AICAR (acadesine)

Overview

AICAR is a small molecule (a nucleoside, not a peptide) that tricks cells into acting as if they are low on energy, switching on an enzyme called AMPK. It became famous as an "exercise in a pill" after a 2008 mouse study showed it boosted running endurance. It has never been approved as a medicine, failed a large heart-surgery trial, and is banned in sport.

How it works

Established in cells and animals: AICAR enters cells and is converted to ZMP, which mimics AMP (a signal of low energy) and activates AMP-activated protein kinase (AMPK). AMPK increases glucose uptake and fat burning and turns on genes for oxidative (endurance-type) metabolism in muscle; in mice this effect depended partly on PPARδ. In humans, intravenous AICAR raised muscle glucose uptake in healthy men and lowered liver glucose output in people with type 2 diabetes in small studies. Separately, it was developed as acadesine, an "adenosine-regulating agent" meant to protect heart muscle during surgery.

What research shows

• Mouse study (Cell 2008): 4 weeks of AICAR in sedentary mice increased running distance by 44% and running time by 23% and turned on endurance-related muscle genes, without exercise training.
• RED-CABG RCT (n=3,080 high-risk bypass surgery patients): acadesine infusion did not reduce death, stroke or need for heart support at 28 days (5.1% vs 5.0% placebo); stopped for futility.
• Small human infusion studies: AICAR acutely increased skeletal muscle glucose uptake in healthy men and reduced liver glucose output and fat breakdown in people with type 2 diabetes.
• Phase I/II trial in relapsed or refractory chronic lymphocytic leukemia (published 2013); acadesine did not progress to approval.
• No human trials show that AICAR improves athletic performance, fat loss or lifespan.

Doses studied in people

The only human doses found are hospital IV infusions from surgery and cancer trials; there is no tested dose for performance, fat loss or anti-aging use.

Read this first: these are the amounts given to participants in published studies or written on official prescribing labels, reported for reference. They are not recommendations. Trial doses were chosen for specific patients under medical supervision, and a dose that is safe in one person can be harmful in another.

Safety

• In the 3,080-patient RED-CABG trial, death, stroke and serious heart outcomes were similar to placebo, but the drug showed no benefit.
• Long-term safety in healthy people is unknown; no trials have tested repeated use outside hospital settings.
• Products sold online are unapproved, and their identity and purity are not controlled.
• Use by athletes can be detected: carbon isotope testing picked up a single oral dose for more than 40 hours.

Report side effects of any drug or product to the FDA through MedWatch. For a possible poisoning in the US, call Poison Control at 1-800-222-1222.

Legal status

FDA

Not FDA-approved (acadesine was investigated but never approved).

Compounding

Not listed on FDA's 503A bulk-substance nominations list (May 14, 2026) and not part of an approved drug, so it is not eligible for 503A compounding.

Sports (WADA)

Prohibited at all times: named as an example of AMPK activators under S4.4 (metabolic modulators).

Other

Not a controlled substance in the US.

Rules change often. See Legal status of peptides for how these categories work.

History

Acadesine was first developed as a heart-protecting drug for coronary bypass surgery; five earlier studies with more than 4,000 patients had suggested benefit. In 2008, Narkar and colleagues reported that four weeks of AICAR increased running distance in sedentary mice by 44%, prompting worries about doping. The large RED-CABG trial (3,080 patients) was stopped early for futility and published in JAMA in 2012. A small phase I/II trial in relapsed chronic lymphocytic leukemia was published in 2013. WADA prohibits AICAR as an AMPK activator, and anti-doping labs use carbon isotope testing to tell drug AICAR from the body's own.

Common questions

Related compounds

Sources

1. Narkar VA et al. AMPK and PPARδ agonists are exercise mimetics. Cell 2008;134:405–415 Journal
2. ACC summary: RED-CABG trial (Newman MF et al. JAMA 2012;308:157–164) Journal
3. AICAR acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men. Diabetes 2007 (PubMed 17513706) Journal
4. Intravenous AICAR administration reduces hepatic glucose output and inhibits whole body lipolysis in type 2 diabetic patients. (PubMed 18709353) Journal
5. Van Den Neste E et al. Acadesine for patients with relapsed/refractory CLL: a multicenter phase I/II study. Cancer Chemother Pharmacol 2013 Journal
6. Piper T et al. Determination of 13C/12C ratios of endogenous urinary AICAR. Rapid Commun Mass Spectrom 2014;28:1194–1203 Journal
7. PubChem: Acadesine (CID 17513) Regulatory
8. FDA: Bulk drug substances nominated for use in compounding under section 503A (updated May 14, 2026) Regulatory
9. WADA Prohibited List Regulatory