Presence of higenamine in beetroot containing ‘foodstuffs’ and the implication for WADA‐relevant anti‐doping testing

Leaney, Amy E.; Heath, Jenna; Midforth, Emma; Beck, Paul; Brown, Paul D.; Mawson, Deborah H.

doi:10.1002/dta.3383

Cited by 7 publications

(7 citation statements)

References 21 publications

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“…Leaney et al investigated the potential of beetroot to contribute to higenamine findings in the context of sports drug testing and demonstrated the presence of higenamine in various processed beetroot products up to ca. 300 ng/g 86 . Elimination studies with such products resulted in urinary higenamine levels below 0.1 ng/mL, that is, approximately 100‐fold below the currently applied MRL of 10 ng/mL.…”

Section: β2‐agonists Hormone and Metabolic Modulatorsmentioning

confidence: 96%

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Annual banned‐substance review 16^th edition—Analytical approaches in human sports drug testing 2022/2023

Thevis,

Kuuranne,

Geyer

2023

Drug Testing and Analysis

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In this 16th edition of the annual banned‐substance review on analytical approaches in human sports drug testing, literature on recent developments in this particular section of global anti‐doping efforts that was published between October 2022 and September 2023 is summarized and discussed. Most recent additions to the continuously growing portfolio of doping control analytical approaches and investigations into analytical challenges in the context of adverse analytical findings are presented, taking into account existing as well as emerging challenges in anti‐doping, with specific focus on substances and methods of doping recognized in the World Anti‐Doping Agency's 2023 Prohibited List. As in previous years, focus is put particularly on new or enhanced analytical options in human doping controls, appreciating the exigence and core mission of anti‐doping and, equally, the conflict arising from the opposingly trending extent of the athlete's exposome and the sensitivity of instruments nowadays commonly available in anti‐doping laboratories.

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Section: β2‐agonists Hormone and Metabolic Modulatorsmentioning

confidence: 96%

“…300 ng/g. 86 Elimination studies with such products resulted in urinary higenamine levels below 0.1 ng/mL, that is, approximately 100-fold below the currently applied MRL of 10 ng/mL.…”

Section: Steroid Profiling In Urine and Bloodmentioning

confidence: 99%

Annual banned‐substance review 16^th edition—Analytical approaches in human sports drug testing 2022/2023

Thevis,

Kuuranne,

Geyer

2023

Drug Testing and Analysis

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“…Methylated fractions were then subjected to nuclear magnetic resonance spectroscopy (NMR). Therefore, the substances of interest were dissolved and transferred into the NMR tube using 50 μL of deuterated dimethylsulfoxide (DMSO-D 6 ), and 1 H, 1 H, 1 H-COSY, 13 C-1 H-HSQC, and 13 C-1 H-HMBC experiments were conducted utilizing a BRUKER AVANCE NEO 800 MHz NMR spectrometer (Bruker, Karlsruhe, Germany).…”

Section: Higenamine Sulfo-conjugates Synthesis and Structural Charact...mentioning

confidence: 99%

“…[3][4][5][6][7] Higenamine has been described as a key component of a great variety of natural plants such as Nandina domestica, Tinospora crispa, and recently Beta vulgaris. [8][9][10][11][12][13] The content of higenamine in natural plants can vary greatly, prompting numerous studies to investigate whether the consumption of plant extracts or products commonly used in popular medicine can lead to an AAF. In some cases, these studies have demonstrated the risk of unintentional anti-doping rule violations (e.g., Nelumbo nucifera).…”

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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“…As previously mentioned, the study by Kozhuharov, Ivanov, and Ivanova [11] analyzed 50 studies published between 1996 and June 21, 2021, and found a prevalence of 28% of contamination among food supplements. After this period, in our searches, using the same descriptors and research platforms, we found four more studies [31][32][33][34] whose objective was to evaluate the contamination of sports food supplements.…”

Section: Prevalence Of Contamination Of Food Supplements Their Main C...mentioning

confidence: 99%

Protocolo de redução de risco de doping não intencional causado por consumo de suplementos alimentares

Mendes,

Prado

2023

Rev Bras Fisiol Exerc

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Introdução: A suplementação alimentar tem sido considerada a principal causa de doping não intencional entre atletas; no entanto, a prevalência de consumo de suplementos por atletas de elite é próxima a 100%, e a conscientização sobre o risco de doping não intencional não parece ser efetiva. A literatura científica tem apontado alguns possíveis fatores relacionados à má qualidade dos produtos disponíveis no mercado; entretanto, não propõe qualquer protocolo que oriente, objetivamente, profissionais da área da saúde e atletas quanto à redução de risco doping e danos à saúde causados por suplementos contaminados com substâncias proibidas não listadas no rótulo. Objetivo: Propor um protocolo de redução de risco de doping não intencional, a partir de uma revisão narrativa sobre estudos que tenham discutido os fatores regulatórios relacionados aos suplementos alimentares, prevalência de contaminação de suplementos, seus principais contaminantes, possíveis efeitos adversos à saúde humana, conscientização de atletas sobre as indicações para uso de suplementos e os riscos de doping não intencional. Métodos: Revisão narrativa e análise documental nos sites das agências internacionais relacionadas à política antidopagem, como a Agência Mundial Antidopagem (WADA) e a Autoridade Brasileira de Controle de Dopagem (ABCD). Resultados: Foi elaborado um protocolo de seis passos, que propõe métodos potencialmente capazes de reduzir o risco de doping não intencional. Conclusão: Esse instrumento poderia ser de elevada relevância no âmbito esportivo, especialmente entre atletas de elite, no entanto, sem excluir a importância para outros consumidores desse tipo de produto, uma vez que foram identificadas elevadas prevalências de contaminação de suplementos alimentares e de consumo desse produto, bem como insuficiente grau de conscientização por parte de seus consumidores.

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Presence of higenamine in beetroot containing ‘foodstuffs’ and the implication for WADA‐relevant anti‐doping testing

Cited by 7 publications

References 21 publications

Annual banned‐substance review 16^th edition—Analytical approaches in human sports drug testing 2022/2023

Annual banned‐substance review 16^th edition—Analytical approaches in human sports drug testing 2022/2023

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

Protocolo de redução de risco de doping não intencional causado por consumo de suplementos alimentares

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Presence of higenamine in beetroot containing ‘foodstuffs’ and the implication for WADA‐relevant anti‐doping testing

Cited by 7 publications

References 21 publications

Annual banned‐substance review 16th edition—Analytical approaches in human sports drug testing 2022/2023

Annual banned‐substance review 16th edition—Analytical approaches in human sports drug testing 2022/2023

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

Protocolo de redução de risco de doping não intencional causado por consumo de suplementos alimentares

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Product

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Annual banned‐substance review 16^th edition—Analytical approaches in human sports drug testing 2022/2023

Annual banned‐substance review 16^th edition—Analytical approaches in human sports drug testing 2022/2023