AICAR (5-Aminoimidazole-4-carboxamide ribonucleotide) was first developed to protect the heart during low oxygen levels. It works by mimicking a natural molecule in your body called AMP, which activates AMPK. This enzyme acts like a “metabolic switch” that boosts fat burning, increases insulin sensitivity, and supports the production of new mitochondria – the energy factories in your cells. Research shows AICAR may improve endurance, support weight loss, and help with metabolic health, making it interesting for athletes and people focused on longevity.
In a landmark study by the Salk Institute, it was shown that four weeks of treatment with AICAR increased running performance by 44% in non-motile mice. This occurred through the activation of AMPK, which led to the conversion of muscle fibers into endurance, fat-burning type I fibers. Remarkably, these effects were achieved without physical training, positioning AICAR as a potential “training mimetic”.
Another study investigated the role of AMPK in the regulation of mitochondrial function and oxidative stress management in skeletal muscle. The researchers treated mice daily with AICAR (500 mg/kg) for four weeks and observed an AMPK-dependent increase in SIRT3 and MnSOD in skeletal muscle. These results suggest that AICAR improves mitochondrial function and reduces oxidative stress through AMPK activation
References
Višnjić D, Lalić H, Dembitz V, Tomić B, Smoljo T. AICAr, a Widely Used AMPK Activator with Important AMPK-Independent Effects: A Systematic Review. Cells. 2021; 10(5):1095. https://doi.org/10.3390/cells10051095
Brandauer J, Andersen MA, Kellezi H, Risis S, Frøsig C, Vienberg SG, Treebak JT. AMP-activated protein kinase controls exercise training- and AICAR-induced increases in SIRT3 and MnSOD. Front Physiol. 2015 Mar 24;6:85. doi: 10.3389/fphys.2015.00085. PMID: 25852572; PMCID: PMC4371692.