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.

Association between low-calorie sweetener consumption during pregnancy and child health: A systematic review and meta-analysis.

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.

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.

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.

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.

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).

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.

Acesulfame potassium upregulates PD-L1 in HCC cells by attenuating autophagic degradation.

Artificial sweeteners, which contain no or few calories, have been widely used in various foods and beverages, and are regarded as safe alternatives to sugar by the Food and Drug Administration. While several studies suggest that artificial sweeteners are not related to cancer development, some research has reported their potential association with the risk of cancers, including hepatocellular carcinoma (HCC). Here, we investigated whether acesulfame potassium (Ace K), a commonly used artificial sweetener, induces immune evasion of HCC cells by upregulating programmed death ligand-1 (PD-L1). Ace K elevated the protein levels of PD-L1 in HCC cells without increasing its mRNA levels. The upregulation of PD-L1 protein levels in HCC cells by Ace K was induced by attenuated autophagic degradation of PD-L1, which was mediated by the Ace K-stimulated ERK1/2-mTORC1 signaling pathway. Ace K-induced upregulation of PD-L1 attenuated T cell-mediated death of HCC cells, thereby promoting immune evasion of HCC cells. In summary, the present study suggests that Ace K promotes HCC progression by upregulating the PD-L1 protein level.

Patterns and Predictors of Low-Calorie Sweetener Consumption during Pregnancy: Findings from a National Survey.

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.

Effects of Low-Calorie Sweetener Restriction on Glycemic Variability and Cardiometabolic Health in Children with Type 1 Diabetes: Findings of a Pilot and Feasibility Study.

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.

Benchmarking the Persistence of Active Pharmaceutical Ingredients in River Systems.

Assessing the persistence of organic micropollutants from field data has been notoriously laborious, requiring extensive data including emissions and chemical properties, and the application of detailed mass-balance models, which often contain parameters that are impossible to measure. To overcome some of these obstacles, we developed the concept of persistence benchmarking for large rivers that receive numerous emissions and provide enough residence time to observe the dissipation of compounds. We estimated the dissipation rate constants of 41 compounds (mostly active pharmaceutical ingredients) from five measurement campaigns in the Rhine and Danube rivers using concentration rate profiles with respect to carbamazepine. Dissipation rates clearly distinguished between known fast- and slow-degrading compounds, and campaign-specific boundary conditions had an influence on a minor subset of compounds only. Benchmarking provided reasonable estimates on summer total system half-lives in the Rhine compared to previous laboratory experiments and a mass-balance modeling study. Consequently, benchmarking can be a straightforward persistence assessment method of continuously emitted organic micropollutants in large river systems, especially when it is supported by field monitoring campaigns of proper analytical quality and spatial resolution.

Aspartame Safety as a Food Sweetener and Related Health Hazards.

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.

Oral exposure to an acceptable daily intake dose of aspartame induced a delayed proinflammatory cytokine response in the cerebrospinal fluid of rats.

This study aimed to investigate the effect of exposure to aspartame (ASP) at safe levels on proinflammatory cytokines in the cerebrospinal fluid (CSF) of rats. Sprague Dawley rats were sacrificed after 1, 2, 4 or 8 week(s) of continuous exposure to ASP (40 mg/kg body weight). Serum, CSF and brain tissue samples were prepared, and the levels of the IL-1ß, IL-6 and TNF-α were analyzed by ELISA. In serum, the levels of all three cytokines showed a two-phase alteration, a decrease followed by an increase in the ASP group. In the brain, their levels increased from the second or fourth week compared with the control group. In CSF, the levels of these cytokines showed a similar change to that in brain tissue, but the increase appeared at a later time point. For each cytokine, there was a significant positive correlation between its levels in serum, brain tissue and CSF. This is the first discovery that ASP exposure increased the levels of proinflammatory cytokines in CSF in rats, which emerged later than in blood and brain tissue. This study suggests the necessity of conducting related clinical studies to evaluate potential neuroinflammatory effects induced by chronic ASP exposure through CSF analysis.

Long-Term Consumption of Sucralose Induces Hepatic Insulin Resistance through an Extracellular Signal-Regulated Kinase 1/2-Dependent Pathway.

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.

Maternal Intake of Either Fructose or the Artificial Sweetener Acesulfame-K Results in Differential and Sex-Specific Alterations in Markers of Skin Inflammation and Wound Healing Responsiveness in Mouse Offspring: A Pilot Study.

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.

Impact of Long-Term Cyclamate and Saccharin Consumption on Biochemical Parameters in Healthy Individuals and Type 2 Diabetes Mellitus Patients.

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.

Artificially Sweetened Beverages Beyond the Metabolic Risks: A Systematic Review of the Literature.

We carried out a review of the available literature on the effects that artificially sweetened beverages (ASBs) such as diet soda (DS) have on health, particularly those not related to incident diabetes mellitus, obesity, and metabolic syndrome. A search of scientific articles was carried out using 11 different databases: PubMed, Cochrane, LILACS, MEDLINE Ovid, JAMA Network, IBECS, Cumed, Scopus, SciELO, MEDLINE-EBSCO, and Taylor & Francis Online. Articles published in the last 10 years were considered, considering cross-sectional studies, retrospective or prospective cohort studies, case-control studies, and randomized controlled clinical trials. Only articles in Spanish or English were considered using the MeSH (Medical Subject Heading) and DeCS (Descriptores en Ciencias de la Salud) terms, including "Diet soda," "Health," "Artificial sweetener," "Gaseosa sin azúcar," "Refresco sin azúcar," and "Salud." Additionally, Boolean operators "AND" and "Y" were used. A total of 1,323 articles were obtained in the initial search, of which 21 main ones were selected for review, which included the topic of DS consumption and explored the health consequences that it poses on different organs. The question of whether ASBs such as DS are a preferred substitute is becoming more and more important in terms of public policy due to mounting evidence of the potential negative health effects of their excessive consumption. This systematic review, the first of its kind to our knowledge, sheds light on how excessive DS consumption can affect multiple organ systems, and associations have been made to mental health burden, delays in child neurodevelopment, cardiac remodeling, worsening retinopathy in diabetics, incidental end-stage renal disease, non-Hodgkin's lymphoma and multiple myeloma in men, rheumatoid arthritis in women, hip fractures, dental erosion, increases in breath alcohol concentration when used in alcoholic beverages, and accelerated cell aging. Further studies should delve further to understand the pathophysiologic mechanisms of these associations.

Occurrence, distribution, and ecological risk assessment of artificial sweeteners in surface and ground waters of the middle and lower reaches of the Yellow River (Henan section, China).

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.

Early-life influences of low-calorie sweetener consumption on sugar taste.

Children and adolescents are the highest consumers of added sugars, particularly from sugar-sweetened beverages (SSB). Regular consumption of SSB early in life induces a variety of negative consequences on health that can last into adulthood. Low-calorie sweeteners (LCS) are increasingly used as an alternative to added sugars because they provide a sweet sensation without adding calories to the diet. However, the long-term effects of early-life consumption of LCS are not well understood. Considering LCS engage at least one of the same taste receptors as sugars and potentially modulate cellular mechanisms of glucose transport and metabolism, it is especially important to understand how early-life LCS consumption impacts intake of and regulatory responses to caloric sugars. In our recent study, we found that habitual intake of LCS during the juvenile-adolescence period significantly changed how rats responded to sugar later in life. Here, we review evidence that LCS and sugars are sensed via common and distinct gustatory pathways, and then discuss the implications this has for shaping sugar-associated appetitive, consummatory, and physiological responses. Ultimately, the review highlights the diverse gaps in knowledge that will be necessary to fill to understand the consequences of regular LCS consumption during important phases of development.