Is Trimetazidine A Safe Performance Enhancing Drug?

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The human body is a complex structure that requires energy for normal everyday function. In human cells, mitochondria generate energy in the form of ATP. The ATP is then used for cellular metabolism and essential functions. Without mitochondria and ATP, our cells cannot function normally. Organs that use a lot of cellular energy, including the brain, heart, and skeletal muscle, are especially dependent on mitochondrial function and energy production.  

In healthy individuals, the human heart typically uses a combination of free fatty acids and carbohydrates to synthesize ATP within mitochondria. Free fatty acids, which are derived from fats and oils, are plentiful in the body. Compared with carbohydrates, free fatty acids are a better fuel for energy production by the heart under normal conditions. However, when the heart is stressed due to exertion or is not working properly, its metabolism changes, and carbohydrates become a more efficient source of cardiac energy than free fatty acids. Under these conditions, ATP production from carbohydrate metabolism is the preferred source of energy for the heart. Drugs that shift cardiac energy production from the use of free fatty acids to use of carbohydrates can optimize the heart’s metabolic function under stress. Theoretically, this can lead to improved exercise tolerance.

Trimetazidine, also known as “TMZ”, is a drug that blocks free fatty acid metabolism and enhances carbohydrate utilization in the heart. It has been used for years in Asian and European countries as a treatment for heart disease, including stable angina. Trimetazidine has also been investigated as a potential treatment to increase functional performance in patients who have peripheral artery disease. In at least two studies, trimetazidine improved exercise capacity in patients with peripheral artery disease, suggesting that the drug may also improve energy utilization in skeletal muscle.

Because of these beneficial effects on exercise capacity and energy utilization, trimetazidine has been used as a performance-enhancing drug. While it does not have the muscle building or stimulant-like effects of many commonly recognized performance-enhancing or doping drugs, trimetazidine may enhance athletes’ physical efficiency and endurance. When used as a performance-enhancing drug, trimetazidine starts to work within hours of swallowing a single dose, and the clinical effects can last for days. Trimetazidine may be detected in athletes’ urine for several days after the last use of the drug. Side effects of trimetazidine include gastrointestinal distress, tremors, and weakness. Serious adverse reactions, including Parkinsonian symptoms, involuntary muscle movements, and difficulty walking, have been reported after the long-term use of trimetazidine. 

Trimetazidine is not approved by the FDA for clinical use in the United States and is not well known as a doping drug in this country. Overseas, trimetazidine has been detected in urine samples of athletes involved in various sports including cycling, swimming, soccer, and weightlifting. Trimetazidine was initially recognized as a “metabolic modulator” by the World Anti-Doping Agency (WADA) in 2014 and is currently included in their Prohibited List as a drug that is banned both in and out of competition. Trimetazidine is also a metabolite of lomerizine, a drug used for the treatment of migraine headaches. Lomerizine is not currently on the WADA’s Prohibited List. Because of this, specialized testing must be used when evaluating for the presence of trimetazidine in athletes’ urine, to ensure accurate identification of either the lomerizine byproduct or the banned trimetazidine.

If you suspect poisonings related to use of stimulants, steroids, or other performance-enhancing drugs, get an immediate personalized recommendation online or call Poison Control at 1-800-222-1222. Both options are free, confidential, and available 24 hours a day.

Kelly Johnson-Arbor, MD
Medical Toxicologist