CYP1A2 activity, gender and smoking, as variables influencing the toxicity of caffeine

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Abstract
We have investigated several factors that might be related to the occurrence of toxic effects during the performance of a urinary test with caffeine (300 mg p.o.), in 120 healthy volunteers. A total of 218 toxic effects were self-reported by eighty-two (68%) subjects. Females and nonsmokers were at the highest risk (chi-square test, P = 0.01). Furthermore, two nonsmoking females experienced a symptomatology with delirium, restlessness, muscle tremor, vomiting and wakefulness. Among females and nonsmokers, those subjects who experienced toxic effects had lower caffeine N3-demethylation index (CYP1A2 activity) compared with unaffected females (1.87 +/- 0.51 vs 1.47 +/- 0.27, P < 0.0005) and nonsmokers (1.69 +/- 0.23 vs 1.49 +/- 0.31, P < 0.02). Caffeine N1- and N7-demethylations indices were also lower among females (P < 0.0005) and nonsmokers (P < 0.02) who reported toxic symptoms. We conclude that CYP1A2 activity, gender and smoking are variables to be considered as influencing the toxicity of caffeine.

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