Acute effect of ephedrine on 24-h energy balance

Ephedrine is used to help achieve weight control. Data on its true efficacy and mechanisms in altering energy balance in human subjects are limited. We aimed to determine the acute effect of ephedrine on 24-h energy expenditure, mechanical work and urinary catecholamines in a double-blind, randomized, placebo-controlled, two-period crossover study. Ten healthy volunteers were given ephedrine (50 mg) or placebo thrice daily during each of two 24-h periods (ephedrine and placebo) in a whole-room indirect calorimeter, which accurately measures minute-by-minute energy expenditure and mechanical work. Measurements were taken of 24-h energy expenditure, mechanical work, urinary catecholamines and binding of(+/-)ephedrine in vitro to hu man beta(1)-, beta(2)- and beta(3)-adrenoreceptors. Twenty-four-hour energy expend itu re was 3.6% greater (8965+/-1301 versus 8648+/-1347 kJ, P < 0.05) with ephedrine than with placebo, but mechanical work was not different between the ephedrine and placebo periods. Noradrenaline excretion was lower with ephedrine (0.032+/-0.011 mu g/mg creatinine) compared with placebo (0.044+/-0.012 mu g/mg creatinine) (P < 0.05). (+/-)Ephedrine is a relatively weak partial agonist of hu man beta(1)- and beta(2)-adrenoreceptors, and had no detectable activity at human beta(3)-adrenoreceptors. Ephedrine (50 mg thrice daily) modestly increases energy expenditure in normal human subjects. A lack of binding of ephedrine to beta(3)-adrenoreceptors and the observed decrease in urinary noradrenaline during ephedrine treatment suggest that the thermogenic effect of ephedrine results from direct beta(1)-/beta(2)-adrenoreceptor agonism. An indirect beta(3)-adrenergic effect through the release of noradrenaline seems unlikely as urinary noradrenaline decreased significantly with ephedrine.