AICA Riboside · Acadesine · Z-Riboside
AICAR (5-aminoimidazole-4-carboxamide ribonucleotide, also called acadesine) is an intermediate in de novo purine biosynthesis and an activator of AMP-activated protein kinase (AMPK) - the cellular master switch for energy-deficit signaling. It is not FDA-approved for any human indication. Clinically it has been investigated as an adjunct in acute myeloid leukemia, as an ischemia-reperfusion adjunct in cardiac surgery, and in metabolic disease models, but no approval has emerged.
Typical off-label protocols dose 50-100 mg subcutaneously once daily, often pre-workout, though the 8-minute half-life means any pre-workout timing benefit is brief. Reconstitute with bacteriostatic water and use within 1-2 weeks refrigerated. Expect subtle-to-absent subjective effects - AICAR does not produce the CNS stimulation of yohimbine or clenbuterol.
Start here. Every protocol below is ordered lowest-first. Begin at the smallest effective dose, hold about a week to assess tolerance, and step up only if needed.
AICAR enters cells via adenosine transporters and is phosphorylated intracellularly to ZMP (AICA ribotide monophosphate), a direct AMP-mimetic that allosterically activates AMP-activated protein kinase (AMPK). AMPK is a heterotrimeric kinase that senses cellular energy status via the AMP:ATP ratio and, when activated, shifts metabolism from ATP consumption to ATP production - increasing fatty acid oxidation, glucose uptake via GLUT4, mitochondrial biogenesis (via PGC-1-alpha upregulation), and autophagy, while suppressing lipogenesis, gluconeogenesis, and anabolic protein synthesis.
In rodent skeletal muscle, chronic AICAR administration increases slow-twitch (oxidative) fiber proportion, raises mitochondrial density, and improves endurance running time even in sedentary animals - the effect that produced the 'exercise mimetic' framing. In humans, the very short plasma half-life (~8 minutes) and poor tissue delivery have limited effect size, and most published human studies have been small safety/pharmacokinetic trials rather than efficacy trials for endurance.
AICAR is not a receptor agonist and does not bind a hormone receptor - it acts through the intracellular AMPK pathway. It is typically administered parenterally (subcutaneous or intravenous) because oral bioavailability is extremely poor. Because AMPK activation is broad and tissue-non-selective, off-target metabolic effects are theoretically possible - most notably transient hyperuricemia from the purine load.
First 1-2 weeks: subtle or absent subjective effects. No CNS stimulation. Some users report modestly reduced perceived exertion during steady-state cardio.
Week 2-4: cellular adaptations (AMPK-driven transcriptional shifts, mitochondrial biogenesis) accumulate but are not clinically perceptible in most users.
Week 4-8: peak theoretical benefit. Human evidence for the 'exercise mimetic' claim is weak - expect modest or unnoticeable practical effects in a trained human. The rodent magnitude has not translated.
Each reference below was re-fetched from its PubMed record, and the quoted sentence was confirmed to appear in that abstract and to support the claim it sits under. Follow any of them to read the source.
Mechanism boundary: AICAR activated AMPK in adipocytes in a time- and dose-dependent manner; this is in vitro.
Both isoforms of the catalytic alpha-subunit of AMPK are expressed in 3T3-L1 adipocytes, in which AICAR stimulated AMPK activity in a time- and dose-dependent fashion.
Evidence scope. In vitro; 3T3-L1 mouse adipocyte cell line; no animal or human in-vivo data in this paper.
Mechanism: AICAR is an AMPK activator; in rats it was investigated through the JAK/STAT/SOCS pathway.
We investigated the protective effect of the adenosine monophosphate protein kinase (AMPK) activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) against cisplatin-induced AKI.
Evidence scope. Animal (Sprague-Dawley rat) in vivo plus rat kidney cell line (NRK-52E) in vitro; cisplatin-induced AKI model; not human data.
Claims we could not support
No abstract we checked supports these for this molecule at this route. That is not the same as saying they are false — it marks where the evidence is missing.
Dose/route: 10 mg SubQ daily. The checked papers were in vitro or used intraperitoneal animal dosing, not 10 mg subcutaneous dosing in humans.
Primary safety concern: clinically significant hypoglycemia at the displayed regimen. No checked abstract directly established this risk for 10 mg SubQ AICAR in humans.
Very short
SubQ
Poor oral; SubQ/IV delivery required for meaningful plasma levels
Short plasma presence but longer downstream AMPK-driven transcriptional effects; supports daily dosing despite short half-life
Renal excretion of unchanged compound and metabolites; cellular incorporation into purine pool.
Storage. Lyophilized vial: store refrigerated (2-8°C / 36-46°F) or frozen (-20°C) for long-term storage. Protect from light. After reconstitution with bacteriostatic water: refrigerate and use within 1-2 weeks. Do not freeze reconstituted solution. Discard if solution becomes cloudy or discolored.
Not FDA-approved for any human indication in the United States. Investigated clinically as acadesine for acute myeloid leukemia and cardiac ischemia-reperfusion without achieving approval. Sold only as a research chemical / 'not for human use' peptide through research-supply vendors. Prohibited by the World Anti-Doping Agency (WADA) under class S4 (hormone and metabolic modulators) both in and out of competition. Not a controlled substance under the Controlled Substances Act, but sale for human use is prohibited by FDA regulation.
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