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Mildronate has a lot of controversy surrounding its use in sport, and you may have heard its name involved in sporting scandals, but do you actually know what Mildronate is? In this article you’ll learn everything you need to know about Mildronate, the facts, the inaccuracies, and the science behind the name.
Mildronate is the brand name used for the drug meldonium. It’s a drug that was originally designed in Latvia for increased oxygen flow, and the World Anti-Doping Agency (WADA) took measures to ban the substance in Olympic sports after athletes began using it for performance-enhancing purposes.
Meldonium is primarily produced by a Latvian pharmaceutical company called Grindeks. While ‘meldonium’ is the simple and easy to recognise name of the drug, you may also come across it in its Latvian spelling: Mildronāts, or the less recognisable names Quaterine, MET-88, THP, trimethylhydrazinium propionate, and 3-(2,2,2-trimethylhydraziniumyl)propionate.
For the purpose of this article, we’ll stick with Mildronate and meldonium.
1970: the drug is developed by Ivars Kalvins at the USSR Latvia Institute of Organic Synthesis.
2015: At the start of the year WADA adds Meldonium to their watch list.
2015: There was a high prevalence of meldonium use by athletes at the Baku 2015 European
Games. 13 medallists were taking meldonium, and it was detected in athletes competing in 15 of the 21 sports taking place at the games. Most athletes did not declare the drug on their doping forms. 66 of 762 urine samples tested positive for meldonium, and only 23 declared their use.
2015: In December a study in the journal Drug Testing and Analysis  argued that meldonium “demonstrates an increase in endurance performance of athletes, improved rehabilitation after exercise, protection against stress, and enhanced activations of central nervous system functions.” However, the study itself presents no evidence for this claim, and goes on to talk about two approaches to confidently identify meldonium.
2016: January 1st WADA added meldonium to their list of banned substances because of “evidence of its use by athletes with intention of enhancing performance.” They class meldonium as a metabolic modulator.
2016: On March 7th the former number-one tennis player, Maria Sharapova, brought the drug into the spotlight by testing positive for the substance. She contested that she had been taking meldonium for over ten years to treat an on-going medical issue.
2016: On the same day (March 7th) Russian ice dancer Ekaterina Bobrova announced that she too had tested positive for meldonium at the 2016 European Figure Skating Championships. She said she was shocked because she didn’t believe she had taken the substance.
2016: On April 13th WADA decided to overturn the bans of athletes who tested positive for this drug before March 1st, 2016, because they had no reliable data to know how long it took for meldonium to exit the system, and preliminary tests showed that it could take weeks or months for the drug to leave the body fully.
2016: In May professional Russian Boxer Alexander Povetkin (former two-time World Boxing Association Heavyweight Champion) tested positive for the substance. An upcoming title match was postponed indefinitely.
2016: On June 8th Sharapova was suspended for two years.
2018: Alexander Krushelnitsky won medals in curling for Russia at the Pyongyang Winter Olympics and was the subject of widespread doping allegations. The Olympic committee stripped him of his medals and banned him for two years.
Currently: It is still currently banned by WADA.
1.Meldonium has licenses throughout Eastern Europe and Central Asia for a number of health conditions but is not currently licensed for use in the United States in humans.
2.Meldonium has a patent in the US, Germany, France and the UK which allows it for use in animals. This document state that Meldonium allegedly is used for growth increase in livestock. Although there haven’t been any reports of someone actually doing it.
3.In 2010 A study found  that meldonium increased the sexual behaviour and semen quality in boars. Study also finds that Meldonium does increase activity of spermatozoons in oar semen.
4.Where licenced, it is mainly used to treat heart conditions because it helps increase the body’s ability to carry oxygen, according to one of the drug’s designers, Ivar Kalvins. In many parts of Asia it is also used to treat circulation problems in the brain, such as stroke.
5.Meldonium is still banned by WADA for use in sports at least until year 2020, and the ban has caught out many athletes since the ban was introduced in 2016.
6.Sales of the drug reached 56 million euros in 2013 and is one of Latvia’s biggest medical exports. Surprisingly, sales soared in Russia in the month after Sharapova’s ban, doubling the sale of over-the-counter sales.
7.From 1979 – 1989 Large quantities of the drug was shipped to Soviet troops in Afghanistan to help increase their endurance in high altitudes. This fact raised suspicions that Meldonium was actually researched and designed for military use not for livestock.
8. A 2005 study found  that when meldonium was used in combination with lisinopril (an angiotensin-converting enzyme inhibitor) people saw improved exercise capability in those with heart conditions. And a following Chinese study in 2013 found  that meldonium is also is efftrective in treating stroke victims.
9.In 2013 Revenue for the drug Mildronate® reached 56 million euros  and is one of the biggest medical exports for Latvia. This is not counting other brands names. As Latvian manufactured Meldonium by Olainpharm and few others who manufacture it in Russia.
10.In countries where it is sold , it is available over the counter and significant amount of population have used it for shorter or longer time periods. The main over the counter use cases are coping with stress, recovering from stressful life periods and mildly increasing energy levels.
Meldonium is a fatty acid oxidation inhibitor, and it works by altering pathways for carnitine, which is a nutrient involved in fat metabolism. This drug is said to expand the arteries and increase blood flow (and thus oxygen exchange efficiency is increased).
In countries where it holds licences, it is mainly used to treat cardiac conditions like angina, cardiac arrest, and heart failure.
WADA classes it as a metabolic modulator (as it does insulin), and they define this class as substances that can modify how some hormones accelerate or slow different enzymatic reactions in the body. These modulators can block the body’s conversion of testosterone into oestrogen. They have been banned since 2001 for men’s competition and 2005 for women’s.
Some of the controversy surrounding meldonium is due to lack of knowledge about the drug. Many countries are still uncertain of its effects. This mainly is beacause the research and approvement of such medicines in new countries takes a lot of time and resources. The company behind Mildronate is pushing for these licenses in several regions where they feel that it will be woth while.
Altough Mildronate is known to be a substance with few side effects, there are side effects which are seen in some users. According to official leaf let of Mildronate these are some of the common side effects:
Common (may affect more than 1 in 10 patients):
Rare (may affect less than 1 in 1 000 patients):
Studies are yet to report any serious side effects, the long term effects are a different question. Mildronate is not ment to be used for years in a row, the usual course of usage is 1-2 months and then it is recommended to stop. On other hand in countries where it is sold, it has been around for almost 50 years now.
The manufacturer, Grindeks, does not believe meldonium’s use should be banned for athletes, though the drug mainly reduces damage to cells that are caused by by-products of carnitine. They said it could not improve athletic performance, but that it can stop tissue damage where there is a lack of blood flow to a certain area of the body.
The views in scientific community differs , anaesthesiologist professor Michael Joyner at the Mayo Clinic, who studies how humans respond to physical and mental stress during exercise and other activities, told Forbes “evidence is lacking for many compounds believed to enhance athletic performance. Its use has a sort of urban legend element and there is not much out there that is clearly that effective. I would be shocked if this stuff had an effect greater than caffeine or creatine .”
So, although WADA has banned the substance, scientist yet to have provide solid proof about performance enhancing properties of Meldonium. Many believe that Meldonium was banned too soon and immaturely.There is little to no evidence that meldonium has any performing enhancing effects beyond those of allowed substances, like caffeine and creatine. And this, my dear readers, is the biggest controversy in all of the Mildronate story.
1.Meldonium use by athletes at the Baku 2015 European Games ,Mark Stuart, Christian Schneider, Klaus Steinbach. https://bjsm.bmj.com/content/50/11/694?int_source=trendmd&int_medium=trendmd&int_campaign=trendmd
2.Mildronate (Meldonium) in professional sports – monitoring doping control urine samples using hydrophilic interaction liquid chromatography – high resolution/high accuracy mass spectrometryn Christian Görgens, Sven Guddat, Josef Dib, Hans Geyer, Wilhelm Schänzer, Mario Thevis https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066279/
4.INFLUENCE OF PREPARATION MILDRONAT ON SEXUAL BEHAVIOR AND SEMEN QUALITY OF BOARS Vita Antāne , Ilmārs Stonāns , Jāzeps Rimeicāns , Māra Mangale , Zigmunds Brūveris , Alberts Auzāns , Aleksandrs Mednis , Ivars Lūsis http://llufb.llu.lv/conference/animal-health-food/2010/Latvia-Animal-health-foodhygiene-2010-5-11.pdf
5. Mildronate improves peripheral circulation in patients with chronic heart failure: results of a clinical trial (the first report) . Vilnis Dzerve, Dace Matisone, Indulis Kukulis, Janina Romanova https://www.researchgate.net/publication/228637069_Mildronate_improves_peripheral_circulation_in_patients_with_chronic_heart_failure_results_of_a_clinical_trial_the_first_report
6. Efficacy and safety of mildronate for acute ischemic stroke: a randomized, double-blind, active-controlled phase II multicenter trial. Zhu Y, Zhang G, Zhao J, Li D, Yan X, Liu J, Liu X, Zhao H, Xia J, Zhang X, Li Z, Zhang B, Guo Z, Feng L, Zhang Z, Qu F, Zhao G https://www.ncbi.nlm.nih.gov/pubmed/23949899