Considering (on the basis of published data) an expected coffee effect in at least 40% of exposed subjects, with 1 control for case, with 5% alpha error and with 80% power, the sample size required (20 cases and 20 controls) corresponded to the selected sample for the study. Additionally, in this study, given the cross over design in which each patient is investigated twice, once during coffee exposure and once during abstinence, the actual number of patients investigated is of 40 per arm, twice as high therefore, than required.