AICAR
5-Aminoimidazole-4-carboxamide Ribonucleotide | AMPK Activator
AICAR is a cell-permeable nucleoside analog that activates AMP-activated protein kinase (AMPK), a key regulator of cellular energy homeostasis. Originally studied for cardiac ischemia protection, it gained attention as an 'exercise mimetic' due to its metabolic effects.
Mechanism of Action
Once inside cells, AICAR is phosphorylated to ZMP, which mimics AMP and activates AMPK. This triggers metabolic pathways typically activated during exercise: increased glucose uptake, fatty acid oxidation, and mitochondrial biogenesis.
Key Benefits
- AMPK pathway activation
- Enhanced fatty acid oxidation
- Improved glucose uptake
- Potential endurance enhancement
- Mitochondrial biogenesis stimulation
Metabolic
- AMPK Activation
Directly activates the master metabolic regulator through ZMP accumulation.
- Fatty Acid Oxidation
Increases fat burning through AMPK-mediated pathways.
- Glucose Metabolism
Enhances glucose uptake independent of insulin in some tissues.
Performance
- Endurance Enhancement
Animal studies showed increased running endurance; human data limited.
- Mitochondrial Biogenesis
AMPK activation promotes new mitochondria formation over time.
Cardioprotection
- Ischemia Protection
Original clinical interest; may protect heart tissue during reduced blood flow.
Subcutaneous injection once daily. Progressive dosing protocols are common to assess tolerance.
| Goal | Dose | Frequency | Route |
|---|---|---|---|
| Standard Protocol | 1-3mg | Daily | SubQ |
| Gradual Introduction | 1mg → 2mg → 3mg | Daily, titrating over 4 weeks | SubQ |
| Advanced Protocol | 3-5mg | Daily for 8-12 weeks | SubQ |
Reconstitution Instructions
- AICAR lyophilized powder (typically 50mg vial)
- Bacteriostatic water (3.0mL recommended)
- Insulin syringes (29-31 gauge)
- Alcohol swabs
- 1 Allow vial to reach room temperature
- 2 Clean rubber stopper with alcohol swab
- 3 Add 3.0mL bacteriostatic water for ~16.7mg/mL concentration
- 4 Inject slowly along vial wall to avoid foaming
- 5 Gently swirl to dissolve; never shake
- 6 Label with date and store refrigerated at 2-8°C
- 7 Use within 4 weeks of reconstitution
Both activate AMPK through different mechanisms. Combined use may have additive effects on glucose metabolism.
Different pathways (AMPK vs PPARδ) that may complement metabolic effects. Popular research combination.
Rev-ErbA agonist with complementary metabolic effects.
Subtle changes in energy levels; body adjusting to AMPK activation
Potential improvements in endurance capacity and metabolic markers
Cumulative metabolic adaptations; enhanced fat oxidation
Full effects on mitochondrial density and metabolic efficiency
Common Side Effects
- Injection site reactions
- Mild fatigue during adaptation
- Potential hypoglycemia
Stop Signs - Discontinue if:
- Severe hypoglycemia symptoms
- Lactic acidosis symptoms (muscle pain, weakness, difficulty breathing)
- Unusual cardiac symptoms
- Severe fatigue or weakness
Contraindications
- Diabetes (risk of hypoglycemia)
- Cardiac conditions
- Pregnancy or breastfeeding
- Competitive athletes (WADA prohibited)
Good Signs
- White to off-white lyophilized powder
- Clear solution after reconstitution
- Certificate of Analysis with purity testing
Warning Signs
- Slight yellowing may occur but should dissolve clearly
Bad Signs
- Discolored or clumped powder
- Cloudy solution after reconstitution
- Particulate matter visible
- AMPK and Exercise: Glucose Uptake and Insulin Sensitivity(2012)
Review of AMPK role in exercise-induced metabolic adaptations and AICAR as pharmacological activator.
- AICAR Mouse Endurance Study(2008)
Mice treated with AICAR showed 44% increase in running endurance without training.
Disclaimer
This information is for educational and research purposes only. Consult a healthcare professional before use.