Electrochemical Simulation of the Oxidative Capsaicin Metabolism

Abstract

Capsaicin, primarily known as the pungent ingredient in hot peppers, is rapidly metabolized in the human body by enzymatic processes altering the pharmacological as well as toxicological properties. Herein, the oxidative transformation of capsaicin was investigated in vitro with electrochemistry as well as human liver microsomal incubations. The reaction mixtures were analyzed with liquid chromatography−mass spectrometry. Structure elucidation involved accurate mass measurements and multistage tandem mass spectrometry experiments. In total, 126 transformation products were detected. Electrochemistry provided evidence for 101 transformation products and the microsomal incubations for 46 species. 21 compounds were observed with both approaches. Identified oxidative pathways likely occurring during the phase I metabolism included dehydrogenation, O-demethylation, and hydroxylation reactions as well as combinations thereof. Furthermore, trapping of reactive intermediates either with glutathione or with electrochemically activated ribonucleosides provided evidence for the possible production of phase II metabolites and covalent adducts with a genetic material. Evidence for the occurrence of some capsaicin metabolites in humans was obtained by urine screening.

Capsaicin for Weight Control: “Exercise in a Pill” (or Just Another Fad)?

“…Probably not. Although capsaicin is readily absorbed from the GI tract of both rats [ 94 ] and men [ 95 , 96 ], it is rapidly metabolized in the liver, producing 126 transformation products [ 97 , 98 ]. Although some of the capsaicin metabolites were detected in human urine [ 98 ], it is not known if any of these compounds may mimic capsaicin actions on adipose cells.…”

“…Although capsaicin is readily absorbed from the GI tract of both rats [ 94 ] and men [ 95 , 96 ], it is rapidly metabolized in the liver, producing 126 transformation products [ 97 , 98 ]. Although some of the capsaicin metabolites were detected in human urine [ 98 ], it is not known if any of these compounds may mimic capsaicin actions on adipose cells. In human volunteers, the half-life of capsaicin in the blood was approximately 25 min with a peak concentration of 8.2 nM [ 96 ]: this should be compared to the affinity of capsaicin for human TRPV1, 640 nM [ 99 ].…”