Investigational / not FDA-approved

AICAR

Acadesine (AICA-riboside) — ≠ ZMP; mouse exercise-mimetic ≠ human fitness claim.

Editorial review:

What evidence says

Evidence snapshot

This drawer marks papers. It is not a plan, a dose, or a source. A paper is a bounded report. It is not a protocol. Grades name the object. They are not a safety rating.

Identity lock. “AICAR” in AMPK literature usually means acadesine (5-aminoimidazole-4-carboxamide ribonucleoside / AICA-riboside), a cell-permeable precursor that is phosphorylated intracellularly to ZMP (AICA ribotide). Acadesine PubChem CID 17513; formula C9H14N4O5 / MW 258.23; CAS 2627-69-2. ZMP / AICA ribotide CID 65110; formula C9H15N4O8P / MW 338.21. Do not badge the wrong CID — acadesine ≠ ZMP. AICAR is not a peptide, not 5-Amino-1MQ, and not an approved exercise-mimetic drug for fitness use. Historical acadesine CABG cardioprotection programs and small human metabolic infusion studies are different objects from mouse “exercise mimetic” headlines. Refuse athletic/fitness use language entirely. This drawer marks papers. It is not use advice.

Bottom line

Mouse “exercise mimetic” fame (Narkar 2008) is real as a Cell paper and not a human sports-medicine approval. Small human infusion studies report acute effects on muscle glucose uptake / hepatic glucose output. Acadesine’s large CABG program: an early meta-analysis looked promising; the later RED-CABG trial was stopped for futility (no primary-outcome benefit). Systematic reviews stress AMPK-independent effects of AICAr. Keep RED-CABG beside older meta optimism. Refuse human fitness glow.

Papers

Mouse exercise-mimetic / metabolic preclinical

PMID 18674809 — Narkar 2008

Tested: AMPK agonist AICAR and PPARδ agonists as exercise mimetics on endurance and metabolic gene programs in mice.

Does not show: a human exercise-mimetic indication, or that AICAR is safe/legal for athletic use.

PMID 16901342 — Giri 2006

Tested: AICAR effects on adipocyte differentiation in vitro and metabolic alterations in diet-induced obesity mice.

Does not show: a human weight-loss trial.

PMID 12061777 — Halseth 2002

Tested: acute and chronic AICAR treatment lowering blood glucose in ob/ob and db/db mice.

Does not show: a human diabetes drug approval for AICAR.

Human metabolic / muscle infusion studies (small, acute)

PMID 17513706 — Cuthbertson 2007

Tested: acute AICAR stimulation of skeletal-muscle 2-deoxyglucose uptake in healthy people (with limited whole-body glucose-disposal effect).

Does not show: chronic training replacement, weight-loss efficacy, or an approved metabolic indication.

PMID 19190259 — Babraj 2009

Tested: AICAR-induced human skeletal-muscle glucose uptake in older men with and without type 2 diabetes (age-related blunting framing).

Does not show: a large Phase 3 diabetes outcome trial for AICAR.

PMID 18709353 — Boon 2008

Tested: intravenous AICAR administration effects on hepatic glucose output and whole-body lipolysis in type 2 diabetic patients (acute physiologic study).

Does not show: chronic glycemic control approval or exercise-mimetic licensing.

Acadesine cardioprotection (CABG) — promise then futility

PMID 9002496 — Mangano 1997

Tested: meta-analysis of five international randomized trials of perioperative acadesine on myocardial infarction, stroke, and death after CABG.

Does not show: a final definitive modern CABG standard; later RED-CABG supersedes optimism.

PMID 22782417 — Newman 2012

Tested: RED-CABG — randomized trial of acadesine on a composite of death, stroke, and severe left-ventricular dysfunction after CABG; stopped after futility analysis.

Does not show: cardioprotection benefit on the primary composite (no difference vs placebo).

PMID 18671468 — Drew 2008

Tested: review of acadesine as an adenosine-regulating agent with potential indications.

Does not show: completed modern approval for fitness or metabolic consumer use.

Mechanism caution / secondary

PMID 34064363 — Višnjić 2021

Tested: systematic review of AICAr as a widely used AMPK activator with important AMPK-independent effects.

Does not show: that every AICAR phenotype is AMPK-mediated, or human efficacy for unlabeled use.

What is not established

Any approved exercise-mimetic or body-composition indication. That mouse treadmill papers equal human performance enhancement. That early CABG meta-analysis optimism survived RED-CABG (it did not). Equivalence of acadesine vs ZMP CIDs in product identity badges. Safety/legality for athletic or wellness self-administration. This drawer does not provide use advice, schedules, or sourcing.

Selected sources

18674809 16901342 12061777 17513706 19190259 18709353 9002496 22782417 18671468 34064363

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