Effect of a Dietary Supplement Containing Raspberry Ketone on Cytochrome P450 3A Activity

Abstract

Objective: Various herbal medicines and dietary supplements are known to alter the effects of drugs and cause severe complications. One of the most famous examples is St. John’s wort, which promotes an increase of cytochrome P450 2C9 (CYP2C9), CYP2C19, and CYP3A4 expression, and reduces the effects of a large number of drugs. Raspberry ketone, an aromatic ingredient extracted from raspberries, is sold in Japan as a herbal supplement with a claimed slimming effect; however, its effect on CYP activity is unknown. To clarify the risk of an interaction between raspberry ketone-related supplements and CYP3A substrates, we performed an in vivo pharmacokinetic study using rats. Methods: We investigated the effect of the oral administration of raspberry ketone on the pharmacokinetics of midazolam, a typical CYP3A substrate, in rats. St. John’s wort, as a positive control, and raspberry ketone tablets at a dose of 50 mg/kg were administered every 12 h for 7 days, and at 24 h after the final treatment, 10 mg/kg midazolam was administered orally. The plasma concentration of midazolam was analyzed by high-performance liquid chromatography. Results: Oral clearance of midazolam in the St. John’s wort-treated group increased to 161% of that observed in the control group. Conversely, there was no significant difference between the raspberry ketone-treated and control groups. The mean residence time was essentially the same in all groups. Conclusion: Because raspberry ketone is considered to suppress the accumulation of body fat, it is mainly taken by young healthy women for weight loss. Considering this population, information about the interaction of raspberry ketone with oral contraceptives, which are substrates of CYP3A, is of clinical importance. In this study, raspberry ketone was found to have little impact on CYP3A activity, unlike St. John’s wort. These data indicate the low risk of an interaction between raspberry ketone-related supplements and many drugs metabolized by CYP3A.