Design Optimization of a Novel Catalytic Approach for Transglucosylated Isomaltooligosaccharides into Dietary Polyols Structures by Leuconostoc mesenteroides Dextransucrase.

Polyols, or sugar alcohols, are widely used in the industry as sweeteners and food formulation ingredients, aiming to combat the incidence of diet-related Non-Communicable Diseases. Given the attractive use of Generally Regarded As Safe (GRAS) enzymes in both academia and industry, this study reports on an optimized process to achieve polyols transglucosylation using a dextransucrase enzyme derived from Leuconostoc mesenteroides. These enzyme modifications could lead to the creation of a new generation of glucosylated polyols with isomalto-oligosaccharides (IMOS) structures, potentially offering added functionalities such as prebiotic effects. These reactions were guided by a design of experiment framework, aimed at maximizing the yields of potential new sweeteners. Under the optimized conditions, dextransucrase first cleared the glycosidic bond of sucrose, releasing fructose with the formation of an enzyme-glucosyl covalent intermediate complex. Then, the acceptor substrate (i.e., polyols) is bound to the enzyme-glucosyl intermediate, resulting in the transfer of glucosyl unit to the tested polyols. Structural insights into the reaction products were obtained through nuclear maneic resonance (NMR) and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) analyses, which revealed the presence of linear α(1 → 6) glycosidic linkages attached to the polyols, yielding oligosaccharide structures containing from 4 to 10 glucose residues. These new polyols-based oligosaccharides hold promise as innovative prebiotic sweeteners, potentially offering valuable health benefits.

Sweetness interaction between a novel glycosylated rebaudioside A and various sweeteners in a binary mixture system.

The present study investigated the sweetness interaction and the sensory characteristics of a novel glycosylated rebaudioside A (g-reb_A) when mixed with other sweeteners. Binary sweetener mixtures were formulated by mixing g-reb_A with four types of sweeteners (sucrose, aspartame, acesulfame-K, saccharin). The sweetness potencies of sweeteners were measured at various concentrations. G-reb_A was mixed with each of the four other sweeteners at the concentration ratio of 35:65 or 50:50 to match the sweetness of a 10% sucrose solution. A generic descriptive analysis was conducted to evaluate the binary samples compared to the 10% sucrose solution. Most binary mixtures exhibited an additive effect on sweetness. A marginal sweetness synergistic effect was observed when g-reb_A was mixed with sucrose at the 50:50 ratio. The sensory characteristics of the binary mixture depended on the type of sweetener mixed with g-reb_A. Mixtures of g-reb_Aacesulfame-K or g-reb_Asaccharin elicited significantly higher bitter taste than the other binary mixtures.

Association of coffee consumption with cardiometabolic multimorbidity: A prospective cohort study in the UK biobank.

BACKGROUND AND AIMS: 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). METHODS AND RESULTS: 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. CONCLUSIONS: Coffee consumption was associated with lower risk for almost all transition phases of CMM development and consistent findings were observed with unsweetened coffee.

Exploring the chemical composition of granola formulated with different sweeteners and produced via oven and microwave baking.

The objective of this study was to create and characterize an innovative granola, a popular choice in quick breakfasts. The granola samples were sweetened with agave syrup (A), honey (H), and stevia (S) and produced using conventional oven (1) and microwave (2) baking techniques at temperatures of 160°C and 300 W, respectively. Among the samples, H1 exhibited the highest total sugar content (26.64 ng/µL), with fructose being the predominant monosaccharide in A and H samples, whereas saccharose and maltose were more prominent in S-containing samples. Hydroxymethylfurfural was absent in S2, but its concentrations ranged between 10.52 and 85.78 ppm in the other samples. Linoleic acid constituted nearly 52% of the fatty acid composition in all granolas. In terms of organic acid composition, malic acid ranged between 1189.55 and 2022.95 µg/mL, and citric acid fell within the range of 341.58 and 1824.04 µg/mL. The granola specimens also contained individual phenolic compounds, such as vanillic acid, vanillin, ferulic acid, propyl gallate, and pyrocatechol. PRACTICAL APPLICATION: This study demonstrates that both baking method and sweetener choice significantly impact the chemical quality attributes of granola, which is a popular breakfast cereal. Microwave baking can be a faster and potentially healthier option, whereas stevia offers a low-calorie sweetener alternative. Further research is needed to maximize health benefits of granola products.

Evaluation of Conflicts of Financial Interest in Publications on the Consumption of High-Intensity Sweeteners and Body-Weight Changes: A Systematic Review.

CONTEXT: Diseases related to excessive sugar consumption have become a public health concern. However, there may be a direct association between the consumption of artificial sweeteners and changes in body weight. OBJECTIVE: The aim was to evaluate potential industry financial conflicts of interest in publications on the relationship between high-intensity sweetener consumption and changes in body weight in observational and intervention studies. DATA SOURCES: The systematic review used the Medline, Embase, Cochrane, Scopus, and the VHL (Virtual Health Library) Regional Portal, including the LILACS databases. The PICOS strategy were used in the search strategy for intervention studies and for observational studies used the exposure factor as the criterion. DATA EXTRACTION: Inclusion criteria were observational and intervention studies in adults, without population or health status restrictions, without restriction on the year of publication, but restricted to full articles in Portuguese, English, and Spanish. Exclusion criteria were humans younger than 18 years, cross-sectional studies, and animal and in vitro studies. DATA ANALYSIS: There were extracted effect estimates, odds ratios, and linear associations, quantifying the effects per unit of intake of high-intensity sweeteners. The risk of bias in the intervention studies was assessed using the Cochrane Collaboration Risk of Bias tool (RoB). The Newcastle Ottawa Scale was used for observational studies (case-control and cohort). CONCLUSION: Most clinical trials favor using artificial sweeteners and receive contributions from the food industry. Observational studies, for the most part, show that the use of artificial sweeteners is unfavorable. In these studies, there was no sponsorship from the food industry, only from regulatory bodies. This result suggests that studies that had the support of the food industry had their influence on their outcomes. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration no: CRD42016036204.

Trends in nonsugar sweetener use among United States adults by chronic diseases presence: 1999 to March 2020.

BACKGROUND: Although long-term health effects of nonsugar sweeteners (NSSs) are uncertain, they are widely used as a common alternative to added sugar, especially among people with chronic diseases. It is essential to evaluate trends in NSS use to inform policy makers. OBJECTIVES: This study aimed to investigate trends in NSS use overall and by chronic diseases presence in United States adults. METHODS: The analysis used data of United States adults (≥20 y) collected in National Health and Nutrition Examination Survey [NHANES (1999 to March 2020)]. Age-adjusted percentage of individuals consuming NSS beverages, NSS foods, tabletop NSS, or any of them during the first 24-h dietary recall period was calculated in each NHANES survey cycle. Weighted multivariable logistic or linear regression models were used to examine trends in NSS use over time. RESULTS: A total of 51,703 United States adults were included in the analysis. In total population, age-adjusted percentage of individuals consuming NSS in the past day increased from 29.3% in 1999-2000 to 37.5% in 2005-2006 and decreased to 24.1% in 2017 to March 2020 (P < 0.001 for nonlinear trend). Similar trends were observed for different subcategories of NSS-containing product consumption (NSS beverages, foods, and tabletop sweeteners). Similar trends were found among individuals with or without chronic disease. Among individuals with ≥1 chronic disease (cancer, cardiovascular disease, diabetes, hypertension, obesity, hyperlipemia), age-adjusted percentage of individuals consuming NSS in the past day increased from 34.5% in 1999-2000 to 41.1% in 2005-2008 and decreased to 28.1% in 2017 to March 2020, while NSS consumption increased from 20.0% in 1999-2000 to 27.4% in 2005-2008 and decreased to 14.3% in 2017 to March 2020 among individuals without chronic diseases (all P < 0.001 for nonlinear trend). CONCLUSIONS: NSS use increased from 1999 to 2006 and decreased until March 2020 among entire United States adults and individuals with or without chronic diseases. Moreover, NSS use is generally higher among individuals with chronic diseases during study periods.

Impact of artificial sweeteners and rare sugars on the gut microbiome.

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.

Effect of stevia on blood glucose and HbA1C: A meta-analysis.

BACKGROUND: The study investigates substituting non-nutritive sweeteners (NNS) for sugar to address health concerns related to excess sugar intake. It specifically examines how stevia affects insulin and blood glucose levels. The systematic review and meta-analysis aim to evaluate stevia's impact on glycemic indices. METHODS: We conducted a systematic review and meta-analysis following PRISMA guidelines, including 26 studies with 1439 participants. The PROSPERO registration number for this research is CRD42023414411. We systematically searched PubMed (MEDLINE), Scopus, Web of Science, and Google Scholar. Additionally, we thoroughly reviewed the reference lists of the articles we extracted and relevant reviews. Two evaluators independently carried out screening, quality assessment, and data extraction. The GRADE (grading of recommendations, assessment, development, and evaluation) approach was utilized to evaluate the certainty of the evidence. RESULTS: Stevia consumption was associated with significantly reducing blood glucose levels (WMD: -3.84; 95 % CI: -7.15, -0.53; P = 0.02, low certainty), especially in individuals with higher BMI, diabetes, and hypertension. Dose-response analysis revealed a decrease in blood glucose for ≥3342 mg/day of stevia consumption. Stevia consumption has been shown to reduce blood glucose levels within 1-4 months, as evidenced by dose-response analysis (less than 120 days) and subgroup analysis (more than four weeks). However, stevia did not significantly affect insulin concentration or HbA1C levels (very low and low certainty, respectively). CONCLUSIONS: Low certainty evidence showed that stevia improved blood glucose control, especially when consumed for less than 120 days. However, more randomized trials with higher stevia dosages are required.

New Sweet-Tasting Gypenosides from "Jiaogulan" (Gynostemma pentaphyllum) and Their Interactions with the Homology Model of Sweet Taste Receptors.

Gynostemma pentaphyllum has been used as an herbal tea, vegetable, and dietary supplement for hundreds of years in East Asia. The sweet variety, grown in large areas in Fujian Province, China, is an essential source of "Jiaogulan" herbal tea. However, its sweet components are unknown. To investigate the sweet constituents of Fujian "Jiaogulan" and discover new natural high-potency sweeteners, phytochemical and sensory evaluations were combined to obtain 15 saponins, of which 11 (1-11) were sweet-tasting, including 2 new ones with sweetness intensities 20-200 times higher than that of sucrose, and four (12-15) were bitter-tasting. Their structures were elucidated using spectroscopic methods (NMR, MS, IR, UV), hydrolysis, and comparison with literature data. The contents of the 15 saponins were quantitatively analyzed using UPLC-MS/MS in multiple reaction monitoring mode. The contents of 1 and 2 sweet-tasting gypenosides were 9.913 ± 1.735 and 35.852 ± 1.739 mg/kg, respectively. The content of the sweetest compound (6) was 124.969 ± 0.961 mg/kg. Additionally, compound 4 was the most abundant sweet component (422.530 ± 3.702 mg/kg). Furthermore, molecular docking results suggested interactions of sweet saponins with sweet taste receptors. In general, this study revealed the material basis of the Fujian "Jiaogulan" taste.

Rotational Spectroscopy as a Tool to Characterize Sweet Taste: The Study of Dulcin.

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.

Artificial sweetener and respiratory system cancer: A Mendelian randomization analysis.

BACKGROUND & AIMS: The association between artificial sweeteners and various cancers has been investigated, but their relationship with respiratory system cancers remains uncertain. To address this knowledge gap, we conducted a comprehensive Mendelian Randomization (MR) analysis. METHODS: We looked for SNPs associated with artificial sweetener intake and respiratory system cancers from the IEU OpenGWAS project, as well as SNPs related to sweet taste in artificial sweeteners from Hwang et al.'s study. Rigorous quality control procedures were implemented to select instrumental Single Nucleotide Polymorphisms that were closely linked to artificial sweetener intake. To ensure the reliability of our findings, we employed five different analytical methods, with the inverse variance weighting method being the primary approach. Additionally, we thoroughly assessed heterogeneity, pleiotropy, and sensitivity. Finally, we conducted Multivariable Mendelian Randomization (MVMR) to validate our results. RESULTS: Intake of artificial sweetener added to cereal showed a positive association with malignant neoplasm of the lip, oral cavity, and pharynx (OR: 1027.54; 95% CI: 4.8-219994.46; P = 0.011), and the result was also confirmed by the MVMR analysis. In addition, better perceived intensity of aspartame was negatively associated with cancers in these regions (OR: 0.49; 95% CI: 0.28-0.88; P = 0.016). Intake of artificial sweetener added to coffee or tea was not related with respiratory system cancer. CONCLUSIONS: Our research offers evidence that the consumption of artificial sweeteners in cereals could increase the risk of cancers in the lip, oral cavity, and pharynx. Additionally, a greater sensitivity to the taste of aspartame may lower this risk.

Effect of perinatal consumption of low-calorie sweetener on maternal health: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Evidence regarding perinatal low-calorie (or artificial) sweetener (LCS) consumption and its effect on maternal health outcomes is limited and inconclusive. The primary outcomes of our systematic review and meta-analysis were the effect of preconception and pregnancy LCS exposure on reproductive and pregnancy outcomes. Secondary outcomes included long-term maternal health. METHODS: A systematic search of electronic databases, including PubMed, Embase, CINAHL, the Cochrane Library, Scopus, Web of Science, PsycINFO, ProQuest Health and Medical, ClinicalTrials.gov and Google Scholar, was conducted up to 20 November 2023. Primary studies, including clinical trials, cohort studies, case-control studies, which reported any LCS consumption during perinatal period and pregnancy and maternal health outcomes were eligible. A random effects model with restricted maximum likelihood estimation was used for the meta-analysis. We appraised the quality of the included studies using the National Institute of Health study quality appraisal tool and the overall quality of evidence using the Grading of Recommendations Assessment, Development, and Evaluation tool. RESULTS: A total of 19 eligible studies with 203,706 participants were included. LCS consumption during pregnancy was associated with 11% increased risk of preterm birth (RR = 1.11, 95% CI: 1.07-1.16, I2 = 0.01%) and 42% increased risk of gestational diabetes (RR = 1.42, 95% CI: 0.98-2.04, I2 = 67.60%) compared with no consumption, however, the effect size for gestational diabetes was not precise as the 95% CI indicated that the effect estimate could range from 2% lower risk to 204% (or 2.04 times) higher risk. We found no association between LCS consumption during pregnancy and gestational weight gain (standardized mean difference (SMD) = 0.04; 95% CI: -0.17 - 0.24, I2 = 41.31%) or gestational age at birth (SMD = 0.00; 95% CI: -0.13 - 0.14, I2 = 80.13%). The effect of LCS consumption on reproductive treatment outcomes were inconsistent. CONCLUSIONS: Based on the evidence available, LCS consumption in pregnancy was associated with increased risk of preterm birth and gestational diabetes. Robust research, such as well-designed randomized trials and large prospective cohort studies, is required to confirm the causal effect of LCS consumption during perinatal period on adverse maternal health outcomes.

Effect of Replacing Sucrose in Beverages with Nonnutritive Sweetener Sucralose on Cardiometabolic Risk Factors Among Asian Indian Adults with Type 2 Diabetes: A 12-Week Randomized Controlled Trial.

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).

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

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

Natural sweetener glycyrrhizin protects against precocious puberty by modulating the gut microbiome.

AIMS: Precocious puberty (PP) may lead to many adverse outcomes. Recent evidence suggests that PP is a gut-brain disease. On the other hand, the use of glycyrrhizin, a natural sweetener, has become popular in the past decade. Glycyrrhizin possesses various health benefits, but its impact on PP has yet to be investigated. We aimed to explore the protective effects of glycyrrhizin against PP in both humans (observational) and animals (interventional). MATERIALS AND METHODS: In the human cohort, we investigated the association between glycyrrhizin consumption and risk of PP. In the animal experiment, we observed puberty onset after feeding danazol-induced PP rats with glycyrrizin. Blood, fecal, and hypothalamic samples were harvested to evaluate potential mechanistic pathways. We also performed a fecal microbiota transplantation to confirm to causal relationship between glycyrrhizin and PP risk. KEY FINDINGS: Glycyrrhizin exhibited a protective effect against PP in children (OR 0.60, 95%CI: 0.39-0.89, p = 0.013), primarily driven by its significance in girls, while no significant effect was observed in boys. This effect was consistent with findings in rodents. These benefits were achieved through the modulation of the gut microbiome, which functionally suppressed the hypothalamic-pituitary-gonadal axis and prevented PP progression. A fecal microbiota transplantation indicated that the causal correlation between glycyrrhizin intake and PP is mediated by the gut microbiome alterations. SIGNIFICANCE: Our findings suggest that glycyrrhizin can protect against PP by altering the gut microbiome. Long term use of glycyrrhizin is safe and tolerable. Therefore, glycyrrhizin can serve as a safe and affordable complementary therapy for PP.

Soluble natural sweetener from date palm (Phoenix dactylifera L.) extract using colloidal gas aphrons generated with a food-grade non-ionic surfactant.

Date palm (Phoenix dactylifera L.) is the most commonly cultivated fruit tree in the Middle East and North Africa. Date fruits are an excellent source of nutrition due to their high sugar content and high levels of phenols, minerals, and antioxidants. This work aimed to prepare a soluble natural sweetener from date fruit extract using colloidal gas aprons (CGAs) generated with a food-grade non-ionic surfactant (Tween 20). Various process parameters, such as the flow rate of the CGAs, the volume of the feed, the temperature of the CGAs, and the feed solution, were varied to obtain the optimal parameters. In the foam phase, the maximum soluble sugar enrichment of 92% was obtained at a flow rate of 50 mL/min of CGA and a solution temperature of 23 °C. The formation of intermolecular hydrogen bonding between the glucose molecules and the surfactant Tween 20 was confirmed by molecular modeling studies. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05907-9.

Xylitol is prothrombotic and associated with cardiovascular risk.

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.

Aspartame carcinogenic potential revealed through network toxicology and molecular docking insights.

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

Effects of flavoring additives on feed intake, growth performance, temperament, and markers of immune function for newly received feedlot cattle.

Ninety Angus × Hereford steers (259.9 ±â€…36.18 kg body weight [BW]) were used in a 56-d experiment to assess the effects of flavoring additives on feed intake, and stress and immune response of newly received feedlot cattle. Steers were homogenously distributed by BW into six pens equipped with an individual feed intake monitoring system, and pen was randomly assigned to one of three treatments (15 heads per pen; 30 heads per treatment): a standard feedlot receiving diet (CT), or the same diet with a flavoring additive comprised of either sweeteners (Luctarom Feedlot, SW) or a mix of basic tastes (Luctarom Feedlot Mix, MX) at 1 kg/mT. Pens were equipped with a feed intake monitoring system, while BW, chute behavior, flight speed, blood and saliva samples were collected bi-weekly, and hair samples were collected at 4-wk intervals during the study. Data were analyzed using a mixed-effects model for a pen study using individual animal records with repeated measures. There was a treatment × week interaction (P < 0.01) where meal duration was greater in SW steers than MX and CT on week 3, and then CT on weeks 7 and 8. A trend for treatment × week interaction (P = 0.06) showed that the number of visits per day tended to be greater in SW than MX steers on weeks 4 and 5, and it tended to be greater in SW than MX and CT on week 5. The concentration of IL-6 was greater (P < 0.01) on days 1 and 28 than on day 14. The IgM concentration was greater (P < 0.01) on day 1 compared to days 14, 28, and 56. The concentration of haptoglobin was greater (P < 0.01) on 14 than days 28, 42, and 56, and it was greater (P < 0.01) on day 1 than days 42 and 56. The concentration of serum amyloid A was greater (P < 0.01) on day 1 compared to the rest of sampling days. Fibrinogen concentration was greater (P < 0.01) on day 1 compared to days 14 and 42. The neutrophil-to-lymphocyte ratio was greater (P < 0.01) on days 42 and 56 compared to days 1 and 28, and greater (P < 0.01) on day 14 compared to day 28. Hair and saliva cortisol concentrations were lower (P < 0.01) on day 56 compared to days 1 and 28, respectively. The use of flavoring additives, particularly when based on sweeteners (SW), caused some changes in the feeding pattern of newly received steers. These changes, however, were not consistent over the 56-d feeding period and were not accompanied by a change in growth performance, temperament, biomarkers of stress, inflammation, or immune function.

Feedlot-receiving calves are typically exposed to a series of stressful events, such as weaning, transportation, commingling, a change of environment, and illness, that have a negative impact on feed intake. The objective of this study was to assess the effects of feed flavors on feed intake, indicators of stress, and markers of the immune response for newly received feedlot cattle. Under the conditions of this study, the addition of flavoring agents showed some effects on the feeding pattern of newly arrived feedlot cattle, compatible with a positive hedonic response to the treatments. These effects, however, were limited to specific periods of time during the experiment and were not present when considering their performance over the whole 56-d feeding period. Furthermore, the addition of flavoring agents did not have a consistent effect on the concentration of inflammatory mediators, biomarkers of stress, or immune function. Future research should explore whether these or other flavoring agents, at different doses or used at different times, could cause biologically relevant effects to improve the resilience of calves during the feedlot receiving period.

Sugar substitutes on caries prevention in permanent teeth among children and adolescents: a systematic review and meta-analysis.

OBJECTIVES: This study aimed to systematically review the effect of sugar substitute consumption on caries prevention in permanent teeth among children and adolescents. DATA: Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) comparing the clinical effect of sugar substitutes (both high- and low-intensity sweeteners) in preventing caries in permanent teeth among children and adolescents aged 6-19 were included. SOURCES: A systematic search was conducted in three databases (PubMed, Web of Science and Embase) without any restrictions on publication year. STUDY SELECTION: The initial search found 1,859 items, and finally, 15 studies (11 RCTs and 4 CCTs) with a total of 6325 participants (age: 6-18 years) were included. The Cochrane risk-of-bias assessment tools were used for quality assessment. Most (80%, 12/15) were graded as having a 'moderate' or 'high' risk of bias. All trials investigated sugar alcohol, which is a low-intensity sweetener. Xylitol was the most commonly investigated (73.3%, 11/15), followed by sorbitol (46.7%, 7/15), and erythritol (13.3%, 2/15). Results of the meta-analysis showed that both xylitol (standardized mean difference [SMD]: -0.50, 95% confidence interval [CI] -0.85 to -0.16, P = 0.005) and sorbitol (SMD: -0.10, 95% CI: -0.19 to -0.01, P = 0.03) had a significant effect in preventing dental caries compared to no treatment/placebo. No clinical trials on high-intensity sweeteners such as aspartame and saccharin were found. CONCLUSION: The consumption of xylitol or sorbitol is potentially effective in preventing caries in permanent teeth among children and adolescents. No clinical evidence is available regarding the role of high-intensity sweeteners in caries prevention. CLINICAL SIGNIFICANCE: The use of xylitol or sorbitol as sugar substitutes has a beneficial effect in preventing dental caries among children and adolescents.