Effect of chewing gum containing nicotine and caffeine on energy expenditure and substrate utilization in men

BACKGROUND: Nicotine replacement therapy limits weight gain after smoking cessation. This finding is partly attributable to the thermogenic effect of nicotine, which may be enhanced by caffeine. OBJECTIVE: We assessed the acute thermogenic effects of chewing gum containing different doses of nicotine and caffeine. DESIGN: This randomized, double-blind, placebo-controlled, crossover study included 12 healthy, normal-weight men (aged 18-45 y). Energy expenditure was measured with indirect calorimetry before and 2.5 h after subjects chewed each of 7 different types of gum containing the following doses of nicotine/caffeine: 0/0, 1/0, 2/0, 1/50, 2/50, 1/100, and 2/100 mg/mg. RESULTS: The thermogenic responses (increases over the response to placebo) were 3.7%, 4.9%, 7.9%, 6.3%, 8.5%, and 9.8%, respectively, for the gums containing 1/0, 2/0, 1/50, 2/50, 1/100, and 2/100 mg nicotine/mg caffeine (P < 0.05 for all). Adding caffeine to 1 and 2 mg nicotine significantly enhanced the thermogenic response, but changing the caffeine dose (from 50 to 100 mg) did not change the thermogenic effect. None of the combinations changed the respiratory quotient compared with placebo, which indicates that glucose and fat oxidation rates were increased to a similar extent. Side effects occurred only with 2 mg nicotine. CONCLUSIONS: One milligram of nicotine has a pronounced thermogenic effect, which can be increased by approximately 100% by adding 100 mg caffeine. Increasing the nicotine dose to 2 mg does not increase the thermogenic effect but produces side effects in most subjects. Caffeine may be useful in preventing weight gain after smoking cessation if its thermogenic effect can be used to enhance nicotine's effect on long-term energy balance.