AICAR

The AICAR evidence base cited here is 7 sources — 4 preclinical, 2 review. Critically, that evidence is almost entirely preclinical (animal and in-vitro) — no human clinical trials are cited, so efficacy and safety in people remain unproven. Regulatory status: Not FDA-approved.

• Narkar et al. (Cell, 2008) demonstrated that 4 weeks of AICAR in sedentary mice enhanced treadmill running endurance by 44% and upregulated oxidative metabolism genes in skeletal muscle without any exercise — establishing AICAR as the prototypical 'exercise in a pill' and leading to its addition to WADA's prohibited list.
• AICAR activates AMPK by mimicking AMP, triggering downstream phosphorylation of ACC and PGC-1α activation, which drives mitochondrial biogenesis, fatty acid oxidation, and slow-twitch (type I) fiber specification; however, systematic review evidence confirms that numerous AICAR effects are AMPK-independent, including some NF-κB suppression in human macrophages.
• AICAR inhibits NF-κB DNA binding independently of AMPK in primary human macrophages, reducing LPS-induced pro-inflammatory gene expression — a distinct anti-inflammatory pathway relevant to insulin resistance and metabolic syndrome where chronic low-grade inflammation is a driver.

All citations link to the original source (PubMed, journal site, or regulatory filing). Independent research database — no vendor influence on what's cited.