Caffeine metabolism in a healthy Spanish population: N-Acetylator phenotype and oxidation pathways

Abstract

We studied the oxidative and N-acetylator caffeine metabolic profile in 107 healthy Spanish volunteers. Smokers had significantly higher N-1- and N-3-demethylations activities than nonsmokers (p = 0.03 and p = 0.02, respectively), and the three caffeine demethylations indexes were strongly correlated with each other (r > 0.7; p < 0.001). Our in vivo studies suggest that CYP1A2 is involved, at least in part, in the primary N-demethylations of caffeine. A non-normal and possibly bimodal distribution was detected in the xanthine oxidase activity (p = 0.04), with about 4% of subjects deficient of this metabolic activity. The population exhibited a trimodal distribution of acetylator phenotype determined by use of the 5-acetylamino-6-amino-3-methyluracil/1-methylxanthine ratio (normality test; p = 0.004). Seventy subjects (65.4%) were phenotyped as slow acetylators. The mutated gene frequency was 0.81, which is similar to other white populations.

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

“…One hundred and twenty healthy volunteers (59 males Caffeine is probably the most frequently ingested drug in the world and is present in a variety of common and 61 females), took part in a urinary caffeine test in a population study [ 4]. They were aware of the purpose beverages (coffee, tea, soft-drinks), products containing cocoa or chocolate, and in medications, including and gave written informed consent.…”

“…A total of 218 toxic effects were selfreported by eighty-two subjects (68%) after the intake The initial population study [4 ] was not a standardized and controlled phase I clinical trial with caffeine of caffeine, 300 mg orally. The list of symptoms and frequency included: restlessness or muscle tremor, 69; examining toxicity profiles.…”

“…Widespread caffeine use prompted us to deal with those variables that might be avoid methylxanthine-containing foods and beverages for at least 48 h before and during the study. Before the influencing the occurrence of toxic effects during the performance of a urinary test with caffeine in a healthy administration of caffeine, each subject emptied their bladder and collected a blank urine sample to detect population [4 ].…”

“…body weight was 65.1±12.4 kg (males: 74.5±10.2, females: 56.0±5.6) and mean height (±s.d.) was activities in humans [2][3][4]. The term caffeinism refers to a state of acute or chronic toxicity resulting from 169±9.5 cm (males: 176±7.1, females: 162±6.1 ).…”

“…mean) cigarettes day−1. Urinary concentrations of rate of caffeine elimination is reduced, leading to a greater systemic accumulation of this xanthine and caffeine and its metabolites were measured according to Carrillo & Benítez [ 4]. Subjects were requested to consequent toxicity [ 7,8].…”