D tier · weak
The famous endurance result is a single 2008 mouse experiment at 500 mg/kg/day by injection, the one large human randomised trial was for cardiac surgery and stopped for futility, and it is prohibited in sport at all times with no approved therapeutic use anywhere.
aicar
AICAR is a cell-permeable AMP analogue that activates AMP-activated protein kinase and produced a well-known increase in running endurance in sedentary mice. For athletic or body-composition purposes the evidence remains essentially preclinical; the largest human randomised trial tested it for cardioprotection during bypass surgery and was stopped early for futility.
// we supply this one
available as a research reagent
≥ 98% HPLC · lyophilised powder · batch certificate published. Grade D above is our own and is not adjusted because we stock it.
the explanation
AICAR switches on an energy sensor in cells that normally responds to exercise, and mice given large injected doses ran further without training. In humans it has only been tested for unrelated medical reasons, one big trial found no benefit, and it is banned in tested sport.
regulatory status
Not approved for any indication anywhere; prohibited at all times in sport
AICAR is listed under WADA class S4, Hormone and Metabolic Modulators, as an AMPK activator, prohibited both in and out of competition. USADA notes that because AICAR is not approved for human therapeutic use anywhere in the world, it is not eligible for a Therapeutic Use Exemption. WADA has funded work on detecting AICAR-ribotide in red blood cells as a long-term marker of illicit use. Only two studies with AICAR or acadesine as an intervention appear on ClinicalTrials.gov, in type 2 diabetes and Lesch-Nyhan disease — none for athletic performance or body composition.
how it works · proposed mechanism
AICAR imitates the intracellular signal that tells a cell it is running out of energy, triggering the same catabolic switch exercise activates.
ZMP as an AMP mimetic
Once inside the cell, AICAR is phosphorylated to ZMP, which mimics AMP and allosterically activates AMP-activated protein kinase. This happens without the cell actually depleting ATP, which is what makes it a pharmacological rather than physiological signal.
AMPK-driven oxidative programme
Activated AMPK shifts metabolism toward glucose uptake and fatty acid oxidation and engages PGC-1α-linked mitochondrial biogenesis in skeletal muscle. In mice this produced measurable gains in running endurance without any training stimulus.
Poor oral translation
The mouse endurance work used 500 mg/kg/day by intraperitoneal injection for four weeks, and human trials of acadesine used intravenous infusion. There is no published evidence that oral administration reproduces the exposures behind the rodent findings.
what’s reported
evidence shape
6 sourcesThe composition of the cited literature by study type. This describes the shape of the evidence, not its quality — and it does not by itself set the grade.
⚠ the catch
The single most-cited fact about AICAR — that it made mice run 44% further without training — came from four weeks of intraperitoneal injection at 500 mg/kg/day, a dose and route with no human analogue. Where humans have actually been given the compound at scale, in a 3,080-patient randomised cardiac surgery trial, it produced no benefit at all and was stopped early for futility.
key published findings
- Rodent: sedentary male C57Bl/6J mice given 500 mg/kg/day AICAR intraperitoneally for 4 weeks ran approximately 23% longer and approximately 44% further than vehicle-treated mice, with no exercise training (Narkar et al., Cell 2008;134(3):405-415).
- Rodent: in the same paper, the PPARδ agonist GW1516 alone (5 mg/kg/day oral) failed to alter fibre type composition or endurance in sedentary mice despite inducing oxidative gene expression — only AICAR monotherapy produced endurance gains.
- Human trial: RED-CABG, a randomised double-blind placebo-controlled trial across 300 sites in 7 countries, gave 42 mg/kg intravenous acadesine to intermediate-to-high-risk on-pump CABG patients; the primary composite of all-cause mortality, nonfatal stroke or severe LV dysfunction requiring mechanical support occurred in 5.1% of acadesine versus 5.0% of placebo patients (OR 1.01, 95% CI 0.73-1.41, P=0.94), and the trial was stopped for futility after 3,080 of a projected 7,500 participants (Newman et al., JAMA 2012;308(2):157-164).
- Official: only two studies list AICAR or acadesine as an intervention on ClinicalTrials.gov — one in type 2 diabetes (NCT00168519) and a phase 2 pilot in Lesch-Nyhan disease (NCT00004314); neither concerns athletic performance or body composition.
- Official: USADA states AICAR is prohibited as an AMPK activator under WADA's Hormone and Metabolic Modulators class, that it has not been extensively studied in people, and that it is not eligible for a Therapeutic Use Exemption because it is unapproved for human therapeutic use anywhere.
limitations of the evidence
- The rodent endurance dose of 500 mg/kg/day by intraperitoneal injection is enormous and route-specific; nothing in the literature establishes that any human exposure reproduces the relevant intracellular ZMP concentrations.
- AICAR has poor oral bioavailability and short-lived intracellular activity, so the mismatch between how it was studied and how it is used is not a technicality.
- The only large randomised human dataset is in cardiac surgery, an entirely different indication and administration setting, and it was negative — so it establishes tolerability in that context but says nothing about performance.
documented safety signals
- USADA describes AICAR as an experimental compound not extensively studied in people and warns of potential serious effects including neurodegeneration and interference with cell division.
- Prohibited at all times under WADA class S4; WADA has developed detection of AICAR-ribotide in red blood cells as a long-term marker of illicit use, so any tested athlete faces a sanction risk that persists after use.
- AMPK activation is a broad, non-tissue-selective signal, and no chronic human safety data exists at exposures relevant to the rodent findings.
- Not approved for human therapeutic use in any jurisdiction, so no regulator has reviewed a safety package for it.
identity
| full name | AICAR (acadesine, 5-aminoimidazole-4-carboxamide riboside) |
| category | Metabolic |
| modality | small molecule |
| formula | C9H14N4O5 |
| molar mass | 258.2 g/mol |
| cas | 2627-69-2 |
laboratory handling
| storage | Solid stored at -20 °C per supplier specification; solutions prepared fresh or stored frozen. |
| solubility | Water-soluble relative to the other compounds in this index. Cayman Chemical reports DMSO 20 mg/mL, DMF 10 mg/mL, PBS pH 7.2 2 mg/mL, and ethanol 1 mg/mL. |
| co-studied with | The Narkar 2008 paper is also the origin of the AICAR-plus-GW1516 pairing that circulates in performance contexts; in that study GW1516 alone did not improve endurance in sedentary mice, and its synergy was reported with exercise training rather than as a validated human stack. No human combination data exists, and GW1516 (cardarine) is itself prohibited in sport. |
Handling information describes laboratory practice for a research reagent. It is not a preparation guide for use in humans.
the receipts
6 citedU.S. Anti-Doping Agency · 2026 · official
World Anti-Doping Agency · 2026 · official
U.S. National Library of Medicine · 2026 · official
Cayman Chemical · 2026 · official
Cell 2008;134(3):405-415 · 2008 · preclinical
JAMA 2012;308(2):157-164 · 2012 · randomized
others in Metabolic