Dietary higenamine from Annonaceae family fruits as a possible source of unintentional doping

Muniz‐Santos, Renan; Avezum, Juliana; Abidão-Neto, Bichara; Cameron, Luiz Cláudio

doi:10.1016/j.forsciint.2022.111539

Cited by 8 publications

(1 citation statement)

References 35 publications

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“…8,11 The tropical Annonaceae family, which comprises more than 2000 species and has considerable economic importance, mainly as a source of edible fruit, has also been described as a natural source of higenamine. [14][15][16] Hence, one of the aims of this study was to investigate whether ingesting such fruits could lead to AAFs in sports by conducting controlled single-dose and multidose administration studies with three of the most widely consumed Annona species (i.e., Annona muricata, Annona cherimola, and Annona squamosa). Further investigations into higenamine phase-II metabolites were conducted.…”

Section: Introductionmentioning

confidence: 99%

Investigations into Annona fruit consumption as a potential source of dietary higenamine intake in the context of sports drug testing

Rubio

Thomas

Euler

et al. 2023

Drug Testing and Analysis

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Higenamine is prohibited in sports as a β2‐agonist by the World Anti‐Doping Agency. As a key component of a great variety of plants, including the Annonaceae family, one aim of this research project was to evaluate whether the ingestion of Annona fruit could lead to higenamine adverse analytical findings. Single‐dose administration studies including three Annona species (i.e., Annona muricata, Annona cherimola, and Annona squamosa) were conducted, leading to higenamine findings below the established minimum reporting level (MRL) of 10 ng/mL in urine. In consideration of cmax values (7.8 ng/mL) observed for higenamine up to 24 h, a multidose administration study was also conducted, indicating cumulative effects, which can increase the risk of exceeding the applicable MRL doping after Annona fruit ingestion. In this study, however, the MRL was not exceeded at any time point. Further, the major urinary excretion of higenamine in its sulfo‐conjugated form was corroborated, its stability in urine was assessed, and in the absence of reference material, higenamine sulfo‐conjugates were synthesized and comprehensively characterized, suggesting the predominant presence of higenamine 7‐sulfate. In addition, the option to include complementary biomarkers of diet‐related higenamine intake into routine doping controls was investigated. A characteristic urinary pattern attributed to isococlaurine, reticuline, and a yet not fully characterized bismethylated higenamine glucuronide was observed after Annona ingestion but not after supplement use, providing a promising dataset of urinary biomarkers, which supports the discrimination between different sources of urinary higenamine detected in sports drug testing programs.

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Section: Introductionmentioning

confidence: 99%