AICAR: The Complete Guide
The original "exercise in a pill", a headline built on one mouse study, followed by a 3,000-patient human trial that found nothing at all. Here is the full arc, including the parts that never made the press release.
This guide covers the pharmacology, animal findings, completed human trials and regulatory position of AICAR (acadesine). It is educational only and not a substitute for advice from a qualified healthcare professional. Sources are listed at the end.
Read this before the rest of the page
AICAR is named individually on the WADA Prohibited List and has been since 2009. It appears under hormone and metabolic modulators as an AMPK activator, and it is prohibited at all times — in and out of competition. This is not a compound swept up by a catch-all clause; anti-doping authorities named it specifically, and a detection method was developed alongside the research that made it famous. Endurance athletes are the audience this compound is marketed to and the audience with the most to lose from using it. If you compete in any tested sport, including many amateur, masters and age-group events, treat AICAR as disqualifying and confirm the current position with your national anti-doping organisation before going near it.
AICAR occupies an unusual position among the compounds discussed in this catalogue. Most of them suffer from too little human data. AICAR has the opposite problem: it has been through large, well-conducted, placebo-controlled human trials, and those trials are the reason to be sceptical of it rather than the reason to be interested.
It is also the compound that gave the world the phrase "exercise in a pill" — a description that has followed it since 2008 and which its own discoverers were considerably more careful about than the coverage suggested.
What AICAR Is
The full name is 5-aminoimidazole-4-carboxamide ribonucleotide. Its international non-proprietary name is acadesine, which is what regulators and clinical trials call it.
Two things to establish immediately. First, AICAR is not a peptide. It is a nucleoside — the same broad chemical family as the building blocks of DNA and RNA — and it contains no amino acids at all. It sits in peptide catalogues for commercial reasons rather than chemical ones, alongside compounds like 5-Amino-1MQ and SLU-PP-332 that are similarly misfiled. Our guide to the different types of peptides explains why that distinction matters for absorption, storage and handling.
Second, it is not new. AICAR occurs naturally as an intermediate in the pathway your cells use to build purines from scratch. Pharmaceutical development began in the 1980s, and by the 1990s it was in large cardiac surgery trials. The bodybuilding and endurance interest arrived roughly two decades after the medical interest did.
How It Works
AICAR gets into cells through nucleoside transporters, and once inside is phosphorylated into a molecule called ZMP. ZMP closely resembles AMP — the signal a cell produces when it is running short of energy — and it binds the same site on AMPK.
The result is AMPK activation without the cell actually being depleted. AMPK is the switch that shifts a cell from storing to burning: glucose transporters move to the muscle surface, fat oxidation increases, and energy-expensive building programmes are throttled back. It is the same enzyme that MOTS-c reaches by a different route.
Simplified. The adenosine-regulating action and the AMPK action are distinct, and the cardiac trials were built around the first.
AMPK activation
Via ZMP mimicking AMP. Drives the metabolic gene programme that overlaps with what endurance training produces.
Adenosine regulation
Raises local adenosine by competing for the transporter and inhibiting adenosine deaminase. The basis of the cardiac programme.
Fibre-type gene expression
In mice, four weeks of treatment shifted muscle gene expression toward an oxidative, endurance-type profile without training.
Purine pathway effects
As a purine intermediate, it perturbs nucleotide metabolism — which is the likely route to the raised uric acid seen in trials.
The Study That Made It Famous
In July 2008, Ronald Evans's group at the Salk Institute published a paper in Cell that produced one of the most-quoted results in exercise science.
They had been testing GW1516, a PPARδ agonist, expecting it to reprogram muscle for endurance. In sedentary mice it did nothing for performance — the lead author described the metabolic markers improving with "no effect, absolutely none, on exercise performance." Combined with treadmill training, the same compound produced a 60 to 75 percent endurance increase.
That result pointed at AMPK as the missing ingredient, since training activates it. So they gave AICAR to untrained mice for four weeks and put them on the treadmill. The sedentary, drug-treated mice ran roughly 44 percent longer than untreated, untrained controls — with no exercise at all.
What that finding does and doesn't establish
It is a real, well-conducted result and it changed how researchers thought about exercise signalling. It is also a result in mice, at doses and by a route that do not translate simply, measured on a treadmill test rather than on anything a person cares about. Seventeen years later, nobody has replicated it in humans — not because the attempt failed, but because the trial has never been run. Every human study of this compound was designed around a different question entirely.
Worth noting what the researchers did next. Rather than pursuing performance, Evans's group developed a detection assay and took it to the World Anti-Doping Agency, explicitly because they expected the compound to be abused. That is an unusual thing for a discovery team to do, and it tells you how they read their own result.
What Happened in Humans
AICAR has more human trial data behind it than almost any compound in this catalogue. The story that data tells is not the one the marketing tells.
The cardiac programme
Because of its adenosine-regulating action, acadesine was developed to reduce ischaemic injury during coronary artery bypass surgery. Trials through the 1990s used intravenous infusion during and after surgery. A 1995 study across twenty US centres randomised 633 patients to placebo or one of two infusion rates.
In 1997, a meta-analysis of five randomised trials, published in JAMA, reported that acadesine was associated with reduced early cardiac death, myocardial infarction and combined adverse cardiac outcomes. That looked like a compound on its way to approval.
The trial that settled it
RED-CABG was the confirmatory study: randomised, double-blind, placebo-controlled, across 300 sites in seven countries, in intermediate-to-high-risk patients undergoing bypass surgery. Patients received acadesine at 0.1 mg per kilogram per minute for seven hours, plus acadesine added to the cardioplegic solution.
It was stopped early. A prespecified futility analysis showed a very low likelihood of a significant result, and enrolment halted at 3,080 patients of a planned 7,500.
| RED-CABG primary outcome | Placebo | Acadesine |
|---|---|---|
| Death, non-fatal stroke, or severe LV dysfunction needing mechanical support, through day 28 | 75 of 1,493 (5.0%) | 76 of 1,493 (5.1%) |
| Odds ratio | 1.01 (95% CI 0.73–1.41) | |
| Key secondary endpoints | No differences found | |
That is about as flat a result as a large trial can produce. The published analysis drew a broader lesson from it, about the risk of planning confirmatory trials on the strength of promising meta-analyses — which is a fair description of what happened here.
The oncology attempt
Acadesine was later examined in blood cancers. A French phase 1/2 trial in high-risk myelodysplastic syndromes and related conditions tested escalating doses from 140 mg per kilogram per day upward. It was terminated, with renal toxicity recorded as the reason for stopping. That is a documented safety signal at high exposure, and it comes from the trial registry rather than from anyone's opinion.
The Dose Problem
This is where AICAR differs most sharply from the other compounds in this catalogue, and it deserves plain arithmetic.
| Setting | Dose reported | Route | What it works out to |
|---|---|---|---|
| Cardiac surgery trials | 0.1 mg/kg/min for 7 hours | Intravenous infusion | About 2.9 g for a 70 kg adult, per session |
| Earlier cardiac trial, low arm | 0.05 mg/kg/min for 7 hours | Intravenous infusion | About 1.5 g for a 70 kg adult |
| Oncology trial | 140–315 mg/kg/day | Intravenous | Roughly 10–22 g per day for a 70 kg adult |
| Community protocol convention | Tens of milligrams | Subcutaneous | Not derived from any published human study |
Community figures reflect what circulates in protocol literature, not a published trial. No subcutaneous dose of AICAR has been studied in humans.
Two things follow. The trials used continuous infusion rather than a single injection, which tells you the compound clears quickly and needs sustained delivery to hold a concentration. And at gram quantities, AICAR becomes genuinely expensive — the economics of the research market alone make trial-equivalent dosing impractical.
Whether a fifty-milligram subcutaneous injection does anything at all is unknown. It has never been tested. The honest reading is that the community dose and the studied dose are not the same intervention.
Side Effects & Safety
Unusually for this catalogue, there is a real human safety database — from thousands of surgical patients under close monitoring.
In the 633-patient cardiac study, adverse event rates were broadly similar between acadesine and placebo, with one exception: serum uric acid rose transiently in the high-dose group. That is mechanistically unsurprising given AICAR's position in purine metabolism, and it is the most consistently reported biochemical effect.
The larger RED-CABG trial found no efficacy benefit and no differences in the secondary endpoints measured. The oncology trial's termination for renal toxicity is the clearest adverse signal in the record, and it occurred at doses roughly five to ten times the cardiac infusion.
Where caution applies
Gout or high uric acid. Raised uric acid is the best-documented biochemical effect of this compound. Anyone with a history of gout, kidney stones or hyperuricaemia should treat that as a direct contraindication rather than a theoretical one. Kidney disease. A clinical trial was stopped for renal toxicity at high exposure. Impaired renal function is not a good starting point for a compound with that history. Cardiac medication or cardiac history. AICAR raises local adenosine, which affects heart rate and conduction — this is the property the cardiac programme was built around, and it means interactions with cardiac drugs are plausible and unstudied. See peptide drug interactions. Diabetes medication. AMPK activation and glucose-lowering agents push in the same direction, with no interaction data. Pregnancy and breastfeeding. No data — avoid.
What the safety record does not cover is repeated subcutaneous self-administration over months, which is how the compound is actually used outside a hospital. Short intravenous exposure in monitored patients is a poor guide to that.
How It Compares
| Compound | Mechanism | Human evidence | Anti-doping status |
|---|---|---|---|
| AICAR | ZMP mimics AMP, activating AMPK directly | Large trials for cardiac surgery; the biggest was null. None for performance | Named individually; prohibited at all times |
| MOTS-c | AMPK via folate-cycle inhibition and AICAR accumulation | Genetic and observational only; no interventional trial | Named individually; prohibited at all times |
| SLU-PP-332 | ERR agonist; endurance programme without AMPK | Rodent only | Not named; treat as prohibited |
| 5-Amino-1MQ | NNMT inhibition; preserves NAD+ and SAM | None — no trials at all | Not named; treat as prohibited |
| Metformin | Multiple metabolic effects including AMPK | Decades of trials; approved medicine | Not prohibited |
| Endurance training | Activates AMPK, and everything else | The strongest evidence base of anything listed | Encouraged |
The last row is doing real work. AICAR's entire appeal is producing the adaptations that training produces. Training produces them reliably, in humans, with an evidence base nothing else here approaches, and without a WADA problem. If the goal is endurance, that comparison is not close.
Regulatory & Anti-Doping
AICAR has never been approved as a medicine in any jurisdiction. It went through a full development programme, failed its confirmatory trial, and was not pursued further. It is sold as a research compound, and our guide to research versus pharmaceutical peptides covers what that means for manufacturing and oversight.
On anti-doping, the position is unusually clear-cut. AICAR is named explicitly on the WADA Prohibited List under hormone and metabolic modulators, in the AMPK activator subcategory, and has been prohibited since 2009 — among the first compounds added to that class. A detection assay was developed in parallel with the research that publicised it, so this is not a substance that flew under testing while regulators caught up.
Because it is not approved by any governmental health authority for human therapeutic use, it would also fall under WADA's non-approved substances clause even if it were not named. Both routes lead to the same place.
Common Questions
Does AICAR actually work as an exercise mimetic in people?
Unknown, because the study has never been done. The 44 percent endurance result is from sedentary mice, and no human trial has ever measured performance. The human trials that exist were designed around cardiac surgery and found no benefit for that.
Is AICAR a peptide?
No. It is a nucleoside, chemically related to the building blocks of DNA and RNA, with no amino acids in it. It is grouped with peptides commercially rather than chemically.
Why did the big trial fail if the earlier ones looked positive?
This is a common pattern rather than a scandal. Small trials with favourable results get pooled into a meta-analysis, the pooled estimate looks convincing, and a large confirmatory trial finds nothing. Publication bias, small-study effects and chance all contribute. The RED-CABG authors made exactly this point about their own field.
Is oral AICAR effective?
The mouse work used oral delivery, but the human trials all used intravenous infusion — which tells you something about how the developers viewed absorption and clearance in people. No human study has established an effective oral dose.
Will it raise my uric acid?
It did so transiently in trial patients at the higher infusion rate, and the mechanism makes that expected given where AICAR sits in purine metabolism. Whether much smaller subcutaneous doses do the same has not been studied. Anyone with gout should treat this as a reason to avoid it entirely.
Can I combine it with metformin or berberine?
Both push on AMPK signalling and glucose handling, and the combination has never been studied. Stacking two glucose-lowering agents without data is how people end up hypoglycaemic. If you take prescribed glucose-lowering medication, this is a conversation for your prescriber.
Why is it so expensive?
Synthesis cost, and the quantities involved. At the doses used in trials — grams per session — the material cost alone would be prohibitive, which is part of why trial-equivalent dosing never migrated into the research market. The doses people actually use are small partly for economic reasons rather than pharmacological ones.
How is it stored and reconstituted?
As a small molecule rather than a peptide, it is generally more stable than the lyophilized peptides in this catalogue, but sealed vials should still be kept cool and dark, and any reconstituted solution refrigerated. Our guides on reconstitution and storage in tropical climates cover the practical side.
What does Peptides Costa Rica carry, and what does it cost?
Current vial sizes, pricing and stock are on the AICAR product page, and five or more vials of the same product carry an automatic 15% discount. If you compete in a tested sport, read the warning at the top of this page before ordering — we would rather tell you than have you find out from a testing panel.
Is it legal in Costa Rica?
It is sold here as a research compound and is not approved as a finished pharmaceutical drug by the Ministerio de Salud, the FDA or the EMA. Legality of possession and anti-doping eligibility are separate questions — a substance can be legal to buy and still end a competitive career. Our FAQ page covers ordering locally.
Questions about AICAR?
We would rather walk you through what the trials actually found than sell you a headline from 2008. If your goal is endurance and something else fits better, we'll say so.
Contact Us on WhatsAppImportant disclaimer: The information in this guide is general educational content only. It is not medical advice, a prescription, or a personalized recommendation. AICAR, also known as acadesine, is not approved by the FDA, the EMA, or Costa Rica's Ministerio de Salud as a finished pharmaceutical drug for human use, and is sold as a research compound intended for laboratory and scientific study. It is not a treatment for any condition. It is not a peptide; it is a nucleoside analogue. The endurance findings described here come from studies in mice; no human trial has ever measured exercise performance with this compound, and the mouse result has not been replicated in humans. The human trials that exist were designed to reduce ischaemic injury during cardiac surgery: a meta-analysis of five earlier trials suggested benefit, but the large confirmatory RED-CABG trial was stopped for futility and found no difference from placebo on its primary or secondary endpoints. A separate oncology trial was terminated with renal toxicity recorded as the reason. Transient elevation of serum uric acid has been reported at higher infusion rates. Dosing figures discussed reflect what is reported in published research and in community use; they are not endorsements of those doses for any specific individual, and no subcutaneous dose has been studied in humans — every human dose that produced measurable effects was administered intravenously in gram quantities under clinical supervision. No interaction studies exist with cardiac medication, glucose-lowering agents or any other drug class. No safety data exists for pregnancy, breastfeeding, or long-term self-administration. AICAR is named explicitly on the World Anti-Doping Agency Prohibited List as an AMPK activator and has been prohibited at all times, in and out of competition, since 2009; a validated detection method exists. Always consult a qualified healthcare professional before beginning any protocol. Products sold by Peptides Costa Rica are intended for laboratory and research purposes only.
- Cell (Narkar, Downes, Evans et al., 2008): AMPK and PPARδ agonists reprogram muscle gene expression; four weeks of AICAR increased running endurance by approximately 44% in sedentary mice, while GW1516 improved endurance only in combination with training.
- Salk Institute research communications (2008): Account of the study, the "exercise in a pill" framing, and the development of a detection assay in cooperation with the World Anti-Doping Agency.
- JAMA (Newman et al., 2012;308:157–164): The RED-CABG randomised controlled trial — 3,080 patients of a planned 7,500 across 300 sites, acadesine 0.1 mg/kg/min for 7 hours, stopped for futility, primary outcome 5.0% placebo versus 5.1% acadesine, odds ratio 1.01 (95% CI 0.73–1.41), no differences in secondary endpoints.
- JAMA (1997) meta-analysis of five randomised trials: Perioperative acadesine infusion associated with reduced early cardiac death, myocardial infarction and combined adverse cardiac outcomes — the basis on which the confirmatory trial was planned.
- Anesthesiology (Multicenter Study of Perioperative Ischemia, 1995): 633 patients randomised to placebo or acadesine at 0.05 or 0.1 mg/kg/min; similar adverse event rates across groups except a transient rise in serum uric acid in the high-dose group.
- Nature Reviews Cardiology (2012): Commentary on the RED-CABG result and acadesine's mechanism as an adenosine-regulating agent acting on the nucleoside transporter and adenosine deaminase alongside AMPK.
- ClinicalTrials.gov (NCT01813838): Phase 1/2 trial of acadesine at 140–315 mg/kg/day in high-risk myelodysplastic syndromes and related conditions, terminated with renal toxicity recorded as the reason for stopping.
- World Anti-Doping Agency: Prohibited List, hormone and metabolic modulators, naming AICAR among prohibited AMPK activators; prohibited at all times since 2009.
