Metabolism of stevioside in pigs and intestinal absorption characteristics of stevioside, rebaudioside A and steviol

Geuns, Jan; Augustijns, Patrick; Mols, Raf; Buyse, Johan; Driessen, Bert

doi:10.1016/s0278-6915(03)00191-1

Cited by 107 publications

(82 citation statements)

References 27 publications

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“…Steviol glycosides pass undigested through the upper gastrointestinal tract to the colon where they are hydrolyzed to steviol by sequential removal of one sugar moiety at a time, prior to absorption of steviol (Wingard et al, 1980;Hutapea et al, 1997;Gardana et al, 2003;Koyama et al, 2003a,b;Geuns et al, 2003Geuns et al, , 2007Renwick and Tarka, 2008;Purkayastha et al, 2015). In rats (Roberts and Renwick, 2008), pigs (Geuns et al, 2003) and humans Wheeler et al, 2008) exposures to the parent steviol glycosides are negligible following oral exposure. Once absorbed from the gastrointestinal tract, steviol undergoes conjugation with glucuronic acid in the liver to form steviol glucuronide.…”

Section: Introductionmentioning

confidence: 99%

Chemical-specific adjustment factors (inter-species toxicokinetics) to establish the ADI for steviol glycosides

Roberts

Lynch

Rogerson

et al. 2016

Regulatory Toxicology and Pharmacology

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Abbreviations: λz, terminal elimination constant; ADI, acceptable daily intake; AUC0-last, area under the curve from time zero until the last sampling time point; AE, adverse events; AUC, area under the plasma concentration-time curve; AUC-0.75-inf, AUC from time zero to infinity; AUClast, AUC to the last quantifiable observation; BLQ, below the limit of quantification; BMI, body mass index; bw, body weight; Cmax, concentration maximum; CSAF, chemical-specific adjustment factor; EE, efficacy evaluable population; EKG, electrocardiogram; HBsAg, hepatitis B surface antigen; IQR, interquartile range; IRB, Institutional Review Board; JECFA, Joint FAO/WHO Expert Committee on Food Additives; LC-MS/MS, liquid chromatography-tandem mass spectrometry; LLOQ, lower limit of quantification, LOQ, limit of quantification; NOAEL, noobserved-adverse-effect level; PP, per protocol population; SD, standard deviation; T1/2, half-life; Tmax, time to maximum concentration; WHO, World Health Organization * Corresponding author: Tel: +1-905-542-2900 E-mail address: ashley.roberts@intertek.com AbstractThe acceptable daily intake (ADI) of commercially available steviol glycosides is currently 4 mg/kg body weight (bw)/day, based on application of a 100-fold uncertainty factor to a noobserved-adverse-effect-level value from a chronic rat study. Within the 100-fold uncertainty factor is a 10-fold uncertainty factor to account for inter-species differences in toxicokinetics (4-fold) and toxicodynamics (2.5-fold). Single dose pharmacokinetics of stevioside were studied in rats (40 and 1,000 mg/kg bw) and in male human subjects (40 mg/kg bw) to generate a chemical-specific, inter-species toxicokinetic adjustment factor. Tmax values for steviol were at ~8 and ~20 hours after administration in rats and humans, respectively. Peak concentrations of steviol were similar in rats and humans, while steviol glucuronide concentrations were significantly higher in humans. Glucuronidation in rats was not saturated over the dose range 40-1,000 mg/kg bw. The AUC0-last for steviol was approximately 2.8-fold greater in humans compared to rats. Chemical-specific adjustment factors for extrapolating toxicokinetics from rat to human of 1 and 2.8 were established based on Cmax and AUC0-last data respectively. Because these factors are lower than the default value of 4.0, a higher ADI for steviol glycosides of between 6 to 16 mg/kg bw/d is justified.

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Section: Introductionmentioning

confidence: 99%

Chemical-specific adjustment factors (inter-species toxicokinetics) to establish the ADI for steviol glycosides

Roberts

Lynch

Rogerson

et al. 2016

Regulatory Toxicology and Pharmacology

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“…These glycosides and their derivatives are known to account for 4-20% of the dry weight of stevia leaves (Oliveira-Filho et al, 1989;Geuns et al, 2003). There is a preferential accumulation of different glycosides in different parts of the plant (Alves and Ruddat, 1979;Richman et al, 1999) more apparent in mature than young stevia tissues for sweetening glycosides (Geuns, 2004).…”

Section: Introductionmentioning

confidence: 99%

Potential use of stevia rebaudiana in animal feeds

et al. 2011

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SHORT NOTE ADDITIONAL KEYWORDSNutritional value. Poultry feed. PALABRAS CLAVE ADICIONALESValor nutritivo. Alimento aves. SUMMARYThe nutritional profile of the leaves and stem of Stevia rebaudiana, and their potential utilization in an animal model were studied. Stevia leaves and stem had 16% and 6.7% crude protein and were low in fat content (2.6 and 1.1%) respectively. The fatty acid profile of fat showed a preponderance of unsaturated fatty acids (65.8% and 71.4% for leaves and stem respectively). Linolenic acid was the most abundant fatty acid in stevia leaf oil (36%) whereas linoleic acid was the highest in stems (38%). The crude fiber contents on dry fat free basis were 6.8% and 45.4% for leaves and stem respectively. The K content of stevia leaves and stem were comparable; Ca, Mg, Fe, Cu, Zn and Mn were higher in leaves and the opposite was true for Na. The tests with broiler chickens showed that apparent, nitrogen corrected, and true metabolisable energy values for leaves were 2113, 2098 and 2223 kcal/kg and for stems 1573, 1554 and 1675 kcal/kg respectively. Retention of the protein from the leaves and stems by chickens was 63% and 65.7% respectively. Stevia leaves contain other nutritional attributes besides of the sweetening components.

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“…As González, et al [19] have reported stevioside and rebaudioside A have multiple advantages as dietary supplements. They are non-metabolizable (non-caloric) [57][58][59] non acidogenic, and do not cause dental caries [60]. Another notable benefit is that the consumption of both steviol glycosides is safe for human health and there are no restrictions on their use by people suffering from diabetes [46, 48-50, 52, 53].…”

Section: Studies On Safe Consumption Of the Stevia And Its Use By Conmentioning

confidence: 99%

Stevia Derivative and its Potential Uses in Diabetic-Directed Foods. Review

Pérez

González

Vaillant

et al. 2016

Journal of Nutrients

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Metabolism of stevioside in pigs and intestinal absorption characteristics of stevioside, rebaudioside A and steviol

Cited by 107 publications

References 27 publications

Chemical-specific adjustment factors (inter-species toxicokinetics) to establish the ADI for steviol glycosides

Chemical-specific adjustment factors (inter-species toxicokinetics) to establish the ADI for steviol glycosides

Potential use of stevia rebaudiana in animal feeds

Stevia Derivative and its Potential Uses in Diabetic-Directed Foods. Review

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