Ephedrine may work through both direct and indirect methods. Directly it can attach to
beta receptors itself. However at the concentration seen with therapeutic doses, ephedrine does
not appear to bind well to beta-receptors (8). Indirectly ephedrine causes a release in the body of
adrenaline and noradrenaline both of which have potent effects at both beta and alpha receptors
in the body (8). It seems that most of ephedrine’s thermogenic effect is through the indirect
mechanism of adrenaline and noradrenaline release, rather than through direct binding to fat cell
adrenoreceptors (8).
There have been numerous research studies done on ephedrine as an adjunct to low calorie
diets for the treatment of obesity (9,10). Through this research, it was found that the
combination of ephedrine and caffeine gave better results than ephedrine alone (8,9). One study
suggests that the combination of ephedrine and caffeine is more effective than the appetite
suppressant dexfenfluramine (11). Some research suggests that adding aspirin to the
combination of ephedrine and caffeine may provide even greater results (8,12,13). Side effects
from ephedrine include jitters, hand tremor, increased heart rate/blood pressure, and insomnia (9,.
In general, the side effects from ephedrine use typically go away in several weeks (9), while
the thermogenic effects may increase with time (8,10). Thus, unlike most diet compounds which
have a positive tolerance curve, meaning that dieters must take more to get the same effect,
ephedrine appears to have a negative tolerance curve, meaning that the same amount gives a
greater effect. Additionally, the addition of ephedrine to a calorically restricted diet appears to
prevent some of the muscle loss which would otherwise occur.
Caffeine
When ephedrine increases thermogenesis in the body, the body attempts to return itself to
homeostasis through various mechanisms. One is to increase activity of an enzyme called
phosphodiesterase (PDE). When noradrenaline attaches to the beta receptors, it causes an
increase in a substance called cAMP which is involved in regulating fat burning. The body raises
levels of PDE to inhibit the cAMP from doing its job (8,15). Caffeine indirectly blocks PDE by
attaching to adenosine receptors on the cell, preventing the decrease in cAMP levels (8). Thus,
caffeine inhibits the enzyme which inhibits fat burning. The net result is an increase in use of fat
for fuel.
Dieters who do not wish to use ephedrine, or cannot tolerate its effect, may still derive
some benefit from caffeine taken by itself as this increases thermogenesis and enhances fat
utilization (16,17). Consuming caffeine prior to exercise increases the use of FFA for fuel and
may be useful for fat loss (18). In fact, this occurs to a greater degree when carbohydrates are
restricted (18).
Aspirin
Another mechanism the body uses to reduce the increase in metabolic rate is through the
release of prostaglandins, specifically the PGE2 type, which accelerates the breakdown of
noradrenaline (15). Aspirin generally inhibits prostaglandin release further potentiating the