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Kristina I Rother - One of the best experts on this subject based on the ideXlab platform.
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effects of Sucralose ingestion versus Sucralose taste on metabolic responses to an oral glucose tolerance test in participants with normal weight and obesity a randomized crossover trial
Nutrients, 2019Co-Authors: Alexander D Nichol, Kristina I Rother, Clara Salame, Yanina M PepinoAbstract:Here, we tested the hypothesis that Sucralose differentially affects metabolic responses to labeled oral glucose tolerance tests (OGTTs) in participants with normal weight and obesity. Participants (10 with normal weight and 11 with obesity) without diabetes underwent three dual-tracer OGTTs preceded, in a randomized order, by consuming Sucralose or water, or by tasting and expectorating Sucralose (e.g., sham-fed; sweetness control). Indices of β-cell function and insulin sensitivity (SI) were estimated using oral minimal models of glucose, insulin, and C-peptide kinetics. Compared with water, Sucralose ingested (but not sham-fed) resulted in a 30 ± 10% increased glucose area under the curve in both weight groups. In contrast, the insulin response to Sucralose ingestion differed depending on the presence of obesity: decreased within 20–40 min of the OGTT in normal-weight participants but increased within 90–120 min in participants with obesity. Sham-fed Sucralose similarly decreased insulin concentrations within 60 min of the OGTT in both weight groups. Sucralose ingested (but not sham-fed) increased SI in normal-weight participants by 52 ± 20% but did not affect SI in participants with obesity. Sucralose did not affect glucose rates of appearance or β-cell function in either weight group. Our data underscore a physiological role for taste perception in postprandial glucose responses, suggesting sweeteners should be consumed in moderation.
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widespread Sucralose exposure in a randomized clinical trial in healthy young adults
The American Journal of Clinical Nutrition, 2017Co-Authors: Martin H Garraffo, Allison C Sylvetsky, Peter Walter, Kim Robien, Kristina I RotherAbstract:Background: Low-calorie sweeteners (LCSs) are found in many foods and beverages, but consumers may not realize their presence, and their role in appetite, weight, and health is controversial. Although consumption limits based on toxicologic safety are well established, the threshold required to exert clinically relevant metabolic effects is unknown. Objectives: This study aimed to determine whether individuals who do not report consumption of LCSs can be correctly characterized as “unexposed” and to investigate whether instructions to avoid LCSs are effective in minimizing exposure. Design: Eighteen healthy 18- to 35-y-old “nonconsumers” (<1 food or beverage with LCSs/mo) enrolled in a 2-wk trial designed to evaluate the effects of LCSs on the gut microbiota. The trial consisted of 3 visits. At baseline, participants were counseled extensively about avoiding LCSs. After the run-in, participants were randomly assigned to consume diet soda containing Sucralose or carbonated water (control) 3 times/d for 1 wk. Food diaries were maintained throughout the study, and a spot urine sample was collected at each visit. Results: At baseline, 8 participants had Sucralose in their urine (29.9–239.0 ng/mL; mean ± SD: 111.4 ± 91.5 ng/mL). After the run-in, Sucralose was found in 8 individuals (2 of whom did not have detectable Sucralose at baseline) and ranged from 25.0 to 1062.0 ng/mL (mean ± SD: 191.7 ± 354.2 ng/mL). Only 1 participant reported consumption of an LCS-containing food before her visit. After the intervention, Sucralose was detected in 3 individuals randomly assigned to receive carbonated water (26–121 ng/mL; mean ± SD: 60.7 ± 52.4 ng/mL). Conclusions: Despite the selection of healthy volunteers with minimal reported LCS consumption, more than one-third were exposed to Sucralose at baseline and/or before randomization, and nearly half were exposed after assignment to the control. This shows that instructions to avoid LCSs are not effective and that nondietary sources (e.g., personal care products) may be important contributors to overall exposure. This trial was registered at clinicaltrials.gov as {"type":"clinical-trial","attrs":{"text":"NCT02877186","term_id":"NCT02877186"}}NCT02877186.
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plasma concentrations of Sucralose in children and adults
Toxicological & Environmental Chemistry, 2017Co-Authors: Allison C Sylvetsky, Viviana Bauman, Jenny E Blau, Martin H Garraffo, Peter Walter, Kristina I RotherAbstract:ABSTRACTWe aimed to measure concentrations of the commonly used artificial sweetener Sucralose, following ingestion of doses reflecting a range of consumption and to compare concentrations in children and adults. Eleven adults consumed 355 mL water containing 0 mg (control), 68, 170, or 250 mg Sucralose (equivalent to 1–4 diet sodas). A second group of adults (n = 11) consumed 355 mL Diet Rite Cola™ (68 mg Sucralose and 41 mg acesulfame-potassium (ace-K)) or 68 mg Sucralose and 41 mg ace-K in seltzer. Beverages were provided at separate visits in randomized order, prior to an oral glucose tolerance test. Eleven children consumed 0 or 68 mg Sucralose in 240 mL water, in an identical study design. Blood was collected before beverage ingestion and serially for 120 min. Sucralose doses (corrected for weight) resulted in similar plasma concentrations in children and adults. Concentrations were comparable whether Sucralose was administered in water, combined with ace-K, or in diet soda. Due to their lower body ...
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Sucralose a synthetic organochlorine sweetener overview of biological issues
Journal of Toxicology and Environmental Health-part B-critical Reviews, 2013Co-Authors: Susan S Schiffman, Kristina I RotherAbstract:Sucralose is a synthetic organochlorine sweetener (OC) that is a common ingredient in the world’s food supply. Sucralose interacts with chemosensors in the alimentary tract that play a role in sweet taste sensation and hormone secretion. In rats, Sucralose ingestion was shown to increase the expression of the efflux transporter P-glycoprotein (P-gp) and two cytochrome P-450 (CYP) isozymes in the intestine. P-gp and CYP are key components of the presystemic detoxification system involved in first-pass drug metabolism. The effect of Sucralose on first-pass drug metabolism in humans, however, has not yet been determined. In rats, Sucralose alters the microbial composition in the gastrointestinal tract (GIT), with relatively greater reduction in beneficial bacteria. Although early studies asserted that Sucralose passes through the GIT unchanged, subsequent analysis suggested that some of the ingested sweetener is metabolized in the GIT, as indicated by multiple peaks found in thin-layer radiochromatographic profiles of methanolic fecal extracts after oral Sucralose administration. The identity and safety profile of these putative Sucralose metabolites are not known at this time. Sucralose and one of its hydrolysis products were found to be mutagenic at elevated concentrations in several testing methods. Cooking with Sucralose at high temperatures was reported to generate chloropropanols, a potentially toxic class of compounds. Both human and rodent studies demonstrated that Sucralose may alter glucose, insulin, and glucagon-like peptide 1 (GLP-1) levels. Taken together, these findings indicate that Sucralose is not a biologically inert compound.
Lee V Grotz - One of the best experts on this subject based on the ideXlab platform.
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a 12 week randomized clinical trial investigating the potential for Sucralose to affect glucose homeostasis
Regulatory Toxicology and Pharmacology, 2017Co-Authors: Lee V Grotz, Ashley Roberts, Xavier Pisunyer, Daniel Porte, Richard J TroutAbstract:Abstract The discovery of gut sweet taste receptors has led to speculations that non-nutritive sweeteners, including Sucralose, may affect glucose control. A double-blind, parallel, randomized clinical trial, reported here and previously submitted to regulatory agencies, helps to clarify the role of Sucralose in this regard. This was primarily an out-patient study, with 4-week screening, 12-week test, and 4-week follow-up phases. Normoglycemic male volunteers (47) consumed ∼333.3 mg encapsulated Sucralose or placebo 3x/day at mealtimes. HbA1c, fasting glucose, insulin, and C-peptide were measured weekly. OGTTs were conducted in-clinic overnight, following overnight fasting twice during screening phase, twice during test phase, and once at follow-up. Throughout the study, glucose, insulin, C-peptide and HbA1c levels were within normal range. No statistically significant differences between Sucralose and placebo groups in change from baseline for fasting glucose, insulin, C-peptide and HbA1c, no clinically meaningful differences in time to peak levels or return towards basal levels in OGTTs, and no treatment group differences in mean glucose, insulin, or C-peptide AUC change from baseline were observed. The results of other relevant clinical trials and studies of gastrointestinal sweet taste receptors are compared to these findings. The collective evidence supports that Sucralose has no effect on glycemic control.
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Sucralose non carcinogenicity a review of the scientific and regulatory rationale
Nutrition and Cancer, 2016Co-Authors: Colin Berry, Lee V Grotz, David Brusick, Samuel Monroe Cohen, Jerry F Hardisty, Gary M WilliamsAbstract:Regulatory authorities worldwide have found the nonnutritive sweetener, Sucralose, to be noncarcinogenic, based on a range of studies. A review of these and other studies found through a comprehensive search of electronic databases, using appropriate key terms, was conducted and results of that review are reported here. An overview of the types of studies relied upon by regulatory agencies to assess carcinogenicity potential is also provided as context. Physiochemical and pharmacokinetic/toxicokinetic studies confirm stability under conditions of use and reveal no metabolites of carcinogenic potential. In vitro and in vivo assays reveal no confirmed genotoxic activity. Long-term carcinogenicity studies in animal models provide no evidence of carcinogenic potential for Sucralose. In studies in healthy adults, Sucralose was well-tolerated and without evidence of toxicity or other changes that might suggest a potential for carcinogenic effects. In summary, Sucralose does not demonstrate carcinogenic activity even when exposure levels are several orders of magnitude greater than the range of anticipated daily ingestion levels.
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an overview of the safety of Sucralose
Regulatory Toxicology and Pharmacology, 2009Co-Authors: Lee V Grotz, Ian C MunroAbstract:Abstract Sucralose is a non-nutritive sweetener used in a broad range of foods and beverages and is the non-nutritive sweetener in retail SPLENDA® Sweetening Products, composed of Sucralose and common food ingredients. A review of the extensive body of evidence that supports the safety of Sucralose is provided. The results of an independent review of a new study investigating the safety of a Sucralose-mixture retail product, Granulated SPLENDA® No Calorie Sweetener, are also discussed. The collective evidence supports the conclusion that the ingredient, Sucralose, is safe for use in food and that the Sucralose-mixture product, Granulated SPLENDA® No Calorie Sweetener, is also safe for its intended use.
Anthony Sclafani - One of the best experts on this subject based on the ideXlab platform.
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rats display a robust bimodal preference profile for Sucralose
Chemical Senses, 2011Co-Authors: Gregory C Loney, Anthony Sclafani, Annmarie Torregrossa, James C Smith, Lisa A EckelAbstract:Female Sprague–Dawley rats display considerable variability in their preference for the artificial sweetener Sucralose over water. While some rats can be classified as Sucralose preferrers (SP), as they prefer Sucralose across a broad range of concentrations, others can be classified as Sucralose avoiders (SA), as they avoid Sucralose at concentrations above 0.1 g/L. Here, we expand on a previous report of this phenomenon by demonstrating, in a series of 2-bottle 24-h preference tests involving water and an ascending series of Sucralose concentrations, that this variability in Sucralose preference is robust across sex, stage of the estrous cycle, and 2 rat strains (Long–Evans and Sprague–Dawley). In a second experiment involving a large sample of rats (n = 50), we established that the ratio of SP to SA is approximately 35–65%. This bimodal behavioral response to Sucralose appears to be driven by taste because rats display a similar bimodal licking response to a range of Sucralose solutions presented during brief-access tests. Finally, we have shown that Sucralose avoidance is extremely robust as 23-h water-deprived SA continue to avoid Sucralose in 1-h single-bottle intake tests. Based on their reduced licking responses to Sucralose during brief-access (taste driven) tests, and the fact that their distaste for Sucralose cannot be overcome by the motivation to rehydrate, we conclude that SA detect a negative taste quality of Sucralose that SP are relatively insensitive to.
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female rats show a bimodal preference response to the artificial sweetener Sucralose
Chemical Senses, 2004Co-Authors: Anthony Sclafani, Richard A ClareAbstract:The preference of female Sprague–Dawley rats for Sucralose, a non-nutritive sweetener derived from sucrose, was evaluated in 23 h two-bottle tests with water or saccharin. Overall, the rats displayed weak or no preferences for Sucralose (0.25–4 g/l) over water but strong preferences for saccharin (0.5–8 g/l) over water and saccharin (1 g/l) over Sucralose (0.5 g/l). The rats also preferred a saccharin + sucrose mixture to sucrose, but sucrose to a Sucralose + sucrose mixture. There were marked individual differences in Sucralose preferences: about half the rats preferred Sucralose to water at some concentrations while most remaining rats avoided Sucralose. Both subgroups preferred saccharin to Sucralose. Sucralose appears to have an aversive offtaste that reduces its palatability to rats.
J P Finn - One of the best experts on this subject based on the ideXlab platform.
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A carcinogenicity study of Sucralose in the CD-1 mouse.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2020Co-Authors: S W Mann, M M Yuschak, S J Amyes, P Aughton, J P FinnAbstract:The potential carcinogenicity of Sucralose was evaluated by feeding groups of 52 male and 52 female CD-1 mice a diet containing Sucralose at 0.3% (3000 ppm), 1.0% (10,000 ppm) or 3.0% (30,000 ppm) for 104 weeks. A group of 72 male and 72 female mice received diet without Sucralose and served as controls. Week 1 achieved doses ranging from 543 to 5870mg/kg body weight/day in the low-dose males and high-dose females, respectively. Sucralose had no adverse effect on survival. No significant changes attributable to Sucralose were found in the clinical condition or behaviour of the mice. Organ weights and the gross appearance of tissues were unaffected by treatment. The mean erythrocyte counts of females receiving the highest dietary concentration were slightly, but statistically significantly, lower than those of the controls after 104 weeks of treatment. Group mean body weight gain at the highest dietary concentration of Sucralose was significantly less than that of the control in mice of both sexes. Food consumption, after correction for Sucralose content, was lower for female mice, but not statistically significant. Water consumption for male mice receiving the highest dietary concentration was approximately 9% higher than that of the controls. There were statistically significant increases in the incidence of several non-neoplastic findings, but these were not considered to be related to Sucralose administration. Treatment with Sucralose did not increase the incidence of any tumour or influence the types of tumours observed. It was concluded that Sucralose is not carcinogenic in CD-1 mice. The body weight gain and erythrocyte observations at the 3.0% dietary level were of limited biological significance as they were not accompanied by any histopathologic finding and had no impact on survival. The remaining dose levels were judged to have no effects.
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A combined chronic toxicity/carcinogenicity study of Sucralose in Sprague-Dawley rats.
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association, 2020Co-Authors: S W Mann, M M Yuschak, S J Amyes, P Aughton, J P FinnAbstract:The chronic toxicity and potential carcinogenicity of Sucralose was evaluated by exposing Sprague-Dawley rats to dietary concentrations of this low-calorie sweetener both in utero and for up to 104 weeks following parturition. The rats assigned to the toxicity phase of this investigation were administered diets containing either 0% (control), 0.3% (3000 ppm), 1.0% (10,000 ppm) or 3.0% (30,000 ppm) Sucralose. Each treatment group comprised 30 male and 30 female rats, of which 15 males and 15 females were sacrificed after 52 weeks of treatment. The surviving rats were killed following 78 weeks of Sucralose administration. In the carcinogenicity phase of this investigation, groups of 50 male and 50 female rats were administered dietary Sucralose at concentrations of 0% (control 1), 0% (control 2), 0.3%, 1.0% or 3.0% for 104 weeks. Evaluation of the data obtained from the two phases of this study showed that Sucralose was not carcinogenic. Sucralose did not adversely affect the survival or clinical condition of the rats, and there were no toxicologically significant findings. Group mean body weight gain and food consumption were significantly decreased in a dose-dependent manner in Sucralose-treated rats throughout the treatment period as compared to the controls. The primary effect of Sucralose on food consumption, and secondarily on body weight gain, was established in later studies to be due to the fact that diets containing high concentrations of Sucralose are unpalatable to rats. These subsequent studies established that the reduction of body weight gain seen in previous rat studies using Sucralose in the diet at concentrations of 1% and below resulted from reduced food intake as a direct consequence of the unpalatable nature of Sucralose. Similarly, at concentrations of 3% in the diet, it was shown that approximately 95% of the effect on body weight gain could be attributed to the reduction in food intake due to the reduced palatability of the diet, the remainder apparently due to a physiologic response to the high concentrations of non-digestible Sucralose in the rats' diet. Complete toxicological evaluations of gavage studies with histopathological evaluations demonstrated that even at the 3% dietary level, toxicity was not responsible for the small body weight gain decrement. Gross and histopathologic examinations revealed that the administration of Sucralose affected neither the types nor incidence of the tumours observed. The incidences of some non-neoplastic findings were statistically significantly increased in the Sucralose treated groups relative to the controls. These included: renal pelvic epithelial hyperplasia in all female treatment groups, renal pelvic mineralization in females administered the intermediate or highest dietary concentrations of Sucralose, adrenal cortical haemorrhagic degeneration in high-dose group female rats, and the histopathologic incidence of cataracts at necropsy in high-dose group male rats. The non-neoplastic findings that occurred were of no toxicological significance since they were either spontaneous findings commonly observed in aged rats of this strain or the physiological response to high dietary levels of a poorly absorbed compound.
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a combined chronic toxicity carcinogenicity study of Sucralose in sprague dawley rats
Food and Chemical Toxicology, 2000Co-Authors: S W Mann, M M Yuschak, S J Amyes, P Aughton, J P FinnAbstract:Abstract The chronic toxicity and potential carcinogenicity of Sucralose was evaluated by exposing Sprague–Dawley rats to dietary concentrations of this low-calorie sweetener both in utero and for up to 104 weeks following parturition. The rats assigned to the toxicity phase of this investigation were administered diets containing either 0% (control), 0.3% (3000 ppm), 1.0% (10,000 ppm) or 3.0% (30,000 ppm) Sucralose. Each treatment group comprised 30 male and 30 female rats, of which 15 males and 15 females were sacrificed after 52 weeks of treatment. The surviving rats were killed following 78 weeks of Sucralose administration. In the carcinogenicity phase of this investigation, groups of 50 male and 50 female rats were administered dietary Sucralose at concentrations of 0% (control 1), 0% (control 2), 0.3%, 1.0% or 3.0% for 104 weeks. Evaluation of the data obtained from the two phases of this study showed that Sucralose was not carcinogenic. Sucralose did not adversely affect the survival or clinical condition of the rats, and there were no toxicologically significant findings. Group mean body weight gain and food consumption were significantly decreased in a dose-dependent manner in Sucralose-treated rats throughout the treatment period as compared to the controls. The primary effect of Sucralose on food consumption, and secondarily on body weight gain, was established in later studies to be due to the fact that diets containing high concentrations of Sucralose are unpalatable to rats. These subsequent studies established that the reduction of body weight gain seen in previous rat studies using Sucralose in the diet at concentrations of 1% and below resulted from reduced food intake as a direct consequence of the unpalatable nature of Sucralose. Similarly, at concentrations of 3% in the diet, it was shown that approximately 95% of the effect on body weight gain could be attributed to the reduction in food intake due to the reduced palatability of the diet, the remainder apparently due to a physiologic response to the high concentrations of non-digestible Sucralose in the rats’ diet. Complete toxicological evaluations of gavage studies with histopathological evaluations demonstrated that even at the 3% dietary level, toxicity was not responsible for the small body weight gain decrement. Gross and histopathologic examinations revealed that the administration of Sucralose affected neither the types nor incidence of the tumours observed. The incidences of some non-neoplastic findings were statistically significantly increased in the Sucralose treated groups relative to the controls. These included: renal pelvic epithelial hyperplasia in all female treatment groups, renal pelvic mineralization in females administered the intermediate or highest dietary concentrations of Sucralose, adrenal cortical haemorrhagic degeneration in high-dose group female rats, and the histopathologic incidence of cataracts at necropsy in high-dose group male rats. The non-neoplastic findings that occurred were of no toxicological significance since they were either spontaneous findings commonly observed in aged rats of this strain or the physiological response to high dietary levels of a poorly absorbed compound.
Lisa A Eckel - One of the best experts on this subject based on the ideXlab platform.
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preference for Sucralose predicts behavioral responses to sweet and bittersweet tastants
Chemical Senses, 2012Co-Authors: Gregory C Loney, Annmarie Torregrossa, Chris Carballo, Lisa A EckelAbstract:Rats can be classified as either Sucralose avoiders (SA) or Sucralose preferrers (SP) based on their behavioral responses in 2-bottle preference, 1-bottle intake, and brief-access licking tests. The present study demonstrates that this robust phenotypic variation in the preference for Sucralose predicts acceptance of saccharin, an artificial sweetener with a purported concentration-dependent “bitter” side taste and a 0.25 M sucrose solution adulterated with increasing concentrations of quinine hydrochloride (QHCl). Specifically, SA displayed decreased preference for and intakes of saccharin (≥41.5 mM) and sucrose–QHCl (>0.5 mM QHCl) solutions, relative to SP. In a second experiment involving brief-access (30-s) tests, SP and SA did not differ in their unconditioned licking responses across a range of sodium chloride or QHCl solutions (0.03–1 mM). However, the acceptability threshold for sucrose was lower in SA, relative to SP (0.06 and 0.13 M, respectively). Our findings suggest that phenotypic differences in Sucralose preference are indicative of a more general difference in the hedonic processing of stimuli containing “bittersweet” or “sweet” taste qualities.
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rats display a robust bimodal preference profile for Sucralose
Chemical Senses, 2011Co-Authors: Gregory C Loney, Anthony Sclafani, Annmarie Torregrossa, James C Smith, Lisa A EckelAbstract:Female Sprague–Dawley rats display considerable variability in their preference for the artificial sweetener Sucralose over water. While some rats can be classified as Sucralose preferrers (SP), as they prefer Sucralose across a broad range of concentrations, others can be classified as Sucralose avoiders (SA), as they avoid Sucralose at concentrations above 0.1 g/L. Here, we expand on a previous report of this phenomenon by demonstrating, in a series of 2-bottle 24-h preference tests involving water and an ascending series of Sucralose concentrations, that this variability in Sucralose preference is robust across sex, stage of the estrous cycle, and 2 rat strains (Long–Evans and Sprague–Dawley). In a second experiment involving a large sample of rats (n = 50), we established that the ratio of SP to SA is approximately 35–65%. This bimodal behavioral response to Sucralose appears to be driven by taste because rats display a similar bimodal licking response to a range of Sucralose solutions presented during brief-access tests. Finally, we have shown that Sucralose avoidance is extremely robust as 23-h water-deprived SA continue to avoid Sucralose in 1-h single-bottle intake tests. Based on their reduced licking responses to Sucralose during brief-access (taste driven) tests, and the fact that their distaste for Sucralose cannot be overcome by the motivation to rehydrate, we conclude that SA detect a negative taste quality of Sucralose that SP are relatively insensitive to.
