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Exactly which synephrine alkaloids does Citrus aurantium (bitter orange) contain?

Abstract

Following the withdrawal of ephedrine from the dietary supplement marketplace sales of products containing Citrus aurantium (CA) (bitter orange) for weight loss are believed to have increased dramatically. CA contains a number of constituents speculated to lead to weight loss, of which the most frequently cited constituent is synephrine. Concerns have been raised about the safety of products containing synephrine. To develop an adequate basis for clinical and public health recommendations, it is necessary to understand the nature of the synephrine alkaloids in CA. There are six possible isomers of synephrine (para, meta, ortho; and for each a d or l form). Some authors have stated that CA contains only p-synephrine, whereas other authors have stated that CA contains m-synephrine. This is an important distinction because the two molecules have different pharmacologic properties, which may differentially affect safety and efficacy. We are unable to identify published data that explicitly show whether CA contains p-synephrine, m-synephrine, or both. In this brief report, we show that at least one product purportedly containing synephrine alkaloids from CA contains both p-synephrine and m-synephrine. We believe this justifies further investigation into which synephrine alkaloids are present in CA and products purportedly containing synephrine alkaloids from CA and the relative quantities of each of the different isomers.

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Acknowledgements

This work was supported by NIH P30DK056336. Support for the purchase and installation of the Sciex API III mass spectrometer used was provided by a Shared Instrumentation grant (S10 RR06487) from the National Center for Research Resources and the UAB Office of the Provost. Ongoing support for the operation of the mass spectrometry facility has been provided by a grant (P30 CA13148) from the National Cancer Institute to the UAB Comprehensive Cancer Center (Al Lobuglio, PI).

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Correspondence to D B Allison.

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Editors' Note: The article below is a technical report of the constituents of bitter orange, a commonly used over-the-counter (OTC) preparation for weight loss. The US Food and Drug Administration has called for the scientific community to assess existing and future OTC weight loss preparations to determine if they contain constituents that might produce adverse events in susceptible individuals. Allison and colleagues have determined that one such preparation of bitter orange contains both p-synephrine and m-synephrine. Their report confirms that it is not possible to rely on ingredient labels of OTC weight reduction preparations, and additional studies should be performed to determine if ingredients that may cause harm are present.

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Allison, D., Cutter, G., Poehlman, E. et al. Exactly which synephrine alkaloids does Citrus aurantium (bitter orange) contain?. Int J Obes 29, 443–446 (2005). https://doi.org/10.1038/sj.ijo.0802879

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  • DOI: https://doi.org/10.1038/sj.ijo.0802879

Keywords

  • Citrus aurantium
  • synephrine alkaloids
  • phenylephrine
  • bitter orange

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