AICAR
AICAR (5-Aminoimidazole-4-Carboxamide Ribonucleoside)
AMPK Activator for Endurance and Metabolic Performance
What is AICAR?
AICAR (5-aminoimidazole-4-carboxamide ribonucleoside, also written as acadesine or AICA-riboside) is a nucleoside analogue that is taken up by cells and phosphorylated to form ZMP, a structural analogue of AMP. ZMP accumulation mimics the cell's perception of low energy status by activating AMP-activated protein kinase (AMPK), a central metabolic sensor that governs cellular energy homeostasis across virtually all tissues. AMPK is sometimes described as the cell's master energy switch: it is activated when the AMP-to-ATP ratio rises and it orchestrates a coordinated response to restore energy balance.
By activating AMPK pharmacologically without requiring actual energy stress, AICAR simulates many of the adaptive metabolic responses associated with endurance exercise. Key downstream effects include increased mitochondrial biogenesis, enhanced fatty acid oxidation, upregulation of glucose transporter expression (GLUT-4 and GLUT-1), increased oxidative fiber specification in skeletal muscle, and improved insulin sensitivity. Research published in Cell in 2008 by Evans and colleagues at the Salk Institute demonstrated that four weeks of AICAR administration in sedentary mice enhanced running endurance by 44% and induced a gene expression profile in skeletal muscle resembling that of trained athletes, without any exercise training.
Subsequent research has provided important nuance. A systematic review published in Cells in 2021 documented that AICAR has numerous biological effects that are independent of AMPK activation, complicating the interpretation of earlier research. AICAR also inhibits AMP deaminase, affects adenosine signaling, and alters purine synthesis pathways. These off-target effects can influence inflammation, immune function, and cardiovascular biology in ways that are not fully characterized.
AICAR has been on the World Anti-Doping Agency (WADA) Prohibited List since 2011, classified under Hormone and Metabolic Modulators. It is prohibited at all times in competitive sport due to its potential to enhance endurance performance. AICAR has no FDA-approved therapeutic indication and is an investigational research compound available for laboratory and preclinical research use only.
Research Supply
Source high-purity AICAR for your research
Dosage Guide
Route: Subcutaneous or intramuscular injection (reconstituted from lyophilized powder)
Dosing Schedule
| Period | Dose |
|---|---|
| Sedentary mice (Evans lab, Cell 2008) | 500 mg/kg/day IP for 4 weeks |
| Various rodent studies | 250-500 mg/kg/day |
| Estimated human equivalent (60 kg adult) | ~42 mg/kg (single dose pharmacokinetics studied) |
| Human tolerability study | Up to 210 mg/kg single dose |
Reconstitution
Injection Volumes
| Dose | Volume | Syringe Units |
|---|
Administration Tips
- AICAR is typically supplied as a lyophilized powder and is reconstituted with sterile saline or bacteriostatic water for injection
- Reconstituted solutions should be stored at 2-8 degrees Celsius and used within 30 days
- Rodent doses of 250-500 mg/kg do not translate reliably to human equivalent doses for performance purposes
- No standard human dosing protocol exists with validated safety and efficacy data
- Prohibited at all times under WADA rules; competitive athletes should not use AICAR
Risks & Side Effects
Commonly Reported
Serious Risks
Severe hypoglycemia
The glucose-lowering effects of AICAR can be clinically significant, particularly at higher doses or in combination with insulin, metformin, or sulfonylureas. Symptomatic hypoglycemia requiring intervention has been reported in research contexts.
Cardiac arrhythmia
AICAR has complex effects on cardiac electrophysiology via AMPK and adenosine pathways. Arrhythmias have been observed in preclinical cardiac studies at high doses.
Unknown long-term consequences
AICAR's AMPK-independent effects (particularly on adenosine signaling, purine biosynthesis, and immune function) are not fully characterized over extended administration.
Immunosuppression
AMPK activation and adenosine pathway modulation can suppress immune responses, potentially increasing susceptibility to infection.
Contraindications
- Diabetes mellitus or any condition requiring tight glycemic control (severe hypoglycemia risk)
- Concurrent use of insulin, sulfonylureas, or other hypoglycemic agents
- Gout or hyperuricemia
- Pre-existing cardiac arrhythmia or conduction defects
- Immunocompromised states or active infection
- Pregnancy and breastfeeding (no safety data)
- Pediatric use
- Competitive athletes subject to WADA anti-doping rules (AICAR is prohibited at all times)
Frequently Asked Questions
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LEGAL DISCLAIMER
The information provided on this page is for educational and informational purposes only and is not intended as medical advice. AICAR has not been approved by the FDA for any medical condition. AICAR is prohibited under the World Anti-Doping Agency (WADA) Prohibited List. Always consult with a qualified healthcare professional before starting any research compound. Individual results may vary. Peptides Institute is not responsible for any adverse effects resulting from the use of information provided on this site.