Caffeine is a fairly simple molecule, categorized as a trimethyl xanthine. One function of caffeine is to promote the cAMP signal generated by the B-adrenergic drugs or hormones. It does this by acting as an adenosine antagonist, meaning it counters or interferes with the signal that normally prevents cAMP production.10 Caffeine increases the release of stored fat by prolonging the fat breakdown signal generated by adrenalin, ephedrine, clenbuterol and similar drugs. This includes the B-receptor stimulation that exists from the normal sympathetic tone.

The newly released FFA (non-estrified free fatty acid) travels the bloodstream to enter active areas, such as the liver or exercising muscle, to be burned for energy (oxidative lipid disposal). If there is no need for additional energy (calories), then the FFA will return, through the bloodstream, to fat cells. The release of FFA from a fat cell, only to return to the fat cell to be stored is called non-oxidative lipid turnover or futile cycling.5 It reminds one of the old phrase "you're just running in circles," meaning a lot of activity that accomplishes nothing. Fat release without fat burning accomplishes nothing in regard to fat loss; the FFA just "runs in circles."

Measuring Fat Release
Acheson's group used a series of tests and measures to determine the amount of fat released normally and after taking caffeine.5 Through further measures, they evaluated the eventual fate of the released FFA. The results showed that under the influence of caffeine (10 milligrams per kilogram body fat), the amount of FFA released by fat cells more than doubled (130 percent increase). Simultaneously, the demand for calories increased, though only by 13 percent. For most people, that only translates to approximately 250 calories per day. As the amount of FFA released far exceeded the amount needed to meet the increased demand for calories, a great percentage of the released FFA was returned to the fat cell and re-stored as fat. The authors of the study referred to this as "futile cycling," as the fat was broken down, shuffled around and stored away again, resulting in no net fat loss for that percentage of the released fat.

Fortunately, there was a measurable increase in energy expenditure (the number of calories burned).5 The process by which caffeine increases calorie burning is more complex and less well understood than the process by which it increases fat release. In humans, an increase in energy expenditure is usually due to an increase in activity, as a result of the greater metabolic demand of skeletal muscle. When skeletal muscle contracts and relaxes, it uses ATP (the energy molecule) at a much greater rate. The ATP needs of exercising muscle are met through an increased rate of calorie burning. Most writers believe caffeine's effect on skeletal muscle is solely due to an amplification of the effect of adrenaline. This is because the most easily recognized side effect of caffeine excess is the jitters. Increasing the sympathetic tone of the skeletal muscle increases the twitching of muscle, which is an increase in activity requiring more ATP, thus the increase in energy expenditure.

However, there is another mechanism that may contribute to caffeine's effect on energy use. Caffeine, as well as its three major metabolites, increases the levels of free calcium ions in the muscle cell interior.5,11,12 Calcium ions are tightly regulated, as they are very potent triggers of biological reactions, including muscle contractions. When calcium interacts with the actin-myosin heads of muscle fibers, it causes the muscle to contract. Caffeine causes free calcium levels to increase in the muscle cell by interacting with another receptor called the ryanodine receptor. By increasing the amount of free calcium present in the muscle cell at rest, it makes the muscle more likely to contract and do so with greater force when stimulated.

One benefit of caffeine noted by Acheson was that the potent release of stored fat actually increased the proportion of fat (compared to carbohydrates) burned for calories.5,13,14 This is one reason why taking caffeine before early morning cardio (before eating breakfast) is so effective at reducing body fat.