MEDICAL DISCLAIMER: Educational research guidelines only. Lyophilized peptides are investigational chemical compounds and are NOT approved for human consumption, diagnosis, or therapy. Consult a licensed physician before any research application.
AICAR Dosage Chart, Schedule & Reconstitution Protocol
Quickstart Highlights
AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) is an adenosine analog that is phosphorylated intracellularly to ZMP, an AMP mimetic that allosterically activates AMP-activated protein kinase (AMPK) without altering cellular ATP or AMP levels. AMPK activation drives glucose uptake, fatty acid oxidation, mitochondrial biogenesis, and a shift toward slow-twitch oxidative muscle fiber gene programs. Narkar and colleagues' 2008 Cell paper demonstrated that sedentary mice given AICAR for four weeks showed approximately 44 percent improvement in running endurance, an effect that established AICAR as the prototype pharmacologic exercise mimetic [PMID: 18674809]. It is studied for metabolic disease, insulin resistance, ischemia-reperfusion protection, and rare metabolic indications such as AICA-ribosiduria. AICAR has been on the WADA Prohibited List as a metabolic modulator since 2011 and has limited clinical use; human data come mostly from short metabolic and cardiac studies.
Reconstitute: Add 3 mL bacteriostatic water → 16.7 mg/mL concentration.
Easy measuring: At 16.7 mg/mL, 1 unit = 0.01 mL = 0.167 mg (167 mcg) on a U-100 insulin syringe.
Storage: Lyophilized frozen at −20 °C; reconstituted refrigerated 2–8 °C for up to 4 weeks[14].
WADA banned (S4 class): AICAR is explicitly prohibited in and out of competition under WADA's S4 hormone and metabolic modulators category. Detection is routine in elite endurance athlete urine screens.
Short half-life, high doses: Plasma half-life is roughly 30 minutes, and rodent exercise-mimetic dosing translates to gram-scale human equivalents. Published human cardiac protection trials used 0.1 mg/kg/min IV infusions, not chronic dosing.
Hyperuricemia and lactic acidosis risk: Because ZMP is metabolized through the purine and adenosine pathways, AICAR can elevate uric acid, trigger gout flares, and at high doses produce lactic acidosis. It is not benign at exercise-mimetic doses.
Quick Protocol Navigation
Reconstitution Instruction & Mixing Step-by-Step
Lyophilized powder must be reconstituted carefully. Agitating peptide chains can shear disulfide bonds and render the peptide biologically inert.
Draw 3.0 mL bacteriostatic water with a sterile syringe.
Inject slowly down the vial wall; avoid foaming.
Gently swirl/roll until dissolved (do not shake).
Inject slowly; wait a few seconds before withdrawing the needle.
Inject slowly and steadily; do not aspirate for subcutaneous injections[12].
Interactive AICAR Syringe Calculator
Currently visualizing the 50 mg vial reconstituted with 3 mL bacteriostatic water. Adjust the target dose to dynamically render syringe units.
Reconstitution Calculation: 50mg dry powder in 3mL water yields 16.67 mg/mL. To evaluate a 250mcg dose, pull to 1.5 units (2 syringe ticks).
U-100 Syringe Representation
1.5 Units (2 Ticks)
Educational reference visual. Assumes standard U-100 insulin syringe where 1.0 mL volume = 100 units.
Titration & Dose Escalation Schedules
| Week/Phase | Daily Dose | Units (per injection) (mL) |
|---|---|---|
| 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) |
Administration guidelines: Refer to guidelines | 3 mL Reconstitution
| Week/Phase | Daily Dose | Units (per injection) (mL) |
|---|---|---|
| Weeks 1–2 | 2,000 mcg (2 mg) | 12 units (0.12 mL) |
| Weeks 3–6 | 3,000 mcg (3 mg) | 18 units (0.18 mL) |
| Weeks 7–12 | 5,000 mcg (5 mg) | 30 units (0.30 mL) |
Administration guidelines: Refer to guidelines | 3 mL Reconstitution
Research Supplies Quantity Planner
Scientific mathematical planning of syringes, bacteriostatic water and dry vials needed for extended research blocks using the 50 mg vial.
Peptide Vials (AICAR, 50 mg each):
- check8 weeks (gradual 1–3 mg/day) ≈ 3 vials
- check12 weeks (2–5 mg/day advanced) ≈ 8 vials
Insulin Syringes (U-100, or 30/50-unit for precision):
- checkPer week: 7 syringes (1/day)
- check8 weeks: 56 syringes
- check12 weeks: 84 syringes
Bacteriostatic Water (10 mL bottles): Use 3.0 mL per vial for reconstitution.
- check8 weeks (3 vials): 9 mL → 1 × 10 mL bottle
- check12 weeks (8 vials): 24 mL → 3 × 10 mL bottles
Alcohol Swabs: One for the vial stopper + one for the injection site each day.
- checkPer week: 14 swabs (2/day)
- check8 weeks: 112 swabs → recommend 2 × 100-count boxes
- check12 weeks: 168 swabs → recommend 2 × 100-count boxes
Mechanism of Action (MOA)
AICAR (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside), also called acadesine and originally developed as a cardioprotective agent under the brand name Arasine, is a cell-permeable nucleoside that enters cells through adenosine transporters and is phosphorylated by adenosine kinase to AICA-ribotide (ZMP). ZMP is a structural and functional mimetic of cellular AMP and binds to the γ subunit of AMP-activated protein kinase (AMPK), driving allosteric activation and promoting phosphorylation at Thr172 in the α subunit by upstream kinases including LKB1 [1]. AMPK is the master cellular energy sensor that responds to falling ATP and rising AMP and ADP by switching cellular metabolism away from ATP-consuming anabolic processes toward ATP-generating catabolic pathways. Activated AMPK phosphorylates more than fifty substrates, including acetyl-CoA carboxylase (inhibiting fatty acid synthesis and de-repressing β-oxidation), HMG-CoA reductase (inhibiting cholesterol synthesis), TSC2 (inhibiting mTORC1), TBC1D1 and AS160 (promoting GLUT4 translocation and glucose uptake), and PGC-1α (driving mitochondrial biogenesis and oxidative gene expression). The net effect of sustained AMPK activation is increased fatty acid oxidation, glucose uptake, mitochondrial content, and oxidative capacity—a metabolic phenotype that overlaps substantially with the response to endurance exercise [2]. Narkar and colleagues published a landmark 2008 study in Cell demonstrating that four weeks of AICAR administration at 500 mg/kg/day to sedentary mice increased treadmill running endurance by approximately 44 percent and induced expression of oxidative metabolism genes in skeletal muscle. They further showed that combining AICAR with a PPARδ agonist (GW501516) produced additive endurance benefits, establishing the concept of pharmacological exercise mimetics and prompting the World Anti-Doping Agency to formally prohibit AICAR as an anabolic-metabolic modulator in 2009 [3]. In humans, intravenous acadesine has been studied in two principal clinical contexts. In coronary artery bypass surgery, acadesine infusions at 0.1 mg/kg/min for approximately seven hours (totaling 42 mg/kg) demonstrated cardioprotective effects against ischemia-reperfusion injury in early phase trials, although a large definitive Phase III program failed to confirm survival benefit and the drug was not advanced [4]. In acute myeloid leukemia and chronic lymphocytic leukemia, acadesine produces apoptosis of malignant cells through AMPK activation and has been investigated in Phase I/II trials at intravenous doses up to 210 mg/kg over four hours. Outside these supervised intravenous research contexts, AICAR has been adopted by athletic and biohacking communities at subcutaneous research doses of approximately 10–50 mg per session, often two to five times per week. There is no published human pharmacokinetic, safety, or efficacy data for chronic subcutaneous AICAR at these doses, and the rationale for self-administration rests entirely on rodent endurance data and theoretical AMPK-mediated metabolic benefits. Importantly, AICAR has substantial AMPK-independent effects, including activation of glycogen synthase, modulation of adenosine signaling, and direct effects on purine metabolism, complicating interpretation of any biological response and contributing to its variable side-effect profile [2].
Clinical Trial Efficacy Highlights
- starNarkar and colleagues (Cell 2008) demonstrated that four weeks of AICAR administration at 500 mg/kg/day to sedentary mice increased treadmill running endurance by approximately 44 percent and induced expression of oxidative metabolism genes in skeletal muscle, providing the foundational rodent evidence supporting AICAR's classification as a pharmacological exercise mimetic [3].
- starMengozzi and colleagues investigated intravenous acadesine at 0.1 mg/kg/min during and after coronary artery bypass grafting and reported reductions in postoperative myocardial infarction, ventricular tachyarrhythmia, and cardiac death in pooled meta-analyses of early-phase trials, although a definitive Phase III RED-CABG study failed to confirm a survival benefit [4].
- starPhase I/II oncology studies of intravenous acadesine in chronic lymphocytic leukemia and acute myeloid leukemia demonstrated dose-dependent induction of apoptosis in circulating malignant lymphocytes and acceptable short-term safety at doses up to 210 mg/kg over four-hour infusions, supporting ongoing investigation of AICAR-class compounds in hematologic malignancy [1].
- starMechanistic studies show that AICAR activates AMPK in skeletal muscle, liver, adipose tissue, and pancreatic beta cells; downstream effects include GLUT4 translocation, increased fatty acid oxidation, suppression of hepatic glucose output, and improved insulin sensitivity in rodent models of type 2 diabetes and metabolic syndrome [2].
- starVisnjic and colleagues' 2021 systematic review documented over four decades of AICAR research and highlighted that many reported biological effects involve AMPK-independent mechanisms, including direct modulation of purine metabolism, glycogen synthase activation, and adenosine receptor signaling, complicating clinical interpretation and underscoring the need for selective AMPK activators [2].
- starDespite robust preclinical data and decades of pharmacological investigation, AICAR has not been approved for any chronic indication in humans, and chronic subcutaneous self-administration lacks pharmacokinetic, safety, or efficacy validation; the World Anti-Doping Agency prohibits AICAR in competitive sport as an anabolic-metabolic modulator [3].
Side Effects & Tolerability Profile
Clinical subjects transiently report mild side effects. Slowly escalating the titration dose represents the single most effective intervention to limit side effects.
- warningIntravenous acadesine in clinical trials has been associated with transient hypotension, headache, dizziness, nausea, and reductions in serum uric acid; high doses can produce significant lactic acidosis through AMPK-mediated changes in substrate utilization.
- warningAICAR can produce hypoglycemia, particularly when combined with insulin, sulfonylureas, or other glucose-lowering agents, due to enhanced peripheral glucose uptake and decreased hepatic glucose output.
- warningHyperuricemia or hypouricemia and reduced renal urate clearance have been reported, and AICAR can cause crystallization of intermediates in the purine salvage pathway, particularly at high parenteral doses.
- warningSubcutaneous self-administration at research doses (10–50 mg) has no published safety data and carries risks of injection-site reactions, infection from non-sterile preparations, and unpredictable systemic exposure due to variable bioavailability.
- warningLong-term effects of chronic AMPK activation are uncharacterized; theoretical concerns include effects on cancer cell metabolism (potentially both protective and promotive depending on context), cardiac remodeling, and bone density.
- warningAICAR is prohibited at all times by the World Anti-Doping Agency, and athletes using AICAR risk competition bans even at low subcutaneous doses; testing methods detect AICAR and its metabolites in urine.
Subcutaneous Injection Technique
Most research peptides require subcutaneous injection into fatty tissue. Never inject directly into a blood vessel or deep muscle tissue unless clinically detailed.
1. Site Selection
Common locations include the abdomen (2 inches from navel), outer upper arms, or thighs.
2. Sanitization
Thoroughly clean the selected site, stopper and vial top using 70% isopropyl alcohol prep swabs.
3. Angle & Push
Pinch the skin and insert the needle at a 45 to 90-degree angle. Depress plunger smoothly.
4. Site Rotation
Rotate injection sites continuously to avoid lipodystrophy or tissue scarring.
Frequently Asked Questions
What is the typical AICAR dosage?expand_more
Clinical IV acadesine has been studied at 0.1 mg/kg/min for several hours (cardiac surgery) and up to 210 mg/kg over four hours (oncology). There is no validated chronic human dose. Research subcutaneous self-administration uses 10–50 mg per session, two to five times weekly, with no safety validation.
How is AICAR administered?expand_more
In published clinical trials AICAR is administered intravenously under medical supervision. Outside formal trials, research subcutaneous self-injection has been used but lacks any pharmacokinetic basis. Oral AICAR has very low bioavailability and is not used clinically.
Can AICAR be combined with other compounds?expand_more
AICAR has been combined experimentally with PPARδ agonists (GW501516) and PGC-1α activators in rodents to enhance endurance effects. Combination with insulin or sulfonylureas increases hypoglycemia risk. Stacking with other unapproved exercise mimetics carries amplified safety risk and is discouraged.
What are the side effects of AICAR?expand_more
IV acadesine causes transient hypotension, headache, nausea, lactic acidosis at high doses, hyperuricemia, and hypoglycemia. Subcutaneous self-administration adds injection-site reactions and infection risk. Long-term safety in humans is uncharacterized.
Is AICAR FDA approved?expand_more
No. AICAR (acadesine) has been studied in cardiac surgery and oncology but has not received FDA approval for any indication. It is sold strictly as a research chemical and is prohibited at all times by the World Anti-Doping Agency for competitive athletes.
Academic References & Study Citations
Corton JM, Gillespie JG, Hawley SA, Hardie DG. 5-Aminoimidazole-4-carboxamide ribonucleoside. A specific method for activating AMP-activated protein kinase in intact cells? Eur J Biochem. 1995;229(2):558-565. View Scientific Paper →
Visnjic D, Lalic H, Dembitz V, Tomic B, Smoljo T. AICAr, a widely used AMPK activator with important AMPK-independent effects: a systematic review. Cells. 2021;10(5):1095. View Scientific Paper →
Narkar VA, Downes M, Yu RT, et al. AMPK and PPARδ agonists are exercise mimetics. Cell. 2008;134(3):405-415. View Scientific Paper →
Mangano DT, Miao Y, Tudor IC, Dietzel C; Investigators of the Multicenter Study of Perioperative Ischemia (McSPI) Research Group; Ischemia Research and Education Foundation (IREF). Post-reperfusion myocardial infarction: long-term survival improvement using adenosine regulation with acadesine. J Am Coll Cardiol. 2006;48(1):206-214. View Scientific Paper →
Hardie DG, Ross FA, Hawley SA. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol. 2012;13(4):251-262. View Scientific Paper →
Winder WW, Holmes BF, Rubink DS, Jensen EB, Chen M, Holloszy JO. Activation of AMP-activated protein kinase increases mitochondrial enzymes in skeletal muscle. J Appl Physiol. 2000;88(6):2219-2226. View Scientific Paper →
Drake JC, Wilson RJ, Yan Z. Molecular mechanisms for mitochondrial adaptation to exercise training in skeletal muscle. FASEB J. 2016;30(1):13-22. View Scientific Paper →
Van Den Neste E, Cazin B, Janssens A, et al. Acadesine for patients with previously treated chronic lymphocytic leukemia: a multicenter phase I/II study. Cancer Chemother Pharmacol. 2013;71(3):581-591. View Scientific Paper →
Newsholme P, Cruzat VF, Keane KN, Carlessi R, de Bittencourt PI Jr. Molecular mechanisms of ROS production and oxidative stress in diabetes. Biochem J. 2016;473(24):4527-4550. View Scientific Paper →