Potential risk of higenamine misuse in sports: Evaluation of lotus plumule extract products and a human study

Since 2017, higenamine has been added to the World Anti-Doping Agency (WADA) prohibited list as a β2-agonist prohibited at all times for sportspersons. According to WADA’s report, positive cases of higenamine misuse have been increasing yearly. However, higenamine occurs naturally in the Chinese herb lotus plumule—the green embryo of lotus (Nelumbo nucifera Gaertn) seeds—commercially available as concentrated powder on the Asian market. This study evaluated the major phytochemical components of lotus plumule products using an appropriate extraction method, followed by a human study in which the products were orally administered in multiple doses to investigate the risk of doping violations. Comparing various extraction methods revealed that optimized microwave-assisted extraction exhibited the highest extraction efficiency (extraction time, 26 min; power, 1046 W; and temperature, 120 °C). Subsequently, the alkaloids in lotus plumule products were quantitatively confirmed and compared. Human study participants (n = 6) consumed 0.8 g of lotus plumule (equivalent to 679.6 μg of higenamine) three times daily for three consecutive days. All participants’ urinary higenamine concentrations exceeded the WADA reporting cut-off of 10.0 ng/mL. Accordingly, lotus plumule consumption may engender adverse analytical findings regarding higenamine. Athletes should avoid consuming lotus plumule-containing products during in-and out-of-competition periods.