The AMPK activator that made "exercise in a bottle" headlines in the 2000s — real mechanism, real animal data, but dose-cost and limited human trials keep it experimental.
AICAR (5-Aminoimidazole-4-carboxamide ribonucleoside) is a nucleoside that’s metabolized inside cells to ZMP — an AMP analog that directly activates AMPK, the master cellular energy sensor. Activating AMPK triggers most of the metabolic adaptations the body makes to caloric restriction and endurance exercise.
Narkar et al. (2008, Cell, PMID 18674809) made headlines showing four weeks of AICAR alone raised running endurance 44% in sedentary mice. That result is real and it is where the "exercise in a bottle" framing comes from.
What usually gets left out is that AICAR has been through large human trials — just not for endurance, and not successfully. Under the name acadesine it was given intravenously to thousands of cardiac-surgery patients and to leukaemia patients, at gram-scale doses. The biggest of those trials was stopped early for futility. So the honest summary is not "untested in humans" but "tested in humans, for other things, and it did not deliver" — see the evidence section.
Not FDA approved. WADA prohibited (S4 — Hormone & Metabolic Modulators). Research chemical; controversial due to cost vs evidence ratio.
ZMP (AICAR’s active metabolite) mimics AMP inside cells and allosterically activates AMPK. Downstream: fatty-acid oxidation up, mitochondrial biogenesis up, gluconeogenesis down, PGC-1α activation — the same effectors that endurance training engages.
The caveat matters for reading any AICAR study: a 2021 systematic review (PMID 34064363) found that a large number of effects historically attributed to AICAR-driven AMPK activation are in fact AMPK-independent. AICAR is a nucleoside that enters purine metabolism, and it does things beyond AMPK. Because so much of the early AMPK literature used AICAR as its only tool, some of what is described as "the AMPK pathway" may not be.
In animal models, chronic AICAR produces a slow-twitch (oxidative) fiber shift in skeletal muscle — the adaptation that defines endurance-trained muscle.
Narkar’s mouse studies used 500 mg/kg/day. Scaled allometrically, effective human doses land in the grams — and the human trial record confirms that scale rather than contradicting it. Acadesine was infused at 0.1 mg/kg/min for 7 hours in cardiac surgery (about 3.4 g for an 80 kg adult) and single intravenous doses up to a 210 mg/kg maximum tolerated dose in leukaemia (about 16.8 g). Research-chem AICAR is expensive enough at that volume that cost becomes the practical ceiling for personal use.
| Benefit | Evidence |
|---|---|
| Endurance (animal) | Narkar 2008 (PMID 18674809): four weeks of AICAR raised running endurance 44% in sedentary mice, orally active. The foundational result — and still the only strong endurance finding, in any species. |
| Fat loss | Improved fat oxidation in animal models; modest human data |
| Insulin sensitivity | AMPK-mediated glucose uptake improvement |
| Diabetes research | Studied as a metformin-alternative pathway |
| Cardiac surgery (human) — negative | RED-CABG (Newman 2012, JAMA, PMID 22782417): randomised, double-blind, placebo-controlled, 300 sites across 7 countries. Acadesine 0.1 mg/kg/min for 7 hours around bypass surgery. Stopped early for futility — a prespecified analysis found a very low likelihood of showing benefit on death, nonfatal stroke or severe LV dysfunction. This is the largest human trial of the molecule and it failed. |
| Leukaemia (human) — dose-finding | Phase I/II in relapsed/refractory CLL (PMID 23228986), 24 patients, 4-hour IV infusions at 50–315 mg/kg. Maximum tolerated dose 210 mg/kg. Efficacy signals were variable and inconclusive. Useful here mainly because it is the only real human dose-ranging and safety dataset that exists. |
| Human endurance trials | None. No trial has tested AICAR for endurance, body composition or fat loss in humans at any dose. Every endurance claim traces to rodents. |
MOTS-C and SLU-PP-332 hit similar AMPK / mitochondrial endpoints at more practical doses. Most users interested in the "exercise mimetic" idea end up there instead of AICAR.
Build your protocol, log every dose, monitor your body's response, and get reminders so you never miss a dose.
Start Tracking FreeNot medical advice. These figures describe what is reported in the literature and what practitioners and communities do — not a recommendation, and for most compounds here no human dose-finding study exists. Talk to a qualified healthcare provider.
No established human dosing for this purpose — these are extrapolated community estimates, not clinical guidelines. Expect the effect to be subtle at any dose you can actually afford.
Unusually for this site, the community range sits below the studied doses rather than above them. Acadesine trials used roughly 3.4 g over seven hours in cardiac surgery, and single doses up to a 210 mg/kg maximum tolerated dose — about 16.8 g for an 80 kg adult — in leukaemia.
Two caveats keep that from being reassurance. Every one of those doses was intravenous, given under hospital supervision with monitoring; no trial has ever administered AICAR subcutaneously, so the route most people use here has no human data behind it at all. And tolerability was established in acutely ill patients over hours to days, not in healthy adults dosing daily for a month or more.
Protocols in the 10–50 mg/day range also circulate. That is two to three orders of magnitude below anything ever given to a human and below any dose shown to do anything in any species. If a dose that low produces an effect, nothing in the published record explains why.
Not medical advice. These figures describe what is reported in the literature and what practitioners and communities do — not a recommendation, and for most compounds here no human dose-finding study exists. Talk to a qualified healthcare provider.
AICAR is supplied as a lyophilized powder. Because doses are so much higher than typical research peptides (hundreds of mg rather than mcg), reconstitution math differs — you’re injecting meaningful volumes.
A typical 500 mg vial reconstituted to a tolerable SubQ volume (say 2–3 mL BAC water) gives a concentration of 170–250 mg/mL. A 500 mg dose = the full 2–3 mL. Multiple injection sites may be needed.
Pre-filled with a typical AICAR setup. Edit any field — the draw updates live.
Insulin syringe — 100 units = 1 mL
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AICAR is a research peptide not approved by the FDA for human use. It is sold only as a research chemical, and StackTrax does not endorse or facilitate personal use.
Quality varies enormously among research-chemical suppliers. At minimum, look for:
Lyvn does not carry AICAR. They are the vendor we recommend elsewhere on this site, and they publish the full independent panel per batch — which makes their catalogue a useful yardstick for the criteria above even on a compound they do not stock. We are not recommending a specific supplier for AICAR itself, because we have no basis to.
For research use only. Not for human consumption. 21+.
Build your protocol, log every dose, monitor your body's response, and get reminders so you never miss a dose.
Start Tracking FreeAICAR (5-Aminoimidazole-4-carboxamide ribonucleoside) is a nucleoside that is metabolized inside cells to ZMP, an AMP analog that directly activates AMPK, the master cellular energy sensor. Activating AMPK triggers most of the metabolic adaptations the body makes to caloric restriction and endurance exercise, including increased fatty-acid oxidation, mitochondrial biogenesis, reduced gluconeogenesis, and PGC-1α activation.
It is a real AMPK activator, but the exercise-mimetic headline outruns the human evidence. Narkar et al. 2008 in Cell showed that sedentary mice ran 44% longer on AICAR alone, and in animal models chronic AICAR produces a slow-twitch oxidative fiber shift in skeletal muscle. The gap between proven in mice and proven in humans has not closed, and human endurance trials are limited. MOTS-C and SLU-PP-332 hit similar AMPK and mitochondrial endpoints at more practical doses, and most users interested in the exercise-mimetic idea end up there instead.
AICAR is WADA prohibited under S4 (Hormone and Metabolic Modulators) because it pharmacologically reproduces the metabolic effects of endurance training, including fiber-type shift and improved fat oxidation. Use by tested athletes will trigger anti-doping tests.
Narkar's mouse studies used 500 mg/kg/day. Scaled to human body size with allometric conversion, effective human doses would be in the grams. Community-reported low-confidence dosing is 500 mg to 2 g SubQ daily for 30 to 60 day cycles with long breaks. No established human dosing exists; these are extrapolated community estimates from animal-study doses, not clinical guidelines. Effective doses at research-chem pricing run $200+/week, so cost becomes prohibitive for most personal use and expect the effect to be subtle at any dose you can actually afford.
AICAR is supplied as a lyophilized powder, and because doses are hundreds of mg rather than mcg, reconstitution math differs from typical peptides. A typical 500 mg vial reconstituted to 2 to 3 mL of bacteriostatic water gives 170 to 250 mg/mL, so a 500 mg dose is the full 2 to 3 mL SubQ. Multiple injection sites may be needed. Store powder refrigerated (or frozen long term) and reconstituted product refrigerated, used within 14 days.
Reported effects include injection site reactions (large SubQ volumes can be uncomfortable), fatigue during the first week, transient lactate elevation, and mild GI upset. Active cancer is more than a vague caution: PMID 39197808 documents that AMPK activation plays a dual role in cancer, potentially both suppressing and actively promoting tumor proliferation, survival, metastasis, and impaired anti-tumor immunity depending on context. Treat active malignancy as a contraindication pending clearer human evidence. Use caution with kidney disease, hypoglycemia-unaware diabetes, pregnancy, and liver disease.
Disclaimer: This guide is for educational and informational purposes only and is not intended as medical advice, diagnosis, or treatment. The compounds discussed are not FDA approved for human use. Always consult a qualified healthcare provider before starting any new supplement or peptide protocol. StackTrax does not sell peptides or supplements directly — purchase links go to third-party vendors. StackTrax is not responsible for the products, quality, or business practices of any third-party vendor.
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StackTrax guides cover peptides and compounds that are not FDA-approved for the uses discussed. The dosing, reconstitution, and safety information is compiled from published research and community protocols for educational purposes only.
Before using any compound mentioned here, consult a qualified healthcare provider. StackTrax does not sell, prescribe, or recommend these substances for personal use.