On the other hand our conclusion is supported by data obtained by Nabben et al. in skeletal muscle of UCP32/2 mice, and showing no evidence for the function of UCP3 being basal or induced uncoupling. Thus, how does EC treatment increase RMR value in obese women? It has been shown that ephedrine stimulates brown adipocyte respiration via b-adrenoceptors, and that the thermogenic action of ephedrine can be enhanced by methylxanthines, such as caffeine, through their ability to inhibit the phosphodiesterase-induced degradation of intracellular cyclic AMP, and to antagonize the inhibitory action of adenosine. Anyway, several human studies have shown positive effects on body-weight management of EC. Besides activating b2- adrenoceptors, EC treatment was found to enhance the b3- adrenoceptor expression in white adipocytes of obese subjects, following hypocaloric diet, when compared to placebo. Together, those and our results allow to speculate that long-term treatment with EC further increases the already high level of SNS activity in morbidly obese patients. No significant changes in the studied biochemical parameters were observed, and only a mild increase in creatinine level, a reliable indicator to estimate skeletal muscle mass status, was detected. We did not find any other considerable variations, and the differences between the two groups were not statistically significant. These data would strengthen the safety profile of EC in morbid obesity, although during the last years there have been raising safety concerns about the use of ephedrine for pharmaceutical preparations, and the combination was banned by the U.S. Food and Drug Administration.