AICAR's heart surgery trial enrolled 3,080 patients. It was stopped for futility.

One molecule, two reputations

Acadesine is the drug name for AICA riboside, 5-amino-1-β-D-ribofuranosylimidazole-4-carboxamide, which trial reports describe as a purine nucleoside analog meant to raise adenosine in ischemic tissue.[4] Metabolism researchers call the same compound AICAR and use it as a tool to activate AMPK, an energy-sensing enzyme.[6][8] In blood it is rapidly taken up by red cells and converted to its monophosphate.[7]

The World Anti-Doping Agency's 2026 list names AICAR, along with MOTS-c and BAM15 , as AMPK activators prohibited at all times.[13] pepmg found no FDA approval for acadesine in Drugs@FDA, searched on October 18, 2026.[14]

The heart surgery program

Promising pooled results, then a null trial

Acadesine was given to bypass surgery patients as an intravenous infusion for about seven hours, starting before anesthesia, and was also added to the solution used to stop the heart.[3][4] In a 633-patient U.S. trial published in 1995, it did not reduce heart attacks by the prespecified definition (24%, 26% and 21% across the placebo, low-dose and high-dose groups; P = 0.574); a stricter definition applied after the study found fewer attacks on the higher dose.[4]

A 1997 analysis pooling individual patient data from five trials, 4,043 patients evaluable for efficacy, reported that acadesine cut perioperative heart attacks by 27% in relative terms (odds ratio 0.69, 95% CI 0.51 to 0.95) and cardiac death through day 4 (odds ratio 0.52, 95% CI 0.27 to 0.98); stroke was not significantly reduced.[3] A 2006 analysis looked only at the 100 patients who had a heart attack during surgery, a group defined by an event after randomization, and reported two-year death in 15 of 54 on placebo versus 3 of 46 on acadesine.[5]

RED-CABG was the large trial that followed, run at 300 sites in 7 countries from 2009 to 2010 with Merck Sharp & Dohme as sponsor.[1][2] Its primary outcome was different from the earlier trials: death, nonfatal stroke or need for mechanical heart support through day 28. A prespecified futility analysis stopped it after 3,080 of a planned 7,500 patients. The primary outcome occurred in 76 of 1,493 on acadesine (5.1%) and 75 of 1,493 on placebo (5.0%), odds ratio 1.01 (95% CI 0.73 to 1.41), with no differences in key secondary outcomes.[1]

The trial's registry results, which count all 1,536 and 1,544 randomized patients, show 4.9% in both groups.[2] Serious adverse events through day 28 were similar (327 of 1,442 treated on acadesine, 329 of 1,457 on placebo), and 34 versus 23 patients left the study for adverse events.[2] The earlier trials and pooled analysis noted a transient rise in uric acid on acadesine.[3][4]

Where the exercise claim comes from

Mice, injected, at 500 mg/kg a day

The "exercise in a pill" label traces to a 2008 Cell paper. Sedentary mice given AICAR at 500 mg/kg a day by intraperitoneal injection for four weeks ran about 23% longer and about 44% farther on a treadmill than untreated mice; that test used 15 to 20 mice.[6] The paper's abstract calls AICAR "orally active," but these mice received it by injection.[6]

In people, a 1991 study in healthy men by researchers at Gensia Pharmaceuticals found oral AICAR in solution was less than 5% bioavailable, with an intravenous half-life of about 1.4 hours; each dose level had four men on drug and two on placebo.[7]

What human metabolism studies show

Hours-long infusions, small groups, lab measures

In 29 healthy men, an AICAR infusion raised muscle glucose uptake about 2.1-fold after three hours, versus 4.7-fold with cycling, and raised whole-body glucose disposal by 7%. AMPK activity in muscle did not measurably change.[8] A follow-up in 22 men found smaller uptake increases in older men, with or without type 2 diabetes, again without detectable AMPK activation.[9] In 10 men with type 2 diabetes, an infusion lowered liver glucose output, blood glucose and circulating fatty acids.[10]

These were hours-long infusion experiments measuring metabolism, not trials of weight, body fat or performance. A PubMed search on October 18, 2026 for clinical trials of AICAR or acadesine on endurance, performance, weight loss, obesity or fat found no human AICAR trial, and none of the five ClinicalTrials.gov entries for AICAR, acadesine or AICA-riboside tests endurance or fat loss; the newest started in 2013.[15]

Cancer trials

Large doses, kidney problems

Acadesine was later tested in blood cancers. In a 24-patient phase I/II study in relapsed chronic lymphocytic leukemia, four-hour infusions of 50 to 315 mg/kg set a maximum tolerated single dose of 210 mg/kg. Hyperuricemia was common, and adverse events included renal impairment and clinically significant infusion-related low blood pressure; signs of efficacy were variable.[11] A phase I-II trial in myelodysplastic syndromes and related leukemias, run by the Groupe Francophone des Myélodysplasies, enrolled five patients and was terminated for "renal toxicity".[12]

These doses come from cancer patients treated in hospital trials and are reported here only as the published record.

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