Caffeine: A Cause of Insulin Resistance?

Caffeine is arguably the most widely consumed drug in Western society. The annual world consumption of coffee exceeds 4 million tons. Caffeine constitutes 1–2% of roasted coffee beans and is present in many over-the-counter preparations for the treatment of cold and allergies, headaches, diuretics, and stimulants. In general, one cup of coffee is assumed to contain 100 mg of caffeine, and soft drinks contain ∼10–50 mg of caffeine per 12-oz serving. The per capita consumption of caffeine averages ∼200 mg/day, but in some countries, it can exceed 400 mg/day (1). There has been great interest, therefore, in defining the mechanism of action of caffeine and determining the health consequences of its consumption. Progress has been made on both accounts, but not without controversy.

It is now evident that caffeine acts as an antagonist of adenosine receptors (1,2). Only concentrations reaching toxic effects are effective in increasing intracellular calcium or inhibiting cyclic nucleotide phosphodiesterases (1), the alternative mechanisms of action. Caffeine (1,3,7-trimethylxanthine) and the closely related theophylline (1,3-dimethylxanthine) are relatively poor adenosine receptor antagonists, with EC₅₀ values in the low μmol/l range. These concentrations, however, are readily achieved during habitual caffeine consumption. In experimental studies in humans, an oral dose of caffeine at 250 mg t.i.d. (∼5–7 cups of coffee/day), which is well tolerated, produced plasma caffeine concentrations in excess of …