AICAR (acadesine)

updated

AICAR is sold for endurance on the strength of a 2008 mouse study in which 4 weeks of treatment enhanced running endurance by 44% in sedentary mice. No human trial of AICAR or acadesine for endurance, performance or body composition was found, and every human exposure in the sources reviewed was an intravenous infusion. Acadesine reduced perioperative myocardial infarction in a 1997 pooled analysis of 4043 bypass patients, but the phase 3 RED-CABG trial was stopped for futility (odds ratio 1.01).

Nucleoside (AICA riboside) used as an AMPK activator

  • The 2008 mouse study is real: 4 weeks of AICAR enhanced treadmill running endurance by 44% in sedentary mice, and the abstract states no dose, route or strain.
  • Two molecules share the name: acadesine (AICA riboside, the nucleoside given in every human trial cited) and AICA ribonucleotide (ZMP, the AMPK-activating form made inside cells).
  • A 1997 pooled analysis of 4043 bypass surgery patients found 27% fewer perioperative myocardial infarctions with intravenous acadesine; RED-CABG (3080 patients) was stopped for futility, with the primary outcome at 5.0% versus 5.1%.
  • In 4 healthy men, intact acadesine was measurable for only 2 hours after a 15-minute intravenous infusion, and uric acid accounted for all plasma radiolabel at 6 hours.
  • A 2015 review links the 2008 mouse study to the World Anti-Doping Agency's listing of certain AMPK activators.
  • A PubMed search on 9 October 2026 returned 2 records on AICAR or acadesine with exercise performance terms in healthy people; neither was a human trial of AICAR for exercise.

What is AICAR, and is it the same as acadesine?

Two molecules share the name. Acadesine (AICA riboside) is the nucleoside given in every human study cited, and AICA ribonucleotide (ZMP) is the phosphorylated form made inside cells. An openFDA query on 9 October 2026 returned no application for either.

Acadesine, also called AICA riboside, is PubChem CID 17513 (C9H14N4O5, 258.23 g/mol, CAS 2627-69-2), with synonyms including Arasine, AIC-riboside and GP-1-110. It is the nucleoside given to patients in every human trial cited here.

AICA ribonucleotide, also called ZMP or AICAR, is PubChem CID 65110 (C9H15N4O8P, 338.21 g/mol, CAS 3031-94-5). It is the phosphorylated nucleotide, the actual AMPK-activating species, and it forms inside cells after the riboside is taken up. The two records differ by a phosphate group and 80 g/mol, and dose figures taken from one do not transfer to the other. A vendor product sold as AICAR is almost certainly the riboside.

An openFDA Drugs@FDA exact brand-name and generic-name query returned no matching application for acadesine and none for AICAR on 9 October 2026. That supports a US-scoped statement that no FDA-approved product of either exists. It is not a worldwide statement.

PubChem: acadesine CID 17513 (riboside) and AICA ribonucleotide CID 65110 are different molecules

Chemical identity record

National Library of Medicine. PubChem compound records CID 17513 (acadesine, AICA riboside) and CID 65110 (AICA ribonucleotide, ZMP).

Two different molecules share this name. Acadesine, also called AICA riboside: PubChem CID 17513, C9H14N4O5, 258.23 g/mol, CAS 2627-69-2, synonyms including Arasine, AIC-riboside and GP-1-110. This is the nucleoside given to patients in every human trial cited. AICA ribonucleotide, also called ZMP or AICAR: PubChem CID 65110, C9H15N4O8P, 338.21 g/mol, CAS 3031-94-5. This is the phosphorylated nucleotide, the actual AMPK-activating species, formed inside cells after the riboside is taken up. A vendor product sold as 'AICAR' is almost certainly the riboside; the two records differ by a phosphate group and 80 g/mol, and dose figures taken from one do not transfer to the other.

Participants / model
Chemical identity, not a clinical population
Treatment
Two defined molecules, no approved formulation
Follow-up
Not applicable
Study design
NLM chemical records
Funding
not stated in the source

Identity records only; they say nothing about efficacy or safety. The link opens the acadesine (riboside) record.

Read the original source
openFDA queries, 9 October 2026: no acadesine or AICAR application returned

Regulatory record

U.S. Food and Drug Administration. openFDA Drugs@FDA API queries for brand name and generic name acadesine and for AICAR, run on 9 October 2026.

An openFDA Drugs@FDA exact brand-name and generic-name query returned no matching application for acadesine and no matching application for AICAR on 9 October 2026. This supports the US-scoped statement that no FDA-approved product of either exists. It is not a worldwide statement.

Participants / model
FDA application database, not a clinical population
Treatment
Exact substance-name searches
Follow-up
Queries run on 9 October 2026
Study design
Database query
Funding
not stated in the source

A US-scoped search result. The link shows the acadesine query.

Read the original source

What have people been given acadesine for, and what happened?

Acadesine was given intravenously in cardiac surgery and leukemia studies. A 1997 pooled analysis of 4043 bypass patients found fewer perioperative myocardial infarctions, but the phase 3 RED-CABG trial was stopped for futility with an odds ratio of 1.01 on its primary outcome.

An individual-patient-data meta-analysis of 5 randomized, placebo-controlled, double-blind trials across 81 medical centers in the United States, Canada and Europe pooled 4043 patients undergoing coronary artery bypass graft surgery, randomized to placebo (n=2031) or acadesine 0.1 mg per kg per minute by intravenous infusion for 7 continuous hours plus administration via the cardioplegia solution (n=2012). Acadesine decreased perioperative myocardial infarction by 27% (OR 0.69, 95% CI 0.51 to 0.95, P=.02), cardiac death through postoperative day 4 by 50% (OR 0.52, 95% CI 0.27 to 0.98, P=.04) and the combined outcome of MI, stroke or cardiac death by 26% (OR 0.73, 95% CI 0.57 to 0.93, P=.01). Cerebrovascular accident was not significantly reduced (OR 0.69, 95% CI 0.44 to 1.08, P=.10).

RED-CABG was built to confirm that result. It was a randomized, double-blind, placebo-controlled, parallel-group evaluation of intermediate-to-high-risk patients (median age 66) undergoing nonemergency on-pump CABG surgery at 300 sites in 7 countries, with acadesine 0.1 mg per kg per minute for 7 hours or placebo, both also added to cardioplegic solutions. A prespecified futility analysis indicated a very low likelihood of a statistically significant efficacious outcome, and the trial was stopped after 3080 of the originally projected 7500 participants were randomized. The primary composite of all-cause mortality, nonfatal stroke or need for mechanical support for severe left ventricular dysfunction through postoperative day 28 occurred in 75 of 1493 (5.0%) on placebo and 76 of 1493 (5.1%) on acadesine, odds ratio 1.01 (95% CI 0.73 to 1.41). There were no differences in key secondary endpoints.

Both studies were in cardiac surgery patients given intravenous acadesine. A ClinicalTrials.gov query on 9 October 2026 returned four studies matching acadesine or AICAR, and none tested exercise, endurance, body composition or performance.

1997 pooled analysis: 4043 bypass patients, perioperative myocardial infarction down 27%

Systematic review and meta-analysis

Mangano DT. JAMA. 1997;277(4):325-32. PMID 9002496.

An individual-patient-data meta-analysis of 5 randomized, placebo-controlled, double-blind trials across 81 medical centers in the United States, Canada and Europe pooled 4043 patients undergoing coronary artery bypass graft surgery, randomized to placebo (n=2031) or acadesine 0.1 mg per kg per minute by intravenous infusion for 7 continuous hours plus administration via the cardioplegia solution (n=2012). Acadesine decreased perioperative myocardial infarction by 27% (OR 0.69, 95% CI 0.51 to 0.95, P=.02), cardiac death through postoperative day 4 by 50% (OR 0.52, 95% CI 0.27 to 0.98, P=.04) and the combined outcome of MI, stroke or cardiac death by 26% (OR 0.73, 95% CI 0.57 to 0.93, P=.01). Cerebrovascular accident was not significantly reduced (OR 0.69, 95% CI 0.44 to 1.08, P=.10). Adverse event rates were similar to placebo except for a transient increase in serum uric acid.

Participants / model
4043 adults undergoing CABG surgery
Treatment
Intravenous acadesine, 0.1 mg/kg/min for 7 hours plus cardioplegia solution, or placebo
Follow-up
Perioperative; cardiac death assessed through postoperative day 4
Study design
Individual-patient-data meta-analysis of 5 randomized, placebo-controlled, double-blind trials
Funding
not stated in the source

A cardiac surgery population given intravenous acadesine. It says nothing about exercise or oral use.

Read the original source
RED-CABG phase 3: 3080 patients, stopped for futility, primary outcome 5.0% versus 5.1%

Randomized controlled trial

Newman MF et al. JAMA. 2012;308(2):157-64. PMID 22782417.

RED-CABG was a randomized, double-blind, placebo-controlled, parallel-group evaluation of intermediate-to-high-risk patients (median age 66) undergoing nonemergency on-pump CABG surgery at 300 sites in 7 countries, enrolling from 6 May 2009 to 30 July 2010. Participants were randomized 1:1 to acadesine 0.1 mg per kg per minute for 7 hours or placebo, both also added to cardioplegic solutions. A prespecified futility analysis indicated a very low likelihood of a statistically significant efficacious outcome and the trial was stopped after 3080 of the originally projected 7500 participants were randomized. The primary composite of all-cause mortality, nonfatal stroke or need for mechanical support for severe left ventricular dysfunction through postoperative day 28 occurred in 75 of 1493 (5.0%) on placebo and 76 of 1493 (5.1%) on acadesine, odds ratio 1.01 (95% CI 0.73 to 1.41). There were no differences in key secondary endpoints.

Participants / model
3080 adults undergoing nonemergency on-pump CABG surgery
Treatment
Intravenous acadesine, 0.1 mg/kg/min for 7 hours plus cardioplegic solution, or placebo
Follow-up
Primary outcome through postoperative day 28
Study design
Randomized, double-blind, placebo-controlled phase 3 trial, stopped for futility
Funding
not stated in the source

Built to confirm the positive pooled analysis and did not. A cardiac surgery population given intravenous acadesine.

Read the original source
Registry, 9 October 2026: four studies, none on exercise, endurance or performance

Trial registry record

ClinicalTrials.gov query for acadesine and AICAR run on 9 October 2026; records NCT00872001, NCT00559624, NCT01813838 and NCT06845501.

A ClinicalTrials.gov query on 9 October 2026 returned four studies: NCT00872001 (phase 3, n=3080, terminated, results posted, the RED-CABG trial), NCT00559624 (phase 1/2, n=40, completed, no results posted, B-CLL), NCT01813838 (phase 1/2, n=5, terminated, no results posted) and NCT06845501 (n=10, recruiting, purine supplementation in AICA-ribosiduria, an inherited metabolic disorder and not an acadesine intervention study). No registered study of acadesine or AICAR for exercise, endurance, body composition or performance was located.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Query run on 9 October 2026
Study design
Registry query
Funding
not stated in the source

The link opens the RED-CABG record, NCT00872001, which has posted results.

Read the original source

Does AICAR build endurance without training?

In sedentary mice, 4 weeks of AICAR enhanced treadmill running endurance by 44%, so the supplier's number is correct. No human trial of AICAR or acadesine for endurance, performance, VO2 or body composition was found.

Sellers promote AICAR for endurance and metabolic conditioning without additional training, citing a 2008 study that showed about 44% better endurance in sedentary mice.

The study is real and the number is correct. It tested pathway-specific drugs on the endurance capacity of mice in a treadmill running test. A PPAR-beta/delta agonist and exercise training synergistically increased oxidative myofibers and running endurance in adult mice. The authors then tested whether AICAR alone could substitute for exercise, and report that even in sedentary mice, 4 weeks of AICAR treatment alone induced metabolic genes and enhanced running endurance by 44%. The abstract states no dose, route or strain, so none is given here, and there was no human arm.

A PubMed search on 9 October 2026 for AICAR, AICAr, acadesine or AICA riboside with exercise performance, endurance training, time trial, VO2max or aerobic capacity terms, restricted to healthy people, athletes or volunteers and to the humans MeSH term, returned 2 records. Neither is a trial of AICAR in people: one is a 2015 review, and the other reports that skeletal muscle NAMPT is induced by exercise in humans. Every human exposure in the sources reviewed was an intravenous infusion.

2008 mouse study: 4 weeks of AICAR enhanced treadmill endurance by 44% in sedentary mice

Animal study

Narkar VA et al. Cell. 2008;134(3):405-15. PMID 18674809.

Pathway-specific drugs were tested on the endurance capacity of mice in a treadmill running test. A PPAR-beta/delta agonist and exercise training synergistically increased oxidative myofibers and running endurance in adult mice. The authors then tested whether AICAR alone could substitute for the exercise requirement, and report that even in sedentary mice, 4 weeks of AICAR treatment alone induced metabolic genes and enhanced running endurance by 44%. The abstract describes AICAR as an orally active AMPK agonist but states no dose, route or strain for the mouse experiments.

Participants / model
Adult mice, including a sedentary group
Treatment
AICAR; dose and route not stated in the abstract; 4 weeks
Follow-up
4 weeks
Study design
Original animal study
Funding
not stated in the source

The 44% figure belongs to sedentary mice on a treadmill over 4 weeks. There is no human arm, and no dose, route or strain is carried to this page.

Read the original source
PubMed search, 9 October 2026: 2 records, no human trial of AICAR for exercise

PubMed search record

PubMed search run on 9 October 2026: (AICAR OR acadesine OR "AICA riboside") AND ("exercise performance" OR "endurance training" OR "time trial" OR "VO2max" OR "aerobic capacity") AND humans[mh]. 2 records returned.

The search, restricted to healthy people, athletes or volunteers and to the humans MeSH term, returned 2 records. Neither is a trial of AICAR in people: one is the 2015 Sports Medicine review, and the other reports that skeletal muscle NAMPT is induced by exercise in humans. In the records reviewed there is no human trial of AICAR or acadesine for endurance, performance, VO2 or body composition, by any route, at any dose. Every human exposure in the sources reviewed was an intravenous infusion.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Search run on 9 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
Registry, 9 October 2026: four studies, none on exercise, endurance or performance

Trial registry record

ClinicalTrials.gov query for acadesine and AICAR run on 9 October 2026; records NCT00872001, NCT00559624, NCT01813838 and NCT06845501.

A ClinicalTrials.gov query on 9 October 2026 returned four studies: NCT00872001 (phase 3, n=3080, terminated, results posted, the RED-CABG trial), NCT00559624 (phase 1/2, n=40, completed, no results posted, B-CLL), NCT01813838 (phase 1/2, n=5, terminated, no results posted) and NCT06845501 (n=10, recruiting, purine supplementation in AICA-ribosiduria, an inherited metabolic disorder and not an acadesine intervention study). No registered study of acadesine or AICAR for exercise, endurance, body composition or performance was located.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Query run on 9 October 2026
Study design
Registry query
Funding
not stated in the source

The link opens the RED-CABG record, NCT00872001, which has posted results.

Read the original source

Why is AICAR on anti-doping lists?

A 2015 review links the 2008 mouse study to the World Anti-Doping Agency's decision to list certain AMPK activators, and a 2019 laboratory paper states AICAR is prohibited in sport. Because AICAR is endogenous, laboratories rely on isotope ratio analysis to separate administered from self-produced.

A review of AMPK activation and exercise capacity states that a study published in 2008, directly before the Olympic Games in Beijing, showed that the AMPK activator AICAR increased the running capacity of mice without any training, and that this prompted the World Anti-Doping Agency to include certain AMPK activators in the list of forbidden drugs. The supplier's selling point and the reason the compound is prohibited are the same mouse experiment.

A reference-population study from the UCLA Olympic Analytical Laboratory states that both AICAR and mannitol are prohibited for use in sports. In 12,377 US athlete urine samples, mean urinary AICAR was 647 +/- 365 ng/mL, median 574 ng/mL, 99th percentile 1786 ng/mL and 99.7th percentile 2151 ng/mL. The authors suggest that any sample above 2000 or 2500 ng/mL be analyzed by carbon isotope ratio mass spectrometry to establish the origin. AICAR is an endogenous compound, so presence alone is not a finding.

This page does not establish whether AICAR appears by name on the current prohibited list. The sources are a 2015 review and a 2019 laboratory paper, and both state it is prohibited.

2015 review: the 2008 mouse study prompted WADA to list certain AMPK activators

Animal study

Niederberger E et al. Sports Med. 2015;45(11):1497-509. PMID 26186961.

A review of AMPK activation and exercise capacity states that a study published in 2008, directly before the Olympic Games in Beijing, showed that the AMPK activator AICAR increased the running capacity of mice without any training, and that this prompted the World Anti-Doping Agency to include certain AMPK activators in the list of forbidden drugs.

Participants / model
Records reviewed; mice in the underlying study
Treatment
Not applicable
Follow-up
not stated in the source
Study design
Narrative review
Funding
not stated in the source

A summary of the regulatory consequence of the 2008 study. It is not a new experiment.

Read the original source
Anti-doping reference study: 12,377 athlete urine samples, AICAR is endogenous

Human study

Sobolevsky T et al. Drug Test Anal. 2019;11(3):530-535. PMID 30548818.

A reference-population study from the UCLA Olympic Analytical Laboratory states that both AICAR and mannitol are prohibited for use in sports. Analysis of 12,377 US athlete samples gave a mean urinary AICAR concentration of 647 +/- 365 ng/mL, median 574 ng/mL, 99th percentile 1786 ng/mL and 99.7th percentile 2151 ng/mL. The authors suggest that any sample above 2000 or 2500 ng/mL be analyzed by carbon isotope ratio mass spectrometry to establish the origin. AICAR is an endogenous compound, so presence alone is not a finding, and laboratories rely on isotope ratio work to separate administered from self-produced.

Participants / model
12,377 urine samples from US athletes
Treatment
Not applicable; endogenous and administered AICAR in urine
Follow-up
not stated in the source
Study design
Anti-doping reference-population study
Funding
not stated in the source

An analytical reference study of urine samples, not an efficacy or safety study.

Read the original source

How does AICAR work, and what does the body do with it?

The AMPK-activating species is the nucleotide ZMP, formed inside cells from the riboside. A systematic review warns that many effects attributed to AICAr are AMPK-independent, and in healthy men intact acadesine was measurable for only about 2 hours after an intravenous infusion.

AICA ribonucleotide (ZMP) is the phosphorylated nucleotide, the actual AMPK-activating species, and it is formed inside cells after the riboside is taken up.

A systematic review of AICAr as a pharmacological AMPK modulator notes that the majority of early studies on the role of AMPK, in metabolism and in cancer, relied solely on AICAr as an AMPK activator, and that an increasing number of studies show many AICAr effects previously attributed to AMPK activation are AMPK-independent. It covers metabolism, hypoxia, exercise, nucleotide synthesis and cancer, and calls for caution in interpreting AICAr-based studies as evidence about AMPK signaling.

Four healthy men received a 15-minute intravenous infusion of 25 mg/kg of 14C-acadesine. Total plasma radiolabel declined with an apparent terminal half-life of about 1 week, but intact acadesine was measurable for only 2 hours. Total plasma clearance was 2.2 +/- 0.2 L per hour per kg, and plasma protein binding was about 1%. Uric acid, the end product of purine metabolism in humans, accounted for all plasma radiolabel at 6 hours, and acadesine 5'-monophosphate was confined to red blood cells (30% of total blood radiolabel at the end of the infusion). Over 2 weeks, urine and feces recovered 48% of the dose, 44% in urine and 4% in feces, with 5% of the dose excreted in urine as intact acadesine.

Every figure is for an intravenous infusion in healthy men. No oral dose, oral bioavailability or oral half-life can be stated for acadesine, because no source reviewed provides one.

PubChem: acadesine CID 17513 (riboside) and AICA ribonucleotide CID 65110 are different molecules

Chemical identity record

National Library of Medicine. PubChem compound records CID 17513 (acadesine, AICA riboside) and CID 65110 (AICA ribonucleotide, ZMP).

Two different molecules share this name. Acadesine, also called AICA riboside: PubChem CID 17513, C9H14N4O5, 258.23 g/mol, CAS 2627-69-2, synonyms including Arasine, AIC-riboside and GP-1-110. This is the nucleoside given to patients in every human trial cited. AICA ribonucleotide, also called ZMP or AICAR: PubChem CID 65110, C9H15N4O8P, 338.21 g/mol, CAS 3031-94-5. This is the phosphorylated nucleotide, the actual AMPK-activating species, formed inside cells after the riboside is taken up. A vendor product sold as 'AICAR' is almost certainly the riboside; the two records differ by a phosphate group and 80 g/mol, and dose figures taken from one do not transfer to the other.

Participants / model
Chemical identity, not a clinical population
Treatment
Two defined molecules, no approved formulation
Follow-up
Not applicable
Study design
NLM chemical records
Funding
not stated in the source

Identity records only; they say nothing about efficacy or safety. The link opens the acadesine (riboside) record.

Read the original source
Systematic review: many AICAr effects once attributed to AMPK are AMPK-independent

Systematic review and meta-analysis

Višnjić D et al. Cells. 2021;10(5). PMID 34064363.

A systematic review of AICAr as a pharmacological AMPK modulator notes that the majority of early studies on the role of AMPK, both in physiological regulation of metabolism and in cancer pathogenesis, were based solely on the use of AICAr as an AMPK activator, and that an increasing number of studies show numerous AICAr effects previously attributed to AMPK activation are in fact AMPK-independent. The review covers metabolism, hypoxia, exercise, nucleotide synthesis and cancer, and calls for caution in interpreting AICAr-based studies as evidence about AMPK signaling.

Participants / model
Studies reviewed, not a population
Treatment
Not applicable
Follow-up
not stated in the source
Study design
Systematic review
Funding
not stated in the source

Any AMPK activator framing for AICAR carries this qualifier.

Read the original source
Human PK: 4 healthy men, intact acadesine measurable for 2 hours, uric acid the main metabolite

Human study

Dixon R et al. J Clin Pharmacol. 1993;33(10):955-8. PMID 8227467.

Four healthy males received a 15-minute intravenous infusion of 25 mg/kg of 2-14C-acadesine. Postinfusion total 14C in plasma declined multiexponentially with an apparent terminal half-life of about 1 week, but intact acadesine was only measurable for 2 hours after the infusion. Total plasma clearance was 2.2 +/- 0.2 L per hour per kg, the blood to plasma ratio was unity, and plasma protein binding was negligible at approximately 1%. Uric acid, the end product of purine metabolism in humans, was the major plasma metabolite and accounted for all of the total plasma 14C at 6 hours. Acadesine 5'-monophosphate was present in red blood cells and represented 30% of total blood 14C at the end of the infusion, confined to the red cells and absent from plasma. Over 2 weeks, urine and fecal recovery accounted for 48% of the dose, 44% in urine and 4% in feces, with only 5% of the dose excreted in urine as intact acadesine.

Participants / model
4 healthy adult males
Treatment
Intravenous 2-14C-acadesine, 25 mg/kg over 15 minutes
Follow-up
2 weeks of urine and fecal collection
Study design
Original human PK study
Funding
not stated in the source

Every number is for a 15-minute intravenous infusion in healthy men. No oral exposure was measured.

Read the original source

What risks do the studies in people report?

In the only modern dose-escalation study, in 24 leukemia patients, hyperuricemia was common and other adverse events included renal impairment and transient hypotension described as clinically significant. In pooled bypass surgery trials, adverse event rates matched placebo except for a transient rise in serum uric acid.

Twenty-four patients with relapsed or refractory chronic lymphocytic leukemia received acadesine intravenously as a 4-hour infusion: 18 in Part I at single doses of 50 to 315 mg/kg, and 6 in Part II at 210 mg/kg. A manageable and predictable safety profile was reported between 50 and 210 mg/kg, and 210 mg/kg was the maximum tolerated dose. Grade 2 or higher hyperuricemia occurred commonly, described as not clinically significant and resolving with prophylactic allopurinol. Other adverse events included transient anemia or thrombocytopenia described as not clinically significant, renal impairment, and transient infusion-related hypotension described as clinically significant.

In the pooled analysis of 4043 bypass surgery patients, adverse event rates were similar to placebo except for a transient increase in serum uric acid. In the pharmacokinetic study, uric acid accounted for all plasma radiolabel at 6 hours.

These findings come from intravenous infusions in leukemia and cardiac surgery patients. No source reviewed gives safety data for oral use or for use in exercise.

Leukemia dose escalation: 24 patients, maximum tolerated dose 210 mg/kg, hyperuricemia common

Clinical trial

Van Den Neste E et al. Cancer Chemother Pharmacol. 2013;71(3):581-91. PMID 23228986.

Twenty-four patients with relapsed or refractory chronic lymphocytic leukemia received acadesine intravenously as a 4-hour infusion: 18 in Part I at single doses of 50 to 315 mg/kg, and 6 in Part II, three with two doses at 210 mg/kg and three with five doses at 210 mg/kg. A manageable and predictable safety profile was demonstrated between 50 and 210 mg/kg; 210 mg/kg was the maximum tolerated dose and the optimal biological dose. Grade 2 or higher hyperuricemia occurred commonly, described as not clinically significant and resolving with prophylactic allopurinol. Other adverse events included transient anemia or thrombocytopenia described as not clinically significant, renal impairment, and transient infusion-related hypotension described as clinically significant. Trends toward reduction of peripheral CLL cells and lymphadenopathy were observed but variable given the small population and dose range.

Participants / model
24 adults with relapsed or refractory chronic lymphocytic leukemia
Treatment
Intravenous acadesine, 4-hour infusion, 50 to 315 mg/kg
Follow-up
Single doses (Part I); two or five doses (Part II)
Study design
Phase 1/2 dose-escalation trial
Funding
not stated in the source

A leukemia population given intravenous infusions. The findings do not apply to exercise or oral use.

Read the original source
1997 pooled analysis: 4043 bypass patients, perioperative myocardial infarction down 27%

Systematic review and meta-analysis

Mangano DT. JAMA. 1997;277(4):325-32. PMID 9002496.

An individual-patient-data meta-analysis of 5 randomized, placebo-controlled, double-blind trials across 81 medical centers in the United States, Canada and Europe pooled 4043 patients undergoing coronary artery bypass graft surgery, randomized to placebo (n=2031) or acadesine 0.1 mg per kg per minute by intravenous infusion for 7 continuous hours plus administration via the cardioplegia solution (n=2012). Acadesine decreased perioperative myocardial infarction by 27% (OR 0.69, 95% CI 0.51 to 0.95, P=.02), cardiac death through postoperative day 4 by 50% (OR 0.52, 95% CI 0.27 to 0.98, P=.04) and the combined outcome of MI, stroke or cardiac death by 26% (OR 0.73, 95% CI 0.57 to 0.93, P=.01). Cerebrovascular accident was not significantly reduced (OR 0.69, 95% CI 0.44 to 1.08, P=.10). Adverse event rates were similar to placebo except for a transient increase in serum uric acid.

Participants / model
4043 adults undergoing CABG surgery
Treatment
Intravenous acadesine, 0.1 mg/kg/min for 7 hours plus cardioplegia solution, or placebo
Follow-up
Perioperative; cardiac death assessed through postoperative day 4
Study design
Individual-patient-data meta-analysis of 5 randomized, placebo-controlled, double-blind trials
Funding
not stated in the source

A cardiac surgery population given intravenous acadesine. It says nothing about exercise or oral use.

Read the original source
Human PK: 4 healthy men, intact acadesine measurable for 2 hours, uric acid the main metabolite

Human study

Dixon R et al. J Clin Pharmacol. 1993;33(10):955-8. PMID 8227467.

Four healthy males received a 15-minute intravenous infusion of 25 mg/kg of 2-14C-acadesine. Postinfusion total 14C in plasma declined multiexponentially with an apparent terminal half-life of about 1 week, but intact acadesine was only measurable for 2 hours after the infusion. Total plasma clearance was 2.2 +/- 0.2 L per hour per kg, the blood to plasma ratio was unity, and plasma protein binding was negligible at approximately 1%. Uric acid, the end product of purine metabolism in humans, was the major plasma metabolite and accounted for all of the total plasma 14C at 6 hours. Acadesine 5'-monophosphate was present in red blood cells and represented 30% of total blood 14C at the end of the infusion, confined to the red cells and absent from plasma. Over 2 weeks, urine and fecal recovery accounted for 48% of the dose, 44% in urine and 4% in feces, with only 5% of the dose excreted in urine as intact acadesine.

Participants / model
4 healthy adult males
Treatment
Intravenous 2-14C-acadesine, 25 mg/kg over 15 minutes
Follow-up
2 weeks of urine and fecal collection
Study design
Original human PK study
Funding
not stated in the source

Every number is for a 15-minute intravenous infusion in healthy men. No oral exposure was measured.

Read the original source

Why does AICAR sit in D tier?

The supplier's mouse number is correct, but no human has been given AICAR for endurance in the sources reviewed. The human data are intravenous acadesine in cardiac surgery, where the phase 3 trial built to confirm a positive pooled result was stopped for futility.

More than 7,000 randomized patients were studied across the 1997 pooled analysis (4043) and RED-CABG (3080). The data are about myocardial infarction after bypass surgery, given as a 7-hour intravenous infusion, and the phase 3 trial built to confirm the positive pooled analysis was stopped for futility with an odds ratio of 1.01.

The supplier's claim is about endurance in healthy adults. The 2008 study is real, and the number is 44% in sedentary mice over 4 weeks. What the sales text leaves out is that the same study is the reason AMPK activators were listed by the World Anti-Doping Agency, that the one human PK study found intact acadesine measurable for only 2 hours after an intravenous dose, that the adverse events in the leukemia study included hyperuricemia, renal impairment and clinically significant hypotension, and that a 2021 systematic review concludes many effects attributed to AICAr are not AMPK-mediated. No human oral bioavailability figure appears in the sources reviewed.

1997 pooled analysis: 4043 bypass patients, perioperative myocardial infarction down 27%

Systematic review and meta-analysis

Mangano DT. JAMA. 1997;277(4):325-32. PMID 9002496.

An individual-patient-data meta-analysis of 5 randomized, placebo-controlled, double-blind trials across 81 medical centers in the United States, Canada and Europe pooled 4043 patients undergoing coronary artery bypass graft surgery, randomized to placebo (n=2031) or acadesine 0.1 mg per kg per minute by intravenous infusion for 7 continuous hours plus administration via the cardioplegia solution (n=2012). Acadesine decreased perioperative myocardial infarction by 27% (OR 0.69, 95% CI 0.51 to 0.95, P=.02), cardiac death through postoperative day 4 by 50% (OR 0.52, 95% CI 0.27 to 0.98, P=.04) and the combined outcome of MI, stroke or cardiac death by 26% (OR 0.73, 95% CI 0.57 to 0.93, P=.01). Cerebrovascular accident was not significantly reduced (OR 0.69, 95% CI 0.44 to 1.08, P=.10). Adverse event rates were similar to placebo except for a transient increase in serum uric acid.

Participants / model
4043 adults undergoing CABG surgery
Treatment
Intravenous acadesine, 0.1 mg/kg/min for 7 hours plus cardioplegia solution, or placebo
Follow-up
Perioperative; cardiac death assessed through postoperative day 4
Study design
Individual-patient-data meta-analysis of 5 randomized, placebo-controlled, double-blind trials
Funding
not stated in the source

A cardiac surgery population given intravenous acadesine. It says nothing about exercise or oral use.

Read the original source
RED-CABG phase 3: 3080 patients, stopped for futility, primary outcome 5.0% versus 5.1%

Randomized controlled trial

Newman MF et al. JAMA. 2012;308(2):157-64. PMID 22782417.

RED-CABG was a randomized, double-blind, placebo-controlled, parallel-group evaluation of intermediate-to-high-risk patients (median age 66) undergoing nonemergency on-pump CABG surgery at 300 sites in 7 countries, enrolling from 6 May 2009 to 30 July 2010. Participants were randomized 1:1 to acadesine 0.1 mg per kg per minute for 7 hours or placebo, both also added to cardioplegic solutions. A prespecified futility analysis indicated a very low likelihood of a statistically significant efficacious outcome and the trial was stopped after 3080 of the originally projected 7500 participants were randomized. The primary composite of all-cause mortality, nonfatal stroke or need for mechanical support for severe left ventricular dysfunction through postoperative day 28 occurred in 75 of 1493 (5.0%) on placebo and 76 of 1493 (5.1%) on acadesine, odds ratio 1.01 (95% CI 0.73 to 1.41). There were no differences in key secondary endpoints.

Participants / model
3080 adults undergoing nonemergency on-pump CABG surgery
Treatment
Intravenous acadesine, 0.1 mg/kg/min for 7 hours plus cardioplegic solution, or placebo
Follow-up
Primary outcome through postoperative day 28
Study design
Randomized, double-blind, placebo-controlled phase 3 trial, stopped for futility
Funding
not stated in the source

Built to confirm the positive pooled analysis and did not. A cardiac surgery population given intravenous acadesine.

Read the original source
2008 mouse study: 4 weeks of AICAR enhanced treadmill endurance by 44% in sedentary mice

Animal study

Narkar VA et al. Cell. 2008;134(3):405-15. PMID 18674809.

Pathway-specific drugs were tested on the endurance capacity of mice in a treadmill running test. A PPAR-beta/delta agonist and exercise training synergistically increased oxidative myofibers and running endurance in adult mice. The authors then tested whether AICAR alone could substitute for the exercise requirement, and report that even in sedentary mice, 4 weeks of AICAR treatment alone induced metabolic genes and enhanced running endurance by 44%. The abstract describes AICAR as an orally active AMPK agonist but states no dose, route or strain for the mouse experiments.

Participants / model
Adult mice, including a sedentary group
Treatment
AICAR; dose and route not stated in the abstract; 4 weeks
Follow-up
4 weeks
Study design
Original animal study
Funding
not stated in the source

The 44% figure belongs to sedentary mice on a treadmill over 4 weeks. There is no human arm, and no dose, route or strain is carried to this page.

Read the original source
2015 review: the 2008 mouse study prompted WADA to list certain AMPK activators

Animal study

Niederberger E et al. Sports Med. 2015;45(11):1497-509. PMID 26186961.

A review of AMPK activation and exercise capacity states that a study published in 2008, directly before the Olympic Games in Beijing, showed that the AMPK activator AICAR increased the running capacity of mice without any training, and that this prompted the World Anti-Doping Agency to include certain AMPK activators in the list of forbidden drugs.

Participants / model
Records reviewed; mice in the underlying study
Treatment
Not applicable
Follow-up
not stated in the source
Study design
Narrative review
Funding
not stated in the source

A summary of the regulatory consequence of the 2008 study. It is not a new experiment.

Read the original source
Systematic review: many AICAr effects once attributed to AMPK are AMPK-independent

Systematic review and meta-analysis

Višnjić D et al. Cells. 2021;10(5). PMID 34064363.

A systematic review of AICAr as a pharmacological AMPK modulator notes that the majority of early studies on the role of AMPK, both in physiological regulation of metabolism and in cancer pathogenesis, were based solely on the use of AICAr as an AMPK activator, and that an increasing number of studies show numerous AICAr effects previously attributed to AMPK activation are in fact AMPK-independent. The review covers metabolism, hypoxia, exercise, nucleotide synthesis and cancer, and calls for caution in interpreting AICAr-based studies as evidence about AMPK signaling.

Participants / model
Studies reviewed, not a population
Treatment
Not applicable
Follow-up
not stated in the source
Study design
Systematic review
Funding
not stated in the source

Any AMPK activator framing for AICAR carries this qualifier.

Read the original source

Studies and sources

PubChem: acadesine CID 17513 (riboside) and AICA ribonucleotide CID 65110 are different molecules

Chemical identity record

National Library of Medicine. PubChem compound records CID 17513 (acadesine, AICA riboside) and CID 65110 (AICA ribonucleotide, ZMP).

Two different molecules share this name. Acadesine, also called AICA riboside: PubChem CID 17513, C9H14N4O5, 258.23 g/mol, CAS 2627-69-2, synonyms including Arasine, AIC-riboside and GP-1-110. This is the nucleoside given to patients in every human trial cited. AICA ribonucleotide, also called ZMP or AICAR: PubChem CID 65110, C9H15N4O8P, 338.21 g/mol, CAS 3031-94-5. This is the phosphorylated nucleotide, the actual AMPK-activating species, formed inside cells after the riboside is taken up. A vendor product sold as 'AICAR' is almost certainly the riboside; the two records differ by a phosphate group and 80 g/mol, and dose figures taken from one do not transfer to the other.

Participants / model
Chemical identity, not a clinical population
Treatment
Two defined molecules, no approved formulation
Follow-up
Not applicable
Study design
NLM chemical records
Funding
not stated in the source

Identity records only; they say nothing about efficacy or safety. The link opens the acadesine (riboside) record.

Read the original source
2008 mouse study: 4 weeks of AICAR enhanced treadmill endurance by 44% in sedentary mice

Animal study

Narkar VA et al. Cell. 2008;134(3):405-15. PMID 18674809.

Pathway-specific drugs were tested on the endurance capacity of mice in a treadmill running test. A PPAR-beta/delta agonist and exercise training synergistically increased oxidative myofibers and running endurance in adult mice. The authors then tested whether AICAR alone could substitute for the exercise requirement, and report that even in sedentary mice, 4 weeks of AICAR treatment alone induced metabolic genes and enhanced running endurance by 44%. The abstract describes AICAR as an orally active AMPK agonist but states no dose, route or strain for the mouse experiments.

Participants / model
Adult mice, including a sedentary group
Treatment
AICAR; dose and route not stated in the abstract; 4 weeks
Follow-up
4 weeks
Study design
Original animal study
Funding
not stated in the source

The 44% figure belongs to sedentary mice on a treadmill over 4 weeks. There is no human arm, and no dose, route or strain is carried to this page.

Read the original source
2015 review: the 2008 mouse study prompted WADA to list certain AMPK activators

Animal study

Niederberger E et al. Sports Med. 2015;45(11):1497-509. PMID 26186961.

A review of AMPK activation and exercise capacity states that a study published in 2008, directly before the Olympic Games in Beijing, showed that the AMPK activator AICAR increased the running capacity of mice without any training, and that this prompted the World Anti-Doping Agency to include certain AMPK activators in the list of forbidden drugs.

Participants / model
Records reviewed; mice in the underlying study
Treatment
Not applicable
Follow-up
not stated in the source
Study design
Narrative review
Funding
not stated in the source

A summary of the regulatory consequence of the 2008 study. It is not a new experiment.

Read the original source
Anti-doping reference study: 12,377 athlete urine samples, AICAR is endogenous

Human study

Sobolevsky T et al. Drug Test Anal. 2019;11(3):530-535. PMID 30548818.

A reference-population study from the UCLA Olympic Analytical Laboratory states that both AICAR and mannitol are prohibited for use in sports. Analysis of 12,377 US athlete samples gave a mean urinary AICAR concentration of 647 +/- 365 ng/mL, median 574 ng/mL, 99th percentile 1786 ng/mL and 99.7th percentile 2151 ng/mL. The authors suggest that any sample above 2000 or 2500 ng/mL be analyzed by carbon isotope ratio mass spectrometry to establish the origin. AICAR is an endogenous compound, so presence alone is not a finding, and laboratories rely on isotope ratio work to separate administered from self-produced.

Participants / model
12,377 urine samples from US athletes
Treatment
Not applicable; endogenous and administered AICAR in urine
Follow-up
not stated in the source
Study design
Anti-doping reference-population study
Funding
not stated in the source

An analytical reference study of urine samples, not an efficacy or safety study.

Read the original source
1997 pooled analysis: 4043 bypass patients, perioperative myocardial infarction down 27%

Systematic review and meta-analysis

Mangano DT. JAMA. 1997;277(4):325-32. PMID 9002496.

An individual-patient-data meta-analysis of 5 randomized, placebo-controlled, double-blind trials across 81 medical centers in the United States, Canada and Europe pooled 4043 patients undergoing coronary artery bypass graft surgery, randomized to placebo (n=2031) or acadesine 0.1 mg per kg per minute by intravenous infusion for 7 continuous hours plus administration via the cardioplegia solution (n=2012). Acadesine decreased perioperative myocardial infarction by 27% (OR 0.69, 95% CI 0.51 to 0.95, P=.02), cardiac death through postoperative day 4 by 50% (OR 0.52, 95% CI 0.27 to 0.98, P=.04) and the combined outcome of MI, stroke or cardiac death by 26% (OR 0.73, 95% CI 0.57 to 0.93, P=.01). Cerebrovascular accident was not significantly reduced (OR 0.69, 95% CI 0.44 to 1.08, P=.10). Adverse event rates were similar to placebo except for a transient increase in serum uric acid.

Participants / model
4043 adults undergoing CABG surgery
Treatment
Intravenous acadesine, 0.1 mg/kg/min for 7 hours plus cardioplegia solution, or placebo
Follow-up
Perioperative; cardiac death assessed through postoperative day 4
Study design
Individual-patient-data meta-analysis of 5 randomized, placebo-controlled, double-blind trials
Funding
not stated in the source

A cardiac surgery population given intravenous acadesine. It says nothing about exercise or oral use.

Read the original source
RED-CABG phase 3: 3080 patients, stopped for futility, primary outcome 5.0% versus 5.1%

Randomized controlled trial

Newman MF et al. JAMA. 2012;308(2):157-64. PMID 22782417.

RED-CABG was a randomized, double-blind, placebo-controlled, parallel-group evaluation of intermediate-to-high-risk patients (median age 66) undergoing nonemergency on-pump CABG surgery at 300 sites in 7 countries, enrolling from 6 May 2009 to 30 July 2010. Participants were randomized 1:1 to acadesine 0.1 mg per kg per minute for 7 hours or placebo, both also added to cardioplegic solutions. A prespecified futility analysis indicated a very low likelihood of a statistically significant efficacious outcome and the trial was stopped after 3080 of the originally projected 7500 participants were randomized. The primary composite of all-cause mortality, nonfatal stroke or need for mechanical support for severe left ventricular dysfunction through postoperative day 28 occurred in 75 of 1493 (5.0%) on placebo and 76 of 1493 (5.1%) on acadesine, odds ratio 1.01 (95% CI 0.73 to 1.41). There were no differences in key secondary endpoints.

Participants / model
3080 adults undergoing nonemergency on-pump CABG surgery
Treatment
Intravenous acadesine, 0.1 mg/kg/min for 7 hours plus cardioplegic solution, or placebo
Follow-up
Primary outcome through postoperative day 28
Study design
Randomized, double-blind, placebo-controlled phase 3 trial, stopped for futility
Funding
not stated in the source

Built to confirm the positive pooled analysis and did not. A cardiac surgery population given intravenous acadesine.

Read the original source
Human PK: 4 healthy men, intact acadesine measurable for 2 hours, uric acid the main metabolite

Human study

Dixon R et al. J Clin Pharmacol. 1993;33(10):955-8. PMID 8227467.

Four healthy males received a 15-minute intravenous infusion of 25 mg/kg of 2-14C-acadesine. Postinfusion total 14C in plasma declined multiexponentially with an apparent terminal half-life of about 1 week, but intact acadesine was only measurable for 2 hours after the infusion. Total plasma clearance was 2.2 +/- 0.2 L per hour per kg, the blood to plasma ratio was unity, and plasma protein binding was negligible at approximately 1%. Uric acid, the end product of purine metabolism in humans, was the major plasma metabolite and accounted for all of the total plasma 14C at 6 hours. Acadesine 5'-monophosphate was present in red blood cells and represented 30% of total blood 14C at the end of the infusion, confined to the red cells and absent from plasma. Over 2 weeks, urine and fecal recovery accounted for 48% of the dose, 44% in urine and 4% in feces, with only 5% of the dose excreted in urine as intact acadesine.

Participants / model
4 healthy adult males
Treatment
Intravenous 2-14C-acadesine, 25 mg/kg over 15 minutes
Follow-up
2 weeks of urine and fecal collection
Study design
Original human PK study
Funding
not stated in the source

Every number is for a 15-minute intravenous infusion in healthy men. No oral exposure was measured.

Read the original source
Leukemia dose escalation: 24 patients, maximum tolerated dose 210 mg/kg, hyperuricemia common

Clinical trial

Van Den Neste E et al. Cancer Chemother Pharmacol. 2013;71(3):581-91. PMID 23228986.

Twenty-four patients with relapsed or refractory chronic lymphocytic leukemia received acadesine intravenously as a 4-hour infusion: 18 in Part I at single doses of 50 to 315 mg/kg, and 6 in Part II, three with two doses at 210 mg/kg and three with five doses at 210 mg/kg. A manageable and predictable safety profile was demonstrated between 50 and 210 mg/kg; 210 mg/kg was the maximum tolerated dose and the optimal biological dose. Grade 2 or higher hyperuricemia occurred commonly, described as not clinically significant and resolving with prophylactic allopurinol. Other adverse events included transient anemia or thrombocytopenia described as not clinically significant, renal impairment, and transient infusion-related hypotension described as clinically significant. Trends toward reduction of peripheral CLL cells and lymphadenopathy were observed but variable given the small population and dose range.

Participants / model
24 adults with relapsed or refractory chronic lymphocytic leukemia
Treatment
Intravenous acadesine, 4-hour infusion, 50 to 315 mg/kg
Follow-up
Single doses (Part I); two or five doses (Part II)
Study design
Phase 1/2 dose-escalation trial
Funding
not stated in the source

A leukemia population given intravenous infusions. The findings do not apply to exercise or oral use.

Read the original source
Systematic review: many AICAr effects once attributed to AMPK are AMPK-independent

Systematic review and meta-analysis

Višnjić D et al. Cells. 2021;10(5). PMID 34064363.

A systematic review of AICAr as a pharmacological AMPK modulator notes that the majority of early studies on the role of AMPK, both in physiological regulation of metabolism and in cancer pathogenesis, were based solely on the use of AICAr as an AMPK activator, and that an increasing number of studies show numerous AICAr effects previously attributed to AMPK activation are in fact AMPK-independent. The review covers metabolism, hypoxia, exercise, nucleotide synthesis and cancer, and calls for caution in interpreting AICAr-based studies as evidence about AMPK signaling.

Participants / model
Studies reviewed, not a population
Treatment
Not applicable
Follow-up
not stated in the source
Study design
Systematic review
Funding
not stated in the source

Any AMPK activator framing for AICAR carries this qualifier.

Read the original source
Registry, 9 October 2026: four studies, none on exercise, endurance or performance

Trial registry record

ClinicalTrials.gov query for acadesine and AICAR run on 9 October 2026; records NCT00872001, NCT00559624, NCT01813838 and NCT06845501.

A ClinicalTrials.gov query on 9 October 2026 returned four studies: NCT00872001 (phase 3, n=3080, terminated, results posted, the RED-CABG trial), NCT00559624 (phase 1/2, n=40, completed, no results posted, B-CLL), NCT01813838 (phase 1/2, n=5, terminated, no results posted) and NCT06845501 (n=10, recruiting, purine supplementation in AICA-ribosiduria, an inherited metabolic disorder and not an acadesine intervention study). No registered study of acadesine or AICAR for exercise, endurance, body composition or performance was located.

Participants / model
Records returned, not a population
Treatment
Not applicable
Follow-up
Query run on 9 October 2026
Study design
Registry query
Funding
not stated in the source

The link opens the RED-CABG record, NCT00872001, which has posted results.

Read the original source

Why is AICAR (acadesine) in D tier?

D fits a compound whose claim rests on one mouse study. More than 7,000 randomized patients were studied across a 1997 pooled analysis and RED-CABG, but those studies concern myocardial infarction after bypass surgery, given as a 7-hour intravenous infusion, and the phase 3 trial built to confirm the positive pooled result was stopped for futility. No human has been given AICAR for endurance in the sources reviewed, and a systematic review finds that many effects attributed to AICAr are not AMPK-mediated.