Stevia Metabolites in Biosamples Ranging from Fetal Life to Adulthood. (29th May 2020) - Halasa, Brianna
Abstract: Objectives: Stevia rebaudiana (Bertoni) is a perennial herb native to South America. Its sweetness (∼200–400 times sweeter than sucrose) results from steviol glycosides, particularly stevioside and rebaudioside A. Steviol glycosides are hydrolyzed in the gastrointestinal tract resulting in steviol, which is incompletely absorbed in the colon. In the liver, steviol is converted into its glucuronide derivative and renally excreted. While the use of stevia leaves and crude extracts is still prohibited in the US, steviol glycosides have been 'generally recognized as safe' (GRAS) by the Food and Drug Administration (FDA) in 2008. We aimed to determine whether steviol glycosides and glucuronidation products can be found in biosamples collected as early as 2004. Methods: In 38 adults, steviol glycosides and glucuronide were analyzed in plasma and in corresponding cerebrospinal fluid samples (CSF); additional 2 persons had only CSF tested. Prenatal exposure was determined in biosamples from 28 individuals (13 amniotic fluid, 15 cord blood). We used ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) utilizing a Thermo Scientific Vanquish UPLC and a Thermo Scientific Altis triple quadruple mass spectrometer with heated electrospray ionization (HESI-II, Thermo Scientific) in negative ion mode (2500 V). Results: Seven of 38 adults (18%) had detectable steviol glucuronide concentrations (5 in plasma only, 2 in both plasma and CSF). Maximal concentrations in plasma were 805.4 ng/mL and in CSF 3.3 ng/mL. Two of 13 amniotic fluid samples were positive for steviol glucuronide (max. conc. 93.5 ng/mL) and 1 of 15 cord blood samples contained a trace. In contrast to steviol glucuronide, steviol glycoside could not be measured. Conclusions: Steviol glucuronide was found in all types of biosamples (plasma, CSF, amniotic fluid and cord blood), most commonly in plasma (18%). This indicates that exposure to steviol metabolites starts in prenatal life and that these metabolites cross various barriers (e.g., blood-CSF, blood-amniotic fluid). Only samples obtained in and after 2008 were positive for steviol glucuronide, which coincides with the FDA approval. Potential health consequences of exposure to stevia metabolites require further study. Funding Sources: N/A.