Meldonium (Mildronate)
A cardioprotective anti-ischaemic drug developed in Latvia and widely prescribed across the former Soviet bloc. It shifts myocardial energy metabolism away from fatty-acid oxidation toward glucose oxidation, which lowers oxygen demand during ischaemia. It became infamous in sport after WADA banned it in 2016 and dozens of athletes, including Maria Sharapova, tested positive.
01 Overview
Meldonium (3-(2,2,2-trimethylhydrazinium)propionate) inhibits gamma-butyrobetaine hydroxylase and carnitine biosynthesis, reducing carnitine-dependent long-chain fatty-acid transport into mitochondria. The clinical rationale is that during ischaemia, glucose oxidation is more oxygen-efficient than fatty-acid oxidation, so forcing the shift protects marginally perfused tissue. It carries regional marketing approval (Latvia, Russia and neighbours) for angina and chronic heart failure but is not approved by the FDA or EMA.
Athletes used it for claimed improvements in exercise tolerance and recovery. Human ergogenic data are weak, but it was detected so widely in elite sport that WADA added it to the Prohibited List in January 2016. Its long and variable clearance caught out many athletes who had stopped dosing before the ban took effect.
02 Mechanism
Inhibits gamma-butyrobetaine hydroxylase, lowering L-carnitine synthesis and thereby reducing mitochondrial long-chain fatty-acid oxidation while promoting more oxygen-efficient glucose oxidation during ischaemia.
03 Dosing
| Tier | Dose | Route | Notes |
|---|---|---|---|
| Athletic (non-medical) | 500–1000 mg/day | Oral | Off-label ergogenic use; banned in competition. |
| Angina/heart failure | 500–1000 mg/day | Oral | Typical regional label dosing, often split twice daily. |
04 Effects
| Effect | Magnitude | Evidence | |
|---|---|---|---|
| Improved anginal exercise toleranceSmall trials in stable angina report increased exercise duration when added to standard therapy. | modest | Clinical | |
| Anti-ischaemic cardioprotectionMetabolic shift toward glucose oxidation reduces myocardial oxygen demand in ischaemic tissue. | modest | Clinical | |
| Claimed endurance/recovery boostWidely used by athletes for perceived recovery benefits; controlled ergogenic evidence in healthy athletes is thin. | Anecdotal |
05 Side effects
| Effect | Severity | Frequency | Evidence | Countermeasures |
|---|---|---|---|---|
| Gastrointestinal upsetDyspepsia and nausea reported at higher doses. | Mild | Occasional | Clinical | |
| Overstimulation / insomniaSome users report agitation or sleep disturbance, so evening dosing is discouraged. | Mild | Occasional | Observational | |
| Sanctioned doping violationProhibited in and out of competition by WADA since 2016; positive tests carry bans. | Severe | For competing athletes | Clinical |