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Background: Artificial sweeteners (AS) have been widely utilized in the food, beverage, and pharmaceutical industries for decades. While numerous publications have suggested a potential link between AS and diseases, particularly cancer, controversy still surrounds this issue. This study aims to investigate the association between AS consumption and cancer risk. Methods: Targets associated with commonly used AS were screened and validated using databases such as CTD, STITCH, Super-PRED, Swiss Target Prediction, SEA, PharmMapper, and GalaxySagittarius. Cancer-related targets were sourced from GeneCards, OMIM, and TTD databases. AS-cancer targets were identified through the intersection of these datasets. A network visualization ('AS-targets-cancer') was constructed using Cytoscape 3.9.0. Protein–protein interaction analysis was conducted using the STRING database to identify significant AS-cancer targets. GO and KEGG enrichment analyses were performed using the DAVID database. Core targets were identified from significant targets and genes involved in the 'Pathways in cancer' (map05200). Molecular docking and dynamics simulations were employed to verify interactions between AS and target proteins. Pan-cancer and univariate Cox regression analyses of core targets across 33 cancer types were conducted using GEPIA 2 and SangerBox, respectively. Gene chip datasets (GSE53757 for KIRC, GSE21354 for LGG, GSE42568 for BRCA, and GSE46602 for PRAD) were retrieved from the GEO database, while transcriptome and overall survival data were obtained from TCGA. Data normalization and identification of differentially expressed genes (DEGs) were performed on these datasets using R (version 4.3.2). Gene Set Enrichment Analysis (GSEA) was employed to identify critical pathways in the gene expression profiles between normal and cancer groups. A cancer risk prognostic model was constructed for key targets to further elucidate their significance in cancer initiation and progression. Finally, the HPA database was utilized to investigate variations in the expression of key AS-cancer target proteins across KIRC, LGG, BRCA, PRAD, and normal tissues. Results: Seven commonly used AS (Aspartame, Acesulfame, Sucralose, NHDC, Cyclamate, Neotame, and Saccharin) were selected for study. A total of 368 AS-cancer intersection targets were identified, with 48 notable AS-cancer targets, including TP53, EGFR, SRC, PIK3R1, and EP300, retrieved. GO biological process analysis indicated that these targets are involved in the regulation of apoptosis, gene expression, and cell proliferation. Thirty-five core targets were identified from the intersection of the 48 significant AS-cancer targets and genes in the 'Pathways in cancer' (map05200). KEGG enrichment analysis of these core targets revealed associations with several cancer types and the PI3K-Akt signaling pathway. Molecular docking and dynamics simulations confirmed interactions between AS and these core targets. HSP90AA1 was found to be highly expressed across the 33 cancer types, while EGF showed the opposite trend. Univariate Cox regression analysis demonstrated strong associations of core targets with KIRC, LGG, BRCA, and PRAD. DEGs of AS-cancer core targets across these four cancers were analyzed. GSEA revealed upregulated and downregulated pathways enriched in KIRC, LGG, BRCA, and PRAD. Cancer risk prognostic models were constructed to elucidate the significant roles of key targets in cancer initiation and progression. Finally, the HPA database confirmed the crucial function of these targets in KIRC, LGG, BRCA, and PRAD. Conclusion: This study integrated data mining, machine learning, network toxicology, molecular docking, molecular dynamics simulations, and clinical sample analysis to demonstrate that AS increases the risk of kidney cancer, low-grade glioma, breast cancer, and prostate cancer through multiple targets and signaling pathways. This paper provides a valuable reference for the safety assessment and cancer risk evaluation of food additives. It urges food safety regulatory agencies to strengthen oversight and encourages the public to reduce consumption of foods and beverages containing artificial sweeteners and other additives. [ABSTRACT FROM AUTHOR]

We examined the association between low‐calorie sweeteners (LCS) consumption during preconception, pregnancy, and breastfeeding and child health outcomes. A systematic search of electronic databases in PubMed, Embase, Cumulated Index to Nursing and Allied Health Literature, the Cochrane Library, Scopus, Web of Science, PsycINFO, ProQuest Health and Medical, ClinicalTrials.gov, and Google Scholar was conducted up to 21 September 2023. A random effects model with restricted maximum likelihood estimation was used for the meta‐analysis. Seventeen eligible studies were included. The standardised mean difference (SMD) and 95% confidence interval (CI) in birth weight between those who frequently consumed LCS (≥1 serve/day) during pregnancy and those who did not consume LCS was 0.04 (0.00, 0.08) (four cohort studies). Any LCS consumption during pregnancy compared with no consumption was not associated with birth weight [SMD (95% CI) = 0.03 (−0.03, 0.08)] (four cohort studies). Any LCS consumption during pregnancy was not associated with body mass index z‐scores. The weighted mean difference (95% CI) was 0.00 (−0.05, 0.06) at birth, 0.06 (−0.29, 0.40) at 6 months, −0.04 (−0.19, 0.10) at 1 year, 0.00 (−0.16, 0.17) at 3 years, and 0.10 (−0.15, 0.34) at 7 years of the child age, compared with no intake (five cohort studies). The odds of being overweight at 1 year among children exposed to LCS during pregnancy was 1.19 (OR [95% CI]: 1.19 [0.81, 1.58]) compared with unexposed children (two cohort studies). The effect sizes were not precise for all the outcomes as the 95% CI indicated the effect estimates could range from small protective to a higher risk. The effect of LCS consumption on child behaviour and cognition was inconsistent. There is not enough evidence to confirm LCS consumption during pregnancy affects birth weight and risk of overweight in children. However, frequent consumption increased birth weight and the risk of overweight at different ages, though the effects were imprecise. More robust research evidence is required as the quality of evidence is low. Key messages: Evidence regarding the effect of perinatal low‐calorie sweeteners (LCS) consumption and child health is limited and inconclusive.Our systematic review and meta‐analysis showed that any LCS consumption during pregnancy was not associated with birth weight and the risk of overweight in childhood. However, frequent LCS consumption during pregnancy was associated with a small but imprecise increase in birth weight and body mass index z‐score at different ages.Evidence regarding the effect of maternal LCS consumption on child behaviour, cognition, and the risk of other chronic disease is limited.The overall quality of the evidence remains low, warranting further high‐quality research. [ABSTRACT FROM AUTHOR]

Previous observational studies have investigated the association between coffee consumption and single cardiometabolic disease. Yet, the extent to which coffee might confer health advantages to individuals with a singular cardiometabolic disease remains unclear. This study aimed to further investigate the association of coffee consumption and the onset and progression from single cardiometabolic disease to cardiometabolic multimorbidity (CMM). This prospective cohort study included 185,112 participants from the UK Biobank who were enrolled between 2006 and 2010 and followed up until 2020. Coffee consumption was collected using a 24-h dietary questionnaire. CMM was defined as the coexistence of at least two cardiometabolic diseases, including type 2 diabetes (T2D), coronary heart disease (CHD) and stroke. Cox proportional hazards and multi-state models estimated the associations between coffee consumption and CMM. During a median follow-up of 11.4 years, 1585 participants developed CMM. Compared with nonconsumers, coffee consumers had lower risks for the transitions from baseline to single cardiometabolic disease, with the respective lowest hazard ratios and 95% confidence intervals (CIs) for the transitions from baseline to T2D, CHD and stroke after multivariable adjustment being 0.79 (CI, 0.72–0.87), 0.91 (CI, 0.86–0.97) and 0.87 (CI, 0.78–0.96). Coffee consumption resulted in a significant reduction in the risk of the transitions from CHD and stroke to CMM, with the lowest estimates were 0.56 (CI, 0.43–0.73) and 0.60 (CI, 0.43–0.83). Similar associations were observed in unsweetened coffee. Sugar-sweetened coffee was associated with some transitions at low levels of consumption. The associations between artificially sweetened coffee and CMM were less consistent. Coffee consumption was associated with lower risk for almost all transition phases of CMM development and consistent findings were observed with unsweetened coffee. [Display omitted] • Coffee consumption was associated with the lower risk of CMM. • Unsweetened coffee is an optimal choice for reducing the risk of CMM. • People should limit the consumption of sugar and artificial sweetened coffee. [ABSTRACT FROM AUTHOR]

Objective: There is concern about the potential health implications of low-calorie sweetener (LCS) consumption. This study aimed to determine the prevalence and patterns of LCS use among women of reproductive age (WRA) in Australia. Methods: This cross-sectional study involved a two-stage analysis. First, latent class analyses (LCA) were employed to identify patterns of LCS use. Subsequently, regression analyses were conducted to assess the association between sociodemographic and lifestyle characteristics and the two outcomes: (1) self-reported LCS use, and (2) the identified LCS consumption patterns/classes. Results: A total of 405 WRA completed the survey (mean age 32.0 ± 8.6 years, mean BMI 28.71 ± 11.1 kg/m2), with 44.7% reporting LCS consumption. LCA analysis identified three distinct LCS consumption patterns: light users (45.9%), moderate users (26.0%) and heavy users (28.6%). A high proportion of participants did not meet the Australian dietary guidelines for recommended servings of vegetables (57.8%), dairy (44.2%), meat (48.2%) and grains (74.8%). Compared to Caucasian women, those from South Asian backgrounds (OR 4.16; 95% CI 1.71–10.1) and Aboriginal and Torres Strait Islander women (OR 1.40; 95% CI 0.42–4.63) were more likely to use LCS. Women who participated in the weight loss programs, with overweight/obesity, and those using LCS for weight loss purposes were more likely to be moderate or heavy LCS users than light users. Additionally, socioeconomically disadvantaged women were less likely to be moderate or heavy LCS users. Conclusions: This study highlights the widespread use of LCS among WRA in Australia, with distinct consumption patterns influenced by cultural, health-related, and socioeconomic factors. These findings underscore the need for targeted interventions to promote healthy eating practices within this population. [ABSTRACT FROM AUTHOR]

According to old theories of sweetness, the perception of sweet substances is closely linked to the arrangement of atoms within them. To assess the validity of these theories, we conducted an analysis of the structure of the artificial sweetener dulcin for the first time, utilizing microwave spectroscopy and a laser ablation source. These techniques have enabled the identification of two conformers, which are stabilized by an intramolecular hydrogen bond between the amino group and the phenyl ring. The observed conformations were examined in light of the Shallenberger‐Acree‐Kier molecular theory of sweet taste, and they align with the hypothesized criteria. Furthermore, the study illustrates how conformational relaxation can alter the equilibrium conformational distribution, resulting in the absence of certain conformers in the conformational landscape. [ABSTRACT FROM AUTHOR]

Abstract Background Artificial sweeteners (AS) have been widely utilized in the food, beverage, and pharmaceutical industries for decades. While numerous publications have suggested a potential link between AS and diseases, particularly cancer, controversy still surrounds this issue. This study aims to investigate the association between AS consumption and cancer risk. Methods Targets associated with commonly used AS were screened and validated using databases such as CTD, STITCH, Super-PRED, Swiss Target Prediction, SEA, PharmMapper, and GalaxySagittarius. Cancer-related targets were sourced from GeneCards, OMIM, and TTD databases. AS-cancer targets were identified through the intersection of these datasets. A network visualization (‘AS-targets-cancer’) was constructed using Cytoscape 3.9.0. Protein–protein interaction analysis was conducted using the STRING database to identify significant AS-cancer targets. GO and KEGG enrichment analyses were performed using the DAVID database. Core targets were identified from significant targets and genes involved in the ‘Pathways in cancer’ (map05200). Molecular docking and dynamics simulations were employed to verify interactions between AS and target proteins. Pan-cancer and univariate Cox regression analyses of core targets across 33 cancer types were conducted using GEPIA 2 and SangerBox, respectively. Gene chip datasets (GSE53757 for KIRC, GSE21354 for LGG, GSE42568 for BRCA, and GSE46602 for PRAD) were retrieved from the GEO database, while transcriptome and overall survival data were obtained from TCGA. Data normalization and identification of differentially expressed genes (DEGs) were performed on these datasets using R (version 4.3.2). Gene Set Enrichment Analysis (GSEA) was employed to identify critical pathways in the gene expression profiles between normal and cancer groups. A cancer risk prognostic model was constructed for key targets to further elucidate their significance in cancer initiation and progression. Finally, the HPA database was utilized to investigate variations in the expression of key AS-cancer target proteins across KIRC, LGG, BRCA, PRAD, and normal tissues. Results Seven commonly used AS (Aspartame, Acesulfame, Sucralose, NHDC, Cyclamate, Neotame, and Saccharin) were selected for study. A total of 368 AS-cancer intersection targets were identified, with 48 notable AS-cancer targets, including TP53, EGFR, SRC, PIK3R1, and EP300, retrieved. GO biological process analysis indicated that these targets are involved in the regulation of apoptosis, gene expression, and cell proliferation. Thirty-five core targets were identified from the intersection of the 48 significant AS-cancer targets and genes in the 'Pathways in cancer' (map05200). KEGG enrichment analysis of these core targets revealed associations with several cancer types and the PI3K-Akt signaling pathway. Molecular docking and dynamics simulations confirmed interactions between AS and these core targets. HSP90AA1 was found to be highly expressed across the 33 cancer types, while EGF showed the opposite trend. Univariate Cox regression analysis demonstrated strong associations of core targets with KIRC, LGG, BRCA, and PRAD. DEGs of AS-cancer core targets across these four cancers were analyzed. GSEA revealed upregulated and downregulated pathways enriched in KIRC, LGG, BRCA, and PRAD. Cancer risk prognostic models were constructed to elucidate the significant roles of key targets in cancer initiation and progression. Finally, the HPA database confirmed the crucial function of these targets in KIRC, LGG, BRCA, and PRAD. Conclusion This study integrated data mining, machine learning, network toxicology, molecular docking, molecular dynamics simulations, and clinical sample analysis to demonstrate that AS increases the risk of kidney cancer, low-grade glioma, breast cancer, and prostate cancer through multiple targets and signaling pathways. This paper provides a valuable reference for the safety assessment and cancer risk evaluation of food additives. It urges food safety regulatory agencies to strengthen oversight and encourages the public to reduce consumption of foods and beverages containing artificial sweeteners and other additives.

Artificial sweeteners are generally used and recommended to alternate added sugar for health promotion. However, the health effects of artificial sweeteners remain unclear. In this study, we included 6371 participants from the National Health and Nutrition Examination Survey with artificial sweetener intake records. Logistic regression and Cox regression were applied to explore the associations between artificial sweeteners and risks of cardiometabolic disorders and mortality. Mendelian randomisation was performed to verify the causal associations. We observed that participants with higher consumption of artificial sweeteners were more likely to be female and older and have above medium socio-economic status. After multivariable adjustment, frequent consumers presented the OR (95 % CI) for hypertension (1·52 (1·29, 1·80)), hypercholesterolaemia (1·28 (1·10, 1·50)), diabetes (3·74 (3·06, 4·57)), obesity (1·52 (1·29, 1·80)), congestive heart failure (1·89 (1·35, 2·62)) and heart attack (1·51 (1·10, 2·04)). Mendelian randomisation confirmed the increased risks of hypertension and type 2 diabetes. Moreover, an increased risk of diabetic mortality was identified in participants who had artificial sweeteners ≥ 1 daily (HR = 2·62 (1·46, 4·69), P = 0·001). Higher consumption of artificial sweeteners is associated with increased risks of cardiometabolic disorders and diabetic mortality. These results suggest that using artificial sweeteners as sugar substitutes may not be beneficial. [ABSTRACT FROM AUTHOR]

Background: This study investigates the associations between coffee consumption and metabolic syndrome and its components, as well as the effect of milk, sugar, and artificial sweeteners on these associations. Methods: A cross‐sectional analysis was conducted with 351805 UK Biobank participants. Coffee consumption data were collected via food frequency questionnaires and 24‐h recall. Metabolic syndrome was identified through blood biochemistry and self‐reported medication use. Odds ratios were calculated using multivariable logistic regression, and results were verified with two‐sample Mendelian randomization. Results: Consuming up to two cups of coffee per day was inversely associated with metabolic syndrome (1 cup/day: odds ratio [OR]: 0.88, 95% confidence interval [CI]: 0.85–0.92; 2 cups/day: OR: 0.90, 95% CI: 0.86–0.93). Higher intakes showed near‐null associations. Mendelian randomization did not support a causal link between coffee intake and metabolic syndrome. Both self‐reported and genetically predicted high coffee consumption (four cups per day or more) were associated with central obesity. The inverse association between coffee consumption and metabolic syndrome was more profound among drinkers of ground coffee than those of instant coffee. Results were similar when stratified by the use of milk and sugar, yet the use of artificial sweetener with coffee was positively associated with metabolic syndrome and all component conditions. Conclusions: Coffee consumption may increase the risk of central obesity but is unlikely to impact the risk of metabolic syndrome. The potential health effects of artificial sweeteners in coffee need further investigation. [ABSTRACT FROM AUTHOR]

The relationship between the intake of artificial sweetener (AS) and adverse pregnancy outcomes is under-researched, and existing studies yield inconsistent conclusions. A Mendelian randomization (MR) approach was employed to investigate the causal relationship between the intake of AS and adverse pregnancy outcomes. Instrumental variables related to the exposure phenotype were selected for analysis. The analysis was conducted using genome-wide association study summary data from public datasets. The inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted mode methods were used to evaluate the causal relationship between exposure and outcomes. Sensitivity analysis and multivariable Mendelian randomization enrolling body mass index, type 2 diabetes mellitus, and fasting glucose were employed to further validate the consistency and robustness of the results. In univariable MR, the intake of AS added to tea was associated with an increased risk of ectopic pregnancy [OR = 1.821 (1.118–2.967), p = 0.016]. In multivariable MR adjusting for body mass index and type 2 diabetes mellitus, the intake of AS added to cereal was linked to a reduced risk of ectopic pregnancy [OR = 0.361 (0.145–0.895), p = 0.028] and premature rupture of membranes [OR = 0.116 (0.019–0.704), p = 0.019], while the intake of artificial sweetener added to coffee was associated with an increased risk of placenta previa [OR = 1.617 (1.042–2.510), p = 0.032]. No causal relationship was identified between the intake of artificial sweetener and other adverse pregnancy outcomes. The consumption of artificial sweetener during pregnancy warrants careful consideration. [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]

Introduction: Country-specific evidence-based research is crucial for understanding the role of nonnutritive sweeteners (NNS) in managing type 2 diabetes (T2D). The main aim of this study was to explore the effect of replacing sucrose with sucralose in coffee/tea in Asian Indians with type 2 diabetes (T2D). Methods: This 12-week, parallel-arm randomized controlled trial included 210 participants with T2D, assigned to the intervention group, where sugar/sucrose in coffee or tea was substituted with sucralose, or the control group, where sugar/sucrose was continued. Lifestyle factors remained unchanged. The primary outcome was change in HbA1c. Secondary outcomes were changes in body weight (BW), body mass index (BMI), waist circumference (WC), lipid profiles, and inflammatory markers. Results: At the end of 12 weeks, no change was observed in HbA1c, fasting plasma glucose, lipid profile, and inflammatory markers between or within groups. There was a small but significant reduction in BW (− 0.5 kg [95% CI − 1.0, − 0.1]; p = 0.02), BMI (− 0.2 kg/m2 [− 0.4, 0.0]; p = 0.03), and WC (− 0.8 cm [− 1.4, − 0.3]; p = 0.002) in the intervention group. Improvements were also observed in lipid accumulation product (p = 0.01), visceral adiposity index (p = 0.04), triglyceride/glucose index (p = 0.04), total energy intake (p = 0.04), and carbohydrate intake (p < 0.0001). Conclusions: In Asian Indians with T2D, replacing about 60 kcal of added sucrose with sucralose in coffee/ tea had no benefit on glycemia but resulted in a small reduction in body weight, body mass index, and waist circumference. Trial Registration: Clinical Trials Registry of India (CTRI/2021/04/032686). [ABSTRACT FROM AUTHOR]

Abstract We examined the association between low‐calorie sweeteners (LCS) consumption during preconception, pregnancy, and breastfeeding and child health outcomes. A systematic search of electronic databases in PubMed, Embase, Cumulated Index to Nursing and Allied Health Literature, the Cochrane Library, Scopus, Web of Science, PsycINFO, ProQuest Health and Medical, ClinicalTrials.gov, and Google Scholar was conducted up to 21 September 2023. A random effects model with restricted maximum likelihood estimation was used for the meta‐analysis. Seventeen eligible studies were included. The standardised mean difference (SMD) and 95% confidence interval (CI) in birth weight between those who frequently consumed LCS (≥1 serve/day) during pregnancy and those who did not consume LCS was 0.04 (0.00, 0.08) (four cohort studies). Any LCS consumption during pregnancy compared with no consumption was not associated with birth weight [SMD (95% CI) = 0.03 (−0.03, 0.08)] (four cohort studies). Any LCS consumption during pregnancy was not associated with body mass index z‐scores. The weighted mean difference (95% CI) was 0.00 (−0.05, 0.06) at birth, 0.06 (−0.29, 0.40) at 6 months, −0.04 (−0.19, 0.10) at 1 year, 0.00 (−0.16, 0.17) at 3 years, and 0.10 (−0.15, 0.34) at 7 years of the child age, compared with no intake (five cohort studies). The odds of being overweight at 1 year among children exposed to LCS during pregnancy was 1.19 (OR [95% CI]: 1.19 [0.81, 1.58]) compared with unexposed children (two cohort studies). The effect sizes were not precise for all the outcomes as the 95% CI indicated the effect estimates could range from small protective to a higher risk. The effect of LCS consumption on child behaviour and cognition was inconsistent. There is not enough evidence to confirm LCS consumption during pregnancy affects birth weight and risk of overweight in children. However, frequent consumption increased birth weight and the risk of overweight at different ages, though the effects were imprecise. More robust research evidence is required as the quality of evidence is low.

Abstract According to old theories of sweetness, the perception of sweet substances is closely linked to the arrangement of atoms within them. To assess the validity of these theories, we conducted an analysis of the structure of the artificial sweetener dulcin for the first time, utilizing microwave spectroscopy and a laser ablation source. These techniques have enabled the identification of two conformers, which are stabilized by an intramolecular hydrogen bond between the amino group and the phenyl ring. The observed conformations were examined in light of the Shallenberger‐Acree‐Kier molecular theory of sweet taste, and they align with the hypothesized criteria. Furthermore, the study illustrates how conformational relaxation can alter the equilibrium conformational distribution, resulting in the absence of certain conformers in the conformational landscape.

Background and Aims The pathways and metabolites that contribute to residual cardiovascular disease risks are unclear. Low-calorie sweeteners are widely used sugar substitutes in processed foods with presumed health benefits. Many low-calorie sweeteners are sugar alcohols that also are produced endogenously, albeit at levels over 1000-fold lower than observed following consumption as a sugar substitute. Methods Untargeted metabolomics studies were performed on overnight fasting plasma samples in a discovery cohort (n = 1157) of sequential stable subjects undergoing elective diagnostic cardiac evaluations; subsequent stable isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses were performed on an independent, non-overlapping validation cohort (n = 2149). Complementary isolated human platelet, platelet-rich plasma, whole blood, and animal model studies examined the effect of xylitol on platelet responsiveness and thrombus formation in vivo. Finally, an intervention study was performed to assess the effects of xylitol consumption on platelet function in healthy volunteers (n = 10). Results In initial untargeted metabolomics studies (discovery cohort), circulating levels of a polyol tentatively assigned as xylitol were associated with incident (3-year) major adverse cardiovascular event (MACE) risk. Subsequent stable isotope dilution LC-MS/MS analyses (validation cohort) specific for xylitol (and not its structural isomers) confirmed its association with incident MACE risk [third vs. first tertile adjusted hazard ratio (95% confidence interval), 1.57 (1.12–2.21), P <.01]. Complementary mechanistic studies showed xylitol-enhanced multiple indices of platelet reactivity and in vivo thrombosis formation at levels observed in fasting plasma. In interventional studies, consumption of a xylitol-sweetened drink markedly raised plasma levels and enhanced multiple functional measures of platelet responsiveness in all subjects. Conclusions Xylitol is associated with incident MACE risk. Moreover, xylitol both enhanced platelet reactivity and thrombosis potential in vivo. Further studies examining the cardiovascular safety of xylitol are warranted. [ABSTRACT FROM AUTHOR]

Alternative sugars are often used as sugar substitutes because of their low calories and glycemic index. Recently, consumption of these sweeteners in diet foods and beverages has increased dramatically, raising concerns about their health effects. This review examines the types and characteristics of artificial sweeteners and rare sugars and analyzes their impact on the gut microbiome. In the section on artificial sweeteners, we have described the chemical structures of different sweeteners, their digestion and absorption processes, and their effects on the gut microbiota. We have also discussed the biochemical properties and production methods of rare sugars and their positive and negative effects on gut microbial communities. Finally, we have described how artificial sweeteners and rare sugars alter the gut microbiome and how these changes affect the gut environment. Our observations aim to improve our understanding regarding the potential health implications of the consumption of artificial sweeteners and low-calorie sugars. [ABSTRACT FROM AUTHOR]

Abstract Background This study investigates the associations between coffee consumption and metabolic syndrome and its components, as well as the effect of milk, sugar, and artificial sweeteners on these associations. Methods A cross‐sectional analysis was conducted with 351805 UK Biobank participants. Coffee consumption data were collected via food frequency questionnaires and 24‐h recall. Metabolic syndrome was identified through blood biochemistry and self‐reported medication use. Odds ratios were calculated using multivariable logistic regression, and results were verified with two‐sample Mendelian randomization. Results Consuming up to two cups of coffee per day was inversely associated with metabolic syndrome (1 cup/day: odds ratio [OR]: 0.88, 95% confidence interval [CI]: 0.85–0.92; 2 cups/day: OR: 0.90, 95% CI: 0.86–0.93). Higher intakes showed near‐null associations. Mendelian randomization did not support a causal link between coffee intake and metabolic syndrome. Both self‐reported and genetically predicted high coffee consumption (four cups per day or more) were associated with central obesity. The inverse association between coffee consumption and metabolic syndrome was more profound among drinkers of ground coffee than those of instant coffee. Results were similar when stratified by the use of milk and sugar, yet the use of artificial sweetener with coffee was positively associated with metabolic syndrome and all component conditions. Conclusions Coffee consumption may increase the risk of central obesity but is unlikely to impact the risk of metabolic syndrome. The potential health effects of artificial sweeteners in coffee need further investigation.

BackgroundInsufficient data exist to conclude whether consumption of artificially sweetened beverages is associated with a higher risk of urinary tract cancers.ObjectiveWe sought to investigate whether urinary tract cancer incidence differed among women who consumed various amounts of artificially sweetened beverages.Design setting and participantsThis was a secondary analysis of data from the Women's Health Initiative Observational Study, a multicenter longitudinal prospective study of the health of 93 676 postmenopausal women with a mean follow-up time of 13.5 yr. Women were identified at 40 clinical centers across the USA and enrolled from 1993 to 1998. Women between the ages of 50 and 79 yr were enrolled. We included women who answered questions about artificially sweetened beverage consumption and reported no prior urinary tract cancer diagnoses. The frequency of artificially sweetened beverage consumption was categorized as follows: rare artificially sweetened beverage consumption (never to fewer than one serving per week), frequent consumption (one to six servings per week), and daily consumption (more than one servings per day).Outcome measurements and statistical analysisThe incidence of urinary tract cancer reported during subsequent visits until February 28, 2020 was recorded. Demographic characteristics were compared between those with varying levels of artificially sweetened beverage consumption. Descriptive statistics were used to report the rates of urinary tract cancer diagnosis, and Cox regression models were constructed to determine hazard ratios and adjust for potential confounders.Results and limitationsWe identified 80 388 participants who met the inclusion criteria. Most participants (64%) were infrequent consumers of artificially sweetened beverages, with 13% (n = 10 494) consuming more than one servings per day. The incidence of urinary tract cancers was low, with only 804 cases identified. Cox regression models showed that frequent artificially sweetened beverage consumption was associated with a higher risk of kidney cancer (adjusted hazard ratio 1.34, 95% confidence interval 1.03-1.75). There was no significant association between artificially sweetened beverage intake and bladder cancer.ConclusionsFrequent consumption of artificially sweetened beverages may be associated with a higher risk of kidney cancer among postmenopausal women.Patient summaryA secondary analysis of the Women's Health Initiative Observational Study showed that higher consumption of artificially sweetened beverages was associated with a higher risk of kidney cancer.

Introduction Stevia rebaudiana, an indigenous plant of South America, is becoming increasingly popular because of its potent sweetness obtained from steviol glycosides, which are considerably sweeter than sucrose. Due to its low calorie content and this characteristic, Stevia is considered a favoured sugar alternative in a wide range of food products. In addition to being a substitute for sugar, Stevia provides a range of metabolic benefits. Studies have shown that extracts from this plant have antihypertensive and antihyperlipidemic qualities, can control blood glucose and insulin levels, enhance kidney function, and may have potential anticancer effects. The wide range of advantageous characteristics linked to Stevia highlights its promise as a subject for further exploration of its health-promoting effects. This article offers an analysis of scientific research and reliable sources, presenting the metabolic advantages and health impacts of steviol glycosides obtained from Stevia in the human body. Aim of the study This review aims to identify the metabolic benefits of Stevia rebaudiana on the human body. The main objective is to present its action as a component in the fight against obesity, diabetes, hypertension, dyslipidaemia and cancer cells. Material and method This article presents the current state of knowledge about the range of metabolic benefits of Stevia rebaudiana. Publications describing the effects of Stevia rebaudiana use on the metabolism and health of the human body were reviewed using the PubMed platform. The search included the keywords 'stevia', 'artificial sweetener', 'sugar substitute', 'obesity'.

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.

Recently, the World Health Organization recommended avoiding low-calorie sweeteners (LCS) during pregnancy due to concerns that it may be linked to adverse pregnancy outcomes and offspring wellbeing. This study examined the patterns and predictors of LCS consumption among pregnant women in Australia. A survey was conducted among 422 pregnant women aged 18–50 years. Sociodemographic, lifestyle, dietary intake including LCS consumption, pregnancy-related characteristics, and awareness about the health effects of LCS were assessed. We used latent class analysis and multinomial logistic regression to identify LCS consumption patterns and predictors of consumption patterns, respectively. The mean (SD) age of the women was 30 (4.6) years. Three LCS consumption patterns were identified: infrequent or non-consumers representing 50% of the women, moderate consumers encompassing 40% of the women, and the remaining were habitual consumers. Over two-thirds (71%) of women were not aware of the potential adverse effects of LCS, and only a quarter of them were concerned about the possible adverse effects on their health and their offspring. Increasing age and living with a medical condition decreased the likelihood of moderate consumption by 7% and 55%, respectively. Frequent sugar-sweetened beverage consumption and gestational diabetes predicted habitual LCS consumption. This research suggested widespread LCS consumption among pregnant women in Australia, but lower awareness of its potential adverse health effects. Interventions to increase awareness of potential adverse effects are warranted. [ABSTRACT FROM AUTHOR]

Low-calorie sweeteners (LCS) are commonly consumed by children with type 1 diabetes (T1D), yet their role in cardiometabolic health is unclear. This study examined the feasibility, acceptability, and preliminary effects of 12 weeks of LCS restriction among children with T1D. Children (n = 31) with T1D completed a two-week run-in (n = 28) and were randomly assigned to avoid LCS (LCS restriction, n = 15) or continue their usual LCS intake (n = 13). Feasibility was assessed using recruitment, retention, and adherence rates percentages. Acceptability was assessed through parents completing a qualitative interview (subset, n = 15) and a satisfaction survey at follow-up. Preliminary outcomes were between-group differences in change in average daily time-in-range (TIR) over 12 weeks (primary), and other measures of glycemic variability, lipids, inflammatory biomarkers, visceral adiposity, and dietary intake (secondary). Linear regression, unadjusted and adjusted for age, sex, race, and change in BMI, was used to compare mean changes in all outcomes between groups. LCS restriction was feasible and acceptable. No between-group differences in change in TIR or other measures of glycemic variability were observed. However, significant decreases in TNF-alpha (−0.23 ± 0.08 pg/mL) and improvements in cholesterol (−0.31 ± 0.18 mmol/L) and LDL (−0.60 ± 0.39 mmol/L) were observed with usual LCS intake, compared with LCS restriction. Those randomized to LCS restriction did not report increases in total or added sugar intake, and lower energy intake was reported in both groups (−190.8 ± 106.40 kcal LCS restriction, −245.3 ± 112.90 kcal usual LCS intake group). Decreases in percent energy from carbohydrates (−8.5 ± 2.61) and increases in percent energy from protein (3.2 ± 1.16) and fat (5.2 ± 2.02) were reported with usual LCS intake compared with LCS restriction. Twelve weeks of LCS restriction did not compromise glycemic variability or cardiometabolic outcomes in this small sample of youth with T1D. Further examination of LCS restriction among children with T1D is warranted. [ABSTRACT FROM AUTHOR]

Objective This study aimed to investigate human fetal exposure to non-nutritive sweeteners (NNS) by analyzing amniotic fluid and umbilical cord blood. Study Design Concentrations of four NNS (acesulfame-potassium [ace-K], saccharin, steviol glucuronide, and sucralose) were measured in amniotic fluid (n = 13) and cord blood samples (n = 15) using liquid chromatography-mass spectrometry. Amniotic fluid samples were obtained for research purposes at the time of term elective cesarean birth or clinically indicated third trimester amnioreduction at Mercy Hospital for Women (Melbourne, Australia). All except four women were in the fasting state. Cord blood samples were obtained from an independent cohort of newborns whose mothers were enrolled in a separate clinical trial at the National Institutes of Health. Results Ten of 13 amniotic fluid samples contained at least one NNS (ace-K, saccharin, steviol glucuronide, and/or sucralose). Maximum amniotic fluid NNS concentrations of ace-K, saccharin, steviol glucuronide, and sucralose were 78.9, 55.9, 93.5, and 30.6 ng/mL, respectively. Ace-K and saccharin were present in 100% and 80% of the cord blood samples, with maximal concentrations of 6.5 and 2.7 ng/mL, respectively. Sucralose was not detected and steviol glucuronide was not measurable in any of the cord blood samples. Conclusion Our results provide evidence of human transplacental transmission of NNS. Based on results predominantly obtained from rodent models, we speculate that NNS exposure may adversely influence the offsprings' metabolic health. Well-designed, prospective clinical trials are necessary to understand the impact of NNS intake during pregnancy on human development and long-term health. Key Points NNS consumption during pregnancy has increased in recent years. Maternal NNS intake during pregnancy is associated with preterm birth and higher infant weight gain in epidemiologic studies. In rodents, in utero NNS exposure induces metabolic abnormalities in mothers and their offspring, alters offspring gut microbiota composition, and promotes sweet taste preference in adulthood. It is presently unknown whether and to what degree maternal NNS ingestion in humans leads to direct in utero exposure. This study provides the first evidence of in utero NNS exposure in humans and highlights the urgent need to investigate clinical consequences of early life NNS exposure on metabolism, weight, taste preference, and general health. [ABSTRACT FROM AUTHOR]

Aspartame is the methyl-ester of the aspartate-phenylalanine dipeptide. Over time, it has become a very popular artificial sweetener. However, since its approval by the main food safety agencies, several concerns have been raised related to neuropsychiatric effects and neurotoxicity due to its ability to activate glutamate receptors, as well as carcinogenic risks due to the increased production of reactive oxygen species. Within this review, we critically evaluate reports concerning the safety of aspartame. Some studies evidenced subtle mood and behavioral changes upon daily high-dose intake below the admitted limit. Epidemiology studies also evidenced associations between daily aspartame intake and a higher predisposition for malignant diseases, like non-Hodgkin lymphomas and multiple myelomas, particularly in males, but an association by chance still could not be excluded. While the debate over the carcinogenic risk of aspartame is ongoing, it is clear that its use may pose some dangers in peculiar cases, such as patients with seizures or other neurological diseases; it should be totally forbidden for patients with phenylketonuria, and reduced doses or complete avoidance are advisable during pregnancy. It would be also highly desirable for every product containing aspartame to clearly indicate on the label the exact amount of the substance and some risk warnings. [ABSTRACT FROM AUTHOR]

Sugar substitutes have been recommended to be used for weight and glycemic control. However, numerous studies indicate that consumption of artificial sweeteners exerts adverse effects on glycemic homeostasis. Although sucralose is among the most extensively utilized sweeteners in food products, the effects and detailed mechanisms of sucralose on insulin sensitivity remain ambiguous. In this study, we found that bolus administration of sucralose by oral gavage enhanced insulin secretion to decrease plasma glucose levels in mice. In addition, mice were randomly allocated into three groups, chow diet, high-fat diet (HFD), and HFD supplemented with sucralose (HFSUC), to investigate the effects of long-term consumption of sucralose on glucose homeostasis. In contrast to the effects of sucralose with bolus administration, the supplement of sucralose augmented HFD-induced insulin resistance and glucose intolerance, determined by glucose and insulin tolerance tests. In addition, we found that administration of extracellular signal-regulated kinase (ERK)-1/2 inhibitor reversed the effects of sucralose on glucose intolerance and insulin resistance in mice. Moreover, blockade of taste receptor type 1 member 3 (T1R3) by lactisole or pretreatment of endoplasmic reticulum stress inhibitors diminished sucralose-induced insulin resistance in HepG2 cells. Taken together, sucralose augmented HFD-induced insulin resistance in mice, and interrupted insulin signals through a T1R3-ERK1/2-dependent pathway in the liver. [ABSTRACT FROM AUTHOR]

Nonnutritive sweeteners and low-calorie sweeteners are commonly used as sugar substitutes. Many Web sites cite concern for potential adverse effects, most often related to inflammation. A comprehensive literature search was conducted to identify all of the available studies related to acute adverse effects associated with these sweeteners. In general, acute adverse effects associated with the consumption of nonnutritive sweeteners and low-calorie sweeteners are rare. The most common adverse effects reported include gastrointestinal disturbance, headaches, lightheadedness, hypersensitivity reactions, impaired spatial orientation, depression, and pain. Nonnutritive sweeteners (NNSs) and low-calorie sweeteners (LCSs) are commonly used as sugar substitutes. Many popular media Web sites caution against the use of these sweeteners because of their potential adverse effects such as inflammation; however, there are limited supporting data. A Medline search of articles published between 2010 and 2020 was conducted, resulting in 833 articles, of which 12 relevant studies were included in this review. Acute adverse effects associated with the consumption of NNSs and LCSs are rare. A few studies cite reports of acute adverse effects, including mild gastrointestinal disturbance, headaches, lightheadedness, hypersensitivity reactions, impaired spatial orientation, depression, and pain. Little scientific evidence has been reported in the literature since 2010 to support these warning statements to consumers about acute adverse effects to NNSs and LCSs. [ABSTRACT FROM AUTHOR]

Growing evidence has demonstrated that maternal artificial sweetener (AS) consumption may not be a beneficial alternative when compared to sugar-sweetened beverages and potentially leads to metabolic dysfunction in adult offspring. Compromised skin integrity and wound healing associated with type 2 diabetes can lead to complications such as diabetic pressure injury (PI). In this context, the skin plays an important role in the maintenance of metabolic homeostasis, yet there is limited information on the influence of sugar- or AS-sweetened beverages during pregnancy on developmental programming and offspring skin homeostasis. This study examined the impact of maternal fructose or acesulfame-k consumption on offspring wound healing. Female C57Bl/6 mice received a chow diet ad libitum with either water (CD), fructose (FR; 34.7 mM fructose), or AS (AS; 12.5 mM Acesulfame-K) throughout pregnancy and lactation. PIs were induced in offspring at 9 weeks of age (n = 6/sex/diet). PIs and healthy skin biopsies were collected for later analysis. Maternal AS intake increased skin inflammatory markers in healthy biopsies while an FR diet increased Tgfb expression, and both diets induced subtle changes in inflammatory markers post-wound inducement in a sex-specific manner. Furthermore, a maternal FR diet had a significant effect on pressure wound severity and early wound healing delay, while AS maternal diet had a sex-specific effect on the course of the healing process. This study demonstrates the need for a better understanding of developmental programming as a mediator of later-life skin integrity and wound responsiveness. [ABSTRACT FROM AUTHOR]

The excess use of artificial sweeteners poses a serious issue to the environment and human health. Acesulfame-K (Ace-K) is a non-nutritive artificial sweetener excessively used as an alternative sugar substitute in various foods and beverages. Here a simple, selective and rapid method to determine Ace-K in dietary products is proposed. In this study, a molecularly imprinted polymer (MIP) based electrochemical sensor is designed for the sensitive and selective determination of Ace-K. MIP was developed by the electropolymerization of ortho-phenylenediamine (o-PD) thin film around template molecules (Ace-K) on a glassy carbon electrode. Various parameters such as deposition cycle, template removal and rebinding parameters were optimized for sensor fabrication. The sensor was characterized after each stage of fabrication using cyclic voltammetry (CV), differential pulse voltammetry (DPV), electrochemical impedance spectroscopy (EIS) and atomic force microscopy (AFM) analysis. The MIP sensor exhibited wide linear range for the determination of Ace-K from 0.1 to 17.0 μM. The developed sensor attained the limit of detection (LOD) and limit of quantification (LOQ) of 0.35 µM and 1.2 µM, respectively. The applicability of the proposed sensor was examined for Ace-K determination in real samples. The MIP sensor exhibited excellent selectivity, repeatability, stability and commercialization potential for Ace-K detection.

As a new class of water contaminants, artificial sweeteners (ASs) have attracted much attention due to their environmental persistence and potential adverse effects to human and the environment. This study systematically investigated the occurrence and distribution of four commonly used ASs in the effluent of wastewater treatment plants (WWTPs), surface water and groundwater in the middle and lower reaches of the Yellow River (Henan section). Sucralose (SUC) was dominant in WWTP effluents and had the highest mass loading. Acesulfame (ACE), cyclamate (CYC), saccharin (SAC), and SUC were consistently detected in surface water at concentrations ranging from 1.364 ng/L (CYC) to 7786 ng/L (ACE). Spatial analysis showed that the pollution level of ASs in the trunk stream was lower than that in most tributaries. The total concentrations of ASs detected in surface water ranged between 308.7 and 10,498 ng/L, while in groundwater, the total concentration of ASs detected was between ND–4863 ng/L. ACE and SUC are the main pollutants in surface water and groundwater within this survey area. The risk assessment showed that the risks of the four target ASs to aquatic organisms were negligible (risk quotient (RQ) values < 0.1), and the maximum risk quotient of the mixtures (MRQ) values of all rivers were all much less than 0.1. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the association between non-nutritive sweetener (NNS) consumption and stress and anxiety, among a sample of college students. Two-hundred and twenty-seven students from a large mid-western university participated in this cross-sectional study. Students completed an online survey that evaluated NNS using a validated food frequency questionnaire. Stress and anxiety were evaluated using previously validated instruments. Most students reported very low/low/average concern for stress (63.9%), and had low/moderate anxiety (82.3%). Participants experiencing high and very high levels of stress had significantly higher NNS consumption compared to those with a very low and low risk, and concern for stress (p <.046; d = 0.28). There was no difference however for NNS intake and anxiety. Reduction of artificial sweetener intake may be associated with stress levels among college students. However, more research is needed to examine any causal relationship between artificial sweetener intake and stress. [ABSTRACT FROM AUTHOR]

Background: Previous studies on saccharin and cyclamate were either limited to experimental animals or lacked evaluation of their long-term consumption effects in humans. Objectives: This study evaluated the effect of chronic consumption of saccharin and cyclamate on biochemical parameters in healthy individuals and patients with type 2 diabetes mellitus. Material and Methods: Healthy and diabetic individuals were classified into two groups based on whether they consumed sweeteners or not. The participants were classified according to the amount of sweetener consumed per day and duration of consumption. Serum catalase activity, peroxynitrite, ceruloplasmin, and malondialdehyde concentrations were determined. Glycated hemoglobin, fasting glucose, creatinine, alanine transaminase, and lipid profile were also evaluated. The results suggest that saccharin and cyclamate increased HbA1C (+11.16%), MDA (+52.38%), TG (+16.74%), LDL (+13.39%), and TC/HDL (+13.11%) in healthy volunteers. Diabetic patients consuming sweeteners showed increased FSG (+17.51%), ceruloplasmin (+13.17%), and MDA (+8.92%). Diabetic patients showed a positive correlation between the number of tablets consumed per day with FSG and serum creatinine. A positive correlation was found between the duration of sweetener consumption and FSG as well as TG. Conclusion: Consumption of saccharin and cyclamate affected biochemical parameters related to metabolic functions in a time and dose-dependent manner and appear to increase oxidative stress in healthy and diabetic type 2 patients. [ABSTRACT FROM AUTHOR]

Aim: We compared the impact of artificially- and sugar-sweetened beverages co-ingested with a mixed meal on postprandial fat and carbohydrate oxidation, blood glucose, and plasma insulin and triglyceride concentrations. Methods: Eight college-aged, healthy males completed three randomly assigned trials, which consisted of a mixed macronutrient meal test with 20oz of Diet-Coke (AS), Coca-Cola (NS), or water (CON). One week separated each trial and each participant served as his own control. Resting energy expenditure (REE) via indirect calorimetry, blood pressure, and blood samples were obtained immediately before, 5, 10, 30, 60, 120, and 180 min after meal and beverage ingestion. A two-way (treatment × time) repeated-measures ANOVA was conducted to assess REE, fat and carbohydrate oxidation rates, blood glucose, and plasma insulin and triglyceride concentrations. Results: There was a significant main effect of treatment on total fat oxidation (P = 0.006), fat oxidation was significantly higher after AS (P = 0.006) and CON (P = 0.001) compared to following NS. There was a significant main effect of treatment on total carbohydrate oxidation (P = 0.005), carbohydrate oxidation was significantly lower after AS (P = 0.014) and CON (P = 0.001) compared to following NS. Plasma insulin concentration AUC was significantly lower after AS (P = 0.019) and trended lower in CON (P = 0.054) compared to following NS. Conclusion: Ingestion of a mixed meal with an artificially-sweetened beverage does not impact postprandial metabolism, whereas a sugar-sweetened beverage suppresses fat oxidation and increases carbohydrate oxidation compared to artificially-sweetened beverage and water. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance is one of the most pressing concerns of our time. The human diet is rich with compounds that alter bacterial gut communities and virulence‐associated behaviours, suggesting food additives may be a niche for the discovery of novel anti‐virulence compounds. Here, we identify three artificial sweeteners, saccharin, cyclamate and acesulfame‐K (ace‐K), that have a major growth inhibitory effect on priority pathogens. We further characterise the impact of ace‐K on multidrug‐resistant Acinetobacter baumannii, demonstrating that it can disable virulence behaviours such as biofilm formation, motility and the ability to acquire exogenous antibiotic‐resistant genes. Further analysis revealed the mechanism of growth inhibition is through bulge‐mediated cell lysis and that cells can be rescued by cation supplementation. Antibiotic sensitivity assays demonstrated that at sub‐lethal concentrations, ace‐K can resensitise A. baumannii to last resort antibiotics, including carbapenems. Using a novel ex vivo porcine skin wound model, we show that ace‐K antimicrobial activity is maintained in the wound microenvironment. Our findings demonstrate the influence of artificial sweeteners on pathogen behaviour and uncover their therapeutic potential. Synopsis: Artificial sweeteners can inhibit the growth of multidrug‐resistant pathogens, disrupt virulence associated behaviours and potentiate antibiotic activity. In wound models the sweetener, Acesulfame K, shows potential as a topical wound treatment. Artificial sweeteners can significantly impact the growth of bacterial pathogens.Ace‐K can inhibit a range of virulence traits such as biofilm formation, motility and natural transformation.It weakens the bacterial cell membrane leading to loss of morphology and bulge‐mediated cell lysis.It can also potentiate the activity of antibiotics including carbapenems.Ace‐K shows clinical potential as a topical wound therapeutic. [ABSTRACT FROM AUTHOR]

We report the effects of aspartame on anxiety-like behavior, neurotransmitter signaling and gene expression in the amygdala, a brain region associated with the regulation of anxiety and fear responses. C57BL/6 mice consumed drinking water containing 0.015% or 0.03% aspartame, a dose equivalent of 8 to 15% of the FDA recommended maximum human daily intake, or plain drinking water. Robust anxiety-like behavior (evaluated using open field test and elevated zero maze) was observed in male and female mice consuming the aspartame-containing water. Diazepam, an allosteric modulator of the GABA-A receptor, alleviated the anxiety-like behavior. RNA sequencing of the amygdala followed by KEGG biological pathway analysis of differentially expressed genes showed glutamatergic and GABAergic synapse pathways as significantly enriched. Quantitative PCR showed upregulation of mRNA for the glutamate NMDA receptor subunit 2D (Grin2d) and metabotropic receptor 4 (Grm4) and downregulation of the GABA-A receptor associated protein (Gabarap) mRNA. Thus, taken together, our diazepam and gene expression data show that aspartame consumption shifted the excitation-inhibition equilibrium in the amygdala toward excitation. Even more strikingly, the anxiety-like behavior, its response to diazepam, and changes in amygdala gene expression were transmitted to male and female offspring in two generations descending from the aspartame-exposed males. Extrapolation of the findings to humans suggests that aspartame consumption at doses below the FDA recommended maximum daily intake may produce neurobehavioral changes in aspartame-consuming individuals and their descendants. Thus, human population at risk of aspartame's potential mental health effects may be larger than current expectations, which only include aspartame-consuming individuals. [ABSTRACT FROM AUTHOR]

Abstract Antimicrobial resistance is one of the most pressing concerns of our time. The human diet is rich with compounds that alter bacterial gut communities and virulence‐associated behaviours, suggesting food additives may be a niche for the discovery of novel anti‐virulence compounds. Here, we identify three artificial sweeteners, saccharin, cyclamate and acesulfame‐K (ace‐K), that have a major growth inhibitory effect on priority pathogens. We further characterise the impact of ace‐K on multidrug‐resistant Acinetobacter baumannii, demonstrating that it can disable virulence behaviours such as biofilm formation, motility and the ability to acquire exogenous antibiotic‐resistant genes. Further analysis revealed the mechanism of growth inhibition is through bulge‐mediated cell lysis and that cells can be rescued by cation supplementation. Antibiotic sensitivity assays demonstrated that at sub‐lethal concentrations, ace‐K can resensitise A. baumannii to last resort antibiotics, including carbapenems. Using a novel ex vivo porcine skin wound model, we show that ace‐K antimicrobial activity is maintained in the wound microenvironment. Our findings demonstrate the influence of artificial sweeteners on pathogen behaviour and uncover their therapeutic potential.

As rates of obesity, diabetes, and related comorbidities have increased, the consumption of artificial sweeteners (ASs) as sugar substitutes has also risen in popularity as they are perceived as a healthier alternative to sugar sweetened products. However, there is conflicting evidence regarding the impact of AS intake on metabolic and reproductive health. Glucose intolerance during pregnancy due to intake of sugar sweetened foods can result in an increased risk for the development of type 2 diabetes post-pregnancy. However, limited information exists on the impact of AS intake during pregnancy and lactation on the mother's health in later life. We hypothesised both AS and fructose would impair metabolic health post-partum (PP) following maternal consumption during pregnancy and lactation. Female C57Bl/6 mice received a standard control diet ad libitum with either water (CD), fructose (Fr; 34.7 mm intake), or AS (AS;12.5 mm Acesulfame-K) throughout pregnancy and lactation. Post-weaning, AS and Fr dams were fed the CD diet for the remainder of the experiment. Oral glucose tolerance tests were undertaken 8 weeks PP and dams were humanely killed at 9 weeks PP, with adipose tissue and ovaries collected for analysis. Experimental diets did not influence maternal bodyweight. At 8 weeks PP, increased glucose intolerance was evident in both AS and Fr dams. Adipocyte size was significantly increased in both the AS and Fr groups PP. Further, in the ovary, AS increased expression of genes associated with follicular development and ovulation. Therefore, ASs may not represent beneficial substitutes to fructose during pregnancy, with the potential to increase the risk of T2DM in later life in mothers. [ABSTRACT FROM AUTHOR]

Consumer health concerns and regulatory policies lead to a growing demand for sugar-sweetened beverage alternatives. A reduced energy content can be achieved using artificial sweeteners, which often also convey a metallic or bitter off-flavor. Therefore, the alteration of sweetness perception and masking of potential off-flavors are paramount for improving sweet beverages. Trigeminal stimuli, such as capsaicin (spicy) or menthol (cooling), have been used to influence taste perception in food items, although their use in beverages has not yet been systematically investigated. Here, the influence of menthol on sweetness perception in an aqueous solution is examined both on the sensory and psychophysiological level. The addition of menthol had no sensory effect on sweetness perception; however, psychophysiological measurements suggest a boost in the physiological response to cold perception through the addition of sugar. Moreover, menthol addition shifted the recognition threshold of unpleasant bitterness of the sweetener acesulfame-K from 21.35 to 36.93 mg/L, masking the off-flavor. These findings illuminate the complexity of trigeminal perception influences on taste. Further investigation of these effects can render trigeminal stimuli an effective tool to enhance beverage aroma and flavor. [ABSTRACT FROM AUTHOR]

Sales of low-calorie sweeteners are increasing in the Unites States, with sucralose representing the second largest of the U.S. market share. Since >99% of ingested sucralose is excreted as the parent compound, it represents a contaminant of emerging concern and has been proposed as an indicator of pollution of natural waters by anthropogenic waste. Many report that it is increasingly omnipresent in surface, coastal, and drinking water. Given the increasing consumption of low-calorie sweeteners, changes in influent and effluent sucralose concentrations presage their concentrations in natural waters. The aim of this research was to quantify sucralose at a constructed treatment wetland that was designed to remove nutrients (nitrogen and phosphorus) from secondary treated wastewater. We report the concentrations of sucralose in the surface water, sediment, and porewater throughout the flow train of the wetlands over a period of three years and include surface water sampling following an extreme weather event. The average influent surface water concentration of sucralose was 24 ± 2 ppb, and the average outfall concentration was 20 ± 6 ppb, indicating the sucralose is not subjected to chemical or physical adsorption in the sediment within the wetland. [ABSTRACT FROM AUTHOR]

The fate of indicator bacteria and wastewater micropollutants (WWMPs) discharged from water resource recovery facilities (WRRFs) and combined sewer overflows (CSOs) needs to be understood for the protection of drinking water sources. This study investigated the partitioning behavior in wet and dry weather of Escherichia coli and 6 WWMPs including acetaminophen (ACET), caffeine (CAF), theophylline (THEO), carbamazepine (CBZ), 2-hydroxycarbamazepine (CBZ-2OH), and the artificial sweetener aspartame (ASP) between the water, suspended particulate matter (SPM), and sediments. ACET, CAF, THEO and CBZ were detected in all matrices. In contrast, CBZ-2OH and ASP were strongly associated with suspended particles, being exclusively detected in SPM and sediments. When comparing dry to wet weather concentrations, three main patterns were observed depending on the compounds and CSO locations: (i) compounds with low removal efficiency by wastewater treatment (CBZ, CBZ-2OH and ASP) are diluted with the addition of stormwater in the aqueous and SPM phases; (ii) contaminants with high removal efficiency (E. coli, ACET, CAF, THEO) saw an increase in their particle associated fraction (39 to 59% for E. coli, and from 12%–43% to 42%–91% for WWMPs); and (iii) no significant difference was observed for surficial sediment concentrations after rainfall events, although spatial variability was observed. Results highlight the importance of monitoring the SPM phase to overcome dilution effects in the dissolved phase. Analyzing SPM with regards to micropollutants and indicator bacteria may be more relevant for risk assessment and the assessment of the relative contribution of CSO bypass flows and treated wastewater effluents loads.

[Display omitted] • Fates of acesulfame (ACE) and sucralose (SUC) during composting were investigated. • The combination of biochar and laccase led to a reduction in NH 3 emissions. • The additions of biochar and laccase enhanced the SUC and ACE degradation by ∼70 %. • The additive-treatments promoted cooperative relationship of bacterial community. This study investigates the effects of biochar, laccase, and their combined application on nitrogen transformation, the degradation of sucralose (SUC) and acesulfame (ACE), and the dynamics of bacterial communities during sewage sludge composting. The results indicated that NH 3 emissions were reduced by 41.2 %, 17.5%, and 40.8 % in the biochar, laccase, and biochar-laccase treatments, respectively, compared to the control. Meanwhile, N 2 O emissions decreased significantly by 26.8 % and 16.0 % for the biochar and biochar-laccase treatments, respectively, but increased by 8.1 % for the laccase treatment. Additionally, the biochar, laccase, and biochar-laccase treatments enhanced the degradation of SUC and ACE by 36.6–68.3 % and 49.2–69.8 %, relative to the control, respectively. Network analysis showed that the additive-treatment enhanced the cooperation within bacterial communities, and solidified artificial sweeteners degradation, especially under biochar-laccase application. Phylogenetic investigation of communities by reconstruction of unobserved states further indicated that biochar, laccase, biochar-laccase treatment increased enzymes associated with the degradations of organic matter and artificial sweeteners. In conclusion, it suggested that a combined addition of biochar and laccase was an effectively way to reduce nitrogen loss and promote artificial sweeteners degradations during sewage sludge composting. [ABSTRACT FROM AUTHOR]

Objective: Instead of sugar, artificial sweeteners that do not contain energy are widely used. However, contrary to popular belief, artificial sweeteners are thought to affect metabolism. Thus, purpose of this present study was to evaluate effects of saccharin on serum ghrelin, appetite, and food consumption. Methods: Nine healthy males aged 20-29 participated in the randomized, controlled, and cross-over study. Each participant received 300 ml water, and 300 ml water containing 75 grams sucrose and 240 milligrams saccharin. At baseline, 30th, 60th, 90th, 120th, and 180th min, Visual Analog Scale was applied to evaluate appetite, and blood samples were taken to analyze ghrelin. After 180th min, participants consumed ad libitum diet, and kept 24-hours dietary food intake records until the end of this day. Results: At 60th and 120th min, mean ghrelin level was higher in drinks containing only water and saccharin compared to drink containing sucrose (p=0.001, p=0.003 respectively). In addition, in 90th min following drink consumption, mean ghrelin level was higher in drink containing saccharin than sucrose test drink (p=0.001). Mean prospective food consumption and desire to eat score at 120th min after drink consumption was higher in saccharin test drink than sucrose test drink (p<0.05). Difference between energy and macronutrient intake was statistically insignificant (p>0.05). Conclusions: In this study, which examined the effect of acute intake of saccharin an artificial sweetener, it is remarkable that high ghrelin levels and high scores related to appetite in some intervals after drink consumption containing saccharin. However, studies on the longer-term consumption of saccharin are needed to clarify these effects on appetite metabolism. [ABSTRACT FROM AUTHOR]

Abstract Background Aspartame is one of the world’s most widely used artificial sweeteners and is an ingredient in more than 5000 food products globally. A particularly important use is in low-calorie beverages consumed by children and pregnant women. The Ramazzini Institute (RI) reported in 2006 and 2007 that aspartame causes dose-related increases in malignant tumors in multiple organs in rats and mice. Increased cancer risk was seen even at low exposure levels approaching the Acceptable Daily Intake (ADI). Prenatal exposures caused increased malignancies in rodent offspring at lower doses than in adults. These findings generated intense controversy focused on the accuracy of RI’s diagnoses of hematopoietic and lymphoid tissue tumors (HLTs). Critics made the claim that pulmonary lesions observed in aspartame-exposed animals were inflammatory lesions caused by Mycoplasma infection rather than malignant neoplasms. Methods To address this question, RI subjected all HLTs from aspartame-exposed animals to immunohistochemical analysis using a battery of markers and to morphological reassessment using the most recent Internationally Harmonized Nomenclature and Diagnostic (INHAND) criteria. Findings This immunohistochemical and morphological re-evaluation confirmed the original diagnoses of malignancy in 92.3% of cases. Six lesions originally diagnosed as lymphoma (8% of all HLTs) were reclassified: 3 to lymphoid hyperplasia, and 3 to chronic inflammation with fibrosis. There was no evidence of Mycoplasma infection. Interpretation These new findings confirm that aspartame is a chemical carcinogen in rodents. They confirm the very worrisome finding that prenatal exposure to aspartame increases cancer risk in rodent offspring. They validate the conclusions of the original RI studies. These findings are of great importance for public health. In light of them, we encourage all national and international public health agencies to urgently reexamine their assessments of aspartame’s health risks - especially the risks of prenatal and early postnatal exposures. We call upon food agencies to reassess Acceptable Daily Intake (ADI) levels for aspartame. We note that an Advisory Group to the International Agency for Research on Cancer has recommended high-priority reevaluation of aspartame’s carcinogenicity to humans.

Understanding the factors which influence fertility is essential for developing appropriate nutritional recommendations for couples trying to conceive. Non-caloric sweeteners (NCS) are increasing in the food chain and despite being no/low calorie, several adverse metabolic consequences have been attributed to their consumption. Their effects on reproduction have been relatively under-researched, particularly in males. This review aims to systematically review the literature for evidence of the effect of NCS on male fertility in rodents, with sperm parameters (sperm quantity and quality) assessed as primary outcomes. Given the lack of information available in humans this review has been carried out using evidence from rodent models. Risk of bias assessment was carried out using the Syrcle risk of bias tool. Nine studies met the inclusion criteria. Forty-four percent showed a negative effect of NCS on male reproductive parameters compared with controls. The effects of NCS on fertility have been conflicting and selected studies have been heterogeneous in relation to study design. It is unclear if NCS has an impact on male reproductive function. There is a need for randomized controlled trials using a standardized protocol for analysis, to formulate a clear message in terms of male fertility.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease globally, and it is strongly associated with obesity. To combat obesity, artificial sweeteners are often used to replace natural sugars, and sucralose is one of the most extensively used sweeteners. It was known that sucralose exerted effects on lipid metabolism dysregulation, and hepatic inflammation; however, the effects of sucralose on hepatic steatosis were still obscure. In this study, we found that supplements of sucralose enhanced high-fat-diet (HFD)-induced hepatic steatosis. In addition, treatment of sucralose increased reactive oxygen species (ROS) generation and induced endoplasmic reticulum (ER) stress in HepG2 cells. Pretreatment of ROS or ER stress inhibitors reversed the effects of sucralose on lipogenesis. Furthermore, pretreatment of taste receptor type 1 membrane 3 (T1R3) inhibitor or T1R3 knockdown reversed sucralose-induced lipogenesis in HepG2 cells. Taken together, sucralose might activate T1R3 to generate ROS and promote ER stress and lipogenesis, and further accelerate to the development of hepatic steatosis.

Background: The food we consume will have sugar in one or the other form, which is not ideal for our teeth. This can be replaced by the use of sugar substitutes available in the market. Sugar substitutes have beneficial and adverse effects on health. In spite of their beneficial effects, long-term use of sugar substitutes is not recommended because of their health-related complications. Therefore, before consuming any sugar substitutes, everyone needs to know about both health benefits and their health hazards; hence, the present study was designed to assess the awareness, knowledge, and utilization of sugar substitutes among the general population in Riyadh Region, Kingdom of Saudi Arabia. Objectives: The aim is to assess the awareness and knowledge about sugar substitutes. Methodology: Questionnaire consisting of demographic details, awareness, and knowledge about sugar substitutes were sent through social media and it was in the Arabic and English Language. After completing the questionnaire, participants are requested to send the link to their friends and relatives. Results: About 60.20% of participants were aware of sugar substitutes. Statistically significant difference was observed for gender and awareness of sugar substitutes (P < 0.05). About 31.5% of the participants are of the view that sugar substitutes have got side effects. About 61.9% of participants are of the view that Sugar substitute reduces the chance of occurrence of dental caries. Conclusions: Overall, 60.2% of study participants were aware of sugar substitutes, but the controversy on most of the artificial sweeteners cannot be ignored. Hence, the safety of these sweeteners is of prime importance for scientists. Any usage of sugar substitutes should be weighed against the adverse effects.

Background: Knowledge and attitude are the main indicators of awareness about the use of artificial sweeteners. Objectives: This study aimed to evaluate the knowledge, attitude, and practices (KAPs) of patients with type 2 diabetes mellitus (T2DM) in relation to the consumption of low-calorie artificial sweeteners. Methods: In this descriptive-analytical study, 400 diabetic patients admitted to the diabetes clinic of Bu-Ali hospital in Zahedan were selected by the census method. After recording the demographic characteristics, we assessed participants’ knowledge and attitude through a researcher-made questionnaire. Also, the subjects’ practices were evaluated based on their nutritional behaviors. The answers were marked as good, moderate, and poor. Results: The knowledge and attitude of the study population were 39% and 34.8%, respectively at the ‘poor’ level, 58% and 58.3% at the ‘moderate’ level, and 3% and 7% at the ‘good’ level. There was a significant relationship between patients’ knowledge, attitude and their demographic indicators (p

Background and purpose: Artificial sweeteners are increasingly used in food products, so, it is necessary to study the effects of these additives on liver. Materials and methods: In this experimental study, 30 immature male rats were divided into five groups (n=6 per group) and acesulfame k at 50, 100, 200, and 400 mg/kg were injected intraperitoneally to all groups for 30 days. One and 30 days after the last injection, blood samples were taken from the rats' eye, and the levels of FBS, HDL, LDL, AST, ALT, ALP, triglyceride, and cholesterol were measured. A number of rats were dissected in each group and their livers were removed to prepare tissue sections. The slides were examined by optical microscopy and data were analyzed applying ANOVA. Results: The study showed that acesulfame k for 30 days, at 200 and 400mg/kg caused a significant increase in glucose level (P