Overview
Overview
AICAR (5-aminoimidazole-4-carboxamide ribonucleoside) is a research compound that activates AMP-activated protein kinase (AMPK)[1], earning the nickname “exercise pill” after studies showed sedentary animals given AICAR experienced dramatic endurance improvements[2]. AICAR is prohibited in sports (WADA classifies it as a metabolic modulator) and is not approved for therapeutic use in humans[1]. This educational protocol presents a once-daily subcutaneous approach for research purposes only. Rec
- Category
- Weight Loss
- Routes
- subcutaneous
Mechanism
AICAR
Mechanism of action
Mechanism of action
AICAR functions as an AMPK agonist, essentially mimicking an energy-depleted cellular state [6] . After administration, AICAR enters skeletal muscle and other cells where it is metabolized to ZMP (AICAR monophosphate), an analog of AMP that directly activates AMP-activated protein kinase (AMPK) [6] . AMPK serves as the master regulator of cellular energy homeostasis, and its activation stimulates glucose uptake and fatty-acid oxidation in muscle while promoting mitochondrial biogenesis to boost cellular energy output [1] [6] . This metabolic shift “tricks” cells into responding as if exercising or fasting, activating pathways that improve energy metabolism and endurance capacity without actual physical activity.
Key research findings
- 01
AICAR (5-aminoimidazole-4-carboxamide ribonucleotide; also called acadesine) is a small-molecule AMP analog that activates AMP-activated protein kinase (AMPK), a central cellular energy-sensing pathway (in vitro / mechanistic).
- 02
In sedentary mice, AICAR administration was associated with increased running endurance and a shift toward oxidative metabolism, contributing to its description as an "exercise mimetic" (animal model; Narkar et al., Cell, 2008).
- 03
Preclinical work links AMPK activation to increased fatty-acid oxidation and altered glucose uptake in muscle (in vitro / animal model).
- 04
Human exposure to acadesine has occurred mainly in cardiovascular/ischemia research contexts; robust human evidence for body-weight or fat-loss endpoints is not established (human studies limited to other contexts).
- 05
AICAR is listed on the World Anti-Doping Agency (WADA) Prohibited List as a metabolic modulator.
Primary source: The metabolic and exercise-mimetic research base for AICAR is predominantly preclinical (cell and rodent AMPK studies). Human exposure has mainly occurred in cardiovascular/ischemia research rather than weight-related endpoints, so weight-focused human evidence is limited.
Researched Effects
Researched benefits
Areas of active research and investigation. Results may vary and are based on preclinical or early clinical data.
Endurance Enhancement: Sedentary mice treated with AICAR showed a remarkable +44% increase in endurance without training[2], demonstrating exercise-mimetic effects.
Metabolic Improvements: Increases mitochondrial enzymes, fatty-acid oxidation capacity, and skeletal muscle glucose uptake[3][6]; improves insulin sensitivity in animal models.
Protocol Reference
Protocol reference
Commonly cited research range: 1–5 mg, daily.
Reference figures reported in the research literature — not a dosing recommendation. For interactive vial math and scheduling, see the Calculator and Schedule tabs.
Cited protocol & reconstitution guide
Source-backed reference fields by phase, including any volume fields authored in the cited guide.
Weeks 1–2
1,000 mcg (1 mg)
Weeks 3–4
2,000 mcg (2 mg)
Weeks 5–8
3,000 mcg (3 mg)
| Phase | Reference amount | Units / volume |
|---|---|---|
| Weeks 1–2 | 1,000 mcg (1 mg) | 6 units (0.06 mL) |
| Weeks 3–4 | 2,000 mcg (2 mg) | 12 units (0.12 mL) |
| Weeks 5–8 | 3,000 mcg (3 mg) | 18 units (0.18 mL) |
Storage & Handling
Storage requirements(typical for most peptides)
Can be stored for extended periods. Protect from moisture.
Store in refrigerator door. Never freeze after reconstitution.
Label vials with reconstitution date. Discard if cloudy.
Reconstitution steps
- 01🌡️Draw 3.0 mL bacteriostatic water with a sterile syringe.
- 02🧴Inject slowly down the vial wall; avoid foaming.
- 03💉Gently swirl/roll until dissolved (do not shake).
- 04💧Label and refrigerate at 2–8 °C (35.6–46.4 °F), protected from light.
- 05🔄Advanced Protocol (Higher Doses)
- 06🏷️WEEK/PHASE DAILY DOSE UNITS (PER INJECTION) (ML)
- 07❄️Weeks 1–2 2,000 mcg (2 mg) 12 units (0.12 mL)
- 08💉Weeks 3–6 3,000 mcg (3 mg) 18 units (0.18 mL)
- 09💉Weeks 7–12 5,000 mcg (5 mg) 30 units (0.30 mL)
- 10💉Note: Higher-dose protocols should only be considered when explicitly supported by literature[4]. Research doses remain well below human safety studies (up to 210 mg/kg IV)[5], providing a wide safety margin.
- 11💉Important: This guide is for educational and research purposes only and is not medical advice. Not for human consumption.
Additional storage notes
Store at −20 °C (−4 °F) in dry, dark conditions; stable up to 24 months [14] .
Refrigerate at 2–8 °C (35.6–46.4 °F); use bacteriostatic water; stable ~4 weeks [14] .
Avoid repeated cycles; consider aliquots for long-term storage at −20 °C (−4 °F) (3–6 months) [14] .
Allow vials to reach room temperature before opening to minimize condensation.
Clinical Evidence
Clinical evidence
Preclinical studies report enhanced endurance and metabolic activity (an 'exercise-mimetic' effect), largely in animal models.
The metabolic and exercise-mimetic research base for AICAR is predominantly preclinical (cell and rodent AMPK studies). Human exposure has mainly occurred in cardiovascular/ischemia research rather than weight-related endpoints, so weight-focused human evidence is limited.
- 01AICAR (5-aminoimidazole-4-carboxamide ribonucleotide; also called acadesine) is a small-molecule AMP analog that activates AMP-activated protein kinase (AMPK), a central cellular energy-sensing pathway (in vitro / mechanistic).
- 02In sedentary mice, AICAR administration was associated with increased running endurance and a shift toward oxidative metabolism, contributing to its description as an "exercise mimetic" (animal model; Narkar et al., Cell, 2008).
- 03Preclinical work links AMPK activation to increased fatty-acid oxidation and altered glucose uptake in muscle (in vitro / animal model).
- 04Human exposure to acadesine has occurred mainly in cardiovascular/ischemia research contexts; robust human evidence for body-weight or fat-loss endpoints is not established (human studies limited to other contexts).
- 05AICAR is listed on the World Anti-Doping Agency (WADA) Prohibited List as a metabolic modulator.
Evidence maturity varies by compound; much peptide research is preclinical (in vitro or animal-model). Where human data are limited, findings should be read as research observations, not clinical conclusions.
References
Literature references
Published research articles and sources related to AICAR.
- 01U.S. Anti-Doping Agency (USADA) — What Athletes Should Know About AICAR and Other Prohibited AMPK Activated Protein Kinase Activators (official guidance, 2022) View Sourceet al. (2022)
- 02PubMed — Doping control study of AICAR; endurance enhancement in sedentary animals (Drug Testing and Analysis, 2017) View Sourceet al. (2017)
- 03PMC (PubMed Central) — AICAR treatment for 14 days normalizes obesity-induced dysregulation in skeletal muscle (Am. J. Physiol., 2010) View Sourceet al. (2010)
- 04MDPI (International Journal of Molecular Sciences) — AICAR prevents and reverses diabetic polyneuropathy by regulating mitophagy (2024) View Sourceet al. (2024)
- 05PubMed — Acadesine (AICAR) Phase I/II study; maximum tolerated dose 210 mg/kg IV (Cancer Chemotherapy and Pharmacology, 2013) View Sourceet al. (2013)
- 06Cell Signaling Technology — AICAR (Acadesine) Product Data Sheet; AMPK activation mechanism and cellular effects (2021) View Sourceet al. (2021)
- 07JAMA Network — Effect of adenosine-regulating agent acadesine in cardiac surgery; IV infusion protocol (JAMA, 1997) View Sourceet al. (1997)
- 08Endocrinology (Oxford University Press) — AICAR stimulates fatty acid oxidation via β-adrenergic pathway in skeletal muscle View Source
- 09PMC — AICAR enhances glucose transport and mitochondrial function in muscle cells View Source
- 10NCBI Bookshelf — Best practices for injection procedures; asepsis, preparation, and administration guidelines View Source
- 11MedlinePlus Medical Encyclopedia — Subcutaneous (SQ) injections: patient instructions for proper technique and site rotation (NIH, 2023) View Sourceet al. (2023)
- 12CDC — Vaccine administration: subcutaneous route guidelines (angle, site selection, no aspiration) View Source
- 13PMC — Pharmacologic considerations of subcutaneous drug injection; bioavailability and technique review View Source
- 14Pure Lab Peptides — AICAR 50mg product specification and storage instructions; quality documentation (2025) View Sourceet al. (2025)
- 15Biolog Life Science Institute — Technical Information about AICAR-5′-MP (AICA Ribonucleotide); stability and handling (2018) View Sourceet al. (2018)
Research Considerations
Research considerations
Research Use Only - not for human or veterinary therapeutic use. Current evidence is limited to in vitro and/or animal-model research; human data are minimal or absent. Consult a licensed healthcare professional for any clinical decisions.
Factors noted in the research literature; not patient-specific medical advice.
Regulatory Status
Regulatory status
RUO
Comparisons
Comparisons
| Compound | Mechanism | Route | Status |
|---|---|---|---|
| AICARthis | A cell-permeable nucleoside phosphorylated intracellularly to ZMP, an AMP-mimetic that activates AMP-activated protein kinase (AMPK), shifting cells toward oxidative metabolism. | subcutaneous | Investigational / RUO |
| AOD-9604 | Stimulates lipolysis and inhibits lipogenesis. Fragment retains fat-reducing properties without metabolic side effects of full GH. | subcutaneous | Investigational / RUO |
| Cagrilintide | A long-acting acylated amylin analog that activates central amylin (calcitonin-family) receptors to promote satiety and slow gastric emptying. | subcutaneous | Investigational / RUO |
| L-Carnitine | An amino acid derivative essential for transporting long-chain fatty acids into mitochondria for beta-oxidation and energy production. | subcutaneous | Investigational / RUO |
| Mazdutide | A long-acting dual agonist of GLP-1 and glucagon receptors, combining GLP-1 appetite/glycemic signaling with glucagon-mediated energy expenditure. | subcutaneous | Investigational / RUO |
| Ara-290 | An 11-amino-acid non-erythropoietic peptide derived from erythropoietin's helix-B domain that selectively activates the innate repair receptor (an EPOR/CD131 heterocomplex), studied for tissue protection and resolution of inflammation. | subcutaneous | Investigational / RUO |
| BPC-157 | Promotes angiogenesis, accelerates wound healing, and protects organs. Interacts with growth hormone receptors and NO system. | subcutaneous, intramuscular | Investigational / RUO |
Attributes shown for research comparison only; not a statement of efficacy or therapeutic equivalence.
FAQ
Frequently asked questions
No. AICAR is a small-molecule nucleotide (AMP) analog, not a peptide. It is grouped here for its studied role in energy metabolism.
Research describes AICAR as an AMPK activator that mimics a low-energy cellular state, which in preclinical models is associated with increased oxidative metabolism. This is a mechanistic description, not a therapeutic claim.
Metabolic and endurance findings are largely preclinical (rodent and cell models). Human data exist mainly from unrelated cardiovascular research, so weight-related conclusions in humans are not supported.
No. AICAR appears on the WADA Prohibited List, so it is banned in regulated competition.
As a small-molecule research chemical, handling follows the supplier certificate of analysis and protocol reference (typically dry, cool storage). This is laboratory handling information, not human-use guidance.
AICAR is not an approved weight-management drug; it is handled as a research-use-only compound and is prohibited in sport.
Research-use notice
Research Use Only. This educational content and calculation support is intended for private research documentation. It does not provide medical advice, human-use directions, or claims of safety or effectiveness.