Evidence memo / Anabolic androgens & PEDs

Meldonium

Also: mildronate · MET-88

A cardiac drug licensed in parts of Eastern Europe and never approved in the West, banned in sport in 2016 after it turned out a large fraction of elite athletes were already taking it, with a metabolic rationale that is more interesting than its human performance evidence.

Claim-specific / contestedContext-dependentInvestigationalSafety / regulatory watch

The verdict

Our read at a glance.

Whether shifting cardiac and muscle metabolism away from fatty acids improves performance or recovery in healthy athletes.

The signal
Meldonium has a genuine clinical literature in the countries where it is licensed, studied in ischaemic heart disease, heart failure and cerebrovascular contexts, with registered trials and published cardiology work behind that use. The mechanism is well described. What is much thinner is controlled evidence that it improves performance or recovery in healthy trained people, which is the claim that drove its use in sport. Its most notable appearance in the international literature is pharmacokinetic and analytical work generated after the ban, examining how long excretion continues - the question that decided a large number of contested cases.
The unknown
Whether there is any ergogenic effect in healthy athletes at all, since almost nothing in the literature tests that directly.
Our read
A real drug for a real cardiac indication in the countries that license it, adopted by athletes on the strength of a mechanism rather than a trial. The most rigorous science it generated in the West was about how long it takes to leave the body.

The mechanism

How it works.

Carnitine is the shuttle that carries long-chain fatty acids into mitochondria to be burned. Meldonium inhibits gamma-butyrobetaine hydroxylase, the enzyme that makes carnitine, lowering carnitine levels and therefore restricting fatty acid transport. The cell compensates by burning more glucose. That matters in ischaemia because glucose oxidation yields more ATP per unit of oxygen than fatty acid oxidation does, so under low oxygen a heart running on glucose is better off - which is the coherent rationale behind its cardiology use. Extending that to a healthy athlete requires assuming the same substrate shift helps a well-perfused muscle with adequate oxygen, and that is precisely the step the evidence does not cover.

Safety & regulatory boundary

The consequential part.

Not approved by FDA or EMA; approved in several Eastern European countries. Prohibited in sport since 2016. Because there is no Western approval, product obtained outside those markets has no regulatory manufacturing oversight. The safety record within its licensed use is reasonable, but that record was generated in cardiac patients under supervision, not in healthy athletes self-administering.

What's next

What we're watching.

Any controlled trial with performance endpoints in healthy subjects, which would be the first real test of the claim.

Context

Why this is discussed.

The 2016 ban produced a wave of positive tests among elite athletes, which told everyone that a lot of people believed it worked.

The evidence base

19 cited references.

Registered trials7

Novel Approach to Increase EPA and DHA Levels

ClinicalTrials.gov · PHASE1 · COMPLETED · 2023-04-06

Impact of Medically Supervised Performance-Enhancing Substances (PES) on Elite Athletes

ClinicalTrials.gov · NA · ENROLLING_BY_INVITATION · 2026-03-12

Mildronate for Acute Ischemic Stroke

ClinicalTrials.gov · PHASE2 · COMPLETED · 2008-07

Efficacy and Safety of Mildronate for Acute Ischemic Stroke

ClinicalTrials.gov · PHASE2 · UNKNOWN · 2013-01

Indexed literature (PubMed)12

[Meldonium: current and emerging therapeutic applications]

Ponamarczuk H et al. · Postepy Biochem · 2025

Keep reading

Related published memos.