Caffeine is perhaps the most widely used agent to mobilize fat for use as fuel, and one that actually helps burn that fat by elevating energy expenditure (basal metabolic rate). Several studies have shown that caffeine promotes lipolysis, the breakdown of stored fats into fatty acids which can be used by working muscle and other tissues for fuel while sparing glycogen in the process.

The traditional theory on how caffeine promotes lipolysis rests on the fact that at relatively high concentrations caffeine acts as a phophodiesterase inhibitor, maintaining elevated levels of cAMP (cyclic AMP) and in the process amplifying the effects of the body’s natural lipolytic hormones epinephrine and norepinephrine.

During the lipolytic (fat mobilizing) signaling cascade, natural hormones like norepinephrine and epinephrine (or synthetic analogs like ephedrine or clenbuterol) bind to so-called alpha-1 and beta-1 and beta-2 adrenergic receptors on the surface of fat cells, activating cyclic Adenosine Monophosphate, or cAMP. cAMP ultimately acts to turn on the enzyme Hormone Sensitive Lipase (HSL). HSL breaks up stored fat so that it can be used for fuel.

cAMP is deactivated by an enzyme called phosphodiesterase. Caffeine inhibits the action of phospodiesterase thereby prolonging lipolysis. Besides acting as a cutting agent, caffeine posses ergogenic (sports performance enhancing) properties. The fat burning/glycogen sparing effect above may contribute to this.