Several studies have demonstrated that the predominant effect of ephedra and caffeine when given in low does, is on the stimulation of sympathetic post synaptic nerves to release greater amounts of norepinephrine (NE) onto the richly innervated adipose tissue. This central effect stimulates thermogenesis indirectly by increasing sympathetic stimulation throughout the body. The thermogenic response is blunted in the presence of a chemical sympathetic denervating agent, suggesting that intact sympathetic nerve endings releasing NE are necessary for the effects. However, Dulloo et al demonstrated that there is also a direct effect on peripheral tissues. By using rat brown adipose tissue as a peripheral tissue raget, and using tissue respiration (production of O2) as a marker of thermogenesis, the direct effects of ephedra and caffeine were measure. Ephedra, as a sympathomimetic, is a beta adrenergic dependent synthesis of cyclic adenosine monophosphate (cAMP). Elevation of cytoplasmic cAMP is responsible for the increased thermogenesis. Caffeine, while not a sympathomimetic, is know to increase cAMP levels by inhibitng the enzyme responsible for destruction of cAMP, phosphodiesterase (PDE). Also, caffeine is an adenosine receptor antagonist, preventing the inhibition of NE release by extracellular adenosine, thereby increasing cAMP levels in the adipose cell. It is believe that the multiple mechanisms utilized by ephedra and caffeine for increasing intracellur cAMP are responsible for the synergistic interaction that increases thermogenesis. Follow up stdies on adipose tissue were conducted in the presence of either PDE inhibitors or adenosine antagonists and shoed that the PDE inhibition, and not adenosine antagonism, has a more substantial role in facilitating ephedra plus caffeine interactions. It was also shown that caffeine metabolites, specifically theobromine, theophylline, and paraxanthine, an mimic caffeine’s interaction with sympathetic stimulation to increase thermogenesis.
An additional claim made by proponents of ephedra plus caffeine induced weight loss is that the thermogenic effects are limited to fat catabolism, and that there is no protein catabolism increased heart rat, or tremors which are associated with other sympathetic stimulation. One hypothesis is that the main stimulation by ephedra is through beta2 and beta3 adrenergic receptor subtypes, both of which are predominantly responsible for lipolysis and protein synthesis, but are not associated with cardiovascular and central nervous system effects mediated by beta1 receptor. Tolerance rapidly develops to the effects of ephedra or heart rate, but does not develop to the thermogenic effects, and that ephedra has longer acting effects on thermogenesis.
Ephedra, with and without caffeine, has been marketed in the United States since the early 1990’s. In fact, approximately 425million ephedra servings were sold in 1995. By 1999, that number has risen to approximately 3 billion servings of ephedra being sold annually. Of particular interest is that the Adverse Event Reposts (AER) on file with the FDA demonstrated a reporting grate of less that 10 such reports per billion servings sold. These reports came from ephedra extract products that contained ephedrine alkaloids, which varied in standardization and potency. Thermo-Z, on the other hand, with it unique constituent profile, has not been the subject of even one AER to date. Thermo-Z is the prefect weight loss aid with a virtually side effect free safety profile, which Hi Tech expects to continue offering consumers to help them reach their weight loss goals.