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Nucleoside compound (not a peptide)Human trialsNot FDA approved

AICAR

5-aminoimidazole-4-carboxamide ribonucleoside (acadesine)

Last reviewed October 27, 2026 · 21 sources · Written for general readers · Compare with another compound →

The bottom line

AICAR made headlines as exercise in a pill after untrained mice ran much longer on it. In people, it was tested as a heart surgery drug and failed in a trial of more than 3,000 patients, and short IV studies in healthy men showed weak effects on muscle plus a faster heartbeat. No trial has tested it for fitness, fat loss or aging, it is not an approved medicine, and WADA bans it at all times.

Where the evidence stands

What it is

AICAR, also called acadesine, is a small molecule called a nucleoside, a sugar joined to a ring shaped base. It is not a peptide. Its formula is C9H14N4O5.[1][2]

Small amounts occur naturally, because the body makes a related form while building purines, the A and G letters of DNA.[3] Anti doping labs routinely measure natural AICAR in athletes' urine.[4]

Doctors tested it for years as a drug to protect the heart during bypass surgery. Early pooled results looked good, but a large confirming trial found no benefit.[5][6]

It became famous in sport after a 2008 mouse study labeled it an exercise mimetic, a drug that copies some effects of exercise.[7][8]

It does not appear on FDA's list of substances nominated for pharmacy compounding.[9]

Name
AICAR (5-aminoimidazole-4-carboxamide ribonucleoside (acadesine))
Other names
acadesine, AICA riboside
Type
Nucleoside compound (not a peptide)
CAS number
2627-69-2
Formula
C9H14N4O5
Molecular weight
About 258.2 g/mol

What it does in the body

Inside cells, AICAR is turned into ZMP, a look alike of AMP, the signal cells make when they run low on energy. ZMP switches on AMPK, an enzyme that acts like the cell's fuel gauge and tells it to burn more fuel and build less fat.[10] Many of its effects, though, happen without AMPK.[3]

This is the biology, area by area. A change measured in the body, like a higher blood level, does not always mean a person feels a benefit. The claims check below covers that.

Energy and cells

Measured in people

In rat liver cells, AICAR built up as ZMP and switched on AMPK without changing the cell's real energy levels, and it nearly shut down the making of fats and cholesterol.[10] In people given an IV drip, red blood cells took AICAR up quickly and turned it into ZMP.[11] A 2021 review warns that many effects once credited to AMPK are actually caused by other actions of AICAR, including effects on how cells build DNA letters.[3]

Muscle and strength

Measured in people

In 29 healthy young men, an AICAR drip roughly doubled sugar uptake into thigh muscle, while cycling raised it almost five times.[2] The muscle response was weaker in older men and men with diabetes.[12] In 10 healthy people whose insulin was held high, AICAR added no extra sugar uptake into forearm muscle.[11] In old mice, a month of injections prevented a 24.5% drop in running ability and raised muscle force by about 26%.[13]

Fat and appetite

Measured in people

In isolated rat fat cells, AICAR blocked the release of stored fat.[10] The same thing showed up in 10 men with type 2 diabetes, where an AICAR drip lowered the release of fat into the blood rather than raising it.[14] That is the opposite of what fat burning marketing suggests.

Liver and blood sugar

Measured in people

In 10 men with type 2 diabetes, an AICAR drip cut the amount of sugar the liver released and lowered blood sugar.[14] Whole body sugar use rose only about 7% in healthy young men.[2]

Heart and blood vessels

Measured in people

In healthy people, an AICAR drip raised heart rate by about 20% over an hour, compared with about 5% on salt water, and lowered blood pressure, likely by widening blood vessels.[11] In heart surgery trials it was given to boost adenosine, a natural signal that protects heart tissue when blood flow is low, but the largest trial found no benefit.[6]

Kidneys and uric acid

Measured in people

Uric acid rose briefly in the pooled surgery trials.[5] In 24 people with chronic lymphocytic leukemia given repeated drips, high uric acid was common and some had short lived kidney problems.[15]

Brain and mood

Seen in animals

In aged mice, two weeks of AICAR improved memory in a water maze and balance tests. Mice with a blocked AMPK in muscle did not improve, which suggests the effect came through muscle.[16] This has not been studied in people.

How it works

AICAR switches on AMPK, an enzyme that works like a cell's fuel gauge and normally turns on when energy runs low.[7][17]

  • Cells turn AICAR into ZMP, which mimics AMP and switches AMPK on without a real energy shortage.[10]
  • In mice, AICAR boosted running endurance without any training.[8]
  • In healthy men, an AICAR drip raised sugar uptake into muscle, but researchers could not detect AMPK being switched on in the muscle samples.[2]
  • A later study in 22 men also found no rise in AMPK activity in muscle. The sugar uptake tracked a different signal, called ERK.[12]
  • In surgery trials it was given to help regulate adenosine, a natural signal that protects heart tissue when blood flow is low.[6]

The fuel gauge effect is clear in cells and mice. Whether the same thing happens in human muscle is uncertain, and many effects do not depend on AMPK at all.

What the research shows

We keep animal and human evidence apart. A result in animals is a reason to study something in people, not proof that it works in people.

Animal and lab studies

Mice ran longer and rats had better blood fats

  • Untrained mice given AICAR for four weeks ran about 44% longer than untreated mice, a gain the researchers compared to regular exercise.[8]
  • The 2008 study in the journal Cell described AMPK activators such as AICAR as exercise mimetics.[7]
  • In 23 month old mice, 31 days of daily injections prevented the 24.5% drop in treadmill running seen in untreated old mice, raised muscle force about 26%, and raised two markers of mitochondria by about 22% and 33%.[13]
  • In aged mice, 14 days of AICAR improved memory and balance, an effect that depended on AMPK in muscle.[16]
  • In obese Zucker rats, a strain bred to develop insulin resistance, seven weeks of daily injections lowered blood pressure by about 15 points, lowered triglycerides and free fatty acids, and raised HDL cholesterol.[18]
  • In rat liver and fat cells, AICAR nearly stopped the making of fats and cholesterol and blocked the release of stored fat.[10]

Limit: These were rodent results, some from researchers with funding ties to AMPK drug companies. No trial has tested AICAR for endurance, fat loss or aging in people.

Human studies

Heart surgery trials failed in the end; no fitness trials

  • Five early surgery trials, pooled in 1997, included 4,043 bypass patients given an IV drip of acadesine or placebo. The odds of a heart attack around surgery were about 27% lower, and heart deaths in the first four days were about half as common, on acadesine. Side effects were similar except for a short rise in uric acid.[5]
  • The RED-CABG trial then gave acadesine or placebo drips to 3,080 higher risk bypass patients at 300 sites. Death, stroke or severe heart pumping failure within 28 days happened in 5.1% on acadesine and 5.0% on placebo. The trial was stopped early for futility.[6]
  • In 29 healthy young men, an AICAR drip roughly doubled muscle sugar uptake, compared with almost five times higher after cycling. Whole body sugar use rose only about 7%.[2]
  • In 10 men with type 2 diabetes, average age 64, an AICAR drip lowered liver sugar output and blood sugar, and reduced fat release into the blood. AMPK in muscle was not detectably switched on.[14]
  • In 22 men, muscle sugar uptake rose about 2.9 times in young healthy men, but only about 1.8 times in healthy older men and 1.6 times in men with type 2 diabetes.[12]
  • In 10 healthy volunteers studied twice, once with an AICAR drip and once with salt water, AICAR did not change sugar uptake in forearm muscle or the whole body. Heart rate rose about 20% versus about 5% with salt water, and blood pressure fell.[11]
  • In 24 people with returning chronic lymphocytic leukemia, AICAR drips often raised uric acid. Other problems included short drops in blood counts, temporary kidney trouble and low blood pressure during the drip. Some patients' cancer measures improved, but results varied.[15]
  • AICAR occurs naturally in urine. In 499 athletes tested by anti doping labs, levels varied by sex, sport and whether the test was in or out of competition, so labs use extra tests to tell natural AICAR from a dose.[4][19]
  • We found no human trial of AICAR for fitness, fat loss, muscle or aging.

Limit: Every human study used hospital IV drips for surgery, diabetes research or cancer, not the uses promoted online.

Claims check

The most common claims about this compound, and what studies actually found. Verdicts rate the evidence, not whether you should use it.

Exercise in a pill that boosts endurance

Only in animals

Untrained mice given AICAR for four weeks ran about 44% longer than untreated mice.[8] In 23 month old mice, a month of AICAR prevented a 24.5% loss of running ability seen in untreated old mice.[13] No human trial has tested AICAR for endurance or fitness. In healthy men, its effect on muscle sugar uptake was far weaker than a bout of cycling.[2]

Lowers blood sugar

Mixed results

In 29 healthy young men, an AICAR drip roughly doubled muscle sugar uptake, but whole body sugar use rose only about 7%.[2] In 10 men with type 2 diabetes, a drip cut sugar output from the liver and lowered blood sugar.[14] In 10 healthy people with insulin held high, AICAR added nothing to sugar uptake.[11] All were short hospital drip studies, not treatment trials.

Melts body fat

Only in animals

In obese rats, seven weeks of AICAR injections lowered blood triglycerides and free fatty acids and raised HDL cholesterol.[18] No human trial has measured fat loss. In 10 men with type 2 diabetes, a drip actually reduced the release of fat from fat stores into the blood.[14]

Builds muscle and strength with age

Only in animals

In old mice, a month of daily injections raised the weight of a thigh muscle by about 8% and its force by about 26% compared with salt water injections.[13] No study has tested this in people.

Sharpens memory

Only in animals

Aged mice given AICAR for 14 days did better in a water maze memory test and on balance tests.[16] No human study has tested memory.

Protects the heart

No benefit in trials so far

A 1997 pooled analysis of five surgery trials with 4,043 patients found fewer heart attacks and heart deaths with acadesine.[5] But the larger confirming trial in 3,080 bypass patients found death, stroke or severe heart failure in 5.1% on acadesine and 5.0% on placebo, and was stopped early for futility.[6]

Lowers blood pressure

Only in animals

In obese rats, seven weeks of injections lowered the top blood pressure number by about 15 points.[18] In people, a drop in blood pressure showed up as a side effect during drips, along with a faster heartbeat, not as a tested benefit.[11][15]

Fights cancer

Mixed results

In 24 people with returning chronic lymphocytic leukemia, a blood cancer, some patients' cancer measures improved on AICAR drips, but results varied and side effects were common.[15] No larger controlled cancer trial has been published.

Known risks and side effects

  • High uric acid. Uric acid rose in the pooled surgery trials, and high uric acid, which can cause gout and kidney stones, was common in the cancer study.[5][15]
  • Heart rate, blood pressure and kidney effects. In healthy people, an AICAR drip sped up the heart and lowered blood pressure.[11] Temporary kidney problems, short drops in blood counts and significant low blood pressure during the drip were reported in the cancer study.[15]
  • No proven benefit in people. Its largest trial found no benefit, and its effect on human muscle was far weaker than exercise.[6][2]
  • Banned in sport, and testable. WADA bans AICAR at all times as a metabolic modulator, and the 2027 list keeps it there.[17][20] Labs use carbon isotope tests and marker ratios to tell a dose from natural AICAR. One 2024 method flagged a dose in urine collected up to 16 hours later, and its authors cite a 40 hour window reported by others.[21][19]
  • Unregulated online products. AICAR is not on FDA's compounding nomination list, so products sold online as research chemicals are unapproved and unchecked for purity or strength.[9]

Regulatory status

Today: AICAR is not an FDA approved drug, its largest drug trial was stopped for futility, and it does not appear on FDA's compounding nomination list.[6][9] WADA bans it at all times, on the 2026 list now in force and on the 2027 list that starts January 1, 2027.[17][20]

  1. A pooled analysis of five surgery trials suggests acadesine lowers heart attacks after bypass surgery.[5]
  2. A mouse study in Cell calls AICAR an exercise mimetic, and its lead scientist says he is working with anti doping officials on a test.[7][8]
  3. The RED-CABG heart surgery trial is published after being stopped early for futility.[6]
  4. The 2026 WADA Prohibited List takes effect, again naming AICAR as a banned AMPK activator.[17]
  5. The 2027 WADA list takes effect, still naming AICAR among banned AMPK activators.[20]

Sources

  1. U.S. FDA and NCATS Global Substance Registration System (GSRS). Acadesine, UNII 53IEF47846. FDA GSRS
  2. Cuthbertson DJ, Babraj JA, Mustard KJ, Towler MC, Green KA, Wackerhage H, et al. 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men. Diabetes. 2007;56(8):2078-2084. PMID 17513706
  3. Višnjić D, Lalić H, Dembitz V, Tomić B, Smoljo T. AICAr, a Widely Used AMPK Activator with Important AMPK-Independent Effects: A Systematic Review. Cells. 2021;10(5):1095. PMID 34064363
  4. Thomas A, Beuck S, Eickhoff JC, Guddat S, et al. Quantification of urinary AICAR concentrations as a matter of doping controls. Anal Bioanal Chem. 2010;396(8):2899-2908. PMID 20225061
  5. Mangano DT. Effects of acadesine on myocardial infarction, stroke, and death following surgery. A meta-analysis of the 5 international randomized trials. JAMA. 1997;277(4):325-332. PMID 9002496
  6. Newman MF, Ferguson TB, White JA, Ambrosio G, Koglin J, Nussmeier NA, et al. Effect of adenosine-regulating agent acadesine on morbidity and mortality associated with coronary artery bypass grafting: the RED-CABG randomized controlled trial. JAMA. 2012;308(2):157-164. PMID 22782417
  7. Narkar VA, Downes M, Yu RT, Embler E, Wang YX, Banayo E, et al. AMPK and PPARdelta agonists are exercise mimetics. Cell. 2008;134(3):405-415. PMID 18674809
  8. Salk Institute for Biological Studies. Exercise in a pill. News release. July 31, 2008. Salk Institute
  9. U.S. Food and Drug Administration. Bulk Drug Substances Nominated for Use in Compounding Under Section 503A of the Federal Food, Drug, and Cosmetic Act. Updated May 14, 2026. FDA 503A nominations list
  10. Corton JM, Gillespie JG, Hawley SA, Hardie DG. 5-aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells? Eur J Biochem. 1995;229(2):558-565. PMID 7744080
  11. Bosselaar M, Smits P, van Loon LJ, Tack CJ. Intravenous AICAR during hyperinsulinemia induces systemic hemodynamic changes but has no local metabolic effect. J Clin Pharmacol. 2011;51(10):1449-1458. PMID 21148051
  12. Babraj JA, Mustard K, Sutherland C, Towler MC, Chen S, Smith K, et al. Blunting of AICAR-induced human skeletal muscle glucose uptake in type 2 diabetes is dependent on age rather than diabetic status. Am J Physiol Endocrinol Metab. 2009;296(5):E1042-E1048. PMID 19190259
  13. Wilcox SH, Calixto J, Dray SD, Rasch DM, Smith AH, Brodowski KD, et al. Chronic treatment of old mice with AICAR reverses age-related changes in exercise performance and skeletal muscle gene expression. FASEB Bioadv. 2025;7(3):e1491. PMID 40060947
  14. Boon H, Bosselaar M, Praet SF, Blaak EE, Saris WH, Wagenmakers AJ, et al. Intravenous AICAR administration reduces hepatic glucose output and inhibits whole body lipolysis in type 2 diabetic patients. Diabetologia. 2008;51(10):1893-1900. PMID 18709353
  15. Van Den Neste E, Cazin B, Janssens A, González-Barca E, Terol MJ, Levy V, et al. Acadesine for patients with relapsed/refractory chronic lymphocytic leukemia (CLL): a multicenter phase I/II study. Cancer Chemother Pharmacol. 2013;71(3):581-591. PMID 23228986
  16. Kobilo T, Guerrieri D, Zhang Y, Collica SC, Becker KG, van Praag H. AMPK agonist AICAR improves cognition and motor coordination in young and aged mice. Learn Mem. 2014;21(2):119-126. PMID 24443745
  17. World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026. Effective January 1, 2026. WADA 2026 Prohibited List
  18. Buhl ES, Jessen N, Pold R, Ledet T, Flyvbjerg A, et al. Long-term AICAR administration reduces metabolic disturbances and lowers blood pressure in rats displaying features of the insulin resistance syndrome. Diabetes. 2002;51(7):2199-2206. PMID 12086950
  19. Sobolevsky T, Piper T, Ahrens B, Thevis M. AICAr to SAICAr ratio can serve as additional marker of AICAr use. Drug Test Anal. 2022;14(11-12):2017-2025. PMID 36342242
  20. World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2027. Comes into effect January 1, 2027. WADA 2027 Prohibited List
  21. Wang Y, Fan J, Fang X, Zhuo Y, et al. Two-Dimensional Liquid Chromatography Purified GC/C/IRMS Doping Control Method: Analysis of Endogenous and Exogenous Sources in Urine Samples from Asian Subjects Administered a Low Dose of AICAR. J Chromatogr A. 2024;1735:465312. PMID 39232419
Medical disclaimer

This page is educational information only. It is not medical advice and does not replace care from a licensed medical provider. Do not use this page to decide whether to take any substance. Talk to a licensed medical provider first.

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