Human brain metabolic response to caffeine and the effects of tolerance

Objective: Since there is limited information concerning caffeine's metabol ic effects on the human brain, the authors applied a rapid proton echo-plan ar spectroscopic imaging technique to dynamically measure regional brain me tabolic responses to caffeine ingestion. They specifically measured changes in brain lactate due to the combined effects of caffeine's stimulation of glycolysis and reduction of cerebral blood flow. Method: Nine heavy caffein e users and nine caffeine-intolerant individuals, who had previously discon tinued or substantially curtailed use of caffeinated products because of as sociated anxiety and discomforting physiological arousal, were studied at b aseline and then during 1 hour following ingestion of caffeine citrate (10 mg/kg). To assess state-trait contributions and the effects of caffeine tol erance, five of the caffeine users were restudied after a 1- to 2-month caf feine holiday. Results: The caffeine-intolerant individuals, but not the re gular caffeine users, experienced substantial psychological and physiologic al distress in response to caffeine ingestion. Significant increases in glo bal and regionally specific brain lactate were observed only among the caff eine-intolerant subjects. Reexposure of the regular caffeine users to caffe ine after a caffeine holiday resulted in little or no adverse clinical reac tion but significant rises in brain lactate which were of a magnitude simil ar to that observed for the caffeine-intolerant group. Conclusions: These r esults provide direct evidence for the loss of caffeine tolerance in the hu man brain subsequent to caffeine discontinuation and suggest mechanisms for the phenomenon of caffeine intolerance other than its metabolic effects on elevating brain lactate.