AICAR: what the studies show, status and safety
Summary
AICAR, also known as acadesine, is not a peptide. It is a nucleoside, a small molecule that the human body makes and excretes by itself, and it is listed in this register because it is sold alongside peptides. Its largest trial gave 3,080 heart surgery patients either acadesine or a dummy infusion and found no difference whatsoever. No country has ever approved it, and it is banned in sport at all times.
Key findings at a glance
- The largest trial found nothing at all. Among 3,080 patients undergoing bypass surgery, the main outcome occurred in 76 of 1,493 (5.1 per cent) given acadesine and 75 of 1,493 (5.0 per cent) given placebo, an odds ratio of 1.01 (95 % confidence interval 0.73 to 1.41) [1].
- It was stopped early because it was pointless to continue. Recruitment ended at 3,080 of a planned 7,500 patients after a pre-planned futility analysis [1], [2].
- The earlier, positive evidence did not survive. A pooled analysis of five randomised trials in 4,043 patients had found 27 per cent fewer heart attacks around surgery (odds ratio 0.69; 95 % confidence interval 0.51 to 0.95; p = 0.02). That result is what the failed trial was built on [3].
- "Exercise in a pill" describes mice. Untrained mice given 500 mg/kg per day into the abdomen for four weeks ran roughly 44 per cent further and roughly 23 per cent longer (p < 0.05), with 15 to 20 animals per group [4].
- No human study has ever measured endurance under AICAR. The nearest one, in 29 healthy men, found muscle glucose uptake rising 2.1 ± 0.8-fold against 4.7 ± 1.7-fold for cycling, and no measurable activation of the enzyme it is supposed to switch on [5].
- It is banned in sport at all times, named on the 2026 prohibited list under S4.4.1 as a non-specified substance, and named in German criminal law with a threshold quantity of 7 000 mg [6], [7], [8].
- The safety signals are specific, not vague. Uric acid rises because uric acid is the main breakdown product; systemic lactate rose by up to 60 per cent (p < 0.001); and a later trial stopped after five patients, with "renal toxicity" recorded as the reason [9], [10], [11].
What it is
AICAR is a purine nucleoside: an imidazole base joined to a ribose sugar, with a mass of 258.23 g/mol. It contains no amino acids and no peptide bond, so it is not a peptide, and the World Anti-Doping Agency does not file it with the peptide hormones either [12], [6].
The name is used for two different chemicals, and that is the single most useful thing to know about it. Strictly, the abbreviation AICAR denotes the ribotide ZMP, the phosphate form, which the chemical database PubChem lists as CID 65110. In sport, in law and in trade, "AICAR" means the riboside acadesine, CID 17513. This page describes the riboside [12].
The distinction matters because the riboside is the form that was studied and is sold, while the ribotide is what the cell makes from it. Basic researchers often write "AICAr" with a small r to mark the riboside [13].
Quick facts
| Field | Value | Ref |
|---|---|---|
| Name | AICAR; international non-proprietary name acadesine | [12], [14] |
| Other names | AICA riboside, acadesine, Z-riboside, GP 1-110, ARA-100, SCH 900395 | [12] |
| Class | Purine nucleoside analogue; developed as an adenosine-regulating agent, later described as an activator of AMP-activated protein kinase | [15], [13] |
| Structure | 5-aminoimidazole-4-carboxamide base joined to beta-D-ribofuranose; no amino acids, no sequence | [12] |
| Formula and mass | C9H14N4O5, 258.23 g/mol | [12] |
| Active form in the cell | ZMP, the monophosphate; C9H15N4O8P, 338.21 g/mol, CID 65110 | [12], [16] |
| Half-life | 1.4 hours in the blood after infusion; oral availability under 5 per cent | [17] |
| Status | Not approved in any market; development discontinued | [1], [18] |
| Developed by | Gensia Pharmaceuticals from the late 1980s, later Metabasis, PeriCor and Schering-Plough; Advancell for blood cancer | [15] |
| CAS registry number | 2627-69-2 | [12] |
| PubChem CID | 17513 | [12] |
| UNII, InChIKey | 53IEF47846; RTRQQBHATOEIAF-UUOKFMHZSA-N | [12] |
| ChEBI, ChEMBL, DrugBank | CHEBI:28498, CHEMBL1551724, DB04944 | [19] |
| ATC code | C01EB13, a classification number with no defined daily dose | [14] |
How it works
AICAR is inactive until the cell converts it. Transporters carry it inside, an enzyme adds a phosphate group, and the result is ZMP, which looks enough like the cell's own energy sensor signal to be mistaken for it [20].
- The signal is a look-alike. ZMP resembles AMP, the molecule that tells a cell its energy is running low, and it may switch on AMP-activated protein kinase without the cell's actual energy balance having changed [20].
- Uptake and phosphorylation are both required. Blocking either the transporter or the phosphorylating enzyme in leukaemia cells abolished both the enzyme activation and the cell death [20].
- The active substance is the phosphate, not AICAR. A combined metabolic and protein study identified ZMP as the toxic form and found many binding partners for it outside the intended enzyme [16].
- Much of the effect bypasses that enzyme entirely. A 2021 systematic review concluded that numerous effects once credited to it are independent of it, and warned against over-reading studies based on this substance [13].
- The original idea was different. The whole cardiac programme rested on the hope that AICAR would raise adenosine locally in oxygen-starved tissue and protect the heart. That hypothesis was tested properly once, and failed [3], [1].
This is where AICAR parts company with the peptides it sits beside in catalogues. Those act on receptors on the cell surface. AICAR must first be taken up and rebuilt inside the cell [20].
What the studies found
More than 10,000 people have received acadesine in clinical studies over five decades, which is unusual for a substance sold as a research chemical. The results are unusually clear as well, and mostly negative.
Heart surgery: the trial that ended the programme
Phase 3 randomised trial RED-CABG randomly assigned 3,080 adults at medium to high risk before planned bypass surgery, at 300 centres in seven countries, with a median age of 66 years. The main outcome combined death from any cause, non-fatal stroke and the need for mechanical circulatory support up to day 28 [1].
Phase 3 randomised trial It occurred in 76 of 1,493 patients (5.1 per cent) on acadesine and 75 of 1,493 (5.0 per cent) on placebo. The odds ratio was 1.01, with a 95 % confidence interval from 0.73 to 1.41. No important secondary outcome differed either [1].
Randomised, double-blind phase 3 trial in 3,080 adults before bypass surgery, 300 centres in seven countries, stopped early for futility; 76 of 1,493 against 75 of 1,493 patients, odds ratio 1.01 (95 % confidence interval 0.73 to 1.41). Sources [1], [2].
Phase 3 randomised trial The registry figures for everyone randomised, 1,536 against 1,544 patients, tell the same story. The combined outcome came to 4.9 against 4.9 per cent. Death from any cause was 1.9 against 1.7 per cent, non-fatal stroke 1.7 against 1.7 per cent, and mechanical support 2.2 against 2.3 per cent [2].
Recruitment ran from 6 May 2009 to 30 July 2010. It stopped at 3,080 of the 7,500 patients originally planned, after a futility analysis agreed in advance [1], [2].
Why anyone expected otherwise
Meta-analysis In 1997 an analysis pooling the individual records of 4,043 bypass patients from five randomised trials in 81 centres reported 27 per cent fewer heart attacks around surgery (odds ratio 0.69; 95 % confidence interval 0.51 to 0.95; p = 0.02) and half as many cardiac deaths by day 4 (odds ratio 0.52; 0.27 to 0.98; p = 0.04) [3].
Meta-analysis The combined outcome of heart attack, stroke or cardiac death fell by 26 per cent (odds ratio 0.73; 0.57 to 0.93; p = 0.01). Stroke alone did not fall significantly (odds ratio 0.69; 0.44 to 1.08; p = 0.10) [3].
Meta-analysis Deaths after a heart attack by day 4 fell from 13.3 per cent (13 of 98) to 1.4 per cent (1 of 71), p = 0.003 [3].
Randomised trial, subgroup A two-year follow-up of 2,698 patients at 54 centres pointed the same way. A heart attack around surgery raised two-year mortality 4.2-fold (p < 0.001). Among those patients it fell from 27.8 per cent (15 of 54) to 6.5 per cent (3 of 46) with acadesine, p = 0.006 [21].
Randomised trial, subgroup That figure rests on 18 deaths in total [21].
This is the sequence that matters. Older, smaller, pooled evidence looked convincing; one larger prospective trial dissolved it. The 1997 analysis is now of historical interest only [3], [1].
The individual heart trials
Randomised trial The Multinational Acadesine Study randomised 821 bypass patients, 403 of them to acadesine. Its main outcomes were missed. In a subgroup defined in advance as high risk, Q-wave heart attacks fell from 19.7 to 10.0 per cent (p = 0.032), while all adverse cardiovascular events, 19.4 against 18.4 per cent, and total mortality, 3.4 against 2.7 per cent, did not differ [22].
Randomised trial In 116 bypass patients across three groups, nothing reached statistical significance. Ultrasound signs of oxygen shortage before bypass appeared in 6, 15 and 19 per cent (p = 0.22). Afterwards, electrocardiogram signs appeared in 11, 22 and 18 per cent (p = 0.42) and ultrasound signs in 24, 27 and 29 per cent (p = 0.86) [23].
Randomised crossover trial In 12 patients with stable angina, four doses were compared against placebo. The placebo-corrected change in time to a 1 mm ST depression was -0.1 ± 6.2, 11.1 ± 13.8, 12.9 ± 8.6 and -3.2 ± 6.8 per cent. None of these was significant, and the highest dose performed worse than the middle ones [24].
Muscle, blood sugar and the endurance claim
Human physiology study In 29 healthy men, aged 26 ± 8 years with a body mass index of 25 ± 4 kg/m2, three hours of AICAR raised glucose uptake into muscle 2.1 ± 0.8-fold. Cycling raised it 4.7 ± 1.7-fold in the same study [5].
29 healthy men, aged 26 ± 8 years, body mass index 25 ± 4 kg/m2; 2-deoxyglucose uptake measured in muscle. Whole-body glucose disposal rose 7 per cent, from 9.3 ± 0.6 to 10.0 ± 0.6 mg/kg per minute (p < 0.05), and no activation of AMP-activated protein kinase was measurable. Source [5].
Human physiology study The mechanism did not show up where it was expected. Enzyme activity and its phosphorylation were unchanged after 20 minutes and after three hours, while cycling raised both. Whole-body glucose disposal rose 7 per cent, from 9.3 ± 0.6 to 10.0 ± 0.6 mg/kg per minute (p < 0.05) [5].
Animal data The famous headline comes from a mouse study published in 2008. Untrained mice received 500 mg/kg per day into the abdomen for four weeks, with 15 to 20 animals per group. They ran roughly 44 per cent further and roughly 23 per cent longer (p < 0.05). Body weight did not change, and oxygen consumption rose [4].
No evidence A literature search on 13 September 2026 found no published human study measuring endurance, body composition, muscle mass or training adaptation under AICAR. Every performance claim traces back to those mice or to marketing [4], [5].
Blood cancers
Laboratory study In cells from 70 patients with chronic lymphocytic leukaemia, acadesine triggered cell death at a half-maximal concentration of 380 ± 60 micromoles per litre. Healthy B lymphocytes were just as sensitive; T cells were barely affected up to 4 millimoles per litre [20].
Phase 1/2 trial In 24 patients with leukaemia that had returned or resisted treatment, no formal measure of benefit was met. The authors report only trends, which they themselves call variable given the small number of patients and the wide range of doses [25].
Terminated trial The follow-on study in bone marrow disease closed after five patients. The registry gives the reason in two words: "renal toxicity" [11].
What is still unknown
- Anything about use under the skin. Every human dose on record went into a vein. Nothing has been published about the route that grey-market sellers assume [17].
- Anything about repeated use in healthy people. The longest documented human exposure is five infusions over 20 days, or twelve days of continuous infusion in two patients [25], [26].
- Anything about swallowing it. Oral availability in healthy men was under 5 per cent, and no study of long-term oral use exists [17].
- Cancer risk and effects on fertility or offspring. No such data are publicly available for this substance.
- Interactions. Nothing has been published on combining AICAR with metformin or other drugs acting on the same pathway.
- Whether the enzyme it activates helps or harms tumour growth. The literature is contradictory, and there are no long-term human data either way [13].
Side effects and safety
In the low infusion doses of heart surgery, acadesine was about as well tolerated as placebo. That statement covers roughly 42 mg/kg given over seven hours, and nothing else. The oncology studies used twenty to forty times more, and that is where the problems appear [1], [2], [25].
- Uric acid rises, and it cannot not rise. A radiolabel study in four healthy men found uric acid to be the main breakdown product, accounting for essentially all the radioactivity left in plasma six hours after infusion. In the pooled bypass data it was the only safety difference against placebo [9], [3].
- In the smaller surgical trial the rise was measured. Plasma uric acid increased on average by 1.6 ± 0.2 mg/dl, in the high-dose group only, without clinical consequences [23].
- The kidneys are the documented limit. Impaired kidney function appeared among adverse events in the leukaemia study at 50 to 315 mg/kg, and the follow-on study at 140 to 315 mg/kg per day stopped after five patients for renal toxicity [25], [11].
- In the big surgical trial, kidney events were balanced. Serious kidney failure occurred in 20 of 1,442 patients on acadesine against 14 of 1,457 on placebo, and acute kidney failure in 9 against 10 [2].
- Lactate rises with the dose. In 47 patients with coronary disease receiving 5 to 50 mg/kg, systemic lactate rose by up to 60 per cent against placebo (p < 0.001), which the authors read as a push towards energy production without oxygen [10].
- Low blood sugar was the one imbalance against the drug. Serious hypoglycaemia was recorded in 6 of 1,442 patients on acadesine and 0 of 1,457 on placebo. The numbers are small, but they point one way [2].
- Infusions can drop blood pressure. The leukaemia study explicitly graded this as clinically significant. In the surgical trial, low blood pressure was equally common in both arms, 280 of 1,442 against 280 of 1,457 [25], [2].
- Blood counts moved little. Anaemia occurred in 384 against 383 patients and low platelets in 119 against 129, with no signal against placebo [2].
- Two further serious events came out numerically uneven. Respiratory failure was recorded in 33 of 1,442 patients on acadesine against 23 of 1,457 on placebo, and cardiac arrest in 12 against 7. The trial was not designed to test these outcomes, and the overall rate of serious events was the same in both arms [2].
Overall in the surgical trial, serious adverse events occurred in 327 of 1,442 patients (22.7 per cent) on acadesine and 329 of 1,457 (22.6 per cent) on placebo. Other events occurred in 1,154 (80.0 per cent) against 1,189 (81.6 per cent). Treatment was stopped for adverse events in 34 against 23 patients [2].
Two further findings belong here. The trial in bone marrow disease was not stopped for lack of effect but for organ damage. And the toxic species is the phosphate the cell builds, not the substance that enters it, which makes the dose that reaches a cell harder to reason about [11], [16].
There is also a rare inherited disease, AICA-ribosiduria, in which this exact molecule accumulates from birth. The picture is severe: profound developmental impairment, visual loss from retinal degeneration, restricted growth, curvature of the spine and often epilepsy that resists treatment [27].
That is not a forecast for anyone taking a single infusion. It does show that the body does not treat this molecule as inert [27].
No contraindications can be listed, because no approved product and no prescribing information exist. From the studies, three situations stand out as risky: impaired kidney function, gout or raised uric acid, and any condition with elevated lactate [25], [10].
Doses used in studies
The doses below are simply what the cited studies gave, listed so that the results can be understood. They are not advice on how to use anything.
| Study | Population or model | Dose | Route | Duration | Ref |
|---|---|---|---|---|---|
| Dixon 1991, first human study | Healthy men, 4 active and 2 placebo per dose level | 10, 25, 50 and 100 mg/kg | Into a vein, and by mouth after a week's gap | Single doses | [17] |
| Dixon 1993, radiolabel study | 4 healthy men | 25 mg/kg | Into a vein | One 15-minute infusion | [9] |
| Holdright 1994, stable angina | 12 patients, five-way crossover | 6, 12, 24 and 48 mg/kg against placebo | Into a vein | One infusion per study period | [24] |
| de Jonge 1997, oxygen shortage under pacing | 47 patients during coronary angiography | 5, 10, 20 and 50 mg/kg | Into a vein | Single | [10] |
| Leung 1994, bypass surgery | 116 patients, three groups | Two dose levels, not stated in mg/kg, plus placebo | Into a vein and in the heart-stopping solution | 7 hours | [23] |
| Menasche 1995, bypass surgery | 821 patients, 403 on acadesine | 0.1 mg/kg per minute plus 5 µg/ml in the heart-stopping solution | Into a vein and into the heart-stopping solution | 7 hours | [22] |
| McSPI pooled analysis 1997 | 4,043 patients, 2,012 on acadesine | 0.1 mg/kg per minute | Into a vein and into the heart-stopping solution | 7 hours | [3] |
| Mangano 2006, two-year follow-up | 2,698 patients, 1,352 on acadesine | 0.1 mg/kg per minute plus 5 µg/ml | Into a vein and into the heart-stopping solution | 7 hours | [21] |
| RED-CABG 2012 | 3,080 patients, 1,536 on acadesine | 42 mg/kg in total, infused at 0.1 mg/kg per minute, plus 5 µg/ml in the heart-stopping and pump priming solutions | Into a vein, into the heart-stopping solution and into the bypass circuit | About 7 hours | [1], [2] |
| Van Den Neste 2013, chronic lymphocytic leukaemia | 24 adults | Part I 50 to 315 mg/kg; part II 210 mg/kg, the highest tolerated level | Into a vein | Four-hour infusions, up to five over 20 days | [25] |
| GFM study 2013 to 2015, bone marrow disease | 5 adults | 140, 210 and 315 mg/kg per day as planned steps | Into a vein | Terminated early | [11] |
| NCT00004314, Lesch-Nyhan disease | 2 patients | Not stated in the registry | Continuous infusion | 12 days after 3 baseline days | [26] |
| Narkar 2008, mouse study | Untrained mice, 15 to 20 per group | 500 mg/kg per day; 250 mg/kg per day in a six-day arm | Into the abdomen | 4 weeks, or 6 days | [4] |
| Wong 2017, doping control in horses | 1 mare | 2 g | Into a vein | Single | [28] |
Every human figure above was given into a vein under hospital supervision, most of it in an operating theatre. Nothing at all is known about giving AICAR under the skin. Animal amounts in milligrams per kilogram do not translate to people, particularly for a substance that is less than 5 per cent available when swallowed [17].
Development and approval status
AICAR has never been approved as a medicine, in any country, for any condition, at any time. Register checks on 13 September 2026 found nothing anywhere, and no interventional trial is currently testing it [1], [18].
Four decades from a heart drug candidate to an empty registry
- 1991First human studyPharmacokinetics in healthy men; oral availability under 5 per cent, ref [17]
- 1994-1995The first surgical trials116 patients, then 821; main outcomes missed in both, refs [23], [22]
- 1997The pooled analysis4,043 patients, 27 per cent fewer heart attacks around surgery, ref [3]
- 2005European orphan designationEU/3/05/280 for chronic lymphocytic leukaemia, granted 27 May, ref [18]
- 2006Two-year follow-up published2,698 patients; better survival after a heart attack around surgery, ref [21]
- 2009-2010RED-CABG recruits3,080 of 7,500 planned patients, then stopped for futility, refs [1], [2]
- 2012The result ends the programme5.1 against 5.0 per cent, odds ratio 1.01, ref [1]
- 2013-2015Last trial terminatedFive patients enrolled; registry reason renal toxicity, ref [11]
- Late 1980s Gensia Pharmaceuticals develops the substance as an adenosine-regulating agent under the codes GP 1-110 and ARA-100 [15].
- 1997 to 2005 the programme passes from Gensia Sicor to Metabasis, then to PeriCor Therapeutics, and finally to Schering-Plough, later Merck [15].
- 2005 the European Commission grants orphan designation EU/3/05/280 for chronic lymphocytic leukaemia, on a positive committee opinion of 7 April [18].
- 2007 to 2010 Advancell runs the leukaemia study in 24 patients, registered under the product name "Acadra" [29], [25].
- 2009 to 2012 RED-CABG recruits, stops and reports; the cardiac programme ends [1], [2].
- 2013 to 2015 the last trial, in bone marrow disease, is terminated after five patients [11].
| Market | Status | Since or note |
|---|---|---|
| United States | Unapproved | Not even nominated for compounding |
| European Union | Unapproved | Orphan designation only |
| Germany | Unapproved | Named in doping law |
| United Kingdom | Unapproved | Unlicensed |
| Australia | Unapproved | Not scheduled |
| Canada | Unapproved | No database entry |
| Switzerland | Unapproved | No authorisation |
Five of these entries rest on database queries run alongside a control substance in the same system. An empty answer therefore means absence rather than a broken query [30], [31], [32], [33], [34]. The British entry is weaker, because the register could not be queried on the day, so the status is inferred from the worldwide picture [35].
Two entries are regularly misread. The European orphan designation is a support status for developing a drug against a rare disease, and the agency states plainly that it is not a marketing authorisation. No application ever followed it. The ATC code C01EB13 is a statistical classification number, issued without any daily dose being defined [18], [14].
One further point separates AICAR from most substances in this register. It appears on no American list of bulk substances nominated for pharmacy compounding, while ipamorelin appears ten times in the same document. Nobody ever asked for a lawful way to make it for people [36].
The wider legal picture is under are peptides legal and FDA-approved peptides.
Anti-doping
AICAR is prohibited at all times, in and out of competition, and it is named on the 2026 list rather than caught by a general clause. The entry reads: "Activators of the AMP-activated protein kinase (AMPK), e.g. 5-N,6-N-bis(2-fluorophenyl)-[1,2,5]oxadiazolo3,4-bpyrazine-5,6-diamine (BAM15), AICAR, mitochondrial open reading frame of the 12S rRNA-c (MOTS-c)" [6].
That entry sits in section S4.4.1, among the metabolic modulators, not among the peptide hormones of section S2. Substances in S4.3 and S4.4 are non-specified substances, the category with the stricter sanction range [6].
Germany goes further than the sporting rules. The annex to the anti-doping act names AICAR as an example of AMPK-axis agonists, and a 2023 regulation fixes the threshold quantity for that line at 7 000 mg. Above that, acquisition and possession are criminal offences [7], [8].
Detecting it is the hard part, because everyone has AICAR in their urine. Laboratories therefore work with population limits. In 12 377 samples from athletes the mean concentration was 647 ± 365 ng/ml and the middle value 574 ng/ml. The 99th percentile was 1786 ng/ml and the 99.7th percentile 2151 ng/ml [37].
Samples above 2000 to 2500 ng/ml were proposed for further checking by isotope analysis [37].
Two further tools support that. The ratio of AICAR to a related compound, SAICAr, varies within narrow limits across 5517 samples. In men the middle value was 3.3 with a 99th percentile of 9.3, in women 4.2 and 14 [38].
A carbon isotope method also separates the body's own molecule from an administered one. It was validated in a reference group of 63 people, and detected a single dose by mouth for more than 40 hours [39]. The full picture for this class is at peptides banned in sport.
Compared with related peptides
| Substance | How it acts | Human evidence | Sport status | Ref |
|---|---|---|---|---|
| AICAR | Nucleoside; converted inside the cell to ZMP | Over 10,000 patients treated; largest trial neutral | Named, S4.4.1 | [1], [6] |
| MOTS-c | Mitochondrial peptide affecting metabolism | See its own page | Named in the same list entry | [6] |
| SLU-PP-332 | Small molecule acting on nuclear receptors | None; see its own page | See its own page | — |
| 5-Amino-1MQ | Blocks an enzyme of fat-cell metabolism | See its own page | See its own page | — |
| GW501516 | Small molecule acting on a nuclear receptor | See the register entry | Threshold quantity 225 mg in German law | [8] |
The table shows a family resemblance rather than a chemical one. MOTS-c is a peptide and AICAR is not, yet the anti-doping list names them in the same line, because both are sold on the promise of mimicking training [6].
The contrast in evidence is the useful part. SLU-PP-332 and 5-Amino-1MQ have almost no human data, so nothing about them can be ruled out yet. AICAR has 3,080 patients in a single well-run trial, and what they show is an odds ratio of 1.01 [1].
German law treats these substances very differently by quantity. The threshold for the AICAR line is 7 000 mg; for the GW501516 line it is 225 mg, about thirty times lower [8].
Common misconceptions
- "AICAR is a peptide." It is a nucleoside of 258.23 g/mol, with no amino acids and no peptide bond. Trading it among peptides is a shop-shelf decision, not a chemical one [12].
- "The bypass trials showed it prevents heart attacks." That was the state of knowledge between 1997 and 2012. Then 3,080 patients produced 5.1 against 5.0 per cent and an odds ratio of 1.01, and the trial was stopped as pointless [3], [1].
- "Exercise in a pill." Mice, four weeks, 500 mg/kg per day into the abdomen. In people, none of it has been tested, and "pill" is wrong in any case, since less than 5 per cent survives being swallowed [4], [17].
- "It has European approval, it has an orphan designation." A designation supports development against a rare disease and is expressly not an authorisation. No application ever followed, and no assessment report exists [18].
- "The ATC code proves it was an approved heart drug." Codes are classification numbers issued on request, including for substances never approved. No daily dose is defined for this one [14].
- "It is just an AMPK activator, so it is well understood." A 2021 systematic review found many of its effects independent of that enzyme, and a protein study named the phosphate form as the toxic one [13], [16].
- "The body makes it anyway, so it is harmless." Both halves are true and the conclusion still does not follow. The inherited disease in which it accumulates is devastating, and a trial using high doses stopped for kidney damage [27], [11].
- "It kills cancer cells selectively." In the study behind that claim, healthy B lymphocytes were exactly as sensitive as the leukaemia cells [20].
- "There is a current trial, so interest is reviving." The registry entry people cite concerns purine supplements in people with AICA-ribosiduria, a disease of AICAR excess, and no AICAR is given [40].
Frequently asked questions
Is AICAR a peptide?
No. It is a nucleoside, a small molecule of 258.23 g/mol made of an imidazole base and a ribose sugar, with no amino acids and no peptide bond. It appears in this register because it is sold and discussed alongside peptides, not because it is one. The anti-doping list files it with metabolic modulators rather than peptide hormones.
What is the difference between AICAR and acadesine?
They are two names for the same page's subject, with a chemical twist. Acadesine is the international non-proprietary name for the riboside, PubChem CID 17513. Strictly, the abbreviation AICAR denotes the ribotide ZMP, CID 65110, which is the phosphate the cell builds from it. Everyday use, trade and the anti-doping list all mean the riboside.
Did the large trial of AICAR work?
No, and it is one of the clearest negative results in this register. RED-CABG randomised 3,080 patients before bypass surgery. The main outcome occurred in 5.1 per cent on acadesine and 5.0 per cent on placebo, an odds ratio of 1.01 with a confidence interval from 0.73 to 1.41. Recruitment stopped early because continuing was pointless.
Does AICAR improve endurance in humans?
No study has ever measured it. The endurance claim comes from 15 to 20 untrained mice per group that ran roughly 44 per cent further and roughly 23 per cent longer after four weeks of 500 mg/kg per day injected into the abdomen. The nearest human study measured glucose uptake into muscle for three hours in 29 men and found less than half the effect of cycling.
Is AICAR banned in sport?
Yes, at all times, in and out of competition. It is named on the 2026 prohibited list under S4.4.1, among activators of AMP-activated protein kinase, and counts as a non-specified substance. Because everyone has AICAR in their urine naturally, laboratories rely on population limits and a carbon isotope method rather than simple detection.
Is AICAR legal to possess?
That depends entirely on where you live, and it is your own responsibility to know. Germany is the strictest of the markets checked here: AICAR is named in the annex to the anti-doping act, and a 2023 regulation sets a threshold quantity of 7 000 mg, above which acquisition and possession are criminal offences.
Is AICAR approved as a medicine anywhere?
No. Checks of the American, Canadian, Swiss, German and Australian databases on 13 September 2026 found no entry, each alongside a control substance that the same query did find. The European orphan designation from 2005 is a development status, not an authorisation, and no application ever followed it.
What are the known side effects of AICAR?
Uric acid rises, because uric acid is the main breakdown product. Systemic lactate rose by up to 60 per cent in one study. Kidney damage is the documented limit: a trial using 140 to 315 mg/kg per day stopped after five patients for renal toxicity. Serious low blood sugar appeared in six patients on acadesine and none on placebo in the largest trial.
Why is AICAR sold as a research chemical?
Because there is nothing else it can lawfully be. Development ended without an approval anywhere, so no medicinal product exists, and no pharmacy route was ever opened for it either. Sellers label it as not for human use, which does not change how medicines law treats a product promoted for people.
Sources
- Newman MF, Ferguson TB, White JA, Ambrosio G, Koglin J, Nussmeier NA, et al. (2012). Effect of adenosine-regulating agent acadesine on morbidity and mortality associated with coronary artery bypass grafting: the RED-CABG randomized controlled trial. JAMA 308(2):157-164. PMID 22782417. DOI 10.1001/jama.2012.7633. Abstract read in full on 13 September 2026: 3,080 patients randomised at 300 centres in seven countries, recruitment 6 May 2009 to 30 July 2010, stopped after a pre-planned futility analysis at 3,080 of 7,500 planned; main outcome 76/1,493 (5.1 per cent) against 75/1,493 (5.0 per cent), odds ratio 1.01 (95 % confidence interval 0.73 to 1.41).
- ClinicalTrials.gov NCT00872001, "The Effect Of Acadesine On Reducing Cardiovascular and Cerebrovascular Adverse Events In Coronary Artery Bypass Graft (CABG) Surgery" (Study P05633 AM1). Merck Sharp & Dohme LLC with the Duke Clinical Research Institute. Phase 3, 3,080 participants, terminated. Study record and results sections retrieved through API v2 on 13 September 2026: intervention 42 mg/kg at 0.1 mg/kg per minute with 5 µg/ml in the cardioplegia and pump priming solutions, substance code SCH 900395; participant flow 1,536 against 1,544; safety population 1,442 against 1,457 with 327 against 329 serious adverse events. https://clinicaltrials.gov/study/NCT00872001
- Mangano DT; Multicenter Study of Perioperative Ischemia (McSPI) Research Group (1997). Effects of acadesine on myocardial infarction, stroke, and death following surgery. A meta-analysis of the 5 international randomized trials. JAMA 277(4):325-332. PMID 9002496. DOI 10.1001/jama.277.4.325. Individual patient data from 4,043 bypass patients at 81 centres, 2,031 on placebo and 2,012 on acadesine.
- Narkar VA, Downes M, Yu RT, Embler E, Wang YX, Banayo E, et al. (2008). AMPK and PPARdelta agonists are exercise mimetics. Cell 134(3):405-415. PMID 18674809. DOI 10.1016/j.cell.2008.06.051. Full text read at PMC2706130. Untrained mice, 15 to 20 per group, 500 mg/kg per day into the abdomen for four weeks: running time up roughly 23 per cent and running distance up roughly 44 per cent (p < 0.05); a separate six-day arm used 250 mg/kg per day.
- Cuthbertson DJ, Babraj JA, Mustard KJ, Towler MC, Green KA, Wackerhage H, et al. (2007). 5-aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men. Diabetes 56(8):2078-2084. PMID 17513706. DOI 10.2337/db06-1716. 29 healthy men; muscle uptake 2.1 ± 0.8-fold against 4.7 ± 1.7-fold for cycling; no change in enzyme activity or phosphorylation; whole-body glucose disposal up 7 per cent, from 9.3 ± 0.6 to 10.0 ± 0.6 mg/kg per minute (p < 0.05). The publisher returned an error for the full text on 13 September 2026, so the dose is not listed on this page.
- World Anti-Doping Agency. World Anti-Doping Code International Standard: Prohibited List 2026, in force 1 January 2026. https://www.wada-ama.org/sites/default/files/2025-09/2026list_en_final_clean_september_2025.pdf Downloaded and searched in full text on 13 September 2026. AICAR is named in section S4.4.1 under the heading "S4 HORMONE AND METABOLIC MODULATORS / PROHIBITED AT ALL TIMES (IN- AND OUT-OF-COMPETITION)" and appears again in the alphabetical index. The list states that substances in classes S4.3 and S4.4 are non-specified substances.
- Germany, annex to the anti-doping act (Anti-Doping-Gesetz). https://www.gesetze-im-internet.de/antidopg/anlage.html Retrieved 13 September 2026. Section III, item 4 "metabolic modulators" carries the line "AMPK (PPARd-AMP-activated protein kinase)-Axis-Agonisten / Zum Beispiel: AICAR"; the annex expressly includes salts, esters, ethers, isomers, mixtures of isomers, complexes and derivatives.
- Germany, regulation setting threshold quantities for doping substances (Dopingmittel-Mengen-Verordnung) of 10 March 2023, Federal Law Gazette 2023 I no. 67, p. 5, in force from 16 March 2023. https://www.gesetze-im-internet.de/dmmv_2023/DmMV.pdf Downloaded and extracted on 13 September 2026. The AMPK-axis line, with AICAR as the example, carries a threshold of 7 000 mg; the PPARd line with GW1516 carries 225 mg, SR9009 75 mg and meldonium 42 000 mg.
- Dixon R, Fujitaki J, Sandoval T, Kisicki J (1993). Acadesine (AICA-riboside): disposition and metabolism of an adenosine-regulating agent. Journal of Clinical Pharmacology 33(10):955-958. PMID 8227467. DOI 10.1002/j.1552-4604.1993.tb01929.x. Radiolabel study in four healthy men, 25 mg/kg as a 15-minute infusion: uric acid was the main breakdown product and accounted for essentially all plasma radioactivity six hours after the infusion; ZMP was found only in red blood cells; 48 per cent of the dose was recovered over two weeks, only 5 per cent of it unchanged.
- de Jonge R, Macleod DC, Suryapranata H, van Es GA, Friedman J, Serruys PW (1997). Effect of acadesine on myocardial ischaemia in patients with coronary artery disease. European Journal of Pharmacology 337(1):41-44. PMID 9389379. DOI 10.1016/s0014-2999(97)01239-9. 47 patients given 5 to 50 mg/kg into a vein; systemic lactate rose dose-dependently by up to 60 per cent against placebo (p < 0.001).
- ClinicalTrials.gov NCT01813838, "GFM-Acadesine: A Phase I-II Trial of Acadesine in IPSS High and Int-2 MDS, AML With 20-30% Marrow Blasts and CMML Type 2 Not Responding to Azacitidine or Decitabine". Groupe Francophone des Myelodysplasies with Advancell. Phase 1/2, 5 participants, terminated; the registry field for the reason reads "Renal toxicity"; planned dose steps 140, 210 and 315 mg/kg per day. Retrieved through API v2 on 13 September 2026. https://clinicaltrials.gov/study/NCT01813838
- PubChem (National Center for Biotechnology Information), compound CID 17513 "Acadesine" (C9H14N4O5, 258.23 g/mol, InChIKey RTRQQBHATOEIAF-UUOKFMHZSA-N, CAS 2627-69-2, UNII 53IEF47846) and compound CID 65110 "AICA Ribotide" (C9H15N4O8P, 338.21 g/mol, CAS 3031-94-5, UNII F0X88YW0YK). Queried through the PUG-REST interface on 13 September 2026.
- Visnjic D, Lalic H, Dembitz V, Tomic B, Smoljo T (2021). AICAr, a widely used AMPK activator with important AMPK-independent effects: a systematic review. Cells 10(5):1095. PMID 34064363. Concludes that many effects on metabolism, the oxygen-shortage response, nucleotide synthesis and tumour cells are independent of the enzyme, and warns against over-interpreting studies based on this substance.
- WHO Collaborating Centre for Drug Statistics Methodology, ATC/DDD Index, code C01EB13 "acadesine", group C01EB "other cardiac preparations". https://atcddd.fhi.no/atc_ddd_index/?code=C01EB13 Retrieved 13 September 2026, page dated "Last updated: 2026-01-20". No defined daily dose is recorded.
- Adis R&D Profile (2008). Acadesine: AICA riboside, ARA 100, arasine, GP 1 110. Drugs in R&D 9(3):169-175. PMID 18457469. DOI 10.2165/00126839-200809030-00004. Development chronology from Gensia Sicor to Metabasis in December 1997, a licence in November 2000, PeriCor Therapeutics in January 2005 and then Schering-Plough, alongside the Advancell programme in blood cancer; names the European orphan status and the development brand names, none of which belong to an approved product.
- Douillet DC, Pinson B, Ceschin J, Huerlimann HC, Saint-Marc C, Laporte D, et al. (2019). Metabolomics and proteomics identify the toxic form and the associated cellular binding targets of the anti-proliferative drug AICAR. Journal of Biological Chemistry 294(3):805-815. PMID 30478173. DOI 10.1074/jbc.RA117.001068. Identifies the ribotide ZMP, rather than AICAR itself, as the toxic form.
- Dixon R, Gourzis J, McDermott D, Fujitaki J, Dewland P, Gruber H (1991). AICA-riboside: safety, tolerance, and pharmacokinetics of a novel adenosine-regulating agent. Journal of Clinical Pharmacology 31(4):342-347. PMID 2037706. DOI 10.1002/j.1552-4604.1991.tb03715.x. First human pharmacokinetics: 10, 25, 50 and 100 mg/kg into a vein and by mouth, four active and two placebo per level; terminal half-life 1.4 hours, clearance 2.5 l/h/kg, volume of distribution 1.6 l/kg, renal clearance 0.2 l/h/kg with 8 per cent excreted unchanged; availability by mouth under 5 per cent.
- European Medicines Agency. EU/3/05/280 — orphan designation for the treatment of B-cell chronic lymphocytic leukaemia, active substance acadesine. https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu-3-05-280 Retrieved 13 September 2026. Designation granted on 27 May 2005 to Advanced In Vitro Cell Technologies S.L., Spain, later Advancell, on a committee opinion of 7 April 2005; prevalence at designation 2.7 per 10 000 people in the European Union, against a limit of 5 per 10 000. The page states: "An orphan designation is not a marketing authorisation." No assessment report and no authorisation exist.
- Wikidata, entity Q4671562 "acadesine". https://www.wikidata.org/wiki/Special:EntityData/Q4671562.json Retrieved 13 September 2026: CAS 2627-69-2, PubChem CID 17513, UNII 53IEF47846, ChEBI 28498, ChEMBL CHEMBL1551724, DrugBank DB04944, ATC C01EB13.
- Campas C, Lopez JM, Santidrian AF, Barragan M, Bellosillo B, Colomer D, et al. (2003). Acadesine activates AMPK and induces apoptosis in B-cell chronic lymphocytic leukemia cells but not in T lymphocytes. Blood 101(9):3674-3680. PMID 12522004. DOI 10.1182/blood-2002-07-2339. Cells from 70 patients; half-maximal effective concentration 380 ± 60 micromoles per litre; blocking the transporter or the phosphorylating enzyme abolished the effect; normal B lymphocytes were equally sensitive.
- Mangano DT, Miao Y, Tudor IC, Dietzel C (2006). Post-reperfusion myocardial infarction: long-term survival improvement using adenosine regulation with acadesine. Journal of the American College of Cardiology 48(1):206-214. PMID 16814669. DOI 10.1016/j.jacc.2006.04.044. 2,698 patients at 54 centres; heart attack around surgery in 100 patients (3.7 per cent); two-year mortality in that subgroup 27.8 per cent (15/54) against 6.5 per cent (3/46), p = 0.006.
- Menasche P, Jamieson WR, Flameng W, Davies MK; Multinational Acadesine Study Group (1995). Acadesine: a new drug that may improve myocardial protection in coronary artery bypass grafting. Results of the first international multicenter study. Journal of Thoracic and Cardiovascular Surgery 110(4 Pt 1):1096-1106. PMID 7475138. DOI 10.1016/s0022-5223(05)80179-5. 821 patients, 418 on placebo and 403 on acadesine; main outcomes missed.
- Leung JM, Stanley T, Mathew J, Curling P, Barash P, Salmenpera M, et al.; SPI Research Group (1994). An initial multicenter, randomized controlled trial on the safety and efficacy of acadesine in patients undergoing coronary artery bypass graft surgery. Anesthesia & Analgesia 78(3):420-434. PMID 7818622. DOI 10.1213/00000539-199403000-00002. 116 patients in three groups, seven-hour infusion; no significant differences; plasma uric acid up 1.6 ± 0.2 mg/dl in the high-dose group only.
- Holdright DR, Sparrow JL, Wright CL, Steiner J, Fox KM (1994). Effect of acadesine, a new metabolic agent, on exercise-induced myocardial ischemia in chronic stable angina. Cardiovascular Drugs and Therapy 8(2):193-197. PMID 7918131. DOI 10.1007/BF00877327. 12 patients, five-way crossover with 6, 12, 24 and 48 mg/kg; no significant change in exercise measures.
- Van Den Neste E, Cazin B, Janssens A, Gonzalez-Barca E, Terol MJ, Levy V, et al. (2013). Acadesine for patients with relapsed/refractory chronic lymphocytic leukemia (CLL): a multicenter phase I/II study. Cancer Chemotherapy and Pharmacology 71(3):581-591. PMID 23228986. 24 patients; part I single doses of 50 to 315 mg/kg in 18 patients, part II 210 mg/kg in 6; highest tolerated dose 210 mg/kg; raised uric acid from grade 2 upwards, managed with preventive allopurinol; also anaemia, low platelets, impaired kidney function and clinically significant infusion-related low blood pressure.
- ClinicalTrials.gov NCT00004314, "Phase II Pilot Study of Aminoimidazole Carboxamide Riboside (AICAR), a Precursor of Purine Synthesis, for Lesch-Nyhan Disease". National Center for Research Resources with the University of California, San Diego. Two patients, from February 1996; continuous infusion over 12 days after three baseline days; no dose stated in the registry and no results posted. Retrieved through API v2 on 13 September 2026.
- Ramond F, Rio M, Heron B, Imbard A, Marie S, Billiemaz K, et al. (2020). AICA-ribosiduria due to ATIC deficiency: delineation of the phenotype with three novel cases, and long-term update on the first case. Journal of Inherited Metabolic Disease 43(6):1254-1264. PMID 32557644. DOI 10.1002/jimd.12274. Describes the inherited disease of AICA-riboside accumulation and points to a cell-damaging mechanism.
- Wong JKY, Kwok WH, Chan GHM, Choi TLS, Ho ENM, Jaubert M, et al. (2017). Doping control study of AICAR in post-race urine and plasma samples from horses. Drug Testing and Analysis 9(9):1363-1371. PMID 28407446. DOI 10.1002/dta.2205. 1470 race urine samples from Australia, France and Hong Kong; proposed screening limit 600 ng/ml; after 2 g into a vein in one mare the detection window was about 4.5 hours.
- ClinicalTrials.gov NCT00559624, "A Phase I/II Open Label Dose Escalation Study to Investigate the Safety and Tolerability of Acadesine in Patients With B-cell Chronic Lymphocytic Leukemia". Advancell - Advanced In Vitro Cell Technologies, S.A., with Nexus Oncology Ltd, product name "Acadra". Completed December 2010, no results posted. Retrieved through API v2 on 13 September 2026.
- US Food and Drug Administration, openFDA. Approvals endpoint https://api.fda.gov/drug/drugsfda.json and product code endpoint https://api.fda.gov/drug/ndc.json, queried 13 September 2026. Searches for "acadesine" returned no record in either, while the control query for tesamorelin returned records.
- Health Canada, Drug Product Database, active ingredient endpoint https://health-products.canada.ca/api/drug/activeingredient/?ingredientname=acadesine Queried 13 September 2026: empty result, against two records for the control substance tesamorelin.
- Swissmedic, extended list of authorised human medicines (XLSX), downloaded 13 September 2026 and searched: no match for "Acadesin", "AICAR" or "Aminoimidazol", against 147 matches for the control substance metformin.
- Therapeutic Goods (Poisons Standard — June 2026) Instrument 2026, F2026L00633, version of 28 May 2026, 674 pages. https://www.legislation.gov.au/F2026L00633 Downloaded and converted to 39 488 lines of text on 13 September 2026: no match for "acadesine", "AICAR" or "imidazole-4-carboxamide", against three matches for the control substance ipamorelin. Not being scheduled by name does not make an unregistered therapeutic good lawful to supply or import.
- Germany, annex 1 to the regulation on prescription-only medicines (Arzneimittelverschreibungsverordnung). https://www.gesetze-im-internet.de/amvv/anlage_1.html Retrieved 13 September 2026: no entry for "Acadesin", "AICAR" or "Aminoimidazol", against 10 matches for insulin and 1 for metformin. The substance is not prescription-only because it is not an authorised medicine at all.
- United Kingdom: the medicines regulator’s product index returned only an empty page frame on 13 September 2026, because results load dynamically, so no control query was possible either. The British status on this page is inferred from the absence of any approval worldwide, not from a database match.
- US Food and Drug Administration, "Certain bulk drug substances for use in compounding that may present significant safety risks" and the pages listing substances nominated under sections 503A and 503B. https://www.fda.gov/drugs/human-drug-compounding/certain-bulk-drug-substances-use-compounding-may-present-significant-safety-risks Retrieved 13 September 2026: no match for "acadesine" or "AICAR", against 10 matches for ipamorelin in the same document.
- Sobolevsky T, Ahrens B (2019). Urinary concentrations of AICAR and mannitol in athlete population. Drug Testing and Analysis 11(3):530-535. PMID 30548818. DOI 10.1002/dta.2557. 12 377 urine samples: mean 647 ± 365 ng/ml, middle value 574 ng/ml, 99th percentile 1786 ng/ml, 99.7th percentile 2151 ng/ml; samples above 2000 to 2500 ng/ml proposed for isotope checking.
- Sobolevsky T, Piper T, Ahrens B, Thevis M (2022). AICAr to SAICAr ratio can serve as additional marker of AICAr use. Drug Testing and Analysis 14(11-12):2017-2025. PMID 36342242. DOI 10.1002/dta.3399. 5517 athlete samples: middle value of the ratio 3.3 with a 99th percentile of 9.3 in men, and 4.2 with 14 in women.
- Piper T, Thomas A, Baume N, Sobolevsky T, Saugy M, Rodchenkov G, et al. (2014). Determination of 13C/12C ratios of endogenous urinary 5-amino-imidazole-4-carboxamide 1beta-D-ribofuranoside (AICAR). Rapid Communications in Mass Spectrometry 28(11):1194-1202. PMID 24760559. DOI 10.1002/rcm.6891. Carbon isotope method separating the body’s own molecule from an administered one; reference group of 63 people; detection for more than 40 hours after a single dose by mouth.
- ClinicalTrials.gov NCT06845501, "Purine Supplementation in Patients With AICA-Ribosiduria". Centre Hospitalier Universitaire de Saint-Etienne, 10 participants, recruiting. No AICAR is administered; the study concerns a disease in which the molecule accumulates. Found through the registry search for "acadesine" on 13 September 2026.
Cite this page
The facts on this page were checked on 13 September 2026, and every register behind the status table was queried on that day. Two things are weaker than the rest: the British entry rests on inference rather than a database match, and it could not be established whether an American application was ever filed and refused in the 1990s.
myPeptides Research & Editing. (2026). AICAR: what the studies show, status and safety. Version 1.0, 13 September 2026. myPeptides Peptide Register. Retrieved from https://mypep.app/peptides/aicar
How pages in this register are compiled and graded is described under methodology; the full register is at peptides.
| Version | Date | Change |
|---|---|---|
| 1.0 | 2026-09-13 | Initial publication |
Last verified: 13 September 2026. Next review: on any new registered trial, on any change to the anti-doping classification, or on any regulatory decision in a market not checked here.