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Surface here is educational only; do not use without medical supervision. Our editorial verdict is SKIP-FOR-NOW — current cost / risk / redundancy puts it below the line.

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Meldonium

Foreign-Approved / WADA-Banned

Mildronate | MET-88 | 3-(2,2,2-trimethylhydrazinium)propionate

Aliases (8)

Mildronate · mildronate · MET-88 · THP · Quaterine · 3-(2,2,2-trimethylhydrazinium)propionate · trimethylhydrazinium propionate · MeldoniumDihydrate

TYPICAL DOSE

500-1000 mg/day

500-1000 mg/day in 1-2 divided doses

ROUTE

Oral (capsule)

Oral capsule (250 mg or 500 mg)

CYCLE

2-4 weeks on, 4-8 weeks off

Cyclic — 2-4 weeks on, 4-8 weeks off (avoid chronic continuous use)

STORAGE

Room temp; original blister

Room temperature in original blister; protect from moisture

Overview

What is Meldonium?

Meldonium (Mildronate, MET-88) is a Soviet-developed cardio-metabolic modulator first synthesized in Latvia in the 1970s by the Latvian Institute of Organic Synthesis (later commercialized by Grindeks JSC). Approved Rx in Russia, Latvia, Ukraine, Belarus, Kazakhstan, and Georgia for ischemic heart disease and post-stroke recovery; NOT FDA-approved in the US and NOT EMA-approved in the EU. Added to the WADA Prohibited List S4.5.1 effective 1 January 2016 — the basis of the famous Maria Sharapova positive test (announced 7 March 2016, suspension reduced from 24 to 15 months on appeal).

Key Benefits

Forces a cellular fuel-substrate shift from long-chain fatty-acid β-oxidation toward glucose oxidation, improving ATP yield per mole of O2 by ~12%. Cardioprotective under ischemia (reduced acyl-carnitine accumulation, NO/eNOS upregulation via GBB buildup). Modest endurance signal in untrained subjects (3-7% VO2max, ~10-15% time-to-exhaustion); minimal in trained athletes whose endogenous metabolic flexibility already covers the pharmacological switch. Approved-indication benefit in stable angina, post-stroke recovery, and Russian/Soviet military altitude/cold tolerance protocols.

Mechanism of Action

Reversibly inhibits γ-butyrobetaine hydroxylase (BBOX1, Ki ~16-62 µM) — the final enzyme in carnitine biosynthesis — and competes with carnitine at the SLC22A5/OCTN2 transporter. Net result: endogenous carnitine production drops ~18-29%, tissue carnitine drops 30-50%, and long-chain fatty acids can no longer be imported into mitochondria. Cells switch to glucose oxidation, which yields more ATP per O2 — significant under hypoxia/ischemia, modest under normoxia. Accumulating γ-butyrobetaine secondarily activates the eNOS-NO pathway, producing mild vasodilation.

Pharmacokinetics

PeakHalf-life

Approximate curve — visual aid only, not data-precise PK

Peptide Interactions

L-carnitine / ALCAR:

Synergistic

paradoxical — meldonium *blocks* carnitine synthesis and uptake; supplementing carnitine partially defeats the mechanism. Some Eastern European protocols pai…

Coenzyme Q10:

Synergistic

supports the same mitochondrial efficiency goal via a different mechanism (electron transport chain). Plausible synergy; no published data.

Trimetazidine

Synergistic

(another fatty-acid oxidation inhibitor, 3-KAT inhibitor — also S4.5.1 banned): mechanistically overlapping; sometimes co-prescribed in Russian cardiology. F…

MOTS-c:

Synergistic

mitochondrial peptide that increases AMPK signaling and improves metabolic flexibility — plausible synergy on the "metabolic flexibility under stress" axis; …

ITPP (myo-inositol trispyrophosphate):

Synergistic

allosteric Hb modulator that increases tissue O₂ release — mechanistically complementary (meldonium reduces O₂ demand per ATP, ITPP increases O₂ supply). WAD…

Insulin / sulfonylureas / GLP-1 agonists

Avoid

(high-dose) — additive glucose-lowering; hypoglycemia risk.

Cardiac glycosides (digoxin)

Avoid

theoretical interaction on sodium-potassium ATPase pathways; limited data.

Other fatty-acid oxidation inhibitors

Avoid

(trimetazidine, ranolazine, perhexiline) — additive metabolic shift, unclear safety.

Quality Indicators

✓

Grindeks Mildronate (Latvia) — original blister pack

Original manufacturer Grindeks JSC (Latvia). Sealed blister of 250 mg or 500 mg capsules in original retail box with Russian/Latvian labeling. Lot number visible. Highest reliability path for the molecule itself.

Indian generic Mildronate

Bioequivalence not formally established. Some batches reportedly underdose. Acceptable for non-critical use if vendor is reputable; do not assume label dose equals delivered dose.

✗

Chinese research-chem powder, no COA

Common form for 'research' sales. 2018-2022 spot tests showed adulteration with inert filler in ~15% of samples. Avoid unless independent third-party assay is available.

✗

Counterfeit packaging (mismatched lot numbers, language errors)

Russian-language counterfeits of Grindeks Mildronate appeared on gray-market channels post-2016 ban. Mismatched font, incorrect Latvian regulatory codes, or absent lot tracking are red flags.

What to Expect

Onset
30-90 min after oral dose (Tmax ~1-2 hr after 500 mg oral, ~78% bioavailability).
Peak
2-4 hours; effect on metabolism takes 2-7 days to fully manifest as tissue carnitine drops.

Side Effects & Safety 8

Side Effects

1Mild GI upset (nausea, dyspepsia, diarrhea) — 5-10% in trials, usually self-limited.
2Headache — 3-7%, week 1-2.
3Mild dyspepsia.
4Skin rash (uncommon, hypersensitivity-type).
5Tachycardia, palpitations.
6BP changes — usually mild reduction (NO-mediated vasodilation), occasionally mild elevation.
7Agitation / restlessness.
8Eosinophilia (rare).

When to Stop

Hypoglycemia in insulin-dependent diabetics — the forced glucose-oxidation shift can amplify insulin's effect; case reports exist. Caution if combining with insulin or sulfonylureas.
Renal accumulation in CrCl < 30 mL/min — plasma half-life can exceed 24 hours; toxicity profile in this setting is poorly characterized.
Hypersensitivity reactions — rare but reported.
Theoretical: prolonged carnitine depletion in chronic users — long-term tissue carnitine depletion has not been studied in healthy populations beyond ~12 weeks. Whether chronic depletion of cardiac carnitine in an *otherwise healthy* heart produces any deleterious phenotype is unknown. Soviet/Russian use was always cyclic, partly for this reason.
First 2 weeks: GI tolerance, headache, sleep onset.
4-6 weeks: carnitine depletion plateau; reassess goal achievement and stop.
Renal function: check BUN/creatinine baseline if any history of renal disease; avoid if CrCl < 30 mL/min.

References

Liepinsh, E., Vilskersts, R., Loca, D., et al. 2011 — Mildronate, an inhibitor of carnitine biosynthesis, induces an increase in gamma-butyrobetaine contents and cardioprotection in isolated rat heart infarction (Cardiovasc Drugs Ther / mechanism review)

pubmed.ncbi.nlm.nih.gov · 2011

foundational mechanism paper from the Latvian Institute of Organic Synthesis (Grindeks-affiliated).

Meldonium

Overview

What is Meldonium?

Key Benefits

Mechanism of Action

Pharmacokinetics

Peptide Interactions

Quality Indicators

Grindeks Mildronate (Latvia) — original blister pack

Indian generic Mildronate

Chinese research-chem powder, no COA

Counterfeit packaging (mismatched lot numbers, language errors)

What to Expect

Side Effects & Safety 8

Side Effects

When to Stop

References

Liepinsh, E., Vilskersts, R., Loca, D., et al. 2011 — Mildronate, an inhibitor of carnitine biosynthesis, induces an increase in gamma-butyrobetaine contents and cardioprotection in isolated rat heart infarction (Cardiovasc Drugs Ther / mechanism review)

Schobersberger, W., Hoffmann, G., Grünewald, M., et al. 1990 — Carnitine biosynthesis: occurrence and physiological significance (Innsbruck — early Western confirmation of the BBOX1 pathway)

Dzintare, M., Baumane, L., Meirena, D., et al. 2010 — Multicentric Latvian cardiovascular trial of meldonium in stable angina (Medicina Kaunas)

Dambrova, M., Liepinsh, E., Kalvinsh, I. 2014 — Mildronate: cardioprotective action through carnitine-lowering effect (Trends Cardiovasc Med review)

Görgens, C., Guddat, S., Dib, J., et al. 2016 — Mildronate (Meldonium) in professional sports — monitoring doping control urine samples using hydrophilic interaction liquid chromatography high-resolution / high-accuracy mass spectrometry (Drug Test Anal — WADA detection methodology)

WADA — The 2016 Prohibited List (Effective 1 January 2016)

WADA — Notice on Meldonium Cases (April 2016)

Eichner, A.K., Lewis, L.A., Leonard, B., et al. 2017 — Generalisability of urinary meldonium excretion data: meta-analysis of cleared meldonium adverse analytical findings (Drug Test Anal)

CAS Decision in Sharapova v. ITF (CAS 2016/A/4643, 30 September 2016)

Aguilaniu, B., Gillet, J., Wuyam, B. 1992 — Effects of meldonium on aerobic capacity in trained subjects (early Western trial)

Statsenko, M.E., Turkina, S.V., Chumachek, E.V. 2009 — Use of meldonium in patients with stable angina pectoris (Russian Journal of Cardiology / pooled clinical experience)

Sjakste, N., Gutcaits, A., Kalvinsh, I. 2015 — Mildronate: an antiischemic drug for neurological indications (CNS Drug Reviews update)

Skvortsova, V.I., Stakhovskaia, L.V., Naridzhanova, T.S., Pleshakov, V.T. 2007 — Use of meldonium in acute ischemic stroke (Zh Nevrol Psikhiatr Im S S Korsakova)

Maria Sharapova WADA / ITF Case Summary — BBC Sport (March 2016)

Meldonium — Wikipedia 2026 (regulatory and PK summary)

WADA 2016 Adverse Analytical Findings Statistics — Annual Report

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