Assessment of the adverse event reports associated with Citrus aurantium (bitter orange) from April 2004 to October 2009

From April 2004 through October 2009, the FDA received 22 adverse event reports (AERs) involving products that were reported to contain Citrus aurantium (bitter orange) extract (BOE). During this same time, 10 clinical cases reports were published involving adverse events associated with products that contained BOE (C. aurantium) or its predominant alkaloid p-synephrine. A review and assessment of these reports was made. All products involved in these reports were poly-herbal and poly-alkaloidal in composition. The conclusion that BOE and p-synephrine are responsible for adverse events presented in these reports is unjustified, based on the presence of confounding factors, the paucity of detailed information in many reports, current knowledge of the pharmacokinetic and adrenoreceptor binding properties of p-synephrine, the high probability of concurrent but independent events, knowledge of dose-response relationships, and the widespread use of BOE containing supplements and p-synephrine containing juice and food products.