Neotame

Acute and two-week effects of neotame, stevia rebaudioside M and sucrose-sweetened biscuits on postprandial appetite and endocrine response in adults with overweight/obesity-a randomised crossover trial from the SWEET consortium.[Pubmed:38553262]

EBioMedicine. 2024 Apr;102:105005.

BACKGROUND: Sweeteners and sweetness enhancers (S&SE) are used to replace energy yielding sugars and maintain sweet taste in a wide range of products, but controversy exists about their effects on appetite and endocrine responses in reduced or no added sugar solid foods. The aim of the current study was to evaluate the acute (1 day) and repeated (two-week daily) ingestive effects of 2 S&SE vs. sucrose formulations of biscuit with fruit filling on appetite and endocrine responses in adults with overweight and obesity. METHODS: In a randomised crossover trial, 53 healthy adults (33 female, 20 male) with overweight/obesity in England and France consumed biscuits with fruit filling containing 1) sucrose, or reformulated with either 2) Stevia Rebaudioside M (StRebM) or 3) Neotame daily during three, two-week intervention periods with a two-week washout. The primary outcome was composite appetite score defined as [desire to eat + hunger + (100 - fullness) + prospective consumption]/4. FINDINGS: Each formulation elicited a similar reduction in appetite sensations (3-h postprandial net iAUC). Postprandial insulin (2-h iAUC) was lower after Neotame (95% CI (0.093, 0.166); p < 0.001; d = -0.71) and StRebM (95% CI (0.133, 0.205); p < 0.001; d = -1.01) compared to sucrose, and glucose was lower after StRebM (95% CI (0.023, 0.171); p < 0.05; d = -0.39) but not after Neotame (95% CI (-0.007, 0.145); p = 0.074; d = -0.25) compared to sucrose. There were no differences between S&SE or sucrose formulations on ghrelin, glucagon-like peptide 1 or pancreatic polypeptide iAUCs. No clinically meaningful differences between acute vs. two-weeks of daily consumption were found. INTERPRETATION: In conclusion, biscuits reformulated to replace sugar using StRebM or Neotame showed no differences in appetite or endocrine responses, acutely or after a two-week exposure, but can reduce postprandial insulin and glucose response in adults with overweight or obesity. FUNDING: The present study was funded by the Horizon 2020 program: Sweeteners and sweetness enhancers: Impact on health, obesity, safety and sustainability (acronym: SWEET, grant no: 774293).

Obesogenic potentials of environmental artificial sweeteners with disturbances on both lipid metabolism and neural responses.[Pubmed:38340820]

Sci Total Environ. 2024 Apr 1;919:170755.

Artificial sweeteners (ASs) entered the environments after application and emissions. Recent studies showed that some ASs had obesogenic risks. However, it remained unclear whether such risks are common and how they provoke such effects. Presently, the effects of 8 widely used ASs on lipid accumulation were measured in Caenorhabditis elegans. Potential mechanisms were explored with feeding and locomotion behavior, lipid metabolism and neural regulation. Results showed that acesulfame (ACE), aspartame (ASP), saccharin sodium (SOD), sucralose (SUC) and cyclamate (CYC) stimulated lipid accumulation at mug/L levels, showing obesogenic potentials. Behavior investigation showed that ACE, ASP, SOD, SUC and CYC biased more feeding in the energy intake aspect against the locomotion in the energy consumption one. Neotame (NEO), saccharin (SAC) and alitame (ALT) reduced the lipid accumulation without significant obesogenic potentials in the present study. However, all 8 ASs commonly disturbed enzymes (e.g., acetyl-CoA carboxylase) in lipogenesis and those (e.g., carnitine palmitoyl transferase) in lipolysis. In addition, ASs disturbed PPARgamma (via expressions of nhr-49), TGF-beta/DAF-7 (daf-7) and SREBP (sbp-1) pathways. Moreover, they also interfered neurotransmitters including serotonin (5-HT), dopamine (DA) and acetylcholine (ACh), with influences in Gsalpha (e.g., via expressions of gsalpha-1, ser-7), glutamate (e.g., mgl-1), and cGMP-dependent signaling pathways (e.g., egl-4). In summary, environmental ASs commonly disturbed neural regulation connecting behavior and lipid metabolism, and 5 out of 8 showed clear obesogenic potentials. ENVIRONMENTAL IMPLICATION: Artificial sweeteners (ASs) are become emerging pollutants after wide application and continuous emission. Recent studies showed that some environmental ASs had obesogenic risks. The present study employed Caenorhabditis elegans to explore the influences of 8 commonly used ASs on lipid metabolisms and also the underlying mechanisms. Five out of 8 ASs stimulated lipid accumulation at mug/L levels, and they biased energy intake against energy consumption. The other three ASs reduced the lipid accumulation. ASs commonly disturbed lipogenesis and lipolysis via PPARgamma, TGF-beta and SREBP pathways, and also influenced neurotransmitters with Gsalpha, glutamate and cGMP-dependent signaling pathways.

Enantioselective Recognition of Functional Organic Molecules in Water by Biomimetic Macrocyclic Hosts.[Pubmed:38294833]

J Am Chem Soc. 2024 Feb 14;146(6):3900-3909.

Enantioselective recognition of functional organic molecules in water is routine in nature but remains a formidable challenge for synthetic hosts. Here, we reported two pairs of chiral naphthotubes with chiral centers located in the neighborhood of the inward-directing amide groups. These naphthotubes, with a chiral twisted cavity, show highly enantioselective recognition in water to a wide scope of organic molecules (90 chiral guests). The highest enantioselectivity of 34 was achieved with Neotame. Small differences between all of the noncovalent interactions shielded in the hydrophobic cavity were revealed to be responsible for the enantioselective recognition in water, which is different from the traditional views. Moreover, these hosts can differentiate the analogues of aspartame using fluorescence spectroscopy. These chiral naphthotubes have made unprecedented achievements in enantioselective recognition, providing the basis for their applications in chiral analysis and separations.

Simultaneous analysis of natural and artificial sweeteners in sugar-free drinks and urine samples by column-switching UHPLC-charged aerosol detection method.[Pubmed:38041977]

J Chromatogr A. 2024 Jan 4;1713:464533.

Sweeteners are considered an alternative to high-calorie foods or drinks and have been widely used globally. However, the simultaneous separation and detection of high-polarity natural and artificial sweeteners are challenging owing to their broad-spectrum physical and chemical properties. Herein, we developed a column-switching UHPLCCAD method and used it for detecting and quantitating 12 sweeteners, including natural sweeteners (erythritol, mannitol, xylitol, sorbitol and stevioside) and artificial sweeteners (acesulfame potassium, saccharin sodium salt, sodium cyclamate, sucralose, aspartame, alitame and Neotame). The LOD and LOQ were 0.932-6.25 mug/mL and 3.10-20.83 mug/mL, respectively, and the method demonstrated excellent linearity (R(2) >/= 0.9990), good precision (intraday and interday precision was 0.59-6.88 %), and high recovery (average recoveries were 85.16-108.64 %). This method was applied to determine the sweeteners in 15 sugar-free drinks purchased from the local Chinese supermarkets. What's more, natural sweetener erythritol and artificial sweetener acesulfame potassium were suspected over addition in sugar-free drinks. Meanwhile the method was applied to the sweeteners in various sugar-free drinks and the dynamic monitoring of transit and excretion in vivo after drinking. Those prove that the method can be used to the detection of sugar free drinks and quality control of the sweeteners. The study highlights the potential of UHPLC-charged aerosol detection technology in detection of multiple components in food industry.

Simultaneous determination of nine high-intensity sweeteners in liquid and powder tabletop sweeteners.[Pubmed:37695976]

Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2023 Oct;40(10):1298-1306.

Government regulatory actions and public policies have been recently implemented in Brazil due to the excessive consumption of sugar. Therefore, it becomes relevant to determine the levels of high-intensity sweeteners in tabletop sweeteners consumed by the Brazilian population. Thus, an analytical method was developed and validated for the simultaneous determination of nine sweeteners (acesulfame potassium, aspartame, advantame, sodium cyclamate, Neotame, saccharin, sucralose, stevioside, and rebaudioside A) by using ultra-high performance liquid chromatography coupled to mass spectrometry in tandem. The sample preparation encompassed only dilution steps. The method was validated taking into account the parameters of linearity, precision, accuracy, and matrix effects. The analytes were determined in two different batches of 21 commercial liquid and powder tabletop sweeteners available on the local market, totaling 42 samples. A minimum of one and a maximum of four sweeteners were found in the analyzed products and sweeteners that were not described on the label were not detected. It is expected that the established method can be used in monitoring programs and that the presented results can contribute to exposure assessments performed nationally.

Untreated wastewater impact and environmental risk assessment of artificial sweeteners in river water and sediments of the Danube River Basin in Serbia.[Pubmed:37368207]

Environ Sci Pollut Res Int. 2023 Jul;30(35):84583-84594.

Artificial sweeteners are receiving increasing attention as newly recognized emerging contaminants that mainly reach the aquatic environment through the discharge of municipal wastewater containing large amount of these compounds. In this study, the impact of raw untreated wastewater discharges on the levels and the water/sediment distribution of artificial sweeteners in the Danube River and its largest tributaries in Serbia was evaluated, and a comprehensive assessment of environmental risks for freshwater and benthic organisms was performed. Acesulfame and sucralose were detected in all river water samples (100%), while saccharin (59%) and cyclamate (12%) were less frequently found, indicating long-term continuous sewage-derived pollution. Aspartame (100%) and Neotame (60%) were the only artificial sweeteners recorded in the sediment samples due to their preference to sorb to particulate matter in the water/sediment system. In terms of ecotoxicological risk, a low risk for aquatic organisms was determined at the detected levels of saccharin in river water, while a high to medium risk was found for benthic biota at the concentrations of Neotame and aspartame detected in sediments. The largest contribution to the pollution of the Danube River Basin with artificial sweeteners, and consequently the highest environmental risk, was determined in the two largest cities, the capital Belgrade and Novi Sad, which raises the issue of transboundary pollution.

Determination of neotame in various foods by high-performance liquid chromatography coupled with ultraviolet and mass spectrometric detection.[Pubmed:36898340]

Food Chem. 2023 Aug 1;416:135863.

A new analytical technique involving protein precipitation, heating, lipid degreasing, and SPE procedures combined with HPLC-UV and HPLC-MS/MS has been developed for the determination of Neotame in a variety of food samples. This method is applicable for high-protein, high-lipid, or gum-based solid samples. The limit of detection of the HPLC-UV method was 0.5 mug/mL, while that of the HPLC-MS/MS method was 3.3 ng/mL. The spiked recoveries of Neotame in 73 kinds of foods were in the range of 81.1-107.2 % with UV detection. The spiked recoveries obtained by HPLC-MS/MS in 14 kinds of foods ranged from 81.6 % to 105.8 %. This technique was successfully used to determine the contents of Neotame in two positive samples, indicating its applicability in food analysis.

Occurrence and removal of four artificial sweeteners in wastewater treatment plants of China.[Pubmed:36476784]

Environ Sci Process Impacts. 2023 Jan 25;25(1):75-84.

Artificial sweeteners discharged into aquatic environments have raised concern because of their ubiquitous occurrence and potential biological effect. And some of them, such as sucralose (SUC) and acesulfame (ACE), have been identified as emerging contaminants. Wastewater treatment plants (WWTPs) are considered as important sources and sinks of artificial sweeteners discharged into the environment. In this study, the occurrence and removal of four representative artificial sweeteners in 12 WWTPs located in different provinces of China were investigated. The results showed that artificial sweeteners were detected widely in the investigated WWTPs. The median concentrations of the four target artificial sweeteners were detected in influents at levels of 0.03-3.85 mug L(-1) and decreased in the order of SUC > ACE > aspartame (APM) > Neotame (NTM). Additionally, the per capita mass loads of total artificial sweeteners in the WWTPs could be affected by the location of the WWTPs and were higher in southern cities than in northern cities. It was also found that there was a distinct linear correlation between the per capita mass load of ACE in influents and population density. During the treatment of WWTPs, the overall removal efficiency of artificial sweeteners ranged from -116% to 99.1%. Among the target artificial sweeteners, SUC and ACE might have potential risk to aquatic environments based on the calculation of the risk quotient. Thus, advanced treatment processes were carried to further remove SUC and ACE to reduce their long-term cumulative effect. Overall, UV/H(2)O(2) and UV/PDS showed a better effect than granular activated carbon (GAC) adsorption in the removal of artificial sweeteners. The reaction constants of ACE by UV/H(2)O(2) and UV/PDS were higher than those of SUC, which is related to molar extinction coefficients. Meanwhile, the adsorption ability of GAC adsorption for SUC was better than that of ACE, which is in correlation with the octanol-water partition coefficient. By comparison of removal efficiency, UV/PDS was considered as the most suitable advanced treatment process to remove ACE and SUC.

An updated multifaceted overview of sweet proteins and dipeptides as sugar substitutes; the chemistry, health benefits, gut interactions, and safety.[Pubmed:36461268]

Food Res Int. 2022 Dec;162(Pt A):111853.

Artificial sweeteners have become increasingly popular worldwide owing to their lower calorie content in addition to the claims of health benefits such as weight control, blood glucose level regulation in diabetics, and protection against dental caries. Nevertheless, there is still controversy regarding their safety, especially when administered over the long term, taking into account that most of the safety studies are based on animal models and only a few human studies. This review focuses on low-calorie protein/peptide sweeteners. These include artificial sweeteners, i.e. aspartame, advantame, Neotame, and alitame which are synthetic, versus those of natural origin such as thaumatin, monellin, brazzein, pentadin, mabinlin, curculin, and egg white lysozyme. We conducted a systematic literature survey to ensure the accuracy of the data regarding the chemical properties, synthesis, and industrial applications. The health benefits and safety of these sweeteners in humans are presented for the first time in context to their metabolic profiles and gut interaction.

A comprehensive database of declared high-intensity sweeteners in Brazilian commercial products and updated exposure assessment.[Pubmed:36192918]

Food Res Int. 2022 Nov;161:111899.

Government regulatory actions and public policies to reduce sugar consumption were recently implemented in Brazil. To evaluate their potential impact on the supply of products containing high-intensity sweeteners (HIS) and on dietary exposure to these substances, this study aimed to create a comprehensive database on HIS declared in Brazilian commercial products and estimate their intake through consumption of these products. The occurrence of HIS was evaluated through labeling information of 1869 commercial products available in the Brazilian market, collected between January 2021 and August 2021, and the daily intake was estimated for eight HIS (acesulfame K, advantame, aspartame, cyclamate, steviol glycosides, Neotame, saccharin and sucralose) using a deterministic approach by multiplying the maximum permitted levels of HIS in foods and beverages by the consumption data of these products. The consumption data were obtained from the report of Household Budget Survey (POF/IBGE), conducted from 2017 to 2018 through a 24-hour dietary recall applied to 46,164 individuals aged 10 years and over, which included only average data (i.e. average consumption for the general population or subgroups). The most frequent HIS in the investigated products were sucralose (26.8 %; n = 938) and acesulfame K (21.7 %; n = 759), and although the combination of sweeteners is a common practice in the food industry, there was a predominance of only one substance in the investigated products (46.7 %; n = 873). The estimated intake of HIS for average consumers was below the Acceptable Daily Intake (ADI) and does not suggest a toxicological concern. A similar scenario was observed for high consumers, except for cyclamate and steviol glycosides, which corresponded to 144 % and 131 % of their respective ADIs in the general population. To our knowledge, this is the most comprehensive database on HIS in Brazil and the most recent exposure assessment performed nationally.

Seasonal occurrence, removal and mass loads of artificial sweeteners in the largest water reclamation plant in China.[Pubmed:36181830]

Sci Total Environ. 2023 Jan 15;856(Pt 1):159133.

Artificial sweeteners (ASs) are of growing concern as an emerging contaminant. In the study, the seasonal occurrence, removal and mass load of six ASs in sewage, suspended particulate matter (SPM) and sludge were investigated throughout the treatment process of the largest water reclamation plant in China. The highest ASs concentrations in the influent (13.0 mug/L), effluent (2.22 mug/L), SPM (4.48 mug/g) and sludge (0.15 mug/g) were observed in the dry season, which were 1.24- to 5.0-fold higher than in the normal season and 1.06- to 37.5-fold higher than the flood season. Following treatment, ASs concentrations decreased by 24.3 %, 51.7 % and 5.1 % (on average) in primary, secondary and reclaimed processes, respectively. Among the investigated ASs, acesulfame (93.1 %) and cyclamate (98.4 %) were removed most efficiently, with removal occurring mainly in secondary processes, while sucralose exhibited the lowest removal efficiency (38.7 %). Seasonal characteristics affect the consumption of ASs, which subsequently changes the input and discharge ASs loads of STPs. The maximum mass load of ASs occurred in the dry season, ranging from 0.002 (Neotame) to 1.33 mg/d/person (cyclamate), while the maximum emission load occurred in the flood season, ranging from 0.003 (Neotame) to 0.83 mg/d/person (sucralose). The mass and emission load of ASs in Beijing is significantly lower than in European or the United States, due to Beijing having low per capita consumption of ASs (5.50 mg/d/person). The highest ASs risk in the receiving water occurred in the flood season due to the input of other pollution sources by rainfall runoff. Meanwhile, attention should be paid to the risk of receiving water close to the STP outlet in the dry seasons for the highest ASs concentration in the STP effluent in the season. The present study provides important guidance on controlling the input and reducing the emission of ASs in different seasons.

New strategies for identifying and masking the bitter taste in traditional herbal medicines: The example of Huanglian Jiedu Decoction.[Pubmed:36060004]

Front Pharmacol. 2022 Aug 17;13:843821.

Suppressing the bitter taste of traditional Chinese medicine (TCM) largely has been a major clinical challenge due to complex and diverse metabolites and high dispersion of bitter metabolites in liquid preparations. In this work, we developed a novel strategy for recognizing bitter substances, hiding their bitter taste, and elucidated the mechanism of flavor masking in TCM. Huanglian Jie-Du Decoction (HLJDD) with an intense bitter taste was studied as a typical case. UHPLC-MS/MS was used to analyze the chemical components in HLJDD, whereas the bitter substances were identified by pharmacophores. Additionally, the screening results of the pharmacophores were further validated by using experimental assays. The mask formula of HLJDD was effectively screened under the condition of clear bitter substances. Subsequently, computational chemistry, molecular docking, and infrared characterization (IR) techniques were then used to explicate the mechanism of flavor masking. Consequently, Neotame, gamma-CD, and mPEG(2000)-PLLA(2000) significantly reduced the bitterness of HLJDD. Specifically, mPEG(2000)-PLLA(2000) increased the colloid proportion in the decoction system and minimized the distribution of bitter components in the real solution. Sweetener Neotame suppressed the perception of bitter taste and inhibited bitter taste receptor activation to eventually reduce the bitter taste. The gamma-CD included in the decoction bound the hydrophobic groups of the bitter metabolites in real solution and "packed" all or part of the bitter metabolites into the "cavity". We established a novel approach for screening bitter substances in TCM by integrating virtual screening and experimental assays. Based on this strategy, the bitter taste masking of TCM was performed from three different aspects, namely, changing the drug phase state, component distribution, and interfering with bitter taste signal transduction. Collectively, the methods achieved a significant effect on bitter taste suppression and taste masking. Our findings will provide a novel strategy for masking the taste of TCM liquid preparation/decoction, which will in return help in improving the clinical efficacy of TCM.

Deciphering natural and anthropogenic nitrate and recharge sources in arid region groundwater.[Pubmed:35882321]

Sci Total Environ. 2022 Nov 20;848:157345.

Recently, the subsoils of ephemeral stream (arroyos) floodplains in the northern Chihuahuan Desert were discovered to contain large naturally occurring NO(3)(-) reservoirs (floodplain: ~38,000 kg NO(3)-N/ha; background: ~60 kg NO(3)-N/ha). These reservoirs may be mobilized through land use change or natural stream channel migration which makes differentiating between anthropogenic and natural groundwater NO(3)(-) sources challenging. In this study, the fate and sources of NO(3)(-) were investigated in an area with multiple NO(3)(-) sources such as accidental sewer line releases and sewage lagoons as well as natural reservoirs of subsoil NO(3)(-). To differentiate sources, this study used a large suite of geochemical tools including delta(15)N[NO(3)], delta(18)O[NO(3)], delta(15)N[N(2)], delta(13)C[DIC], (14)C, tritium ((3)H), dissolved gas concentrations, major ion chemistry, and contaminants of emerging concern (CEC) including artificial sweeteners. NO(3)(-) at sites with the highest concentrations (25 to 229 mg/L NO(3)-N) were determined to be largely sourced from naturally occurring subsoil NO(3)(-) based on delta(15)N[NO(3)] (<8 per thousand) and mass ratios of Cl(-)/Br(-) (<100) and NO(3)(-)/Cl(-) (>1.5). Anthropogenic NO(3)(-) was deciphered using mass ratios of Cl(-)/Br(-) (>120) and NO(3)(-)/Cl(-) (<1), delta(15)N[NO(3)] (>8 per thousand), and CEC detections. Nitrogen isotope analyses indicated that denitrification is fairly limited in the field area. CEC were detected at 67 % of sites including (3)H dead sites (<1 pCi/L) with low percent modern carbon-14 (PMC; <30 %). Local supply wells are (3)H dead with low PMC; as (3)H does not re-equilibrate and (14)C is very slow to re-equilibrate during recirculation through infrastructure, sites with low PMC, (3)H < 1 pCi/L, and CEC detections were interpreted as locations with substantial anthropogenic groundwater recharge. Neotame was used to identify locations of very recent (<15 years before present) or ongoing wastewater influxes to the aquifer. This work shows the important influence of naturally occurring subsoil NO(3)(-) reservoirs on groundwater in arid regions and the major contribution of artificial recharge.

The Effect of Artificial Sweeteners Use on Sweet Taste Perception and Weight Loss Efficacy: A Review.[Pubmed:35334918]

Nutrients. 2022 Mar 16;14(6):1261.

Excessive consumption of sugar-rich foods is currently one of the most important factors that has led to the development of the global pandemic of obesity. On the other hand, there is evidence that obesity contributes to reduced sensitivity to sweet taste and hormonal changes affecting appetite, leading to an increased craving for sweets. A high intake of sugars increases the caloric value of the diet and, consequently, leads to weight gain. Moreover, attention is drawn to the concept of the addictive properties of sugar and sugary foods. A potential method to reduce the energy value of diet while maintaining the sweet taste is using non-nutritive sweeteners (NNS). NNS are commonly used as table sugar substitutes. This wide group of chemical compounds features high sweetness almost without calories due to its high sweetening strength. NNS include aspartame, acesulfame-K, sucralose, saccharin, cyclamate, neohesperidin dihydrochalcone (neohesperidin DC), Neotame, taumatin, and advantame. The available evidence suggests that replacing sugar with NNS may support weight control. However, the effect of NNS on the regulation of appetite and sweet taste perception is not clear. Therefore, the review aimed to summarize the current knowledge about the use of NNS as a potential strategy for weight loss and their impact on sweet taste perception. Most studies have demonstrated that consumption of NNS-sweetened foods does not increase sweetness preference orenergy intake. Nonetheless, further research is required to determine the long-term effects of NNS on weight management.

Descriptive Sensory Profile and Consumer Study Impact of Different Nutritive and Non-Nutritive Sweeteners on the Descriptive, Temporal Profile, and Consumer Acceptance in a Peach Juice Matrix.[Pubmed:35053976]

Foods. 2022 Jan 17;11(2):244.

The study evaluated the effect of peach juice sweetened with sucrose, widely used non-nutritive sweeteners, the artificial sucralose, Neotame blend, and the natural stevia extract with different rebaudioside A concentrations on the temporal and quantitative descriptive profile, and consumer acceptance of the beverage. The sensory profiling was determined by quantitative descriptive and time-intensity analyses. The results showed that the sweeteners Neotame and sucralose present higher sweetening power, and the different rebaudioside A concentrations did not affect the sweetening power of the stevia extract. The samples sweetened with stevia with 40% and 95% of rebaudioside A were characterized by the sensory attributes bitter taste, bitter aftertaste, astringency, and black tea flavor, with a negative influence on the consumers' acceptance. The different concentrations of rebaudioside A in stevia interfered substantially in the descriptors bitter taste and bitter aftertaste, showing that the higher the percentage of rebaudioside A, the lower bitterness of peach juice.