A new direction for my Drugs in Sport blog

A while ago, I was thinking of a follow up to Run Swim Throw Cheat. One idea was to  write a similar book on supplements. Maybe I could look at different kinds of pills? I could explain the science behind how they might work and look at the evidence whether they did actually work. At the same I would highlight the key research papers if readers wanted to dig deeper into any topic. The idea never got beyond a web site url as my EPSRC Senior Media Fellowship ended and my more “normal” academic life intervened filled with its usual grant writing, research papers and university teaching and administration. However, the idea never quite went away. In fact I think now it would be interesting to apply the same strategy to explore the biochemistry, physiology and performance benefits of all the prohibited drugs and methods listed on the WADA prohibited list. 

 

I will write three blogs per compound attempting to answer the following questions :

 

1.     What is the biochemistry and/or physiology of the drug that might enhance performance?

2.     What is the best evidence that the drug does indeed enhance performance?

3.     Are there good examples of the drug being used by elite athletes?

 

 

So where to start? Well it so happens that one of the hottest current topics – the trimetazidine that Kamila Valieva tested positive for – is in one of the most interesting class of molecules for us biochemists, namely metabolic modulators. These sit in Section S4.4 of the WADA list, are prohibited at all times (in- and out-of-competition) and are “non specified” substances. A specified substance is one that is more likely to have been consumed or used by an Athlete for a purpose other than the enhancement of sport performance. This means that it can incur a lower punishment. In contrast a non specified substance – like all the metabolic modulators -  is likely to have been consumed by an Athlete for the enhancement of sport performance and there is no mitigating defence. 

 

Metabolic Modulators are listed by WADA (S4.4) as 

 

4.1 Activators of the AMP-activated protein kinase (AMPK), e.g. AICAR, SR9009;

and peroxisome proliferator-activated receptor delta (PPARδ) agonists, e.g. 2-(2-methyl-4-((4-methyl-2-(4-(trifluoromethyl)phenyl)thiazol-5-yl)methylthio)phenoxy) acetic acid (GW1516, GW501516)

4.2 Insulins and insulin-mimetics 

4.3 Meldonium

4.4 Trimetazidine

 

To start topically, I will write first about Trimetazidine. Two final points:

 

1.     I will try and write one blog a week, but don’t hold me to that!

2.     I will try and open the blogs for comments. Last time I did this I was inundated with people trying to plug the sale of peptides and had to shut down all comments. Let’s see if it works any better this time! 

  

Kamila Valieva CAS ruling – what it means

 So the Court of Arbitration for Sport (CAS) has ruled that Kamila Valieva can compete in the individual ice-skating competition [1]. As I suggested in my last blog this seems to be largely based on her “protected person” status given that she is a minor. I don’t find this surprising, especially as a doping offence has not been admitted by the athlete or her team and – apparently – the B sample has not been tested. However, neither the IOC [2] nor WADA [3] are happy about this; indeed WADA feels that CAS did not understand the WADA rules. Also it blames Russia for not requesting that her sample be fast tracked so that the result was known prior to the start of the Olympics. 

 

However, the CAS judgement was ONLY with regards to whether she can compete in the event. Not whether she (or more reasonably those who are responsible for her wellbeing) committed a doping offence. She  - and indeed the whole ROC team – could still lose all their medals. And no medal ceremonies will be held for either the team or individual women’s ice skating at these Olympics. An extra (25^th) athlete is being allowed to skate in the final free skating in the (admittedly unlikely chance) that the 25^th best skater would have been denied a medal if Valieva was later banned. 

 

Meanwhile WADA have said they will investigate the role of Valieva’s support personnel, a process already started by the Russian Anti-Doping Agency. I could comment but as this is more (all?) about the law rather than the science of doping – and laced with bit of politics of course – there is not much more that I can usefully ad as a scientist. 

 

[1] 

https://www.tas-cas.org/fileadmin/user_upload/CAS_Ad_Hoc_Media_Release_Beijing_8.pdf

 

[2] 

https://olympics.com/en/news/ioc-eb-decides-no-medal-ceremonies-following-cas-decision-on-the-case-of-roc-ska

 

[3] 

https://www.wada-ama.org/en/news/wada-statement-following-cas-decision-not-reinstate-skaters-provisional-suspension

Kamila Valieva, trimetazidine and figure skating's elusive quad jumps

Interestingly I was contacted only a few weeks ago by the journalist Sarah Stodola who was writing an article for New York magazine [1] . She asked me whether I thought Russian skaters might be using drugs to enable them to do their quadruple jumps, given how they were so much better than anyone else. I replied that figure skating is not my area of expertise, but I didn’t think there was an obvious drug that would help so specific a goal. Power/weight ratio obviously matters but how that transfers into the number of spins possible (let alone what counts as a full rotation) was outside my expertise. So I didn’t have a view as to what drugs would or wouldn't benefit. And – of course – my view is always to assume an athlete’s innocence until proven otherwise.

 

My not seeing how drugs might improve figure skating performance doesn't mean people wouldn’t try though of course. Well, now we have the story that a Russian skater  - actually not just any old Russian skater but their golden girl, Kamila Valieva -  tested positive for the banned performance enhancing drug trimetazidine. This anti-angina drug inhibits fatty acid oxidation, allowing the heart to make greater proportion of the more efficient glucose as its metabolic fuel. 

 

The Russian anti-doping agency (RUSADA) originally banned her, then allowed her appeal the next day. The IOC are appealing the RUSADA appeal decision; the Court of Arbitration for Sport (CAS) will presumably deliver their verdict in the next couple of days

 

Obviously, this story has hit the news [2]. There’s not a lot I can add to what is being currently discussed until then. Still some points seem relatively uncontentious.

 

Namely:

 

·       The anti-angina drug Trimetazidine has been banned at all times since 2015 [3] as it has the possibility to make the heart use fuel more efficiently. In this it has some features similar to meldonium, a drug that was frequently used by athletes in Eastern Europe until it was banned by WADA in 2016

·       Trimetazidine use within the World Anti-Doping Rules would require a TEU (therapeutic use exemption), presumably given for an athlete suffering from angina. 

·       A TUE seems unlikely for a teenager, but I am not a clinician so cannot really answer to this point

·       It seems unlikely a valid TUE was in place for Valieva or the case would not have got this far. 

·       There are rare circumstances where a positive case can result in a very short ban (or even very unusually no ban). This would require the athlete to provide definitive proof that they were not taking the substance knowingly and that - even then - there was no performance benefit. It is up to the athlete to prove this unequivocally. Ignorance is no defence.

I await the CAS decision with interest.....

[post original blog edit]. In the case of a minor like Valieva,  I have just realised that "strict liability" does not apply as she is a "protected person" under WADA's rules [4].  More flexible sanctioning rules apply to minors (persons under 18) with no requirement to establish how a prohibited substance entered the athlete’s system to benefit from the No Significant Fault or Negligence rule. The Minimum sanction is a reprimand when No Significant Fault is established. So I think this means that even if she does not know how the drug got into her system, she can still get away with just a reprimand. So no suspension for at all. But I’m not a lawyer. I [still] await the CAS decision with interest.....

 

[1] https://www.thecut.com/2022/02/quadruple-jumps-womens-figure-skating-winter-olympics.html

 [2] https://www.theguardian.com/sport/2022/feb/10/kamila-valieva-russian-skater-positive-test-winter-olympics-trimetazidine

 [3] Trimetazidine was originally banned as a “stimulant" in 2014. So only banned ”in competition”. But it was reclassified as a “metabolic modulator” in 2015 and thus banned at all times. This has resulted in some confusion in the press yesterday. Under the 2014 rules Valieva would not have been banned as the test was taken on Christmas Day (out of competition). But under the 2015 rules and beyond, she would have been banned. The 2015 change was well publicised. Again ignorance is no defence. Even in high profile doping cases like Maria Sharapova and meldonium, ignorance (arguing her team didn’t check the updated WADA list) only resulted in a shortening of the length of her ban.

[4] https://www.wada-ama.org/sites/default/files/resources/files/worldconferencebackgrounder_0.pdf