By Michael C. Prevost Ph.D.
The role of the �-agonist (beta agonist) pathway in controlling the body's fat stores, muscle hypertrophy (growth), the body's response to exercise and even muscle fiber type has been brought to light in the last 10 years through the efforts of hundreds of scientists with literally thousands of papers being published on the subject. Clearly, the �-agonist pathway is one of the most important signalling pathways in the body. To understand how the �-agonist pathway works and what role Caffeine, Ephedrine and Aspirin plays in the system one must first understand what a �-agonist is and what they do.
On the surfaces of many of the cells of the body (for our purposes the most important tissues are muscle and fat cells) are located b receptors. These b receptors bind b-agonists (adrenaline and noradrenaline). When a �-agonist is bound to a b receptor, the receptor initiates a series of chemical reactions that results in the production of a chemical messenger called C-AMP. This C-AMP then activates enzymes that phosphorylate proteins. Why is this important? Well, many of these proteins are enzymes and phosphorylation activates some enzymes and de-acitvates others. In fat cells enzymes are activated that induce lipolysis (fat breakdown). In muscle cells enzymes are activated that increase metabolism and cause a host of other important reactions which control muscle growth, fiber type and enzyme concentration. So, how do ephedrine, caffeine and aspirin fit into this pathway? Ephedrine enhances �-agonist production and even acts as a �-agonist itself. Caffeine inhibits the breakdown of C-AMP. Aspirin inhibits the negative feedback loop that would reduce �-agonist production. So taken together these agents enhance three to four different steps in the �-agonist pathway.
Ephedrine's role as a lipolytic agent (one that breaks down body fat to be used as energy) has been known for some time. It has been shown that ephedrine when taken in therapeutic doses is mildly effective in the management of obesity. The problem was that the initial lipolytic effects of ephedrine were soon diminished as other steps in the pathway were reduced in a negative feedback cycle. In an effort to enhance these steps that were being downregulated due to negative feedback, scientists added caffeine and aspirin to the regime. The result was a very effective combination in the management of obesity (dosages given were 20mg ephedrine, 300mg caffeine, and 80mg aspirin, roughly equivalent to one typical ephedrine tablet, a cup of coffee and one aspirin). In fact, not only did the results (lipolysis) not decrease over time as with most drugs, but they actually increased with time. The effects of the combination of ephedrine, caffeine and aspirin were categorized into desirable and undesirable effects. The desirable effects were lipolysis and protein sparing (subjects on the drug combination retained more muscle mass while dieting than the subjects on placebo). Again, these desirable effects did not diminish over time. The undesirable effects, increased heart rate and muscle tremors, lasted only a few days and never returned. In fact, after 1 year of supplementation subjects were experiencing no side effects but were still experiencing the desired effects of lipolysis and protein sparing. To date it has not been determined if the ephedrine, caffeine and aspirin combination can enhance muscle growth and fat loss in healthy, exercising adults. However, based on what we know about the �-agonist system, it is certainly possible. It is important to note, however, that a small handful of subjects among the large subject pool had to drop out of the study due to an intolerance to the supplementation regime. So it appears that most people can use the ephedrine, caffeine and aspirin combination with no problems, while a small handful of people may be intolerant. A consultation with a physician is suggested before beginning this supplementation regime.
The �-agonist pathway may effect processes other than muscle sparing and fat loss. In fact in chickens �-agonists were shown to be stronger growth promoting agents than steroids (believe it or not but poultry science folks are doing a lot of research trying to produce more muscular chickens since the muscle is the meat that we eat). In fact �-agonists seem to produce muscle growth without the stimulus of exercise, something steroids have failed to do. However �-agonists are not as effective in rats and the effects on humans is unknown. The �-agonist clenbuterol can cause slow twitch muscle fibers to be converted to fast twitch fibers. It can also prevent muscle atrophy due to disuse. Other studies have shown that b-antagonists (agents that block b-receptors and prevent them from functioning) cause muscles to shift from fast twitch to slow twitch and cause muscle atrophy (muscle wasting or breakdown). These studies indicate that �-agonists might play an important role in the maintenance of fast twitch muscle fibers and in maintaining and perhaps increasing muscle mass. It may be no coincidence then that large amounts of �-agonists (adrenaline and noradrenaline) are produced during high intensity training sessions. Perhaps these �-agonists are necessary in initiating the muscle growth stimulus.
It is important to note that some �-agonists can be dangerous (for example clenbuterol and cocaine) and illegal and these substances are not recommended. Also, as mentioned earlier, although the �-agonist combination of caffeine, ephedrine and aspirin appears to be safe (and of course legal) a small number of people are intolerant and consultation with a physician is suggested. Everyone should visit there doctor prior to using any of these substances for a clean bill of health

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