Mechanism of enhanced cold tolerance by an ephedrine-caffeine mixture in humans

The influence of a thermogenic mixture of ephedrine- (1 mg/kg) caffeine (2.5 mg/kg) on cold tolerance was investigated in nine healthy young male subjects during two seminude exposures to cold air (3 h at 10 degrees C). The drug ingestion reduced the total drop in core, mean skin, and mean body temperatures (P less than 0.01), thus producing significantly warmer final core, mean skin, and mean body temperatures compared with the placebo ingestion. The drug ingestion increased the total 3-h energy expenditure by 18.6% compared with that of the placebo ingestion in the cold (P less than 0.01). By means of the nonprotein respiratory exchange ratio to calculate the rates of substrate oxidation, it was found that the drug ingestion increased carbohydrate oxidation by as much as 41.7% above that of the placebo (P less than 0.05). In contrast, the drug mixture had no significant influence on lipid or protein metabolism. The results demonstrate that the ingestion of an ephedrine-caffeine mixture improves cold tolerance in humans by significantly increasing body temperatures in the cold. These improvements were not caused by an increased conservation of heat but by a greater energy expenditure, which appears to be dependent on an enhanced carbohydrate utilization.