AICAR

Structure: A nucleoside analog, not a peptide. It is taken up by cells via adenosine transporters and phosphorylated by adenosine kinase to ZMP, which mimics AMP closely enough to allosterically activate AMP-activated protein kinase (AMPK), the cell's low-energy sensor. Activating AMPK pharmacologically is meant to reproduce the metabolic signature of exercise without the exercise.

Dosage:

• There is no established human dose for performance. The only substantial human exposure was as acadesine, given intravenously at gram quantities during cardiac surgery.
• Grey-market protocols typically quote 30-60mg SubQ daily, sometimes higher, extrapolated loosely from the mouse work.
• The mouse study used 500mg/kg per day by intraperitoneal injection. Even applying conservative interspecies scaling, the human-equivalent exposure is orders of magnitude above what people actually inject, and would run to grams per day at a cost that makes the protocol unrealistic. This gap is the most useful single fact about AICAR: most users are dosing far below anything shown to do anything.

Administration:

• SubQ or IM injection for the research chemical form
• Oral bioavailability is poor (in the region of 5%), so oral products are a further step away from meaningful exposure
• Short plasma half-life means daily or twice-daily dosing in most protocols

Key Notes:

• The origin story oversells it. The 2008 Cell paper by Narkar and colleagues showed sedentary mice given AICAR for four weeks ran substantially longer than controls, and the press coverage christened it exercise in a pill. It was a genuinely important paper about AMPK and PPAR-delta biology. It was not a demonstration that a human can inject a few milligrams and gain endurance.
• There are no human performance trials. None. The human clinical record is acadesine given intravenously for myocardial protection during coronary artery bypass surgery, and the large Phase 3 trial in that setting did not meet its primary endpoint. Nothing in that programme speaks to endurance, body composition, or fat loss in a healthy trained adult.
• WADA prohibits it at all times under S4 (hormone and metabolic modulators). If you compete in any tested federation, this ends your career, and it is specifically named rather than caught by a catch-all clause.
• The cancer signalling question is worth stating honestly. AMPK sits downstream of the tumour suppressor LKB1 and is classically described as tumour-suppressive, which is where the "AMPK activation is protective" framing comes from. The more recent literature is less tidy: in established tumours, AMPK activation can be cytoprotective, helping cancer cells survive nutrient deprivation and hypoxia. Chronic pharmacological AMPK activation in a healthy person is therefore not unambiguously safe, and the direction of the effect appears to depend on context. This is an open question, not an established danger, but it is not nothing either.
• It actively opposes what most users want. AMPK activation inhibits mTORC1, the central node of muscle protein synthesis. Running a chronic AMPK activator during a mass phase, or alongside anabolics whose entire point is mTOR-driven hypertrophy, is working against yourself. If you are using AICAR at all, the coherent time to use it is a cut, not a bulk.
• Hypoglycaemia is plausible given increased glucose uptake, particularly if dosed fasted, before cardio, or alongside exogenous insulin or Metformin, which activates AMPK by a different route.
• Source quality is unverifiable and the compound is expensive to produce in real quantities, which creates an obvious incentive to underdose.

Bloodwork Monitoring:

• Glucose: the practical one. AMPK activation increases glucose disposal, so check fasting glucose and use a glucometer if dosing around fasted training.
• Uric Acid: AICAR is an intermediate in de novo purine synthesis, and dosing increases purine turnover. A rising uric acid on AICAR is mechanistically expected, and it matters if you have any gout history or are already running compounds that raise it.
• ALT and AST: baseline and follow-up. The liver is a primary site of AMPK action and there is no long-term human safety data to reassure you here.
• Creatinine and eGFR: include them, both because of the purine load and because there is no chronic dosing safety record at all.
• HbA1c, Insulin and HOMA-IR: if the theory is that AICAR improves insulin sensitivity, these are the markers that would show it. In practice, most users see nothing, which is informative.
• Lactate is raised by intravenous acadesine in clinical studies. It is not a routine panel marker, but unexplained exercise intolerance or unusual lactate response is worth noting if you are dosing high.