What Is Meldonium/Mildronate?
The widely used drug was added to the WADA list of banned substances on January 1, 2016 because of “evidence of its use by athletes with the intention of enhancing performance.”
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In early March, Abebe Aregawi, the 2013 women’s 1500m world champion, was provisionally suspended after the drug meldonium was found in her system. Days later, Endeshaw Negesse, the 2015 Tokyo marathon champion with a personal best of 2:04.52, was also banned after reportedly testing positive for the same substance. This news came in the same week that Solomon Meaza, the general secretary of Ethiopia’s anti-doping agency, told the Associated Press that nine of the country’s runners, five of them “top athletes,” are under investigation for doping. Aregawi represents Sweden, but was born and resides in Ethiopia, and Negesse is also Ethiopian.
With the recent news that Russia’s entire world championship hockey team has been replaced by younger players under suspicion of meldonium use, we take a closer look at what the drug actually is, and the associated ban. Here’s what you need to know.
What It Is
Meldonium is a drug used to treat angina, myocardial infarction, and chronic heart failure. It’s manufactured in Latvia under the commercial name Mildronate and is one of the country’s largest exports, with turnover reaching close to 75 million dollars in 2013. It is not yet approved by the FDA for use in the U.S.
Meldonium was added to the WADA list of banned substances on January 1, 2016 because of “evidence of its use by athletes with the intention of enhancing performance.” As a result, none of the athletes banned for this substance will have performances prior to that date removed from their records, and Aregawi will keep her 2013 world title.
Why It Might Be Used as a PED
Meldonium shifts the metabolism, so that it is geared more towards carbohydrate metabolism than fat metabolism. Using carbohydrate as a fuel requires less oxygen to produce energy, so this change can be beneficial in low oxygen conditions. In heart disease, the heart muscle is deprived of oxygen, and the effects of meldonium have been shown to be very beneficial in this disease state. There is also evidence to suggest that meldonium could be equally beneficial under the low oxygen conditions induced by intense endurance exercise.
One review of the effects of meldonium on exercise performance listed the following benefits:
- Decreased levels of lactate and urea in blood
- Improved economy of glycogen: level of glycogen increased in the cells during the long-lasting exercise
- Increased endurance properties and aerobic capabilities of athletes
- Improved functional parameters of heart activity
- Increased physical work capabilities
- Increased rate of recovery after maximal and sub-maximal loads
- Activates CNS functions and protects against stress
A published human research study on the effects of meldonium on sports performance used Russian judokas and gave them a dose of 0.5-1.0 g twice a day before training, as a 14-21 day course during the training period 10-14 days before competition. Some of the above effects published in the review article were reported from this study. Unfortunately, quite a lot of the research into this topic is only published in Russian. Another Russian study, translated into English, showed a significant improvement in the swimming of rats after meldonium supplementation.
Why It Was Banned
The process by which WADA adds a substance to the banned list involves that substance first being placed on the WADA monitoring program. The addition of a substance to the monitoring program usually comes about as a result of athlete statements and any other evidence that WADA collects.
The “other evidence” in this case was that WADA repeatedly detected meldonium in urine samples during the validation of their new high resolution/high accuracy mass spectrometry multi-target screening assay. A peak at 147.1128 appeared in the MS spectra of many but not all urine samples during the validation process, indicating that the peak represented an exogenous substance. WADA determined that this peak indicated the presence of meldonium. This evidence, coupled with athlete statements, led to the addition of meldonium to the WADA monitoring program a year prior to the ban, on January 1, 2015.
What WADA Found
WADA decided that there was enough evidence to investigate further as they developed two separate tests for meldonium. Both tests use a urine sample—the first is easily compatible with current tests carried out for other substances in anti-doping laboratories and could be used to screen large numbers of samples, while the second is more specific to meldonium and could unequivocally determine its presence in a sample.
Using these two tests in combination, a total of 8320 random doping control urine samples covering different classes of sport either from in- or out-of-competition were analyzed for the presence of meldonium. One hundred and eighty two positive Meldonium findings (2.2%) in a concentration range between 0.1 and 1428 μg/mL were detected and confirmed using the more sensitive assay. This is shown in the graph below.
What It All Means
This data, along with the several bans that have arisen since meldonium was placed on the banned list on January 1, indicates that the use of meldonium is fairly widespread and we should expect to see several more cases in the coming weeks and months. Besides track and field, there has also been a confirmed positive case in cycling for Eduard Vorganov, the Katusha former Russian national road champion and 19th place Tour de France finisher, who was an important dometique rider for Joaquim Rodriguez in his second place finish in last year's Vuelta a Espana. There have also been two positives for fairly high-profile Ukranian biathletes. Given that the drug is manufactured and distributed mostly in Eastern Europe, most positive cases will likely come from athletes in that region. It is being reported that a Ukrainian doctor may have been involved in the transportation of the substance into Ethiopia, so we may see more positives from Ethiopian athletes as well.