The Drugs (don't) Work



In terms of any news circulating around the sports scene, how often is it good? Something which has always been a problem, but that more and more people are now realising is a widespread problem, is doping. We have all the headlines; this constitutes doping, that does not, and this other medication only counts as doping if taken in competition at a dose of more than 200mg per day. It's a total minefield, and it can be hard to find the facts among everything else. I have chosen to pursue a career as an expert in medicines, and am currently in my final year, so hopefully I'll be able to explain this in a way that everyone can understand!

So, what is Meldonium? Technically speaking, it's a competitive inhibitor of gamma-butyrobetainehydroxylase, but sure, what does that mean? This is an enzyme, which is involved in the synthesis of L-carnitine, which you may have heard a certain athlete got injections of! L-carnitine is involved in 'shifting' fatty acids to the mitochondria, which in turn provides a source of energy, which then enables us to carry out exercise. Basically, fat = fuel. The flipside of providing energy, is that this process increases oxidative stress, which can put a strain on the heart and skeletal muscle (which is why Meldonium is used in cardiac conditions). Oxidative stress is when there is an imbalance between the amount of reactive oxygen in the body, compared with the body's ability to detoxify it. This then causes a build-up of reactive oxygen, which can damage tissues in the body. Meldonium blocks this process, so reducing oxidative stress. As the fatty acid shifting is blocked, the body turns to glucose metabolism for the production of energy, and this is where it is thought that Meldonium is used as a 'pre-conditioning' agent for athletes. It is also thought that Meldonium reduces mitochondrial injury due to the reduced fatty acid oxidation. There is some evidence that Meldonium has an effect on the production of Nitric Oxde, which is a vasodilator. This is basically a substance which opens up the blood vessels and allowed increased blood flow. Helpful for an athlete, isn't it?

In terms of the medical conditions that it is used to treat, it is used in Eastern European and Asian countries for cardiac complaints, and there is also some information regarding its use in Diabetic patients, due to a favourable impact on insulin resistance. I believe this was also explained during Maria Sharapova's press conference, where she said it was being used as a treatment for pre-diabetes. With long-term use, it is said that there are effects such as; - Lowered blood glucose levels; - Cardioprotective effects; - Prevention or reduction in Diabetic complications.

The performance-enhancing effects are hotly debated, and some experts would argue that it shouldn't be banned at all, whilst others say that the risk of misuse is there, and so it needs to stay banned. Even before it was banned by the World Anti-Doping Agency, there were studies underway to analyse the performance-enhancing effects of Meldonium. It is currently banned under the section 'Metabolic Modulators,' meaning it does *something* to the metabolism of substances in the body.

So, what are the performance-enhancing effects that are being debated? (Gorgens et all, 2015) - Increased endurance; - Better rehabilitation after exercise; - Protection against stress; - There is also some evidence linking Meldonium to better activation of the Central Nervous system, so better reaction times, potentially; - Rather conversely, it is also seen to have some mood-enhancing effects, and increased learning and memory capacity.

Now, for me, this was the most worrying part of the Maria Sharapova case, and also for anyone else who is taking this drug outside of the licensed countries. Meldonium is not licensed in the U.S. or U.K., nor is it licensed in large parts of Europe. Now, usually, drugs companies will go to the FDA for U.S. approval first, as it's a larger market. I couldn't find any information on whether Meldonium was rejected by the FDA, or whether it just wasn't submitted for approval there. FDA regulate safe and effective medical products and devices in the U.S., but their decisions generally do have weighting worldwide. They will approve medicines for use unless they have concerns with regards to issues such as; - Safety, could the drug have some dangerous side-effects? - Efficacy, does the drug do what it says it does? Are there more effective and safer alternatives? For drugs which have a potential for abuse, they are generally put under more stringent rules, such as is the case with Controlled Drugs in the U.K.

160 athletes were found to have samples containing Meldonium in the short time after the ban was announced, and although this number has decreased over the time since then, we have had new cases as recent at the Winter Olympics last month. From Athletics to Boxing, Mixed Martial Arts to Curling, this drug has seemed not to discriminate between sports and for me, there must be something in it. I may be sceptical, but I find it hard to believe that all of the athletes who have tested positive for it have genuine reasons for taking it. If they do, that's great, but as the number of positive tests keep adding up, that becomes an ever-decreasing possibility.

That is the end of my ramblings on this, hopefully you've found it interesting! If I come across any more interesting doping cases, I will be only too glad to write up about the implicated drug! Feel free to share your comments below; how widespread do you think the issue of doping in sport is? What do you think of the whole Meldonium situation?

Alan Wilson

Very interesting and informative Anna, although in my ignorance I thought you were going to talk about a new element when I saw the title

Mike Barry

Very good insight Anna. I had never heard of it prior to the Maria S. Situation. My question is, how does WADA figure out how exactly it benefits the taker, and wouldnt they want to run tests on actual people to get a handle on it ! Anyway. Keep up the great investigative work !!!! Mike

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