Trimetazidine and Athletic Performance: Is There an Effect?
Trimetazidine became widely known outside cardiology when it featured in high-profile doping cases, including in figure skating. It is often described online as a "heart protector" for athletes. The editorial team examines what this medicine actually does, whether it enhances performance in healthy people and why it is prohibited in sport.
What trimetazidine is
Trimetazidine is a prescription medicine used in a number of European and other countries as an add-on treatment for stable angina, chest pain caused by reduced blood flow to the heart muscle. It is not licensed in the United Kingdom and is not approved in the United States, so British patients will very rarely encounter it in routine care.
Unlike most anti-anginal drugs, trimetazidine does not lower heart rate or blood pressure, nor does it dilate blood vessels in a meaningful way. Instead, it is classed as a metabolic modulator: it changes the way heart cells produce energy.
The drug was introduced decades ago and, in the countries where it is licensed, is typically prescribed as a modified-release tablet. Its role was reassessed by the European Medicines Agency in 2012, which concluded that it should only be used as a second-line, add-on treatment for angina and withdrew other indications such as tinnitus and vertigo.
That reassessment followed concerns about movement disorders, including parkinsonian symptoms, tremor and gait instability, particularly in older patients and in people with reduced kidney function. These side effects are among the main reasons the drug's use has been restricted.
How it changes cardiac energy metabolism
The heart normally obtains most of its energy from burning fatty acids, with glucose contributing a smaller share. Fatty acid oxidation yields a lot of ATP but requires more oxygen per unit of energy than glucose oxidation. When oxygen supply is limited, as in ischaemia, this becomes a disadvantage.
Trimetazidine partially inhibits an enzyme of fatty acid oxidation known as long-chain 3-ketoacyl-CoA thiolase. As a result, heart cells shift towards burning more glucose. This was demonstrated in a well-known experimental study published in Circulation Research in 2000, using isolated rat hearts.
In a heart with restricted blood supply, this shift means more energy can be produced for the same amount of oxygen, and less harmful build-up of lactate and acidity occurs. That is the rationale for its use in angina and, experimentally, in heart failure.
It is important to note that the benefit of this metabolic switch depends on oxygen being the limiting factor. In a healthy heart with normal coronary blood flow, the situation is different, and the theoretical advantage is much less clear.
Evidence on performance in healthy people
There is a striking gap between the reputation of trimetazidine in sport and the evidence behind it. Controlled trials in healthy, trained athletes are extremely scarce, and the editorial team is not aware of any robust randomised study showing that trimetazidine improves endurance, power or recovery in people without heart disease.
Studies in patients with angina or heart failure have shown improvements in exercise tolerance on treadmill tests, such as longer time to chest pain or ST-segment changes. These results reflect relief of ischaemia in diseased hearts, not an enhancement of normal physiology, and they cannot be transferred to healthy athletes.
Large outcome trials have also tempered expectations even in cardiology. The ATPCI trial, published in The Lancet in 2020, included more than 6,000 patients after coronary angioplasty and found no reduction in cardiac events or recurrence of angina with trimetazidine compared with placebo over several years.
Why, then, has it been used in sport? Plausibly because of the belief that metabolic efficiency could help the heart under extreme loads, combined with its easy availability in some countries and an initially lower awareness of its prohibited status. Belief and availability, rather than evidence, appear to have driven its use.
Anti-doping status
Trimetazidine was added to the WADA Prohibited List in 2014 as a stimulant and was reclassified from 2015 into the category of hormone and metabolic modulators (S4). It is prohibited at all times, both in and out of competition.
| Aspect | Status |
|---|---|
| WADA category | S4 Hormone and metabolic modulators |
| When prohibited | At all times (in and out of competition) |
| Licensed in the UK | No |
| Licensed in parts of the EU | Yes, as add-on therapy for stable angina |
| Therapeutic Use Exemption | Possible only with documented medical need |
UK Anti-Doping operates under the World Anti-Doping Code and the principle of strict liability. An athlete is responsible for any prohibited substance found in their sample, regardless of how it got there. Contamination claims are investigated, but the burden of proof rests heavily on the athlete.
The case involving a young Russian figure skater at the 2022 Winter Olympics, eventually resolved by the Court of Arbitration for Sport with a period of ineligibility, brought global attention to trimetazidine. It also highlighted the role of adult entourage members when minors test positive for medicines.
Side effects and safety concerns
Trimetazidine is often perceived as a "gentle" or "metabolic" drug, but it has a defined side-effect profile. The most important concerns are neurological: parkinsonism, tremor, muscle rigidity, restless legs and gait disturbances. These are usually reversible on stopping the drug but may take months to resolve.
- Neurological: parkinsonian symptoms, tremor, restless legs, unsteadiness.
- Gastrointestinal: abdominal pain, nausea, indigestion.
- General: dizziness, headache, fatigue, skin reactions.
- Special groups: greater risk in older people and with impaired kidney function.
In the countries where it is prescribed, it is contraindicated in Parkinson's disease and related movement disorders and in severe kidney impairment. Prescribing information recommends dose adjustment in moderate renal impairment, which is why it is not a drug to be taken without supervision.
Using an unlicensed, imported prescription drug without a medical indication also carries the usual risks of uncertain product quality and of masking symptoms that may need investigation. Chest pain or breathlessness during exercise should prompt a medical assessment, not self-treatment.
Conclusions of the editorial team
Trimetazidine is an anti-anginal drug that shifts heart energy metabolism from fat towards glucose, which can help an oxygen-starved heart.
There is no convincing evidence that it improves performance in healthy athletes, and even in cardiology its benefits have been questioned by large trials.
It is prohibited at all times by WADA, not licensed in the UK, and carries real risks of movement disorders. For athletes, the risk-benefit balance is clearly unfavourable.
Readers may also be interested in our articles on meldonium and its history in sport, on the athlete's heart versus cardiomyopathy, and on how Therapeutic Use Exemptions work.
References
- Kantor PF, Lucien A, Kozak R, Lopaschuk GD. The antianginal drug trimetazidine shifts cardiac energy metabolism from fatty acid oxidation to glucose oxidation by inhibiting mitochondrial long-chain 3-ketoacyl coenzyme A thiolase. Circ Res. 2000;86(5):580–588.
- Ferrari R, Ford I, Fox K, et al. Efficacy and safety of trimetazidine after percutaneous coronary intervention (ATPCI): a randomised, double-blind, placebo-controlled trial. Lancet. 2020;396(10254):830–838.
- European Medicines Agency. Assessment report: trimetazidine-containing medicinal products (Article 31 referral). London: EMA; 2012.
- World Anti-Doping Agency. Prohibited List. Montreal: WADA; updated annually.
- Pope HG Jr, Wood RI, Rogol A, et al. Adverse health consequences of performance-enhancing drugs: an Endocrine Society scientific statement. Endocr Rev. 2014;35(3):341–375.
