Meldonium

updated

Meldonium (Mildronate) is authorized in Austria, Finland, Ireland and Norway for supplementary treatment of mild long-term heart failure, and no FDA-approved product turned up. In MILSS I, 512 patients with chronic coronary heart disease gained exercise time on the 1000 mg daily dose (35.18 seconds versus -7.10 seconds on placebo). A PubMed search on 10 October 2026 found no randomized trial of exercise performance or recovery in healthy people.

Metabolic modulator, described as a carnitine synthesis and transport blocker

  • An Irish package leaflet revised 05/2024 names AS Grindeks of Riga, Latvia as marketing authorization holder and lists authorization in Austria, Finland, Ireland and Norway for mild long-term heart failure.
  • openFDA Drugs@FDA and DailyMed searches on 10 October 2026 found no FDA-approved meldonium product or label.
  • MILSS I (512 patients with chronic coronary heart disease, 12 weeks) found exercise time changed by -7.10 seconds on placebo and rose 35.18 seconds on 1000 mg a day (P = 0.002).
  • WADA added meldonium to the Prohibited List in the January 2016 edition because of evidence of use with intent to enhance performance, and the 2026 List still names it.
  • At the Baku 2015 European Games, 66 of 762 athlete urine samples (8.7%) tested positive for meldonium.
  • PubMed searches on 10 October 2026 returned 55 performance records and 5 anabolic steroid records, and none tested performance or recovery in healthy people or cardiac protection in steroid users.

What is meldonium, and where is it authorized?

Meldonium (Mildronate) is authorized as a national medicine in Austria, Finland, Ireland and Norway for supplementary treatment of mild long-term heart failure in adults. No FDA-approved meldonium product turned up.

An Irish package leaflet last revised 05/2024 for Mildronate 500 mg hard capsules names AS Grindeks of Riga, Latvia as marketing authorization holder and says the medicine is authorized in Austria, Finland, Ireland and Norway under local names. The listed use is supplementary treatment of mild long-term heart failure in adults, and the leaflet says it is not for children. These are national authorizations. They are not an FDA approval and should not be read as equivalent to FDA or EMA review. Registrations in other countries are not confirmed here.

The leaflet makes no claim for exercise performance, recovery or use in healthy people. It carries an anti-doping warning that the medicine may cause a positive test.

On 10 October 2026, openFDA Drugs@FDA searches on the generic name meldonium, the active ingredient meldonium and the brand name mildronate each returned no matches, and DailyMed label searches for meldonium, meldonium dihydrate and mildronate returned no labels. That says nothing about imports or supplements, and US dietary-supplement status was not examined.

Meldonium, also called mildronate, MET-88 and THP, is PubChem CID 123868 (C6H14N2O2, 146.19 g/mol, CAS 76144-81-5). The dihydrate in the EU capsules is a separate record (CID 6918082, C6H18N2O4, 182.22 g/mol, CAS 86426-17-7), and label doses are written as the dihydrate: 500 mg of meldonium dihydrate equals 401.14 mg of meldonium.

Irish HPRA leaflet, revised 05/2024: authorized in four EEA states for mild heart failure

Official label

Health Products Regulatory Authority (Ireland). Mildronate 500 mg hard capsules, package leaflet, last revised 05/2024. Marketing authorization holder AS Grindeks, Riga, Latvia.

The leaflet names AS Grindeks of Riga, Latvia as marketing authorization holder and says the medicine is authorized in Austria, Finland, Ireland and Norway under local names, for supplementary treatment of mild long-term heart failure in adults. It is not for children, and an anti-doping warning says it may cause a positive test. Common side effects (up to 1 in 10) are allergic reactions, headache and indigestion. The leaflet makes no claim for exercise performance, recovery or use in healthy people. 500 mg of meldonium dihydrate equals 401.14 mg of meldonium.

Participants / model
Adults with mild long-term heart failure
Treatment
Mildronate 500 mg oral hard capsules (meldonium dihydrate)
Follow-up
Leaflet last revised 05/2024
Study design
Package leaflet from a national regulator
Funding
not stated in the source

These are national authorizations. They are not an FDA approval and are not equivalent to FDA or EMA review.

Read the original source
Searches, 10 October 2026: no FDA application or label

Regulatory record

U.S. Food and Drug Administration. openFDA Drugs@FDA queries on generic name meldonium, active ingredient meldonium and brand name mildronate, with DailyMed label searches for meldonium, meldonium dihydrate and mildronate, all run on 10 October 2026.

Each openFDA Drugs@FDA query returned No matches found, and each DailyMed search returned no labels. No FDA-approved meldonium product turned up.

Participants / model
Records reviewed, not a population
Treatment
Not applicable
Follow-up
Searches run on 10 October 2026
Study design
Dated regulator database search
Funding
not stated in the source

The result covers FDA application and label records. It says nothing about imports or supplements.

Read the original source
PubChem: meldonium and meldonium dihydrate identity

Chemical identity record

National Library of Medicine. PubChem compound records CID 123868 (meldonium) and CID 6918082 (meldonium dihydrate).

Meldonium (mildronate, MET-88, THP): PubChem CID 123868, C6H14N2O2, 146.19 g/mol, CAS 76144-81-5. The dihydrate used in the EU capsules is a separate record: CID 6918082, C6H18N2O4, 182.22 g/mol, CAS 86426-17-7. Doses on EU labels are written as the dihydrate.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule and its dihydrate
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

Read the original source

What did the angina and heart failure trials find?

In MILSS I, a phase 2 trial in 512 patients with chronic coronary heart disease, exercise time rose on the 1000 mg daily dose and not on 100 or 300 mg. In a small Russian-language trial in post-infarction heart failure, meldonium and trimetazidine both lowered functional class, and only trimetazidine raised ejection fraction.

MILSS I randomized 512 patients with chronic coronary heart disease and exercise-induced ischemia at 72 centers in 4 countries to standard therapy plus placebo or plus meldonium at 4 daily doses for 12 weeks, in a double-blind phase 2 design. Change in total exercise time on bicycle ergometry was -7.10 seconds on placebo, -2.12 seconds on 100 mg and 11.48 seconds on 300 mg (neither significant), and 35.18 seconds on 1000 mg (P = 0.002). 3000 mg gave a smaller gain than 1000 mg, and the authors concluded 500 mg twice a day was the most effective dose of those tested. The abstract does not state the sponsor.

This was a dose-finding trial in patients with angina on standard therapy, not in healthy people.

In 65 patients with chronic heart failure more than 6 months after myocardial infarction and an ejection fraction under 40%, randomized to basic therapy plus trimetazidine MB (n = 28), basic therapy plus meldonium dihydrate (n = 25), or basic therapy alone (n = 12) for 6 months, both active groups lowered heart failure functional class and lengthened the 6-minute walk. Ejection fraction rose significantly only with trimetazidine, and the authors preferred trimetazidine. The report is small and in Russian, and the abstract does not state blinding or centers.

MILSS I: 512 patients, 12 weeks, exercise time up on the 1000 mg daily dose

Randomized controlled trial

Dzerve V. Medicina (Kaunas). 2011;47(10):544-51. PMID 22186118.

Change in total exercise time on bicycle ergometry was -7.10 seconds on placebo versus -2.12 seconds on 100 mg and 11.48 seconds on 300 mg (neither significant), and 35.18 seconds on 1000 mg (P = 0.002). 3000 mg gave a smaller gain than 1000 mg. The authors concluded 500 mg twice a day was the most effective dose.

Participants / model
512 patients with chronic coronary heart disease and exercise-induced ischemia (stable angina), at 72 centers in 4 countries
Treatment
Oral meldonium 100, 300, 1000 or 3000 mg a day plus standard therapy, or placebo plus standard therapy
Follow-up
12 weeks
Study design
Double-blind phase 2 randomized trial
Funding
not stated in the source

A phase 2 dose-finding trial in patients with angina on standard therapy, not in healthy people. Endpoints were exercise time on bicycle ergometry, maximum load and time to angina.

Read the original source
Russian-language trial: 65 patients, 6 months, meldonium versus trimetazidine MB

Randomized controlled trial

Vasiuk IuA et al. Ter Arkh. 2007;79(2):51-8. PMID 17460970.

Both active groups lowered heart failure functional class and lengthened the 6-minute walk. Ejection fraction rose significantly only with trimetazidine, and the authors preferred trimetazidine.

Participants / model
65 patients with chronic heart failure more than 6 months after myocardial infarction, ejection fraction under 40%
Treatment
Basic therapy plus trimetazidine MB 70 mg a day (n = 28), basic therapy plus meldonium dihydrate 1000 mg a day (n = 25), or basic therapy alone (n = 12)
Follow-up
6 months
Study design
Randomized three-arm comparison; blinding and centers not stated in the abstract
Funding
not stated in the source

A small Russian-language report. The abstract names meldonium by its chemical name, meldonium dihydrate. Endpoints were functional class, 6-minute walk, PET and SPECT myocardial metabolism and ejection fraction.

Read the original source

Why is meldonium prohibited in sport?

WADA put meldonium on its Prohibited List in the January 2016 edition because of evidence that athletes used it with the intention of enhancing performance, not because a performance effect was shown. The 2026 List still names it.

WADA's January 2016 Prohibited List, stated to come into effect on 1 January 2016, names meldonium as item 5.3 under metabolic modulators in class S4, hormone and metabolic modulators, within the classes prohibited at all times. The 2026 List, in effect from 1 January 2026, still names it, as item S4.4.3.

WADA's explanatory notes dated 16 September 2015 say meldonium (mildronate) was added because of evidence that athletes used it with the intention of enhancing performance, and that it moved from the Monitoring Program to the Prohibited List. The stated reason is evidence of use with that intent, not a demonstrated performance effect. The copy of the notes read here is hosted by the FIA.

At the Baku 2015 European Games, 66 of 762 athlete urine samples (8.7%) tested positive for meldonium, and 23 of 662 tested athletes (3.5%) declared personal use. Athletes from 6 countries declared use, and use was found in 15 of 21 sports. The authors call this widespread and inappropriate use of a prescription drug in a generally healthy athlete population. The abstract does not say the athletes were from Eastern Europe and reports no effect on performance.

WADA 2016 List: meldonium item 5.3, class S4; still listed in 2026

Regulatory record

World Anti-Doping Agency. The 2016 Prohibited List, stated to come into effect on 1 January 2016. The 2026 List, in effect from 1 January 2026, is a separate document that also names meldonium.

The 2016 List names meldonium as item 5.3 under metabolic modulators in class S4, hormone and metabolic modulators, within the classes prohibited at all times. The 2026 List, in effect from 1 January 2026, still lists meldonium, as item S4.4.3.

Participants / model
Not a clinical population
Treatment
Anti-doping rule
Follow-up
In effect from 1 January 2016; 2026 List in effect from 1 January 2026
Study design
Official anti-doping list
Funding
not stated in the source

The 2026 item number comes from the 2026 List document, not from the 2016 edition.

Read the original source
WADA explanatory notes, 16 September 2015: why meldonium was added

Regulatory record

World Anti-Doping Agency. 2016 Prohibited List, Summary of Major Modifications and Explanatory Notes, 16 September 2015. Copy hosted by the FIA.

The notes say meldonium (mildronate) was added because of evidence that athletes used it with the intention of enhancing performance, and that it was moved from the Monitoring Program to the Prohibited List.

Participants / model
Not a clinical population
Treatment
Anti-doping rule
Follow-up
Dated 16 September 2015
Study design
Official anti-doping document
Funding
not stated in the source

The stated reason is evidence of use with that intent, not a demonstrated performance effect.

Read the original source
Baku 2015: 66 of 762 urine samples positive (8.7%)

Human study

Stuart M et al. Br J Sports Med. 2016;50(11):694-8. PMID 27015859.

At the Baku 2015 European Games, 66 of 762 athlete urine samples (8.7%) tested positive for meldonium, and 23 of 662 tested athletes (3.5%) declared personal use. Athletes from 6 countries declared use, and use was found in 15 of 21 sports. The authors call this widespread and inappropriate use of a prescription drug in a generally healthy athlete population.

Participants / model
Athletes at one multi-sport event, mostly healthy
Treatment
Not a treatment trial; surveillance of declarations and urine tests
Follow-up
One multi-sport event, the Baku 2015 European Games
Study design
Surveillance report
Funding
not stated in the source

The abstract does not say the athletes were from Eastern Europe and reports no effect on performance.

Read the original source

Does meldonium improve performance or recovery, or protect the heart during steroid cycles?

No trial found supports those claims in healthy people. A PubMed search on 10 October 2026 returned 55 records on performance and none was a randomized trial of exercise performance or recovery in healthy people, and a second search returned 5 records on anabolic steroids and none tested cardiac protection.

Sellers say meldonium protects the heart and improves efficiency, exercise performance and recovery, that WADA banned it in 2016 after widespread use by Eastern European athletes, and that it protects the heart during heavy anabolic steroid cycles. The WADA listing and widespread athlete use are documented above, though the Baku abstract does not name the athletes' region. The performance, recovery and steroid-cycle claims are separate questions.

A PubMed search on 10 October 2026 for meldonium or mildronate with physical performance, work capacity, VO2, endurance, overtraining or athletes returned 55 records. They covered anti-doping assays and urinary detection, milk and meat residue, rat, mouse and horse studies, patient studies, narrative reviews and unrelated chemistry. None was a randomized trial of exercise performance or recovery in healthy people.

A 2026 narrative review reaches the same view: it finds a profound lack of high-quality randomized placebo-controlled trials showing consistent ergogenic benefit in healthy athletes and a high risk of bias in the human performance studies that exist. Two indexed rodent papers point away from a benefit: no significant gain in strength or endurance in healthy mice, and lower swimming fitness in rats in a 1995 Russian paper.

A second PubMed search on 10 October 2026 for meldonium or mildronate with anabolic agents, anabolic androgenic steroids, bodybuilding or anabolic steroid returned 5 records: three annual banned-substance analytical reviews, one breath-testing paper and one meat-residue detection paper. None tested cardiac protection in people using anabolic steroids.

PubMed search, 10 October 2026: 55 records, none a healthy-human performance trial

PubMed search record

PubMed search run on 10 October 2026: (meldonium OR mildronate) AND (physical performance OR work capacity OR VO2 OR endurance OR overtraining OR athletes). 55 records returned.

The search returned 55 records. They covered anti-doping assays and urinary detection, milk and meat residue, rat, mouse and horse studies, patient studies, narrative reviews and unrelated chemistry. None was a randomized trial of exercise performance or recovery in healthy people. A 2026 narrative review (PMID 42344756) reaches the same view: it finds a profound lack of high-quality randomized placebo-controlled trials showing consistent ergogenic benefit in healthy athletes and a high risk of bias in the human performance studies that exist. Two indexed rodent papers point away from a benefit: no significant gain in strength or endurance in healthy mice (PMID 32389661), and lower swimming fitness in rats in a 1995 Russian paper (PMID 7773090).

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search run on 10 October 2026
Study design
Literature search plus a narrative review of healthy athletes
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source
PubMed search, 10 October 2026: 5 records, none on cardiac protection

PubMed search record

PubMed search run on 10 October 2026: (meldonium OR mildronate) AND ("anabolic agents"[mh] OR "anabolic androgenic steroids" OR bodybuilding OR "anabolic steroid"). 5 records returned.

The search returned 5 records: three annual banned-substance analytical reviews, one breath-testing paper and one meat-residue detection paper. None tested cardiac protection in people using anabolic steroids. The claim of heart protection during heavy anabolic steroid cycles has no human trial among these records.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search run on 10 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source
Healthy mice: gene and gut changes, anxiety-related behavior, no strength gain

Animal study

Gureev AP et al. Toxicol Appl Pharmacol. 2020;398:115031. PMID 32389661.

In healthy mice, long-term mildronate treatment changed liver, heart and brain gene expression, increased gut Proteobacteria, and was linked to anxiety-related behavior and reduced exploration, with no significant gain in strength or endurance.

Participants / model
Healthy mice
Treatment
Long-term mildronate; route and dose not stated in the source
Follow-up
Long-term; exact duration not stated in the source
Study design
Animal study
Funding
not stated in the source

Animal findings only. They cannot be read as human harm or human benefit, and the authors say the issue needs more study.

Read the original source

How does meldonium work, and how long does it stay in the body?

Meldonium is described as blocking carnitine synthesis and transport, which shifts energy use toward glucose, though no source here measures that action. In 10 healthy volunteers, urinary meldonium stayed detectable for up to 65 days after a single dose and up to 117 days after 6 days of twice-daily dosing.

Meldonium is described as blocking carnitine synthesis and transport, which shifts energy use toward glucose. None of the sources on this page measures that action, so it is the described mechanism and not one shown in these trials. In healthy mice, long-term mildronate treatment changed liver, heart and brain gene expression and increased gut Proteobacteria, with no significant gain in strength or endurance.

In 5 healthy volunteers given a single 500 mg oral dose, urinary meldonium stayed above the 10 ng/mL quantification limit for up to 65 days. In 5 healthy volunteers given 500 mg twice a day for 6 days, it stayed above that limit for up to 117 days. The excretion profile was non-linear, dose-dependent and biphasic. The groups were very small and only urine was measured, so no plasma half-life is established here.

Healthy mice: gene and gut changes, anxiety-related behavior, no strength gain

Animal study

Gureev AP et al. Toxicol Appl Pharmacol. 2020;398:115031. PMID 32389661.

In healthy mice, long-term mildronate treatment changed liver, heart and brain gene expression, increased gut Proteobacteria, and was linked to anxiety-related behavior and reduced exploration, with no significant gain in strength or endurance.

Participants / model
Healthy mice
Treatment
Long-term mildronate; route and dose not stated in the source
Follow-up
Long-term; exact duration not stated in the source
Study design
Animal study
Funding
not stated in the source

Animal findings only. They cannot be read as human harm or human benefit, and the authors say the issue needs more study.

Read the original source
Urine detection: 10 healthy volunteers, up to 65 and 117 days

Human study

Görgens C et al. J Pharm Biomed Anal. 2017;138:175-179. PMID 28213178.

Urinary meldonium stayed above the 10 ng/mL quantification limit for up to 65 days after a single 500 mg oral dose in 5 healthy volunteers, and for up to 117 days after 500 mg twice a day for 6 days in 5 healthy volunteers. The excretion profile was non-linear, dose-dependent and biphasic.

Participants / model
10 healthy volunteers, 5 per group
Treatment
Oral meldonium 500 mg as a single dose, or 500 mg twice a day for 6 days
Follow-up
Detection up to 65 days (single dose) and up to 117 days (6 days of dosing)
Study design
Clinical pharmacokinetic study, urine only
Funding
not stated in the source

Very small groups and urine only. No plasma half-life or Tmax is given in the sources reviewed.

Read the original source

What side effects and warnings are reported?

The Irish leaflet lists allergic reactions, headache and indigestion as common side effects, says the medicine is not for children, and warns it may cause a positive anti-doping test. Mouse findings suggest anxiety-related behavior with long-term use and cannot be read as human harm.

Common side effects in the Irish leaflet (up to 1 in 10 people) are allergic reactions, headache and indigestion. The leaflet says the medicine is not for children and warns that it may cause a positive anti-doping test. Urinary detection ran to 65 and 117 days in the pharmacokinetic study above.

In healthy mice, long-term mildronate treatment was linked to anxiety-related behavior and reduced exploration. These are animal findings, and the authors say the issue needs more study. They cannot be read as human harm or human benefit.

Irish HPRA leaflet, revised 05/2024: authorized in four EEA states for mild heart failure

Official label

Health Products Regulatory Authority (Ireland). Mildronate 500 mg hard capsules, package leaflet, last revised 05/2024. Marketing authorization holder AS Grindeks, Riga, Latvia.

The leaflet names AS Grindeks of Riga, Latvia as marketing authorization holder and says the medicine is authorized in Austria, Finland, Ireland and Norway under local names, for supplementary treatment of mild long-term heart failure in adults. It is not for children, and an anti-doping warning says it may cause a positive test. Common side effects (up to 1 in 10) are allergic reactions, headache and indigestion. The leaflet makes no claim for exercise performance, recovery or use in healthy people. 500 mg of meldonium dihydrate equals 401.14 mg of meldonium.

Participants / model
Adults with mild long-term heart failure
Treatment
Mildronate 500 mg oral hard capsules (meldonium dihydrate)
Follow-up
Leaflet last revised 05/2024
Study design
Package leaflet from a national regulator
Funding
not stated in the source

These are national authorizations. They are not an FDA approval and are not equivalent to FDA or EMA review.

Read the original source
Healthy mice: gene and gut changes, anxiety-related behavior, no strength gain

Animal study

Gureev AP et al. Toxicol Appl Pharmacol. 2020;398:115031. PMID 32389661.

In healthy mice, long-term mildronate treatment changed liver, heart and brain gene expression, increased gut Proteobacteria, and was linked to anxiety-related behavior and reduced exploration, with no significant gain in strength or endurance.

Participants / model
Healthy mice
Treatment
Long-term mildronate; route and dose not stated in the source
Follow-up
Long-term; exact duration not stated in the source
Study design
Animal study
Funding
not stated in the source

Animal findings only. They cannot be read as human harm or human benefit, and the authors say the issue needs more study.

Read the original source
Urine detection: 10 healthy volunteers, up to 65 and 117 days

Human study

Görgens C et al. J Pharm Biomed Anal. 2017;138:175-179. PMID 28213178.

Urinary meldonium stayed above the 10 ng/mL quantification limit for up to 65 days after a single 500 mg oral dose in 5 healthy volunteers, and for up to 117 days after 500 mg twice a day for 6 days in 5 healthy volunteers. The excretion profile was non-linear, dose-dependent and biphasic.

Participants / model
10 healthy volunteers, 5 per group
Treatment
Oral meldonium 500 mg as a single dose, or 500 mg twice a day for 6 days
Follow-up
Detection up to 65 days (single dose) and up to 117 days (6 days of dosing)
Study design
Clinical pharmacokinetic study, urine only
Funding
not stated in the source

Very small groups and urine only. No plasma half-life or Tmax is given in the sources reviewed.

Read the original source

Why does meldonium sit in B tier?

B reflects national authorization in four EEA states, one large randomized dose-finding trial in angina with a dose-dependent gain in exercise time, and a small heart failure trial. A missing FDA label and a regional human evidence base hold it below A, and the grade does not cover the performance, recovery or steroid-cycle claims.

The B applies to patients with angina or mild heart failure. For the supplier's claims the picture is split: the heart uses are partly supported in patients, while performance, recovery and heart protection during anabolic steroid cycles have no supporting trial among the records reviewed.

WADA's listing rests on evidence of use with intent to enhance performance, not on a shown effect, and trials of performance in healthy athletes are absent.

Irish HPRA leaflet, revised 05/2024: authorized in four EEA states for mild heart failure

Official label

Health Products Regulatory Authority (Ireland). Mildronate 500 mg hard capsules, package leaflet, last revised 05/2024. Marketing authorization holder AS Grindeks, Riga, Latvia.

The leaflet names AS Grindeks of Riga, Latvia as marketing authorization holder and says the medicine is authorized in Austria, Finland, Ireland and Norway under local names, for supplementary treatment of mild long-term heart failure in adults. It is not for children, and an anti-doping warning says it may cause a positive test. Common side effects (up to 1 in 10) are allergic reactions, headache and indigestion. The leaflet makes no claim for exercise performance, recovery or use in healthy people. 500 mg of meldonium dihydrate equals 401.14 mg of meldonium.

Participants / model
Adults with mild long-term heart failure
Treatment
Mildronate 500 mg oral hard capsules (meldonium dihydrate)
Follow-up
Leaflet last revised 05/2024
Study design
Package leaflet from a national regulator
Funding
not stated in the source

These are national authorizations. They are not an FDA approval and are not equivalent to FDA or EMA review.

Read the original source
MILSS I: 512 patients, 12 weeks, exercise time up on the 1000 mg daily dose

Randomized controlled trial

Dzerve V. Medicina (Kaunas). 2011;47(10):544-51. PMID 22186118.

Change in total exercise time on bicycle ergometry was -7.10 seconds on placebo versus -2.12 seconds on 100 mg and 11.48 seconds on 300 mg (neither significant), and 35.18 seconds on 1000 mg (P = 0.002). 3000 mg gave a smaller gain than 1000 mg. The authors concluded 500 mg twice a day was the most effective dose.

Participants / model
512 patients with chronic coronary heart disease and exercise-induced ischemia (stable angina), at 72 centers in 4 countries
Treatment
Oral meldonium 100, 300, 1000 or 3000 mg a day plus standard therapy, or placebo plus standard therapy
Follow-up
12 weeks
Study design
Double-blind phase 2 randomized trial
Funding
not stated in the source

A phase 2 dose-finding trial in patients with angina on standard therapy, not in healthy people. Endpoints were exercise time on bicycle ergometry, maximum load and time to angina.

Read the original source
Russian-language trial: 65 patients, 6 months, meldonium versus trimetazidine MB

Randomized controlled trial

Vasiuk IuA et al. Ter Arkh. 2007;79(2):51-8. PMID 17460970.

Both active groups lowered heart failure functional class and lengthened the 6-minute walk. Ejection fraction rose significantly only with trimetazidine, and the authors preferred trimetazidine.

Participants / model
65 patients with chronic heart failure more than 6 months after myocardial infarction, ejection fraction under 40%
Treatment
Basic therapy plus trimetazidine MB 70 mg a day (n = 28), basic therapy plus meldonium dihydrate 1000 mg a day (n = 25), or basic therapy alone (n = 12)
Follow-up
6 months
Study design
Randomized three-arm comparison; blinding and centers not stated in the abstract
Funding
not stated in the source

A small Russian-language report. The abstract names meldonium by its chemical name, meldonium dihydrate. Endpoints were functional class, 6-minute walk, PET and SPECT myocardial metabolism and ejection fraction.

Read the original source
WADA explanatory notes, 16 September 2015: why meldonium was added

Regulatory record

World Anti-Doping Agency. 2016 Prohibited List, Summary of Major Modifications and Explanatory Notes, 16 September 2015. Copy hosted by the FIA.

The notes say meldonium (mildronate) was added because of evidence that athletes used it with the intention of enhancing performance, and that it was moved from the Monitoring Program to the Prohibited List.

Participants / model
Not a clinical population
Treatment
Anti-doping rule
Follow-up
Dated 16 September 2015
Study design
Official anti-doping document
Funding
not stated in the source

The stated reason is evidence of use with that intent, not a demonstrated performance effect.

Read the original source
PubMed search, 10 October 2026: 55 records, none a healthy-human performance trial

PubMed search record

PubMed search run on 10 October 2026: (meldonium OR mildronate) AND (physical performance OR work capacity OR VO2 OR endurance OR overtraining OR athletes). 55 records returned.

The search returned 55 records. They covered anti-doping assays and urinary detection, milk and meat residue, rat, mouse and horse studies, patient studies, narrative reviews and unrelated chemistry. None was a randomized trial of exercise performance or recovery in healthy people. A 2026 narrative review (PMID 42344756) reaches the same view: it finds a profound lack of high-quality randomized placebo-controlled trials showing consistent ergogenic benefit in healthy athletes and a high risk of bias in the human performance studies that exist. Two indexed rodent papers point away from a benefit: no significant gain in strength or endurance in healthy mice (PMID 32389661), and lower swimming fitness in rats in a 1995 Russian paper (PMID 7773090).

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search run on 10 October 2026
Study design
Literature search plus a narrative review of healthy athletes
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source
PubMed search, 10 October 2026: 5 records, none on cardiac protection

PubMed search record

PubMed search run on 10 October 2026: (meldonium OR mildronate) AND ("anabolic agents"[mh] OR "anabolic androgenic steroids" OR bodybuilding OR "anabolic steroid"). 5 records returned.

The search returned 5 records: three annual banned-substance analytical reviews, one breath-testing paper and one meat-residue detection paper. None tested cardiac protection in people using anabolic steroids. The claim of heart protection during heavy anabolic steroid cycles has no human trial among these records.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search run on 10 October 2026
Study design
Literature search
Funding
not stated in the source

A search result shows what PubMed returned on that date. It is not proof that no unindexed study exists.

Read the original source

Studies and sources

Irish HPRA leaflet, revised 05/2024: authorized in four EEA states for mild heart failure

Official label

Health Products Regulatory Authority (Ireland). Mildronate 500 mg hard capsules, package leaflet, last revised 05/2024. Marketing authorization holder AS Grindeks, Riga, Latvia.

The leaflet names AS Grindeks of Riga, Latvia as marketing authorization holder and says the medicine is authorized in Austria, Finland, Ireland and Norway under local names, for supplementary treatment of mild long-term heart failure in adults. It is not for children, and an anti-doping warning says it may cause a positive test. Common side effects (up to 1 in 10) are allergic reactions, headache and indigestion. The leaflet makes no claim for exercise performance, recovery or use in healthy people. 500 mg of meldonium dihydrate equals 401.14 mg of meldonium.

Participants / model
Adults with mild long-term heart failure
Treatment
Mildronate 500 mg oral hard capsules (meldonium dihydrate)
Follow-up
Leaflet last revised 05/2024
Study design
Package leaflet from a national regulator
Funding
not stated in the source

These are national authorizations. They are not an FDA approval and are not equivalent to FDA or EMA review.

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WADA 2016 List: meldonium item 5.3, class S4; still listed in 2026

Regulatory record

World Anti-Doping Agency. The 2016 Prohibited List, stated to come into effect on 1 January 2016. The 2026 List, in effect from 1 January 2026, is a separate document that also names meldonium.

The 2016 List names meldonium as item 5.3 under metabolic modulators in class S4, hormone and metabolic modulators, within the classes prohibited at all times. The 2026 List, in effect from 1 January 2026, still lists meldonium, as item S4.4.3.

Participants / model
Not a clinical population
Treatment
Anti-doping rule
Follow-up
In effect from 1 January 2016; 2026 List in effect from 1 January 2026
Study design
Official anti-doping list
Funding
not stated in the source

The 2026 item number comes from the 2026 List document, not from the 2016 edition.

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WADA explanatory notes, 16 September 2015: why meldonium was added

Regulatory record

World Anti-Doping Agency. 2016 Prohibited List, Summary of Major Modifications and Explanatory Notes, 16 September 2015. Copy hosted by the FIA.

The notes say meldonium (mildronate) was added because of evidence that athletes used it with the intention of enhancing performance, and that it was moved from the Monitoring Program to the Prohibited List.

Participants / model
Not a clinical population
Treatment
Anti-doping rule
Follow-up
Dated 16 September 2015
Study design
Official anti-doping document
Funding
not stated in the source

The stated reason is evidence of use with that intent, not a demonstrated performance effect.

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Baku 2015: 66 of 762 urine samples positive (8.7%)

Human study

Stuart M et al. Br J Sports Med. 2016;50(11):694-8. PMID 27015859.

At the Baku 2015 European Games, 66 of 762 athlete urine samples (8.7%) tested positive for meldonium, and 23 of 662 tested athletes (3.5%) declared personal use. Athletes from 6 countries declared use, and use was found in 15 of 21 sports. The authors call this widespread and inappropriate use of a prescription drug in a generally healthy athlete population.

Participants / model
Athletes at one multi-sport event, mostly healthy
Treatment
Not a treatment trial; surveillance of declarations and urine tests
Follow-up
One multi-sport event, the Baku 2015 European Games
Study design
Surveillance report
Funding
not stated in the source

The abstract does not say the athletes were from Eastern Europe and reports no effect on performance.

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MILSS I: 512 patients, 12 weeks, exercise time up on the 1000 mg daily dose

Randomized controlled trial

Dzerve V. Medicina (Kaunas). 2011;47(10):544-51. PMID 22186118.

Change in total exercise time on bicycle ergometry was -7.10 seconds on placebo versus -2.12 seconds on 100 mg and 11.48 seconds on 300 mg (neither significant), and 35.18 seconds on 1000 mg (P = 0.002). 3000 mg gave a smaller gain than 1000 mg. The authors concluded 500 mg twice a day was the most effective dose.

Participants / model
512 patients with chronic coronary heart disease and exercise-induced ischemia (stable angina), at 72 centers in 4 countries
Treatment
Oral meldonium 100, 300, 1000 or 3000 mg a day plus standard therapy, or placebo plus standard therapy
Follow-up
12 weeks
Study design
Double-blind phase 2 randomized trial
Funding
not stated in the source

A phase 2 dose-finding trial in patients with angina on standard therapy, not in healthy people. Endpoints were exercise time on bicycle ergometry, maximum load and time to angina.

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Russian-language trial: 65 patients, 6 months, meldonium versus trimetazidine MB

Randomized controlled trial

Vasiuk IuA et al. Ter Arkh. 2007;79(2):51-8. PMID 17460970.

Both active groups lowered heart failure functional class and lengthened the 6-minute walk. Ejection fraction rose significantly only with trimetazidine, and the authors preferred trimetazidine.

Participants / model
65 patients with chronic heart failure more than 6 months after myocardial infarction, ejection fraction under 40%
Treatment
Basic therapy plus trimetazidine MB 70 mg a day (n = 28), basic therapy plus meldonium dihydrate 1000 mg a day (n = 25), or basic therapy alone (n = 12)
Follow-up
6 months
Study design
Randomized three-arm comparison; blinding and centers not stated in the abstract
Funding
not stated in the source

A small Russian-language report. The abstract names meldonium by its chemical name, meldonium dihydrate. Endpoints were functional class, 6-minute walk, PET and SPECT myocardial metabolism and ejection fraction.

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Urine detection: 10 healthy volunteers, up to 65 and 117 days

Human study

Görgens C et al. J Pharm Biomed Anal. 2017;138:175-179. PMID 28213178.

Urinary meldonium stayed above the 10 ng/mL quantification limit for up to 65 days after a single 500 mg oral dose in 5 healthy volunteers, and for up to 117 days after 500 mg twice a day for 6 days in 5 healthy volunteers. The excretion profile was non-linear, dose-dependent and biphasic.

Participants / model
10 healthy volunteers, 5 per group
Treatment
Oral meldonium 500 mg as a single dose, or 500 mg twice a day for 6 days
Follow-up
Detection up to 65 days (single dose) and up to 117 days (6 days of dosing)
Study design
Clinical pharmacokinetic study, urine only
Funding
not stated in the source

Very small groups and urine only. No plasma half-life or Tmax is given in the sources reviewed.

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Healthy mice: gene and gut changes, anxiety-related behavior, no strength gain

Animal study

Gureev AP et al. Toxicol Appl Pharmacol. 2020;398:115031. PMID 32389661.

In healthy mice, long-term mildronate treatment changed liver, heart and brain gene expression, increased gut Proteobacteria, and was linked to anxiety-related behavior and reduced exploration, with no significant gain in strength or endurance.

Participants / model
Healthy mice
Treatment
Long-term mildronate; route and dose not stated in the source
Follow-up
Long-term; exact duration not stated in the source
Study design
Animal study
Funding
not stated in the source

Animal findings only. They cannot be read as human harm or human benefit, and the authors say the issue needs more study.

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PubChem: meldonium and meldonium dihydrate identity

Chemical identity record

National Library of Medicine. PubChem compound records CID 123868 (meldonium) and CID 6918082 (meldonium dihydrate).

Meldonium (mildronate, MET-88, THP): PubChem CID 123868, C6H14N2O2, 146.19 g/mol, CAS 76144-81-5. The dihydrate used in the EU capsules is a separate record: CID 6918082, C6H18N2O4, 182.22 g/mol, CAS 86426-17-7. Doses on EU labels are written as the dihydrate.

Participants / model
Chemical identity, not a clinical population
Treatment
Defined molecule and its dihydrate
Follow-up
Not applicable
Study design
NLM chemical record
Funding
not stated in the source

Identity record only; it says nothing about efficacy or safety.

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Why is Meldonium in B tier?

B fits a medicine with national authorization in four EEA states, one large randomized dose-finding trial in angina that found a dose-dependent gain in exercise time, and a small heart failure trial. It sits below A because there is no FDA label and no FDA or EMA review, and the human cardiology evidence is regional. The grade covers patients with angina or heart failure, not the supplier's performance, recovery or steroid-cycle claims.