The objective of this study was to determine the pharmacokinetics of caffeine after single administration of a coffee enema versus coffee consumed orally in healthy male subjects. The study design was an open-label, randomized two-phase crossover study. Eleven healthy subjects were randomly assigned either to receive 500 mL of coffee enema for 10 minutes or to consume 180 mL of ready-to-drink coffee beverage. After a washout period of at least 10 days, all the subjects were switched to receive the alternate coffee procedure. Blood samples were collected immediately before and at specific time points until 12 hours after coffee administration in each phase. The mean caffeine content in both the coffee solution prepared for the coffee enema and the ready-to-drink coffee beverage was not statistically different. The C max and AUC of caffeine obtained from the coffee enema were about 3.5 times significantly less than those of the coffee consumed orally, despite having slightly but statistically faster T max. The t 1/2 of caffeine obtained following both coffee procedures did not statistically differ. In summary, the relative bioavailability of caffeine obtained from the coffee enema was about 3.5 times significantly less than those of the coffee consumed orally.

We designed an open-label, randomized two-phase crossover study to investigate the antioxidant effects after single and multiple doses of a coffee enema versus coffee consumed orally. Eleven healthy subjects were randomly assigned to either receive a coffee enema (3 times weekly for 6 visits) or consume ready-to-drink coffee (2 times daily for 11 days). After a washout period, subjects were switched to receive the alternate coffee procedure. Blood samples were collected at specific time points for the determination of serum levels of glutathione (GSH), malondialdehyde (MDA) and trolox equivalent antioxidant capacity (TEAC). The findings showed that either single or multiple administrations of the coffee enema or orally consumed coffee doses seemed not to produce any beneficial effects to enhance serum GSH levels or to decrease serum MDA levels over the study period of 12 days. In contrast, mean serum TEAC levels at day 12 after the coffee enema and at days 6 and 12 after oral coffee consumption were significantly reduced from their corresponding baseline values. Thus, no beneficial effects with respect to an enhancement of serum GSH and TEAC levels or a decrease in serum MDA concentrations were demonstrated after coffee enema or orally consumed ready-to-drink coffee.