1. We investigated the effects of the chronic administration of a sympathomimetic agent on energy expenditure, protein metabolism and levels of thyroid hormones and catecholamines in 10 obese subjects after a 6-week very-low-calorie-diet programme (1965 kJ, 60 g of protein, 45 g of carbohydrates). l-(-)-Ephedrine hydrochloride (50 mg three times a day by mouth) or placebo were administered during 2-week periods (weeks 2-5 of the VLCD programme) in a randomized, double-blind, crossover design. Five subjects began with ephedrine and five with placebo.

2. The results were analysed separately in the two groups. No difference was found between them as regards weight loss during the very-low-calorie diet and drug treatments. Conversely, ephedrine therapy induced a significantly lower daily urinary excretion of nitrogen (and, consequently, a better nitrogen balance) with respect to placebo, independently of the drug sequence. Daily urinary levels of 3-methylhistidine during ephedrine and placebo treatments were similar. The fasting resting metabolic rate (oxygen consumption, ml STP/min) fell significantly during the very-low-calorie diet in both groups, but this effect was partially and significantly prevented by administration of ephedrine. Diet therapy significantly reduced 24 h urine levels of vanillylmandelic acid and homovanillic acid, which, however, increased to pretreatment values during ephedrine treatment. No significant effects were shown on 24 h urinary concentrations of adrenaline, noradrenaline and dopamine during the very-low-calorie diet and/or ephedrine treatment. There were also no effects on the serum levels of thyrotropin, thyroxine, free-tri-iodothyronine and free-thyroxine, but ephedrine significantly prevented a further fall in the serum tri-iodothyronine level and the serum triiodothyronine/thyroxine ratio during the very-low-calorie diet.

3. These findings demonstrate that in obese subjects following a very-low-calorie-diet programme, administration of chronic adrenoceptor agonists, such as ephedrine, partially prevented the fall in resting metabolic rate and significantly improved the nitrogen balance. These effects may be of importance in the treatment of patients in whom a reduced capacity for energy expenditure may be involved in their obese state.

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