-doping community, have been suspicious of Russian doping. Nor is Russia alone in having issues, we have seen problems previously with Chinese swimmers, East German athletes, and even in the U.S. with result shredding scandals and ‘educational’ testing in the 80’s.

 

Q. Some have gone so far as to suggest that systematic doping threatens the very existence of the Olympics. How concerned are you that we could actually reach a tipping point where the general public might no longer believe the Olympics is a fair competition?

Dr. Catlin: The Olympics have been involved with controversies for many years, including doping scandals. I think back to the Ben Johnson affair at the 1988 Summer Olympics at Seoul, South Korea, and what that did to shake up the system at the time. The Olympics have survived all such controversies in the past and will likely survive this one. It is true that each drug scandal takes its toll, and this one is pretty gross. But a scandal can also help expose systemic weakness, which if addressed, can improve anti-doping efforts for the future.

Mr. Catlin: It’s sad that the Russian doping scandal has cast a pall over the Rio Olympics. The silver lining is that it has put the anti-doping issue on center stage, as it should be given its importance to the Olympic family. Years ago, my father helped to create the International Olympic Charter against Doping in Sport, and hopefully commitment to those ideas will help lead us past the current situation. The important thing is for us to recognize the problems and find real solutions.

 

Q. What changes or solutions do you think are necessary to protect against these kinds of concerns at the Olympics in the future?

Dr. Catlin: One thing we need to evaluate is the process involved in reviewing and reporting positive results and to create more oversight when it comes to results management. For years we have put result management largely in the hands of stakeholders without adequate independent review. In WADA’s review and criticism of its own activities a year or two ago, they suggested they needed more commitment and participation on behalf of stakeholders. If we continue to allow results decisions to be managed by state sport agencies or federations like IAAF, we face the risk of result manipulation. Decision-making is not always in the hands of the experts anymore. Twenty years ago the IOC doping control system was largely managed by a group of lab directors and scientific experts. Today the IOC has abdicated much of the responsibility and expertise and put it on the shoulders of WADA, an administrative body. In its zeal to conduct its mission, WADA has at times created an adversarial relationship with lab directors, which can diminish their impact and value. I would like to see the system return to a more collegial process in the future.

Mr. Catlin: In addition to added oversight, I think we need to review the resources available to the pursuit of anti-doping. The world expects a lot out of anti-doping forces, and rightly so, but the resources also have to be there to support the task at hand. The worldwide budget for anti-doping is perhaps $300 million. That sounds like a lot until you consider that we have to test a pool of 100,000 or more athletes around the globe, staff and maintain more than 35 laboratories, and must create methods to find clandestine and evolving doping agents and improve detection capabilities. The resources dopers have to thwart the system have been shown to far exceed the resources we have available to fight for clean sport.

 

Q. Russian media outlets and others in Russia have asked you what can be done to legitimize the participation of their athletes in this summer’s Olympics. What do you tell them?

Dr. Catlin: It is hard to evaluate things on an athlete-by-athlete basis with the extent of the Russian doping now exposed. Some may have been effectively tested outside of the Russian system and perhaps those athletes could be allowed to participate legitimately. Ultimately, Russia needs to replace all the agencies that have been involved and put a new person in charge, someone who is clearly not involved with doping, and then build from there. The process will not be quick or easy. The international community needs to ensure oversight in the process in order for us to trust the new system.

Mr. Catlin: The big question is what percentage of Russian Olympic athletes were involved in the state sponsored doping; 5%, 20%, 50%? It spanned many athletes and sports based on the report statistics, but I don’t know if we really have all the necessary facts to answer that question. Were other undetectable drugs being used that we don’t yet know about that might still be in use? I am not aware of any consistent guidelines being used to consider whether Russian athletes should be allowed to participate, and without those how do we come to consistent decisions?

 

Q. What are your thoughts about the retesting of samples from the 2012 London Summer Olympics and the 2008 Beijing Games that have led to a number of positive test results?

Dr. Catlin: This is a marvelous idea, and one that I supported over the years. It puts the doper at risk of being penalized for activities that may have been undetectable at the time.  The testing methods are always improving and sometimes it takes anti-doping science a few years to develop an effective test for drugs that we know are being abused. This is a great mechanism for dissuading athletes from pursuing clandestine doping strategies.  The IOC has shown that retesting is a potent addition to the process.

Mr. Catlin: Retesting has certainly proven to be valuable. Historically there are usually only a handful of positive results that occur during an Olympic Games. The retesting has exposed three times as many results per Olympics, sometimes even more. The added deterrence is certainly significant. The shame is that the doper benefits for several years to the detriment of the clean athletes that get elevated in placement years later.

 

Q. Dr. Catlin, you voiced concerns in media interviews about WADA’s closure of the Rio Olympic laboratory weeks before the Olympics were about to begin. Are you glad the lab has been reaccredited and will now handle the drug testing after all?

Dr. Catlin:  Yes, I am very pleased that the lab has been reaccredited. There is much secretiveness about WADA’s actions so we never, if ever, know what the extent of the problem was that led to the loss of accreditation. While it is possible to send the samples to another lab, doing so is difficult and expensive and has many complications. Whenever the Olympics come to town the home country’s lab receives support from experts from around the globe and I have faith that the group assembled will do a great job of conducting the testing during the Rio Games.

Mr. Catlin: Some people have considered the loss of accreditation to be a flaw in the system, when in fact it is evidence of the system working. If deficiencies are found, they are identified and addressed.

 

Q. The drugs meldonium and oral-turinabol/dehydrochlormethyltestosterone (DHCMT) have been in the news lately. What impact, if any, do you think these substances might have at the Rio Olympics?

Dr. Catlin: I don’t think that either drug will have a major impact on the Games. The lack of consideration of meldonium withdrawal times was embarrassing and certainly resulted in a lot of wasted money and effort, but we are mostly beyond that at this point. As for oral-turinabol, or DHCMT, I do not know why there have been so many positive cases recently. The testing method for DHCMT was improved in the last few years with the detection of long-term metabolites extending the detection window from several days to several months. Perhaps that is one reason. Unfortunately, the drug remains prevalent online and has been seen as a contaminant in dietary supplement products as well. If the drug infiltrates the raw material supply for supplements, it could lead to trace amounts of contamination that the new urine-testing methodology would be more likely to expose.

Mr. Catlin: I think some athletes continue to claim they were affected by discrepancies in meldonium findings before or after the cutoff dates for withdrawal time to be considered a valid reason for a positive finding. This might impact which athletes get to participate in the Rio Games. In the case of meldonium, the WADA system addressed a substance that athletes were apparently using for performance enhancement. In the case of DHCMT, the system is now using an improved method that has a longer window of detection. In either case, additional loopholes were closed, which would seem to be good for the system overall.

 

Q. As key figures in both overseeing the testing of Olympic athletes and helping to protect them by providing quality supplement information, testing and certification, what general advice do you offer Olympic athletes about consumption of supplements?

Dr. Catlin: There have been numerous examples where athletes have been harmed by supplements that were spiked with drugs on the WADA Prohibited List. Over the years I helped a number of athletes fight cases against supplement companies after they had tested positive. That is one reason we created BSCG. Athletes should be cautious when considering supplements and should only take those that have been tested to make sure they are ‘clean.’

Mr. Catlin: We have worked on a number of cases over the years where supplements have been involved in a positive drug test in some fashion and have impacted careers or health. Athletes like Kicker Vencill, Jareem Gunter, and Jessica Hardy. The issues involved are complex. Some supplements include active ingredients that may be banned substances in disguise. That was the case with the Superdrol product Gunter used; it contained the powerful anabolic steroid methasterone, which also contributed to his liver failure. Other products can be contaminated with trace amounts of banned substances that can still result in a positive drug test. This was the case with Hardy, who, as a result of using a supplement, lost out on her chance to compete in the 2008 Olympic Games in the prime of her career. We started our company BSCG to test and certify products to be free of banned substances so that athletes could have confidence when using them, and to give responsible supplement manufacturers a way to distinguish themselves from others in the industry. If athletes elect to use supplements—as many do, surveys have shown—we recommend they only consume products that have been certified by a reputable third party.

Colabello, Oral Turinabol and the MLB Positive Drug Tests

Intrigue continues to swirl after a recent article in SportsNet brought up potential questions surrounding Chris Colabello’s Major League Baseball positive drug test for Dehydrochlormethyltestosterone, otherwise known as DHCMT or Oral Turinabol. The article quoted statements by our Chief Science Officer, Don Catlin, M.D., apparently questioning the test results and also exploring a common point source of DHCMT. We wished to provide additional clarity as to Dr. Catlin’s views on the test results and add some thoughts on Colabello, oral turinabol and the MLB positive drug tests.

First we wanted to clarify the comments made as to the test results and laboratory data. Dr. Catlin was quoted in the article in the excerpt below:

“The one (DHCMT) case where I looked at the laboratory data, I didn’t think it was very good,” he said in an interview with Sportsnet.

Asked what that meant, Catlin, who has overseen drug testing at multiple Olympics and years ago received a grant from Major League Baseball to help develop a test for HGH, replied: “There’s a long process involved and I just didn’t think the laboratory did a very good job in demonstrating that the (DHCMT) metabolite was present in the urine. But I didn’t want to get into it because of a whole bunch of other issues.”

While that doesn’t necessarily exonerate the players, from a scientific perspective, isn’t that an issue?

“It’s a huge issue, yes.”

Enough of an issue that a player can use it in appeal process?

“Sure.”

And present a reasonable case, and perhaps even win?

“Yes. But that would be a huge concern for baseball and (the testing lab in) Montreal.”

Because it would call into question the results of other tests and open the door for multiple athletes to contest their doping sanction?

“Right. I did not wish to get into it. But I was interested not so much in the chemistry, but in the source. The three baseball players I talked to were all adamant that they had never used it, didn’t know what it was. And that’s fairly typical, but it also suggests that there’s a source of it somewhere, and my view of it was that it was probably coming from a supplement that they all took.”

Please allow us to distill the intended meaning behind those comments in relation to Colabello, oral turinabol and the MLB positive drug tests. Before we begin, please consider that Dr. Catlin has been reviewing laboratory documentation packages for more than three decades, both those from his own UCLA Olympic Analytical Laboratory, as well as those from other laboratories in the WADA system. He is regarded in the anti-doping arena not only as one of the most renowned scientists but as one of its most frank individuals.

In this situation, Dr. Catlin was taking issue with the way in which the data in the documentation package was presented, not the underlying chemistry involved. This should not come as a surprise to our friend and dedicated colleague Christiane Ayotte, Ph.D., director of the respected Montreal laboratory; it is probably not the first time she has heard Dr. Catlin gripe about her doc packs (Madame Ayotte, malheursement le Don reste inchangé). Gripes aside, it does not mean the results were wrong.

Is it, “Enough of an issue that a player can use it in appeal process?” In Dr. Catlin’s view, if a documentation package is not presented in a clear fashion, it can leave room for athletes or their representatives and experts to attempt to construct a reasonable case to refute the finding. That is what he was alluding to in his response.

As for the chemistry, Dr. Catlin said he did not want to get into it, but wanted to focus instead on the possible source of the issue. As for Colabello, oral turinabol, and the MLB positive drug tests the results ultimately indicated the presence of a long-term metabolite of DHCMT. No parent drug was found and no other metabolite was identified, which is common when relying on the recently identified DHCMT long-term metabolite to detect long-term use of the drug. The finding was considered to be a trace finding for the long-term metabolite of DHCMT.

Before exploring potential sources of DHCMT, we wanted to comment on the DHCMT test itself, and the chemistry involved. Oral turinabol is an old drug that became infamous when it was the primary drug fueling the East German state-sponsored doping from 1968-88. The testing for the drug initially had a short window of detection of a few days. As research expanded on the drug and additional metabolites were identified, the retrospectivity of the testing improved to about 20 days.

In the last several years, a new long-term metabolite, referred to as the M4 metabolite, was identified that increases the window of detection to at least 40-50 days, perhaps longer. The chemistry of DHCMT, however, appears to be such that after 20 days only the long-term metabolite would be detectable, while the parent and other identifying metabolites would no longer be detectable. While not many drugs in the WADA system rely on the presence of a single metabolite to demonstrate the presence of a drug, doing so is certainly acceptable.

When validating such methods, it is commonplace to verify that there are no ‘false positives.’ Whether there could be a genetic anomaly that may produce a ‘false positive’ circumstance that did not present itself during the validation process remains a remote possibility that presents a difficult theory to explore. Many of the athletes in question have been tested before and did not produce positive results. Chasing an inconsistent anomaly could prove to be an endless pursuit. Cody Stanley’s circumstances certainly heighten the intrigue behind the theory, but it has yet to be considered or proven.

Unfortunately, limited research dollars are available to the anti-doping community and labs rightfully use those to validate and demonstrate new testing methods, as they have in the case of DHCMT. However, the community is certainly not afforded the resources to research all the theories on how a ‘false positive’ might occur. As you can imagine, we hear a lot of theories in that regard. If such a possibility does exist, we know our dedicated colleagues in anti-doping like Dr. Ayotte, the experienced folks at Kings College, Cologne, the UCLA Olympic Analytical Laboratory and others will be working diligently to evaluate it and further improve the testing platform for DHCMT.

As for the potential sources of DHCMT, unfortunately it is not hard to find. A quick google search for supplements that contain DHCMT or oral turinabol brings up at least ten different websites where you can buy the drug in pill form. It is clear that oral turinabol remains available, likely through raw material providers in China or elsewhere. Unfortunately, many of these raw material providers also offer legitimate and legal supplement ingredients to the supplement marketplace, leaving open the real possibility for inadvertent contamination of benign products.

In that regard, we recommend that athletes take supplements that have been certified to be free of banned substances by an independent third-party—through programs like ours at BSCG Certified Drug Free® or the others you can explore on our comparison chart. Make sure to evaluate the technical details of such programs to ensure they provide adequate protection against banned substances. Athletes should verify that a particular lot number has been certified to ensure a representative sample of what they consume has been cleared of prohibited drugs.

Since DHCMT remains prevalent online and as a raw material, it is plausible that a contaminated supplement could have been responsible for the rash of recent DHCMT positive drug tests. Several supplements included on the USADA High Risk List present oral turinabol concerns, like Alpha-4D, OrlaTEST, and Osta RX. Osta RX was labelled to contain the banned substance ostarine, a selective androgen receptor modulator (SARM), but instead testing revealed the presence of oral turinabol.

However, since multiple athletes are involved, who use a variety of different supplements, the possibility of a single point source of DHCMT being a single supplement product common to the athletes is unlikely. The players say they were using only certified supplements, so that possibility is further diminished. Whether there could be widespread trace contamination of a single ingredient that may have resulted in multiple supplements being contaminated with trace amounts of DHCMT seems like a slim possibility but still in the realm of consideration.

Ultimately, the following scenarios remain plausible in regards to Colabello, oral turinabol and the MLB positive drug tests: The athletes in question took oral turinabol after purchasing it online as part of a doping regiment that had worked in the past, believing the window of detection was still narrow. There could be contamination coming from dietary supplements, or their ingredients, that resulted in trace findings for the long term DHCMT metabolite in the various athlete urine samples. Finally, there is the theory that a common genetic anomaly, or another substance related to DHCMT that is present in the environment, could produce the same long-term DHCMT metabolite used for detection in trace amounts in some athletes—remote possibilities that have yet to be demonstrated.

A few questions remain open, but none seem to present a significant possibility of providing an explanation. Nonetheless, we will certainly be watching with great intrigue to see if the burgeoning list of DHCMT positives continues to grow in MLB and elsewhere.

Gordon Adds Another Dee to PED Discussion – The Steroid Dilemma Continues for MLB

Baseball Stadium – 2000 Sydney Olympic Games, Photo by Oliver Catlin

While most people were waking up to a wonderful Friday morning, baseball fans were discovering some more depressing news in the announcement that Dee Gordon, infielder for the Miami Marlins, has been suspended 80 games due to test results revealing two performance-enhancing drugs (PED) in his system. Gordon had originally appealed the decision, but decided against appealing Friday morning.

Thursday night, Gordon revealed to his teammates, after a 4-game sweep of his former team in Los Angeles, that he tested positive earlier this year for synthetic testosterone and Clostebol, an anabolic steroid. He released a statement this morning through the MLB Players Association saying the following:  “Though I did not do so knowingly, I have been informed that test results showed I ingested something that contained prohibited substances. The hardest part about this is feeling that I have let down my teammates, the organization and the fans. I have been careful to avoid products that could contain something banned by MLB and the 20+ tests that I have taken and passed throughout my career prove this. I made a mistake, and I accept the consequences.”

Responses to the statement have been coming faster than Dee Gordon stealing second. Players, from all teams, are showing concern and making comments on the news about Gordon’s suspension.

Figure 1 Tweets by MLB players in response to Dee Gordon’s PED suspension

Justin Verlander’s Twitter response adds powerful perspective to the issue and shows how personal it is to the players, the majority of whom love and respect our national pastime.

Figure 2 Twitter post made by Justin Verlander from the Detroit Tigers. 

Why was Gordon Allowed to continue playing when these test results came in?

Gordon won the National League batting title in 2015 and was an All-Star player while with the Dodgers and the Marlins. Having him on the field obviously makes him a valuable asset to a team. You can ask anyone who was at Dodger Stadium Thursday night when Gordon “delivered the game-tying RBI single for the Marlins in the seventh inning,” which more or less solidified the series sweep.

Gordon had originally appealed the test results, meaning that nothing was going to be released publicly until the situation had been decided, which is in accordance with MLB policy. He was allowed to continue to take the field while the case was going through the appeal process. The news became public Friday morning, because Gordon decided to no longer appeal the results. But his answer just leads to more questions.

Should the punishment be more severe for players who cheat?

The topic of performance-enhancing drugs in the league has been trending lately due to the recent announcement of the Chris Colabello doping violation a week ago, Taylor Teagarden’s suspension earlier this month, as well as allegations of Chicago Cubs’ pitcher, Jake Arrieta, cheating after his recent successes on the field drew attention. Gordon’s suspension has further catalyzed conversations already in motion about what to do with his test results as well as the punishments associated with them.

The USA Today summarized the MLB penalties as of March 28, 2014 as follows: “Players and owners announce penalties will increase to 80 games for a first testing violation and to 162 for a second, and a season-long suspension will result in a complete loss of that year’s salary, rather than 162-183rds. A player who serves a PED suspension during the season will be ineligible for that year’s postseason.”

Even with these changes made, is it enough to incentivize players to not cheat? Many aren’t so sure. In an article released on April 21, by Fox Sports, the opinions players have about the MLB drug-testing program were discussed. Ever opinionated on the topic, Verlander discussed a potential way to clean up the league. “Maybe more severe punishments,” he said. He also mentioned that “It’s too easy for guys to serve a suspension and come back and still get paid,” which is what will happen with Gordon.

Another player, Matt Holliday from the St. Louis Cardinals, gave his take on punishments for cheating players in the article. “If you’re caught taking something where they prove that you’re trying to cheat,” he said, “that it’s a legitimate steroid or testosterone. I’m all for a year, two years, to keep guys from trying to cheat…for as harsh a penalty as possible. I’m all for second chances. But if you make the penalty super, super stiff, guys will think twice. They’ll look at 80 games and think, ‘That’s not that big a deal.’ But if you start taking away two years, that’s a lot of money. That might be different.”

We can all speculate that harsher punishments would make it a more difficult decision for players to take banned substances. They would also make it even more of a priority to be aware of what is in dietary supplement products or other medications athletes use. Lack of knowledge in this area can lead to problems, just ask Maria Sharapova, who tested positive at the Australian Open for the banned substance Meldonium. Thankfully, in the case of supplements, third-party certification programs like the BSCG Certified Drug Free® program are available that evaluate and test supplements to ensure they are free of banned substances to help mitigate the risks for athletes.

Is there incentive for players to cheat, regardless of the current punishments?

Gordon was traded to the Miami Marlins at the end of his best season with the Los Angeles Dodgers in 2014. Flash Gordon looked great in Dodger blue. Many fans in Chavez Ravine were sad to see him leave, especially having seen his stats soar after leaving. Of course, now that Gordon added another Dee to the PED discussion opinions have changed as we don’t need another superstar turned PED poster boy in L.A.

Last season, Gordon won the National League batting title with a .333 average. That was a big deal, due to the fact that he was neck-and-neck with Washington Nationals outfielder, Bryce Harper. He also led the league in stolen bases, with 58, a number not seen since JACKIE ROBINSON (yes, that guy) did it in 1949. Dee Gordon ended 2015 with the label “Big Deal” associated with his name and, as a result, was given a five-year, $50 million contract extension with the Miami Marlins.

Interviews were conducted before the 4-game series against the Dodgers on April 25th, prior to Gordon’s announcement. It was there, when Don Mattingly, who you might know as Donnie Baseball or the manager of the Los Angeles Dodgers from 2011 to 2015, discussed being the new manager of the Marlins and his thoughts of Gordon as a player, “What I always liked about him was his swing. You have to remember he was 140-something pounds when he started and now he’s brought it up to about 170. This is a kid that’s put on a lot of mature strength and his speed tools aren’t going away. That’s something that makes you feel really good about what he can do.”

As his manager ironically noted, Gordon was getting bigger, stronger, and better. The pressures that come with playing at this level include maintaining his skills in order to prove he is deserving of that label “Big Deal”. It isn’t unfathomable for a player to resort to taking performance-enhancing drugs in order to keep oneself at that professional level. It has been done before!

Gordon’s current punishment, aside from the 80-game suspension, includes a fine of $1.65 million. One might think that is a lot of money, until you realize it doesn’t even touch the $48.35 million he is still guaranteed on his contract. This being said, one could conclude that Gordon fought hard to earn this big paycheck, at any means possible, because cheating was worth close to fifty million dollars for him.   

Did Gordon use performance-enhancing drugs with mal intent? Did he cheat to gain weight and strength throughout his career? Was he trying to keep that “Big Deal” label while in Miami, or make it even bigger? Could this be something that happened unknowingly as his public statement claims?

While those questions linger, a single theme seems to resonate in professional baseball; even though a player’s failed test leads to a tarnished reputation, or demotion to the minor leagues, or retirement, or 80 game sanctions, he still makes millions of dollars. This is perhaps one reason why the issue of abusing banned substances in professional sports can be rationalized by players. Buster Olney’s statement about Gordon’s suspension puts it well, “the incentive to cheat will far outweigh the risks involved in being caught. Whatever the intent, whatever the justification, PED crime in baseball pays well.”

If we can learn anything from the past two days, it is that the PED discussion is far from over in MLB. Those who thought the steroid era was over may need to reconsider. We also need to reconsider how the system can be improved and made stronger for the sake of the players and the fans who love our nation’s pastime. For now, Gordon is just another name added to the list of MLB players that have tested positive for PEDs. He isn’t the first, sadly–he won’t be the last.

Maria Sharapova and Meldonium – Consideration of a Therapeutic Use Exemption After a Positive Drug Test

Maria Sharapova – London 2012 – Photo by Oliver Catlin, http://www.bscg.org

The coverage of Maria Sharapova’s announcement of her positive drug test for meldonium, or mildronate, has been astounding. Her case is yet another amazing example of a great champion falling victim to performance-enhancing drugs in one way or another. We wrote an immediate blog post about it an attempt to consider the two potential sides to a doping issue. That post still provides an interesting view of the perspective we were aiming to provide and we stand behind the bulk of the content.

In our haste to give Ms. Sharapova the benefit of the doubt in the situation, however, as we did in our conclusion and in the suggestion that perhaps her therapeutic use would be considered retrospectively, we did not fully consider the realities behind Ms. Sharapova’s claim of therapeutic use. Thankfully our friends in the anti-doping doping community have elegantly expounded on this element of the case.

The expert analysis below on therapeutic use and application in World Anti-Doping Agency (WADA) doping control is important to consider. It corrects the notion that a TUE could be granted retroactively and impact a pending sanction, which would be extremely rare if not completely unique in the field of anti-doping.

The information below was written by Dr. Ken Fitch and distributed by Jim Ferstle, both valued friends and colleagues who care deeply about clean sport and anti-doping and have spent their careers fighting for the cause as we have. The points of primary interest: retroactive TUEs would be unlikely to be considered from a standpoint of sanction relief, and the defined timeframe and clinical guidelines for use of a drug should always be scrutinized when evaluating potential therapeutic use. Thank you, Ken, for providing an insightful explanation of the criteria involved in the consideration of therapeutic use exemptions and the potential application to meldonium.

Dr. Ken Fitch is an Australian doctor and Professor, School of Sports Science, Exercise and Health, Faculty of Life Science University of Western Australia. Dr. Fitch wrote the original rules for TUEs in 1991 for the IOC, chaired the IOC’s TUE Committee for 20 years, chaired WADA’s interim committee (2001-2003) that established the initial International Standard for TUE (2004) and chaired Australia’s national TUE Committee for 22 years.

Maria Sharapova’s lawyer exploring a possible TUE to exempt a sanction
by Ken Fitch, M.D.

The ludicrous suggestion by Sharapova’s lawyer that she might seek a retroactive Therapeutic Use Exemption (TUE) to avoid a sanction for testing positive to meldonium demands a response. Ignoring whether the 2016 World Anti-Doping Code and the 2015 International Standard for TUEs does or does not make a retroactive TUE a possibility in her circumstances, if anybody examines the criteria that must be met to grant a TUE, he/she would understand that no respectable TUE Committee could approve any such application.

WADA states that there are four criteria, all of which must be met to grant a TUE.

1. The drug is necessary to treat an acute or chronic medical condition and the athlete would experience a significant impairment to health if it were to be withheld.
2. The therapeutic use of the prohibited drug is highly unlikely to produce any additional enhancement of performance beyond what might be anticipated by a return to the athlete’s normal state of health following the treatment.
   
3. There is no reasonable therapeutic alternative to the use of the prohibited drug.
4. The necessity to use of the prohibited drug is not a consequence of prior use of a prohibited drug or method.

Would Sharapova’s health be significantly impaired if she was denied a TUE? The Latvian makers of meldonium advise that it should be taken in intermittent courses of 4-6 weeks and for what period of time Sharapova administered meldonium during the past ten years, has yet to be disclosed. As the only acceptable medical indications are for ischemic cardiac and ischemic cerebral conditions, it is unthinkable that Sharapova has either. Hence any claim that should she be denied the right to take meldonium would impair her health is simply fanciful. Any TUE application must fail criterion 1.

The second criterion was introduced because some athletes had an essential need to take a prohibited drug. For example, an insulin dependent diabetic would die if denied insulin which has been prohibited in sport since 1998 and their daily insulin injections that are permitted with a TUE do not enhance performance. Whether meldonium actually enhances performance in humans has yet to be demonstrated. That WADA has advised that in less than two months since it was added to the Prohibited List, 99 athletes have tested positive for meldonium would appear to indicate that many athletes and their advisors believe that it does. No athlete could claim that meldonium was essential to restore their health back to normal levels. To claim that without it, a person’s health would be less than normal is surely fictitious. Fails criterion 2.

There are many drugs that have been demonstrated in scientific trials to be valuable in cardiac ischemia and the vast majority would be far superior to meldonium. The few meldonium studies performed in humans have been on persons who recently had experienced a myocardial infarction or an acute coronary syndrome. That the makers of meldonium recommend that it be administered only in intermittent courses in contrast to most of the widely acceptable, prescribed alternatives that are to be taken daily, is further evidence of the non-essential status of meldonium to treat cardiac ischemia. As the drug is marketed in only ten countries globally and Sharapova has lived in the USA for much of her life where meldonium is not approved for human use, this poses further questions for the tennis player.

Drug therapy for cerebral ischemia is generally ineffective and less frequently used than for cardiac ischemia but those patients on whom meldonium was trialled had had either a recent stroke or evidence of deteriorating brain function. As Sharapova could not possibly demonstrate that she has either of these or indeed significant cardiac or cerebral ischemia, and if she could, alternative permitted drugs are at least as effective if not more so, she fails criterion 3.

Hence Sharapova fails 3/3 and the fourth criterion has no relevance. Finally, should an unscrupulous or ignorant TUE Committee happen to grant Sharapova a retroactive or even a prospective TUE for meldonium, WADA would be certain to appeal to CAS and the decision would be or should be overturned.

Maria Sharapova and Meldonium – Consideration of a Positive Drug Test

Maria Sharapova – 2012 London Olympic Games – Photo by Oliver Catlin, www.bscg.org

Before jumping to conclusions and lambasting Maria Sharapova as a deliberate doper over recent revelations, we should attempt to educate ourselves and arrive at an informed decision based on the circumstances at hand. There is much to consider when reviewing Ms. Sharapova’s recent positive drug test at the Australian Open for the drug Meldonium.

First, we start with the drug, Meldonium, also known as Mildronate. You can review the pubchem listing for mildronate if you are interested. Other synonyms for the drug include “Quaterin; 76144-81-5; Kvaterin.” The long IUPAC chemical name is 3-[(trimethylazaniumyl)amino]propanoate.

In medicine, Meldonium is used to treat cardiac conditions like angina and vascular disease. It was developed by a Latvian company Grindeks and is approved in the Russian Federation and other countries but not in the Unites States. The description on Drugs.com describes it in two therapeutic categories; “treatment of cardiac disorders” and “inhibitor of carnitine synthesis.” Drugs.com includes 11 brand names across the Russian Federation, Latvia, Georgia and Lithuania: “Cardionate, Meldonium Olainfarm, Meldonium-MIK, Mildronat, Mildronat Grindeks, Mildronats, Mildroxyn, Vazomag, Midromax, Mildronate, Milkor.” There are 189 publications to explore via PubMed if you want to want to spend the time perusing them.

It appears Ms. Sharapova tested positive for the drug in an ITF (International Tennis Federation) drug test on Jan. 26 at the Australian Open. This information comes from her own accounts and the various media summaries of her case, including one from the New York Times that includes a video of her press conference in which she disclosed the positive test results. She explains the details saying, “I was legally taking the drug for the last ten years. I was getting sick very often, I had a deficiency in magnesium. I had irregular EKG results, and I had a family history of diabetes.” She added she had used the drug since 2006 based on treatment advice from her doctor.

Meldonium was added to the World Anti-Doping Agency (WADA) Prohibited List for 2016 under the category ‘S4. Hormone and Metabolic Modulators’. Prior to 2016, Meldonium was on WADA’s monitoring program list, meaning they were watching to see if it was being abused by athletes. The notes from WADA’s 2016 Prohibited List – Summary of Major Modifications and Explanatory Notes that came out on September 16, 2015, says that “Meldonium (Mildronate) was added because of evidence of its use by athletes with the intention of enhancing performance.”

More specifically, an abstract from a publication on Meldonium in Drug Testing and Analysis from December 2015 mentions, “the anti-ischemic drug Mildronate demonstrates an increase in endurance performance of athletes, improved rehabilitation after exercise, protection against stress, and enhanced activations of central nervous system (CNS) functions.” A good explanation on the logic and research leading WADA to prohibit of Meldonium is included in a blog from March 3, 2016, noting the positive drug tests of runners Abebe Aregawi and Endeshaw Negesse, who also recently tested positive for Meldonium.

According to a Roidadvisor.com article, “Performance-enhancing Drugs Used by Athletes That Are Surprisingly Common,” (Oct. 17, 2015),“Meldonium has generally been used by athletes in various sports for its mild stimulant-like properties.” The piece goes on to say, “Of interest to athletes is the finding that it consistently and significantly improves exercise tolerance. Some pharmaceutical companies have recently marketed it explicitly as a performance-enhancing drug. It’s also used as a ‘smart drug’ by non-athletes. Athletes have been using it for over 5 years.” Of additional concern, the article mentions other similar drugs “telmisartan (Micardis) and T3 liothyronine (Cytomel) – are currently being used by numerous elite athletes particularly in endurance sports.”

So, on the one hand there appears to be a plausible and legitimate medical reason for Ms. Sharapova to have used Meldonium. It could have simply been a mistake that she continued to use it in 2016 without realizing it had become prohibited or seeking a therapeutic-use exemption for the drug, which presumably she could have and still might receive if her account holds true. It’s possible that will be evaluated retrospectively. It would appear there was enough time to consider the potential concern as Meldonium was on the WADA monitoring program list since January 1, 2015 and notification of it being added to the Prohibited List came out more than three months before the start of the year. It is not known if the ITF provided any notification to its players in addition to the information WADA provided.

Now, the cynics will probably look at the message board information and say it appears clear that athletes have known about the doping potential of drugs like Meldonium for years now. They may conclude that Ms. Sharapova has come up with a convenient explanation of what happened after the fact. Sadly, that explanation is also plausible.

This issue is the perfect example of a primary challenge we face when confronting the need to conduct anti-doping testing to keep sport clean. All we have is the test results that indicate a positive or negative finding in a urine sample. The results do not speak to the motivations or intentions of the athlete. In situations like this one, or in cases that involve dietary supplement use, it is hard to know whether the athlete is being truthful in their explanation or if they have developed a convenient explanation for their use of the substance involved.

We will see how things conclude in this case. Given what we know about the character of Ms. Sharapova, we have to think this is accidental doping. Of course one can never be certain and the rules of strict liability still apply as they always do in the anti-doping realm, and as she herself notes in her statement. Sadly, she is now subject to a possible two years of sanctions and has had a pall pulled over the culmination of a fabulous career. Tennis will miss her and her the game. This case is the perfect illustration of the need for drug tested athletes to take it upon themselves at the end of each year to be vigilant and review changes in the WADA Prohibited List to ensure their medications and dietary supplements are compliant with the drug testing rules for the next year.

By Oliver Catlin, President, Banned Substances Control Group, www.bscg.org

For a Growing Number of Athletes and Consumers, Supplement Certification is Key

A new survey published recently in the New Zealand Medical Journal reveals 93 percent of elite New Zealand athletes consume dietary supplements. That an overwhelming majority of elite athletes use supplements shouldn’t come as a surprise to anyone. A 2013 survey from the National Marketing Institute in the United States revealed that supplement usage among U.S. adults at large increased from 62 percent in 2009 to 73 percent in 2013.

For competitive athletes, the pressure to be in top physical form is often especially intense. Some supplements can help optimize performance and nutrition without leading to positive drug tests. Supplements can help improve hydration and oxygen levels, support protein and carbohydrate intake and other baseline needs, and maximize key nutrients.

The caveat is that not all dietary and nutritional supplements are safe or free of problematic performance-enhancing drugs. Some products—especially those aimed at muscle-building, pre-workout stimulation, male sexual performance, and weight loss—are often contaminated with pharmaceutical drugs or designer drugs that could be harmful or may be banned in sport. Ingredients lists on supplement products cannot always be trusted, as problematic substances are often hidden in the product and do not appear on the label. These issues put athletes and general consumers at risk

According to WADA (World Anti-Doping Agency) on its website, “A significant number of positive tests have been attributed to the misuse of supplements.” Sporting authorities will not tolerate inadvertent doping, or doping via supplements, as an excuse for a positive drug test. Because every athlete is responsible for every substance found in his or her body, they must take great care in choosing which supplements to consume.

The traditional approach sporting authorities have espoused to athletes is to avoid taking supplements altogether. “The use of dietary supplements,” one common refrain goes, “is not recommended or encouraged as such products can lead to positive drug tests or other health concerns.”

As longtime experts in the field of sports drug testing, we at BSCG (Banned Substances Control Group) do not believe such a rigid approach today is realistic—or necessary. Many supplements can help athletes achieve their goals without risking their health or disqualification.

Today the supplement quandary for athletes and consumers is being solved through certification. Third-party administrators such as BSCG offer rigorous, independent, ISO-accredited supplement certification focused on the protection of athletes, consumers and even animals. A searchable database is provided for supplements that meet the established certification criteria.

Supplement certification helps the growing numbers of athletes and consumers to effectively navigate the supplement marketplace and identify supplement products that have been tested for their security. For more information about supplement certification for athletes, consumers, or animals or to search for BSCG Certified Drug Free® supplements, visit www.BSCG.org.

Banned Sports Doping Agents and Illegal Drugs Marketed as Dietary Supplements on Amazon.com

Designer steroids and prohormones, Selective Androgen Receptor Modulators (SARMs), growth hormone secretagogues, and new blood doping agents like FG-4592 all available to athletes and consumers through the online retailer, often under the guise of dietary supplements

The media has been swarming over possible concerns about Amazon’s poor treatment of its employees. Apparently there is less scrutiny on the products the retailer has available for sale. Those interested in anti-doping and drugs in sport wonder how athletes manage to get their hands on banned doping agents to enhance their performance. One simple answer, products masquerading as dietary supplements on Amazon.com.

For years we have marveled at the easy access to steroids and other drugs via Amazon.com, and have written blog posts about it in 2010, 2011, 2013 and assisted with a Slate article in May 2014. Anabolic steroids like methasterone, new drugs like the SARM Ostarine, prescription drugs, and more have all been available. Ever since we realized the prevalence of doping agents on the site, some of which were on the list of DEA Controlled Substances, we have tracked the issue further.

We recently circled back again to see how Amazon has responded, especially after the passage of the new Designer Anabolic Steroid Control Act in December 2014 (DASCA). We applaud our friends at the United Natural Products Alliance (UNPA) for promoting this bill and the government for finally enacting stronger regulations in this arena.

So what is still available at Amazon.com in the way of sports doping agents, or designer drugs? Plenty. This week, a search for prohormones brings up 94 items. When we were here a week ago there were 96, and it went up to 97 while we were exploring, so the list is constantly in flux. Having reviewed the offerings before, and being reasonably familiar with the products, we focused our review on a few items of interest. It is good that we are familiar, because for some of these potentially dangerous products, which presume to be dietary supplements, no information is provided about the ingredients.

Real problems remain. Take Blackstone Labs Alpha-1 Max, the product description on Amazon merely says, “Great product.” Visiting Strong Supplement Shop online, you find the product, label information and the ingredient, 20mg of Methyl-1-Etiocholenolol-Epietiocholanolone. This drug is otherwise known in the vernacular as Alpha One, Methyl-1-AD, or Methyl-1-Alpha. PubChem lists it as Epietiocholanolone with 43 depositor-supplied-synonyms, so the naming conventions are broad for this one compound, which is part of the challenge in tracking it and others like it.

If you Google the drug name, many links come up. Just pick one and an explanation like the following appears: “Methyl-1-Etiocholenolol-Epietiocholanolone, aka Methyl 1-AD, M1A, or Alpha One is one of the strongest designer steroid/prohormone compounds on the market.” Alpha-1 Max is not alone, Xtreme Alpha-1 contains the same drug, according to the Amazon product description.

The list of steroidal products available on Amazon continues with Xtreme Shed. Strong Supplement Shop has a version of the same product which is no longer available due to the prohormone ban in 2014. According to the Amazon product description Xtreme Shed includes: “(3,3-azo-17a-methyl-5a-androstan-17b-ol) 20mg (6a-Chloro-androst-4-en-17b-ol-3-one) 30mg”. The first ingredient is known as methyldiazirinol, the second hexadrone. Both are prohormones or designer steroids. The StrongSupplementShop listing for Xtreme Shed says the product contained 4-chloro-17a-methyl-androst-4-en-17b-ol3-one, otherwise known as methylclostebol.

Methylclostebol is a steroid that was added to the DEA Controlled Substances list under the DASCA legislation, probably why Xtreme Shed was discontinued at Strong Supplement Shop. The two compounds in Xtreme Shed on Amazon are not listed by name in the DASCA language. Perhaps the one on Amazon is a new version with the ingredients adjusted in hopes of getting around the DASCA legislation? If you thought the prohormone and designer steroid era was over, think again.

It doesn’t stop there. SARMs, a new category of developing drugs that aim to mimic the effects of anabolic steroids, remain available on Amazon.com in offerings like EPG OstaLean, or Osta, or Osta Laxogen. The names and product information suggest they contain the drug Ostarine, which appears on the WADA Prohibited List. Its scientific name is Enobosarm with a long name, (2S)-3-(4-cyanophenoxy)-N-[4-cyano-3-(Trifluoromethyl)phenyl]-2-hydroxy-2-methylpropanamide). In the case of Osta and Osta Laxogen, the Amazon product descriptions include the long name, the same way it is written in an FDA warning letter from December 11, 2014 addressing the sale of the SARM by another company.

Interestingly, if you purchase Osta the order is fulfilled by Amazon. What does it mean to be fulfilled by Amazon? According to the site, “Fulfillment by Amazon (FBA) is a service we offer sellers that lets them store their products in Amazon’s fulfillment centers, and we directly pack, ship, and provide customer service for these products. Something we hope you’ll especially enjoy.” So, in the case of Osta, fulfilled by Amazon apparently means that the product is currently inventoried in an Amazon warehouse, with Amazon shipping and providing customer service, all for a product described to contain a drug that the FDA has issued a warning letter against previously.

The FDA wrote the following in its warning letter, “androgenic modulator products are unapproved new drugs sold in violation of sections 505(a) and 301(d) of the Federal Food, Drug, and Cosmetic Act (FDCA) [21 U.S.C. §§ 355(a) and 331(d)] and are misbranded drugs sold in violation of sections 502 and 301(a) [21 U.S.C. §§ 352 and 331(a)] of the FDCA”. It goes on to say that SARMs, “are not dietary supplements.”

A Maxim magazine article focused on the popularity of SARMs, secretagogues and other unapproved drugs sold as supplements earlier this year. The DEA’s position on SARMs after the passage of DASCA is represented as follows in the article: “The way the statute is written, we have to be able to demonstrate a substance is chemically and pharmaceutically similar to testosterone,” says DEA spokesman Joseph Moses. “That makes them incapable of being controlled under the term anabolic steroid.” Nonetheless, SARMs certainly don’t qualify as legal dietary supplement ingredients, hence the FDA’s warning letter.

Unfortunately, the list of doping agents available at Amazon.com does not stop with steroids and SARMs. Blackstone Labs MK Ultra contains the drug Ibutamoren, also known as MK-677, according to the label and product information found elsewhere. Ibutamoren is in development for the treatment of growth disorders; in the doping realm it is known as a growth hormone secretagogue. Growth hormone secretagogues are listed generally on the WADA Prohibited List, but this specific drug does not appear yet by name. Even the new blood doping agent FG-4592 can be found on Amazon.com, although it is not currently available from the listed supplier nor is it clear if it is offered as a dietary supplement.

Athletes don’t need any kind of clandestine network to get sports doping agents; all they need is Amazon. The reality is banned and unapproved new drugs are at our finger tips often pretending to be dietary supplements. If you don’t believe this is a problem, picture a 16-year-old kid unknowingly buying a potent anabolic steroid on Amazon that can cause serious health issues, like Alpha-1 Max, and it might change your thinking. From the anti-doping perspective, we have a tough fight ahead if new doping drugs appear as supplements on Amazon.com as quickly as we can create the tests to detect them.

New Sports Doping Agent FG-4592 Not the Only HIF Drug Available to Athletes

What drugs are athletes using to dope? This is one of the most commonly asked questions in the realm of sports anti-doping. Recently the answer has been provided in glaring form. During the week of July 29, Dr. Don Catlin, BSCG’s chief science officer and former longtime director of the UCLA Olympic Analytical Laboratory, was interviewed by the New York Times regarding a new drug called FG-4592, which was detected in tests of at least two elite cyclists.

AstraZeneca, one of the drugs’ developers, summarizes FG-4592 as “a small molecule inhibitor of hypoxia-inducible factor (HIF) prolyl hydroxylase. HIF is a protein that responds to oxygen changes in the cellular environment and meets the body’s demands for oxygen by inducing erythropoiesis, the process by which red blood cells are produced.”

FG-4592 is available in pill form and is orally active, unlike its cousin, recombinant erythropoietin, or EPO, which must be injected. Some have dubbed FG-4592 as oxygen in pill form. This new drug is a breakthrough for anemia treatment and other similar blood ailments.  Unfortunately, an effective blood boosting drug in pill form is also the Holy Grail for endurance dopers. Though FG-4592 remains in third-stage clinical trials around the world, it is widely available as a research chemical on the Internet. Its apparent arrival in elite sport is troubling, yet predictable.

Similar to EPO, HIF drugs like FG-4592 help increase oxygen carrying capacity by spurring the production of red blood cells. Some researchers believe HIF stabilizers might be even more effective than EPO as they can help stimulate iron absorption and suppress the inflammation of cytokines.[1] FG-4592 was recently added to the WADA (World Anti-Doping Agency) Prohibited List for 2015, as have cobalt and other HIF stabilizers and activators in general.  No other HIF drugs are named though they would be prohibited if they are detected.

According to PubChem’s listing of Chemical Vendors, there are 18 suppliers of FG-4592 worldwide . One of the vendors, the Houston-based company APExBIO, has eight HIF-related biochemicals available on its website including BAY 87-2243, 2-Methoxyestradiol, PX 12, ML 228, KC7F2, Chetomin, DMOG, and its top seller, IOX2 (Glycine). On PubChem, there are 251 Related Compounds with Annotation to explore.

Recent positive drug tests of two elite cyclists suggest athletes have managed to obtain FG-4592 for use as a performance-enhancer. Though the chemical vendors listed on PubMed are not marketing the drug to athletes, another site does not seem as scrupulous, as it sells research peptides like FG-4592 alongside an array of “performance enhancers.”  Some research peptides at www.superhumanstore.com overlap the list of performance enhancers. Numerous drugs on the WADA Prohibited List are available on this site including Aicar, CJC-1295 (a growth hormone secretagogue), Erythropoietin-mimetic peptide 17 (EMP17), GHRP-2, Sermorelin, Thymosin Beta- 4 and more. Similar drugs are available that are not included on the WADA Prohibited List by name, like BAY 87-2243 and Follistatin 344 (a myostatin inhibitor).

The average professional cyclist in the UCI Tour makes $142,000, according to Ernst & Young.  Top riders can earn up to $5 million. Currently, the average dose of FG-4592 is recommended at 1-2mg/kg, 3 times a week, so $780 for 500mg will buy a two- week’s supply. An athlete could buy a year’s supply for around $20,280. This is a relatively affordable rate, even to an average Tour rider. With the difference between the average salary and the top salaries in elite cycling so significant, the financial incentives to use this new drug, or its cousins, remains high.

The good news is FG-4592 is detectable with drug tests. Similar developing drugs will undoubtedly be pursued and tried by athletes in the not-too-distant future. Whether these other options, particularly those not specified on the WADA Prohibited List, are detectable only time will tell. One thing history has proven, these will not be the last athletes to test positive for a new sports doping agent.

By Oliver Catlin and Joe Taylor

[1] Medscape  (http://www.medscape.org/viewarticle/548667)