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AICAR (Acadesine)Small moleculeNo amino acid sequence. Icon reflects category theme only.Also known as: acadesine, AICA ribonucleoside, ZMP precursor
Sedentary mice ran 44% farther after receiving AICAR for just a few weeks. That 2008 Cell paper by Narkar and colleagues turned this cardiac surgery leftover into the most talked-about "exercise in a pill" candidate in metabolic research. AICAR (5-aminoimidazole-4-carboxamide ribonucleoside, also called acadesine) activates AMP-activated protein kinase, the same metabolic switch that fires during exercise. WADA banned it in 2009. The catch is stark: those mouse doses were 500x higher than what the community injects subcutaneously. No human efficacy trial exists for this route. Users still run short 14-day cycles for metabolic support and fat oxidation, but expectations should match that evidence gap.
AICAR (5-aminoimidazole-4-carboxamide ribonucleoside, also known as acadesine, CAS 2627-69-2) is a cell-permeable nucleoside analog that directly activates AMPK, the same energy sensor that exercise triggers. The Narkar study in Cell [1] made headlines: 44% boost in running endurance without a single training session. It enters cells through adenosine transporters. Once inside, adenosine kinase converts it into ZMP, a compound that mimics AMP and directly activates AMPK. That triggers the same metabolic cascades that exercise does: fatty acid oxidation ramps up, glucose uptake increases, mitochondrial biogenesis kicks in. The compound had an earlier career in cardiology. PeriCor Therapeutics tested it intravenously in over 4,000 cardiac surgery patients during the 1990s [2]. That program ended after a Phase III futility analysis in 2010. Interest shifted entirely toward exercise mimicry, and AICAR became notorious in professional cycling. Reports during the 2013 and 2019 Tour de France alleged riders were using powdered AICAR as a performance booster. WADA had already placed it on the Prohibited List in 2009. Community users inject 10 to 50 mg subcutaneously in short 14-day cycles. The dose gap deserves stating plainly. Mouse efficacy studies used 300 to 500 mg/kg per day. For a 70 kg human, community doses land around 0.14 to 0.7 mg/kg. That is a 500 to 3,500x difference. A 2021 systematic review in Cells [3] confirmed AICAR has documented AMPK-independent effects too, which complicates the picture further. Research status sits at well-researched for the mechanism, but zero completed human efficacy trials exist for subcutaneous administration.
AICAR enters cells through adenosine transporters because its structure looks enough like adenosine to use the same channels. Once intracellular, adenosine kinase phosphorylates it into ZMP (also called AICA ribotide). ZMP binds the gamma subunit of AMPK allosterically, and the kinase complex activates. This is the exact energy-sensing pathway that fires when ATP drops during exercise and AMP accumulates. Downstream, activated AMPK hits several targets simultaneously. It pushes GLUT4 to the cell membrane, pulling glucose into skeletal muscle independent of insulin. It phosphorylates acetyl-CoA carboxylase, which drops malonyl-CoA levels and unlocks mitochondrial fatty acid beta-oxidation. AMPK also turns on PGC-1alpha signaling. That drives mitochondrial biogenesis and shifts muscle fiber type toward slow-twitch (type I); the same remodeling happens with endurance training over months. AICAR also acts through pathways that have nothing to do with AMPK. ZMP inhibits fructose-1,6-bisphosphatase and other enzymes in purine biosynthesis. It competes with adenosine for nucleoside transporters, raising extracellular adenosine concentrations and activating adenosine receptor signaling. A 2018 study confirmed AICAR activates tumor suppressors LATS1 and LATS2 through an AMPK-independent mechanism entirely [4]. These off-target effects matter because they make predicting what AICAR actually does at any given dose much harder.
Strong AMPK activator with well-documented metabolic effects in animals. No completed human efficacy trials for SC use. IV data from cardiac surgery trials showed safety but not efficacy for the studied indication.
Narkar et al. 2008 (PMID 18674809): AICAR increased running endurance 44% in sedentary mice. Confirmed in aged mice by 2025 FASEB BioAdvances study (PMC11886611) showing reversed age-related exercise decline.
All efficacy data is from animal models. The gap between mouse doses (300-500 mg/kg) and community SC doses (0.14-0.7 mg/kg for a 70 kg human) is enormous: roughly 500-3,500x lower. No human PK data exists for SC administration. Significant AMPK-independent effects complicate interpretation of what AICAR actually does at any given dose.
Niche compound with a small but dedicated following. Most users treat it as a metabolic booster or "rest day recovery" tool rather than a primary exercise replacement. Mixed reports on whether subcutaneous doses produce meaningful effects.
Science and community agree AICAR activates AMPK and affects metabolism. But the dose gap is the elephant in the room: mouse studies use 300-500 mg/kg, while humans inject 10-50 mg total. That's a >500x difference even after basic allometric scaling. Community effects at these doses may be real but are likely much weaker than what the mouse data suggests. The science can't confirm or deny community-dose efficacy because nobody has studied it.
| Level | Dose / Injection | Frequency |
|---|---|---|
| Beginner | 10mg | Daily |
| Moderate | 25mg | Daily |
| Aggressive | 50mg | EOD |
AICAR comes as a lyophilized powder, typically in 50 mg vials. Add 2 mL of bacteriostatic water and you get 25 mg/mL concentration. Reconstitution math: at 25 mg/mL, a 10 mg dose is 0.4 mL (40 units on an insulin syringe). A 25 mg dose is 1.0 mL (100 units, a full syringe). The 50 mg aggressive dose uses the entire 2 mL vial per shot; split across two sites or grab a larger syringe. Morning dosing, fasted, aligns with natural metabolic rhythms and the fasted state amplifies AMPK signaling. On training days, inject 30 to 60 minutes before cardio. Cost adds up fast and that's the thing most beginners miss. A 14-day beginner cycle at 10 mg/day runs through about 3 vials ($150 to $195). The intermediate 25 mg/day protocol burns 7 vials ($350 to $455). Budget before you buy. Hydration matters here more than with most compounds. Your kidneys are doing the clearing. Three liters of water daily is the community standard during active cycles. AICAR is not a peptide; it's a small molecule nucleoside analog. It degrades with moisture faster than typical peptides, so keep lyophilized powder dry.
AICAR should not be used for longer than 14 consecutive days due to accumulation toxicity and renal stress risk. Allow at least 4-8 weeks of washout between cycles. No more than 3 cycles per year. Monitor kidney function and uric acid levels during use.
The 14-day max cycle isn't about receptor desensitization: AMPK doesn't desensitize the way hormone receptors do. It's about accumulation toxicity. AICAR's metabolite ZMP builds up with repeated dosing, and the kidneys bear the clearance burden. Chronic AMPK overactivation also has theoretical downsides: FoxO3-mediated muscle autophagy, cardiac hypertrophy, and disrupted normal energy sensing. The 4-8 week washout gives your kidneys time to fully clear metabolites and lets uric acid levels normalize.
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Expected: Subtle increase in energy, mild improvement in fasted exercise tolerance. Fat loss effects minimal at this dose over 2 weeks.
Monitor: Check uric acid and basic metabolic panel before starting and after the cycle.
Aim the stream at the glass wall, not directly into the powder. Swirl gently until fully dissolved. Solution should be clear and colorless.
At 25 mg/mL concentration: 10 mg equals 40 units, 25 mg equals 100 units (full syringe), 50 mg equals 200 units (use two syringes or a 3 mL syringe for the full vial).
Abdomen (two inches from the navel), thigh, or upper arm all work. Rotate sites each day to prevent lipohypertrophy.
Pinch the skin and insert the needle at a 45 to 90 degree angle. Inject slowly over 15 to 30 seconds. For larger volumes (1 mL or more), steady pressure over 30 to 60 seconds reduces lumps. Remove needle and apply light pressure with a cotton ball.
Warming the syringe in your hand for 30 seconds before injecting makes it more comfortable.
Use within 14 days. Do not freeze the reconstituted solution.
Timing: morning, fasted. On training days, 30 to 60 minutes before exercise. Stay well-hydrated (3+ liters daily) throughout your cycle.
Both are mitochondrial-targeted metabolic modulators but work through different mechanisms. MOTS-c activates AMPK through a distinct pathway and also regulates the methionine-folate cycle. Stacking hits AMPK from two angles. Don't overlap active cycles: run sequentially or alternate weeks.
AICAR 14-day cycle, then MOTS-c cycle during AICAR washout
NAD+ supports mitochondrial function and SIRT1 activation, which synergizes with AMPK activation. The AMPK-SIRT1-PGC1α axis is a well-documented metabolic signaling cascade. NAD+ precursors can be taken concurrently.
SS-31 targets mitochondrial cardiolipin and improves electron transport chain efficiency. Combined with AICAR's mitochondrial biogenesis effects, this creates complementary mitochondrial support.
Both activate AMPK. Stacking creates additive AMPK stimulation that may cause excessive glucose lowering or lactic acidosis. This is a pharmacological interaction, not a theoretical one.
Do not combineAICAR improves insulin sensitivity and glucose uptake. Combined with insulin or insulin secretagogues, hypoglycemia risk increases significantly.
Do not combineAICAR raises extracellular adenosine levels by competing for nucleoside transporters. Adenosine receptor agonists on top could amplify cardiovascular effects (hypotension, bradycardia).
Pricing updated 2026-04-09
Hyperuricemia is the side effect that demands the most attention. AICAR elevates uric acid levels, and at higher doses this can trigger gout flares with sudden joint pain and swelling. If that happens mid-cycle, check uric acid immediately. Don't push through it. Prophylactic allopurinol (100 to 300 mg daily) is commonly co-administered in community protocols running 25 mg or above. Kidney stress is the second serious concern. AICAR and its metabolite ZMP are renally cleared. Even at community subcutaneous doses (10 to 50 mg/day), the kidneys carry the full clearance burden. The 14-day cycle limit exists specifically because of accumulation toxicity risk, not receptor desensitization. Creatinine trending upward on mid-cycle labs is a stop signal; don't wait for symptoms. In the cardiac surgery IV trials [2], which used doses up to 210 mg/kg, researchers documented transient anemia and thrombocytopenia. Those doses dwarf community SC protocols. Monitoring CBC on aggressive cycles is still reasonable practice. Hypoglycemia is a real possibility during fasted use. AMPK activation drives glucose uptake independent of insulin through GLUT4 translocation. Stacking fasted training with AICAR, or combining it with metformin, creates additive glucose-lowering. Keep glucose tabs on hand. GI effects show up in some users: nausea, bloating, abdominal discomfort. These tend to be mild and dose-dependent. Injection site reactions (redness, swelling, lumps) are common, especially at higher volumes. Splitting a 1 to 2 mL dose across two sites reduces discomfort. Fatigue in the first two to three days trips up newcomers. AMPK activation shifts metabolism toward fat oxidation and away from glycolytic power output. Feeling more tired rather than energized early on is normal. If that tiredness hasn't resolved by day four, lower the dose or stop the cycle. One theoretical concern: chronic AMPK overactivation may promote muscle atrophy through FoxO3-mediated autophagy. This hasn't been documented at community doses. It is, however, the rationale behind keeping cycles short and washouts long. Contraindications: pregnancy or breastfeeding (zero reproductive safety data), chronic kidney disease, active gout or hyperuricemia, hypoglycemia without medical supervision, children under 18, active malignancy (AMPK has context-dependent effects on tumor growth), and competitive athletes subject to WADA testing.
Verify AICAR (Acadesine) dosing and safety with a second opinion
AICAR is a small molecule nucleoside analog, not a peptide, so it's synthesized chemically, not through solid-phase peptide synthesis. Purity varies significantly between suppliers. The compound is hygroscopic (absorbs moisture), making storage and handling important. Because it's WADA-banned and research-only, there's no pharmaceutical-grade reference standard for consumer products. Underdosing and contamination are both real concerns in the research chemical market.
| Test | When | Target |
|---|---|---|
| Uric acid | Baseline, day 7, and 1 week post-cycle | Below 7.0 mg/dL (male) / 6.0 mg/dL (female). Stop if above 9.0 mg/dL. |
| Basic metabolic panel (BUN, creatinine) | Baseline, day 7, and 1 week post-cycle | Creatinine within normal limits for your baseline. Any upward trend warrants stopping. |
| Fasting blood glucose | Baseline and day 7 | 70-100 mg/dL. Watch for symptoms below 70. |
| CBC (complete blood count) | Baseline and post-cycle (advanced protocol only) | — |
Hyperuricemia is the most common side effect. Catching elevated levels early prevents gout flares and renal complications.
AICAR and ZMP are renally cleared. Even at community doses, kidney stress is the primary safety concern.
AMPK activation drives insulin-independent glucose uptake. Hypoglycemia risk is real, especially if stacking with metformin or fasting protocols.
Transient anemia and thrombocytopenia were observed at high IV doses in clinical trials. Unlikely at community SC doses but worth checking on aggressive protocols.
AMPK activation begins at the cellular level. No outward changes are expected yet. Some users report a subtle increase in energy or warmth. Monitor injection sites for reactions.
Fatty acid oxidation rates start to increase. Mild improvements in exercise tolerance may become noticeable. Blood glucose may trend slightly lower in insulin-resistant subjects. Uric acid levels should be monitored.
Peak metabolic effects within a 14-day cycle. Endurance and fat metabolism improvements are most pronounced. Animal data showed 44% endurance gains at comparable timepoints. Body composition shifts may become measurable.
Final days of the recommended cycle window. Cumulative AMPK activation should be at its highest. Discontinue at day 14 to prevent accumulation-related side effects. Benefits persist for several days after the last dose.
Metabolic benefits gradually return to baseline over 1-2 weeks. AMPK activity normalizes as ZMP clears. Maintain exercise and dietary habits gained during the cycle. Wait at least 4-8 weeks before considering another cycle.
Days 1 through 3 (AMPK activation begins): ZMP starts accumulating inside cells within hours of each injection. AMPK phosphorylation ramps up and metabolic gene expression begins shifting. Some users pick up a subtle warmth or mild energy bump. Others actually feel more tired, which tracks; your metabolism is being pushed toward fat oxidation and away from quick glycolytic output. Injection site redness is common and not a reason to stop. Days 4 through 7 (Metabolic shift): Fatty acid oxidation rates climb. GLUT4 translocation means greater glucose uptake in muscle tissue. Mitochondrial biogenesis genes are being upregulated. Community reports point to better exercise tolerance, especially during cardio. Blood sugar may trend lower. Get uric acid labs at day 7 if you're running 25 mg or above; this is where side effects start showing up on paper before you feel them. Days 8 through 14 (Peak effects): Strongest window in a 14-day cycle. Cumulative AMPK activation hits its highest point. In aged mice, measurable improvements in exercise performance and muscle gene expression showed up at this stage. Community users call this the period where the protocol feels like it's working. Stop at day 14. This is also the highest-risk window for uric acid spikes and kidney stress, so monitoring matters most right now. Weeks 1 through 2 off (Washout begins): ZMP clears within days given the 2 to 3 hour plasma half-life. AMPK activity drifts back to baseline. Mitochondrial adaptations from the cycle (biogenesis, fiber type shifts) may hang around a bit longer if you kept training. Most users feel benefits tapering over one to two weeks. Weeks 3 through 8 off (Full washout): Complete metabolic normalization. Most users report feeling back to baseline by week three or four. This washout period exists for kidney recovery and uric acid normalization, not because AMPK needs a rest. Four weeks minimum before another cycle; longer is better for renal health.
Intracellular ZMP accumulates and AMPK phosphorylation increases within hours of each dose. Metabolic gene expression starts shifting.
Some users notice a subtle warmth or energy bump. Others feel more tired than usual as metabolism shifts. Injection site redness is common.
Fatty acid oxidation rates should be increasing. GLUT4 translocation drives greater glucose uptake in muscle. Mitochondrial biogenesis genes are upregulated.
Improved exercise tolerance starts showing up, especially in cardio. Blood sugar may trend lower. Some fat loss visible in users with good baseline conditioning.
Maximum cumulative AMPK activation. In aged mice, significant improvements in exercise performance and muscle gene expression were measurable by this point.
Best endurance gains reported in this window. Body composition improvements peak. This is where most users feel the protocol is "working." Stop at day 14.
ZMP clears within days given the 2-3 hour half-life. AMPK activity returns to baseline. Metabolic adaptations from the cycle (mitochondrial biogenesis) may persist longer.
Benefits taper off over 1-2 weeks. Some users report maintained endurance if they kept training during the cycle. Energy and body composition gradually return to baseline.
Complete metabolic normalization. Any mitochondrial gains from a 14-day cycle are likely modest and transient without ongoing exercise stimulus.
Most users feel back to baseline by week 3-4. This is the minimum recommended washout before another cycle. Longer is better for kidney recovery.
Source: Estimated from clinical pharmacokinetic data in cardiac surgery patients. AICAR has a short plasma half-life due to rapid cellular uptake and phosphorylation to ZMP. Intracellular ZMP persists longer (PMID 7818622).
Loading the interactive decay curve.
AICAR is classified as a research chemical. It has no FDA approval for any therapeutic indication. The cardiac surgery program (acadesine IV for myocardial ischemia) was abandoned after a Phase III futility analysis in 2010. No new regulatory applications are pending. WADA placed AICAR on the Prohibited List in 2009 under Section S4: Hormone and Metabolic Modulators. It remains banned in-competition and out-of-competition. Anti-doping laboratories have validated specific detection methods for AICAR and its metabolite ZMP in urine [6]. Any athlete subject to anti-doping testing should treat AICAR as a hard disqualification risk. AICAR is available from research chemical suppliers in lyophilized form, typically sold for research purposes only. It is not available through compounding pharmacies. Regulatory status may differ outside the US; check local laws before purchasing. This content is for educational and informational purposes only. It does not constitute medical advice. Consult a licensed healthcare provider before using any research compound. Peptide Schedule does not sell peptides or endorse self-administration.
Peptide Schedule Research TeamReviewed Apr 20267 Citations
