Metabolism of Stevioside and Rebaudioside A from <i>Stevia rebaudiana</i> Extracts by Human Microflora

Gardana, Claudio; Simonetti, Paolo; Canzi, Elena; Zanchi, R.; Pietta, Piergiorgio

doi:10.1021/jf0303619

Cited by 202 publications

(158 citation statements)

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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.…”

Section: Introductionmentioning

confidence: 99%

“…Although steviol glycosides share a common metabolic fate in both rats and humans (Wingard et al, 1980;Hutapea et al, 1997;Gardana et al, 2003;Koyama et al, 2003a;Geuns et al, 2007;Roberts and Renwick, 2008;Wheeler et al, 2008;Nikiforov et al, 2013;Purkayastha et al, 2014Purkayastha et al, , 2015Purkayastha et al, , 2016, some differences in pharmacokinetics have been noted. As evaluated by JECFA at their sixty-ninth meeting (JECFA, 2009), studies comparing the pharmacokinetics of steviol and steviol glucuronide following oral administration of steviol glycosides demonstrated substantial differences in the concentration of circulating plasma steviol and steviol glucuronide between rats and humans (Roberts and Renwick, 2008;Wheeler et al, 2008).…”

Section: Introductionmentioning

confidence: 99%

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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%

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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“…The sweetening property is associated with their contents of several glycosides, stevioside, steviobioside, rebaudiosides A to F, dulcoside A and steviol (Gardana et al, 2003;Geuns, 2004). 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).…”

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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“…These sweeteners can be used under pH conditions ranging from 2 to 10 and at temperatures of up to 120°C [29][30][31][32][33][34].…”

Section: Stability Of Steviol Glycosidesmentioning

confidence: 99%

Main properties of steviol glycosides and their potential in the food industry: a review

González¹,

Tapia²,

Pérez³

et al. 2014

Fruits

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-Introduction. In recent decades, there has been increased interest in developing natural non-caloric sweeteners, providing sensory properties similar to sucrose. One of the most promising alternatives is the steviol glycosides, high-sweetness compounds extracted from the leaves of Stevia rebaudiana Bertoni. Characteristics and properties. In this review article, the characteristics of this plant are described. According to the relevant literature data, this review provides insight into the major steviol glycosides as well as their main characteristics and properties. Toxicity and legislation. We describe the current situation on the toxicity and the legal framework of the above sweeteners. Extraction techniques. This review describes the techniques developed for extraction and purification, including conventional extraction with water/solvent, ion exchange, enzymatic extraction, supercritical fluid and with a focus on membrane filtration, for its proven advantages in the purification of aqueous extract obtained by leaching of the leaves. Applications. This review also presents various evidence relating to the implementation of steviol glycosides in the food industry, with an emphasis on their use in the formulation of fruit juices. Conclusions. Finally, the future prospects of these natural sweeteners are presented. They highlight the need for research in this area, and the great appeal and commercial potential of such compounds, which should be focused on continuous assessment in relation to issues such as the intensity, persistence of sweetness and the absence of other residual flavors, in order to ensure their acceptance, preference and choice by the general public.Stevia rebaudiana / leaves / extraction / glycosides / sweeteners / stevioside / food industry / fruit juices Synthèse sur les principales caractéristiques des glycosides de stéviol et leur intérêt dans l'industrie alimentaire.Résumé -Introduction. Au cours des dernières décennies, il est apparu un intérêt croissant pour le développement des édulcorants naturels, non-caloriques, offrant des propriétés sensorielles similaires à celles du saccharose. Parmi les produits les plus prometteurs apparaissent les glycosides de stéviol, composés très édulcorants extraits des feuilles de Stevia rebaudiana Bertoni. Caractéristiques et propriétés. Dans cette synthèse, nous décrivons les caractéris-tiques de S. rebaudiana. À partir des données de la littérature, cette étude donne un aperçu des principaux glycosides de stéviol et de leurs principales caractéristiques et propriétés ; elle souligne d'autres qualités de ces produits. Toxicité et législation. Nous faisons un point sur la toxicité et le cadre juridique des édulcorants concernés. Techniques d'extraction. Notre synthèse décrit les techniques mises au point pour l'extraction et la purification, y compris l'extraction conventionnelle avec de l'eau ou solvant, l'échange d'ions, l'extraction enzymatique et le fluide supercritique ; elle met l'accent sur la filtration membranaire du fait de ses ava...

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Metabolism of Stevioside and Rebaudioside A from Stevia rebaudiana Extracts by Human Microflora

Cited by 202 publications

References 20 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

Main properties of steviol glycosides and their potential in the food industry: a review

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