Increased plasma levels of non-sugar sweeteners in patients with symptomatic carotid atherosclerosis.

Purpose. The non-sugar sweeteners acesulfame K and saccharin are considered safe, but there is conflicting evidence on their effects on cardiovascular health. Materials and methods. In this explorative pilot study, we measured plasma levels of acesulfame K and saccharin in 15 patients with symptomatic carotid atherosclerosis, 18 asymptomatic patients and 15 control subjects. Fecal microbiota and short-chain fatty acids were analyzed. Dietary and medical history was assessed. Results. Symptomatic patients had higher levels of acesulfame K and saccharin compared to controls. Acesulfame K was associated with increased leukocyte count. Saccharin was associated with more severe carotid stenosis, as well as lower fecal butyric acid.

Study on the taste-masking effect and mechanism of Acesulfame K on berberine hydrochloride.

OBJECTIVE: In our previous taste-masking study, we found that Acesulfame K (AK) had a better taste-masking effect than other high-efficiency sweeteners for several representative bitter natural drugs in aqueous decoction. Furthermore, we performed a preliminary taste-masking study of AK for representative bitter API Berberine Hydrochloride (BH) and found that it had a good taste-masking effect. We also found that flocculent precipitation was generated in the BH solution, but it was not clear whether it was related to the good taste-masking effect. This study was conducted to explore the taste-masking effect and mechanism of AK on BH. METHODS: The taste-masking effect of AK on BH was evaluated based on the Traditional Human Taste Panel Method and the electronic tongue evaluation method. DSC, XRD, and molecular simulation techniques were used to explore the mechanism of AK on BH, from the macro level and molecular level, respectively. RESULTS: When evaluating the taste-masking effect, we found that 0.1% AK had the best taste-masking effect on BH, while higher concentrations had a worse taste-masking effect. DSC and XRD revealed that the flocculent precipitation was a complex AK-BH. Finally, by simulating the binding of AK, BH, and TAS2R46 receptors, we found the unique taste-masking mechanism of AK. CONCLUSION: The sweet taste stimulus of AK can mask the bitter taste stimulus of BH, and AK can generate AK-BH with BH to reduce the contact between BH and bitter taste receptors. Additionally, it could block the expression of the TAS2R46 receptors.

Chronic administration of caffeine alters acesulfame-K intake and features of fungiform taste buds in mice.

The objective of this study was to investigate the effects of chronic administration of caffeine on the anatomical characteristics of taste buds, the expression level of taste receptor protein in mice, and preference for a palatable solution. We found that following a 21-day administration of caffeine, mice showed increased behavioural responses to sweet stimuli (acesulfame-K solution). Mirroring this behavioural change, chronic caffeine treatment evidently decreased the maximal cross-sectional area and height of the longitudinal axis of fungiform taste buds, the number of taste cells per fungiform taste bud, and the expression of G protein α-gustducin, while the expression of the sweet taste receptors T1R2 and T1R3 was reversed. Our findings demonstrate that chronic administration of caffeine has an impact on taste sensitivity and changes in taste bud features, which may contribute to the alteration of taste behaviour.

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

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

Consumption of non-nutritive sweeteners during pregnancy.

In an effort to reduce sugar consumption to prevent diabetes mellitus and cardiovascular diseases, "sugar-free" or "no added sugar" products that substitute sugar with non-nutritive sweeteners (NNSs) (eg, Splenda, Sweet'N Low, and Stevia) have become increasingly popular. The use of these products during pregnancy has also increased, with approximately 30% of pregnant women reporting intentional NNS consumption. In clinical studies with nonpregnant participants and animal models, NNSs were shown to alter gut hormonal secretion, glucose absorption, appetite, kidney function, in vitro insulin secretion, adipogenesis, and microbiome dysbiosis of gut bacteria. In pregnant animal models, NNS consumption has been associated with altered sweet taste preference later in life and metabolic dysregulations in the offspring (eg, elevated body mass index, increased risk of obesity, microbiome dysbiosis, and abnormal liver function tests). Despite the accumulating evidence, no specific guidelines for NNS consumption are available for pregnant women. Furthermore, there are limited clinical studies on the effects of NNS consumption during pregnancy and postpartum and long-term outcomes in the offspring.

A Quantitative Method for Acesulfame K Using the Taste Sensor.

We have developed a method to quantify the sweetness of negatively charged high-potency sweeteners coexisting with other taste substances. This kind of sweetness sensor uses lipid polymer membranes as the taste-sensing part. Two types of outputs have been defined in the measurement of the taste sensor: one is the relative value and the other is the CPA (the change in membrane potential caused by adsorption) value. The CPA value shows a good selectivity for high-potency sweeteners. On the other hand, the relative value is several times higher than the CPA value, but the relative value is influenced by salty substances. In order to obtain both high sensitivity and selectivity, we established a model for predicting the concentration of sweeteners with a nonlinear regression analysis method using the relative values of both the sweetness sensor and the saltiness sensor. The analysis results showed good correlations with the estimated concentration of acesulfame potassium coexisting with salty substances, as represented by R2 = 0.99. This model can correspond well to the prediction of acesulfame K in a concentration of 0.2-0.7 mM, which is commonly used in food and beverages. The results obtained in this paper suggest that this method is useful for the evaluation of acesulfame K using the taste sensors.

The acute effects of the non-nutritive sweeteners aspartame and acesulfame-K in UK diet cola on glycaemic response.

Substituting sugar-sweetened for artificially sweetened beverages may reduce energy intakes. This study aims to ascertain the acute glycaemic effects of the NNS aspartame and acesulfame-K in UK diet-cola (DC). Ten healthy participants attended the laboratory fasted on three occasions. Individuals drank (1) 25 g glucose in 125 mL water + 236 mL water, (2) 25 g glucose in 125 mL water with 236 mL DC and (3) 236 mL sucrose-sweetened cola with 125 mL water. Blood (glucose) was measured pre-test and every 15 minutes over a 120-minute period using portable glucometers. The glucose-control and glucose + DC elicited similar blood glucose rises above pre-prandial levels. Sucrose-sweetened cola showed a non-significant lower rise in postprandial glycaemia, exhibiting the lowest glycaemic index (GI) (77.0 ± 9.1). GI of glucose (100.0 ± 15.2) and glucose + DC (104.3 ± 8.5) was similar and a one-way repeated-measures ANOVA showed no significant differences in glycaemic response between test drinks (F(2,29) = 1.68, p > .05). Results demonstrate the glycaemic inactivity of non-nutritive sweeteners.

Advantame sweetener preference in C57BL/6J mice and Sprague-Dawley rats.

Advantame is a new ultrahigh-intensity noncaloric sweetener derived from aspartame and approved for human use. Rats and mice are not attracted to the taste of aspartame and this study determined their preference for advantame. In 24-h choice tests with water, C57BL/6J mice and Sprague-Dawley rats were indifferent to advantame at concentrations of 0.01, 0.03, and 0.1mM but significantly preferred 0.3 and 1mM advantame to water. Both species also preferred 1mM advantame to 1mM saccharin in direct choice tests, but preferred 10mM saccharin to 1mM advantame, which is near the solubility limit for this sweetener. Mice also preferred 1mM advantame to 1mM sucralose or acesulfame K, but preferred both sweeteners at 10mM to 1mM advantame. In addition, mice preferred 1mM advantame to 1 and 10mM aspartame. Thus, advantame is a potent sweetener for rodents but, because of limited solubility, is not an effective alternative to saccharin, sucralose, or acesulfame K at higher concentrations.

Artificial sweeteners stimulate adipogenesis and suppress lipolysis independently of sweet taste receptors.

G protein-coupled receptors mediate responses to a myriad of ligands, some of which regulate adipocyte differentiation and metabolism. The sweet taste receptors T1R2 and T1R3 are G protein-coupled receptors that function as carbohydrate sensors in taste buds, gut, and pancreas. Here we report that sweet taste receptors T1R2 and T1R3 are expressed throughout adipogenesis and in adipose tissues. Treatment of mouse and human precursor cells with artificial sweeteners, saccharin and acesulfame potassium, enhanced adipogenesis. Saccharin treatment of 3T3-L1 cells and primary mesenchymal stem cells rapidly stimulated phosphorylation of Akt and downstream targets with functions in adipogenesis such as cAMP-response element-binding protein and FOXO1; however, increased expression of peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α was not observed until relatively late in differentiation. Saccharin-stimulated Akt phosphorylation at Thr-308 occurred within 5 min, was phosphatidylinositol 3-kinase-dependent, and occurred in the presence of high concentrations of insulin and dexamethasone; phosphorylation of Ser-473 occurred more gradually. Surprisingly, neither saccharin-stimulated adipogenesis nor Thr-308 phosphorylation was dependent on expression of T1R2 and/or T1R3, although Ser-473 phosphorylation was impaired in T1R2/T1R3 double knock-out precursors. In mature adipocytes, artificial sweetener treatment suppressed lipolysis even in the presence of forskolin, and lipolytic responses were correlated with phosphorylation of hormone-sensitive lipase. Suppression of lipolysis by saccharin in adipocytes was also independent of T1R2 and T1R3. These results suggest that some artificial sweeteners have previously uncharacterized metabolic effects on adipocyte differentiation and metabolism and that effects of artificial sweeteners on adipose tissue biology may be largely independent of the classical sweet taste receptors, T1R2 and T1R3.

Development of low calorie snack food based on intense sweeteners.

Intense sweeteners namely Aspartame, Acesulfame K and Sucralose were used in the preparation of sugar substitute sprinklers and these were used in snack food, replacing sugar. Study was conducted with an objective to develop low calorie snack food. The psychometric study showed that the threshold values for Acesulfame K, Aspartame and Sucralose were 0.012, 0.030 and 0.005 g respectively. The time intensity study revealed that among three sweeteners Aspartame had more lingering sweetness (at 60 s). The sensory evaluation of Shankarpoli prepared using refined wheat flour revealed that there was no significant difference in typical attributes of the snack; Aspartame and Acesulfame K had same sweetness intensity where as Sucralose had higher intensity of sweetness. Consumer acceptance study revealed that 53 % of the consumers liked the snack with Sucralose, which is highest compared to other two sweeteners namely Aspartame and Acesulfame K (47 %). Thus sweeteners can be used as sweetening agents in traditional food preparations.

Hepatic P53 upregulation and the genotoxic potential of acesulfame-K treatment in rats with a special emphasis on in vitro lymphocyte and macrophage activity testing.

Acesulfame-k (Ace-k) is a widely used artificial sweetener in various products, and long-term cumulative and multisource exposure is possible despite inadequate toxicological data confirming its safety. Ninety male rats were divided into two main groups according to their body weight into immature and mature rats. Each group was subdivided into 3 subgroups: control untreated, 30 and 90 mg/kg b. w of Ace-k via gastric intubation. The treatment was performed daily 5 days per week for 12 weeks. At the end of the experimental period, blood samples were collected for in vitro testing of lymphocyte proliferation rate, comet assay, and macrophage activity about nitric oxide (NO) production. In addition, the collection of liver specimens was performed for P53 gene expression and histopathological evaluation. The results revealed that Ace-k induced modulation in lymphocyte proliferation rate and affected the production of NO by macrophages while increasing in tail moment in a dose-dependent manner that varied among different age groups. The upregulation of P53 in the liver was correlated with increased polyploidization and necro apoptotic reaction and various histopathological hepatic alterations. The present data revealed that chronic treatment of rats with Ace-k affects lymphocyte proliferation and macrophage activity in a dose-dependent manner. In addition, the genotoxic and hepatotoxic potential of Ace-k were confirmed.

Quantification of diffusion coefficients of commonly used high-intensity sweeteners through mucin.

Low- and no-calorie sweeteners reduce the amount of carbohydrates in foods and beverages. However, concerns about taste perception surrounding the role of non-nutritive sweeteners in the oral cavity remain unanswered. One of the parameters that influences taste perception is the diffusion coefficient of the sweetener molecules inside the mucin layer lining the mouth. This study investigated the impact of diffusion coefficients of common high-intensity sweeteners on taste perception focusing on the sweeteners' diffusion through mucin. Transwell Permeable Support well plates were used to measure diffusion coefficients of samples that were collected at specific intervals to estimate the coefficients based on concentration measurements. The diffusion coefficients of acesulfame-K, aspartame, rebaudioside M, sucralose, and sucrose with and without NaCl were compared. We found that different sweeteners show different diffusion behavior through mucin and that the presence of salt enhances the diffusion. These findings contribute insights into the diffusion of high-intensity sweeteners, offer a way to evaluate diffusion coefficients in real-time, and inform the development of products with improved taste profiles.

Sweet-bitter taste interactions in binary mixtures of sweeteners: Relationship between taste receptor activities and sensory perception.

This study investigated the effects of various binary sweetener mixtures on sweetness enhancement and their interactions with sweet or bitter taste receptors, focusing on sensory perception and receptor activity. Acesulfame K or saccharin was mixed with allulose, aspartame, erythritol, fructose, glucose, or sucrose to match a target sucrose sweetness. The effects of the mixtures on sweet and bitter taste receptors (in the human embryonic kidney -293 cells) and sensory taste intensities were evaluated. Sweetness enhancement at the sweet taste receptor level was observed in some cases, with several monosaccharides reducing the acesulfame K- or saccharin-induced bitter taste receptor activity. Combining acesulfame K or saccharin with any of the six sweeteners perceptually enhanced sweetness (60% âˆ¼ 100% in 50:50 ratio), correlating with a reduction in inherent bitterness (-35% âˆ¼ -63% in 50:50 ratio). This finding suggests that sweetness perception likely increased because the monosaccharides mitigate the activation of bitter receptors caused by high-potency sweeteners.

Effects of early intraoral acesulfame-K stimulation to mice on the adult's sweet preference and the expression of α-gustducin in fungiform papilla.

Exposure to artificial sweetener acesulfame-K (AK) at early development stages may influence the adult sweet preference and the periphery gustatory system. We observed that the intraoral AK stimulation to mice from postnatal day 4 (P4) to weaning decreased the preference thresholds for AK and sucrose solutions in adulthood, with the preference pattern unchanged. The preference scores were increased in the exposure group significantly when compared with the control group at a range of concentrations for AK or sucrose solution. Meanwhile, more α-Gustducin-labeled fungiform taste buds and cells in a single taste bud were induced from week 7 by the early intraoral AK stimulation. However, the growth in the number of α-Gustducin-positive taste bud or positive cell number per taste bud occurred only in the anterior region, the rostral 1-mm part, but not in the intermediate region, the caudal 4-mm part, of the anterior two-third of the tongue containing fungiform papillae. This work extends our previous observations and provides new information about the developmental and regional expression pattern of α-Gustducin in mouse fungiform taste bud under early AK-stimulated conditions.

Assessment of stability of binary sweetener blend (aspartame x acesulfame-K) during storage in whey lemon beverage.

In the present study, artificial sweeteners-aspartame, acesulfame-K and binary sweetener blend of aspartame x acesulfame-K were assessed for stability during storage in whey lemon beverage. A solid phase extraction method using C18 cartridges was standardized for the isolation of aspartame, acesulfame-K and their degradation products in whey lemon beverage. HPLC analytical conditions were standardized over C18 column for simultaneous separation of multiple sweeteners and their degradation products in sample isolates. Storage studies revealed that increase in acidity and viscosity and decrease in pH and ascorbic acid content of artificially sweetened whey lemon beverage samples were similar to the changes occurring in control samples during storage. Analysis using HPLC showed that aspartame (added either singly or in a blend) and acesulfame-K (added in a blend) were stable in whey lemon beverage under refrigerated condition for 15 days.

Chemical and biological tracers to identify source and transport pathways of septic system contamination to streams in areas with low permeability soils.

Septic systems are widely used in rural areas that lack centralized sewage treatment systems. Incomplete removal of domestic wastewater contaminants in septic systems can lead to leaching of nutrients (P and N), bacteria/viruses, and trace contaminants to surrounding groundwater and surface water. This study focuses on delineating the fate of wastewater contaminants in localities where septic systems are installed in moderate to fine-grained overburden materials to assess potential impacts on groundwater and surface water quality in these settings. Nutrients and a suite of anthropogenic tracers, including host-specific fecal indicator bacteria (bovine- and human-specific Bacteroides), pharmaceutical compounds (caffeine, carbamazepine, gemfibrozil, ibuprofen, naproxen, and sulfamethoxazole), and an artificial sweetener (acesulfame-K), were selected to evaluate differences in transport properties. Surface water samples (n = 103) were collected from streams upstream (US) and downstream (DS) of three rural hamlets up to two times monthly over one year. Results indicate the presence of wastewater indicators in the streams, with DS locations showing significantly elevated concentrations of both chemical and biological anthropogenic tracers. Human-specific Bacteroides, caffeine, and acesulfame-K were consistently observed at elevated concentrations at all DS sites. Nutrients exhibited varied concentrations between US and DS locations at three study sites. The occurrence of human-specific Bacteroides in the surface water samples suggests the presence of preferential flow pathways within the silt/clay overburden. These results demonstrate the advantages of using a combined tracer approach, involving a conservative tracer such as acesulfame-K coupled with the human-specific biological indicator Bacteroides (BacHum), to understand not only impacting sources but also potential transport pathways of septic system contamination to nearby streams. Septic systems may be an underappreciated contaminant source in rural hamlets located in fine-grained overburden materials; although, a distinction of specific nutrient sources (septic systems vs. agriculture) remains challenging.

Sensory Interactions between Sweetness and Fat in a Chocolate Milk Beverage.

Fat and sugar-reduced foods and beverages have become increasingly popular for a variety of reasons, mainly relating to health and wellbeing. Depending on the food or beverage, it may be difficult to reduce the fat and/or sugar content and still maintain optimal sensory properties for the specific product. One way of approaching the problem is to gain a better understanding of how a product is affected by a reduction in fat and/or sugar. This paper aims to investigate the sensory interactions between fat and sweetness perception in a chocolate-flavored milk beverage by using a descriptive analysis with a trained sensory panel. The reduction of fat significantly reduced the sweetness intensity of the chocolate milk, while the reduction of sucrose significantly decreased the cream flavor and the fruity and lactic flavor. The perception of acesulfame-K was affected by fat concentration, similarly to sucrose. These results highlight the importance of considering the effects of reducing either sugar and fat on product attributes that are not directly related to the sugar or fat.

Sweetener System Intervention Shifted Neutrophils from Homeostasis to Priming.

BACKGROUND: Non-nutritive sweeteners (NNS) are part of personalized nutrition strategies supporting healthy glycemic control. In contrast, the consumption of non-nutritive sweeteners has been related to person-specific and microbiome-dependent glycemic impairments. Reports on the effects of NNS on our highly individual cellular immune system are sparse. The recent identification of taste receptor expression in a variety of immune cells, however, suggested their immune-modulatory relevance. METHODS: We studied the influence of a beverage-typical NNS system on the transcriptional profiling of sweetener-cognate taste receptors, selected cytokines and their receptors, and on Ca2+ signaling in isolated blood neutrophils. We determined plasma concentrations of saccharin, acesulfame-K, and cyclamate by HPLC-MS/MS, upon ingestion of a soft drink-typical sweetener surrogate. In an open-labeled, randomized intervention study, we determined pre- versus post-intervention transcript levels by RT-qPCR of sweetener-cognate taste receptors and immune factors. RESULTS: Here we show that the consumption of a food-typical sweetener system modulated the gene expression of cognate taste receptors and induced the transcriptional regulation signatures of early homeostasis- and late receptor/signaling- and inflammation-related genes in blood neutrophils, shifting their transcriptional profile from homeostasis to priming. Notably, sweeteners at postprandial plasma concentrations facilitated fMLF (N-formyl-Met-Leu-Phe)-induced Ca2+ signaling. CONCLUSIONS: Our results support the notion of sweeteners priming neutrophils to higher alertness towards their adequate stimuli.

Cardiotoxic and neurobehavioral effects of sucralose and acesulfame in Daphnia: Toward understanding ecological impacts of artificial sweeteners.

Artificial sweeteners are widely used in food and pharmaceuticals, but their stability and persistence raise concerns about their impact on aquatic life. Although standard toxicity tests do not reveal lethal effects, recent studies suggest a potential neurotoxic mode of action. Using environmentally relevant concentrations, we assessed the effects of sucralose and acesulfame, common sugar substitutes, on Daphnia magna focusing on biochemical (acetylcholinesterase activity; AChE), physiological (heart rate), and behavioural (swimming) endpoints. We found dose-dependent increases in AChE and inhibitory effects on heart rate and behaviour for both substances. Moreover, acesulfame induced a biphasic response in AChE activity, inhibiting it at lower concentrations and stimulating at higher ones. For all endpoints, the EC50 values were lower for acesulfame than for sucralose. Additionally, the relationship between acetylcholinesterase and heart rate differed depending on the substance, suggesting possible differences in the mode of action between sucralose and acesulfame. All observed EC50 values were at µg/l levels, i.e., within the levels reported for wastewater, with adverse effects observed at as low as 0.1 µg acesulfame /l. Our findings emphasise the need to re-evaluate risk assessment thresholds for artificial sweeteners and provide evidence for the neurotoxic effects of artificial sweeteners in the environment, informing international regulatory standards.

Dietary exposure to low-calorie sweeteners in a sample of Brazilian pregnant women.

The dietary exposure to low-calorie sweeteners (LCS) was estimated in a sample of pregnant Brazilian women. Consumption data were obtained with a 24-h Dietary Recall interview. Because of the uncertainty in assessing foods with LCS, they were classified into three scenarios to ensure inclusion of the 15 LCS allowed for use in Brazil: ranging from a less to a more conservative scenario. The concentration of LCS was estimated using the amount declared on the label or the maximum permitted levels and analytical determination data for table-top sweeteners. The frequency of consumption was higher for acesulfame-K, aspartame, and cyclamate. The food groups contributing the most to the consumption of LCS were non-alcoholic beverages, table-top sweeteners, confectionary and desserts. The level of dietary exposure to LCS was within the safety limit. However, continued efforts to monitor their dietary exposure are necessary given the limitations highlighted in this study.