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AICAR (acadesine; 5-aminoimidazole-4-carboxamide ribonucleotide) — AMPK activator
A grey-market AMPK activator marketed as an 'exercise mimetic' on the strength of a single famous mouse study — Narkar 2008, where 4 weeks of AICAR boosted treadmill running endurance 44% in sedentary mice. That endurance signal has NEVER been shown in humans. The only human trials of AICAR (as the drug acadesine) were for a completely different purpose — protecting the heart during cardiac-bypass surgery — and the large, definitive RED-CABG randomized trial was NEGATIVE. AICAR has poor oral bioavailability (it's injected in studies), is WADA-banned as a doping agent, and is not an approved drug or a regulated supplement. There is no human exercise-performance evidence.
Research compound — not a dietary supplement
AICAR (Acadesine) is a research compound, not a regulated dietary supplement. It is sold for research or off-label use. The evidence below is largely preclinical (animal and in-vitro) or early-stage, so no evidence score is assigned. This page is provided for transparency and education — it is not a recommendation to use. Consult a qualified healthcare provider, and be aware that purity, dosing, and legal status vary by jurisdiction.
What the evidence says
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 confidenceBy outcome
AICAR's 'exercise mimetic' reputation rests on a single mouse study (Narkar 2008, +44% running endurance in sedentary mice) — there is no human exercise or performance evidence at all. Its only large human trial, RED-CABG, tested a different indication (cardiac-surgery protection) and was negative. Add poor oral bioavailability and a WADA ban, and the off-label endurance/longevity use is barely-supported.
AICAR (5-aminoimidazole-4-carboxamide ribonucleotide; the drug name is acadesine) is a cell-permeable AMP analogue that activates AMP-activated protein kinase (AMPK), the cell's central energy sensor.
Because endurance exercise also activates AMPK and its downstream coactivator PGC-1α, AICAR has been promoted as an 'exercise mimetic' — a pill that supposedly delivers training adaptations without training.
That entire reputation rests on one landmark animal paper: Narkar et al., Cell 2008, which reported that 4 weeks of AICAR alone induced oxidative metabolic genes and increased treadmill running endurance by 44% in sedentary mice.
It is a genuinely important mechanistic result — but it is a mouse result, and the honest, load-bearing caveat is that nothing like it has ever been demonstrated in a human. There is no human endurance trial, no human performance trial, no human geroprotection trial of AICAR.
The only human clinical evidence comes from a completely separate indication: AICAR, infused intravenously as 'acadesine,' was tested in the 1990s and 2010s to protect the heart from ischemia/reperfusion injury during coronary-artery-bypass-graft (CABG) surgery.
A 1997 individual-patient meta-analysis of five trials (McSPI/Mangano, JAMA) suggested acadesine reduced early cardiac death, myocardial infarction, and combined adverse cardiac events — a positive human signal.
But the definitive, properly powered test, the RED-CABG randomized double-blind trial (Newman et al., JAMA 2012, ~3,000 patients across 300 sites), was NEGATIVE: acadesine did not reduce the composite of all-cause mortality, nonfatal stroke, or severe left-ventricular dysfunction, and the trial was stopped early for futility.
So even in the one indication where AICAR reached large human trials, the best evidence failed to support it — and that indication is cardiac surgery, not exercise or longevity.
Pharmacologically, AICAR has poor oral bioavailability; the meaningful studies dose it by injection or infusion, which is why grey-market oral or even injectable 'AICAR' has no validated human regimen.
It is banned by the World Anti-Doping Agency (WADA) as a metabolic modulator, it is not approved by any regulator as a medicine, and it is not a lawful dietary-supplement ingredient — material sold online is an unregulated research chemical with no identity, purity, or sterility guarantee.
The score is LOW: a striking preclinical mechanism and an interesting (but ultimately negative) human cardiac-surgery story, with zero human exercise-performance evidence, poor bioavailability, and a doping ban.
AICAR is taken into cells and converted to ZMP, an AMP analogue that allosterically activates AMP-activated protein kinase (AMPK) — the master energy sensor that exercise also switches on. This is the proximal mechanism behind every claimed effect.
Downstream of AMPK, PGC-1α coordinates mitochondrial biogenesis and a shift toward oxidative, fatigue-resistant muscle fibres. In sedentary mice this drove the increase in running endurance — demonstrated in rodents, never in humans.
AMPK activation by AICAR promotes GLUT4-mediated glucose uptake (via Tbc1d1) and increases fatty-acid oxidation in muscle — the metabolic basis for the 'exercise-like' phenotype. Shown in cell and animal models only.
How AICAR (Acadesine) works — from molecular targets to health outcomes. Click an edge to see supporting research.This visualization is in beta — pathways are being refined and expanded.
Avoid absolutely — AICAR is WADA-prohibited and will trigger an anti-doping violation.
Avoid — there is no human exercise/longevity evidence; the endurance data are entirely from mice and the human (cardiac) trial was negative.
Avoid entirely — unstudied for this use.
AICAR and metformin both activate the AMPK pathway; combining AMPK activators has not been studied for safety in this context and could compound metabolic effects unpredictably.
AMPK activation promotes glucose uptake; theoretical additive hypoglycemia risk with insulin or insulin secretagogues. No human interaction data for off-label use.
Acadesine infusion caused transient increases in serum uric acid in cardiac-surgery trials; relevance to other settings is unknown.
Tip: Seen with IV acadesine in cardiac-surgery trials; monitor in anyone with gout/urate issues. Other effects of grey-market use are uncharacterized.
Tip: No human has been studied taking AICAR for endurance or longevity — the side-effect profile in that setting is genuinely unknown.
Tip: Grey-market material (especially injectables) has no identity/purity/sterility guarantees; contamination and dosing errors are possible.
AICAR (Acadesine) has an evidence score of 3.1/10 — emerging evidence based on 11 indexed studies, including 1 meta-analysis. A grey-market AMPK activator marketed as an 'exercise mimetic' on the strength of a single famous mouse study — Narkar 2008, where 4 weeks of AICAR boosted treadmill running endurance 44% in sedentary mice. That endurance signal has NEVER been shown in humans. The only human trials of AICAR (as the drug acadesine) were for a completely different purpose — protecting the heart during cardiac-bypass surgery — and the large, definitive RED-CABG randomized trial was NEGATIVE. AICAR has poor oral bioavailability (it's injected in studies), is WADA-banned as a doping agent, and is not an approved drug or a regulated supplement. There is no human exercise-performance evidence. Representative study: PMID 9002496.
The commonly studied dose of AICAR (Acadesine) is No legitimate or recommended dose — AICAR is an unapproved, WADA-banned research chemical with no validated human regimen. We do NOT provide a dosing protocol. The only human dosing on record is intravenous infusion of acadesine during cardiac surgery (0.1 mg/kg/min for ~7 hours), which is a hospital ischemia protocol, not an exercise or longevity dose, and which failed its definitive trial.. Individual needs vary — start at the lower end of the range and adjust based on how you respond.
Timing is flexible for AICAR (Acadesine) — consistent daily use matters more than the time of day. There is no validated human exercise/longevity dosing schedule.
AICAR (Acadesine) should be used with caution — talk to a healthcare provider before taking it. The most commonly reported side effects are transient hyperuricemia (raised serum uric acid), unknown human side-effect profile for exercise/longevity use, harm from an unregulated, impure or non-sterile product. Use caution if any of these apply to you: Not an approved medicine and not a regulated dietary supplement — unapproved grey-market research chemical; do not self-source; Banned by WADA in and out of competition — disqualifying for any tested athlete; No human exercise/longevity safety data exists — every such conclusion would be an extrapolation from animals.
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Reviewed by Dr. Baher Al Hakim · Last reviewed June 2026 · evidence from 11 studies · how we score · editorial policy
This information is for educational purposes only. It is not a substitute for professional medical advice. Always consult a qualified healthcare provider before starting, stopping, or changing any supplement or medication.
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