Consideration of the variability in control tumor incidence data at the Ramazzini Institute in evaluating treatment-related effects following chemical exposure.

The Ramazzini Institute (RI) has been conducting animal carcinogenicity studies for decades, many of which have been considered by authoritative bodies to determine potential carcinogenicity in humans. Unlike other laboratories, such as the U.S. National Toxicology Program (NTP), the RI does not provide a report or record of historical control data. Transparently documenting historical control data is critical in the interpretation of individual study results within the same laboratory. Historical control data allow an assessment of significant trends, either increasing or decreasing, resulting from changes in laboratory methods or genetic drift. In this investigation: (1) we compiled a dataset of the tumors reported in control groups of Sprague-Dawley rats and Swiss mice based on data included in published RI studies on specific substances, and (2) conducted case studies to compare data from this RI control dataset to the findings from multiple RI studies on sweeteners and corresponding breakdown products. We found considerable variability in the tumor incidence across multiple tumor types when comparing across control groups from RI studies. When compared to the tumor incidence in treated groups from multiple studies, the incidence of some tumors considered to be treatment-related fell within the variability of background incidence from the RI control dataset.

A Pharmacological perspective on the temporal properties of sweeteners.

Several non-caloric sweeteners exhibit a delay in sweetness onset and a sweetness linger after sampling. These temporal properties are thought to be the result of non-specific interactions with cell membranes and proteins in the oral cavity. Data and analysis presented in this report also support the potential involvement of receptor affinity and binding kinetics to this phenomenon. In general, affected sweeteners exhibit distinctly higher binding affinity compared to carbohydrate sweeteners, which do not have temporal issues. In addition, binding kinetic simulations illustrate much slower receptor binding association and dissociation kinetics for a set of non-caloric sweeteners presenting temporal issues, in comparison to carbohydrate sweeteners. So, the higher affinity of some non-caloric sweeteners, dictating lower use levels, and affecting binding kinetics, could contribute to their delay and linger in sweetness perception. Simple pharmacology principles could explain, at least in part, some of the temporal issues of sweeteners.

The non-nutritive sweetener sucralose increases ß-arrestin signaling at the constitutively active orphan G protein-coupled receptor GPR52.

Non-nutritive sweeteners are popular food additives owing to their low caloric density and powerful sweetness relative to natural sugars. Their lack of metabolism contributes to evidence proclaiming their safety, yet several studies contradict this, demonstrating that sweeteners activate sweet taste G protein-coupled receptors (GPCRs) and elicit deleterious metabolic functions through unknown mechanisms. We hypothesize that activation of GPCRs, particularly orphan receptors due to their abundance in metabolically active tissues, contributes to the biological activity of sweeteners. We quantified the response of 64 orphans to the sweeteners saccharin and sucralose using a high-throughput ß-arrestin-2 recruitment assay (PRESTO-Tango). GPR52 was the sole receptor that significantly responded to a mixture of sucralose and saccharin. Subsequent experiments revealed sucralose as the activating sweetener. Activation of GPR52 was concentration-dependent, with an EC50 of 0.23 mmol/L and an Emax of 3.43 ± 0.24 fold change at 4 mmol/L. GPR52 constitutively activates CRE pathways; however, we show that sucralose-induced activation of GPR52 does not further activate this pathway. Identification of this novel sucralose-GPCR interaction supports the notion that sucralose elicits off-target signaling through the activation of GPR52, calling into question sucralose's assumed lack of bioactivity.

Differential effects of nutritive and non-nutritive sweet mouth rinsing on appetite in adults with obesity.

BACKGROUND: Excessive added sugar intake has been associated with obesity; however, the effect of dietary sweetness on energy intake (EI) and appetite in adults with and without obesity has not yet been determined. OBJECTIVE: To assess the effect of mouth rinses with and without energy and sweetness on measures of appetite, and to compare responses between subjects with body mass index (BMI) between 18.5 and 24.9 kg/m2 or ≥30 kg/m2. METHODS: In this randomized, double-blind crossover study, 39 subjects (age 23±5y; 17 male, 22 female; BMI 18.5-24.9 kg/m2: n = 21; ≥30 kg/m2: n = 18) performed modified sham-feeding (MSF) with a mouth rinse containing either sucrose, sucralose, maltodextrin, or water for 2min before expectorating the solution. Blood sampling and subjective appetite assessments occurred at baseline (-5) and 15, 30, 60, and 90min post-MSF. After, EI was assessed at a buffet meal and post-meal appetite ratings were assessed hourly for 3h. RESULTS: Post-MSF ghrelin increased for water vs. maltodextrin (water: p = 0.03). Post-MSF cholecystokinin increased following maltodextrin-MSF (p = 0.03) and sucralose-MSF (p = 0.005) vs. sucrose for those with BMI:18.5-24.9 kg/m2 only. There was greater post-MSF desire to eat in response to water vs. sucrose (p = 0.03) and reduced fullness with sucralose for those with BMI≥30 vs. 18.5-24.9 kg/m2 (p < 0.001). There was no difference in EI at the buffet meal by mouth rinse (p = 0.98) or by BMI (p = 0.12). However, there was greater post-meal fullness following sucralose-MSF vs. water (p = 0.03) and sucrose (p = 0.004) for those with BMI≥30 vs. 18.5-24.9 kg/m2. CONCLUSION: Sucralose rinsing led to greater cephalic phase CCK release in adults with a BMI:18.5-24.9 kg/m2 only; however, ghrelin responses to unsweetened rinses were energy-specific for all adults. As subsequent EI was unaffected, further investigation of cephalic phase appetite is warranted.

Sucralose regulates postprandial blood glucose in mice through intestinal sweet taste receptors Tas1r2/Tas1r3.

BACKGROUND: Non-nutritive sweeteners (such as sucralose) bind to sweet receptors Tas1r2/Tas1r3 on intestinal endocrine L cells after diets to upregulate blood glucose. However, the mechanism by which sucralose regulates postprandial blood glucose (PBG) has not been clarified to date. We hypothesized that the gut sweet taste receptor was one of the targets for sucralose to regulate PBG. The aim of this study was to examine the effect of sucralose on PBG based on the gut sweet taste receptor signaling pathway and to explore the mechanism. Therefore, we examined PBG, genes, and proteins associated with the gut sweet receptor pathway in sucralose-exposed mice. RESULTS: The results showed that after 12 weeks of sucralose exposure the PBG of mice increased significantly, and the expression of intestinal sweet taste receptors increased correspondingly. Within the concentration range of this experiment, a significant increase of PBG was observed in mice fed on sucralose with a concentration equal to or higher than 0.33 g L-1 . CONCLUSION: Long-term consumption of sucralose may increase body weight and the risk of elevated PBG, resulting in overexpression of sweetness receptors and glucose transporters. The mechanism of these effects might be the result of non-nutritive sweeteners binding to sweetness receptors Tas1r2/Tas1r3 in gut endocrine cells and upregulating Slc5a1 and Slc2a2. But we cannot rule out that the rise in PBG is the result of a combination of sweet receptors and gut microbes. Therefore, the effect of gut microbes on PBG needs to be studied further. © 2023 Society of Chemical Industry.

Toxicological and pharmacokinetic properties of sucralose-6-acetate and its parent sucralose: in vitro screening assays.

The purpose of this study was to determine the toxicological and pharmacokinetic properties of sucralose-6-acetate, a structural analog of the artificial sweetener sucralose. Sucralose-6-acetate is an intermediate and impurity in the manufacture of sucralose, and recent commercial sucralose samples were found to contain up to 0.67% sucralose-6-acetate. Studies in a rodent model found that sucralose-6-acetate is also present in fecal samples with levels up to 10% relative to sucralose which suggest that sucralose is also acetylated in the intestines. A MultiFlow® assay, a high-throughput genotoxicity screening tool, and a micronucleus (MN) test that detects cytogenetic damage both indicated that sucralose-6-acetate is genotoxic. The mechanism of action was classified as clastogenic (produces DNA strand breaks) using the MultiFlow® assay. The amount of sucralose-6-acetate in a single daily sucralose-sweetened drink might far exceed the threshold of toxicological concern for genotoxicity (TTCgenotox) of 0.15 µg/person/day. The RepliGut® System was employed to expose human intestinal epithelium to sucralose-6-acetate and sucralose, and an RNA-seq analysis was performed to determine gene expression induced by these exposures. Sucralose-6-acetate significantly increased the expression of genes associated with inflammation, oxidative stress, and cancer with greatest expression for the metallothionein 1 G gene (MT1G). Measurements of transepithelial electrical resistance (TEER) and permeability in human transverse colon epithelium indicated that sucralose-6-acetate and sucralose both impaired intestinal barrier integrity. Sucralose-6-acetate also inhibited two members of the cytochrome P450 family (CYP1A2 and CYP2C19). Overall, the toxicological and pharmacokinetic findings for sucralose-6-acetate raise significant health concerns regarding the safety and regulatory status of sucralose itself.

Impact of dietary sucralose and sucrose-sweetened water intake on lipid and glucose metabolism in male mice.

AIMS: Overconsumption of sugar-sweetened beverages (SSBs) is associated with an increased risk of metabolic disorders, including obesity and diabetes. However, accumulating evidence also suggests the potential negative impact of consuming nonnutritive sweeteners (NNSs) on weight and glycaemic control. The metabolic effects of sucralose, the most widely used NNS, remain controversial. This study aimed to compare the impact of intake of dietary sucralose (acceptable daily intake dose, ADI dose) and sucrose-sweetened water (at the same sweetness level) on lipid and glucose metabolism in male mice. MATERIALS AND METHODS: Sucralose (0.1 mg/mL) or sucrose (60 mg/mL) was added to the drinking water of 8-week-old male C57BL/6 mice for 16 weeks, followed by oral glucose and intraperitoneal insulin tolerance tests, and measurements of bone mineral density, plasma lipids, and hormones. After the mice were sacrificed, the duodenum and ileum were used for examination of sweet taste receptors (STRs) and glucose transporters. RESULTS: A significant increase in fat mass was observed in the sucrose group of mice after 16 weeks of sweetened water drinking. Sucrose consumption also led to increased levels of plasma LDL, insulin, lipid deposition in the liver, and increased glucose intolerance in mice. Compared with the sucrose group, mice consuming sucralose showed much lower fat accumulation, hyperlipidaemia, liver steatosis, and glucose intolerance. In addition, the daily dose of sucralose only had a moderate effect on T1R2/3 in the intestine, without affecting glucose transporters and plasma insulin levels. CONCLUSION: Compared with mice consuming sucrose-sweetened water, daily drinking of sucralose within the ADI dose had a much lower impact on glucose and lipid homeostasis.

Human wastewater tracking in tropical Hawaiian island streams using qualitative and quantitative assessments of combined fecal indicating bacteria and sucralose, an organic micropollutant of emerging concern.

Prevalence of cesspools on tropical islands suggests that high concentrations of enteric bacteria in streams and coastal waters are an indicator of groundwater contamination by human wastewater. But enterococci bacteria may also be from homeothermic animals common to these watersheds or bacteria living in sediments. Sucralose, a manufactured chemical not destroyed in passage through the human gut, cesspools, septic systems, or wastewater treatment facilities, was used to test for the presence of human wastewater in streams on the island of Kauai, Hawaii. Effluent from six municipal wastewater treatment plants showed an average concentration of 39,167 ng/L of sucralose, roughly back-calculated to 9 ng/L per person, enough to present itself in cesspool effluent contaminated waters. Of 24 streams tested, 79% were positive for sucralose at least once in four sets of sampling. All streams tested positive for enterococci bacteria above established standards. Serial testing of the pair of indicators in the same location over time and applying the Multiplication Rule to the independent samples provide a probabilistic certainty level that the water is chronically polluted by human waste. When repeatedly paired with tests for enterococci, sucralose testing is a cost-effective means for assessing human health risk and for developing proper waste management programs that has been underutilized in under-developed tropical and island settings.

Development and Validation of Test for "Leaky Gut" Small Intestinal and Colonic Permeability Using Sugars in Healthy Adults.

BACKGROUND: Oral monosaccharides and disaccharides are used to measure in vivo human gut permeability through urinary excretion. AIMS: The aims were as follows: (1) to obtain normative data on small intestinal and colonic permeability; (2) to assess variance on standard 16 g fiber diet performed twice; (3) to determine whether dietary fiber influences gut permeability measurements; and (4) to present pilot data using 2 selected probes in patients with diarrhea-predominant irritable bowel syndrome (IBS-D). METHODS: Sixty healthy female and male adults, age 18-70 years, participated in 3 randomized studies (2 studies on 16.25 g and 1 study on 32.5 g fiber) in otherwise standardized diets. At each test, the following sugars were ingested: 12C-mannitol, 13C-mannitol, rhamnose (monosaccharides), sucralose, and lactulose (disaccharides). Standardized meals were administered from 24 hours before and during 24 hours post-sugars with 3 urine collections: 0-2, 2-8, and 8-24 hours. Sugars were measured using high-performance liquid chromatography-tandem mass spectrometry. Eighteen patients with IBS-D underwent 24-hour excretion studies after oral 13C-mannitol and lactulose. RESULTS: Baseline sugars (>3-fold above lower limits of quantitation) were identified in the 3 studies: 12C-mannitol in all participants; sucralose in 4-8, and rhamnose in 1-3. Median excretions/24 h (percentage of administered dose) for 13C-mannitol, rhamnose, lactulose, and sucralose were ∼30%, ∼15%, 0.32%, and 2.3%, respectively. 13C-mannitol and rhamnose reflected mainly small intestinal permeability. Intraindividual saccharide excretions were consistent, with minor differences with 16.25 g vs 32.5 g fiber diets. Median interindividual coefficient of variation was 76.5% (10-90 percentile: 34.6-111.0). There were no significant effects of sex, age, or body mass index on permeability measurements in health. 13C-mannitol measurements are feasible in IBS-D. CONCLUSIONS: Baseline 12C-mannitol excretion precludes its use; 13C-mannitol is the preferred probe for small intestinal permeability.

The effect of aspartame and sucralose intake on body weight measures and blood metabolites: role of their form (solid and/or liquid) of ingestion.

The ingestion of non-caloric sweeteners (NCS) from food and/or drink was intended to reduce caloric intake without compromising palatability. However, the inconclusive relation between NCS and body weight may partially relate to their form of ingestion (solid or liquid). Thus, two paralleled experiments (aspartame and sucralose) were conducted. In each, Sprague Dawley rats (7-week-old male) were randomly divided into four groups. In Expt 1, aspartame (0·05 %) was added to the diet (AD) or drinking water (AW) or both diet and water (ADW), and a control group (C) was given a non-sweetened diet with plain water. In Expt 2, sucralose (0·016 %) was similarly provided in the diet (SD) or drinking water (SW) or both diet and water (SDW), with a control group (C). All rats had free access to food and water for 7 weeks. Energy intake, body weight and body composition were monitored and blood metabolites were determined. Results showed that aspartame ingestion significantly increased body weight and fat mass mainly due to an increase in energy efficiency. The effect was related to the amount rather than the form of ingestion. Additionally, aspartame ingestion was associated with glucose intolerance. Sucralose ingestion had a similar impact to that of aspartame though to a lesser extent. In conclusion, 7-week ingestion of aspartame and sucralose had adverse effects on body measures that were not related to the form of ingestion.

Effects of nonnutritional sugars on lipid and carbohydrate content, physiological uptake, and excretion in Drosophila suzukii.

The nonnutritive sugar, erythritol, has the potential to be a human-safe management tool for the small fruits and cherry pest, Drosophila suzukii, or spotted-wing drosophila. Feeding on erythritol decreases fly survival and oviposition by starving and creating an osmotic imbalance in the body. Recently, we demonstrated that erythritol combined with another nonnutritive sugar, sucralose, was fed upon more than erythritol alone and hastens D. suzukii mortality. This suggests that sucralose is a suitable nonnutritive phagostimulant alternative to sucrose. Although promising, the nutritional and physiological impacts of sucralose on D. suzukii are unknown. In this study, we investigated whether sucralose is metabolized or excreted by D. suzukii when fed various erythritol, sucrose, and sucralose formulations. We found that sucralose cannot be metabolized or converted into any nutritional substitutes or storage carbohydrates in D. suzukii. Instead, sucralose molecules were largely accumulated in the hemolymph and slowly excreted from the body, creating a significant osmotic imbalance in D. suzukii. To excrete unused sugars, flies will use their own body fluids to restore homeostasis, resulting in losing a substantial amount of body weight and becoming desiccated in the process. In summary, ingesting sucralose leads to starvation and hyperosmotic pressure in the body, causing a decrease in fitness. With confirmation of sucralose being non-metabolizable and phagostimulative to D. suzukii, the erythritol+sucralose formulation is a promising insecticide for growers to use.

Sources of microbial contamination in the watershed and coastal zone of Soufriere, St. Lucia.

The Sustainable Development Goal 6 calls for global progress by 2030 in treating domestic wastewater and providing access to adequate sanitation facilities. However, meeting these goals will be a challenge for most Small Island Developing States, including Caribbean island nations. In the nearshore zone of the Soufriere region on the Caribbean island of St. Lucia, there is a history of high levels of bacteria of fecal origin. Possible land-based sources of microbial contamination in the Soufriere Bay include discharges from the Soufriere River and transport of wastewater, including fecal material from the town of Soufriere. This area is an important tourist destination and supports a local fishery. To identify the sources of microbial contamination in Soufriere Bay, a range of monitoring methods were employed in this study. In grab samples of surface water collected from the Soufriere River, counts of total coliforms and Escherichia coli were elevated above water quality guidelines. However, the spikes in concentrations of these indicator organisms in the river did not necessarily coincide with the spikes in the levels of total coliforms and E. coli detected in samples collected on the same dates in Soufriere Bay, indicating that there are other sources of pollution in the Bay besides discharges from the river. Monitoring for chemical indicators of wastewater (i.e., caffeine, sucralose, fluconazole) in the Soufriere River indicated that there are inputs of sewage or human fecal material throughout the watershed. However, analysis of Bacteroidales 16S rRNA genetic markers for fecal bacteria originating from humans, bovine ruminants, or other warm-blooded animals indicated that the majority of microbial contamination in the river was not from humans. Monitoring for chemical indicators of wastewater using passive samplers deployed in Soufriere Bay indicated that there are two "hot spots" of contamination located offshore of economically depressed areas of the town of Soufriere. This study indicates that efforts to control contamination of Soufriere Bay by fecal microorganisms must include management of pollution originating from both sewage and domestic animals in the watershed.

Calibration and field validation of POCIS passive samplers for tracking artificial sweeteners as indicators of municipal wastewater contamination in surface waters.

Polar organic chemical integrative samplers (POCIS) are widely used to track contaminants in surface waters. However, POCIS have not been used previously to monitor for artificial sweeteners as an indicator of wastewater pollution. In this study, we report for the first time the POCIS sampling rates (Rscal) for four artificial sweetener compounds, acesulfame (0.001 L/day), sucralose (0.114 L/day), cyclamate (0.001 L/day), and saccharin (0.002 L/day). We also prepared a modified POCIS with Strata X-AW anion exchange resin as a sorbent (i.e., ax-POCIS) and determined the sampling rates for sucralose (0.060 L/day) and acesulfame (0.128 L/day). Rscal values were adjusted according to the rate of loss of the performance reference compound, metoprolol-d6 from deployed POCIS to yield field sampling rates (i.e., Rsfield). Field validation of the monitoring method was conducted in Presqu'ile Bay on the north-central coast of Lake Ontario that is impacted by discharges from a sewage lagoon. POCIS were deployed at four sites within the bay and in the lagoon discharge. The four artificial sweeteners, as well as caffeine, ibuprofen, and other microcontaminants of sewage origin, were present throughout the bay at estimated concentrations in the ng/L range, and in the lagoon discharge at estimated concentrations higher by approximately one order of magnitude. Because acesulfame is present in ionic form over the pH range of natural waters, there are uncertainties related to the sampling rates using the standard POCIS. Sucralose is recommended as the best choice for source tracking using POCIS. There was good agreement between the concentrations of sucralose estimated from POCIS and the measured concentrations in grab samples of surface water in the bay. The present study provides key data for monitoring artificial sweeteners using POCIS.

Quantification and cytotoxicity of degradation products (chloropropanols) in sucralose containing e-liquids with propylene glycol and glycerol as base.

Electronic cigarettes (e-cigarettes) have gained increasing popularity in recent years, mostly because they are supposed to be less harmful than regular cigarettes. Therefore, it is highly imperative to investigate possible noxious effects to protect the consumers. E-liquids consist of propylene glycol, glycerol, aroma compounds and sweeteners. One of these sweeteners is a chlorinated version of sucrose, namely sucralose. The aim of this work was to investigate degradation products of sucralose in the presence of propylene glycol and glycerol at different temperatures of commercially available e-cigarettes. Chemical analysis and biological tests were simultaneously performed on e-liquid aerosol condensates. The results of the chemical analysis, which was executed by employing GC-MS/GC-FID, demonstrated high amounts of various chloropropanols. The most abundant one is extremely toxic, namely 3-chloropropane-1,2-diol, which can be detected at concentrations ranging up to 10,000 mg/kg. Furthermore, a cytotoxicity investigation of the condensates was performed on HUVEC/Tert2 cells in which metabolic activity was determined by means of resazurin assay. The cellular metabolic activity significantly decreased by treatment with e-liquid aerosol condensate. Due to the results of this study, we advise against the use of sucralose as sweetener in e-liquids.

The Pattern of Fos-Like Immunoreactivity Expressed Within the Nucleus of the Solitary Tract Is Associated With Individual Variation in the Taste Quality of a Stimulus.

Outbred rats differ in their preference for the artificial sweetener sucralose. Psychophysical assessments have shown that the taste of sucralose is differentially generalized to either sucrose or a sucrose-quinine (QHCl) mixture in sucralose preferers (SP) and sucralose avoiders (SA), respectively. It remains to be determined if these differences in the psychophysical assessment of the taste of sucralose are due to an insensitivity to any bitter-like taste component of sucralose in SP or reduced sensitivity to a sweet-like component in SA that may mask any putative aversive side-taste in SP. Here, we exploited the proposed chemotopic organization of the rostral nucleus of the solitary tract (rNTS) to further parse out the root differences in the perception of the salient taste qualities of sucralose using Fos-like immunoreactivity (FLI) to approximate neural activation following intraoral delivery of sucrose, QHCl, and sucralose solutions in previously categorized SA and SP. First, we confirmed previous reports that the medial third of the NTS is primarily responsive to intraoral infusions of the bitter taste stimulus QHCl while sucrose produces a more diffuse pattern of FLI. Upon comparing the FLI generated by intraoral sucralose, we found that the pattern in SA was indistinguishable from that of QHCl while SP displayed a pattern of FLI more representative of a sucrose-QHCl mixture. We conclude that SA, relative to SP, may be less sensitive to the sucrose-like properties of sucralose and that an enhanced sensitivity to these sucrose-like qualities may mask a QHCl-like quality in SP.

Sweetener influences plasma concentration of flavonoids in humans after an acute intake of a new (poly)phenol-rich beverage.

BACKGROUND AND AIM: The overconsumption of sucrose is closely related to sugar-sweetened beverages and one of the main factors associated with the increase of metabolic diseases, such as type 2 diabetes, obesity, and insulin resistance. So, the addition of alternative sweeteners to new fruit-based drinks could contribute to minimizing the incidence or severity of these pathologies. Nevertheless, current knowledge on the influence of these additives on the bioactive compounds present in these beverages is still scarce.new-onset hypertension, but few data were published in Asian. We aimed to investigate the association of lipid profiles with new-onset hypertension in a Chinese community-based non-hypertensive cohort without lipid-lowering treatment (n = 1802). METHODS AND RESULTS: Hence, to contribute to the understanding of this issue, the plasma concentration of phenolic compounds (anthocyanins and flavanones), after the ingestion of a new maqui-citrus-based beverage, supplemented with sucrose (natural high caloric), stevia (natural non-caloric), or sucralose (artificial non-caloric), was evaluated as evidence of their intestinal absorption and metabolism previous to renal excretion. The beverages were ingested by volunteers (n = 20) and the resulting phenolic metabolites in plasma were analyzed by UHPLC-ESI-MS/MS. A total of 13 metabolites were detected: caffeic acid sulfate, caffeic acid glucuronide, 3,4-dihydroxyfenylacetic, 3,4-dihydroxyfenylacetic sulfate. 3,4-dihydroxyfenylacetic acid di-sulfate, 3,4-dihydroxyfenylacetic di-glucuronide, 3,4-dihydroxyfenylacetic glucuronide-sulfate, trans-ferulic acid glucuronide, naringenin glucuronide, vanillic acid, vanillic acid sulfate, vanillic acid glucuronide-sulfate, and vanillic acid di-glucuronide, being recorded their maximum concentration after 30-60 min. CONCLUSION: In general, sucralose provided the greatest absorption value for most of these metabolites, followed by stevia. Due to this, the present study proposes sucralose and stevia (non-caloric sweeteners) as valuable alternatives to sucrose (high caloric sweetener), to avoid the augmented risk of several metabolic disorders.

Palatability of pediatric formulations: do rats predict aversiveness?

BACKGROUND: The brief-access taste aversion (BATA) model has been used as an alternative taste assessment tool to human taste panels and became an important element of pharmaceutical drug development, especially regarding pediatric patient's compliance. This model has been validated, demonstrating a concentration-dependent sensitivity to drug aversiveness, as well as the capacity to evaluate the taste-masking effects of cyclodextrins. In the BATA model, samples are presented randomly to rodents in numerous sipper tubes and a lickometer is used for the electronic record of licks in a sophisticated approach. OBJECTIVES: The aim of this study was to test possible drug taste-masking strategies. Additionally, we have used an alternative approach to measure the animal lick number in the presence of different compounds, non-simultaneously. RESULTS: In the present work we show for the first time the licking profile of different compounds during the time course of the experiment, with each animal being exposed to only one bottle of testing product. To validate the experiments, quinine hydrochloride dihydrate (QHD) was used as a bitter reference compound. CONCLUSION: The results obtained using this simple approach showed that aversiveness is dependent on the assay duration, and that it is possible to predict the aversiveness just by measuring the mass of the tested substance consumption. Moreover, some taste-masking strategies, such as those used in pediatric formulations and corresponding to the addition of sweeteners or flavors, cannot be predicted from rodents BATA model.

An Assessment of Ambient Water Quality and Challenges with Access to Water and Sanitation Services for Individuals Experiencing Homelessness in Riverine Encampments.

Individuals experiencing unsheltered homelessness face significant barriers to accessing water, sanitation, and hygiene services, but the risks associated with this lack of access and barriers to service provision have been largely understudied. We analyzed water samples upstream and downstream of three homeless encampments in the San Diego River watershed and interviewed service providers from public and nonprofit sectors to assess local perceptions about challenges and potential solutions for water and sanitation service provision in this context. Water upstream from encampments contained detectable levels of caffeine and sucralose. Escherichia coli concentrations downstream of the encampments were significantly greater than concentrations upstream, but there was no significant change in the concentrations of other pollutants, including caffeine and sucralose. The HF183 marker of Bacteroides was only detected in one sample upstream of an encampment and was not detected downstream. Overall, there was insufficient evidence to suggest that the encampments studied here were responsible for contributing pollution to the river. Nevertheless, the presence of caffeine, sucralose, and HF183 indicated that there are anthropogenic sources of contamination in the river during dry weather and potential risks associated with the use of this water by encampment residents. Interviews with service providers revealed perceptions that the provision of water and sanitation services for this population would be prohibitively expensive. Interviewees also reported perceptions that most riverbank residents avoided contact with service providers, which may present challenges for the provision of water and sanitation service unless trust is first built between service providers and residents of riverine encampments.

Mechanistic differences in the effects of sucrose and sucralose on the phase stability of lysozyme solutions.

The effect of two disaccharide analogues, sucrose and sucralose, on the phase stability of aqueous lysozyme solutions has been addressed from a mechanistic viewpoint by a combination of experiment and molecular dynamics (MD) simulations. The influence of the added low molecular weight salts (NaBr, NaI and NaNO3) was considered as well. The cloud-point temperature measurements revealed a larger stabilizing effect of sucralose. Upon increasing sugar concentration, the protein solutions became more stable and differences in the effect of sucralose and sucrose amplified. It was confirmed that the addition of either of the two sugars imposed no secondary structure changes of the lysozyme. Enthalpies of lysozyme-sugar mixing were exothermic and a larger effect was recorded for sucralose. MD simulations indicated that acidic, basic and polar amino acid residues play predominant roles in the sugar-protein interactions, mainly through hydrogen bonding. Such sugar mediated protein-protein interactions are thought to be responsible for the biopreserative nature of sugars. Our observations hint at mechanistic differences in sugar-lysozyme interactions: while sucrose does not interact directly with the protein's surface for the most part (in line with the preferential hydration hypothesis), sucralose forms hydrogen bonds with acidic, basic and polar amino acid residues at the lysozyme's surface (in line with the water replacement hypothesis).

A Novel Urinary Biomarker Approach Reveals Widespread Exposure to Multiple Low-Calorie Sweeteners in Adults.

BACKGROUND: Observational investigations into the health impacts of low-calorie sweeteners (LCSs) in humans fail to adequately identify or fully characterize LCS consumption. OBJECTIVES: We aimed to utilize a novel biomarker approach to investigate exposure to 5 LCSs and to test whether reported low-calorie sweetened beverage (LCSB) consumption effectively identifies exposure to LCSs in adults. METHODS: In this cross-sectional analysis, 2 population studies were conducted in adults. Urinary excretions of 5 LCSs, namely acesulfame-K, saccharin, cyclamate, sucralose, and steviol glycosides, were simultaneously determined using LC tandem-MS. In Study 1, previously collected 24-h urine samples (n = 357) were analyzed. In Study 2, previously collected 24-h urine samples (n = 79) were analyzed to compare urinary excretions of LCSs with self-reported LCSB consumption for identifying LCS exposure. Exposure to LCSs was characterized using descriptive statistics and chi-square tests were performed to assess associations between age-groups and LCS excretion, and to assess the proportion of individuals identified as LCS consumers using biomarker data or reported LCSB consumption. RESULTS: A total of 341 adults (45% men) and 79 adults (39% men) were included in the final analysis of Studies 1 and 2, respectively. In Study 1, >96% of samples contained ≥1 LCS and almost 60% contained ≥3 LCSs. A greater proportion of younger adults (<40 y old) excreted ≥3 LCSs than older adults (>40 y old) (P < 0.001). In Study 2, a much higher prevalence of LCS consumption was observed using biomarker data (92%) than reported LCSB consumption (6%) (P < 0.001). CONCLUSIONS: This work indicates widespread exposure to LCSs, suggesting that population-based research to date into LCS exposure and health may be flawed. Therefore, a urinary biomarker approach offers considerable potential for more robust investigations in this area.