AICAR: the AMPK activator behind the exercise-in-a-pill headlines, and what the human trials found

AICAR stands for 5-aminoimidazole-4-carboxamide ribonucleoside (also written AICA riboside or AICAr). It is a naturally occurring intermediate in the pathway that builds purine nucleotides, and a synthetic version was developed as a drug under the name acadesine. Chemically it is a nucleoside: a small nitrogen-containing ring attached to a ribose sugar, with a molecular weight of 258 ^[14]. It contains no amino acids and is not a peptide, however it is labelled by the stores that sell it.

AICAR appears on PepFinder because the same research peptide suppliers that sell BPC-157 or ipamorelin also sell AICAR powder, often listed as an AICAR peptide, usually alongside other so-called exercise mimetics such as SLU-PP-332 and MOTS-c. We list it so that the evidence behind the marketing can be set out plainly and so that buyers can compare prices and testing in one place.

Its scientific importance is as a research tool. In 1995 Grahame Hardie’s group in Dundee showed that AICAR is taken up by cells and converted to ZMP, a molecule that mimics AMP and switches on AMP-activated protein kinase without changing the cell’s real energy levels ^[1]. That made it the standard laboratory method for activating AMPK, and thousands of cell and animal studies have used it since.

AMPK is the cell’s fuel gauge. When the ratio of AMP to ATP rises, as it does during exercise or fasting, AMPK is activated and shifts the cell towards processes that make energy, such as fatty acid oxidation and glucose uptake, and away from those that consume it. Inside cells AICAR is phosphorylated to ZMP, which binds the same site on AMPK as AMP and activates it ^[1]. In 1997, perfused rat muscle exposed to AICAR showed higher AMPK activity, more fatty acid oxidation and more glucose uptake, an effect that resembled the response to contraction ^[2].

This is why AICAR is called an exercise mimetic: it triggers some of the molecular signals that exercise triggers, without any exercise. Whether that adds up to the benefits of exercise is a different question, and one the human studies below do not answer.

AICAR also has effects that have nothing to do with AMPK. As a purine analogue it raises adenosine levels in stressed tissue, which is why it was developed as an adenosine-regulating agent for heart surgery ^[6], and in blood cancer cells it induces cell death through pathways that do not depend on AMPK ^[10]. Readers should therefore be careful about assuming that every AICAR result is an AMPK result.

The AICAR benefits claimed by sellers are endurance, fat loss and better blood sugar. The endurance claim comes from a single, widely cited 2008 study.

Endurance in mice: Ronald Evans’s laboratory at the Salk Institute tested whether drugs acting on the AMPK and PPAR-delta pathways could mimic training. In sedentary mice, four weeks of daily AICAR injections alone switched on metabolic genes in muscle and increased treadmill running endurance by 44%, with no exercise at all ^[3]. The finding was reported around the world as exercise in a pill, and the paper itself noted that the compounds would need to be detectable by anti-doping laboratories.

Glucose uptake in people: a 2007 Danish study infused AICAR into 29 healthy men and measured glucose uptake into muscle. AICAR roughly doubled muscle uptake of a labelled glucose tracer over three hours, compared with a 4.7-fold increase from cycling exercise, and increased whole-body glucose disposal by a modest 7%. AMPK activity in muscle biopsies did not change measurably ^[4]. A 2008 study in ten men with type 2 diabetes infused AICAR at 0.75 mg/kg per minute and found it reduced glucose output by the liver, lowered blood glucose and reduced the release of fatty acids from fat tissue ^[5]. These are acute effects of an intravenous infusion in a laboratory, not the result of taking a powder for weeks.

Fat loss: we found no controlled human study of AICAR for weight or fat loss. The mouse endurance study did not report body weight as an outcome ^[3], and the acute human infusion studies lasted hours ^[4][5].

Most human data on AICAR come from its development as acadesine, an intravenous drug intended to protect the heart during coronary artery bypass surgery. A 1997 meta-analysis of five randomised, placebo-controlled trials in 4,043 patients found that a seven-hour infusion of 0.1 mg/kg per minute reduced perioperative heart attacks by 27% and also reduced early cardiac death ^[8]. That result led to a much larger confirmatory trial.

The RED-CABG trial randomised intermediate- to high-risk bypass patients at 300 sites in seven countries to the same acadesine regimen or placebo, measuring death, stroke or severe heart failure at 28 days ^[9]. It found no benefit, and the programme was abandoned. The pattern, a promising meta-analysis followed by a negative large trial, is a useful caution for reading any AICAR claim.

In cancer, a 2013 phase 1/2 study gave acadesine as a four-hour intravenous infusion to 24 patients with relapsed chronic lymphocytic leukaemia at single doses of 50 to 315 mg/kg. The maximum tolerated dose was 210 mg/kg; adverse effects included high uric acid, transient anaemia and low platelets, kidney impairment and infusion-related low blood pressure, and there were signs of activity against the leukaemia cells ^[10].

The earliest human studies were safety and pharmacokinetic studies in healthy men. In 1991, doses of 10 to 100 mg/kg given intravenously and by mouth were tolerated with only mild, transient effects; the drug was cleared from plasma with a terminal half-life of 1.4 hours, was rapidly taken up and phosphorylated inside red blood cells, and only 8% appeared unchanged in urine ^[6]. A follow-up radiolabel study found that uric acid was the main metabolite in plasma and that acadesine monophosphate persisted in red cells ^[7].

There are no published trials of AICAR in athletes, in healthy people taking it for weeks, or by subcutaneous injection. The endurance effect seen in mice has never been tested in humans.

The human doses on record are all intravenous and were chosen for surgery or cancer, not for performance. In the heart-surgery trials, acadesine was infused at 0.1 mg/kg per minute for seven hours, with more added to the solution used to stop the heart ^[8][9]. The diabetes study infused 0.75 mg/kg per minute ^[5], and the leukaemia study gave single four-hour infusions of up to 315 mg/kg, with 210 mg/kg the maximum tolerated ^[10]. The 1991 safety study gave 10 to 100 mg/kg intravenously and orally ^[6].

In the mouse endurance study, AICAR was given by daily injection for four weeks at a dose per kilogram far above anything given to people ^[3]. Mouse doses do not scale to human doses by body weight alone, and no human study has tried to reproduce the endurance effect. None of these figures is a recommendation. Forum AICAR cycling protocols, typically daily injections for several weeks, come from users rather than from any trial. Our peptide calculator covers the arithmetic of reconstituting a vial and nothing more.

Every controlled human study of AICAR used intravenous infusion. Oral dosing was tested in the 1991 study, where the drug was absorbed but bioavailability was incomplete ^[6], and it was not pursued. Research suppliers sell AICAR as a powder for reconstitution and injection under the skin, and sometimes as capsules; we found no published human data on either route, so the amount reaching muscle, and its effect, is unknown. AICAR’s short half-life of about 1.4 hours in plasma ^[6] also means that a single injection is cleared quickly, although its phosphorylated form lingers in red blood cells ^[7].

At the doses used in surgery, acadesine was given to thousands of patients under monitoring and the trials reported no safety signal that stopped development; the programme ended for lack of benefit rather than harm ^[8][9]. At the much higher doses used in leukaemia, high uric acid was common enough that patients were given allopurinol to prevent it, and kidney impairment, transient anaemia, low platelets and low blood pressure during infusion were recorded ^[10]. Uric acid is AICAR’s main breakdown product ^[7], which is relevant to anyone with gout or kidney disease.

Because AICAR is an AMP mimic, it interferes with energy sensing across all tissues, not just muscle, and long-term exposure has not been studied in people. In laboratory work ZMP also inhibits other enzymes that bind AMP, and its effects are not confined to AMPK ^[1]. There are no data on repeated subcutaneous injection, on use alongside stimulants or GLP-1 drugs, or on use in people with heart disease outside the surgical setting.

For athletes, the main risk is a doping violation. AICAR is a natural metabolite, so anti-doping laboratories compare urine levels with population thresholds and use carbon-isotope ratios to prove an external source ^[12][13]. It is detectable.

The World Anti-Doping Agency lists AICAR among the AMP-activated protein kinase activators under section S4 of its Prohibited List, the metabolic modulators, which are banned at all times, in and out of competition ^[11]. It was added after the 2008 mouse study and has been named in cycling doping investigations since. AICAR cycling, in the sense of a schedule of doses, is therefore also a doping offence for any tested athlete.

Detection has become more precise. In a 2014 study, laboratories developed a method to measure the carbon isotope ratio of urinary AICAR, which distinguishes synthetic material from the body’s own ^[13]. A 2022 analysis of 5,517 athlete samples found that the ratio of AICAR to its relative SAICAR in urine is narrowly distributed, giving laboratories a second marker to flag suspicious samples before isotope testing ^[12].

AICAR is not an approved medicine in any country. Acadesine reached phase 3 trials for heart surgery but was never licensed ^[9], and its cancer development did not proceed past early trials ^[10]. It has no marketing authorisation from the FDA, MHRA or EMA and is sold either as a laboratory reagent or as a research chemical. In sport it is prohibited at all times ^[11].

For the rules on buying and holding research chemicals and peptides in your country, see our legal status overview, including the UK, US and Australian pages. Because AICAR is not a peptide and not a controlled drug, it generally falls under general consumer and medicines law rather than peptide-specific rules, but selling it with claims of effects on the body can still make it an unlicensed medicine.

AICAR is a small, stable, water-soluble molecule supplied as a white powder. Suppliers generally recommend keeping it cool, dry and away from light, and using solutions promptly. It is more robust than most peptides, but the same principles in our guide to how to store peptides apply, and reconstitution with bacteriostatic water is the usual practice among research buyers.

AICAR is cheap to make and widely available as a reagent, so the risk with research-grade product is less about counterfeiting than about purity and what a store’s certificate actually shows. A COA should identify the compound by mass spectrometry at 258 g/mol ^[14] and state a purity by HPLC. Compare AICAR prices, read how to read a COA, and see our list of third-party tested suppliers.

We track AICAR listings in the UK and the US. Our guides to third-party peptide testing and peptide prices explain what testing is worth paying for and why prices for the same compound vary so widely.