Caffeine Activates Mainly AMPK-alpha1

The ergogenic effects of caffeine (structure, see image on the right; HMDB v2.5) have in parts been established to be AMPK-dependent. AMPK protects cell from ATP, i.e. energy deffiency, and its activation by caffeine has been shown to improve time to exhaustion as well as overall performance. Hypothalamic AMPK also plays a critical role in hormonal and nutrient-derived anorexigenic and orexigenic signals and in energy balance (Minokoshi. 2004). A recent study by Egawa, et.al. (Egawa. 2010) did now reveal that caffeine, at least at lower doses, is a relative specific activator the alpha1 variant of AMPK:

"Incubation of isolated epitrochlearis muscle with 1 mM [and injection of 5mg/kg) of caffeine for 15 min increased AMPKα1 activity, but not AMPKα2 activity; concentrations of ATP, PCr and glycogen were not affected." (Egawa. 2010)

Higher doses of 3 mM of caffeine did however activate AMPKα2 and reduced PCr and glycogen concentrations. Although caffeine is certainly among the most investigated natural ergogenics, the continuous publications with ever new findings on its metabolic and neurological effects indicate that its exact mechanisms of action are still not fully understood.