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Aic3.1

AICAR (Acadesine) Research

Mostly mechanism / observational

11 peer-reviewed studies

What the evidence says

Mostly mechanism / observational

Most AICAR (Acadesine) studies are mechanism or observational rather than RCTs that measure a clinical effect — keep findings provisional.

Most evidence is from medium-quality meta-analyses and randomised trials published 1994–2019 with a typical study size of 4,043 participants.

Based on 11 studies · 1 meta-analysis · 6 RCTs · 4,043 total participants

Confidence

High confidence

By outcome

Cardiac surgery & ischemia (human)
Mostly mechanism / observational7 studies
Metabolic & AMPK
Mostly mechanism / observational4 studies
Endurance & exercise (preclinical)Increased running endurance in sedentary mice as an AMPK "exercise mimetic"; no human exercise/performance evidence, poor oral bioavailability, and WADA-banned. · Not established (no human efficacy data)
Mostly mechanism / observational3 studies
Safety profile
Too few graded studies2 studies

Older research base

Newest study from 2019 · Latest meta-analysis: 1997

199420062019

1RCT2012

Newman MF, Ferguson TB, White JA, Ambrosio G, Koglin J, Nussmeier NA · JAMA (2012)

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2RCT2006

Mangano DT, Miao Y, Tudor IC, Dietzel C · J Am Coll Cardiol (2006)

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3RCT1995

Menasché P, Jamieson WR, Flameng W, Davies MK · J Thorac Cardiovasc Surg (1995)

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4RCT1994

Holdright DR, Sparrow JL, Wright CL, Steiner J, Fox KM · Cardiovasc Drugs Ther (1994)

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5RCT1995

· Anesthesiology (1995)

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6RCT1994

Leung JM, Stanley T, Mathew J, Curling P, Barash P, Salmenpera M · Anesth Analg (1994)

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7Meta-Analysisn=4,043 · very large study1997

In plain English: Treatment with acadesine before and during surgery can reduce early cardiac death, MI, and combined adverse cardiovascular outcomes.

Mangano DT (McSPI Research Group) · JAMA (1997)

Individual-patient meta-analysis of 5 randomized, placebo-controlled CABG trials (4043 patients) — the early positive human signal
Acadesine reduced perioperative myocardial infarction by 27% and the combined MI/stroke/cardiac-death outcome by 26%
Reduced early cardiac death; safety similar to placebo apart from a transient rise in serum uric acid

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8Review2016

In plain English: Such so-called exercise or caloric restriction 'mimetics' have so far mostly been described in pre-clinical, experimental settings with limited translation into humans.

Handschin C · Pharmacological Research (2016)

Review explicitly addressing whether exercise/caloric-restriction mimetics (including AICAR-class AMPK activators) are ready for human use
Concludes they remain largely preclinical with limited human translation — a direct caution against the 'exercise in a pill' framing
Most candidates converge on PGC-1α in skeletal muscle, the same pathway AICAR engages

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9Review2018

In plain English: The most efficacious compounds that induce muscle hypertrophy or endurance are hampered by severe side effects and are classified as doping.

Weihrauch M, Handschin C · Biochemical Pharmacology (2018)

Review of 'exercise mimetics' including AICAR, weighing the AMPK–PGC-1α rationale against translational reality
Notes that the most potent muscle/endurance compounds carry severe side effects and are classified as doping (AICAR is WADA-banned)
Frames the feasibility of pharmacological exercise mimicry as highly debated, not established

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10Animal2008

In plain English: Even in sedentary mice, 4 weeks of AICAR treatment alone induced metabolic genes and enhanced running endurance by 44%.

Narkar VA, Downes M, Yu RT, Embler E, Wang YX, Banayo E, et al. · Cell (2008)

The foundational 'exercise mimetic' study — but entirely in mice: a treadmill running test, not a human trial
The orally active AMPK agonist AICAR, given for 4 weeks to SEDENTARY mice, increased running endurance by 44% with no exercise
AICAR and a PPARβ/δ agonist induced oxidative myofibers and metabolic genes via the AMPK–PGC-1α pathway

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11In Vitro2019

In plain English: Stimuli-inducible GLUT4 release relies on Tbc1d1-evoking proximal stimuli, such as AICAR and intracellular Ca2+.

Hatakeyama H, Morino T, Ishii T, Kanzaki M · The Journal of Biological Chemistry (2019)

Mechanistic cell-based reconstitution study grounding the GLUT4/glucose-uptake arm of AICAR's action
AICAR acts as an exercise-mimetic stimulus that triggers GLUT4 release via the RabGAP Tbc1d1 (the contraction/AMPK pathway, distinct from insulin's AS160 route)
Clarifies how AMPK-type stimuli mobilize glucose transporters in muscle cells

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View in Research Library

AICAR (Acadesine) Research

Mostly mechanism / observational

Effect of adenosine-regulating agent acadesine on morbidity and mortality associated with coronary artery bypass grafting: the RED-CABG randomized controlled trial.

Post-reperfusion myocardial infarction: long-term survival improvement using adenosine regulation with acadesine.

Acadesine: a new drug that may improve myocardial protection in coronary artery bypass grafting. Results of the first international multicenter study. Multinational Acadesine Study Group.

Effect of acadesine, a new metabolic agent, on exercise-induced myocardial ischemia in chronic stable angina.

Effects of acadesine on the incidence of myocardial infarction and adverse cardiac outcomes after coronary artery bypass graft surgery. Multicenter Study of Perioperative Ischemia (McSPI) Research Group.

An initial multicenter, randomized controlled trial on the safety and efficacy of acadesine in patients undergoing coronary artery bypass graft surgery. SPI Research Group.

Effects of acadesine on myocardial infarction, stroke, and death following surgery. A meta-analysis of the 5 international randomized trials.

Caloric restriction and exercise "mimetics": Ready for prime time?

Pharmacological targeting of exercise adaptations in skeletal muscle: Benefits and pitfalls.

AMPK and PPARdelta agonists are exercise mimetics.

Cooperative actions of Tbc1d1 and AS160/Tbc1d4 in GLUT4-trafficking activities.