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(1) Background: Clinical results on the effects of excess sugar consumption on insulin sensitivity are conflicting, possibly due to differences in sugar type and the insulin sensitivity index (ISI) assessed. Therefore, we compared the effects of consuming four different sugars on insulin sensitivity indices derived from oral glucose tolerance tests (OGTT). (2) Methods: Young adults consumed fructose-, glucose-, high-fructose corn syrup (HFCS)-, sucrose-, or aspartame-sweetened beverages (SB) for 2 weeks. Participants underwent OGTT before and at the end of the intervention. Fasting glucose and insulin, Homeostatic Model Assessment-Insulin Resistance (HOMA-IR), glucose and insulin area under the curve, Surrogate Hepatic Insulin Resistance Index, Matsuda ISI, Predicted M ISI, and Stumvoll Index were assessed. Outcomes were analyzed to determine: (1) effects of the five SB; (2) effects of the proportions of fructose and glucose in all SB. (3) Results: Fructose-SB and the fructose component in mixed sugars negatively affected outcomes that assess hepatic insulin sensitivity, while glucose did not. The effects of glucose-SB and the glucose component in mixed sugar on muscle insulin sensitivity were more negative than those of fructose. (4) Conclusion: the effects of consuming sugar-SB on insulin sensitivity varied depending on type of sugar and ISI index because outcomes assessing hepatic insulin sensitivity were negatively affected by fructose, and outcomes assessing muscle insulin sensitivity were more negatively affected by glucose.

Aspartame is a nonnutritive sweetener (NSS), which is widely used in foods and beverages worldwide. The safety of aspartame, a commonly used artificial sweetener, has been debated. Here, we investigated the potential effects and underlying mechanisms of aspartame consumption during pregnancy on placental dysfunction and birth outcomes. Female Sprague Dawley rats were exposed to a low (30 mg/kg) or high (60 mg/kg) dose of aspartame before and during pregnancy; moreover, we assessed placental histopathological structure, oxidative stress markers, and mitochondrial function. In addition, we explored how aspartame affects birth weight in a human maternal–infant cohort. In animal study revealed that aspartame treatment of female rats for 14 weeks (12 week before pregnancy and 18 days of gestation) causes a significant reduction in the number and weight of fetuses, as well as damage to placental structure. These effects are linked to increased oxidative stress in the placenta, possibly damaging placental trophoblasts, impairing mitochondrial function, and initiating a compensatory mitochondrial biosynthesis mechanism. In the human pregnant cohort revealed that aspartame reduces birth weight considerably. These findings suggested the potential risks associated with aspartame consumption during pregnancy. Therefore, the safety of aspartame, particularly in pregnant individuals, should be reconsidered; specifically, tailored, acceptable daily intake guidelines should be developed for aspartame in different populations. [Display omitted] • Aspartame consumption for 14 weeks reduces fetus number and weight in female rats. • Aspartame consumption for 14 weeks damages placental structure via elevated oxidative stress in female rats. • Aspartame consumption of female rats for 14 weeks causes impaired mitochondrial function. [ABSTRACT FROM AUTHOR]

Aspartame is the most common artificial sweetener and a famous sweet‐taste receptor agonist. Macrophages are essential in the antibacterial system to maintain the stability of the intestinal environment. Recently, the sweet taste receptor has been found in macrophages. However, the effects of aspartame on macrophage phagocytosis in the gastrointestinal tract are little known. The current study sought to assess the influence of aspartame intake on the scavenging activity of mice to low‐dose Escherichia coli infection and related mechanisms. Firstly, no inflammatory response or pathological injury was observed in the intestines of mice after oral administration of aspartame (25–100 mg/kg, i.g.) for 2 weeks. Subsequently, aspartame intake was found to enhance the scavenging activity of mice to low‐dose E. coli infection. Similarly, aspartame dose‐dependent strengthened the ability of RAW264.7 cells to phagocytose GFP‐E.coli J96. Further mechanism evaluation reflected that aspartame could enhance macrophage phagocytosis, migration, and rearrangement via PLCβ‐2/Ca2+/PKCβ/Rho A/ROCK1 pathway caused by sweet taste receptor activation. In conclusion, the present study, for the first time, demonstrated that aspartame could enhance the scavenging activity of mice to low‐dose E. coli infection via strengthening macrophage phagocytic function through activating sweet taste receptor. It is then suggested that aspartame may affect the antibacterial activity of human gastrointestinal macrophages, and further studies need to validate these effects. [ABSTRACT FROM AUTHOR]

Saccharin is a widely used sugar substitute, but little is known about the long-term health effects of saccharin intake. Our study aimed to examine the association between saccharin intake and mortality in diabetic and pre-diabetic population and overweight population from NHANES 1988–1994. Cox proportional hazard models were used to evaluate the association between saccharin intake and CVD, cancer and all-cause mortality. After multivariable adjustment, increased absolute saccharin intake was associated with the risk of all-cause mortality (hazard ratio (HR): 1·41, 95 % CI: 1·05, 1·90), CVD mortality (HR: 1·93, 95 % CI: 1·15, 3·25) and cancer mortality (HR: 2·26, 95 % CI: 1·10, 4·45) in diabetic and pre-diabetic population. Among overweight population, higher absolute saccharin intake was associated with the risk of cancer mortality (HR: 7·369, 95 % CI: 2·122, 25·592). Replacing absolute saccharin intake with total sugar significantly reduced all-cause mortality by 12·5 % and CVD mortality by 49·7 % in an equivalent substitution analysis in the diabetic and pre-diabetic population. Aspartame substitution reduced all-cause mortality by 29·2 % and cancer mortality by 30·2 %. Notably, the relative daily intake of saccharin also had similar effects as the absolute intake on all-cause, cardiovascular and cancer mortality in all analyses. This was despite the fact that the relative daily intake in our study was below the Food and Drug Administration limit of 15 mg/kg. In conclusion, our study showed a considerable risk of increased saccharin intake on the all-cause, CVD mortality and cancer mortality. [ABSTRACT FROM AUTHOR]

Low- and no-calorie sweeteners (LNCSs) impart sweetness while providing little or no energy. Their safety and weight management efficacy remain unsettled science that leaves open questions among consumers, researchers, clinicians, and policy makers. The objective of this narrative review is to provide a critical consideration of the safety and efficacy of weight management evidence for LNCSs that have been reviewed/approved by the US Food and Drug Administration and have the highest frequency of use: acesulfame potassium, allulose, aspartame, erythritol, monk fruit, saccharin, stevia, sucralose, and xylitol. Safety assessments by the authoritative bodies for the World Health Organization, European Union, and United States were reviewed. Additionally, emerging topics of interest regarding the safety of these sweeteners commonly cited in the recent literature or highlighted in the media are discussed. Collectively, authoritative assessments and the primary literature support the safety of the sweeteners reviewed herein, with high concordance of safety substantiation across authoritative bodies. Weight management efficacy, measured by various adiposity indices in epidemiological studies, ranges from no effect to a slight positive association. Clinical trials with various mixtures of LNCSs more consistently indicate LNCS use is associated with lower adiposity indices. The latter are ascribed greater evidentiary weight, and recent application of statistical methods to better correct for potential biases in cohort studies reveals they are more consistent with the clinical trial findings. Studies that investigated individual sweeteners were limited but suggestive of differing effects or lack of sufficient data to support any formal conclusions on their efficacy for weight management. Taken together, and consistent with the current 2020-2025 Dietary Guidelines for Americans, the evidence indicates LNCS use is safe and may aid weight management. [ABSTRACT FROM AUTHOR]

Background: Aspartame is a low-calorie artificial non-sugar sweetener and is commonly used as a sugar substitute in foods and beverages. Pancreas has a vital role in carbohydrate metabolism. The aim of the study was to study the effect of aspartame on the structure of pancreas. Methods: Eighteen albino Wistar rats (200-250gm) were divided into three groups; control group, aspartame-treated group, was treated with aspartame (250 mg/kg/day) for six months and withdrawal group: was treated with aspartame (250 mg/kg/day) for six months then left without treatment for another month. Serum amylase and lipase were measured, and histological study of the pancreas was conducted. Results: histopathological changes were detected in both pancreatic acini and islets of Langerhans, increased collagen deposition around the acini and blood vessels. Additionally, aspartame supplementation resulted in elevated levels of serum amylase and lipase. Upon withdrawal of aspartame, an obvious improvement was noticed in the withdrawal group in comparison with the aspartame-treated group. Conclusions: Aspartame produces degenerative changes in the pancreas of the rats and causes uprising of serum pancreatic enzymes. Withdrawal of aspartame results in partial restoration of the histological structure of the pancreas. From these results, it is recommended to spot a light on the dangerous impacts of the usage of aspartame in clinical studies. [ABSTRACT FROM AUTHOR]

An eco-friendly method for the determination of sweeteners (aspartame, acesulfame-K) and preservatives (benzoic acid, sorbic acid, methylparaben, ethylparaben) in functional beverages and flavoured waters using thin film microextraction (TFME) and high-performance liquid chromatography with UV detection (HPLC-UV) was proposed. A series of fourteen green and renewable solidified natural deep eutectic solvents (NADESs) were prepared and tested as 'eutectosorbents' in TFME for the first time. In the proposed method, the NADES containing acetylcholine chloride and 1-docosanol at a 1:3 molar ratio was finally chosen to coat a support. Four factors, i.e., the mass of the NADES, pH of the samples, extraction time, and desorption time, were tested in the central composite design to select the optimal TFME conditions. Limits of detection were equal to 0.022 µg mL−1 for aspartame, 0.020 µg mL−1 for acesulfame-K, 0.018 µg mL−1 for benzoic acid, 0.026 µg mL−1 for sorbic acid, 0.013 µg mL−1 for methylparaben, and 0.011 µg mL−1 for ethylparaben. Satisfactory extraction recoveries between 82% and 96% were achieved with RSDs lower than 6.1% (intra-day) and 7.4% (inter-day). The proposed 'eutectosorbent' presented good stability that enabled effective extractions for 16 cycles with recovery of at least 77%. The proposed NADES-TFME/HPLC-UV method is highly sensitive and selective. However, the use of a solid NADES as a sorbent, synthesized without by-products, without the need for purification, and with good stability on a support with the possibility of reusability increases the ecological benefit of this method. The greenness aspect of the method was evaluated using the Complex modified Green Analytical Procedure Index protocol and is equal to 84/100. [ABSTRACT FROM AUTHOR]

The aim of this research was to produce a diet beverage based on aloe vera and investigate its physicochemical, microbiological, antioxidant, and sensory properties. To achieve this goal, aloe vera gel at concentrations of 5%, 5.7%, and 10% underwent heat treatment at 80°C for 30 minutes (Treatment A) and 90°C for 3 minutes (Treatment B). Aspartame was added at concentrations of 100, 150, and 200 ppm, and the beverages were stored for a period of 31 days. The study was conducted using a fractional factorial design with 34 samples under investigation. Optimization was performed based on a maximum amount of 10 gr of aloe vera, 200 ppm of aspartame, and a minimum amount of 5 gr of aloe vera and 100 ppm of aspartame. The use of the sweetener aspartame was highly effective in improving the taste of the beverage, as it provides a much sweeter sensation compared to saccharide sugars and is beneficial for diabetic patients. Based on the microbiological test results, the heat treatment (pasteurization) was successful. Furthermore, sensory evaluation showed improvements in taste, aroma, texture, and mouthfeel with the addition of aloe vera gel to the samples with no undesirable characteristics observed. After determining the models and variable combinations using the Design Expert software, an optimized sample was introduced, containing 200 ppm of aspartame, 10 gr of aloe vera, and the optimized pasteurization process, which was Treatment B for 30 minutes. The results of this study indicate that a vegetable -based diet beverage containing aloe vera can be successfully produced as a beneficial product with desirable sensory characteristics that are acceptable to consumers. [ABSTRACT FROM AUTHOR]

Background: Non/low-caloric artificial sweeteners (NAS) are recognized as chemical additives substituting sugars to avoid caloric intake and subsequent sugar-derived diseases such as diabetes and hyperglycemia. Six NAS have been claimed safe and are authorized by the US Food and Drug Administration (FDA) for public use, with acceptable daily intake information available: aspartame, acesulfame-K, saccharin, sucralose, neotame, and advantame. However, the impacts of NAS on the gut microbiome have raised potential concerns, since sporadic research revealed NAS-induced microbial changes in the gastrointestinal tracts and alterations in the microbiome–host interactive metabolism. Methods: Given the fact that the gut microbiome influences kaleidoscopic physiological functions in host health, this review aimed to decipher the impacts of NAS on the gut microbiome by implementing a comprehensive two-stage literature analysis based on each NAS. Results: This review documented disturbed microbiomes due to NAS exposure to a maximal resolution of species level using taxonomic clustering analysis, and recorded metabolism alterations involved in gut microbiome–host interactions. Conclusions: The results elucidated that specific NAS exhibited discrepant impacts on the gut microbiome, even though overlapping on the genera and species were identified. Some NAS caused glucose tolerance impairment in the host, but the key metabolites and their underlying mechanisms were different. Furthermore, this review embodied the challenges and future directions of current NAS–gut microbiome research to inspire advanced examination of the NAS exposure–gut microbiome–host metabolism axis. [ABSTRACT FROM AUTHOR]

This study reports an electrochemical sensor for detecting aspartame using square wave voltammetry (SWV) on ZnONP/BDDNP electrode. ZnONP/BDDNP was able to oxidize aspartame at a potential of 0.34 V in a phosphate buffer solution pH 2.0 with a current of 80.1 µA. The limit of detection (LOD) was found to be 0.07 µM, the limit of quantitation (LOQ) was 0.25 µM and sensitivity was 1.23 µA µM-1. The relative standard deviation (RSD) was 1.6%, less than 5% indicating that ZnONP/BDDNP has good precision. ZnONP/BDDNP showed better results compared with the BDDNP electrode. The developed method showed good linearity in the concentration range of 30-100 µM. This method was successfully applied to determine aspartame in beverage samples with a recovery range of 85-110%. This shows that ZnONP/BDDNP with the suggested method is potentially applied in practical used.

This study reports an electrochemical sensor for detecting aspartame using square wave voltammetry (SWV) on ZnONP/BDDNP electrode. ZnONP/BDDNP was able to oxidize aspartame at a potential of 0.34 V in a phosphate buffer solution pH 2.0 with a current of 80.1 µA. The limit of detection (LOD) was found to be 0.07 µM, the limit of quantitation (LOQ) was 0.25 µM and sensitivity was 1.23 µA µM-1. The relative standard deviation (RSD) was 1.6%, less than 5% indicating that ZnONP/BDDNP has good precision. ZnONP/BDDNP showed better results compared with the BDDNP electrode. The developed method showed good linearity in the concentration range of 30-100 µM. This method was successfully applied to determine aspartame in beverage samples with a recovery range of 85-110%. This shows that ZnONP/BDDNP with the suggested method is potentially applied in practical used. [ABSTRACT FROM AUTHOR]

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. 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. 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. [ABSTRACT FROM AUTHOR]

Aspartame is an artificial sweetener used in drinks and many foods. International Agency for Research on Cancer classified aspartame as possibly carcinogenic to humans (IARC Group 2B). In this study, a sensitive and selective spectrofluorimetric method was developed to detect aspartame. The method is based on switching on the fluorescence activity of aspartame upon its condensation with O‐phthalaldehyde (Roth's reaction) in the presence of 2‐mercaptoethanol. The reaction product was detected fluorometrically at λem of 438 nm after λex of 340 nm. All reaction conditions required to yield the optimal fluorescence intensity were observed and investigated. Furthermore, the approach was validated according to ICH guidelines. Upon plotting the concentrations of aspartame against their associated fluorescence intensity values, the relationship between the two variables was linear within the range of 0.5–3.0 μg/mL. Furthermore, the method was employed to analyze the quantity of aspartame in commercial packages and soft drinks with an acceptable level of recovery. In addition, the Green Solvents Selecting Tool, Complementary Green Analytical Procedure Index, and the Analytical Greenness Metric tool were used to evaluate the sustainability and the greenness of the developed methodology. [ABSTRACT FROM AUTHOR]

Acidizing is a vital oil well stimulation exercise but must be done with an effective corrosion inhibitor to reduce corrosion risk. It is, however becoming increasingly difficult to find a corrosion inhibitor that is ecologically compatible and effective in strong acids and high temperatures. In this scientific communication, aspartame (ASP), sodium dodecylsufate (SDS), and potassium iodide (KI) blend is presented as a highly efficient inhibitor for T95 steel in 28 wt.% HCl solution at 60–90 °C. The corrosion inhibition investigation was performed using weight loss and electrochemical (electrochemical impedance spectroscopy [EIS] and potentiodynamic polarization [PDP]) techniques complemented by surface analysis of the corroded steel without and with the inhibitor using scanning electron microscope (SEM)/energy dispersive x-ray spectrophotometer (EDX), and 3D optical profilometry (OP). ASP is an effective corrosion inhibitor for T95 steel in an acidizing environment. The inhibition efficiency (IE) increased with an increase in concentration and temperature. The additives (SDS and KI) enhanced the inhibitive performance of ASP due to synergistic effects, especially at 90 °C where an IE of 96% is tenable. Results from SEM/EDS and OP disclose apparent ASP-based inhibitor adsorption on the T95 surface and a high level of protection. [ABSTRACT FROM AUTHOR]

In a recent study examining the effects of manipulating the gut microbiome on bone, a control group of mice in which the microbiome was altered using a non-caloric, aspartame-based sweetener resulted in whole bone strength being 40% greater than expected from geometry alone, implicating enhanced bone tissue strength. However, the study was not designed to detect changes in bone in this control group and was limited to young male mice. Here we report a replication study examining how changes in the gut microbiome caused by aspartame-based sweetener influence bone. Male and female C57Bl/6 J mice were untreated or treated with a high dose of sweetener (10 g/L) in their drinking water from either 1 to 4 mo of age (young cohort; n = 80) or 1 to 22 mo of age (aged cohort; n = 52). Sweetener did not replicate the modifications to the gut microbiome observed in the initial study and did not result in an increase in bone tissue strength in either sex at either age. Aged male mice dosed with sweetener had larger bones (+17% femur section modulus, p<.001) and greater whole bone strength (+22%, p=.006) but the increased whole bone strength was explained by the associated increase in body mass (+9%, p<.001). No differences in body mass, whole bone strength, or femoral geometry were associated with sweetener dosing in males from the young cohort or females at either age. As we were unable to replicate the gut microbiota observed in the initial experiment, it remains unclear if changes in the gut microbiome can enhance bone tissue strength. Although prior work studying gut microbiome–induced changes in bone with oral antibiotics has been highly repeatable, the current study highlights the variability of nutritional manipulations of the gut microbiota in mice. Lay Summary: To replicate prior findings and to better understand how changes in the gut microbiome caused by aspartame-based sweetener influence bone, mice (both male and female) were treated with high doses of a calorie-free sweetener in their drinking water until the age of 4 mo (young) or 22 mo (aged). Body weight, bone strength, geometry, and microbiome composition were measured in mice receiving sweetener and compared to mice that were untreated. Sweetener did not change in the gut microbiome as much as observed in our prior study and no changes in bone tissue strength were seen at either age in either sex. Aged male mice receiving sweetener had increased body weight and increased whole bone strength as compared to untreated aged male mice. Sweetener treatment did not affect body weight or bone strength and geometry of males in the young cohort or females at either age. Our work highlights the challenges of replicating microbiota composition across studies via dietary manipulations to study bone and the need to preserve live communities of microbiota to improve replication. [ABSTRACT FROM AUTHOR]

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This study employs network toxicology, molecular docking, and molecular dynamics simulations to assess the characteristics and potential molecular mechanisms of aspartame-induced hepatocellular carcinoma (HCC). Utilizing ChEMBL, STITCH, and SwissTargetPrediction databases, potential target proteins associated with aspartame are identified. HCC-related targets are determined through bioinformatics and weighted gene co-expression network analysis (WGCNA). Gene enrichment analysis explores the signaling pathways related to aspartame-induced HCC. Further refinement using the STRING database and Cytoscape software highlights 15 key targets. Molecular docking, conducted using Autodock Vina, assesses the relationships between aspartame and each key target. Molecular dynamics simulations evaluate the binding capabilities of aspartame with core targets obtained through molecular docking. The results indicate that aspartame may induce HCC by modulating apoptosis and proliferation of liver cancer cells, affecting inflammatory signaling pathways, and regulating estrogen metabolism, posing to the occurrence and development of liver toxicity and associated inflammation, thereby leading to a risk of hepatocarcinogenesis. This study provides a theoretical foundation for understanding the molecular mechanisms underlying aspartame-induced HCC. Additionally, our network toxicology approach accelerates the elucidation of toxic pathways for uncharacterized food additives. [ABSTRACT FROM AUTHOR]

An increased understanding of how the acceptor site in Gcn5-related N-acetyltransferase (GNAT) enzymes recognizes various substrates provides important clues for GNAT functional annotation and their use as chemical tools. In this study, we explored how the PA3944 enzyme from Pseudomonas aeruginosa recognizes three different acceptor substrates, including aspartame, NANMO, and polymyxin B, and identified acceptor residues that are critical for substrate specificity. To achieve this, we performed a series of molecular docking simulations and tested methods to identify acceptor substrate binding modes that are catalytically relevant. We found that traditional selection of best docking poses by lowest S scores did not reveal acceptor substrate binding modes that were generally close enough to the donor for productive acetylation. Instead, sorting poses based on distance between the acceptor amine nitrogen atom and donor carbonyl carbon atom placed these acceptor substrates near residues that contribute to substrate specificity and catalysis. To assess whether these residues are indeed contributors to substrate specificity, we mutated seven amino acid residues to alanine and determined their kinetic parameters. We identified several residues that improved the apparent affinity and catalytic efficiency of PA3944, especially for NANMO and/or polymyxin B. Additionally, one mutant (R106A) exhibited substrate inhibition toward NANMO, and we propose scenarios for the cause of this inhibition based on additional substrate docking studies with R106A. Ultimately, we propose that this residue is a key gatekeeper between the acceptor and donor sites by restricting and orienting the acceptor substrate within the acceptor site.

Abstract Background and objective Aspartame (l-aspartyl l-phenylalanine methyl ester) is an artificial sweetener widely used as a sugar substitute. There are concerns regarding the effects of high aspartame doses on the kidney owing to oxidative stress; however, whether the maximum allowed dose of aspartame in humans affects the kidneys remains unknown. Therefore, in this study, we investigated whether the maximum allowed dose of aspartame in humans affects the kidneys. Methods In this study, animals were fed a folate-deficient diet to mimic human aspartame metabolism. Eight-week-old ICR mice were divided into control (CTL), 40 mg/kg/day of aspartame-administered (ASP), folate-deficient diet (FD), and 40 mg/kg/day of aspartame-administered with a folate-deficient diet (FD + ASP) groups. Aspartame was administered orally for eight weeks. Thereafter, we evaluated aspartame’s effect on kidneys via histological analysis. Results There were no differences in serum creatinine and blood urea nitrogen levels between the CTL and ASP groups or between the FD and FD + ASP groups. There was no histological change in the kidneys in any group. The expression of superoxide dismutase and 4-hydroxy-2-nonenal in the kidney did not differ between the CTL and ASP groups or the FD and FD + ASP groups. Conclusion Our findings indicate that the allowed doses of aspartame in humans may not affect kidney function or oxidative states.

Abstract The research employed network toxicology and molecular docking techniques to systematically examine the potential carcinogenic effects and mechanisms of aspartame (l-α-aspartyl-l-phenylalanine methyl ester). Aspartame, a commonly used synthetic sweetener, is widely applied in foods and beverages globally. In recent years, its safety issues, particularly the potential carcinogenic risk, have garnered widespread attention. The study first constructed an interaction network map of aspartame with gastric cancer targets using network toxicology methods and identified key targets and pathways. Preliminary validation was conducted through microarray data analysis and survival analysis, and molecular docking techniques were employed to further examine the binding affinity and modes of action of aspartame with key proteins. The findings suggest that aspartame has the potential to impact various cancer-related proteins, potentially raising the likelihood of cellular carcinogenesis by interfering with biomolecular function. Furthermore, the study found that the action patterns and pathways of aspartame-related targets are like the mechanisms of known carcinogenic pathways, further supporting the scientific hypothesis of its potential carcinogenicity. However, given the complexity of the in vivo environment, we also emphasize the necessity of validating these molecular-level findings in actual biological systems. The study introduces a fresh scientific method for evaluating the safety of food enhancers and provides a theoretical foundation for shaping public health regulations.

Background and objective: Aspartame (l-aspartyl l-phenylalanine methyl ester) is an artificial sweetener widely used as a sugar substitute. There are concerns regarding the effects of high aspartame doses on the kidney owing to oxidative stress; however, whether the maximum allowed dose of aspartame in humans affects the kidneys remains unknown. Therefore, in this study, we investigated whether the maximum allowed dose of aspartame in humans affects the kidneys. Methods: In this study, animals were fed a folate-deficient diet to mimic human aspartame metabolism. Eight-week-old ICR mice were divided into control (CTL), 40 mg/kg/day of aspartame-administered (ASP), folate-deficient diet (FD), and 40 mg/kg/day of aspartame-administered with a folate-deficient diet (FD + ASP) groups. Aspartame was administered orally for eight weeks. Thereafter, we evaluated aspartame's effect on kidneys via histological analysis. Results: There were no differences in serum creatinine and blood urea nitrogen levels between the CTL and ASP groups or between the FD and FD + ASP groups. There was no histological change in the kidneys in any group. The expression of superoxide dismutase and 4-hydroxy-2-nonenal in the kidney did not differ between the CTL and ASP groups or the FD and FD + ASP groups. Conclusion: Our findings indicate that the allowed doses of aspartame in humans may not affect kidney function or oxidative states. [ABSTRACT FROM AUTHOR]

In this study, clinical trials were generalized, summarized, and meta-analyzed to evaluate correlations between artificial sweeteners (ASs) and colorectal cancer (CRC). PubMed, Web of Science, Embase (Ovid platform), MEDLINE, and the Cochrane Library databases were searched from inception until July 24, 2023. The association between AS exposure and CRC incidence was assessed using odds ratios (ORs) and 95% confidence intervals (CIs). STATA software (version 12.0) was used to perform the meta-analysis. Ten studies (three case-control studies and seven cohort studies) involving 711,537 participants were identified. Results showed that the intake of ASs reduced the incidence of CRC (OR = 0.93, 95% CI = [0.87–0.99]) and was not significantly associated with mortality (OR = 0.93, 95% CI = [0.83–1.05]). Subgroup analyses showed that low doses of ASs were associated with lower CRC incidence (OR = 0.90, 95% CI = [0.83–0.99]), and medium/high doses were not associated with CRC incidence (OR = 1.11, 95% CI = [0.93–1.33]; OR = 0.89, 95% CI = [0.79–1.00], respectively). Moreover, low, medium, and high exposures were not associated with an increased risk of mortality due to CRC (OR = 0.95, 95% CI = [0.80–1.14]; OR = 0.99, 95% CI = [0.88–1.11]; OR = 0.93, 95% CI = [0.71–1.21], respectively). The results of our meta-analysis showed that a low intake of ASs may be associated with a lower risk of CRC. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

The research employed network toxicology and molecular docking techniques to systematically examine the potential carcinogenic effects and mechanisms of aspartame (l-α-aspartyl-l-phenylalanine methyl ester). Aspartame, a commonly used synthetic sweetener, is widely applied in foods and beverages globally. In recent years, its safety issues, particularly the potential carcinogenic risk, have garnered widespread attention. The study first constructed an interaction network map of aspartame with gastric cancer targets using network toxicology methods and identified key targets and pathways. Preliminary validation was conducted through microarray data analysis and survival analysis, and molecular docking techniques were employed to further examine the binding affinity and modes of action of aspartame with key proteins. The findings suggest that aspartame has the potential to impact various cancer-related proteins, potentially raising the likelihood of cellular carcinogenesis by interfering with biomolecular function. Furthermore, the study found that the action patterns and pathways of aspartame-related targets are like the mechanisms of known carcinogenic pathways, further supporting the scientific hypothesis of its potential carcinogenicity. However, given the complexity of the in vivo environment, we also emphasize the necessity of validating these molecular-level findings in actual biological systems. The study introduces a fresh scientific method for evaluating the safety of food enhancers and provides a theoretical foundation for shaping public health regulations. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this review was to assess the current evidence regarding the associated physiological and cognitive effects of aspartame (APM) consumption and Parkinson's Disease (PD). Methods: A total of 32 studies demonstrating effects of APM on monoamine deficiencies, oxidative stress, and cognitive changes were reviewed. Results: Multiple studies demonstrated decreased brain dopamine, decreased brain norepinephrine, increased oxidative stress, increased lipid peroxidation, and decreased memory function in rodents after APM use. In addition, PD animal models have been found to be more sensitive to the effects of APM. Discussion: Overall, studies of APM use over time yielded more consistent results; however, no study has examined long-term effects on APM in human PD patients. Based on the current evidence, long-term human based observational research is needed to further investigate the potential effect of APM on PD. [ABSTRACT FROM AUTHOR]

Advanced oxidation processes are the most efficient tool to thwart the overaccumulation of harmful organic compounds in the environment. In this direction bioinspired metal complexes may be a viable solution for oxidative degradations in water. However, their synthesis is often elaborated and their scalability consequently low. This study presents alternative easy-to-synthesize bioinspired metal complexes to promote degradations in water. The metals employed were iron and manganese ions, hence cheap and highly accessible ions. The complexes were tested toward Phenol, Estrone, Triclosan, Oxybenzone, Diclofenac, Carbamazepine, Erythromycin, Aspartame, Acesulfame K, Anisole and 2,4-Dinitrotoluene. The reaction favoured electron-rich compounds reaching a removal efficiency of over 90%. The central ion plays a crucial role. Specifically, Mn(II) induces a non-radical pathway while iron ions a predominant radical one (⋅OH is predominant). The iron systems resulted more versatile toward contaminants, while the manganese ones showed a higher turn-over number, hence higher catalytic behaviour. [ABSTRACT FROM AUTHOR]

The widespread use of non-nutritive sweeteners (NNSs) in the food and beverage industry has become a global trend. A study was undertaken to assess the level of awareness of South Africans of NNSs and to create a scientific product database of NNSs in a sample of packaged products in South Africa. A cross-sectional survey design was chosen. The study was carried out online in South Africa. The study participants were South African adults (n = 388). A consumer awareness survey on NNSs and a scientific product database were created to identify products formulated with NNSs. A large proportion of participants were unfamiliar with most NNSs by name; however, a significant 61% (n = 238) (p < 0.001) of participants were most aware of xylitol, and 45% (n = 174) were aware of aspartame. Despite this, a significant number of participants consumed products labelled 'sugar-free' and/or 'diet' (p < 0.001). Participants were aware of health concerns and health benefits associated with the consumption of NNSs. A scientific product database consisting of 419 products containing NNSs was created during the study. A combination of NNSs was used in the formulations of 65% (n = 273) of the products, while 35% (n = 146) of the products were formulated with a single NNS. The outcome of this research highlights key consumer insights into NNSs and their widespread use in product formulations in South Africa. The outcome of this study shows the need for continuous monitoring of the effects of the increasing use of NNSs in product formulation and their impact on health and diet. Consumer education would advance consumer awareness of NNSs. [ABSTRACT FROM AUTHOR]

Background: Oral Thin Film (OTF) is an emerging approach for oral drug delivery but still there exists a scarcity of evidence for formulation optimization techniques. Herein, we aim to develop OTFs optimized by the QbD approach. Materials and Methods: OTFs were prepared by solvent casting method using Amlodipine as an active ingredient and excipients such as Pectin, Aspartame, Tween 80, and Glycerine. The developed formulation was optimized using QbD software Design Expert version 8.0.4, USA. The independent variables of the experiment were selected as A-pectin, B-Tween-80, and C-glycerine, and the dependent variables were R1-tensile strength (kg/cm2), R2-permeation rate (µg/cm2/hr), R3-disintegration time (in a sec). Finally, the software suggested optimized formulation based on a desirability value closer to 1. Results: The optimized oral films were comparatively evaluated and characterized by various techniques. The drug release was found to be ~96% at 10 min for OTFs and ~94% at 20 min for oral fast-dissolving tablets. The amlodipine was scanned in the UV range of 200 to 400 nm and the λmax was observed to be at 240±2 in a Phosphate of pH 6.8. Conclusion: All results are found satisfactory and well within the acceptance range. This ensures that similar formulations can be optimized by using this technique in the future. [ABSTRACT FROM AUTHOR]

Purpose: Aceclofenac is a nonsteroidal anti-inflammatory drug (NSAID) belonging to BCS Class II, has a constraint over its therapeutic benefits owing to its poor aqueous solubility. Methods: In this study, co-amorphous mixtures of Aceclofenac (ACE) with Aspartame (ASPA) of various molar ratios at specific milling times were produced through ball milling (BM) technique. The characterization was done using FTIR, DSC and PXRD. The pellets formulation was prepared by extrusion spheronization method using 32 full factorial design. The optimized formulation was evaluated for in-vitro and in-vivo performance. Results: Amongst the co amorphous mixtures and pure ACE studied for solubility, ACE: ASPA (1:1) showed the significant increase in solubility and was further formulated as pellets. Solid-state characterization of mixture revealed amorphization of ACE after 120 min of ball milling. In-vitro dissolution study data of F4 pellets formulation revealed (99.00 ± 3.59%) significant increase (P < 0.005) compared to pure drug (50.12 ± 2.52%) and other formulations. The in-vivo studies reveal a significant increase in percent inhibition of inflammation (61.7%) of the prepared formulation (p < 0.05) as compared to the marketed formulation (53.19%), and pure drug (46.8%). Conclusion: Therefore, the prepared pellets of co-amorphous mixture of aceclofenac and aspartame, boost the solubility and stability of aceclofenac which has a potential to be a promising approach in the management of pain. [ABSTRACT FROM AUTHOR]

The world is facing an epidemic of obesity. One of the ways to produce food with reduced or without sugar is with the use of natural sweeteners. Acacia, in addition to maltitol and aspartame as an alternative to sucrose in an instant drink has proven to be an excellent choice for food industry manufacturers. Acacia met expectations not only from a technical point of view in terms of good homogenization but also by providing good solubility in water, as well as good synergy with the other components of the formulation. The good digestibility of dietary fibers only improves the bioavailability of other formulation components in the digestive tract, starting in the oral cavity. In doing so, the protection of the tooth enamel has been fully observed, as well as the maintenance of the low glycemic index. This research aims to make sugar-free instant drinks using different sweeteners. For this purpose, the prepared instant drinks were made with acacia gum at 50%, maltitol at 37.5%, and aspartame at 1%, approximately, as a substitute for sucrose (table sugar). To determine the caloric value of instant drinks, a BeBis software program for food products has been used. For conducting sensory evaluation - the Hedonic Scale method was used, which allows participants to rate their overall liking of the product based on different sensory attributes. Saturated fatty acids and sugars were not detected and had a 0% caloric value, apart from proteins which were present in 0.4% and fat 0.1%, leading to an expected caloric value of approximately 80 kcal on 100 g instant drink with acacia gum. The use of acacia gum, maltitol, and aspartame provides an opportunity to obtain an instant drink that has health aspects, not only as a zero-sugar drink, but also as dietetic fiber, prebiotic, digestive tolerance, glycemic regulation, and enamel protection. That makes this instant drink potentially healthier not only for diabetics but also for the general population. [ABSTRACT FROM AUTHOR]

Aspartame, a widely used artificial sweetener, is present in many food products and beverages worldwide. It has been linked to potential neurotoxicity and developmental defects. However, its teratogenic effect on embryonic development and the underlying potential mechanisms need to be elucidated. We investigated the concentration- and time-dependent effects of aspartame on zebrafish development and teratogenicity. We focused on the role of sirtuin 1 (SIRT1) and Forkhead-box transcription factor (FOXO), two proteins that play key roles in neurodevelopment. It was found that aspartame exposure reduced the formation of larvae and the development of cartilage in zebrafish. It also delayed post-fertilization development by altering the head length and locomotor behavior of zebrafish. RNA-sequencing-based DEG analysis showed that SIRT1 and FOXO3a are involved in neurodevelopment. In silico and in vitro analyses showed that aspartame could target and reduce the expression of SIRT1 and FOXO3a proteins in neuron cells. Additionally, aspartame triggered the reduction of autophagy flux by inhibiting the nuclear translocation of SIRT1 in neuronal cells. The findings suggest that aspartame can cause developmental defects and teratogenicity in zebrafish embryos and reduce autophagy by impairing the SIRT1/FOXO3a axis in neuron cells. [ABSTRACT FROM AUTHOR]

Energy drinks and mango juice are popular beverages. Apart from the natural ingredients and some additives present in these drinks, sugar is an important component of both. It has been established that, other than providing sweetness, sugars are potent to bring about health consequences for their consumers. Sweeteners, both artificial (aspartame, sodium cyclamate, and saccharin) and natural (sucrose), were our centers of interest. This study aimed to determine the presence and levels of these sweeteners in energy drinks and mango juice. Spectrophotometric methods were used to determine the concentration of the mentioned sugars. For this purpose, a total of 42 samples of 7 different brands were collected from different locations in Dhaka city, Bangladesh. The methods were found to be linear over the concentration range of 10-26 µg/mL (r2=0.9989), 137-320 µg/mL (r2=0.9891), 2.5-24 µg/mL (r2=0.9915) and 2354-2784 µg/mL (r2=0.9985) for aspartame, sodium cyclamate, saccharin, and sucrose, respectively. Mango juice contained a relatively lower amount of saccharin compared to energy drinks. In the case of aspartame, one brand of energy drinks had the least amount. Moreover, both energy drinks and mango juice had a similar content of sodium cyclamate, but one brand of mango juice had a relatively low content of sodium cyclamate. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: This commentary explores the landscape of non-nutritive sweeteners, further delves into the historical trajectory and the contemporary surge in the consumption of non-nutritive sweeteners (NNS), along with the accompanying controversies concerning their safety. Objective: The aim is to provide a comprehensive understanding of the influences of NNS, drawn from global studies and diverse perspectives. Methods: The commentary synthesizes findings from global studies, notably the NutriNet-Santé cohort, exploring associations between specific NNS and health consequences such as cerebrovascular events and malignancies. Additionally, it examines the research on consequences of NNS on gut microbiota and explores concerns linked to gestational diabetes, fetal exposure, and health of the offspring. Results: While caution is advised during pregnancy and fetal development due to potential risks, NNS show promise in weight management and short-term dietary goals when used cautiously in lower amounts. The commentary underscores the necessity for inclusive, long-term studies to guide evidence-driven policies and guidelines. Conclusion: While the article underscores the complexities and debates surrounding non-nutritive sweeteners (NNS), it also sheds light on the positive aspects. In the Indian context, where the intake of sweeteners is relatively low and mainly limited to beverages (tea or coffee), NNS appear to be safe, but prudent use is advocated. The article emphasizes the value of public education on NNS usage and concludes that, overall, NNS are reasonably safe when consumed in moderation. Continued research is needed to elucidate their intricate effects on health and impact on global health outcomes. Implications: The article concludes with clear guidelines for using NNS in India, highlighting the need for informed decision-making and ongoing research to elucidate their broader health consequences. [ABSTRACT FROM AUTHOR]

Artificial sweeteners, also known as nonnutritive sweeteners have many benefits like low calories count. It is frequently used for reducing weight, controlling blood sugar levels and decreasing the chances of dental decay. This study evaluated the effects of NNS in the kidney function. Using the blood sample of the albino rats, the level of creatinine and urea was calculated after the use of NNS for 3 weeks. 70 rats were equally divided into 7 groups. The groups were given Stevia 200mg/kg/day, 10% solution of sucrose, Sucralose 3g/kg/day, Saccharine, Aspartame 250mg/kg/day and Acesulfame-k 250mg/kg/day respectively. In the controlled group, distilled water was used as a placebo. The results indicated that saccharin and aspartame both caused the urea to increase to 37±0.5 mg/dl from initial 30±1.5mg/dl and acesulfame-k represented the most increase in the urea, which elevated the levels from 30 mg/dl to 38±1.5 mg/dl. Additionally, saccharine and aspartame increased the creatinine levels from from 0.1 to 0.85±0.05 mg/dl and sucralose elevated the level of creatinine from 0.1 mg/dl to 1.3±0.2 mg/dl. In the stevia group, the results remained the same as in the controlled group. This indicates the nephrotoxic effects of NNS and proves Stevia safe for the daily use as an alternative. [ABSTRACT FROM AUTHOR]

Excessive sucrose consumption leads to diseases such as obesity and diabetes; the industry is focusing on the use of sweeteners with low caloric content. The aim of this study was to profile and evaluate the sensory temporality of five sweeteners using Time Intensity (TI), Temporal Dominance of Sensations (TDS) and temporal acceptability, in aqueous solution and in yogurt in order to provide information on the replacement and reduction of sucrose consumption. The sweeteners evaluated were sucrose, sucralose, stevia, aspartame, and tagatose. The evaluation of the panelists using the TI method in aqueous solutions revealed that the temporal profile of stevia is different from the other sweeteners, with a greater persistence of sweetness in the mouth. The evaluation of the sweeteners in yogurt by consumers using TDS and temporal acceptability method showed that tagatose was the sweetener most similar to sucrose in terms of TDS curves, on the other hand, through temporal acceptability, stevia (5.28) and aspartame (5.13) showed higher acceptability than other sweeteners (9-point scale), explaining the consumer preferences. Stevia was the sweetener with the longest perception time (13 s) of sweetness intensity in aqueous solution, together with greater dominance, temporal acceptability, and one of the most preferred along with aspartame by consumers. [ABSTRACT FROM AUTHOR]

A primary concern for many cancer survivors is getting cancer again or it returning. Unfortunately, recurrence can happen but there is evidence that dietary interventions, generally combined with physical activity, improve overall quality of life and give the body the best chance of warding off recurrence. Being the right weight for height is also important. This article explores dietary and lifestyle considerations, dispels some myths, and considers other aspects of diet and lifestyle and prevention of cancer recurrence, such as alcohol intake, physical activity and food-borne disease. It also looks at the role certain sweeteners may have, along with ultra-processed foods, use of certain supplements and the role of fibre. Definitive evidence is often not available for this aspect of cancer, but this article presents the most up-to-date findings. Specialist post treatment palliative care is not covered. [ABSTRACT FROM AUTHOR]

The use of aspartame (ASP) and potassium acesulfame (ACK) to reduce weight gain is growing; however, contradictory effects in body mass index control and neurobiological alterations resulting from artificial sweeteners consumption have been reported. This study aimed to evaluate the impact of the chronic consumption of ASP and ACK on mood-related behavior and the brain expression of serotonin genes in male Wistar rats. Mood-related behaviors were evaluated using the swim-forced test and defensive burying at two time points: 45 days (juvenile) and 95 days (adult) postweaning. Additionally, the mRNA expression of three serotoninergic genes (Slc6a4, Htr1a, and Htr2c) was measured in the brain areas (prefrontal cortex, hippocampus, and hypothalamus) involved in controlling mood-related behaviors. In terms of mood-related behaviors, rats consuming ACK exhibited anxiety-like behavior only during the juvenile stage. In contrast, rats consuming ASP showed a reduction in depressive-like behavior during the juvenile stage but an increase in the adult stage. The expression of Slc6a4 mRNA increased in the hippocampus of rats consuming artificial sweeteners during the juvenile stage. In the adult stage, there was an upregulation in the relative expression of Slc6a4 and Htr1a in the hypothalamus, while Htr2c expression decreased in the hippocampus of rats consuming ASP. Chronic consumption of ASP and ACK appears to have differential effects during neurodevelopmental stages in mood-related behavior, potentially mediated by alterations in serotoninergic gene expression. [ABSTRACT FROM AUTHOR]

Simple Summary: We propose that having a proper perspective and narrative about the origin and nature of cancer metabolism affects cancer research and cancer care in integrated versus targeted therapy, multimodal versus precision medicine, and drug versus therapy development. Knowing and understanding whether cancer is a metabolic, genetic, or stem cell disease influences how we conduct informative cancer research and how we discover impactful cancer therapy. Although Otto Warburg may be right about the role of glycolysis versus OXPHOS in cancer metabolism, it remains unclear whether an altered metabolism is causative or correlative and is the main driver or a mere passenger in the pathogenesis of cancer. Currently, most of our successful treatments are designed to eliminate non-cancer stem cells (non-CSCs) such as differentiated cancer cells. When the treatments also happen to control CSCs or the stem-ness niche, it is often unintended, unexpected, or undetected for lack of a pertinent theory about the origin of cancer that clarifies whether cancer is a metabolic, genetic, or stem cell disease. Perhaps cellular context matters. After all, metabolic activity may be different in different cell types and their respective microenvironments—whether it is in a normal progenitor stem cell vs. progeny differentiated cell and whether it is in a malignant CSC vs. non-CSC. In this perspective, we re-examine different types of cellular metabolism, e.g., glycolytic vs. mitochondrial, of glucose, glutamine, arginine, and fatty acids in CSCs and non-CSCs. We revisit the Warburg effect, an obesity epidemic, the aspartame story, and a ketogenic diet. We propose that a pertinent scientific theory about the origin of cancer and of cancer metabolism influences the direction of cancer research as well as the design of drug versus therapy development in cancer care. [ABSTRACT FROM AUTHOR]

Aspartame (ASP) as an important sugar substitute is widely used in pharmaceutical and food processing. Here, we compared the effects of ASP and sucrose on mice pancreatic islet cells in vivo and observed that ASP with the condition of high concentration and long-term exposure (HASP) could cause insulin secretion (500 mg/kg for 1 month). Next, we conducted iTRAQ mass spectrometry to profile the global phosphoproteome and found that phosphorylation of zipper-interacting protein kinase (ZIPK) in murine pancreatic islet tissues were induced at Thr197, Thr242, Thr282, and Ser328 by high-sucrose (HS) treatment, but only induced at Thr197 and Ser328 by HASP treatment. Simultaneously, phosphorylation of STAT3 could be induced at Tyr705 and Ser727 by HS but not by HASP. Furthermore, presence of activated STAT3 accompanied with autophagy was observed in HS treatment. In turn, the inactivation of STAT3 as well as enhanced expression of caspase 3 was observed in HASP treatment. We generated Thr242APro and Thr282Pro on ZIPK using CRISPR-Cas9 in β-TC3 cells and found the weakened interaction with STAT3 as well as the reduced phosphorylation of STAT3 even under HS stimulation. Finally, we observed that ankyrin repeat domain containing 11 (ANKRD11) could interact with ZIPK and play an inhibitory role in the phosphorylation of Thr242APro and Thr282Pro of ZIPK. However, HASP can induce the retention of ANKRD11 in the cytoplasm by phenylpyruvic acid (the metabolite of ASP). Taken together, this study determined that ASP with high concentration and long-term exposure could lead to caspase-dependent apoptosis of pancreatic islet cells through ANKRD11/ZIPK/STAT3 inhibition. Our results give evidence of adverse effects of aspartame on islet cells in some extreme conditions, which might help people to reconsider the biosafety of non-nutritive sweeteners. [ABSTRACT FROM AUTHOR]

A high-performance liquid chromatographic method with evaporative light scattering detection (HPLC-ELSD) was optimized for the simultaneous determination of non-caloric sweeteners—NCS (acesulfame-K, aspartame, cyclamic acid, neotame, saccharin, and sucralose) in non-alcoholic beverages. The procedure involved a simple dilute-and-shoot extraction of the six NCS with a formic acid/triethylamine/water solution and filtration (0.22 μm) followed by an HPLC–ELSD analysis. Validation steps included regression of the analytical curve, recovery, repeatability, and intermediate precision (relative standard deviation—RSD and RSDip, respectively), and limits of quantification and detection (LOQ and LOD, respectively). The method allowed lower consumption of solvents in a 35-min run. The figures of merit were satisfactory for all sweeteners (r2 ≥ 0.99; recovery from 99.0 to 101%; RSD and RSDip both < 1.0; LOQ ≤ 4.0 μg/mL; LOD ≤ 1.33 μg/mL). The method was used in the analysis of NCS in 64 non-alcoholic beverages from the market. NCS were not detected in 19 samples that did not declare their use. Higher concentrations of aspartame were found in carbonated soft drinks (7.97 mg/100 mL) and powdered drinks (22.46 mg/100 mL), while nectars had higher levels of acesulfame-K (8.69 mg/100 mL) and sports drinks only had sucralose (1.66 mg/100 mL). The concentrations found were 54.1 up to 194.0% of declared levels. The estimated daily intake of NCS in non-alcoholic beverages by the Brazilian population indicated that men, adolescents, residents of urban areas, and inhabitants of the southern region are the most widely exposed to NCS, but the risk is characterized as low. [ABSTRACT FROM AUTHOR]

An amperometric bienzymatic biosensor was developed for the determination of aspartame in a flow injection analysis (FIA) system, consisting of two enzyme reactor columns packed with immobilized α-chymotrypsin (CHY) and alcohol oxidase (AOX) beads and a hydrogen peroxide electrode, connected in series. The CHY and AOX were separately immobilized on glutaraldehyde (GA)-activated beads through covalent bonding. The biosensor fabrication and operational conditions were optimized. The optimal fabrication conditions were: 2% GA with 120 min activation time; and 250 U/mL CHY and 100 U/mL AOX, with 180 min enzyme immobilization time. The optimal operational conditions were a flow rate of 0.5 mL/min and pH 8.0 at room temperature. The developed biosensor showed linearity over the aspartame concentration range 0.01–1.2 mM, with a detection limit of 0.005 mM. The developed biosensor was satisfactorily applied for detecting aspartame in beverage samples without any excessive pretreatments. [ABSTRACT FROM AUTHOR]

Background: Many reports on the use of aspartame revealed that it releases metabolites which in turn cause brain adverse effect on rats. Our aim was to investigate the impact of aspartame on histopathology and ultrastructure of rat frontal cortex and assess the efficacy of Adipose-Mesenchymal Stem Cells (AD-MSCs) to ameliorate this effect after chronic aspartame administration (40 mg/kg per body weight). Methods: to investigate the effects of aspartame, methotrexate and folate deficient diet was used to induce folate deficiency in rats to imitate the human methanol metabolic process. The animals were distributed into four groups; control group, MTX control, MXT/Aspartame and MXT/aspartame/AD-MSCs group. The histopathology and ultrastructure of frontal cortex along with its cell's expression of Caspase-3 and GFAP were assessed. The used AD-MSCs were characterized by immunohistochemical detection of CD73, CD105 and CD45 markers and tracked in frontal cortex by PCR. Results: White matter density was significantly reduced in MTX/aspartame animals, evidence of gliosis, pyramidal cell intracellular and extracellular vacuolations and Significant increase in Caspase-3 and GFAP stained neuron. Disorganization of ultrastructure organelles and oedematous astrocyte plates around blood vessels were evident when compared to control animals. Almost restoration of the frontal cortex architecture and ultrastructure was established in the MXT//aspartame/AD-MSCs together with significant decrease in Caspase-3 and GFAP stained neuron compared to MXT//aspartame group. Conclusions: AD-MSCs transplantation could mitigate the degenerative impact of aspartame metabolites on the rat frontal cortex. [ABSTRACT FROM AUTHOR]

There are emerging concerns about the potential cerebral cortex injury from aspartame due to the accumulation of the various neurotoxic metabolic components in the central nervous system after long-term dietary exposure. The aim of this study was to evaluate the effect of oral aspartame consumption on cerebral cortex injury in the rat brain, and further evaluate the various underlying molecular mechanisms, with a special focus on oxidative stress, inflammation, mitochondrial dysfunction, and apoptosis pathways. Sprague Dawley rats (nineteen, female) were randomly sub-divided into three groups: (i) normal diet with vehicle: control group (five rats), (ii) low dose of aspartame group (LA): seven rats received 30 mg/kg body weight (bw) daily doses of aspartame, (iii) high dose of aspartame group (HA): seven rats received 60 mg/kg bw daily doses of aspartame. After 8 weeks, the LA and HA groups showed lower expression levels of brain-derived neurotrophic factor (BDNF), antioxidant enzyme activity (SOD2, CAT), antioxidant marker (Nrf2), inflammatory response (IκB), mitochondrial biogenesis (Sirt1, PGC1α, Nrf1, TFAM), mitochondrial DNA (mtDNA) copy number, and apoptosis-related proteins (Bax, Caspase-3) expressions. Aspartame administration also elevated oxidative stress levels (Malondialdehyde, MDA), 8-hydroxy-2-deoxy guanosine (8-OHdG), PGE2 and COX-2 expressions, pro-inflammatory cytokines (TNFα, IL6, IL1β), antioxidant marker expression (Keap1), inflammatory responses (iNOS, NFκB), and glial fibrillary acidic protein (GFAP) levels in the cerebral cortex of the rats, thereby contributing to the reduced survival of pyramidal cells and astrocyte glial cells of the cerebral cortex. Therefore, these findings imply that aspartame-induced neurotoxicity in rats' cerebral cortex could be regulated through four mechanisms: inflammation, enhanced oxidant stress, decreased mitochondrial biogenesis, and apoptosis pathways. [ABSTRACT FROM AUTHOR]

Aspartame, an artificial sweetener used extensively in foods and beverages, has raised health concerns due to its potential adverse effects. However, current analytical methods for detecting aspartame like HPLC and GC-MS are expensive, intricate, and unsuitable for on-site analysis. Therefore, the objective of this work is to develop a rapid, simple, sensitive, and selective electrochemical sensor for aspartame detection in real samples like sports drinks. The sensor is fabricated by combining molecularly imprinted polymers (MIPs) and multi-walled carbon nanotubes (MWCNTs). MIPs provide specificity towards aspartame via tailored binding sites, while MWCNTs enable sensitive electrochemical transduction. Characterization confirms successful preparation of the MIP-MWCNT sensor. The sensor exhibits a linear detection range of 8 nM to 6 µM aspartame with a 22 nM limit of detection. Practical application is demonstrated by accurate quantification of aspartame in spiked sports drink samples. The sensor provides a cost-effective and portable solution for rapid aspartame screening in complex matrices. In summary, this work aims to create an electrochemical molecularly imprinted sensor leveraging MIPs for selectivity and MWCNTs for sensitivity in order to achieve simple, rapid, and reliable detection of aspartame. [ABSTRACT FROM AUTHOR]

The artificial sweeteners (AS) are popular low-calorie substances used as sugar substitutes, providing strong sweetening effects without adding sugar and energy to the diet. The most popular AS are aspartame, saccharin, and acesulfame K. The aim of this study is to investigate the awareness and knowledge on the usage and health effects of the artificial sweeteners in food products in North Macedonia. Therefore, an online survey was conducted, distributed through Forms media platform on different age population, completed by 392 participants aged 12 years and above, where 69 % were at the age of 30 - 64 old. According to the obtained results, 6 % of respondents do not know what AS are, while 23 % are partially familiar with them. Moreover, 19 % of the respondents do not know how to recognize the additives on the product declarations at all. On the question if the respondents could list which artificial sweeteners they know, 43 % did not know how to answer, and 28 % gave a partially correct or incorrect answer. Also, 35 % of respondents answered that they use artificial sweeteners in order to reduce the calorie intake. Regarding the risk of consuming large amounts of AS in the diet, 15 % of respondents are not aware, and 36 % are partially aware. The results suggest that it is necessary to develop effective strategies for greater education, information and awareness of consumers, about the usage of AS in their diet, as well as about the advantages and risks of their intake. [ABSTRACT FROM AUTHOR]

Sweeteners are food additives consumed worldwide, especially by individuals with restrictive diets. This study evaluated the cytotoxic and genotoxic effects of sweeteners widely sold in Brazil through a bioassay with Allium cepa. Onion bulbs were exposed to different concentrations of sweeteners, and their root cells were stained with acetic carmine and analyzed under an optical microscope. Distilled water was used as a negative control, and glyphosate as a positive control. The results demonstrated that the mitotic index (MI) and the chromosome aberration index (CAI) of the three sweeteners tested did not differ significantly from the negative control, indicating that they are not toxic or mutagenic additives. This result is positive for consumers of these products, especially those who need to replace sugar due to dietary restrictions. However, they should be consumed with caution.

Increased interest in the utilization of nutrition management of patients with phenylketonuria is clear. Applications include a small measured amount of phenylalanine given in the form of exchange food, phenylalanine-free protein substitute and low phenylalanine foods. In this article, the essential nutritional contents of low phenylalanine diets and the latest techniques and procedures used for creating several types of low phenylalanine diets from different food sources for persons with phenylketonuria are reviewed. The principles of these methods are described. Most of the techniques and procedures employed to remove Phe from the protein hydrolysate are based on the liberation of the amino acid using enzymatic hydrolysis. Free Phe is then removed via adsorption. Therefore, knowing the phenylalanine (Phe) content of foods as well as principles of procedures and techniques used for creating low Phe diets is very important for managing the diet of patients with phenylketonuria. Allowed foods and foods that should be avoided by persons with phenylketonuria are mentioned. Low Phe cereal based foods (i. e. toast bread, pasta, shamy bread, pan bread and rice) and dairy based foods are also considered. The US FDA regulation of aspartame labeling is also stated.