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AICAR: AMPK activator — the exercise in a vial.

5-Aminoimidazole-4-carboxamide ribonucleoside. Activates AMPK to enhance fat oxidation, endurance, and glucose uptake. SubQ or oral.

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AMPK Activator WADA S2 Prohibited Research Use Only

AICAR
Dosage Protocol

AICAR (5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside) is a cell-permeable nucleoside that is converted intracellularly to ZMP, an AMP mimetic that potently activates AMP-activated protein kinase (AMPK). AMPK activation mimics many of the cellular effects of endurance exercise — increasing fat oxidation, enhancing mitochondrial biogenesis, and improving glucose uptake.

5–25 mg
Daily Dose (SubQ)
≤14 days on / 4 off
Cycle
SubQ
Route
Once daily
Frequency
Overview

What is AICAR?

AICAR is taken up by cells via adenosine transporters and phosphorylated to AICA-ribonucleotide (ZMP), a structural analog of AMP. ZMP allosterically activates AMPK — the master energy-sensing enzyme — mimicking a low-energy cellular state even in the absence of actual exercise or caloric restriction.

Landmark mouse studies from the Salk Institute showed AICAR-treated sedentary mice ran 44% farther than controls, with significant increases in fatty acid oxidation and mitochondrial gene expression. These findings sparked significant research interest. AICAR is prohibited by WADA and has been detected in doping cases in professional cycling, underscoring its performance-relevant mechanism.

⚡
AMPK Activation
Converted to ZMP intracellularly, which allosterically activates AMPK — the master cellular energy sensor — independent of actual AMP/ATP ratio changes.
🔥
Fat Oxidation Enhancement
AMPK phosphorylates ACC (acetyl-CoA carboxylase), reducing malonyl-CoA and de-inhibiting carnitine palmitoyltransferase I to increase mitochondrial fatty acid uptake.
🏃
Endurance Gene Expression
Activates PPAR-δ target genes involved in mitochondrial biogenesis, fiber-type switching, and oxidative metabolism — mimicking exercise adaptations.
🍬
Glucose Uptake
Stimulates GLUT4 translocation to cell membranes and increases skeletal muscle glucose uptake via AMPK-dependent mechanisms.
Dosing Protocol

Dosing Schedule

Parameters documented in published preclinical and clinical research.

⚠️ Research use only. The following documents parameters from published preclinical and clinical research. Not medical advice. Not for human consumption. Consult a licensed healthcare professional before any use.
PhaseDoseFrequencyDurationNotes
Conservative5 mgOnce daily SubQ≤14 daysStart here. Human SubQ dosing — do not use 250–500 mg IV clinical trial doses SubQ.
Working dose10–25 mgOnce daily SubQ≤14 daysAdvance after days 3–5 if tolerated. Do not exceed 14-day cycles — nephrotoxicity risk above 25 mg/day.
Stack10 mg + GW501516Once dailyPer protocolClassic AICAR + PPAR-δ agonist stack for AMPK/endurance gene activation.
Off cycle——4 weeksRest period before repeating. WADA S4 prohibited.
Safety Profile

Safety & Side Effects

✓ Generally Well Tolerated
Well-characterized mechanism from extensive cell and animal studies
Increases glucose uptake — potential metabolic benefits
Synergistic with PPAR-δ agonists for endurance gene expression
Short half-life enables flexible timing
⚠ Potential Concerns
WADA S4 prohibited (metabolic modulators)
Human clinical data limited compared to animal research
Potential hypoglycemia risk — AMPK activation increases glucose uptake
IV route used in trials — SubQ bioavailability variable
⚠️
Research use onlyThis page is an educational reference. None of this constitutes medical advice. Consult a qualified professional before any use. All compounds are for research purposes only.
Evidence Base

Academic References

  1. [1]
    Narkar VA, et al. (2008). AMPK and PPARδ agonists are exercise mimetics. Cell. 134(3):405–15. PubMed ↗
  2. [2]
    Cuthbertson DJ, et al. (2007). 5-Aminoimidazole-4-carboxamide 1-β-D-ribofuranoside acutely stimulates skeletal muscle 2-deoxyglucose uptake in healthy men. Diabetes. 56(8):2078–84. PubMed ↗
  3. [3]
    Corton JM, et al. (1995). 5-Aminoimidazole-4-carboxamide ribonucleoside — a specific method for activating AMP-activated protein kinase in intact cells. Eur J Biochem. 229(2):558–65. PubMed ↗
  4. [4]
    Merrill GF, et al. (1997). AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle. Am J Physiol. 273(6):E1107–12. PubMed ↗
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