Unveiling the profound influence of sucralose on metabolism and its role in shaping obesity trends.

Artificial sweeteners, prominently exemplified by sucralose, have become pervasive in contemporary diets, prompting intriguing questions about their impact on metabolism and their potential role in the unfolding trends of obesity. Covering topics from its discovery to analytical methods for detection and determination in food samples, the manuscript scrutinizes the metabolic effects of sucralose. Notably, the association between sucralose intake and obesity is examined, challenging the conventional belief of its role in weight management. The document comprehensively examines in vivo studies, revealing sucralose's implications on insulin resistance, gut microbiota, and metabolic syndrome, providing a nuanced comprehension of its impact on human health. Additionally, it explores sucralose's effects on glucose and lipid metabolism, blood pressure, and cardiovascular health, underscoring its possible involvement in malignancy development. The review concludes with a call for increased public awareness, education, and updated dietary guidelines to help individuals make informed choices about sweetener consumption. The future perspectives section highlights the need for longitudinal studies, exploring alternative sweeteners, and refining acceptable daily intake limits to ensure public health recommendations align with evolving regulatory guidelines. Overall, the manuscript provides a comprehensive overview of sucralose's multifaceted impact on health, urging further research and a balanced perspective on sweetener consumption.

Artificial sweeteners and their implications in diabetes: a review.

Diabetes is a significant global health concern, highlighting the critical role of dietary strategies in its management and prevention. Artificial sweeteners (ASs), due to their capacity to provide sweetness without contributing to caloric intake, have emerged as a potential tool in diabetes management. This review thoroughly examines the nuanced relationship between artificial sweeteners and diabetes, addressing their benefits and potential risks. ASs have been shown to aid in weight management, a key factor in reducing diabetes risk, and do not impact immediate blood glucose levels, offering improved glucose control for individuals with diabetes. Beyond these benefits, however, artificial sweeteners may interact complexly with gut microbiota, potentially altering its composition and affecting metabolic health. This interaction introduces concerns regarding insulin sensitivity and the risk of insulin resistance, with studies reporting conflicting findings. This comprehensive review highlights the importance of a nuanced approach to understanding the implications of artificial sweeteners in diabetes management. Given the mixed evidence on their health effects, there is a clear need for further research to fully elucidate the role of artificial sweeteners in metabolic health and their suitability as part of dietary interventions for diabetes.

Long-term metabolic effects of non-nutritive sweeteners.

OBJECTIVE: Excessive consumption of added sugars has been linked to the rise in obesity and associated metabolic abnormalities. Non-nutritive sweeteners (NNSs) offer a potential solution to reduce sugar intake, yet their metabolic safety remains debated. This study aimed to systematically assess the long-term metabolic effects of commonly used NNSs under both normal and obesogenic conditions. METHODS: To ensure consistent sweetness level and controlling for the acceptable daily intake (ADI), eight weeks old C57BL/6 male mice were administered with acesulfame K (ace K, 535.25 mg/L), aspartame (411.75 mg/L), sucralose (179.5 mg/L), saccharin (80 mg/L), or steviol glycoside (Reb M, 536.25 mg/L) in the drinking water, on the background of either regular or high-fat diets (in high fat diet 60% of calories from fat). Water or fructose-sweetened water (82.3.gr/L), were used as controls. Anthropometric and metabolic parameters, as well as microbiome composition, were analyzed following 20-weeks of exposure. RESULTS: Under a regular chow diet, chronic NNS consumption did not significantly affect body weight, fat mass, or glucose metabolism as compared to water consumption, with aspartame demonstrating decreased glucose tolerance. In diet-induced obesity, NNS exposure did not increase body weight or alter food intake. Exposure to sucralose and Reb M led to improved insulin sensitivity and decreased weight gain. Reb M specifically was associated with increased prevalence of colonic Lachnospiracea bacteria. CONCLUSIONS: Long-term consumption of commonly used NNSs does not induce adverse metabolic effects, with Reb M demonstrating a mild improvement in metabolic abnormalities. These findings provide valuable insights into the metabolic impact of different NNSs, aiding in the development of strategies to combat obesity and related metabolic disorders.

Intake of Artificial Sweeteners through Soft Drinks in the Preschool- and School-Aged Population.

One of the main public health issues that has recently been observed in a greater number of children is being overweight. The cause certainly lies in the decreasing physical activity of children, but mostly in their eating habits. Soft drinks are recognized as the most significant contributor to body overweight due to high sugar content; thus, as a result of numerous campaigns, part of the sugar is replaced by artificial sweeteners (ASs). Despite their advantage due to their low caloric value, WHO recommends that they should not be used to achieve weight control or as prevention for reducing the risk of non-communicable diseases, as there is no evidence of their effectiveness. Apart from beverages, artificial sweetener combinations are also added to a variety of "low fat" and "high protein" food products, which are highly favored especially among the young population. Therefore, it is necessary to take care of the cumulative intake. The conducted study included a survey of 323 parents of children aged 1-14 years, as well as an analysis of the AS content in the products most often consumed by the respondents. The results of the survey show that a large part of children (40%) aged 3-14 often consume soft drinks. Different products (soft drinks, juices/nectars, syrups) were sampled based on the respondents' responses, and an analysis showed that 54% of them contained one or more ASs. In addition, the survey indicated parents' lack of information about the presence of AS in products, as 51% of parents declared that they do not read the declarations of the products they buy. It is necessary to persist in consumer education and changes in dietary preferences and habits, especially among children.

Understanding the link between aspartame and cancer.

INTRODUCTION: Aspartame, invented in 1965 by GD-Searle, is an intense artificial sweetener taste approximately 200 times as sweet as sucrose and used as an additive in more than 6,000 products. Aspartame (APM) was submitted for pre-marketing safety evaluation in early 1980. The studies, performed by GD-Searle, produced controversial results. AREAS COVERED: Because of the great commercial diffusion of aspartame, in 1997 the Ramazzini Institute (RI) started a large experimental project on rodents to test the carcinogenic effects of aspartame following an experimental model with more sensitive characteristics, namely a large number of rat and mice, starting treatment from prenatal life, observation until spontaneous death. Overall, the project included studying 2270 rats and 852 mice. These studies have shown that aspartame is a carcinogenic agent in experimental animals, inducing a significant dose-related increased incidence of several types of malignant tumors and, among them, hematological neoplasia, and liver cancer. EXPERT OPINION: The results of these studies on aspartame by the Ramazzini Institute opened a real front on the evaluation of artificial sweeteners and their possible health risks. Adequate long-term carcinogenicity bioassays on other diffuse artificial sweeteners such as acesulfame-k, sucralose, saccharin, including their blends, are likewise important for public health.

A homogeneous binary matrix assisted laser desorption/ionization time-of-flight mass spectrometry assay for determination of artificial sweeteners in beverages.

Artificial sweeteners have been widely used as additives in various beverages. Due to the safety risks associated with artificial sweeteners, it is essential to develop a simple, rapid, and high-throughput method for the analysis of artificial sweeteners. Here, we report a homogeneous binary matrix assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) assay for the simultaneous analysis of sweeteners including aspartame (ASP), neotame (NEO), and advantame (ADV) with a simple dilution step. The combination of nanodiamonds with 2,5-dihydroxybenzoic acid effectively improved the signal response of sweeteners, decreased the background noise, and improved the "spot-to-spot" repeatability. After the optimization, the method exhibits low limits of detection (ASP: 20 nΜ; NEO: 10 nΜ; ADV: 5 nΜ), good linearity (r > 0.995), satisfactory accuracy (96.2-103.0%), and lower RSDs (1.5-5.8%). Finally, the target sweeteners in 17 soft beverages were successfully determined with this method, showing the potential for the routine analysis of artificial sweeteners.

Investigating the Sociodemographic and Health Characteristics of Non-Sugar Sweeteners Consumption in Greek School-Aged Children: A Cross-Sectional Study.

BACKGROUND/OBJECTIVES: The childhood consumption of non-sugar-sweetened (NSS) soft drinks is a growing concern due to its potential health implications. This study investigated demographic, anthropometric, and lifestyle factors influencing NSS soft drink consumption among children. METHODS: A sample of 1304 children and their parents were surveyed. RESULTS: Analysis revealed that nearly 60% reported consuming NSS soft drinks at least once a week. Also, positive associations were found between NSS soft drink consumption and lower socioeconomic status, increased total beverage consumption, higher maternal BMI, and parental soft drink habits. However, upon employing multivariable models, only the association between total and NSS soft drinks consumption remained statistically significant (OR = 18.925, p < 0.05 for children; OR = 3.801, p < 0.05 for parents), highlighting the pivotal role of parental behavior in shaping children's consumption patterns. CONCLUSIONS: These findings emphasize the importance of tracking parental habits, revealing a strong correlation between parental behavior and children's soft drink consumption patterns. Understanding these factors is crucial for developing effective public health strategies for children, which should prioritize not only individual behaviors but also parental modeling and household dynamics.

Sucralose and stevia consumption leads to intergenerational alterations in body weight and intestinal expression of histone deacetylase 3.

OBJECTIVES: It is unclear whether parental consumption of non-nutritive sweetener (NNS) can affect subsequent generations. The aim of this study was to determine whether chronic parental consumption of sucralose and stevia in mice affects body weight gain and liver and intestinal expression of histone deacetylase 3 (Hdac3) in these animals and in the subsequent first filial (F1) and second filial (F2) generations. METHODS: Male and female mice (n = 47) were divided into three groups to receive water alone or supplemented with sucralose (0.1 mg/mL) or stevia (0.1 mg/mL) for 16 wk (parental [F0] generation). F0 mice were bred to produce the F1 generation; then, F1 mice were bred to produce the F2 generation. F1 and F2 animals did not receive NNSs. After euthanasia, hepatic and intestinal expression of Hdac3 was determined by quantitative reverse transcription polymerase chain reaction. RESULTS: Body weight gain did not differ between the three groups in the F0 generation, but it was greater in the F1 sucralose and stevia groups than in the control group. Consumption of both NNSs in the F0 generation was associated with lower Hdac3 expression in the liver and higher in the intestine. Hepatic Hdac3 expression was normalized to the control values in the F1 and F2 animals of the sucralose and stevia groups. Intestinal expression was still higher in the F1 generations of the sucralose and stevia groups but was partially normalized in the F2 generation of these groups, compared with control. CONCLUSIONS: NNS consumption differentially affects hepatic and intestinal Hdac3 expression. Changes in hepatic expression are not transmitted to the F1 and F2 generations whereas those in intestinal expression are enhanced in the F1 and attenuated in the F2 generations.

Extraction, physicochemical properties, bioactivities and application of natural sweeteners: A review.

Natural sweeteners generally refer to a sweet chemical component directly extracted from nature or obtained through appropriate modifications, mainly secondary metabolites of plants. Compared to the first-generation sweeteners represented by sucrose and the second-generation sweeteners represented by sodium cyclamate, natural sweeteners usually have high sweetness, low-calorie content, good solubility, high stability, and rarely toxic side effects. Historically, researchers mainly focus on the function of natural sweeteners as substitutes for sugars in the food industry. This paper reviews the bioactivities of several typical natural sweeteners, including anti-cancer, anti-inflammatory, antioxidant, anti-bacterial, and anti-hyperglycemic activities. In addition, we have summarized the extraction, physicochemical properties, and application of natural sweeteners. The article aimed to comprehensively collate vital information about natural sweeteners and review the potentiality of tapping bioactive compounds from natural products. Hopefully, this review provides insights into the further development of natural sweeteners as therapeutic agents and functional foods.

Associations between Intake of Dietary Sugars and Diet Quality: A Systematic Review of Recent Literature.

Understanding the relationship between the intake of sugars and diet quality can inform public health recommendations. This systematic review synthesized recent literature on associations between sugar intake and diet quality in generally healthy populations aged 2 years or older. We searched databases from 2010 to 2022 for studies of any design examining associations between quantified sugar intake in the daily diet and dietary indexes (DIs) or micronutrient intakes. Different sugar types and diet quality measures were analyzed separately. We converted DI results to Pearson's r correlations and grouped indexes with or without a free or added sugar component to facilitate cross-study comparisons. Meta-analysis was deemed inappropriate. From 13,869 screened records, we included 27 cross-sectional studies. NUQUEST risk of bias ratings were neutral (n = 18 studies) or poor (n = 9), and strength of evidence by the GRADE approach was very low due to study design. Most studies reported negative associations for added and free sugars with diet quality indexes (r ranging from -0.13 to -0.42) and nutrients of public health concern (fiber, vitamin D, calcium, potassium), while associations with total sugars were mixed. Due to cross-sectional study designs, the clinical relevance of these findings is unclear. Prospective studies are needed to minimize confounding and inform causal relationships.

Linking artificial sweetener intake with kidney function: insights from NHANES 2003-2006 and findings from Mendelian randomization research.

Background: The current investigation examines the association between artificial sweetener (AS) consumption and the likelihood of developing chronic kidney disease (CKD), along with its impact on kidney function. Methods: We utilized data from the National Health and Nutrition Examination Survey from 2003-2006 to conduct covariance analysis and weighted adjusted logistic regression, aiming to assess the association between artificial sweetener intake and CKD risk, as well as kidney function indicators. Subsequently, we employed Mendelian randomization methods to validate the causal relationship between the intake of artificial sweeteners, CKD risk, and kidney function indicators. Instrumental variable analysis using inverse-variance weighting and Robust adjusted profile score were the primary analytical methods employed. Results: A total of 20,470 participants were included in the study, with 1,257 participants ultimately included in the analysis. In all adjusted logistic regression models, no significant association was found between the intake of artificial sweeteners and CKD risk. Similarly, the summary odds ratios (OR) for each unit change in genetically predicted CKD risk were 2.14 (95% CI: 0.83, 5.21, p = 0.092), 1.41 (95% CI: 0.54, 3.63, p = 0.482), and 1.50 (95% CI: 0.50, 4.52, p = 0.468) for the impact of artificial sweeteners added to cereals, tea, and coffee, respectively. It was only observed that adding artificial sweeteners to coffee was associated with a modest reduction in urinary albumin-to-creatinine ratio (OR = 0.94, 95% CI: -0.108, -0.022, p = 0.003), the effect appeared to be relatively small and may not directly impact the individual level. Conclusion: Our study does not support a causal relationship between artificial sweetener intake and the risk of CKD. However, due to the limitations and potential confounding factors, these findings need to be further validated through larger sample sizes in observational studies and Mendelian randomization analyses.

Artificial and Natural Sweeteners Biased T1R2/T1R3 Taste Receptors Transactivate Glycosylated Receptors on Cancer Cells to Induce Epithelial-Mesenchymal Transition of Metastatic Phenotype.

Understanding the role of biased taste T1R2/T1R3 G protein-coupled receptors (GPCR) agonists on glycosylated receptor signaling may provide insights into the opposing effects mediated by artificial and natural sweeteners, particularly in cancer and metastasis. Sweetener-taste GPCRs can be activated by several active states involving either biased agonism, functional selectivity, or ligand-directed signaling. However, there are increasing arrays of sweetener ligands with different degrees of allosteric biased modulation that can vary dramatically in binding- and signaling-specific manners. Here, emerging evidence proposes the involvement of taste GPCRs in a biased GPCR signaling crosstalk involving matrix metalloproteinase-9 (MMP-9) and neuraminidase-1 (Neu-1) activating glycosylated receptors by modifying sialic acids. The findings revealed that most natural and artificial sweeteners significantly activate Neu-1 sialidase in a dose-dependent fashion in RAW-Blue and PANC-1 cells. To confirm this biased GPCR signaling crosstalk, BIM-23127 (neuromedin B receptor inhibitor, MMP-9i (specific MMP-9 inhibitor), and oseltamivir phosphate (specific Neu-1 inhibitor) significantly block sweetener agonist-induced Neu-1 sialidase activity. To assess the effect of artificial and natural sweeteners on the key survival pathways critical for pancreatic cancer progression, we analyzed the expression of epithelial-mesenchymal markers, CD24, ADLH-1, E-cadherin, and N-cadherin in PANC-1 cells, and assess the cellular migration invasiveness in a scratch wound closure assay, and the tunneling nanotubes (TNTs) in staging the migratory intercellular communication. The artificial and natural sweeteners induced metastatic phenotype of PANC-1 pancreatic cancer cells to promote migratory intercellular communication and invasion. The sweeteners also induced the downstream NFκB activation using the secretory alkaline phosphatase (SEAP) assay. These findings elucidate a novel taste T1R2/T1R3 GPCR functional selectivity of a signaling platform in which sweeteners activate downstream signaling, contributing to tumorigenesis and metastasis via a proposed NFκB-induced epigenetic reprogramming modeling.

DeepRA: A novel deep learning-read-across framework and its application in non-sugar sweeteners mutagenicity prediction.

Non-sugar sweeteners (NSSs) or artificial sweeteners have long been used as food chemicals since World War II. NSSs, however, also raise a concern about their mutagenicity. Evaluating the mutagenic ability of NSSs is crucial for food safety; this step is needed for every new chemical registration in the food and pharmaceutical industries. A computational assessment provides less time, money, and involved animals than the in vivo experiments; thus, this study developed a novel computational method from an ensemble convolutional deep neural network and read-across algorithms, called DeepRA, to classify the mutagenicity of chemicals. The mutagenicity data were obtained from the curated Ames test data set. The DeepRA model was developed using both molecular descriptors and molecular fingerprints. The obtained DeepRA model provides accurate and reliable mutagenicity classification through an independent test set. This model was then used to examine the NSSs-related chemicals, enabling the evaluation of mutagenicity from the NSSs-like substances. Finally, this model was publicly available at https://github.com/taraponglab/deepra for further use in chemical regulation and risk assessment.

Could Insulin Be a Better Regulator of Appetite/Satiety Balance and Body Weight Maintenance in Response to Glucose Exposure Compared to Sucrose Substitutes? Unraveling Current Knowledge and Searching for More Appropriate Choices.

BACKGROUND: Insulin exerts a crucial impact on glucose control, cellular growing, function, and metabolism. It is partially modulated by nutrients, especially as a response to the intake of foods, including carbohydrates. Moreover, insulin can exert an anorexigenic effect when inserted into the hypothalamus of the brain, in which a complex network of an appetite/hunger control system occurs. The current literature review aims at thoroughly summarizing and scrutinizing whether insulin release in response to glucose exposure may be a better choice to control body weight gain and related diseases compared to the use of sucrose substitutes (SSs) in combination with a long-term, well-balanced diet. METHODS: This is a comprehensive literature review, which was performed through searching in-depth for the most accurate scientific databases and applying effective and relevant keywords. RESULTS: The insulin action can be inserted into the hypothalamic orexigenic/anorexigenic complex system, activating several anorexigenic peptides, increasing the hedonic aspect of food intake, and effectively controlling the human body weight. In contrast, SSs appear not to affect the orexigenic/anorexigenic complex system, resulting in more cases of uncontrolled body weight maintenance while also increasing the risk of developing related diseases. CONCLUSIONS: Most evidence, mainly derived from in vitro and in vivo animal studies, has reinforced the insulin anorexigenic action in the hypothalamus of the brain. Simultaneously, most available clinical studies showed that SSs during a well-balanced diet either maintain or even increase body weight, which may indirectly be ascribed to the fact that they cannot cover the hedonic aspect of food intake. However, there is a strong demand for long-term longitudinal surveys to effectively specify the impact of SSs on human metabolic health.

The substitute ENSO 16 has low impact on glucose metabolism in healthy humans: a randomized, double-blind, active-controlled, cross-over trial.

High sugar consumption is associated with cardiovascular diseases and diabetes. Current sugar substitutes may cause taste sensations and gastrointestinal symptoms. ENSO 16 is a combination of 16 different sugar substitutes and plant fibers and has been designed as a sugar alternative. The impact on plasma glucose metabolism as well as on gastrointestinal tolerance has not been investigated yet. 17 healthy participants were enrolled in this randomized, double-blind trial. Participants received a single oral dose of 30 g glucose or 30 g ENSO 16 and crossed over to the alternate treatment after a 7 day wash out period. The study endpoint was the effect on plasma glucose, insulin, C-peptide concentrations and gastrointestinal disorders. A questionnaire regarding gastrointestinal symptoms was used for individual subjective scoring. The mean baseline adjusted plasma glucose AUC0-180 min was significantly greater after glucose administration compared to ENSO 16 (n = 15, p = 0.0128, paired t-test). Maximum plasma glucose elevation over baseline was 117 mg*dl-1 and 20 mg*dl-1 after oral glucose or ENSO 16, respectively. Insulin and C-peptide AUC0-180 min were significantly greater after glucose compared to ENSO 16 intake (p < 0.01, Wilcoxon rank sum test). The mean maximal concentrations of plasma glucose, insulin and C-peptide after glucose intake were 1.5, 4.6 and 2.7-fold greater after glucose intake compared to ENSO 16 intake, respectively. Adverse reactions were mostly mild and not different between treatments. Conclusion. ENSO 16 has only a small impact on plasma glucose metabolism. This may be of interest in a dietary context and may help to reduce calory intake.Trail registration NCT05457400. First registration: 14/07/2022. https://clinicaltrials.gov/study/NCT05457400 .

Determination of high-intensity sweeteners in bakery products marketed in Brazil and dietary exposure assessment.

Bakery products, including biscuits, cakes and breads, generally present a high content of simple sugars of rapid absorption, high fat content and low amount of dietary fiber, which make them highly caloric foods. Although sucrose is a very important ingredient in bakery products for its preservation characteristics and a significant source of energy, there is a growing interest in replacing this sugar with alternative substances, such as high-intensity sweeteners (HIS) that provide sweetness with no or low calories. In Brazil, there is no data on the use of HIS in this class of food. Therefore, the objective of this study was to evaluate the presence of HIS in baked food commercially available in the country and estimate the dietary exposure to these food additives. For that, an analytical method was established for the simultaneous determination of nine HIS in bakery products using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). Sample preparation steps were required based on mechanical kneading for homogenization, hexane extraction of fats, dilution in mobile phase and vortex homogenization, prior to injection into the system. The results obtained during validation showed that coefficients of variation (CV%) for precision were lower than 13.8% and the accuracy was between 91.6% and 109.1%. Aspartame, acesulfame potassium, sodium cyclamate, saccharin, sucralose and steviol glycosides were found in the samples, used alone or in combinations of up five substances. Steviol glycosides were the most found HIS in biscuit samples, while sucralose was the most common sweetener in cake and bread samples. Analysis of product labels revealed only three different claims, .i.e. 'no sugar', 'no added sugar' and 'zero sugar', with the latter being found in 70% of the samples. Exposure to HIS through the consumption of bakery products estimated per eating occasion showed no concerns regarding toxicological risk.

Self -reported knowledge and understanding of added sugars by consumers in Ghana.

The consumption of added sugars has been a major concern among consumers and researchers around the world. Some of these added sugars pose health threats such as obesity, and liver diseases to consumers. Therefore, consumers' understanding and knowledge of added sugars is important in regulating the intake of food items that contain different types and levels of added sugar. In this study, the knowledge and understanding of staff (consumers) of the University of Energy and Natural Resources, Ghana, was assessed through survey The results showed that about 38.5 % of consumers always read food labels whereas 3.1 % never read the labels of food they purchased. However, only about 20 % of consumers considered added sugars as most important information on food labels while most (about 38 %) were concerned about the calorie level in food items purchased. Based on the consumer's knowledge of sugars and sweeteners, there was a high level of disparity in classifying sugars in food as sugars and sweeteners. In addition, most consumers reported that they would adversely avoid food items containing lactose, isoglucose, and saccharin. The awareness of the consumers to the WHO recommendation for sugar reduction, the gender (P = 0.278), age (P = 0.959), level of education (P = 0.888), and staff category (P = 0.944) did not influence their decisions on purchasing food items with added sugars Most consumers were interested in issues of food and nutrition. Therefore, it is recommended that staff are taken through aspects of food nutrition as well as the consumption of added sugar towards the recommended levels.

Sweeteners Show a Plasticizing Effect on PVP K30-A Solution for the Hot-Melt Extrusion of Fixed-Dose Amorphous Curcumin-Hesperetin Solid Dispersions.

The co-administration of curcumin and hesperetin might be beneficial in terms of neuroprotective activity; therefore, in this study, we attempted to develop a fixed-dose formulation comprising these two compounds in an amorphous state. The aim of obtaining an amorphous state was to overcome the limitations of the low solubility of the active compounds. First, we assessed the possibility of using popular sweeteners (erythritol, xylitol, and sorbitol) as plasticizers to reduce the glass transition temperature of PVP K30 to prepare the polymer-excipient blends, which allowed the preparation of amorphous solid dispersions via hot-melt extrusion at a temperature below the original glass transition of PVP K30. Erythritol proved to be the superior plasticizer. Then, we focused on the development of fixed-dose amorphous solid dispersions of curcumin and hesperetin. Powder X-ray diffraction and thermal analysis confirmed the amorphous character of dispersions, whereas infrared spectroscopy helped to assess the presence of intermolecular interactions. The amorphous state of the produced dispersions was maintained for 6 months, as shown in a stability study. Pharmaceutical parameters such as dissolution rate, solubility, and in vitro permeability through artificial membranes were evaluated. The best improvement in these features was noted for the dispersion, which contained 15% of the total content of the active compounds with erythritol used as the plasticizer.

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.

Neural responses to oral administration of erythritol vs. sucrose and sucralose explain differences in subjective liking ratings.

INTRODUCTION: High sugar intake is associated with many chronic diseases. However, non-caloric sweeteners (NCSs) might fail to successfully replace sucrose due to the mismatch between their rewarding sweet taste and lack of caloric content. The natural NCS erythritol has been proposed as a sugar substitute due to its satiating properties despite being non-caloric. We aimed to compare brain responses to erythritol vs. sucrose and the artificial NCS sucralose in a priori taste, homeostatic, and reward brain regions of interest (ROIs). METHODS: We performed a within-subject, single-blind, counterbalanced fMRI study in 30 healthy men (mean ± SEM age:24.3 ± 0.8 years, BMI:22.3 ± 0.3 kg/m2). Before scanning, we individually matched the concentrations of both NCSs to the perceived sweetness intensity of a 10% sucrose solution. During scanning, participants received 1 mL sips of the individually titrated equisweet solutions of sucrose, erythritol, and sucralose, as well as water. After each sip, they rated subjective sweetness liking. RESULTS: Liking ratings were significantly higher for sucrose and sucralose vs. erythritol (both pHolm = 0.0037); water ratings were neutral. General Linear Model (GLM) analyses of brain blood oxygen level-depended (BOLD) responses at qFDR<0.05 showed no differences between any of the sweeteners in a priori ROIs, but distinct differences were found between the individual sweeteners and water. These results were confirmed by Bayesian GLM and machine learning-based models. However, several brain response patterns mediating the differences in liking ratings between the sweeteners were found in whole-brain multivariate mediation analyses. Both subjective and neural responses showed large inter-subject variability. CONCLUSION: We found lower liking ratings in response to oral administration of erythritol vs. sucrose and sucralose, but no differences in neural responses between any of the sweeteners in a priori ROIs. However, differences in liking ratings between erythritol vs. sucrose or sucralose are mediated by multiple whole-brain response patterns.