tag:blogger.com,1999:blog-51978981748564709342024-03-14T03:38:24.937-07:00Run, Swim, Throw, Cheat The science behind Drugs and Doping in Sport by Professor Chris Cooperprofchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.comBlogger88125tag:blogger.com,1999:blog-5197898174856470934.post-77366201671655987962022-03-10T08:40:00.000-08:002022-03-10T08:40:44.508-08:00Trimetazidine (TMZ) – what is it and how does it work? <p><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">Trimetazidine (TMZ) is a small molecule drug that is taken orally. It was invented in the 1960s by entrepreneurial French doctor, Jacques Servier, and patented and marketed by the company – Laboratoires Servier –</span><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"> </span><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"> </span><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">he founded in the 1950s. TMZ belongs to a class of compounds called piperazines. The initial patents on the class of compounds seem to focus on a possible role in increasing blood flow. However, further studies suggest that its mechanism may be nothing to do with physiology (blood flow increases), but instead have a more biochemical role (inhibiting metabolic pathways). The drug was targeted as a possible treatment for angina.</span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">Why does changing blood flow and oxygen metabolism matter in angina? Well angina is chest pain caused by decreased blood flow to the heart muscles. Accompanying the blood is of course the oxygen that is needed to fuel the heart contractions. Lack of oxygen is obviously a problem for the heart. Angina is common and treatable (hence the historic interest from pharmaceutical companies). <o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">An acute angina attack is treated differently to long term (chronic) symptoms. <o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">In an acute attack the goal is to increase blood flow to the heart. A class of drugs called “nitrates” are used. You are probably familiar with people reaching for their nitrate sprays or tablets when suffering an attack. Interesting the compound most commonly used is glycerol trinitrate. This is more commonly known as TNT – the explosive invented by Alfred Nobel. Intriguingly Nobel suffered from angina and was offered the TNT he invented as a treatment. He refused at the time, but it later became a standard treatment. About a hundred years after Nobel died the biological mechanism of action of TNT was discovered. TNT releases a gas called nitric oxide in the blood stream that relaxes smooth muscles and increases blood flow, easing the pain of an angina attack. For this work, in 1998, three scientists were awarded the prize that Nobel himself founded. <o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">Chronic angina is treated by lowering the oxygen requirement for the heart, making it better able to cope with reduced blood flow. The standard treatments here are beta blocker drugs which lower the heart rate and therefore reduce the hearts demand for oxygen. <o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><i><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">[As an aside beta blockers are banned in sports such as archery, shooting golf and ski jumping where lowering your heart rate and/or calming your nerves may be performance enhancing; in certain circumstances athletes with angina can get a Therapeutic Use Exemption (TUE) to enable their use in competition]. <o:p></o:p></span></i></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">So why is TMZ used as a treatment for angina? Like beta blockers it is taken chronically, not to increase blood flow, but instead - it is claimed – to reduce the oxygen cost of a heart contraction. So what is its mechanism of action? <o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">TMZ is suggested to inhibit a specific metabolic pathway; hence its appearance on the WADA list as a “metabolic modulator”. To understand how it works we need to know that there are different routes for getting useful chemical energy from the food that we eat. Three different pathways exist for fats (fatty acids) carbohydrates (glucose) and proteins (amino acids). Proteins are only a minor source of energy so we can focus on fats and carbohydrates.<o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">The amount of chemical energy (ATP) made per molecule of oxygen consumed is measured as a P/O ratio. For a carbohydrate such as glucose this is about 2.3, whereas for a fatty acid such as palmitic acid, the number is 2.1. The difference is subtle and for those who are interested comes about because glucose can generate additional ATP via a pathway called glycolysis that is not available to fatty acids which use a process called beta oxidation instead. <o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">It is hypothesized that TMZ inhibits an enzyme (called 3-ketoacyl coenzyme A thiolase) in the beta oxidation pathway. The heart then adjusts to use more energy via the carbohydrate (glycolytic) route. This results in less oxygen being consumed to produce the same amount of useful chemical energy (ATP). So TMZ could be useful as a treatment for angina, a condition where less oxygen is delivered to the heart muscle. <o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">It is worth mentioning that, whilst TMZ inhibits the enzyme 3-ketoacyl coenzyme A thiolase in the test tube (in vitro), it is not completely proven that this is its major effect in the body (in vivo). TMZ can also have, for example, more direct effects on oxygen consumption in mitochondria and/or activate nitric oxide production. It can also potentially protect the heart by inhibiting cardiac fibrosis, and thus preventing thickening and inflexibility in the heart valves. <o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">Personally, I have some suspicions about a model where TMZ works chronically via significantly altering the balance between fat and carbohydrate metabolism in the heart. These are already under tight hormonal control via insulin, thyroid hormones, growth hormone and cortisol and hormonal changes might counter any chronic effects of TMZ. <o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">In terms of side effects, TMZ is generally well tolerated. The major concern is that in some patients it seems to trigger Parkinson Disease symptoms, such as shaking, slow movement, muscle stiffness and other motor disorders. This concern is serious enough that TMZ is not licensed at all in the USA and is only approved in Europe for treating angina – and then only as add-on to existing treatments in patients who are not adequately controlled by or who are intolerant to other medicines. In fact, when the European Medicines Agency last looked at TMZ, a minority report argued for it being completely withdrawn from use. <o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">Of course, drug prescription is always a cost-benefit analysis. So, the chance of side effects can be tolerated if the efficacy is very high. The further reading below puts both sides of these arguments. <o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">We shall see in the next blog if TMZ really does affect the efficiency of cardiac metabolism and what effect this might have for an athlete.<o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p align="center" class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm; text-align: center;"><b><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">FURTHER READING<o:p></o:p></span></b></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><b><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">1 A paper that discusses the mechanism of action of TMZ and its possible use in treating angina and other diseases<o:p></o:p></span></b></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><a href="https://academic.oup.com/ehjcvp/article/2/4/266/2197104" style="color: purple;">The role of trimetazidine in cardiovascular disease: beyond an anti-anginal agent</a><o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><b><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">2 A paper that describes the differences in efficiency of fat and carbohydrate oxygen metabolism. <o:p></o:p></span></b></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><a href="https://portlandpress.com/biochemsoctrans/article-lookup/doi/10.1042/BST0330897" style="color: purple;">The efficiency and plasticity of mitochondrial energy transduction</a><o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><i><span style="background-color: white; font-family: Arial, sans-serif; font-size: 10.5pt;">This is a complex paper for biochemical aficionados only! But as this topic is covered so badly (and usually incorrectly!) in most text books, I felt the need to present the views of a genuine expert on this topic<o:p></o:p></span></i></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><b><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">3 A recent clinical trial suggesting TMZ may not be beneficial in some patients with angina <o:p></o:p></span></b></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><a href="https://www.thelancet.com/article/S0140-6736(20)31790-6/fulltext" style="color: purple;">Efficacy and safety of trimetazidine after percutaneous coronary intervention (ATPCI): a randomised, double-blind, placebo-controlled trial</a><o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><b><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">4 The European Medicine Agency report on whether – and how – TMZ should be used clinically<o:p></o:p></span></b></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><b><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></b></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><a href="https://www.ema.europa.eu/en/documents/referral/trimetazidine-article-31-referral-assessment-report_en.pdf" style="color: purple;">Assessment Report for trimetazidine containing medicinal products</a><o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p>profchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com0tag:blogger.com,1999:blog-5197898174856470934.post-47808187038339823272022-02-24T06:26:00.000-08:002022-02-24T06:26:22.733-08:00A new direction for my Drugs in Sport blog<style class="WebKit-mso-list-quirks-style">
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</style><p class="MsoNormal" style="font-size: medium;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">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. <o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">I will write three blogs per compound attempting to answer the following questions :<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoListParagraphCxSpFirst" style="mso-list: l0 level1 lfo1; text-indent: -18.0pt;"><!--[if !supportLists]--><span lang="EN-US" style="font-family: Arial, sans-serif; font-size: 11pt;">1.<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]--><span lang="EN-US" style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">What is the biochemistry and/or physiology of the drug that might enhance performance?<o:p></o:p></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -18.0pt;"><!--[if !supportLists]--><span lang="EN-US" style="font-family: Arial, sans-serif; font-size: 11pt;">2.<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]--><span lang="EN-US" style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">What is the best evidence that the drug does indeed enhance performance?<o:p></o:p></span></p><p class="MsoListParagraphCxSpLast" style="mso-list: l0 level1 lfo1; text-indent: -18.0pt;"><!--[if !supportLists]--><span lang="EN-US" style="font-family: Arial, sans-serif; font-size: 11pt;">3.<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]--><span lang="EN-US" style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">Are there good examples of the drug being used by elite athletes?<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium; margin-left: 18pt;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-size: medium; margin-left: 18pt;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">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 <b>“non specified”</b> substances. A specified substance is one that is </span><span lang="EN-US" style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">more likely to have been consumed or used by an <i>Athlete </i>for a purpose other than the enhancement of sport performance. This means that it can incur a lower punishment. In contrast a <b>non specified</b> substance – like all the metabolic modulators - is likely to have been consumed by an <i>Athlete </i>for the enhancement of sport performance and there is no mitigating defence. <o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span lang="EN-US" style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-size: medium;"><b><span lang="EN-US" style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">Metabolic Modulators</span></b><span lang="EN-US" style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"> are listed by WADA (S4.4) as <o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">4.1 Activators of the AMP-activated protein kinase (AMPK), e.g. AICAR, SR9009;<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">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)<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">4.2 Insulins and insulin-mimetics <o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">4.3 Meldonium<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">4.4 Trimetazidine<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">To start topically, I will write first about <b>Trimetazidine</b>. Two final points:<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoListParagraphCxSpFirst" style="mso-list: l1 level1 lfo2; text-indent: -18.0pt;"><!--[if !supportLists]--><span lang="EN-US" style="font-family: Arial, sans-serif; font-size: 11pt;">1.<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]--><span lang="EN-US" style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">I will try and write one blog a week, but don’t hold me to that!<o:p></o:p></span></p><p class="MsoListParagraphCxSpLast" style="mso-list: l1 level1 lfo2; text-indent: -18.0pt;"><!--[if !supportLists]--><span lang="EN-US" style="font-family: Arial, sans-serif; font-size: 11pt;">2.<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]--><span lang="EN-US" style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">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! <o:p></o:p></span></p><p><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"> </span> </p>profchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com0tag:blogger.com,1999:blog-5197898174856470934.post-17865112534502754272022-02-14T10:06:00.000-08:002022-02-14T10:06:51.485-08:00Kamila Valieva CAS ruling – what it means<p> <span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">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.</span><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"> </span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">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<sup>th</sup>) athlete is being allowed to skate in the final free skating in the (admittedly unlikely chance) that the 25<sup>th</sup> best skater would have been denied a medal if Valieva was later banned. <o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 11pt;">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. <o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 10pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 10pt;">[1] <o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 10pt;"><a href="https://www.tas-cas.org/fileadmin/user_upload/CAS_Ad_Hoc_Media_Release_Beijing_8.pdf" style="color: purple;">https://www.tas-cas.org/fileadmin/user_upload/CAS_Ad_Hoc_Media_Release_Beijing_8.pdf</a><o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 10pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 10pt;">[2] <o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 10pt;"><a href="https://olympics.com/en/news/ioc-eb-decides-no-medal-ceremonies-following-cas-decision-on-the-case-of-roc-ska" style="color: purple;">https://olympics.com/en/news/ioc-eb-decides-no-medal-ceremonies-following-cas-decision-on-the-case-of-roc-ska</a><o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 10pt;"><o:p> </o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 10pt;">[3] <o:p></o:p></span></p><p class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm;"><span style="background-color: white; font-family: Arial, sans-serif; font-size: 10pt;"><a href="https://www.wada-ama.org/en/news/wada-statement-following-cas-decision-not-reinstate-skaters-provisional-suspension" style="color: purple;">https://www.wada-ama.org/en/news/wada-statement-following-cas-decision-not-reinstate-skaters-provisional-suspension</a><o:p></o:p></span></p>profchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com0tag:blogger.com,1999:blog-5197898174856470934.post-2494136376844826662022-02-11T04:56:00.001-08:002022-02-11T07:45:24.969-08:00Kamila Valieva, trimetazidine and figure skating's elusive quad jumps<style class="WebKit-mso-list-quirks-style">
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</style><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="font-size: 11pt;">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.<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="font-size: 11pt;"> </span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="font-size: 11pt;">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. <o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="font-size: 11pt;"> </span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="font-size: 11pt;">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<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="font-size: 11pt;"> </span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="font-size: 11pt;">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.<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="font-size: 11pt;"> </span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="font-size: 11pt;">Namely:<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="font-size: 11pt;"> </span></p><p class="MsoListParagraphCxSpFirst" style="mso-list: l0 level1 lfo1; text-indent: -18pt;"><!--[if !supportLists]--><span lang="EN-US" style="font-family: Symbol; font-size: 11pt;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]--><span face="Arial, sans-serif" lang="EN-US" style="font-size: 11pt;">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<o:p></o:p></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -18pt;"><!--[if !supportLists]--><span lang="EN-US" style="font-family: Symbol; font-size: 11pt;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]--><span face="Arial, sans-serif" lang="EN-US" style="font-size: 11pt;">Trimetazidine use within the World Anti-Doping Rules would require a TEU (therapeutic use exemption), presumably given for an athlete suffering from angina. <o:p></o:p></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -18pt;"><!--[if !supportLists]--><span lang="EN-US" style="font-family: Symbol; font-size: 11pt;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]--><span face="Arial, sans-serif" lang="EN-US" style="font-size: 11pt;">A TUE seems unlikely for a teenager, but I am not a clinician so cannot really answer to this point<o:p></o:p></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -18pt;"><!--[if !supportLists]--><span lang="EN-US" style="font-family: Symbol; font-size: 11pt;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]--><span face="Arial, sans-serif" lang="EN-US" style="font-size: 11pt;">It seems unlikely a valid TUE was in place for Valieva or the case would not have got this far. <o:p></o:p></span></p><p class="MsoListParagraphCxSpLast" style="mso-list: l0 level1 lfo1; text-indent: -18pt;"><!--[if !supportLists]--><span lang="EN-US" style="font-family: Symbol; font-size: 11pt;">·<span style="font-family: "Times New Roman"; font-size: 7pt; font-stretch: normal; line-height: normal;"> </span></span><!--[endif]--><span face="Arial, sans-serif" lang="EN-US" style="font-size: 11pt;">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.<o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="font-size: 11pt;"></span></p><p class="MsoNormal"><span face="Arial, sans-serif" style="font-size: 11pt;"><br /></span></p><p class="MsoNormal"><span face="Arial, sans-serif" style="font-size: 11pt;">I await the CAS decision with interest.....<o:p></o:p></span></p><div><span face="Arial, sans-serif" style="font-size: 11pt;"><br /></span></div><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="font-size: 11pt;"><i>[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]. </i></span><i><span style="font-size: 14.666666984558105px;"> More flexible sanctioning rules apply to minors (persons under 18) with n</span><span style="font-size: 14.666666984558105px;">o requirement to establish how a prohibited substance entered the athlete’s system to benefit from the No Significant Fault or Negligence rule. The </span><span style="font-size: 14.666666984558105px;">Minimum sanction is a reprimand when No Significant Fault is established. </span><span style="font-size: 14.666666984558105px;">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. </span><span style="font-size: 14.666666984558105px;">I [still] await the CAS decision with interest.....</span></i></p><p class="MsoNormal" style="font-size: medium;"><span style="background-color: white; font-size: 11pt;"> </span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="background-color: white; font-size: 11pt;">[1] </span><span face="Arial, sans-serif" style="font-size: 11pt;"><a href="https://www.thecut.com/2022/02/quadruple-jumps-womens-figure-skating-winter-olympics.html">https://www.thecut.com/2022/02/quadruple-jumps-womens-figure-skating-winter-olympics.html</a><o:p></o:p></span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="background-color: white; font-size: 11pt;"><o:p> </o:p></span><span style="background-color: white; font-size: 11pt;">[2] </span><a href="https://www.theguardian.com/sport/2022/feb/10/kamila-valieva-russian-skater-positive-test-winter-olympics-trimetazidine" style="background-color: white; font-size: 11pt;">https://www.theguardian.com/sport/2022/feb/10/kamila-valieva-russian-skater-positive-test-winter-olympics-trimetazidine</a></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="background-color: white; font-size: 11pt;"><o:p> </o:p></span><span style="background-color: white; font-size: 11pt;">[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.</span></p><p class="MsoNormal" style="font-size: medium;"><span face="Arial, sans-serif" style="background-color: white; font-size: 11pt;">[4] </span><span style="font-size: 14.666666984558105px;"><a href="https://www.wada-ama.org/sites/default/files/resources/files/worldconferencebackgrounder_0.pdf">https://www.wada-ama.org/sites/default/files/resources/files/worldconferencebackgrounder_0.pdf</a></span></p>profchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com0tag:blogger.com,1999:blog-5197898174856470934.post-6181953847403159012021-09-07T04:41:00.003-07:002021-09-07T04:47:42.207-07:00 Doping at the Tokyo Paralympic Games<p><span style="font-family: arial; font-size: medium;"><span face="Arial, sans-serif" style="background-color: white;">As someone with a chronic, progressive disability, I have mixed views about the Paralympics. For me an inspirational story for someone with a disability is surviving another day in good cheer and not being too much of a burden on others. Interestingly as my disability has got worse my feelings about the Paralympics have, if anything, become more conflicted. I suspect what I am feeling is something akin to what I felt about elite sport when I was young. The realisation of a young boy that I was never good enough to play centre forward for the England football team has now been joined by an ageing man who has been reminded that another opportunity for sporting excellence has passed him by. Probably time to see my therapist again!</span><span face="Arial, sans-serif" style="background-color: white;"> </span></span></p><p class="MsoNormal" style="margin: 0cm;"><span face="Arial, sans-serif" style="background-color: white;"><span style="font-family: arial; font-size: medium;">Anyway, this is a roundabout way of saying that I watch the Paralympics solely as an example of elite sport and view it on those terms. Studies show that elite sport or even hosting the Olympic Games has no discernible benefit in improving the health of physical activity of the nation. I strongly suspect that the Paralympics likewise have minimal, if any, effect on the physical activity and/or rights of disabled people. But, actually why should we put this “burden of inspiration” on Paralympians. Let’s just treat them as elite athletes in their own right. No more, no less. Neither positive nor negative role models. Just ordinary people doing extraordinary deeds. The same as the Olympians. <o:p></o:p></span></span></p><p class="MsoNormal" style="margin: 0cm;"><span face="Arial, sans-serif" style="background-color: white;"><o:p><span style="font-family: arial; font-size: medium;"> </span></o:p></span></p><p class="MsoNormal" style="margin: 0cm;"><span face="Arial, sans-serif" style="background-color: white;"><span style="font-family: arial; font-size: medium;">Viewed in that light, <a href="https://runswimthrowcheat.blogspot.com/2012/09/doping-drugs-and-cheating-at-paralympic_10.html" style="color: #954f72;">as I said about London 2012</a>, we should expect the same issues to arise in Paralympic sport with regards to doping. And they do. In fact, Paralympians with spinal cord injuries even have their own unique way of cheating. <a href="https://www.usada.org/spirit-of-sport/education/what-is-boosting-and-why-is-it-dangerous/" style="color: #954f72;">“Boosting”</a> by blocking a catheter, squeezing a scrotum or breaking a toe can increase performance by inducing a pain free rise in blood pressure. Even in more “normal” doping methods, Paralympians equal or outshine Olympians. We don’t have the Tokyo numbers yet, but in Rio 2016, roughly the same number of doping tests per competitor were carried out at the Olympics and the Paralympics. The Paralympians “won” by having 0.71% positive tests compared to the Olympians 0.59%. <o:p></o:p></span></span></p><p class="MsoNormal" style="margin: 0cm;"><span face="Arial, sans-serif" style="background-color: white;"><o:p><span style="font-family: arial; font-size: medium;"> </span></o:p></span></p><p class="MsoNormal" style="margin: 0cm;"><span face="Arial, sans-serif" style="background-color: white;"><span style="font-family: arial; font-size: medium;">So let’s raise a “tainted” toast to Marcin Polak, the Polish visually impaired tandem cyclist. Polak ‘won’ a bronze medal on August 25, <a href="https://www.uci.org/inside-uci/press-releases/uci-statement-concerning-marcin-polak" target="_blank">but then was informed two days later that he had tested positive for the blood booster EPO in an earlier out of competition test on August 2</a> and so had to cut short his Paralympic “journey” [1]. Polak reminds us that Paralympians are the same as Olympians in all ways, good bad and ugly. And that’s why – on reflection – I think I’ll carry on watching the Paralympics after all. Next stop Paris......<o:p></o:p></span></span></p><p class="MsoNormal" style="margin: 0cm;"><span face="Arial, sans-serif" style="background-color: white;"><o:p><span style="font-family: arial; font-size: medium;"> </span></o:p></span></p><p class="MsoNormal" style="margin: 0cm;"><span face="Arial, sans-serif" style="background-color: white;"><o:p><span style="font-family: arial; font-size: medium;"><br /></span></o:p></span></p><p class="MsoNormal" style="margin: 0cm;"><span face="Arial, sans-serif" style="background-color: white;"><span style="font-family: arial;">[1] For those wondering why Polack was allowed to compete on August 25,when his positive test sample was collected on August 2, this is a most likely due to the peculiarity of EPO testing. The interpretation of the test gel is somewhat subjective, so requires independent verification by a second anti-doping laboratory. So the Warsaw positive result had to be re-analysed, and confirmed by the Tokyo lab, before the athlete would have been informed. Hence the reason for the delay. </span><span style="font-family: "Times New Roman", serif; font-size: 11pt;"><o:p></o:p></span></span></p>profchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com0tag:blogger.com,1999:blog-5197898174856470934.post-56983993598833168902021-09-06T08:59:00.001-07:002021-09-06T08:59:53.197-07:00Doping at the Tokyo Olympic Games<p><span style="font-family: arial; font-size: medium;">My first blog in almost two years. Perhaps because nothing much has changed in the period in the field or perhaps because I had other things to do in my life! Still, hopefully I can be a bit more fruitful in the future.</span></p><p class="MsoNormal"><span style="font-family: arial; font-size: medium;">I covered my current views on the Olympics in a podcast I did for the Economist which is openly accessible by the link below. <o:p></o:p></span></p><p class="MsoNormal"><span style="font-family: arial; font-size: medium;"> </span></p><p class="MsoNormal"><span style="font-family: arial; font-size: medium;"><a href="https://www.economist.com/podcasts/2021/07/20/cloud-of-suspicion-how-doping-is-common-in-elite-sport">https://www.economist.com/podcasts/2021/07/20/cloud-of-suspicion-how-doping-is-common-in-elite-sport</a><o:p></o:p></span></p><p class="MsoNormal"><span style="font-family: arial; font-size: medium;"> </span></p><p class="MsoNormal"><span style="font-family: arial; font-size: medium;"> </span></p><p class="MsoNormal"><span style="font-family: arial; font-size: medium;">For the podcast, I was asked to comment on drugs like AICAR and other so-called “exercise mimetics”. I might follow up on this with a couple of future blogs. <o:p></o:p></span></p><p class="MsoNormal"><span style="font-family: arial; font-size: medium;"> </span></p><p class="MsoNormal"><span style="font-family: arial; font-size: medium;">There was a nice graphic also from the Economist contrasting different countries doping in athletics <o:p></o:p></span></p><p class="MsoNormal"><span style="font-family: arial; font-size: medium;"> </span></p><p class="MsoNormal"><span style="font-family: arial; font-size: medium;"><a href="https://www.economist.com/graphic-detail/2021/08/05/russia-and-kenya-take-the-podium-in-the-athletics-doping-contest">https://www.economist.com/graphic-detail/2021/08/05/russia-and-kenya-take-the-podium-in-the-athletics-doping-contest</a><o:p></o:p></span></p><p class="MsoNormal"><span style="font-family: arial; font-size: medium;"> </span></p><p class="MsoNormal"><span style="font-family: arial; font-size: medium;">I was also featured in an article in the Daily Telegraph newspaper (unfortunately behind a firewall).<o:p></o:p></span></p><p class="MsoNormal"><span style="font-family: arial; font-size: medium;"> </span></p><p class="MsoNormal"><span style="font-family: arial; font-size: medium;"><a href="https://www.telegraph.co.uk/athletics/2021/08/15/catching-suspected-dopers-remains-game-whack-a-mole-tokyo/">https://www.telegraph.co.uk/athletics/2021/08/15/catching-suspected-dopers-remains-game-whack-a-mole-tokyo/</a><o:p></o:p></span></p><p class="MsoNormal"><span style="font-family: arial; font-size: medium;"> </span></p><p class="MsoNormal"><span style="font-family: arial; font-size: medium;">If you don’t have time to follow these links, my take home messages about the Tokyo Olympics are:<o:p></o:p></span></p><p class="MsoNormal"><span style="font-family: arial; font-size: medium;"> </span></p><p class="MsoListParagraphCxSpFirst" style="mso-list: l0 level1 lfo1; text-indent: -18.0pt;"><!--[if !supportLists]--><span style="font-family: arial; font-size: medium;">·<span style="font-stretch: normal; line-height: normal;"> </span><!--[endif]-->It is unclear how much the pandemic has impacted on the effectiveness of out-of-competition anti-doping tests in the run up to the Olympics. Presumably it has been slightly easier to avoid being caught although it also might have been difficult to procure and effectively use doping methods. <o:p></o:p></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -18.0pt;"><!--[if !supportLists]--><span style="font-family: arial; font-size: medium;">·<span style="font-stretch: normal; line-height: normal;"> </span><!--[endif]-->The IAAF’s Athlete Integrity Unit (AIU) are having an impact. I was surprised there was not more media outcry over the significant number of athletes not allowed to compete in the game because they were not tested enough, apparently through no fault of their own. I guess the list of athletes and the countries they represented did not appear high enough profile for the Western media I follow, although I suspect there was more outcry in the countries themselves, such as Nigeria. <a href="https://www.independent.co.uk/sport/olympics/olympics-tokyo-athletes-drug-testing-b1892437.html">https://www.independent.co.uk/sport/olympics/olympics-tokyo-athletes-drug-testing-b1892437.html</a><o:p></o:p></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -18.0pt;"><!--[if !supportLists]--><span style="font-family: arial; font-size: medium;">·<span style="font-stretch: normal; line-height: normal;"> </span><!--[endif]-->We saw one highly significant event; the readmission of essentially the whole Russian team; this despite the Russian anti-doping agency still not being WADA compliant and no admission from Russia that there was any state involvement in cheating. This seems to have put this issue to bed, perhaps in a not altogether satisfactory manner. We await to see how IOC, WADA and CAS deal with the next state player that is involved in doping. It seems the precedent has been set for a mild rebuke for the county concerned. An individual who is selected by that country will still be able to compete with zero penalties unless doping evidence exists against that specific individual. Countries themselves will never suffer the ultimate sanction of their athletes not being allowed to compete in the Olympics. Time will tell if this works as any kind of deterrent. <o:p></o:p></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -18.0pt;"><!--[if !supportLists]--><span style="font-family: arial; font-size: medium;">·<span style="font-stretch: normal; line-height: normal;"> </span><!--[endif]-->The issue of potentially non-performance enhancing drugs being on the banned list arose (at least in the US media) because of the positive test for cannabis of Sha'Carri Richardson in the US Olympic trials. This case just seems to show that even the high-profile athletes in a country with a well-funded and assertive anti-doping agency, still don’t seem to treat the WADA list with enough seriousness. Richardson should have known she would likely be drug tested if she finished in the top three at the US trials and – so whatever her mental state at the time – her elite athlete warning bells should have sounded off that she was breaking a rule that would likely result in a ban. Given how well she ran at the trials, she was obviously superbly prepared in every other way to perform.<o:p></o:p></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -18.0pt;"><!--[if !supportLists]--><span style="font-family: arial; font-size: medium;">·<span style="font-stretch: normal; line-height: normal;"> </span><!--[endif]-->At the games themselves there were the usual spattering of positive tests. The cynical comment is that you only catch the “dopy” dopers at the Games themselves, as those in the know will be well aware of how long a drug lasts in their system and will arrive “clean”. It is true that sometimes a better detection method can catch dopers unawares. However, this happens rarely at the Games themselves, but instead when samples are retested over the next 10 years. Over 130 athletes were retrospectively stripped of their results from the Rio 2016 and London 2012 Games. Athletes who have doped at the 2021 Olympics can really only breathe a sigh of relief that they have got away with cheating when the samples they have given are destroyed in 2031. <o:p></o:p></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -18.0pt;"><!--[if !supportLists]--><span style="font-family: arial; font-size: medium;">·<span style="font-stretch: normal; line-height: normal;"> </span><!--[endif]-->In light of the above it was unusual that a positive test for one of the more high-profile track and field athletes - Blessing Okagbare – was reported at the Games. Okagbare tested positive for human growth hormone. However, although reported at the Games, the test was taken out-of-competition on 19 July. Despite already having received any performance benefit, she would probably have tested ‘clean’ when competing at the Games, again stressing the importance of out of competition testing (it should be noted that Okagbare has so far not admitted to any offence) <a href="https://www.athleticsintegrity.org/downloads/pdfs/disciplinary-process/en/AIU-PRESS-RELEASE-BLESSING-OKAGBARE-OF-NIGERIA-PROVISIONALLY-SUSPENDED.pdf">https://www.athleticsintegrity.org/downloads/pdfs/disciplinary-process/en/AIU-PRESS-RELEASE-BLESSING-OKAGBARE-OF-NIGERIA-PROVISIONALLY-SUSPENDED.pdf</a><o:p></o:p></span></p><p class="MsoListParagraphCxSpMiddle" style="mso-list: l0 level1 lfo1; text-indent: -18.0pt;"><!--[if !supportLists]--><span style="font-family: arial; font-size: medium;">·<span style="font-stretch: normal; line-height: normal;"> </span><!--[endif]-->Of course, for my own country the big issue was the sprinter CJ Ujah, who was one of the athletes in the 4 x 100m silver medal winning team. He tested positive for S23 and ostsarine – two Selective Androgen Receptor Modulators. These are on the banned list for two reasons. First they are aimed at improving muscle mass (like anabolic steroids) but without the adverse sex hormone side effects; and secondly they are both investigational drugs that are not approved for human use anywhere in the world. This doesn’t stop unscrupulous supplement companies adding them to their formulations. Of course, as they are not approved for human use, they won’t be listed on the label. It looks like this ‘mislabelling’ might be the defence CJ Ujah’s laywers will use. <a href="https://www.dailymail.co.uk/sport/olympics/article-9896225/CJ-Ujah-set-blame-labelling-error-positive-test-strip-GB-4x100m-relay-silver.html">https://www.dailymail.co.uk/sport/olympics/article-9896225/CJ-Ujah-set-blame-labelling-error-positive-test-strip-GB-4x100m-relay-silver.html</a>. <br />If Ujah still has the bottle in question, can get it retested and show it contains S23 and ostarine, this might just reduce the length of his penalty. But, I predict that the silver medal will still be lost, as he won’t be able to prove that he did not get a performance benefit from the drug in his system.<br /><br /><o:p></o:p></span></p><p class="MsoListParagraphCxSpLast" style="mso-list: l0 level1 lfo1; text-indent: -18.0pt;"><!--[if !supportLists]--><span style="font-family: arial; font-size: medium;">·<span style="font-stretch: normal; line-height: normal;"> </span><!--[endif]-->I am continually surprised why elite athletes insist on using supplements that have minimal performance benefit (unless they contain anbabolic steroids or SARMS of course). Taking ANY supplement seems a very high risk:reward ratio. It suggests athletes (or their coaches) have not carefully read or digested the comprehensive IAAF Consenus statement on nutrition. The only evidence-based supplements are caffeine, bicarbonate, beta-alanine, nitrate, and creatine (none of which are on the banned list) <a href="https://journals.humankinetics.com/view/journals/ijsnem/29/2/article-p73.xml">https://journals.humankinetics.com/view/journals/ijsnem/29/2/article-p73.xml</a>. <br />It follows that if an athlete sees performance benefits using any other supplement than these five, it is likely a placebo effect or due to a “contaminant” in the bottle. A contaminant that could get you a ban. </span><i><span style="font-family: arial; font-size: medium;">Caveat emptor. </span><span style="font-family: Helvetica;"><o:p></o:p></span></i></p><style class="WebKit-mso-list-quirks-style">
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</style>profchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com0tag:blogger.com,1999:blog-5197898174856470934.post-51046865039508581872019-10-07T07:25:00.001-07:002019-10-07T07:25:30.058-07:00Nobel Prize for working out how EPO works!<div style="font-family: "Times New Roman", serif; margin: 0cm 0cm 0.0001pt;">
<span lang="EN-US" style="font-family: -webkit-standard, serif;">It’s nice to blog about the science of EPO (erythropoietin) without immediately talking about doping for a change. Today three great scientists were awarded the Nobel Prize </span><span style="font-family: -webkit-standard, serif;">in Physiology or Medicine for working out how mammalian cells sense and adapt to oxygen availability. The science underpinning the award to William G. Kaelin Jr, Sir Peter J. Ratcliffe and Gregg L. Semenza <a href="https://www.nobelprize.org/uploads/2019/10/press-medicine2019.pdf" style="color: purple;">is described here.</a> </span></div>
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<span style="font-family: -webkit-standard, serif;">Most sports scientists and athletes know that EPO is a protein that increases the number of red blood cells. Altitude training increase levels of EPO and hence increases the number of red blood cells, </span><span lang="EN-US" style="font-family: -webkit-standard, serif;">increasing the amount of oxygen in the blood and potentially increasing performance. The discoveries of Semenza, Ratcliffe and Kaelin revealed that a protein called HIF-1 alpha </span><span lang="EN-US" style="font-family: -webkit-standard, serif;">binds to DNA and increases the production of several proteins including EPO. EPO then binds to other proteins that increase the synthesis of red blood cells. However, in the presence of oxygen HIF-1 alpha </span><span lang="EN-US"><span style="font-family: Symbol;">i</span></span><span lang="EN-US" style="font-family: -webkit-standard, serif;">s degraded inside the cell in a structure called the proteasome. Thus, when oxygen is abundant there is not enough </span><span lang="EN-US" style="font-family: -webkit-standard, serif;">HIF-1 alpha to bind to DNA, EPO levels fall to normal and red blood cell production decreases. <o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: -webkit-standard, serif;">Of course, directly injecting EPO or receiving a blood transfusion bypasses the clever biological pathways that safely regulate the number of red blood cells in the body that match oxygen supply and demand. Hence the reason for blood doping being banned in sport. In fact, if you look at current research following on from the work of </span><span style="font-family: -webkit-standard, serif;">Kaelin, Ratcliffe and Semenza, you can see other proteins that could be targeted to increase or decrease red blood cell production. This is relevant for developing new drugs to treat anaemia and cancer. Of course it could also be relevant to sports doping; the </span><span lang="EN-US" style="font-family: -webkit-standard, serif;">HIF-1 alpha/ EPO pathway is perhaps the most obvious “known unknown” when it comes to new drugs in sport. By this I mean, we know modifying this pathway could improve sports performance, but it is unknown if anyone is currently exploiting it. Or at least no one has been caught doing it, which amounts to the same thing. But it would not surprise me if people were trying.<o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: -webkit-standard, serif;">In a personal level this is the second time my research career has intersected with research that led to a Nobel Prize. <a href="https://www.nobelprize.org/prizes/medicine/1998/press-release/" style="color: purple;">The other time</a> was the role of the gas nitric oxide that controls blood flow in the body. It is one of the privileges of a scientific career to be close to seeing such clever people in action, even if that closeness sometimes just involves admiring their research at conferences and in publications. </span><span style="font-family: -webkit-standard, serif;"><o:p></o:p></span></div>
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profchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com0tag:blogger.com,1999:blog-5197898174856470934.post-16270928974622164312019-05-29T02:40:00.000-07:002019-05-29T02:40:04.985-07:00Expert reaction to Court of Arbitration for Sport (CAS) ruling on Caster Semenya’s appeal of the IAAF hyperandrogenism regulations<div style="margin: 0cm 0cm 0.0001pt;">
<span lang="EN-US"><span style="font-family: inherit;">I was on holiday during the CAS ruling on the appeal of the CAS hyperandrogenism regulations, so my comments are a bit late. The comments of the other experts who contacted the Science Media Centre can be found at this link<o:p></o:p></span></span></div>
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<a href="https://www.sciencemediacentre.org/expert-reaction-to-ruling-on-caster-semenya-appeal-regarding-athletes-with-differences-of-sex-development-and-testosterone-levels/" style="color: purple;"><span style="font-family: inherit;">https://www.sciencemediacentre.org/expert-reaction-to-ruling-on-caster-semenya-appeal-regarding-athletes-with-differences-of-sex-development-and-testosterone-levels/</span></a><br />
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<span style="color: #111111;"><span style="font-family: inherit;">"In my personal opinion, the IAAF regulations have as good a scientific basis as they are going to get in the foreseeable future. HOWEVER, this does not mean that they are ethically ‘right’. That is a separate matter. We should focus on the ethics of what we want to encourage as participation in female sport, and not get hung up on criticising the fine details of science that is never going to be as conclusive as we would like.<o:p></o:p></span></span></div>
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<span style="font-family: inherit;"><span style="color: #111111;">Although they have not released their detailed reasoning, the CAS decision to disallow the Caster Semenya and Athletics South Africa appeals is not surprising given their previous opinion in the case of Dutee Chand. Chand appealed against the <a href="https://www.tas-cas.org/fileadmin/user_upload/award_internet.pdf"><span style="border: 1pt none windowtext; color: #0c4da2; font-family: inherit, serif; padding: 0cm;">IAAF’s original hyperandrogenism regulations</span></a></span><span style="color: #111111;">. </span></span><span style="color: #111111; font-family: inherit;">In the Chand case, CAS ruled that discrimination based on requiring a defined level of plasma testosterone was permitted if “</span><i style="font-family: inherit;"><span style="border: 1pt none windowtext; color: #111111; padding: 0cm;">on the balance of probabilities the Regulations are a proportionate means of achieving the legitimate objective of ensuring fairness in athletics competition</span></i><span style="color: #111111; font-family: inherit;">.” The Court did not have a fundamental issue with the discrimination itself. It just had to be scientifically justified. The IAAF were then given “</span><i style="font-family: inherit;"><span style="border: 1pt none windowtext; color: #111111; padding: 0cm;">the opportunity to provide the CAS with scientific evidence about the quantitative relationship between enhanced testosterone levels and improved athletic performance in hyperandrogenic athletes</span></i><span style="color: #111111; font-family: inherit;">.” The IAAF then brought forward new regulations based on scientific evidence claiming that there was a significant advantage in certain events, specifically 400m, 800m, 1500m and mile. So the new case hinged not on whether discrimination is justified, but instead how large were the benefits of increased (natural) endogenous testosterone in female athletes. This new IAAF data was based on comparing performance of elite athletes at these distances with their testosterone levels. The published correlational data partially support this decision at 400m and 800m, but are less clear for the mile and 1500m (although scientifically it is hard to see why benefit at 800m would not partially transfer into a benefit at 1500m). Hence the current CAS Panel suggestion that the IAAF “</span><i style="font-family: inherit;"><span style="border: 1pt none windowtext; color: #111111; padding: 0cm;">consider deferring the application of the DSD Regulations to these events until more evidence is available</span></i><span style="color: #111111; font-family: inherit;">.”</span></div>
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<span style="color: #111111; font-family: inherit;">By asking the IAAF to use science to determine quantitively the specific advantage raised testosterone levels bring in elite athletes, CAS are, in my opinion, asking science to do too much. Proving evidence at the level of a specific event for individual athletes is only possible if you are allowed to drop or increase these levels in a controlled manner and measure the change in performance. Some of this individual data may indeed be in the final CAS report (although likely in redacted form). However, even then, individual hyperandrogenic DSD athletes will likely respond differently to changes in their testosterone levels. So any percentage change in performance would not be readily transferable to other DSD athletes. In effect the request for the IAAF to respond to the Chand ruling for more science was doomed to provide some light, but also more confusion. It is likely that this is the reason for the verdict being majority, and not unanimous.</span></div>
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<span style="font-family: inherit;"><span style="color: #111111;">Testosterone increases during development are clearly the dominant, if not sole, reason why male athletes outperform female athletes. The science is reasonably clear that DSD athletes with raised tesosterone levels will have some performance benefit even if their body only partly responds to those increased levels. But other factors clearly contribute to performance. In this context it is worth noting that Caster Semenya won the London 2012 800m when the original IAAF DSD regulations requiring lowered tesosterone were in force; the regulations were lifted for the Rio Olympics and she then won by greater margin. Using the IAAF regulations to handicap athletes with DSDs will have an effect on performance, but will likely not prevent them competing at an elite level. It seems to me predominantly an ethical, not scientific, question whether such discrimination is a “</span><i><span style="border: 1pt none windowtext; color: #111111; padding: 0cm;">necessary, reasonable and proportionate means of achieving the IAAF’s aim of preserving the integrity of female athletics in the Restricted Events.</span></i><span style="color: #111111;">” Asking science to work at the level of granularity requested by CAS of the IAAF is part of the problem not the solution. Instead athletes and the public need to decide if they are happy with the percentage of DSD athletes being significantly over-represented at the elite level, compared to their prevalence in the general population. Adopting the IAAF regulations would decrease this over-representation, but likely not eliminate it entirely. I think this is predominantly a societal question rather than a scientific one.<o:p></o:p></span></span></div>
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<span style="font-family: inherit;"><i><span style="border: 1pt none windowtext; color: #111111; padding: 0cm;">Is there a link to current regulations on transgender athletes and doping?</span></i><span style="color: #111111;"><o:p></o:p></span></span></div>
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<span style="color: #111111;"><span style="font-family: inherit;">The IAAF testosterone regulations regarding DSD (differences in sexual development) need to be seen in the light of their (and the IOC’s) anti-doping and transgender regulations. This is NOT to say that females with DSD or male to female transgender athletes are cheating of course. But the science underpinning the possible performance benefits of their situation is related. And in many cases – perhaps surprisingly – the doping data is easier to access.<o:p></o:p></span></span></div>
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<span style="color: #111111;"><span style="font-family: inherit;">On doping regulations: there is good evidence that increasing exogenous testosterone levels (or taking artificial anabolic steroids) enhances sport performance. This effect is greater in females than males. It is (partially) reversible if anabolic steroids stop being taken. It is no surprise that anabolic steroids preferentially enhanced performance in female athletes in the former East Germany (where they were likely given to junior athletes). Nor that the Russians state doping system had some of its greatest ‘successes’ when giving anabolic steroids to female middle distance runners. Therefore doping is banned.<o:p></o:p></span></span></div>
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<span style="color: #111111;"><span style="font-family: inherit;">On transgender regulations: lowering plasma testosterone levels is the main goal of male to female transgender hormone therapy. Transgender women, who are transitioning or have transitioned from male to female, are treated with hormones (by choice) to lower their plasma testosterone levels to similar levels as required by the IOC regulations. This decreases their performance. Therefore they are allowed to compete in a female category after hormone therapy to lower their testosterone.<o:p></o:p></span></span></div>
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<span style="color: #111111;"><span style="font-family: inherit;">Nothing about elite sports performance is ever going to be amenable to scientific conclusions ‘beyond reasonable doubt’. This is because the fractional differences in competition at the highest level are so small and the population so difficult to study ethically and practically. In my opinion the current evidence is as good as we are going to get to show that both endogenous (natural) and exogenous (doped) testosterone levels enhance female sports performance. In the terms of the Court of Arbitration of Sport, I am personally “comfortably satisfied” that both exogenous and endogenous testosterone increases sports performance in elite female athletes. Of course a lot of other factors, genetic and environmental, also affect sports performance, but that is a separate story."</span><span style="font-family: Georgia, serif; font-size: 13.5pt;"><o:p></o:p></span></span></div>
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profchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com0tag:blogger.com,1999:blog-5197898174856470934.post-50655432589694815932019-03-24T16:56:00.001-07:002019-03-24T16:56:17.350-07:00Expert reaction to editorial about testosterone, women athletes, and rules in elite sportReferring to my last blog the Science Medic Centre has now posted all three of its expert opinions. So you can read them for yourself and see how three experts can come to somewhat different opinions about the same paper. Actually two of them pretty much agreed and one didn't, but now you can read for yourself and make up your own mind.<br />
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<a href="http://www.sciencemediacentre.org/expert-reaction-to-editorial-about-testosterone-women-athletes-and-rules-in-elite-sport/">http://www.sciencemediacentre.org/expert-reaction-to-editorial-about-testosterone-women-athletes-and-rules-in-elite-sport/</a><br />
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Meanwhile the Court of Arbitration for Sport has received new material from both sides of the argument.<br />
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<a href="https://www.tas-cas.org/en/general-information/news-detail/article/semenya-asa-and-iaaf-planning-update.html">https://www.tas-cas.org/en/general-information/news-detail/article/semenya-asa-and-iaaf-planning-update.html</a><br />
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The decision is now delayed from his coming Tuesday (March 26) until the end of Aprilprofchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com0tag:blogger.com,1999:blog-5197898174856470934.post-84190320706291754442019-03-21T04:49:00.001-07:002019-03-21T04:49:57.946-07:00Caster Semenya, IAAF, testosterone levels and editorial in British Medical Journal<div class="MsoNormal" style="font-family: "Times New Roman", serif; margin: 0cm 0cm 0.0001pt;">
<span style="font-family: Helvetica;">I was asked by the <a href="https://www.sciencemediacentre.org/" style="color: purple;">Science Media Centre</a> to provide an expert reaction to an editorial about testosterone, women athletes, and rules in elite sport, as published in the <i>British Medical Journal. </i>The article can be found at this link. <o:p></o:p></span></div>
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<span style="font-family: Helvetica;"><a href="https://www.bmj.com/content/364/bmj.l1120" style="color: purple;">https://www.bmj.com/content/364/bmj.l1120</a><o:p></o:p></span></div>
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<span style="font-family: Helvetica;">As well as my “biochemical” comment, the Science Media Centre received two other expert comments from endocrinologists. Interestingly, whilst one endocrinologist wrote a very short note supportive of the article, the other was highly critical and wrote a lengthy piece outlining the editorial’s scientific shortcomings. I’ll see if I have permission to post that article later on this blog as it is really interesting and chimes with what I think. <o:p></o:p></span></div>
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<span style="font-family: Helvetica;">Interestingly my opinion was quoted very differently (but still correctly) by both the <a href="https://www.bbc.co.uk/news/health-47640359" style="color: purple;">BBC</a> and the <a href="https://www.dailymail.co.uk/health/article-6830651/Controversial-testosterone-rule-female-athletes-unscientific-experts-warn.html?ns_mchannel=rss&ito=1490&ns_campaign=1490" style="color: purple;">Daily Mail</a>! <o:p></o:p></span></div>
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<span style="font-family: Helvetica;">As I say at the end of my piece, there are some good reasons to drop the IAAF regulations on differences in sexual development (DSD). But I don’t think bad supporting science is one of them. In the words of TS Eliot from the play Murder in the Cathedral:<o:p></o:p></span></div>
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<span style="font-family: Helvetica;"> “The last temptation is the greatest treason: To do the right deed for the wrong reason”. <o:p></o:p></span></div>
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<b><span style="font-family: Helvetica;">My full expert opinion on the <a href="https://www.bmj.com/content/364/bmj.l1120" style="color: purple;">BMJ editorial</a> follows below:<o:p></o:p></span></b></div>
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<span lang="EN-US" style="font-family: Helvetica;">First the closer overlap between male and female plasma testosterone levels in elite sport noted in this paper is perhaps not surprising for a number of reasons:</span><span style="font-family: Helvetica;"><o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: Helvetica;">(a) Increases in plasma testosterone in female athletes (in part due to differences in sexual development, DSD) are likely to improve performance more than similar increases in men. Therefore women with higher testosterone levels will probably be overrepresented in elite athletes. It is well known that the proportion of conditions leading to high testosterone levels is higher in elite female athletes compared to the male population. </span><span style="font-family: Helvetica;">For example at the Atlanta 1996 Olympics several female athletes tested positive for the SRY gene on a Y chromosome. SRY induces testosterone production during puberty so this likely led to increased levels of plasma testosterone. This testosterone was considered not to be having an effect on their body (androgen insensitivity syndrome, AIS). So an XY apparently “male” genotype led to a female phenotype. The prevalence of AIS in the non elite athlete population is much lower than the 7 in 3387 found in this sample of Olympians. This suggests that increased testosterone levels either do still slightly increase performance in some AIS females OR make them more likely to choose to become athletes. Either way, this is ONE example of why testosterone levels in female elite athletes may have a closer overlap with male elite athletes than in the population at large.<o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: Helvetica;">(b) Taking artificial anabolic steroids will likely lower the levels of the natural anabolic steroid (testosterone) in athletes. These effects can potentially be quite long term. Without knowing the number of athletes previously steroid doping in any sample this is difficult to correct for. I suspect because of the greater adverse side effects in female athletes rather than males, males take higher steroid doses than females. This would result in anabolic steroid use lowering the natural male testosterone levels more than the female levels, again closing the gap and increasing the overlap.</span><span style="font-family: Helvetica;"><o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: Helvetica;">(c) The major physiological effects of plasma testosterone levels occur during puberty. However, it is not possible to test at puberty in future elite athletes. By its very nature any later testing is of somewhat secondary value. So an elite male athlete might have low testosterone now, but at the crucial time in their development it was significantly different from the future elite female athlete. It is hard to see how any data can be collected in this area. So the IAAF make do with what they can actually measure.</span><span style="font-family: Helvetica;"><o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: Helvetica;">Second, gathering hormone data in elite sport is difficult. It is even harder (and potentially unethical) to gather performance data under conditions where these hormone levels are made to drop or rise due to external factors. Therefore by its very nature correlation data of the type described in this article will become important. But it is individual data that really matters, and this is even harder to get access to for the obvious grounds of medical confidentiality. As the authors mention Caster Semenya, it is perhaps instructive to look at her 800m times* at global championships when the IAAF testosterone levels were in place or not. This is worth mentioning as you can be sure the same discussion has been had amongst other female elite athletes (and also athletics fans). In periods when the testosterone regulations were not in place Semenya won all the global championships she competed in. When they were in place she ran slower and was second to cross the line at global championships. The winner those times (Mariya Savinova) was banned for doping (possibly by taking substances including anabolic steroids) and thus possibly giving her the same advantage by cheating that Semenya (who was not cheating) had been denied by the IAAF regulations.</span><span style="font-family: Helvetica;"><o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: Helvetica;">Third, the IAAF testosterone regulations regarding DSD (differences in sexual development) – although not mentioned explicitly – need to be seen in the light of their (and the IOCs) anti doping and transgender regulations. This is not mentioned by the authors of this article, but seems relevant. This is NOT to say that females with DSD or male to female transgender athletes are cheating of course. But the science underpinning the possible performance benefits of their situation is related. And in many cases – perhaps surprisingly – the doping data is easier to access.</span><span style="font-family: Helvetica;"><o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: Helvetica;">On doping regulations: there is good evidence that increasing exogenous testosterone levels (or taking artificial anabolic steroids) enhances sport performance. This effect is greater in females than males. It is (partially) reversible if anabolic steroids stop being taken. It is no surprise that anabolic steroids preferentially enhanced performance in female athletes in the former East Germany (where they were likely given to junior athletes). Nor that the Russians state doping system had some of its greatest ‘successes’ when giving anabolic steroids to female middle distance runners. Therefore doping is banned.</span><span style="font-family: Helvetica;"><o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: Helvetica;">On transgender regulations: lowering plasma tesosterone levels is the main goal of male to female transgender hormone therapy. </span><span style="font-family: Helvetica;">Transgender women, who are transitioning or have transitioned from male to female, are treated with hormones (by choice) to lower their plasma testosterone levels to similar levels as required by the IOC regulations. This decreases their performance. Therefore they are allowed to compete in a female category after hormone therapy to lower their testosterone.<o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: Helvetica;">Nothing about elite sports performance is ever going to be amenable to scientific conclusions “beyond reasonable doubt”. This is because the fractional differences in competition at the highest level are so small and the population so difficult to study ethically and practically. In my opinion the current evidence is as good as we are going to get to show that both endogenous (natural) and exogenous (doped) testosterone levels enhance female sports performance. In the terms of the Court of Arbitration of Sport, I am personally “comfortably satisfied” that both exogenous and endogenous testosterone increases sports performance in elite female athletes. Of course a lot of other factors, genetic and environmental, also affect sports performance, but that is a separate story.</span><span style="font-family: Helvetica;"><o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: Helvetica;">Summing up, in my personal opinion, the IAAF regulations have as good a scientific basis that they are going to get in the foreseeable future. HOWEVER, this does not mean that they are ethically “right”. That is a separate matter. I write as someone who personally cheered Caster Semenya on to victory in the 800m in the 2017 World Athletic Championships in London (when the DSD regulations were not in force). However, we should focus on the ethics of what we want to encourage as participation in female sport, and not get hung up on criticising the fine details of science that is never going to be as conclusive as we would like.</span><span style="font-family: Helvetica;"><o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: Helvetica;">Finally, I caution against the authors making too much of the effects sport has on the real world. They say <i>“History compels us to ensure that decisions about genetic superiority are supported by objective, rigorous, and reproducible data”</i> and <i>“These issues highlight the fact that although sports policies exist to serve the organisations that develop them, the effect of these policies on individuals, societies, and even medical science has far reaching implications.”</i> Sport – and especially elite sport – as we know it is a social construct created by (largely) males at the end of the 19th Century. We have chosen in society to place a huge value on it and honour its participants with wealth and fame. But it is inherently sexist. </span><span style="font-family: Helvetica;">Biological females have no chance of competing on an equal footing with males – in terms of physical sports performance they demonstrably can’t compete. Equality of opportunity in sport does NOT equal equality of outcome. In fact it does not come close. In nearly all adult sports there would be NO female winners if we did not have a separate female category. This is unlike any other activity we value in our society. Therefore elite sport has created a special protected space for females (female sport). Inevitably this creates tension at the interface as noted in this article. But it is important that writers – such as the authors – do not try and put sport on a pedestal. Decisions, such as those of the IAAF, relate to the rather special social construction of the sporting world. We should note give them added importance by trying to translate them into more important parts of life and society. The Olympic Charter claims that the practice of sport is a human right. Well this may be the case, but in my opinion it is low on the list of ones that we should use as an example of how to construct how we run our society.”<o:p></o:p></span></div>
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<i><span lang="EN-US" style="font-family: Helvetica;">* Caster Semenya times:</span></i><span style="font-family: Helvetica;"><o:p></o:p></span></div>
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<i><span lang="EN-US" style="font-family: Helvetica;">Pre regulation requiring testosterone levels to be dropped (2009 World Championship Berlin): Winner, 1:55.45</span></i><span style="font-family: Helvetica;"><o:p></o:p></span></div>
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<i><span lang="EN-US" style="font-family: Helvetica;">Post Regulation (2011 World Championships Daegu): Second*, 1:56.35</span></i><span style="font-family: Helvetica;"><o:p></o:p></span></div>
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<i><span lang="EN-US" style="font-family: Helvetica;">Post Regulation (2012 Olympics London): Second*, 1:57.23</span></i><span style="font-family: Helvetica;"><o:p></o:p></span></div>
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<i><span lang="EN-US" style="font-family: Helvetica;">Regulations dropped (2016 Olympics Rio): Winner, 1:55.28</span></i><span style="font-family: Helvetica;"><o:p></o:p></span></div>
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<i><span lang="EN-US" style="font-family: Helvetica;">Regulations dropped (2017 World Championships London): Winner, 1:55.16.</span></i><span style="font-family: Helvetica;"><o:p></o:p></span></div>
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<i><span lang="EN-US" style="font-family: Helvetica;">* upgraded to Winner after Mariya Savinova disqualified for doping offences (likely including anabolic steroids).</span></i><span style="font-family: Helvetica;"><o:p></o:p></span></div>
profchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com0tag:blogger.com,1999:blog-5197898174856470934.post-63529950843909880462018-12-14T15:26:00.000-08:002018-12-14T15:26:51.921-08:00An overview of the last five years of drugs in sport and doping science<div class="MsoNormal" style="font-family: "Times New Roman"; margin: 0cm 0cm 0.0001pt;">
<span style="font-family: Helvetica;"><a href="http://www.kinpodo-pub.co.jp/shosai/f0810-1757-3.html" style="color: purple;"><i>Run, Swim, Throw, Cheat </i>has just been published in a Japanese edition</a>. I am very pleased that there is still interest in a book published in 2012. When introducing this edition, I felt it was worth writing an extended update of the doping science scene during the last six years - or at least the five years since I write a new introduction for the 2013 paperback edition of the book. I thought it also might make an interesting – if somewhat lengthy – blog entry for readers of this blog who can’t read Japanese. So here is the English version of the introduction. <o:p></o:p></span></div>
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<b><span style="font-family: Helvetica;">Introduction to Japanese edition of Run, Swim, Throw, Cheat <o:p></o:p></span></b></div>
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<i><span style="font-family: Helvetica;">Run, Swim, Throw, Cheat </span></i><span style="font-family: Helvetica;">was published just in time for the London 2012 Olympics; this was not a coincidence of course! However, most of its subject matter does not date rapidly and everything you will read in this Japanese translation is as sound scientifically as it was when written. Minor updates on new drugs and testing methods were included in the blog I write (and occasionally update) at <a href="http://www.runswimthrowcheat.com/" style="color: purple;">www.runswimthrowcheat.com</a>.<o:p></o:p></span></div>
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<span style="font-family: Helvetica;">What does change is the stories that illustrate the science. Most notably the Lance Armstrong Tour de France scandal came to light the year following that in which the book was published. There is not even a hint of his wrongdoing in the original printing of the book. This was remedied in the 2013 paperback version and much of the introduction I wrote for that edition is given over to discussing the Armstrong saga. <o:p></o:p></span></div>
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<span style="font-family: Helvetica;">The London 2012 Olympics itself had few doping scandals during the event itself, although I did manage to witness the one medal that was overturned. The culprit was the Byelorussian shot putter, Nazdeya Ostapchuk (when you read this book you will realise that it is not surprising that shot putters, especially female ones, are particularly able to benefit from doping). At the time I was sat in the Olympic stadium next to a New Zealand journalist who was cheering for Valerie Adams to retain her gold medal. She did just that, but only received it much later when Ostapchuk was disqualified by the International Olympic Committee (IOC) for doping.<o:p></o:p></span></div>
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<span style="font-family: Helvetica;">The drug Ostapchuk had in her system was the anabolic steroid, metenolone. Athletes seem to favour this steroid as it is claimed to have fewer androgenic (i.e. sexual) side effects. I was surprised that Ostapchuk was caught at the games. I stress in this book that careful planners will stop taking a drug long enough before a prestigious event so it is out of their system when they compete. Although Ostapchuk has never admitted her doping, I thought at the time that she – or her team – must have made a miscalculation. Indeed at her disciplinary hearing she was given a shortened one-year ban, as it was claimed her coach, Alexander Yefimov, had drugged her food. In the words of the head of the Belarusian anti-doping agency, Alexander Vanhadlo, "Yefimov confessed that he added the banned drug metenolone into Ostapchuk's food because he was worried by her unimpressive results ahead of the Olympics”. Yefimov was then banned for four years by the Belarus' national anti-doping agency</span><span style="font-family: Helvetica;">.</span></div>
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<span style="font-family: Helvetica;">However, subsequent events show it was not an isolated incident. Recent re-tests of old urine samples using more modern and sophisticated techniques mean that eight athletes, including Ostapchuk, have since been found guilty of doping at the 2005 World Championships in Helsinki by the International Association of Athletics Federations (IAAF) and at the 2008 Olympic games in Beijing by the IOC. The emerging story is that Ostapchuk (or her team) were using drugs that at the time they thought could not be detected. It now looks like improvements in analytical techniques mean they got their timings wrong for when she should come off the drug. Strike one up for the anti-dopers!<o:p></o:p></span></div>
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<span style="font-family: Helvetica;">There is a depressing note associated with this story. Immediately after the shot put final, the UK discus thrower, Brett Morse, tweeted from the Olympic village that Ostapchuk must be doping; his evidence was primarily that she looked like a man. Readers of my blog will know how much I disagree with unsubstantiated accusations about named athletes. This just tars everyone, even clean athletes, with the doper’s label. Quite rightly Morse was criticized at the time and the offending tweet removed. The fact that Ostapchuk was stripped of her medal was, of course, not surprisingly subsequently seen by Morse as a vindication of his tweet. Since writing this book, I have met many clean athletes unfairly accused of doping – especially on the internet. Morse’s tweet, especially as its substance did proved correct, might have the undesirable effect of leading to more of these unfair accusations. Indeed during London 2012, the biggest “doping” scandal was centred on the Chinese swimmer Ye Shiwen who has never tested positive for doping before or since these games. The suspicion was merely based on her breaking the world record. In the current suspicious times, it pays to not win your event by too large a margin…. <o:p></o:p></span></div>
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<span style="font-family: Helvetica;">Yet, the real scandal of the 2012 Olympics was only revealed five years later, when the full extent of Russia’s state doping system was revealed by a combination of the whistle blowers Grigory Rodchenkov and </span><span lang="EN" style="font-family: Helvetica;">Yuliya Stepanova</span><span style="font-family: Helvetica;">, the German reporter </span><span lang="EN" style="font-family: Helvetica;">Hajo Seppelt </span><span style="font-family: Helvetica;">and the Independent Commission reports of the World Anti Doping Agency (WADA) chaired by Dick Pound and Richard McLaren. Exactly how many Russian were doping in London 2012 (and of course later in the 2014 Winter Olympics in Sochi) will never be known, but as a consequence of retesting, 29 London medals had been returned for doping offences, 13 of which were from the Russian team. As a personal experience visiting the London games in my home city were an amazing uplifting experience, with some of the happiest crowds I had ever seen in the city. How they would have felt if they had known at the time that this level of cheating was occurring is not difficult to imagine. I should mention at this point that Russia still denies it was involved in a “state sponsored” doping regime. This denial is why - as of 2018 – the country is still banned from the Paralympics by the International Paralympic Committee (IPC), although the International Olympic Committee (IOC) has seen fit to reinstate them into the Olympic community. <o:p></o:p></span></div>
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<span style="font-family: Helvetica;">What is clear from London 2012 and Sochi 2014, is that, however clever the drug testing, it is irrelevant if the testers themselves are corrupt; and the state have a unique ability to cover up this kind of cheating. Clever science will always be trumped by clever politics. What is perhaps more interesting from a scientific point of view is that the kind of doping Russian athletes were involved in was not too different from what was found to be effective over 40 years earlier by the East German state sponsored system. Whilst there were some newer drugs of potential - if not scientifically verified - performance benefit such as meldonium, the core of the program was anabolic steroids to increase strength and power in, especially, female athletes. In fact the main difference was possibly the use of lower doses so that the female athletes were less obviously over muscled, decreasing suspicion that they were doping. Where there was a difference is that the effectiveness of blood doping (EPO, blood transfusions) had been discovered since the East German program; this benefitted both male and female athletes. It is one of the conclusions of my book that the real “game-changing” benefits of doping come from anabolic steroid use by female athletes in “power” events and blood doping by male and female athletes in “endurance” events. This conclusion, has if anything, been confirmed by what the Russian whistle-blowers and WADA reports revealed of the Russian program. <o:p></o:p></span></div>
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<span style="font-family: Helvetica;">There was a backlash against WADA, IOC and IPC led by the Russian government and various hacker groups such as <i>Fancy Bears</i>. The Russians complained that they had been unfairly singled out as there was widespread doping elsewhere. This could perhaps be called the “Lance Armstrong” defence. Armstrong claims he should keep his seven Tour de France titles as his rivals were cheating at the same time. Although, in my opinion their abuses were generally more flagrant then their rivals, the Russians and Armstrong were correct that cheating is widespread in sport. Two other Tour de France winners lost their titles due to a doping offence and - if 13 out of 29 London 2012 medal cheats were Russians - 16 out of 29 were obviously not. In May 2016, at the same time as Russia was being investigated, the Anti-Doping Agency of Kenya was declared non compliant by WADA due to concerns about the implementation of its anti doping programs; Kenya only regained its compliance a day before the start of the 2016 Rio Olympics. In August 2013, Renee Anne Shirley, the former executive director of Jamaica’s Anti-Doping Commission (JADCO), revealed her concerns about a lack of adequate out-of-competition drug testing prior to the London 2012 Olympics. This led to an official audit of JADCO by WADA in November 2013, the resignation of the entire JADCO board, and subsequent improvements to the Jamaican anti doping program, following a new partnership with the Canadian Centre for Ethics in Sport. Although the situations described do not mean that individual athletes in these countries are guilty of doping, the lack of effective anti doping regimes in some countries will always make it harder to be confident that a sport is clean. <o:p></o:p></span></div>
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<span style="font-family: Helvetica;">The more interesting backlash, at least scientifically, came from the <i>Fancy Bears</i>hackers. They exposed the use of the Therapeutic Use Exemption (TUE) in athletes, claiming these were a form of “legalised” doping. None of the athletes concerned had committed any doping offence. Indeed, in many of the cases revealed by the cyber hackers, it is hard to see how the drugs taken could be beneficial to performance. But there is still an interesting discussion to be had around the science. TUEs are given for drugs designed to treat an athlete’s medical condition without enhancing performance; being performance “enabling” the intent is that they allow an athlete with a pre-existing medical condition to compete on a level playing field with their healthy peers. A concern is that athletes, their coaches and/or doctors, might “game” the system to their benefit. This was an accusation levelled at the British Olympic and Tour de France Champion cyclist, Sir Bradley Wiggins, over the unusual medication used to treat his severe seasonal hay fever, triamcinolone. Although not a first line medical treatment, as a powerful long lasting anti-inflammatory corticosteroid, triamcinolone is used by some doctors for treating hay fever and rhinitis. The critics’ claim is that a side effect of triamcinolone is weight loss, enabling a rider to lose weight but not power, a potential advantage for a cyclist in a climb. Although this is an interesting idea, the scientific evidence supporting this is weak and Wiggins and his then employers, Team Sky, strenuously denied any performance benefit for what was, it should be remembered, a WADA approved therapeutic use exemption.<o:p></o:p></span></div>
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<span style="font-family: Helvetica;">Another area that is causing current concern in Britain is the inhaled bronchodilator salbutamol, required for many athletes with asthma to breathe freely. A TUE is only required for salbutamol if you need to take an excess in a short period (essentially this equates to eight “puffs” in a eight hour period). It is not clear that exceeding this level is performance enhancing; there is little if any performance effect in short term studies, although WADA claim that over time at high dose it might increase muscle mass. However, once a limit is set, it must be policed. The British multi Tour de France winner, Chris Froome was recently investigated due to the high level of salbutamol recorded in his urine sample during his La Vuelta victory in 2017. The WADA doping threshold in a urine sample (1,000ng/ml) was set to be impossible to reach unless an athlete inhales more than the eight puff limit. However, this has been disputed by some recent scientific research, which shows that the rate of salbutamol transfer from drug inhalation to appearance in the urine is highly variable and it is indeed possible to exceed the limit when an individual is not exceeding the permitted inhalations.<o:p></o:p></span></div>
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<span style="font-family: Helvetica;">Froome and Team Sky disputed that he took too high a dose. The resultant case was all about the science. Could Froome convince the authorities that there is a plausible explanation for the anomalous urine reading? Is it possible given the conditions at the time for Froome to have exceeded the urine threshold whilst only taking the approved levels of the drug? Froome was under the doping limit throughout the rest of the Vuelta and indeed the whole season despite multiple testing in competition, so it seems highly unlikely that he was attempting the kind of long-term use that WADA claim can be performance enhancing. It is notable that few people reporting this case – even the Froome critics – claimed that he would have received a short-term performance benefit for any one off salbutamol abuse. The discussion focused on the science of the test and whether a rule was broken. A week before the start of the 2018 Tour de France, the cycling authorities (UCI) ruled that they were satisfied that Froome did not commit any offence, and WADA decided not to appeal the UCI’s decision. The UCI’s decision was based on experts’ interpretation of data provided by Team Sky and WADA including information about the specific circumstances of Froome’s metabolism of the drug. Sometimes it feels that following elite cycling is as much about the underpinning science as the action itself. It is perhaps no surprise that when I have given presentations about my book, the cycling fans are the most knowledgeable in the audience! <o:p></o:p></span></div>
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<span style="font-family: Helvetica;">Another area of sports science that has become a current hot topic since I wrote this book is the hyperandrogenism and transgender athletes in female sport. Hyperandrogenism is defined as a female with higher than average levels of the sex hormone tesosterone (i.e. in the male range), provided it has also been shown this hormone is able to be exert its physiological effect. <o:p></o:p></span></div>
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<span style="font-family: Helvetica;">This is not a doping issue; no one is claiming the athletes are cheating. However, some of the science is related. Most sports have separate male and female categories. Given the cynical view that some athletes will cheat if they feel they can get away with it, there has been concern as to whether males can get an advantage by masquerading as females. As I discuss in the book, the history of how to “police” this gender boundary has historically been fraught with difficulties and prejudice. In most sports the issue has been quietly forgotten about. However, changes in society have made this veil of ignorance harder to maintain. There is an increasing acceptance of transgender and intersex people as individuals that should not suffer prejudice for who they are. There is also an increasing number of countries where gender can legally be self-determined. These facts have brought sex and gender politics back to the forefront of the sporting regulators. <o:p></o:p></span></div>
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<span style="font-family: Helvetica;">The IAAF and – more recently – the IOC have attempted to scientifically categorise their female separate sports categories. Approved by the IAAF in 2011, the “<i>Regulations Governing Eligibility of Females With Hyperandrogenism to Compete in Women's Competition</i>” state that any female athlete with a level of testosterone above a stated value (i.e. in the “male range”) will not be allowed to compete until they had taken measures to reduce this value. Usually this would require some form of hormone or drug treatment. The IAAF argument was that the difference in sporting performance between elite men and women is predominantly due to higher levels of testosterone in men. This is why women tend to get excess benefits by doping with anabolic steroids (such as testosterone) when compared to men. Therefore it is “unfair” for someone with a natural high level of testosterone to compete as it gives them benefits akin to doping. Note that at no point did the IAAF blame a “hyperandrogenic” athlete nor argue that they were not a woman - just that they should not be allowed to compete in elite women’s sport without corrective treatment.<o:p></o:p></span></div>
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<span style="font-family: Helvetica;">An Indian sprinter – Dutee Chand – refused to lower her testosterone level and challenged the legality of the regulations at the Court of Arbitration for Sport (CAS). On 24 July 2015 CAS issued an Interim Award in the arbitration procedure. They suspended the regulations for two years to give the IAAF the opportunity to provide scientific evidence about the quantitative relationship between enhanced testosterone levels and improved athletic performance in hyperandrogenic athletes. To summarise a long case, essentially the IAAF had argued that natural (endogenous) testosterone gave a female athlete the equivalent benefit that dopers achieved using unnatural added (exogenous) testosterone. CAS did not dispute this idea in principle, but wanted to see proof. In the meantime, from 2015 onwards, female athletes were once again allowed to compete with no checks on their high testosterone levels. <o:p></o:p></span></div>
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<span style="font-family: Helvetica;">The CAS ruling led to a IAAF and WADA funded study that looked at over two thousand observations from elite athletes competing at the 2011 and 2013 IAAF World Athletics Championships. Measurements were made of blood levels of testosterone and comparisons made to performance. The key finding is that after dividing the athletes into thirds – high, medium and low testosterone – women in the highest testosterone category performed significantly better in 400m, 400m hurdles, 800m, hammer throw, and pole vault. In the 400m, 400m hurdles and 800m there was also a correlation between the higher testosterone levels and the amount of the blood oxygen carrying protein, haemoglobin. This pattern was not seen in any male events. </span><span lang="EN-US" style="font-family: Helvetica;">In a separate study, female athletes with serum testosterone concentrations in the normal male range performed on average 5.7% better when their serum testosterone levels were unrestricted, compared to when their serum testosterone levels were suppressed. </span><span style="font-family: Helvetica;"><o:p></o:p></span></div>
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<span style="font-family: Helvetica;">This new science led to the new IAAF eligibility rules for athletes with </span><i><span lang="EN-US" style="font-family: Helvetica;">differences of sex development</span></i><span lang="EN-US" style="font-family: Helvetica;">(DSD), requiring any female athlete with DSD to maintain her blood testosterone level below five (5) nmol/L to compete internationally in the </span><span style="font-family: Helvetica;">400m, 400m hurdles, 800m and 1500m. </span><span lang="EN-US" style="font-family: Helvetica;">This means that athletes such as Castor Semenya will need to have drug therapy to reduce their tesosterone levels, if they still want to compete in their preferred events. The IOC looks set to incorporate these same levels into their new guidelines for transgender athletes. In the latter case the justification, at least in part, is that current best medical practice is to target these lower levels as part of the transition from male to female for transgender individuals. <o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: Helvetica;">How does this relate to the doping issues I discuss in this book? London 2012 was the first Olympic games when </span><span style="font-family: Helvetica;">hyperandrogenic athletes, including world champions such as Castor Semenya competed under regulations restricting their tesosterone levels. Their running times did increase, though Semenya still won the 800m title. However, in the actual race she came second. First past the line was the Russian athlete, </span><span lang="EN" style="font-family: Helvetica;">Mariya Savinova.</span><span style="font-family: Helvetica;">However, in 2014 Savinova was caught in undercover video footage appearing to admit to injecting testosterone and taking the banned steroid oxandrolone. This led to a WADA re-investigation of her blood samples, which found that she had used blood doping between 2010 and 2013. She was subsequently banned by the IAAF for four years, a decision upheld by the Court of Arbitration for Sport (CAS) in February 2017. Savinova is currently appealing this decision, but as it stands, her London result has been forfeited and Semenya awarded the gold medal. So Savinova beat Semenya, but apparently (appeal pending) only by resorting to cheating, taking steroids to increase her muscle mass and blood doping to increase her haemoglobin levels. The 800 m is an event that requires both power (muscle mass) and endurance (oxygen delivery). Tesosterone gives males from birth increases in both muscle mass and blood haemoglobin. Doping or hyperandrogenism mimic these male advantages. <o:p></o:p></span></div>
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<span style="font-family: Helvetica;">If I was writing the prologue to my book again, I would focus not on Ben Johnson’s 100m Olympic win in Seoul nor even the five runners who passed the line one after the other in the 1500m final in Helsinki and who each at some point in their careers was found guilty of doping. Instead I would showcase the London 2012 Olympic games 800m race. Yes, there is complexity in the science of doping and, hopefully, my book will help you understand this and entertain you at the same time. But the key message is simple. What really works – and what is game changing – is the use of anabolic steroids to increase muscle mass (especially in female athletes) and the use of blood doping to increase haemoglobin content in all athletes. Everything else is just noise. <o:p></o:p></span></div>
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<span style="font-family: Helvetica;">It is not clear whether these new IAAF </span><span lang="EN-US" style="font-family: Helvetica;">DSD </span><span style="font-family: Helvetica;">regulations will stand the test of time or whether they will face a new legal challenge. Is it ethical to focus on just one genetic difference that enhances performance? Testosterone is the key sex defining hormone, but it is not the only performance defining molecule in females or males, many of which will be similarly genetically determined. Ultimately the answer will not be down to the science, but to what society will accept. I was fortunate enough to be back in the London Olympic stadium in 2017 for the World Athletics Championships. This event took place during the period when the IAAF hyperandrogenism regulations were suspended. I, along with 60,000 other sports fans, cheered Castor Semenya home to the 800m victory she was denied in London 2012. The same crowd that had roundly booed ex-doper Justin Gatlin’s victory in the 100m race, rose to their feet to support Semenya. The lack of any hyperandrogenism regulations did not seem to be stifling their cheers. It certainly did not feel like an unfair victory to those in the stadium. <o:p></o:p></span></div>
profchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com0tag:blogger.com,1999:blog-5197898174856470934.post-74282030428908729072018-10-26T07:48:00.000-07:002018-10-26T07:48:43.849-07:00Pseudoephedrine: does it work and why is it banned in sport?<div class="MsoNormal" style="-webkit-text-size-adjust: auto; -webkit-text-stroke-width: 0px; caret-color: rgb(0, 0, 0); color: black; font-family: "Times New Roman"; font-size: medium; font-style: normal; font-variant-caps: normal; font-weight: normal; letter-spacing: normal; margin: 0cm 0cm 0.0001pt; orphans: auto; text-align: start; text-decoration: none; text-indent: 0px; text-transform: none; white-space: normal; widows: auto; word-spacing: 0px;">
<span lang="EN-US" style="font-family: Arial;">I have just published an analysis of the scientific literature on the effectiveness of the banned stimulant pseudoephedrine in sport [1]. The full paper is free to read and can be accessed via this link: </span><span style="font-family: Arial;"><a href="https://t.co/CQ9N2y6iTG" title="https://rdcu.be/8EtB"><span style="color: #1da1f2; text-decoration: none;">rdcu.be/8EtB </span></a><span style="background-color: #f5f8fa; background-position: initial initial; background-repeat: initial initial; color: #14171a;">. </span></span><span lang="EN-US" style="font-family: Arial;">Like most research it was a team effort. The original research was undertaken by two talented ex-undergraduate students of mine - Maria Gheorghiev and Farzad Hosseini - as part of their University of Essex degree. An Essex PhD student Jason Moran (now at Hartbury University) re-analysed and re-interpreted the data, adding greatly to the final outcome. </span></div>
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<span lang="EN-US" style="font-family: Arial;">Being a scientific paper, I was forced to write in a somewhat formal style and rein in some of my more florid expressions. However, hopefully it should still make interesting reading for the intelligent layperson. <o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: Arial;">The key points from my paper were <o:p></o:p></span></div>
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<!--[if !supportLists]--><span style="font-family: Symbol; mso-ansi-language: EN-GB; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;"><span style="mso-list: Ignore;">·<span style="font: 7.0pt "Times New Roman";"> </span></span></span><!--[endif]--><span style="font-family: Arial;">Pseudoephedrine use increases heart rate during exercise, but there is no significant effect on time trial performance, perceived effort, or biochemical markers (blood glucose and blood lactate).<o:p></o:p></span></div>
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<!--[if !supportLists]--><span style="font-family: Symbol; mso-ansi-language: EN-GB; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;"><span style="mso-list: Ignore;">·<span style="font: 7.0pt "Times New Roman";"> </span></span></span><!--[endif]--><span style="font-family: Arial;">A small performance benefit could not be completely ruled out, especially in the younger and well-trained athletes of most concern to anti-doping agencies, <o:p></o:p></span></div>
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<!--[if !supportLists]--><span style="font-family: Symbol; mso-ansi-language: EN-GB; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;"><span style="mso-list: Ignore;">·<span style="font: 7.0pt "Times New Roman";"> </span></span></span><!--[endif]--><span style="font-family: Arial;">However, any performance benefit of pseudoephedrine is marginal and certainly less than that obtained through permitted stimulants such as caffeine<o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: Arial;">For those of you who are unfamiliar with </span><span style="font-family: Arial;">pseudoephedrine it is the safest and most effective nasal decongestant available. It clears up the symptoms of blocked nose and sinuses during colds and flu, although it has no effect on the overall progress of the disease. Although available in most countries over the counter, its use is restricted, primarily over concerns that it is used as a precursor in the production of the recreational drug “crystal meth”. For those of you familiar with the TV show “Breaking Bad”, it is the “pseudo” that the characters use to make meth in their RV, before switching to more productive precursors when they move to industrial level production. </span><span style="font-family: Arial;"><o:p></o:p></span></div>
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<span style="font-family: Arial;">In sport, as outlined in my article, the regulation of pseudoephedrine has a chequered history. It has been banned, unbanned and then banned again. As I say in my book, the most tragic case was that </span><span lang="EN-US" style="font-family: Arial;">of the sixteen-year-old Rumanian gymnast Andreaa Răducan. At the 2000 Sydney Olympics the Rumanian women’s gymnastics team obtained a clean sweep of medals in the overall event. Răducan took the gold. However, she subsequently tested positive for </span><span style="font-family: Arial;">pseudoephedrine; her gold medal was withdrawn. The drugs test was as a result of a cold that had struck many members of the Rumanian team. The team doctor had prescribed the painkiller Nurofen, which in its form as a cold medication contains pseudoephedrine. The minimum level of pseudoephedrine allowed in a urine drugs test is not corrected for body mass. Răducan, being the lightest gymnast, registered over the limit; her teammate Simona Amanar, who finished second, also tested positive for pseudoephedrine, but was below the banned level. Amanar was consequently awarded the gold medal – but she then boycotted the medal ceremony claiming that Răducan was the true champion. </span><span lang="EN-US" style="font-family: Arial;"><o:p></o:p></span></div>
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<span style="font-family: Arial;">Given what we know was going on at the Sochi 2014 Winter Olympics games, it is rather ironic that the most high profile positive test actually reported at the Games was not for anabolic steroids or blood doping, but a humble nasal decongestant. The Swedish ice hockey team were deprived of the use of the star player Nicklas Backstrom, just before the gold medal ice hockey game. Shorn of their star player, Sweden were convincingly beaten by Canada 3-0. </span><span style="font-family: Arial;">Backstrom had tested positive for pseudoephedrine. He was taking (and declared on his doping control form) </span><span lang="EN-US" style="font-family: Arial;">Zyrtec-D, a pill that contains both an anti histamine and pseudoephedrine. It seems that he had been taking it every day for seven years. WADA does have a lower limit of pseudoephedrine that does not result in a ban. When tested, Backstrom’s pill put him just over this limit. There are a issues about the timing of the Backstrom ban (just before the ice hockey final) that have caused a lot of upset in Sweden. The controversy did not end after the Games. Originally not awarded a silver medal, the IOC reinstated him and awarded his medal in March 2014. WADA then appealed this decision to the Court of Arbitration for Sport in November 2014. Finally in January 2015, the dispute was settled and B</span><span style="font-family: Arial;">ackstrom</span><span style="font-family: Arial;"><span lang="EN-US">ended with a reprimand, but was allowed to retain his medal.<o:p></o:p></span></span></div>
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<span lang="EN-US" style="font-family: Arial;">I know WADA have more pressing issues to deal with at the moment (to put it mildly!). But it does seem to me that the WADA banned list could do with some significant pruning to remove these drugs and medicines such as pseuodoephedrine that - even if they are potentially performance enhancing - are clearly not “game changing” compared to current, legitimate supplements and methods that athletes are allowed to make use of. The asthma medication Salbutamol, as used by Chris Froome in the Vuelta a Espana -<span> </span>could probably also fall into this category. But that is a subject for my next blog. <o:p></o:p></span></div>
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<span style="font-family: Arial;"><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6173670/">[1] Gheorghiev, M. D., Hosseini, F., Moran, J., and Cooper, C. E. (2018) Effects of pseudoephedrine on parameters affecting exercise performance: a meta-analysis. Sports Med Open 4, 44. 10.1186/s40798-018-0159-7</a></span><span style="font-family: Helvetica;"><o:p></o:p></span></div>
profchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com0tag:blogger.com,1999:blog-5197898174856470934.post-73437217635621404712017-10-18T04:49:00.001-07:002017-10-18T04:52:28.276-07:00“Gender doping”: should women with high testosterone be allowed to compete in athletics?<div class="MsoNormal">
<span lang="EN-US" style="font-family: "helvetica"; mso-bidi-font-family: Helvetica;">At the University of Essex we have just started a new MSc. in Sports
and Exercise Science [1]. As part of my drugs in sport module, I am getting my
students to examine a “hot” research paper each week. They do the background
reading and then we discuss the paper together asking the questions: Why was
the research done? What did the research find? What were the problems and
limitations of the study? What are the consequences for sport? <o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: "helvetica"; mso-bidi-font-family: Helvetica;">I am really enjoying this type of small group teaching. The nine
students are a mix of UK and overseas, some straight from undergraduate degrees
and others with real world experience. The discussions are lively and they all
bring different ideas to the table.<o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: "helvetica"; mso-bidi-font-family: Helvetica;">The first paper we discussed [2] was one about a condition called </span><span style="font-family: "helvetica"; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">hyperandrogenism<span style="mso-spacerun: yes;"> </span>- where someone
has excess levels of the natural anabolic steroid testosterone. </span><span lang="EN-US" style="font-family: "helvetica"; mso-bidi-font-family: Helvetica;">The
paper is about to play a key role in the upcoming (any day now!) verdict from
the Court of Arbitration of Sport with regards to the IAAF’s </span><span style="font-family: "helvetica"; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">hyperandrogenism regulation. Approved in 2011 [3], the “<i style="mso-bidi-font-style: normal;">Regulations Governing Eligibility of Females
With Hyperandrogenism to Compete in Women's Competition</i>” state that any
female athlete with a level of testosterone above a stated value (i.e. in the
“male range”) will not be allowed to compete until they had taken measures to
reduce this value (usually this would require hormone treatment). The IAAF
argument was that the difference in sporting performance between elite men and
women is predominantly due to higher levels of testosterone in men. This is why
women tend to get excess benefits by doping with anabolic steroids (such as
testosterone) when compared to men. Therefore it is “unfair” for someone with a
natural high level of testosterone to compete as it gives them benefits akin to
doping. Note that at no point did the IAAF blame a “hyperandrogeic” athlete nor
argue that they were not a woman - just that they are not allowed to compete in
elite women’s sport (there is a distinction here if you look hard enough I
guess).</span><span lang="EN-US" style="font-family: "helvetica"; mso-bidi-font-family: Helvetica;"><o:p></o:p></span></div>
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<span style="font-family: "helvetica"; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">An Indian sprinter – Dutee Chand – refused
to take treatment to lower her testosterone and challenged the legality of the regulations
at the Court of Arbitration for Sport (CAS). On 24 July 2015 CAS issued an
Interim Award in the arbitration procedure [4]. They suspended the regulations
for two years to give the IAAF the opportunity to provide scientific evidence
about the quantitative relationship between enhanced testosterone levels and
improved athletic performance in hyperandrogenic athletes. I can recommend
reading the full award; it is a fascinating discussion of this difficult area [5].
However, to summarise a long case, essentially the IAAF had argued that natural
(endogenous) testosterone gave a female athlete the equivalent benefit of
unnatural added (exogenous) testosterone. The IAAF did not dispute this idea in
principle, but wanted to see proof. Hence the two-year study that culminated in
the research paper I discussed with my students [1, 2]. In the meantime with
the regulations suspended Dutee Chand and other hyperandrogenic athletes were
allowed to compete with their natural (high) levels of testosterone [6]. <o:p></o:p></span></div>
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<span style="font-family: "helvetica"; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">The IAAF and WADA funded study was published
in the British Journal of Sports Medicine [2]. The study looked at over two
thousand observations from elite athletes competing at the </span><span lang="EN-US" style="font-family: "helvetica"; mso-bidi-font-family: Helvetica;">2011
and 2013 IAAF World Championships. Measurements were made of blood levels of
testosterone and comparisons made to performance. I have some potential issues
with the statistics used in that they seemed a bit too generous towards finding
a performance association, but perhaps that is a story for another day. The key
finding, that no doubt will be forwarded to CAS, is that after dividing the
athletes into thirds – high, medium and low testosterone – women in the highest
testosterone category performed significantly better in 400m, 400m hurdles, 800m,
hammer throw, and pole vault with margins of 2.73%, 2.78%, 1.78%, 4.53%, and
2.94%, respectively. This pattern was not seen in any male events. <span style="mso-spacerun: yes;"> </span><o:p></o:p></span></div>
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<span style="font-family: "helvetica"; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">So what did my students think of it? Well
they made some great observations. Perhaps the most interesting was that the
effects were restricted to so few events. Results in many power-based events showed
no association with increased testosterone. Indeed in the 100m, 100m hurdles
and 200m those with the highest testosterone performed worse than those with
the lowest testosterone. The difference was not <i style="mso-bidi-font-style: normal;">scientifically significant</i>, but clearly is heading in the wrong
direction for the IAAFs case. However, it could be <i style="mso-bidi-font-style: normal;">legally significant</i> given Dutee Chand<span style="mso-spacerun: yes;"> </span>- who bought the case after all – is a 100m sprinter!<span style="mso-spacerun: yes;"> </span><o:p></o:p></span></div>
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<span style="font-family: "helvetica"; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">Actually what was not observed is almost as
important as what was. Across female track and field events there was no
association of testosterone levels with discipline i.e. elite female athletes
in strength events such as shot putters and sprinters do not have higher
testosterone than those competing in distance events like the 10,000m and
marathon. Even more surprising (at least to me as an oxygen “expert”), the
levels of the oxygen carrying protein hemoglobin were not greater in the
“aerobic” events. This result is hidden away in Supplementary Table 8 if you
want to find it. There is a trend for sure, but I would have expected the
difference to be more evident, given that we know that long distance runners
are doing all they can within the rules (altitude training, sleeping in low
oxygen tents) and without the rules (EPO, blood doping) to increase their hemoglobin;
something sprinters don’t bother with at all. <o:p></o:p></span></div>
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<span style="font-family: "helvetica"; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">The fact that a biochemical marker like
hemoglobin that athletes can manipulate and that is known to affect performance
shows such a poor association with performance, does question the whole idea of
these kind of “association studies” even when they include so many athletes. <o:p></o:p></span></div>
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<span style="font-family: "helvetica"; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">Of course the real problem with this study
is that it is – quite rightly - limited by ethics. None of the female
testosterone values in this study were in the “male” range. Otherwise the
athletes would have been banned at that time of course. The best way to prove
that hyperandrogenism is equivalent to testosterone doping is to dope elite athletes
with testosterone for a short time. Then look at their performance when they
are on and off the steroids. Does the increase and decrease mirror those seen
when a hyperandrogenic athlete comes on and off hormone therapy to vary their
natural levels of testosterone? Good luck getting that study through a
university ethics committee! <o:p></o:p></span></div>
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<span style="font-family: "helvetica"; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">One final point is that the paper also
looked at male athletes. Unlike with women, the study did find that male sprinters
had increased testosterone levels compared to other events. However, in no
event was there any association of an individual’s testosterone level with
performance in that event. In the discussion the authors’ suggest there is
“sigmoidal” curve associating testosterone levels and performance. For women
this means that increasing testosterone can have a large effect on performance
(the association curve is steep), but at the higher values seen in men the relationship
smooths out and is undetectable. Of course this begs the question. Why is taking
testosterone and other anabolic steroids banned for male athletes, if the performance
benefit is so marginal as to be unmeasurable? I am not sure the IAAF and WADA
can have things both ways. If associations with performance can be used to ban
female hyperandrogenic athletes from performing, then surely the lack of such
an association can be used to unban male anabolic steroid dopers? I think
Shakespeare called this being hoist on your own petard [see Hamlet Act 3, scene
4). <o:p></o:p></span></div>
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<span style="font-family: "helvetica"; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">What ever CAS decides, at least my students
enjoyed discussing the paper. “Much better than my undergraduate teaching said
one”. Given I taught him as an undergraduate, this was a somewhat back handed
compliment, but I’ll take it anyway! <span style="mso-spacerun: yes;"> </span><o:p></o:p></span></div>
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<span style="font-family: "helvetica"; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">Onwards and upwards ….next week we are
discussing a controversial paper that suggests <span style="mso-spacerun: yes;"> </span>that <span style="mso-spacerun: yes;"> </span>blood doping does not increase performance in
long distance aerobic sports events such as cycling [7]. Can’t wait……<o:p></o:p></span></div>
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<span style="font-family: "helvetica"; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">[1] </span><span lang="EN-US" style="font-family: "helvetica"; mso-bidi-font-family: Helvetica;">MSc. in Sports and
Exercise Science, University of Essex, UK<o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: "helvetica"; mso-bidi-font-family: Helvetica;"><a href="https://www.essex.ac.uk/courses/pg01127/1/msc-sport-and-exercise-science">https://www.essex.ac.uk/courses/pg01127/1/msc-sport-and-exercise-science</a><o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: "helvetica"; mso-bidi-font-family: Helvetica;">[2] Bermon S, Garnier PY (2017) Serum androgen levels and their
relation to performance in track and field: mass spectrometry results from 2127
observations in male and female elite athletes. Br. J. Sports Med. 51:1309-1314.<o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: "helvetica"; mso-bidi-font-family: Helvetica;">The paper can be downloaded from the IAAF web page: <a href="https://www.iaaf.org/news/press-release/hyperandrogenism-research">https://www.iaaf.org/news/press-release/hyperandrogenism-research</a><o:p></o:p></span></div>
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<span style="font-family: "helvetica"; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">[3] IAAF to introduce eligibility rules for
females with hyperandrogenism ; IAAF news April 2011 <o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: "helvetica";"><a href="https://www.iaaf.org/news/iaaf-news/iaaf-to-introduce-eligibility-rules-for-femal-1">https://www.iaaf.org/news/iaaf-news/iaaf-to-introduce-eligibility-rules-for-femal-1</a></span><span lang="EN-US" style="font-family: "helvetica"; mso-bidi-font-family: Helvetica;"><o:p></o:p></span></div>
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<span style="font-family: "helvetica"; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">[4]<span style="mso-spacerun: yes;"> </span>CAS
media release: <i style="mso-bidi-font-style: normal;">CAS suspends the IAAF
hyperandrogenism regulations </i>Lausanne, July 27, 2015 <o:p></o:p></span></div>
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<span style="font-family: "helvetica";"><a href="http://www.tas-cas.org/fileadmin/user_upload/Media_Release_3759_FINAL.pdf">http://www.tas-cas.org/fileadmin/user_upload/Media_Release_3759_FINAL.pdf</a></span><span style="font-family: "helvetica"; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;"><o:p></o:p></span></div>
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<span style="font-family: "helvetica"; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">[5]<span style="mso-spacerun: yes;"> </span>Dutee
Chand v IAF and IAAF, Interim Arbitral Award delivered by the Court of
Arbitration of Sport,<span style="mso-spacerun: yes;"> </span>July 27, 2015 <o:p></o:p></span></div>
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<span style="font-family: "helvetica"; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;"><a href="http://www.tas-cas.org/fileadmin/user_upload/award_internet.pdf">http://www.tas-cas.org/fileadmin/user_upload/award_internet.pdf</a><o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: "helvetica"; mso-bidi-font-family: Helvetica;">[6] The most famous current elite female athlete is the South
African World and Olympic 800 m champion, Caster Semenya. Since the lifting of
the IAAF regulations her success has come under some criticism from fellow
athletes. <o:p></o:p></span></div>
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<u><span lang="EN-US" style="font-family: "helvetica"; mso-bidi-font-family: Helvetica;"><a href="https://www.youtube.com/watch?v=-fZcc6mLg5c">https://www.youtube.com/watch?v=-fZcc6mLg5c</a></span></u><span style="font-family: "helvetica"; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;"><o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: "helvetica"; mso-bidi-font-family: Helvetica;">However, it was notable that this is not necessarily shared by the
athletics watching public. I was at the London Olympic Stadium two months ago
when the crowd were right behind her during her race, in her post racer
interview and during the medal ceremony. <o:p></o:p></span></div>
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<u><span lang="EN-US" style="font-family: "helvetica"; mso-bidi-font-family: Helvetica;"><a href="https://www.youtube.com/watch?v=eck0WpgIT58">https://www.youtube.com/watch?v=eck0WpgIT58</a></span></u><span style="font-family: "helvetica"; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;"><o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: "helvetica"; mso-bidi-font-family: Helvetica;">[7]<span style="mso-spacerun: yes;"> </span>[Heuberger J, Rotmans JI,
Gal P et al (2017) Effects of erythropoietin on cycling performance of well
trained cyclists: a double-blind, randomised, placebo-controlled trial. <i style="mso-bidi-font-style: normal;">Lancet Haemato</i>l 4:e374-e386.<o:p></o:p></span></div>
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<span style="font-family: "helvetica"; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;"><a href="http://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(17)30105-9/fulltext">http://www.thelancet.com/journals/lanhae/article/PIIS2352-3026(17)30105-9/fulltext</a><o:p></o:p></span></div>
profchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com0tag:blogger.com,1999:blog-5197898174856470934.post-32310644414057940482016-10-21T06:15:00.000-07:002016-10-21T06:15:37.405-07:00DENY, DENY, DENY. Gene doping: the future of theatre?<div class="MsoNormal">
<i style="mso-bidi-font-style: normal;"><span lang="EN-US" style="font-family: Helvetica; mso-bidi-font-family: Helvetica;"><a href="https://www.parktheatre.co.uk/whats-on/deny-deny-deny">Deny, Deny, Deny <span style="font-style: normal;">is written by Jonathan Maitland and is due to open at
the Park Theatre, London on November 2<sup>nd</sup></span></a></span></i><span lang="EN-US" style="font-family: Helvetica; mso-bidi-font-family: Helvetica;">. I was
the scientific advisor for this play, which deals with a female sprinter
tempted into experimenting with gene doping. I wrote a short piece for the
program notes, which I reproduce below [note that the last line does not mean I
particularly think any athlete is currently gene doping, although this possibility
can’t be ruled out entirely].<o:p></o:p></span></div>
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<span style="font-family: Helvetica; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">“In 2006 anti doping agencies got the
information they had always feared.<span style="mso-spacerun: yes;">
</span>Police raiding the home of famous German athletics coach, Thomas
Springstein, found this email on his computer: <i style="mso-bidi-font-style: normal;">The new Repoxygen is hard to get. Please give me new instructions soon
so that I can order the product before Christmas.”</i> Repoxygen was an
experimental drug developed by UK biotechnology company Oxford Biomedica. It
was designed to treat anaemia by injecting extra copies of the human
erythropoietin (EPO) gene.<o:p></o:p></span></div>
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<br /></div>
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<span style="font-family: Helvetica; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">EPO is a small protein that increases the
number of oxygen carrying red blood cells in the body. Activating the EPO gene
increases the levels of EPO protein, increasing the number of red blood cells,
enhancing oxygen delivery and improving performance in long distance “aerobic”
sports. Clean athletes try to increase their own levels of EPO by altitude
training. Others, like the cyclist Lance Armstrong, injected synthetic EPO
directly - a process explicitly banned by the World Anti Doping Agency.
Synthetic EPO is detectable, albeit with difficulty. It also needs multiple
injections. How much better coach Springstein thought to inject the EPO gene
itself? This gene would continue to make increased undetectable levels of EPO,
creating a gene doped super athlete! <o:p></o:p></span></div>
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<span style="font-family: Helvetica; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">We don’t know whether Springstein ever got
hold of his black market Repoxygen. We do know that Oxford Biomedica stopped
making it; a combination of poorer than expected animal trials and the ready
availability of new versions of cheap, synthetic EPO protein made further development
uneconomic. Market forces, rather than the vigilance of anti doping agencies
saved the day for clean sport in this instance. <o:p></o:p></span></div>
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<br /></div>
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<span style="font-family: Helvetica; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">Gene doping sits at the heart of <i style="mso-bidi-font-style: normal;">Deny, Deny, Deny</i>. So what is it and is
the plot scientifically feasible? Gene doping is the bastard child of gene
therapy. It uses the same molecular tools but aims at different outcomes.
Whilst gene therapy attempts to cure genetic diseases such as cystic fibrosis
and thalassemia, gene doping aims to improve how well elite athletes can run, swim
or throw.<o:p></o:p></span></div>
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<br /></div>
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<span style="font-family: Helvetica; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">In the 1970s gene therapy was touted as
heralding a new age of medicine. Is gene doping a similar game changer in
sports cheating? The basic science is scarily cheap. You can teach students the
principle in a school project and even get them to make a “dummy” gene
construct. There is an analogy here with nuclear weapons. Everyone knows the
basic theory of how to make one. But the problem - and expense - lies in the
fine details of the engineering. In gene therapy the multi million pound expense
is not in creating the new gene, but in making the final product effective and
safe. As a result there are only a handful of genetic diseases that are
currently treated by gene therapy; the cost of gene therapy per patient runs
into the hundreds of thousands of pounds.</span></div>
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<span style="font-family: Helvetica; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">It is easy to envisage gene doping
increasing the speed of female sprinters. It would only require injecting a
gene that causes a slight increase in levels of testosterone – the natural male
anabolic steroid - to increase female muscle mass and enable a sprinter to
power to victory in the 100m or 200m. But given the costs is gene doping too
expensive and impractical to be successful without the backing of Big Pharma or
a rogue state? I think not. If you had “looser” ethics and were willing to
trade off safety for low cost and high performance, it is easy to envisage an
unscrupulous coach persuading a scientist to inject a gene that would increase
the performance of a female sprinter. Perhaps they already have …….”<o:p></o:p></span></div>
profchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com0tag:blogger.com,1999:blog-5197898174856470934.post-25761282602742216852016-08-31T10:18:00.000-07:002016-08-31T10:18:08.989-07:00Bloody Olympics: Rio, 2016, and the history of illegal blood doping <span style="background-color: white;"><span style="color: #4d4d4d; font-family: liberation-sans, sans-serif;">The below is a reprint of a bog I wrote for Oxford University Press to </span></span><span style="color: #4d4d4d; font-family: liberation-sans, sans-serif;">coincide with the Olympics. Nothing new really, but it was nice to put things in a historical context. To see the original story (with pictures) go to </span><a href="http://blog.oup.com/2016/08/rio-2016-history-blood-doping/">http://blog.oup.com/2016/08/rio-2016-history-blood-doping/</a><br />
<br />
Throughout history
blood has been imbued with magical properties. Drinking blood was viewed as a
source of power for many mythical beasts centuries before the invention of the
modern vampire myth. In Greek mythology Odysseus can revive the dead by giving
them blood to drink. But all blood is not the same – the blood from the veins
on the left side of the snake-headed Gorgon Medusa is deadly, that from the
right side is life-giving. In 1489 the Italian philosopher Marsilio Ficino,
proposed that drinking the blood of healthy young men could rejuvenate the sick
and elderly. Indeed it seems that an attempt was made to cure Pope Innocent
VIII of his stroke by giving him blood from three ten year old boys. More
dramatically the Hungarian princess and serial killer, Countess Elizabeth of
Bathory, was alleged to have drained all the blood from over 600 young girls to
feed her restorative blood baths.<br />
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
<span style="mso-ansi-language: EN-GB;">Drinking fresh blood
was supposed to give you strength, maybe eternal life if you were a vampire.
Even in the post-enlightenment age, the first blood transfusions had nothing to
do with the modern notion of enhancing oxygen supply; instead they were
supposed to heal by replacing old bad blood with strong healthy animal blood.<i style="mso-bidi-font-style: normal;"><o:p></o:p></i></span></div>
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<br /></div>
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<span style="mso-ansi-language: EN-GB;">Sport has long had a fascination
with blood. The blood of the Roman gladiators, moppped by a sponge from the
arena, fed a profitable business; perhaps the athlete’s ultimate commitment to
promoting their brand? Today blood is even more relevant to sport. Indeed
arguably its use and abuse in sport today has come close to destroying the
Olympic movement. <o:p></o:p></span></div>
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<br /></div>
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<span style="mso-ansi-language: EN-GB;">The modern fascination
with blood in the Olympics arose from the new discipline of sports science in
the 1960s and 1970s. <span style="mso-spacerun: yes;"> </span>A key driver was
the 1968 Mexico City Olympics where physiologists recognized the difficulty of getting
sufficient oxygen to tissue in the rarefied 2km high air. Red blood cells transfusions
increase the amount of oxygen given to people suffering from trauma or anaemia.
It was therefore argued that healthy athletes could be given “excess” blood to
increase their ability to deliver oxygen to tissue, and hence enhance their
performance in endurance sport? <o:p></o:p></span></div>
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<br /></div>
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<span style="mso-ansi-language: EN-GB;">Scandinavian
scientists were first to prove this - in 1972, Björn Ekblom at the Institute of
Physiology of Performance in Stockholm, showed a 25% increase in stamina after
a transfusion. It was subsequently alleged that Scandinavian athletes were
putting this laboratory method into practice. Lasse Viren won double gold
medals on the track in 5,000m and 10,000m at the 1972 and 1976 Olympics.
Unproven allegations of blood doping dogged Viren, who always denied them
claiming that altitude training and “reindeer milk” were the keys to his
enhanced performance. Some of his teammates did later confess to blood doping,
however, most notably Kaarlo Maaninka at the 1980 Olympics. Maaninka received
no sanction, which might surprise today’s readers given that blood doping is
one of the main reasons we will not see the Russian track and field team
competing at these Olympics. However, although in the 1970s and 1980s blood
doping was viewed as morally dubious, it did not break any rules. The anti doping
effort of the time focussed more on amphetamines and anaboloic steroids. <o:p></o:p></span></div>
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<br /></div>
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<span style="mso-ansi-language: EN-GB;">This would change in
the 1980s. The LA Olympics in 1984 was the watershed event. There was extensive
use of blood transfusions including by several members of the highly successful
US cycling team. Again no rules were broken, but the IOC had had enough and banned
blood doping in 1985. However, they had no way of testing for this form of
cheating, so it presumably continued in secret. In fact the ready availability
of genetically engineered EPO in the late 1990s, a difficult to detect drug
that increases the number of red blood cells more gradually and naturally than a
blood transfusion, undoubtedly increased the use of banned methods. I could
fill most of the rest of this article with a list of Olympic athletes who are
confirmed or strongly suspected of using EPO and/or blood transfusions to aid their
performance. <o:p></o:p></span></div>
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<br /></div>
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<span style="mso-ansi-language: EN-GB;">So where are we now? Blood
is a part of the Olympics and always will be. Whilst not imbuing you with the
mythical life giving properties of Odysseus, optimizing your number of red
blood cells is a key part of success in endurance events. </span>I can guarantee that
every medal winner in a long distance endurance event will have had their blood
measured frequently by support scientists to conform the success of their training
program, whether that program uses permitted (altitude training, sleeping in
low oxygen tents) or banned (EPO, blood transfusion) methods.</div>
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<br /></div>
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So much for Rio, what
about PyeongChang and the Winter
Olympics? This is, if anything, an even richer source of stories than
the summer games. There are claims of
athletes chosen for ski teams solely so that are the right blood group to donate
blood to their team leader; in 2006 a disgraced ex Austrian ski coach crashed
his car into a roadblock in the Italian alps, whilst attempting to escape the
police. But that’s a blog for two years time ……..</div>
profchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com0tag:blogger.com,1999:blog-5197898174856470934.post-45759502436823498942016-08-31T10:10:00.001-07:002016-08-31T10:10:21.633-07:00Rio Olympics 2016 and doping storiesMost of the interest for me happened pre the Games of course and the "will they, won't they" allow Russia to compete saga. Not surprisingly during the games my TV and radio interviews weren't about science, but about athletes response to other athletes. The extent of finger pointing was unusual for the Olympics, but less extreme than has happened at some other events e.g. Paula Radcliffe unfurling her "EPO cheats out" banner at the 2001 World Championship [1]. Still it was the Olympics so news outlets inevitably focussed on incidents such as the finger wagging between Yulia Efimova and Lilly King [2]. Until of course the light relief/black comedy provided by Ryan Lochte and his co-conspirators [3].<br />
<br />
The main story in my opinion though was the IPC being brave enough to ban Russia completely from the Paralympics. The world didn't end and the ban was even upheld by the Court of Arbitration for Sport. This rather put the lie to the IOC's passing of the buck to the national sporting organisations with its ridiculous one week timescale and wilful misreading of the nature of the McLaren WADA report [3].<br />
<br />
I didn't get asked much about the IPC decision though I did try to bring the contrast with the IOC into some of my interviews. Still I am now really looking forward to the Paralympics. Not clean, but cleaner......<br />
<br />
[1] <a href="https://www.theguardian.com/sport/2001/aug/10/athletics1">https://www.theguardian.com/sport/2001/aug/10/athletics1</a><br />
<br />
[2] <a href="http://www.independent.co.uk/sport/olympics/rio-2016-yulia-efimova-and-lilly-king-show-how-swimmings-code-of-honour-is-shot-to-pieces-by-ioc-a7179891.html">http://www.independent.co.uk/sport/olympics/rio-2016-yulia-efimova-and-lilly-king-show-how-swimmings-code-of-honour-is-shot-to-pieces-by-ioc-a7179891.html</a><br />
<br />
[3] <a href="http://www.breitbart.com/video/2016/08/22/john-oliver-destroys-ryan-lochte-labels-him-americas-idiot-sea-cow/">http://www.breitbart.com/video/2016/08/22/john-oliver-destroys-ryan-lochte-labels-him-americas-idiot-sea-cow/</a><br />
<br />
[4] <span style="font-family: Helvetica; font-size: 12pt;"><a href="https://www.theguardian.com/sport/2016/aug/04/richard-mclaren-ioc-wada-russia-rio-2016-">https://www.theguardian.com/sport/2016/aug/04/richard-mclaren-ioc-wada-russia-rio-2016-</a></span><br />
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<!--StartFragment--><!--EndFragment--><br />profchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com0tag:blogger.com,1999:blog-5197898174856470934.post-43223059995964307072016-03-11T13:08:00.000-08:002016-03-11T13:08:21.122-08:00Sharapova, Pound and Seppelt: Tacking Doping in Sport 2016<div class="MsoNormal">
<span lang="EN-US" style="font-family: Arial; mso-bidi-font-family: Arial;">I’ve just come back from this two-day conference at Twickenham stadium. To
get there I waited once again at the bus stop I used to spend my teenage life hanging
around – a situation made me feel both strangely young and
old at the same time. But what of the conference? You might expect a set of
talks from regulators and lawyers to be dry and drab. However, at times more
sparks flew than even at the most vitriolic academic meeting. Actually the
latter are usually sedate – though intellectually stimulating events – with
tempers and egos well in check (at least until the bar opens).<o:p></o:p></span></div>
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<br /></div>
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<span lang="EN-US" style="font-family: Arial; mso-bidi-font-family: Arial;">So what caused the fuss at Twickenham? Surprisingly it wasn’t the Maria
Sharapova meldonium affair. This just led to incredulity as to how someone
would keep taking a drug – for whatever reason – when it was so clearly
advertised as coming on to the banned list and an effective test had clearly
been developed. The fact that Sharapova has been joined by 99 other athletes in
the space of a few months suggests either a massive breakdown in anti doping
education or a significant level of stupidity amongst dopers. <o:p></o:p></span></div>
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<br /></div>
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<span lang="EN-US" style="font-family: Arial; mso-bidi-font-family: Arial;">So who did get everyone excited? Not Dick Pound for once with his usual
erudite exposition of Russia’s recent failings. Not even Jonathan Taylor from
Bird & Bird who did his best to wind up – well everyone really. No they
were both upstaged by the showing of Hajo Seppelt’s new ARD documentary; this
revealed that banned coaches were still active in Russia. He followed this up
with some direct barbs at the WADA president, Sir Craig Reedie, accusing him of
firing one of his top investigators and having a conflict of interest between his
role at WADA and the IOC (where he is a Vice President). <o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: Arial; mso-bidi-font-family: Arial;">I felt a little bit sheepish giving my own talk immediately after Hajo’s
Tour de Force. Especially as what I was talking about essentially amounted to
studying not doping. I discussed whether much of doping’s effectiveness could
be due to the power of the <i style="mso-bidi-font-style: normal;">placebo</i>
effect i.e. the athlete runs faster</span><span lang="EN-US" style="font-family: Helvetica; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;"> </span><span style="font-family: Helvetica; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">because they believe they have a secret advantage. This contrasts with
the <i style="mso-bidi-font-style: normal;">nocebo </i>effect, where the athlete
runs slower because they believe their opponent is doping and hence can’t be
beaten. The problem is to do the definitive placebo doping study I would need
to give EPO to a elite athletes whilst telling them I was giving them a meaningless
injection. This would reveal exactly how much of EPO’s benefit is due to its
biological, rather than its psychological effect. But it is hard to see a
research ethics committee agreeing to this level of deception. Such a pain when
morality gets in the way of a good piece of science! <o:p></o:p></span></div>
profchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com0tag:blogger.com,1999:blog-5197898174856470934.post-47683757042162579812015-09-09T12:08:00.000-07:002015-09-09T13:44:24.452-07:00Paula Radcliffe, Sky News and me <!--[if gte mso 9]><xml>
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<span style="font-family: Arial;">What I feared from my last blog has come true. It
looks as if athletes are going to be “forced” by media (or political!) pressure
to reveal their blood passport data – well every athlete who is successful in a
high profile sport at least. In this context I was interviewed after Paula
Radcliffe on Sky News this afternoon. When I finished the interviewer thanked me,
but said it was all very complex. Such a response would normally indicate I had failed as a
science communicator. In this case I think I succeeded in getting my point across.
Interpreting anomalous athlete biological passport data is non trivial. That is
why it requires three experts to agree in a blind test (not knowing who the
athlete is). Simple analysis can work on large data sets to indicate the potential
scale of a doping problem. It can’t be done to scapegoat an individual. <o:p></o:p></span></div>
profchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com0tag:blogger.com,1999:blog-5197898174856470934.post-782802339548513522015-08-20T11:12:00.000-07:002015-08-20T11:12:26.545-07:00Doping at the World Athletics Championships – part 1<div class="MsoNormal">
<span style="font-family: Arial; mso-ansi-language: EN-GB;">My
title indicates that I think these championships might take up more than one of
my blogs! Indeed the Sunday Times/IAAF doping story has already messed up my
holiday. I was pestered by well meaning journalists while visiting Yorkshire.
Fortunately I was for the most past saved by dodgy mobile phone signals and an
absence of Wifi. I did, however, make an exception to talk to Radio 5 live
Drive and Radio 4 pm in the BBC radio car parked in the local pub car park.
What could be more surreal? <o:p></o:p></span></div>
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<span style="font-family: Arial; mso-ansi-language: EN-GB;">It
has been hard commenting on the leaks given the fact that the various
protagonists (IAAF and the Sunday Times/</span><span style="color: #424242; font-family: Arial; font-size: 13.0pt;"> </span><span lang="EN-US" style="font-family: Arial;">ARD/WDR) have access to the data but have released only a very limited
amount into the public domain. The IAAF has indicated they will eventually
publish a “prevalence study” sometime in the future. Whether this will go so
far as to make comparisons between countries and whether it will also be
possible to compare individual sporting events remains to be seen. These of
course are the highlights of the leaks, but realistically might be excluded in
an academic type report. <o:p></o:p></span></div>
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<span style="font-family: Arial; mso-ansi-language: EN-GB;">So
what can be said and how does it relate to the upcoming World Athletics
Championships in Beijing? Well, starting with a selfish note, I am pleased that
the 1500m final in the women’s 2005 World Athletics championships is finally
getting the “recognition” it deserves [1]. In the opening pages of my book I
note that, far more than Ben Johnson’s 100m run in the Seoul Olympics, this
race deserved the moniker of the dirtiest race in history [2]. My comment that
the first five athletes to cross the line were alter found guilty of doping
(admittedly in later tests) has now been backed up by anomalous blood readings
taken at the time of the events. <o:p></o:p></span></div>
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<span style="font-family: Arial; mso-ansi-language: EN-GB;">It
is worth noting that the winning time in this infamous race was over a second
slower slower than when the clean athlete, Kelly Holmes, won the 1500m Olympics
title a year earlier. This brings me to my first substantive point. An
anomalous blood reading does not mean someone is necessarily doping. And even
if they are doping it does not mean that they won the race because they were
doping. Although there is good evidence in the scientific literature that increasing
your total haemoglobin levels increases athletic performance, there are
sparingly few results in elite athletes (where performance effects of ergogenic
aids naturally become smaller in size). Even the studies that have been done rarely
use a proper randomised placebo controlled design. There is no control for the
placebo effect. The importance of this cannot be underestimated; a placebo effect
is likely to be doubly powerful when taking a banned substance as these are
assumed to be especially powerful. Interestingly a recent randomised blind
trial on elite cyclists surprisingly showed no effect of altitude training and
suggested previous positive results might be mostly down to placebo [3]. <span style="mso-spacerun: yes;"> </span>“Unfortunately” it will be almost impossible
to do a similar study using EPO or blood doping due to ethical constraints
surrounding giving people potentially harmful drugs. Worse still the definitive
study would involve giving someone the drug and actively telling them they are
getting a placebo [4]; even using microdoses of EPO this would be a real ethical
minefield. <o:p></o:p></span></div>
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<span style="font-family: Arial; mso-ansi-language: EN-GB;">My
second substantive point relates to the success, or not, of the blood passport
program introduced in athletics by the IAAF in 2009. Clearly this has resulted
in a significant number of suspensions. But has it affected the number of
people doping? In cycling there seems to be a clear effect [5]. This was shown
by the drop in the number of cyclists showing abnormally high or low levels of
young red blood cells called reticulocytes (a recent blood transfusion will
likely give a low number and an injection of a high dose of EPO a high number).
The blood doping expert Michael Ashenden was reported in the Sunday Times as
saying that </span><span lang="EN-US" style="font-family: Arial;">“despite the
introduction of the biological passport, analysis of the data shows nearly 70
athletes with suspicious blood test results still escaped censure” [6]. This my
be so, but it would be very interesting to see his detailed analysis of whether
there was any change at all from 2009-2012. </span><span style="font-family: Arial; mso-ansi-language: EN-GB;"><o:p></o:p></span></div>
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<span style="font-family: Arial; mso-ansi-language: EN-GB;">The
relevant data outlining the effect of blood doping on the performance of elite
athletes is hidden from the average scientist in the secret files of doping
athletes and their coaches. Still my “not too controversial” personal view is
that blood transfusions and high dose EPO genuinely provide a performance
benefit in elite athletes. I am currently less convinced that micro dosing of
EPO, of the type designed to fool the biological passport, is as effective. It is
unlikely to create a situation where a clean athlete cannot win a race against
a doper. It is also possible that just by forcing the athletes to change doping
strategies to avoid detection, you make that doping less effective. <o:p></o:p></span></div>
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<span style="font-family: Arial; mso-ansi-language: EN-GB;">In
the worst-case scenario portrayed by the Sunday Times 30% of successful athletes
had anomalous blood readings and so might have been doping; but this still means
that 70% of athletes with “normal” blood readings managed to beat these dopers.
Doping is best seen as one part of a complex set of factors that lead to a gold
medal. It is only occasionally in sport that we see situations where it is
inconceivable that a clean athlete could beat a doper – the most notable being
the period in the 1970s and 1980s when female athletes were dosing with large
amounts of anabolic steroids. The Tour de France in the Armstrong years may
well be another example. <o:p></o:p></span></div>
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<span style="font-family: Arial; mso-ansi-language: EN-GB;">My
final point relates to one I was questioned by on BBC radio recently. Should
athletes reveal their own passport data? Even the athletes themselves are
divided on this [7, 8]. But I feel the cat is out of the bag now. Anyone with a
normal score is going to shout it from the rooftops. Those with anomalies will
be shamed for not revealing them – unless they have a really clear explanation
to hand. Anyone not revealing their scores will be assumed to be hiding their
data because they are doping. My major concern is that the internet will fill
up with well-meaning and not so well-meaning amateurs who will be able to
“prove” that someone is doping from their passport score. <o:p></o:p></span></div>
<div class="MsoNormal">
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<div class="MsoNormal">
<span style="font-family: Arial; mso-ansi-language: EN-GB;">We
have seen this effect with performance data in cycling for a number of years
now. The most recent example was the accusations of doping against Chris Froome
in the Tour de France in the complete absence of any analytical doping data [9]
or any intelligence about dodgy practices garnered from fellow team members
[10]. Another example: the UK 400m runner Roger Black is one of those now
calling for athletes to reveal their passport data [7]. Yet I remember him
telling me he was once confronted by a member of the public who said he could
tell he was cheating just by looking at some of the times he had posted. As
Paula Radcliffe [8] said you can never prove you are not doping. <o:p></o:p></span></div>
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<span style="font-family: Arial; mso-ansi-language: EN-GB;">I
suspect blood passport scores such as reticulocyte count, red cell volume and
haemoglobin concentration will soon become as well known to the world of online
sport comment as performance measures such as peak power, VO<sub>2</sub> max
and lactate threshold are now. In the conclusion of my book I said “W</span><span lang="EN-US" style="font-family: Arial;">hen it comes to making practical and
ethical policy there is a devil in the scientific detail that is absolutely
required if we are to make informed moral and political choices.” In athletics
and doping the time of science is upon us now. </span><span style="font-family: Arial; mso-ansi-language: EN-GB;"><o:p></o:p></span></div>
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<div class="MsoNormal">
<span style="font-family: Arial; mso-ansi-language: EN-GB;">[1] <span style="mso-spacerun: yes;"> </span><a href="https://www.blogger.com/August%202,%202015">Sunday Times <i style="mso-bidi-font-style: normal;">A clean sweep in the dirtiest race. </i>August
2, 2015</a><o:p></o:p></span></div>
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<span style="font-family: Arial; mso-ansi-language: EN-GB;">[2<a href="http://www.amazon.co.uk/Run-Swim-Throw-Cheat-science/dp/0199581460">] Cooper,
C.E. Run Swim Throw Cheat Oxford University Press (2012) Prologue (p 1-10).</a><o:p></o:p></span></div>
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<div class="MsoNormal" style="margin-right: -36.0pt; mso-layout-grid-align: none; mso-pagination: none; text-autospace: none;">
<span style="font-family: Arial; mso-ansi-language: EN-GB;">[3<a href="http://www.ncbi.nlm.nih.gov/pubmed/22033534">] <span lang="EN-US" style="font-family: Helvetica; mso-ansi-language: EN-US; mso-bidi-font-family: Helvetica;">C. Siebenmann, P. Robach, R.A. Jacobs, P. Rasmussen,
N. Nordsborg, V. Diaz, A. Christ, N.V. Olsen, M. Maggiorini, C. Lundby, Live
high-train low" using normobaric hypoxia: a double-blinded,
placebo-controlled study , Journal of Applied Physiology, 112 (2012) 106-117.</span></a></span><span lang="EN-US" style="font-family: Helvetica; mso-bidi-font-family: Helvetica;"><o:p></o:p></span></div>
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<span style="font-family: Arial; mso-ansi-language: EN-GB;">[4] <span style="mso-spacerun: yes;"> </span></span><span lang="EN-US"><a href="http://www.ncbi.nlm.nih.gov/pubmed/18091009"><span style="font-family: Arial;">A.J. Foad, C.J. Beedie, D.A. Coleman, Pharmacological and psychological
effects of caffeine ingestion in 40-km cycling performance, Med. Sci. Sports
Exerc., 40 (2008) 158-165.</span></a></span><span style="font-family: Arial; mso-ansi-language: EN-GB;"><o:p></o:p></span></div>
<div class="MsoNormal">
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<span style="font-family: Arial; mso-ansi-language: EN-GB;">[5]<span style="mso-spacerun: yes;"> </span><a href="http://dx.doi.org/10.1002/dta.173">M.
Zorzoli, and F. Rossi.<span style="mso-spacerun: yes;"> </span>Implementation of
the biological passport: The experience of the International Cycling Union Drug
Test Analysis, vol. 2, pp. 542-547 (2010)</a> <o:p></o:p></span></div>
<div class="MsoNormal">
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<div class="MsoNormal">
<span style="font-family: Arial; mso-ansi-language: EN-GB;"><a href="http://www.thesundaytimes.co.uk/sto/news/uk_news/thedopingscandal/article1588427.ece">[6]<span style="mso-spacerun: yes;"> </span>Sunday Times <i style="mso-bidi-font-style: normal;">Revealed: sport’s dirtiest secret . </i>August 2, 2015</a><o:p></o:p></span></div>
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<div class="MsoNormal">
<span style="font-family: Arial; mso-ansi-language: EN-GB;"><a href="http://www.thetimes.co.uk/tto/sport/athletics/article4522374.ece">[7]<span style="mso-spacerun: yes;"> </span>The Times Study of blood data will not be
enough to track down the cheats.<span style="mso-spacerun: yes;"> </span>August
20, 2015</a><o:p></o:p></span></div>
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<div class="MsoNormal">
<span style="font-family: Arial; mso-ansi-language: EN-GB;"><a href="http://www.bbc.co.uk/sport/0/athletics/33990503">[8]<span style="mso-spacerun: yes;"> </span>BBC Online.<span style="mso-spacerun: yes;">
</span>Paula Radcliffe says athletes should not release blood data August 19,
2015</a><o:p></o:p></span></div>
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<div class="MsoNormal">
<span style="font-family: Arial; mso-ansi-language: EN-GB;"><a href="http://www.bbc.co.uk/sport/0/cycling/33611854">[9] BBC Online.<span style="mso-spacerun: yes;"> </span>Tour de France: Chris Froome data released
amid doping claims July 21, 2015</a><o:p></o:p></span></div>
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<div class="MsoNormal">
<span style="font-family: Arial; mso-ansi-language: EN-GB;">[10]
<a href="http://www.amazon.co.uk/Inside-Team-Sky-Challenge-France/dp/1471133311"><span style="mso-spacerun: yes;"> </span>D. Walsh<span style="mso-spacerun: yes;">
</span><span lang="EN-US" style="mso-ansi-language: EN-US; mso-bidi-font-weight: bold;">Inside Team Sky: The Inside Story of Team Sky and Their Challenge for the
2013 Tour de France Simon & Schuster Ltd (2013)</span></a><o:p></o:p></span></div>
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profchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com0tag:blogger.com,1999:blog-5197898174856470934.post-15996321067844746472015-07-20T14:33:00.000-07:002015-07-20T14:33:21.548-07:00Wheatgrass juice, Channel 4, and blood oxygen – the data says no! <div class="MsoNormal" style="margin-bottom: 12.0pt; mso-layout-grid-align: none; mso-pagination: none; text-autospace: none;">
<span lang="EN-US" style="font-family: Arial;">I just did
a piece for Channel 4 on their superfoods program (<a href="http://www.channel4.com/programmes/superfoods-the-real-story">http://www.channel4.com/programmes/superfoods-the-real-story</a>).
It was looking into the claim that wheatgrass juice improved blood oxygen
content; allegedly this works by increasing the amount of haemoglobin as haem
and chlorophyll look so similar. My incredulity contrasted with the health food
expert who supplied the wheatgrass enema to the presenter. The expert said
there was a lot of scientific evidence that supported her view. There was not
time in the program to give the full account for the reasons for my incredulity
so I thought it worth expanding a bit here in case anyone is interested. <o:p></o:p></span></div>
<div class="MsoListParagraphCxSpFirst" style="margin-bottom: 12.0pt; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l0 level1 lfo1; mso-pagination: none; text-autospace: none; text-indent: -18.0pt;">
<!--[if !supportLists]--><span lang="EN-US" style="font-family: Symbol; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;"><span style="mso-list: Ignore;">·<span style="font: 7.0pt "Times New Roman";">
</span></span></span><!--[endif]--><span lang="EN-US" style="font-family: Arial;">Haem is
an iron porphyrin and chlorophyll is a magnesium chlorin. Superficially haem and
chlorophyll appear similar in chemical structure – one of the ideas that led to
Charles Schnabel in the 1930s suggesting wheatgrass could be a superfood.
Proponents today suggest it can increase the amount of haemoglobin in the
blood. However, in the 1930s the structure of proteins was not known. Not only
does chlorophyll contain magnesium rather than iron at its centre, but it has a
long organic side chain. Even if you could replace the magnesium with iron, you
could not put the iron-chlorin into the haemoglobin structure. It just won’t
fit.<o:p></o:p></span></div>
<div class="MsoListParagraphCxSpMiddle" style="margin-bottom: 12.0pt; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l0 level1 lfo1; mso-pagination: none; text-autospace: none; text-indent: -18.0pt;">
<!--[if !supportLists]--><span style="font-family: Symbol; mso-ansi-language: EN-GB; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;"><span style="mso-list: Ignore;">·<span style="font: 7.0pt "Times New Roman";"> </span></span></span><!--[endif]--><span lang="EN-US" style="font-family: Arial;">So maybe the chlorophyll provides building
blocks to help us make more haem? In this case wheatgrass juice might increase
haemoglobin by an indirect mechanism? There are a number of problems with this
idea. First there is no evidence that we absorb chlorophyll, whether taken
orally or rectally. Even if we did absorb chlorophyll, we cannot convert a
chlorin into a haem. The pathways <b style="mso-bidi-font-weight: normal;">are</b>
linked metabolically; plants make haem and chlorophyll from the same organic starting
materials. But we have don’t have the enzymes to make this conversion.<span style="mso-spacerun: yes;"> </span></span><span style="font-family: Arial; mso-ansi-language: EN-GB;"><o:p></o:p></span></div>
<div class="MsoListParagraphCxSpMiddle" style="margin-bottom: 12.0pt; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l0 level1 lfo1; mso-pagination: none; text-autospace: none; text-indent: -18.0pt;">
<!--[if !supportLists]--><span style="font-family: Symbol; mso-ansi-language: EN-GB; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;"><span style="mso-list: Ignore;">·<span style="font: 7.0pt "Times New Roman";"> </span></span></span><!--[endif]--><span lang="EN-US" style="font-family: Arial;">In contrast to chlorophyll, we do absorb
haem quite efficiently. But we immediately break it down for its iron content,
throwing away the porphyrin cofactor. The result. If you want dietary iron, eat
black pudding not wheatgrass juice.</span><span style="font-family: Arial; mso-ansi-language: EN-GB;"><o:p></o:p></span></div>
<div class="MsoListParagraphCxSpMiddle" style="margin-bottom: 12.0pt; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l0 level1 lfo1; mso-pagination: none; text-autospace: none; text-indent: -18.0pt;">
<!--[if !supportLists]--><span style="font-family: Symbol; mso-ansi-language: EN-GB; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;"><span style="mso-list: Ignore;">·<span style="font: 7.0pt "Times New Roman";"> </span></span></span><!--[endif]--><span style="font-family: Arial; mso-ansi-language: EN-GB;">Still maybe there is an
unknown mechanism for the wheatgrass effect? Is there any science that supports
the effect of wheatgrass juice increasing blood oxygen content? If there was
good human trial data then we could search for a mechanism. After all gut
bacteria are increasingly seen as important to health. Maybe feeding our gut
chlorophyll has an effect on the body, even if none of that chlorophyll is
absorbed? The problem is that there is no good scientific evidence in human
studies of any blood oxygen, health benefit or sports performance effects. I
looked hard and could find only a very few papers. <span style="mso-spacerun: yes;"> </span>The first [1] is full of flaws and, as far as
I can see not peer reviewed. However, let’s assume the study was well
conducted. The effects observed (0.26% increase in arterial blood oxygen
saturation) would have no significant physiological benefit; indeed there was
no performance boost reported in this paper. <o:p></o:p></span></div>
<div class="MsoListParagraphCxSpMiddle" style="margin-bottom: 12.0pt; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l0 level1 lfo1; mso-pagination: none; text-autospace: none; text-indent: -18.0pt;">
<!--[if !supportLists]--><span style="font-family: Symbol; mso-ansi-language: EN-GB; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;"><span style="mso-list: Ignore;">·<span style="font: 7.0pt "Times New Roman";"> </span></span></span><!--[endif]--><span style="font-family: Arial; mso-ansi-language: EN-GB;">If wheatgrass juice really
did increase the number of red blood cells it would be a godsend for many
patients who have anaemia. Who needs epo or blood transfusions if you can just
eat crushed grass? Two papers looked at this effect. The first, a small pilot
study [2], suggested that </span><span lang="EN-US" style="font-family: Arial;">consuming
about 100 mL of wheat grass juice daily </span><span style="font-family: Arial; mso-ansi-language: EN-GB;">could reduce the need for blood transfusions in
patients with </span><span lang="EN-US" style="font-family: Arial; mso-bidi-font-weight: bold;">thalassemia major</span><span style="font-family: Arial; mso-ansi-language: EN-GB;">. However, a later, larger study contradicted this [3]. Neither study
was randomised or blinded. <o:p></o:p></span></div>
<div class="MsoListParagraphCxSpLast" style="margin-bottom: 12.0pt; mso-add-space: auto; mso-layout-grid-align: none; mso-list: l0 level1 lfo1; mso-pagination: none; text-autospace: none; text-indent: -18.0pt;">
<!--[if !supportLists]--><span style="font-family: Symbol; mso-ansi-language: EN-GB; mso-bidi-font-family: Symbol; mso-fareast-font-family: Symbol;"><span style="mso-list: Ignore;">·<span style="font: 7.0pt "Times New Roman";"> </span></span></span><!--[endif]--><span style="font-family: Arial; mso-ansi-language: EN-GB;">Lest I be accused of being a
complete cynic there is one study published that holds some promise. In a small
double blinded, placebo controlled trial in ulcerative colitis (</span><span lang="EN-US" style="font-family: Arial;">inflammatory bowel disease), w</span><span style="font-family: Arial; mso-ansi-language: EN-GB;">wheatgrass seemed to have
some beneficial effects [4]. This study was conducted in 2002 and, as far as I
can tell, has not been followed up. But at least it has the benefit of not
straining credulity – the chlorophyll is suggesting to act where we know it
goes – the gut.<o:p></o:p></span></div>
<div class="MsoNormal" style="margin-bottom: 12.0pt; mso-layout-grid-align: none; mso-pagination: none; text-autospace: none;">
<span style="font-family: Arial; mso-ansi-language: EN-GB;">In short wheatgrass juice is no superfood. At least not when it comes to
increasing the number of red blood cells. There is no reason for WADA to put it
on the sporting banned list or develop chlorophyll anti-doping tests. <o:p></o:p></span></div>
<div class="MsoNormal" style="margin-bottom: 12.0pt; mso-layout-grid-align: none; mso-pagination: none; text-autospace: none;">
<span lang="EN-US" style="font-family: Arial;">[1] <a href="http://ispub.com/IJAM/8/1/12621">M Handzel, J Sibert, T Harvey, H
Deshmukh, C Chambers. <i>Monitoring the Oxygenation of Blood During Exercise
After Ingesting Wheatgrass Juice</i>. The Internet Journal of Alternative
Medicine (2008) Volume 8 Number 1.</a><o:p></o:p></span></div>
<div class="MsoNormal" style="margin-right: -36.0pt; mso-layout-grid-align: none; mso-pagination: none; text-autospace: none;">
<span lang="EN-US" style="font-family: Helvetica; mso-bidi-font-family: Helvetica;">[2] <a href="http://www.indianpediatrics.net/july2004/july-716-720.htm">R.K. Marawaha,
D. Bansal, S. Kaur, A. Trehan, Wheat grass juice reduces transfusion
requirement in patients with thalassemia major: a pilot study, Indian
pediatrics, 41 (2004) 716-720.</a><o:p></o:p></span></div>
<div class="MsoNormal" style="margin-right: -36.0pt; mso-layout-grid-align: none; mso-pagination: none; text-autospace: none;">
<br /></div>
<div class="MsoNormal" style="margin-right: -36.0pt; mso-layout-grid-align: none; mso-pagination: none; text-autospace: none;">
<span lang="EN-US" style="font-family: Helvetica; mso-bidi-font-family: Helvetica;">[3] <a href="http://link.springer.com/article/10.1007%2Fs12098-009-0004-6">D.R.
Choudhary, R. Naithani, I. Panigrahi, R. Kumar, M. Mahapatra, H.P. Pati, R.
Saxena, V.P. Choudhry, <i style="mso-bidi-font-style: normal;">Effect of wheat
grass therapy on transfusion requirement in beta-thalassemia major</i>, Indian
journal of pediatrics, 76 (2009) 375-376.</a><o:p></o:p></span></div>
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profchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com0tag:blogger.com,1999:blog-5197898174856470934.post-89513756737434645922015-07-20T01:21:00.001-07:002015-07-20T01:21:44.251-07:00Epo and doping accusations in the Tour de France – the numbers never lie (or do they?)
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<span lang="EN-US" style="font-family: Arial;">I was
struck by the vehemance of the current anti-Froome accusations. So I thought I
would add my tuppence worth to this story. First let me nail my colours to the
mast. I have a lot of sympathy with Sir Dave Brailsford when he says “<span style="color: #151515;">"It is not possible to prove a negative. I
can't," [1]. </span></span></div>
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<span lang="EN-US" style="font-family: Arial;">Sir Dave is referring to the well-known fallacy in
formal logic known as an <i>argumentum ad ignorantiam</i> or “appeal to
ignorance”. This poses that “something is true only because it has not been
proved false, or that something is false only because it has not been proved
true”. <o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: Arial;">Now there
are some cases where versions of this argument are used by philosophers
(inductive logic relies on it in part). Indeed you cannot prove any future
event true or false until it has happened. Prehistoric man with no knowledge of
physics or astronomy had no definite “proof” that the sun would rise tomorrow
or that walking off a cliff would result in a fatal fall. However, enough
evidence had accumulated from previous life experiences to make these perfectly
reasonable assumptions. Indeed it would be impossible for us to live our lives
without making these kind of inductive “leaps of faith” every day. <o:p></o:p></span></div>
<div class="MsoNormal" style="margin-bottom: 12.0pt; mso-layout-grid-align: none; mso-pagination: none; text-autospace: none;">
<span lang="EN-US" style="font-family: Arial;">Something
ought to go without saying given the scientific literature, but clearly it
needs repeating ad infinitum. Doping allegations based purely on performance
(in this case speed or power data) fall well short of the strong evidence
required for inductive reasoning. Power/time data alone can never prove someone
is doping, or even make it probable. If you doubt this please take time to read
carefully the recent article by <span style="mso-bidi-font-weight: bold;">Hein FM
Lodewijkx </span>“The Epo Fable in Professional Cycling: Facts, Fallacies and
Fabrications” [2].<o:p></o:p></span></div>
<div class="MsoNormal" style="margin-bottom: 12.0pt; mso-layout-grid-align: none; mso-pagination: none; text-autospace: none;">
<span lang="EN-US" style="font-family: Arial;">Not that
the Lodewijkx review does not prove that epo does not improve performance; in fact it
is careful not to say this. <span style="mso-spacerun: yes;"> </span>Times have continually
improved in the Tour and doping could be one of many factors that can affect racing
times. The devil is in the scientific detail. But it does make salutary reading
for people who assume that numbers alone are a reason for crying </span><span style="font-family: Arial; mso-ansi-language: EN-GB;">foul. <o:p></o:p></span></div>
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<span style="font-family: Arial; mso-ansi-language: EN-GB;">One thing that is needed is a proper randomized trail in elite cyclists
testing whether epo doping “works”. Crucially, it should include accounting for
the likely strong placebo effect (as everyone “knows” epo works – see my
previous blog). The definitive study would include giving cyclists epo when
they were told they were getting placebo. This kind of approach has been very successful
in studies comparing drug and placebo effects on performance following caffeine
administration [3]. However, significant ethical issues would need to be
overcome before any epo study could start. Worse still cyclists would need to
volunteer for a “ban” so it also need an end of career altruistic act.<o:p></o:p></span></div>
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<span style="font-family: Arial; mso-ansi-language: EN-GB;">If such a study were performed, my suspicion is that it would show that
epo microdosing is no more effective than a strong placebo. I suspect blood
transfusions or high dose epo <b style="mso-bidi-font-weight: normal;">would</b>
outperform placebo, but I doubt those more severe studies could be done. Still
I don’t “know” these answers – as a scientist I just want the studies to be
done (ethics permitting) to find out! <o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: Arial;">[1] <a href="http://www.bbc.co.uk/sport/0/cycling/33590228">http://www.bbc.co.uk/sport/0/cycling/33590228</a><o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: Arial;">[2] <a href="http://www.omicsonline.org/open-access/the-epo-fable-in-professional-cycling-facts-fallacies-and-fabrications-2161-0673.1000141.php?aid=30915">Lodewijkx
HFM (2014) The Epo Fable in Professional Cycling: Facts, Fallacies and
Fabrications. J Sports Med Doping Stud 4:141. doi: 10.4172/2161-0673.1000141</a><o:p></o:p></span></div>
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<span lang="EN-US" style="font-family: Arial;">[3] <a href="http://www.ncbi.nlm.nih.gov/pubmed/18091009">A.J. Foad, C.J. Beedie, D.A.
Coleman, Pharmacological and psychological effects of caffeine ingestion in
40-km cycling performance, Med. Sci. Sports Exerc., 40 (2008) 158-165.</a><o:p></o:p></span></div>
profchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com0tag:blogger.com,1999:blog-5197898174856470934.post-82650890412535159692015-06-07T14:57:00.000-07:002015-06-07T14:57:07.353-07:00Catch me if you can – the science<div class="MsoNormal" style="margin-left: 7.1pt;">
<span style="font-family: Helvetica; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">I haven’t been able to
blog for a while, in part due to work constraints, but also due to working on
my next book (<i style="mso-bidi-font-style: normal;">Blood: A Very Short
Introduction</i>). Still the book will be finished by the end of this month and
I should have more time to write soon. <o:p></o:p></span></div>
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<br /></div>
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<span style="font-family: Helvetica; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">Still I couldn’t resist
commenting on the latest BBC documentary about doping - Mark Daly’s <i style="mso-bidi-font-style: normal;">Catch Me If You Can</i>. I was actually
invited to talk about it last week on BBC2s <i style="mso-bidi-font-style: normal;">Newsnight;
</i>I couldn’t make it as I was busy talking about my artificial blood research
at a blood transfusion conference in Scotland (for the latest info see <a href="http://www.haemo2.com/">www.haemO2.com</a>). <o:p></o:p></span></div>
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<span style="font-family: Helvetica; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">What I would like to do
here is explore some of the science behind the allegations. First up, the least
interesting part of the piece – the reporter taking EPO himself to see if he
could fool the anti doping biological passport. I am growing to hate this
aspect of science TV documentaries [1].<span style="mso-spacerun: yes;"> </span>They
all do it now (I blame Michael Mosley!) and, although I understand it is used
to engage the viewer, it rarely adds anything to the science. In this case we
know that microdosing is an issue with the biological passport. We also know
that EPO can theoretically improve VO2 max and performance. Actually what we
don’t know is whether in this particular case the EPO enhanced the performance.
The reporter clearly expected the drug to work He also admitted feeling very
different as soon as he took the EPO. One would expect a large placebo effect
under these conditions and, as a non-elite athlete, there was a large room for
improvement. Did the drug really work or was the effect all in the mind? What
the documentary should really have done of course was a double blind crossover
study with a placebo. In fact as a watching scientist I wanted the Swiss expert
Carsten Lundby’s view, not on the passport data, but on whether he thought the EPO-induced
haematocrit change was enough to trigger the measured VO2 max increase. Lundby
is a world authority on the performance link between blood oxygen content and performance
and it would have been really interesting to hear his opinion about this. <o:p></o:p></span></div>
<div class="MsoNormal" style="margin-left: 7.1pt;">
<br /></div>
<div class="MsoNormal" style="margin-left: 7.1pt;">
<span style="font-family: Helvetica; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">That said the journalistic
scoops were really interesting. For me personally the most concerning were the
allegations about Alan Wells, one of my childhood heroes. High dose anabolic
steroids can clearly increase muscle mass and I would be genuinely saddened if
his victories were in part due to steroid use. <o:p></o:p></span></div>
<div class="MsoNormal" style="margin-left: 7.1pt;">
<br /></div>
<div class="MsoNormal" style="margin-left: 7.1pt;">
<span style="font-family: Helvetica; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">But, of course, the
most concerns have been raised about the Galen Rupp and Alberto Salazar
allegations (hotly denied). Leaving aside the truth or otherwise of the stories
what about the science? Well, unlike sprinting, anabolic steroids such as
testosterone are not game changers in long distance running (especially in men).
They have turned up occasionally, the “steroid in my toothpaste” excuse from
Dieter Baumann being perhaps the most famous occasion. The most likely benefit
is in training where they might aid recovery and allow for longer, more intense,
sessions (although even that is not based on mostly anecdotal data). Likewise
asthma therapies like oral corticosteroids. They can stimulate activity, but in
some cases could actually be detrimental to performance. Similarly pre race IV
drips should not be required for a healthy athlete. <o:p></o:p></span></div>
<div class="MsoNormal" style="margin-left: 7.1pt;">
<br /></div>
<div class="MsoNormal" style="margin-left: 7.1pt;">
<span style="font-family: Helvetica; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">My conclusion, albeit
on a one off viewing of a one-hour TV program, is that what was exposed, even if
true, was not what led to Galen Rupp’s strong performances. If he got his
medals by cheating there was most likely something else going on. What the
documentary did expose was a culture that might not have been averse to using a
scientific approach to doping methods (and detection prevention) that really could
make a significant difference in long distance running events. These include EPO
and blood transfusions. That’s what Mo Farah needs to find out when he returns
to America to meet with Salazar. <o:p></o:p></span></div>
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<span style="font-family: Helvetica; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">[1] Hypocrite alert – I
have just taken part in a Channel 4 documentary where this is done. However, at
least this means I can talk with authority about its limitations!<o:p></o:p></span></div>
profchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com0tag:blogger.com,1999:blog-5197898174856470934.post-90143594567514508182015-03-09T10:02:00.001-07:002015-03-09T10:02:56.962-07:00Changes to blog<div class="MsoNormal" style="margin-left: 7.1pt;">
<span style="font-family: Helvetica; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">Dear readers,<o:p></o:p></span></div>
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<br /></div>
<div class="MsoNormal" style="margin-left: 7.1pt;">
<span style="font-family: Helvetica; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">I have chosen to make some
changes to this blog:<o:p></o:p></span></div>
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</span></span></span><!--[endif]--><span style="font-family: Helvetica; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica;">I have instigated a rolling program of deleting
older blogs. The blog is not meant as a formal reference site and this is to
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<span style="font-family: Helvetica;">2</span><span style="font-family: Helvetica;"> </span><span style="font-family: Helvetica;">I have unfortunately had to prevent user
comments by external users. Whilst some were really interesting they are outnumbered over 20:1 by
comments solely sent with the purpose of redirecting readers to the commenter’s
web pages. The vast majority of these are commercial pages selling products
(such as peptides). These were taking too much of my time to filter out. <o:p></o:p></span></div>
profchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com0tag:blogger.com,1999:blog-5197898174856470934.post-64748454144217727532014-07-30T13:14:00.001-07:002014-07-30T13:14:39.203-07:00GW501516: Update on endurobol and doping: some thoughts about dosing<div class="MsoNormal">
<span style="font-family: Helvetica; font-size: 11.0pt; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica; mso-bidi-font-size: 12.0pt;">In
a previous blog [1], I noted that there was no evidence in animals that endurobol
improved performance in animals. I must apologise as I missed a rather
important paper from Ron Evans group in 2008 that showed just that. The
performance effect was only seen if the mice were also doing exercise training
[2].<o:p></o:p></span></div>
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<br /></div>
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<span style="font-family: Helvetica; font-size: 11.0pt; mso-ansi-language: EN-GB; mso-bidi-font-family: Helvetica; mso-bidi-font-size: 12.0pt;">What
is interesting is the doses that were used in this study. The four-week program
of exercise training was paired with </span><span lang="EN-US" style="font-family: Helvetica; font-size: 11.0pt; mso-bidi-font-family: Helvetica; mso-bidi-font-size: 12.0pt;">5 mg/kg/day of the drug. This is at the low range of the long-term
(2 year) toxicity study done by Glaxo [3], which varied from 0 – 80 mg/kg/day.
But some adverse effects were still seen at the 5mg/kg/day level. <o:p></o:p></span></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
<span lang="EN-US" style="font-family: Helvetica; font-size: 11.0pt; mso-bidi-font-family: Helvetica; mso-bidi-font-size: 12.0pt;">Interestingly one
anonymous commentator on my previous blog said that he/she knew people who have
been using it at a dosage of 10 mg per day for fat loss purposes and 20 mg per
day for a performance enhancing benefit. Indeed some companies are selling
pills of 5 mg size [4]. However, these doses are far lower than are shown to
work in the Evans paper (for an average 85 kg human, the “Evans” dose should be
425 mg/day<span style="mso-spacerun: yes;"> </span>- or three full bottles every
day of the pills that some manufacturers are selling. <o:p></o:p></span></div>
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<br /></div>
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<span lang="EN-US" style="font-family: Helvetica; font-size: 11.0pt; mso-bidi-font-family: Helvetica; mso-bidi-font-size: 12.0pt;">The usual caveats
apply. There are long-term toxicity effects of this compound and it is
generally easier to show performance effects in laboratory rats and mice than
highly fit trained athletes. <o:p></o:p></span></div>
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<br /></div>
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<ol>
<li><span lang="EN-US" style="font-family: Helvetica; font-size: 11pt; text-indent: -18pt;"><span style="font-family: 'Times New Roman'; font-size: 7pt;"> </span></span><span lang="EN-US" style="font-family: Helvetica; font-size: 11pt; text-indent: -18pt;"><a href="http://runswimthrowcheat.blogspot.co.uk/2014/02/gw501516-endurobol-and-doping-whats-all.html">http://runswimthrowcheat.blogspot.co.uk/2014/02/gw501516-endurobol-and-doping-whats-all.htm</a></span></li>
<li><span lang="EN-US" style="font-family: Helvetica; font-size: 11pt; text-indent: -18pt;"><span style="font-family: 'Times New Roman'; font-size: 7pt;"> </span></span><span lang="EN-US" style="font-family: Helvetica; font-size: 11pt; text-indent: -18pt;"><a href="http://www.ncbi.nlm.nih.gov/pubmed/18674809">Narkar VA, Downes M, Yu RT
et al (2008) AMPK and PPARdelta agonists are exercise mimetics. Cell
134:405-415.</a></span></li>
<li><span lang="EN-US" style="font-family: Helvetica; font-size: 11pt; text-indent: -18pt;"><span style="font-family: 'Times New Roman'; font-size: 7pt;"> </span></span><span style="font-family: Helvetica; font-size: 11pt; text-indent: -18pt;"><a href="http://www.toxicology.org/AI/Pub/Tox/2009Tox.pdf">Toxicological
Sciences Volume 108, Number 1, March 2009 Abstracts # 895 and 896</a></span><span style="font-family: Helvetica; font-size: 11pt; text-indent: -18pt;"><span style="font-family: 'Times New Roman'; font-size: 7pt;"> </span></span></li>
<li><a href="http://www.sarms-supply.com/gw501516-c-95.html" style="font-family: Helvetica; font-size: 11pt; text-indent: -18pt;">http://www.sarms-supply.com/gw501516-c-95.html</a></li>
</ol>
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profchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com0tag:blogger.com,1999:blog-5197898174856470934.post-46245241779059680652014-07-13T08:27:00.000-07:002014-07-13T08:27:12.368-07:00Doping at the football world cup?<div class="MsoNormal">
<span style="line-height: 115%;">With
today’s final imminent it is worth asking what, if any, role doping played in
the World Cup? It is true that football teams today are required to be much
fitter than before; it is unlikely that even some of the great teams of the
past would have performed optimally in the last 30 minutes of a modern match.
However, the endurance levels required for the footballers of today still
require little more than a sensible diet and a lot of hard work in the gym or
training field (although it has to be said even this does seem beyond some
players).</span></div>
<div class="MsoNormal">
<span style="line-height: 115%;"><br /></span></div>
<div class="MsoNormal">
<span style="line-height: 115%; mso-bidi-font-size: 12.0pt;">Unlike
athletics or cycling, In terms of performance enhancement it is difficult to
make dramatic changes in skills-based team sports performance by chemical
enhancement. It is theoretically possible that “cognitive enhancers” might make
a player more alert, even when tired, such that they find that critical defence
splitting pass. But I suspect any change would be small, and there is no
evidence that teams are attempting to use this route. <o:p></o:p></span></div>
<div class="MsoNormal">
<span style="line-height: 115%; mso-bidi-font-size: 12.0pt;"><br /></span></div>
<div class="MsoNormal">
<span style="line-height: 115%; mso-bidi-font-size: 12.0pt;">Where
there is more concern in drugs that are “performance enabling” i.e. that make a
player play in a match that they would otherwise not be able to. </span>Painkillers
fall into a ‘doping grey-zone’ <a href="file:///%5B2%5D%20Mehallo,%20C%20et%20al,%20Practical%20Management/%20Nonsteroidal%20Antiinflammatory%20Drug%20(NSAID)%20Use%20in%20Athletic%20Injuries,%20Clinical%20Journal%20of%20Sports%20Medicine%202006/16/170-174">[1]</a>
because there is an obvious need to treat an athlete if they’re injured but
they can also be used to shorten the recovery time needed if given in high
enough doses. Non-steroidal anti-inflammatories (NSAIDs) in particular have
been shown to effectively decrease pain and improve early muscle recovery <a href="http://www.ncbi.nlm.nih.gov/pubmed/16603889">[2</a>]. Footballers in
particular might tend towards painkillers before and during games as it may
allow them to both get back on the pitch sooner after an injury and reduce the
severity of any injury that may occur <a href="http://www.bbc.co.uk/news/science-environment-18064904">[3].</a><o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Whilst their use post match to treat an injury is an
accepted exercise, what happens when an athlete takes them before playing? Here
we do have evidence from the football world cup. FIFA’s chief medical officer,
Dr Jiri Dorvak, published a paper looking into the use of medication during the
2010 World Cup [<a href="http://www.bbc.co.uk/news/science-environment-18064904">3</a>,<a href="http://bjsm.bmj.com/content/early/2012/03/21/bjsports-2011-090806">4</a>].
He asked team physicians to provide them with details of all of the medications
each player took ahead of the games. His study showed that 39% of players took
a painkiller in the 72 hours before every game they played in <a href="http://bjsm.bmj.com/content/early/2012/03/21/bjsports-2011-090806">[4]</a>
and that overall painkiller use was increasing year on year. This study
accounted for the number of players taking prescribed medication; due to the
easy availability of painkillers it is likely that the true number is much
higher. <o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Dr Dorvak believes that one of the factors that has resulted
in this rise is the increasing pressure put on team doctors by managers and
sponsors to get players fit and healthy again <a href="http://www.bbc.co.uk/news/science-environment-18064904">[3]</a>; with the
incredibly high potential earnings of top international players it is also unsurprising
that the players themselves want to make sure they keep hold of the job or shine
in a match that could get them their next big transfer. And who would want to
miss a World Cup Final if at all possible? <o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
Another issue that arose from the study was the likelihood
of further increase in painkiller use in youth teams, with 16-19% of under-17
football players abusing them <a href="http://www.bbc.co.uk/news/science-environment-18064904">[3].</a> Due to
the sometimes severe effects that painkillers (NSAIDs in particular) can have
on the kidneys and liver, it is a worrying sign that consumption at this level
is seen at a young age.<o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
As I say in my book <a href="http://www.amazon.co.uk/Run-Swim-Throw-Cheat-science/dp/0199678782/">[5],</a>
we have been here before, and not just in football. Peter Elliott won a silver
medal for Britain in the 1988 Olympic 800m; but only after receiving five cortisone
injections in seven days. Hailed by many at the time (including me) as an
example of bravery, some were critical of the methods employed. <o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
It is no doubt that injecting an athlete with a range of
drugs can aid recovery and enable them to compete at an enhanced level than
they would have been able to without the drug. In many cases this is at the
cost of possible future injury or disability. So, as far as the individual
themselves is concerned, this is not much different from risking long-term
health damage by using a banned performance enhancing drug. And we know this is
not a deterrent for many dopers. The difference, if there is one, is that the
level reached is not “superhuman” i.e. it could be reached without doping if
someone could avoid injury. <o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
I think in this area the medical care of an athlete is
paramount. It is surely the responsibility of the athlete’s doctor to advice on
the health benefits or damage of any treatment. This is yet another reason why
advocates of “clean sport” needs to focus as much on coaches and support team
(including medical staff) as the athletes themselves. <o:p></o:p></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
<i style="mso-bidi-font-style: normal;">[I would like to thank
Jess Pritchard, a student at the University of Leicester in the UK, for doing
some of the original research on this story and writing a preliminary draft.
However, as always all the comments expressed in this blog are my own and not
those of Jess, my publisher or my university].<o:p></o:p></i></div>
<div class="MsoNormal">
<i style="mso-bidi-font-style: normal;"><br /></i></div>
<div class="MsoNormal">
<b style="mso-bidi-font-weight: normal;">References<o:p></o:p></b></div>
<div class="MsoNormal">
<b style="mso-bidi-font-weight: normal;"><br /></b></div>
<div class="MsoNormal">
[1] <i style="mso-bidi-font-style: normal;"><span lang="EN-US" style="mso-ansi-language: EN-US; mso-bidi-font-weight: bold;"><a href="http://www.bbc.co.uk/news/science-environment-18282072">Is pain
medication in sport a form of legal doping?<span style="font-style: normal;">
Matt McGrath</span><span lang="EN-US" style="font-style: normal; mso-ansi-language: EN-GB; mso-bidi-font-weight: normal;"><span lang="EN-US"> BBC News (2012)</span></span></a></span></i><span lang="EN-US" style="mso-ansi-language: EN-US; mso-bidi-font-weight: bold;"> <o:p></o:p></span></div>
<div class="MsoNormal">
<i style="mso-bidi-font-style: normal;"><br /></i></div>
<div class="MsoNormal">
[2] <a href="http://www.ncbi.nlm.nih.gov/pubmed/16603889">Mehallo,
C et al, Practical Management: Nonsteroidal Antiinflammatory Drug (NSAID) Use
in Athletic Injuries, <i style="mso-bidi-font-style: normal;">Clinical Journal of
Sports Medicine </i>2006:<b style="mso-bidi-font-weight: normal;">16</b>:170-174</a><o:p></o:p></div>
<div class="MsoNormal">
<span style="font-size: 6.0pt; line-height: 115%; mso-bidi-font-size: 11.0pt;"><br />
</span>[3] <span lang="EN-US" style="mso-ansi-language: EN-US; mso-bidi-font-weight: bold;"><a href="http://www.bbc.co.uk/news/science-environment-18064904"><i style="mso-bidi-font-style: normal;">Fifa alarmed at widespread 'abuse' of
painkillers</i> Matt McGrath BBC News (2012)</a><b> </b><o:p></o:p></span></div>
<div class="MsoNormal">
<br /></div>
<div class="MsoNormal">
[4] <a href="http://bjsm.bmj.com/content/early/2012/03/21/bjsports-2011-090806">Tscholl,
M., Dorvak, J., Abuse of medication during international football competition
in 2010 – lesson not learned,<i><span style="border: none windowtext 1.0pt; font-size: 9.0pt; line-height: 115%; mso-bidi-font-family: Arial; mso-border-alt: none windowtext 0cm; padding: 0cm;"> </span></i><i><span style="border: none windowtext 1.0pt; line-height: 115%; mso-bidi-font-family: Arial; mso-bidi-font-size: 12.0pt; mso-border-alt: none windowtext 0cm; padding: 0cm;">British Journal of Sports Medicine </span></i><span style="border: none windowtext 1.0pt; line-height: 115%; mso-bidi-font-family: Arial; mso-bidi-font-size: 12.0pt; mso-border-alt: none windowtext 0cm; padding: 0cm;">2012;<b>46</b>:1140-1141</span></a><span style="line-height: 115%; mso-bidi-font-family: Arial; mso-bidi-font-size: 12.0pt;"><o:p></o:p></span></div>
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<span style="mso-spacerun: yes;"> </span>[5] <i style="mso-bidi-font-style: normal;"><a href="http://www.amazon.co.uk/Run-Swim-Throw-Cheat-science/dp/0199678782/">Run,
Swim, Throw Cheat<span style="font-style: normal;"> (2012) Chris Cooper , Oxford
University Press. p. 229</span></a></i><o:p></o:p></div>
profchriscooperhttp://www.blogger.com/profile/14413479161943662975noreply@blogger.com1