Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance.

Non-nutritive sweeteners (NNS) are commonly integrated into human diet and presumed to be inert; however, animal studies suggest that they may impact the microbiome and downstream glycemic responses. We causally assessed NNS impacts in humans and their microbiomes in a randomized-controlled trial encompassing 120 healthy adults, administered saccharin, sucralose, aspartame, and stevia sachets for 2 weeks in doses lower than the acceptable daily intake, compared with controls receiving sachet-contained vehicle glucose or no supplement. As groups, each administered NNS distinctly altered stool and oral microbiome and plasma metabolome, whereas saccharin and sucralose significantly impaired glycemic responses. Importantly, gnotobiotic mice conventionalized with microbiomes from multiple top and bottom responders of each of the four NNS-supplemented groups featured glycemic responses largely reflecting those noted in respective human donors, which were preempted by distinct microbial signals, as exemplified by sucralose. Collectively, human NNS consumption may induce person-specific, microbiome-dependent glycemic alterations, necessitating future assessment of clinical implications.

Ingestion of the Non-Nutritive Sweetener Erythritol, but Not Glucose, Enhances Platelet Reactivity and Thrombosis Potential in Healthy Volunteers-Brief Report.

BACKGROUND: Although artificial and non-nutritive sweeteners are widely used and generally recognized as safe by the US and European Union regulatory agencies, there have been no clinical trials to assess either long-term cardiovascular disease risks or short-term cardiovascular disease-relevant phenotypes. Recent studies report that fasting plasma levels of erythritol, a commonly used sweetener, are clinically associated with heightened incident cardiovascular disease risks and enhance thrombosis potential in vitro and in animal models. Effects of dietary erythritol on thrombosis phenotypes in humans have not been examined. METHODS: Using a prospective interventional study design, we tested the impact of erythritol or glucose consumption on multiple indices of stimulus-dependent platelet responsiveness in healthy volunteers (n=10 per group). Erythritol plasma levels were quantified with liquid chromatography tandem mass spectrometry. Platelet function at baseline and following erythritol or glucose ingestion was assessed via both aggregometry and analysis of granule markers released. RESULTS: Dietary erythritol (30 g), but not glucose (30 g), lead to a >1000-fold increase in erythritol plasma concentration (6480 [5930-7300] versus 3.75 [3.35-3.87] µmol/L; P<0.0001) and exhibited acute enhancement of stimulus-dependent aggregation responses in all subjects, agonists, and doses examined. Erythritol ingestion also enhanced stimulus-dependent release of the platelet dense granule marker serotonin (P<0.0001 for TRAP6 [thrombin activator peptide 6] and P=0.004 for ADP) and the platelet α-granule marker CXCL4 (C-X-C motif ligand-4; P<0.0001 for TRAP6 and P=0.06 for ADP). In contrast, glucose ingestion triggered no significant increases in stimulus-dependent release of either serotonin or CXCL4. CONCLUSIONS: Ingestion of a typical quantity of the non-nutritive sweetener erythritol, but not glucose, enhances platelet reactivity in healthy volunteers, raising concerns that erythritol consumption may enhance thrombosis potential. Combined with recent large-scale clinical observational studies and mechanistic cell-based and animal model studies, the present findings suggest that discussion of whether erythritol should be reevaluated as a food additive with the Generally Recognized as Safe designation is warranted. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04731363.

Comparison of a Daily Steviol Glycoside Beverage compared with a Sucrose Beverage for Four Weeks on Gut Microbiome in Healthy Adults.

BACKGROUND: Recent studies suggest that some nonnutritive sweeteners (NNS) have deleterious effects on the human gut microbiome (HGM). The effect of steviol glycosides on the HGM has not been well studied. OBJECTIVE: We aimed to evaluate the effects of stevia- compared with sucrose-sweetened beverages on the HGM and fecal short-chain fatty acid (SCFA) profiles. METHODS: Using a randomized, double-blinded, parallel-design study, n = 59 healthy adults [female/male, n = 36/23, aged 31±9 y, body mass index (BMI): 22.6±1.7 kg/m2] consumed 16 oz of a beverage containing either 25% of the acceptable daily intake (ADI) of stevia or 30 g of sucrose daily for 4 weeks followed by a 4-week washout. At weeks 0 (baseline), 4, and 8, the HGM was characterized via shotgun sequencing, fecal SCFA concentrations were measured using ultra-high performance liquid chromatography-tandem mass spectrometry and anthropometric measurements, fasting serum glucose, insulin and lipids, blood pressure, pulse, and 3-d diet records were obtained. RESULTS: There were no significant differences in the HGM or fecal SCFA between the stevia and sucrose groups at baseline (P > 0.05). At week 4 (after intervention), there were no significant differences in the HGM at the phylum, family, genus, or species level between the stevia and sucrose groups and no significant differences in fecal SCFA. At week 4, BMI had increased by 0.3 kg/m2 (P = 0.013) in sucrose compared with stevia, but all other anthropometric and cardiometabolic measures and food intake did not differ significantly (P > 0.05). At week 8 (after washout), there were no significant differences in the HGM, fecal SFCA, or any anthropometric or cardiometabolic measure between the stevia and sucrose groups (P > 0.05). CONCLUSIONS: Daily consumption of a beverage sweetened with 25% of the ADI of stevia for 4 weeks had no significant effects on the HGM, fecal SCFA, or fasting cardiometabolic measures, compared with daily consumption of a beverage sweetened with 30 g of sucrose. TRIAL REGISTRATION: clinicaltrials.gov as NCT05264636.

Use of table sugar and non-caloric sweeteners in Brazil: associated factors and changes across a decade.

This study evaluated changes in the use of sweeteners over one decade and the relationship between socio-demographics, diet and weight status with the type of sweetener. Data came from the Brazilian National Dietary Surveys of 2008-2009 and 2017-2018, including ≥ 10-year-old individuals (n 32 749; n 44 744, respectively, after excluding pregnant and lactating women). The use of table sugar, non-caloric sweeteners (NCS), both or none was reported through a specific question. Food consumption was assessed using two non-consecutive food records (2008-2009) and 24-h recalls (2017-2018). For the last survey, means of energy, macro and micronutrient intake, food groups' contribution (%) to daily energy intake and age- and energy-adjusted nutrient intake were estimated according to the type of sweetener used. Differences in means and proportions across the categories of sweeteners used were evaluated based on the 95 % CI. All analyses were stratified by sex and considered sample design and weights. Over 10 years, the use of table sugar decreased by 8 %, while the habit of not using any sweetener increased almost three times, and the use of NCS remained stable. Larger reductions in the use of table sugar were observed in the highest income level and among men. Regardless of sex, compared with NCS users, table sugar users had greater mean intake of energy, carbohydrates and added sugar and lower micronutrient intake means. Although table sugar is still the most used sweetener, the increased choice of 'no sweetener' is noteworthy in Brazil.

Assessing the impact of non-nutritive sweeteners on anthropometric indices and leptin levels in adults: A GRADE-assessed systematic review, meta-analysis, and meta-regression of randomized clinical trials.

In today's world, non-nutritive sweeteners (NNSs) are recognized as substitutes for sugar or other high-calorie sweeteners, and their consumption is increasing dramatically. However, there is ongoing debate regarding the impact of NNSs on anthropometric indices. To fill this gap in knowledge, the current GRADE-assessed systematic review and meta-analysis of randomized controlled trials (RCTs) was conducted to evaluate the effects of artificial- and stevia-based sweeteners consumption on anthropometric indices and serum leptin level which is known as an appetite-regulating hormone. A comprehensive search was conducted on the Scopus, PubMed, and Embase databases up to November 2022 to identify randomized controlled trials (RCTs) investigating the effects of NNSs on anthropometric indices and serum leptin levels. Data extraction from qualified studies was performed independently by two researchers. A random- or fixed-effects model was used to estimate weighted mean differences (WMDs) and 95% confidence intervals (CIs) for anthropometric indices such as body weight (BW), body mass index (BMI), fat mass (FM), fat-free mass (FFM), waist circumference (WC) and serum leptin level. Heterogeneity between studies was assessed using Cochran's Q test and quantified using the I2 statistic. From a pool of 3212 studies initially identified, 20 studies with a total sample size of 2158 subjects were included in the analysis. Results of the pooled analysis showed that NNSs consumption had a significant reducing effect on BW (WMD: -1.02, 95% CI: -1.57, -0.46 Kg), FM (WMD: -1.09, 95% CI: -1.90, -0.29), and FFM (WMD: -0.83, 95% CI: -1.42, -0.23), but did not have any significant effect on BMI (WMD: -0.16, 95% CI: -0.35, 0.02), WC (WMD: -1.03, 95% CI: -2.77, 0.72), or serum leptin level (WMD: -2.17, 95% CI: -4.98, 0.65). The findings of this study indicate that the consumption of artificial- and stevia-based sweeteners may lead to a reduction in body weight, fat mass, and free fat mass.

The effects of artificial- and stevia-based sweeteners on lipid profile in adults: a GRADE-assessed systematic review, meta-analysis, and meta-regression of randomized clinical trials.

It has been posited that Non-nutritive sweeteners (NNS) intake may affect lipid profile. However, its proven effects on lipid profile are unclear, as clinical studies on this topic have produced inconsistent results. To fill this gap in knowledge, this systematic review and meta-analysis of randomized controlled trials (RCTs) sought to evaluate the effects of artificial- and stevia-based sweeteners consumption on lipid profile markers. To identify eligible RCTs, a systematic search up to April 2021 was completed in PubMed/Medline, Scopus, and EMBASE, using relevant keywords. A random-effect model was utilized to estimate the weighted mean difference (WMD) and 95% confidence (95% CI) for TG, TC, and LDL. On the other hand, a fixed-effect model was used to estimate the WMD and 95% CI for HDL. Fourteen RCTs were included in the present meta-analysis. The pooled analysis revealed that NNS did not affect TG (WMD:-1.31, 95% CI:-5.89, 3.27 mg/dl), TC (WMD:-2.27,95% CI:-7.61,3.07 mg/dl), LDL (WMD:1,95% CI: -2.72, 4.71 mg/dl), and HDL (WMD:0.06, 95% CI:-0.62,0.73 mg/dl). Subgroup analysis showed that NNS may be related to a small, but statistically significant, increase in LDL (WMD:4.23, 95% CI:0.50,7.96 mg/dl) in subjects with normal levels of LDL (<100 mg/dl). We found that consumption of artificial- and stevia-based sweeteners is not associated with lipid profile changes in adults. This study has been registered at PROSPERO (registration number: CRD42021250025).

Nutritive/non-nutritive sweeteners and high fat diet contribute to dysregulation of sweet taste receptors and metabolic derangements in oral, intestinal and central nervous tissues.

OBJECTIVES: Overconsumption of non-nutritive sweeteners is associated with obesity, whereas the underlying mechanisms remain controversial. This study aimed to investigate the effects of long-term consumption of nutritive or non-nutritive sweeteners with or without high fat diet on sweet taste receptor expression in nutrient-sensing tissues and energy regulation dependent on sweet-sensing. METHODS: 50 Male Sprague-Dawley rats (140-160 g) were assigned to 10 groups (n = 5/group). All received fructose at 2.5% or 10%, sucralose at 0.01% or 0.015% or water with a normal chow diet or high fat diet for 12 weeks. Food and drink intake were monitored daily. Oral glucose tolerance test and intraperitoneal glucose tolerance test were performed at week 10 and 11 respectively. Serum was obtained for measurement of biochemical parameters. Tongue, duodenum, jejunum, ileum, colon and hypothalamus were rapidly removed to assess gene expression. RESULTS: Long-term consumption of sweeteners impaired glucose tolerance, increased calorie intake and body weight. A significant upregulation of sweet taste receptor expression was observed in all the four intestinal segments in groups fed 0.01% sucralose or 0.015% sucralose, most strikingly in the ileum, accompanied by elevated serum glucagon-like peptide-1 levels and up-regulated expression of sodium-dependent glucose cotransporter 1 and glucose transporter 2. A significant down-regulation in the tongue and hypothalamus was observed in groups fed 10% fructose or 0.015% sucralose, with alterations in hypothalamic appetite signals. The presence of high fat diet differentially modulates sweet taste perception in nutrient-sensing tissues. CONCLUSIONS: Long-term consumption of whether nutritive sweeteners or non-nutritive sweeteners combined with high fat diet contribute to dysregulation of sweet taste receptor expression in oral, intestinal and central nervous tissues.

Association of sweetened beverages consumption with all-cause mortality risk among Dutch adults: the Lifelines Cohort Study (the SWEET project).

PURPOSE: Examined associations between sugar-sweetened beverages (SSB), low/no-calorie beverages (LNCB), and fruit juice (FJ) consumption and all-cause mortality in Dutch adults. METHODS: Data of 118,707 adults participating (mean age = 45 years; 60% was women) the Lifelines Cohort Study were prospectively analyzed. Dietary intake was assessed using a validated food-frequency questionnaire. Participants' vital status was followed-up until February 2022 via the National Personal Records Database. Associations between beverages of interest and all-cause mortality risk were investigated using restricted cubic spline and Cox proportional hazard regression analyses, including substitution analyses. Models were adjusted for demographics, lifestyle, and other dietary factors. RESULTS: During follow-up (median = 9.8 years), a total of 2852 (2.4%) deaths were documented. Median (IQR) of SSB, LNCB, and FJ consumption were 0.1 (0.0-0.6), 0.1 (0.0-0.6), and 0.2 (0.0-0.6) serving/day, respectively. Dose-response analyses showed linear associations between SSB, LNCB, and FJ consumption and mortality risk. For each additional serving of SSB and LNCB, HRs of all-cause mortality risk were 1.09 (95% CI 1.03-1.16) and 1.06 (95% CI 1.00-1.11). Replacing SSB with LNCB showed a nonsignificant association with a lower mortality risk, particularly in women (HR 0.91, 95% CI 0.81-1.01). Finally, an inverse association between FJ and all-cause mortality was observed at moderate consumption with HR of 0.87 (95% CI 0.79-0.95) for > 0-2 servings/week and HR of 0.89 (95% CI 0.81-0.98) for > 2-< 7 servings/week when compared to no consumption. CONCLUSIONS: Our study showed adverse associations between SSB consumption and all-cause mortality. Replacing SSB with LNCB might be associated with lower mortality risk, particularly in women. Moderate intake of FJ was associated with lower all-cause mortality risk.

Sugar and low/no-calorie-sweetened beverage consumption and associations with body weight and waist circumference changes in five European cohort studies: the SWEET project.

PURPOSE: Results of prospective studies investigating associations between low/no-calorie sweeteners (LNCS) and body weight-related outcomes are inconclusive. We conducted dose-response and theoretical replacement individual patient data meta-analyses using harmonised prospective data to evaluate associations between sugar-sweetened beverage (SSB) consumption, low/no-calorie sweetened beverage (LNCB) consumption, and changes in body weight and waist circumference. METHODS: Individual participant data were obtained from five European studies, i.e., Lifelines Cohort Study, NQplus study, Alpha Omega Cohort, Predimed-Plus study, and Feel4diabetes study, including 82,719 adults aged 18-89 with follow-up between 1 and 9 years. Consumption of SSB and LNCB was assessed using food-frequency questionnaires. Multiple regression analyses adjusting for major confounders and including substitution models were conducted to quantify associations in individual cohorts; random-effects meta-analyses were performed to pool individual estimates. RESULTS: Overall, pooled results showed weak adverse associations between SSB consumption and changes in body weight (+ 0.02 kg/y, 95%CI 0.00; 0.04) and waist circumference (+ 0.03 cm/y, 95%CI 0.01; 0.05). LNCB consumption was associated with higher weight gain (+ 0.06 kg/y, 95%CI 0.04; 0.08) but not with waist circumference. No clear associations were observed for any theoretical replacements, i.e., LNCB or water for SSB or water for LNCB. CONCLUSION: In conclusion, this analysis of five European studies found a weak positive association between SSB consumption and weight and waist change, whilst LNCB consumption was associated with weight change only. Theoretical substitutions did not show any clear association. Thus, the benefit of LNCBs as an alternative to SSBs remains unclear.

Global trends in added sugars and non-nutritive sweetener use in the packaged food supply: drivers and implications for public health.

OBJECTIVE: The health implications of excessive added sugar intakes have led to national policy actions to limit their consumption. Subsequently, non-nutritive sweeteners (NNS) may be used to maintain product sweetness. We aimed to assess trends in quantities of added sugars and NNS sold in packaged food and beverages worldwide, and the association between these trends and the number of national policy actions across regions to reduce added sugar consumption. DESIGN: (i) Longitudinal analysis of Euromonitor sales data (2007-2019) to assess the quantity of added sugars (kg) and NNS (g) sold in packaged foods and beverages globally, across regions, and across country income categories; (ii) policy-mapping of policy actions targeting added sugar consumption globally from the NOURISHING database; and (iii) Spearman's correlations to assess the association between national policy actions across regions and changes in added sugar/NNS sales. SETTING: Worldwide. PARTICIPANTS: Not applicable. RESULTS: Per capita volumes of NNS from beverage sales increased globally (36 %). Added sugars from beverage sales decreased in high-income countries (22 %) but increased in upper-middle-income countries (UMIC) and lower-middle-income countries (LMIC) (13-40 %). Added sugars from packaged food sales increased globally (9 %). Regions with more policy actions had a significant increase in NNS quantities from beverage sales (r = 0·68, P = 0·04). The sweetness of the packaged food supply (the sweetness of each NNS and added sugar, relative to sucrose, multiplied by sales volume) increased over time. CONCLUSIONS: The increasing use of NNS to sweeten beverages globally, and in packaged food in UMIC and LMIC, may have health and dietary implications in the future. Their use as a substitute for added sugar should be considered in public health nutrition policymaking.

Non-nutritive sweetener regulation and health: analysing applications to vary Australian and New Zealand food standards.

We aimed to understand the process of setting or varying food standards related to non-nutritive sweeteners (NNS) in Australia and New Zealand. Overconsumption of added sugars is a risk factor for non-communicable diseases. Limiting added sugar consumption is recommended by the World Health Organization. NNS are sweet substances with little to no energy that can be used to maintain the sweetness of packaged food when added sugar is reduced. The health and dietary pattern impacts of NNS are contested. Understanding how and why applications for NNS are submitted, assessed and approved within food regulatory systems is important to contextualize the increasing availability of NNS in the food supply. We completed an interpretive content analysis of applications to change the Food Standards Australia and New Zealand (FSANZ) Code, risk assessments and stakeholder submissions. Literature used in risk assessments were drawn from a mixture of documents supplied by industry and peer-reviewed studies. Risk assessments were primarily focussed on toxicological outcomes, while broader public health outcomes were not explicitly considered. Consumption data available to FSANZ were collected several years prior to dietary exposure assessments, and thus may not accurately represent current intakes. The study findings raise questions about whether the scope of what constitutes a 'risk' to public health in the setting of food standards needs to extend beyond immediate toxicological and food safety concerns, to include longer-term dietary balance considerations.

Is the increment of diabetes mellitus in Brazil associated with the consumption of artificially sweetened beverages? A time trend analysis with 757,386 adults from 2006 to 2020.

OBJECTIVE: To describe trends in the prevalence of diabetes mellitus (DM) in Brazil and to analyze its association with the consumption of artificially sweetened beverages among individuals aged 18 years or older. STUDY DESIGN: This was a repeated cross-sectional study. METHODS: Annual data from VIGITEL surveys (2006-2020) were used, which included adults from all Brazilian state capitals. The outcome was the prevalence of DM (type 1 and type 2). The main exposure variable was consuming beverages like soft drinks and artificial juices, either in its 'diet, light, or zero' form. Covariates included sex, age, sociodemographic characteristics, smoking, alcohol consumption, physical activity, fruit consumption, and obesity. The temporal trend in the indicators and the etiological fraction (population attributable risk [PAR]) were calculated. Analyses were performed using Poisson regression. The association between DM and consumption of beverages was tested, excluding the year 2020 due to the pandemic; restricting the analysis to the final three years (2018-2020). RESULTS: Overall, 757,386 subjects were included. The prevalence of DM increased from 5.5% to 8.2%, with an annual growth of 0.17 percentage points (95% CI 0.11-0.24). Among those who consumed diet/light/zero beverages, the annual percentage change of DM was four times greater. The PAR corresponding to the consumption of diet/light/zero beverages on the occurrence of DM was 17%. CONCLUSIONS: An increasing prevalence of DM was observed, while diet/light/zero beverages consumption remains stable. A substantial reduction in the annual percentage change of DM could be observed if people stopped consuming diet/light soda/juice.

Intake of Artificial Sweeteners by Children: Boon or Bane?

BACKGROUND: Sugar is the main culprit in many health dysfunctions. Excessive sugar intake can negatively affect oral health, precipitate diabetes, and lead to weight gain and obesity. Sucrose is the primary form of sugar, and is strongly correlated with dental caries. Artificial sweeteners are chemically synthesized sugar substitutes that are generally regarded as being low-calorie. OBJECTIVE: This review examines the current evidence in the literature for the need for artificial sweeteners and outlines its implications for the health of children. We briefly outline its adverse effects, and concerns regarding their safety. REVIEW RESULTS: Artificial sweeteners are a widely used food additive. Six main artificial sweeteners are approved by the food and drug administration (FDA). The conflicting results and divergent regulatory norms of each sweetener are a constant cause of concern and debate. However, most studies have spotlighted the beneficial effects of artificial sweeteners. Dental caries diminish with the increase in sweetener intake. An increase in appetite and eventually weight gain is observed in individuals consuming artificial sweeteners. CONCLUSION: Artificial sweeteners are indeed a bane according to present studies, although more research on recently discovered non-nutritive artificial sweeteners is required. It also has a positive effect on overall health disorders. If one curbs the onset of dental caries, then the eventual rise is highly unlikely. CLINICAL SIGNIFICANCE: Artificial sweeteners' effect on lowering dental caries will help to reduce the caries index in general. Oral hygiene is maintained, and the growth of oral bacterium is depressed. Research on novel sweeteners will help to compare their efficacy in caries prevention compared to existing ones. It is necessary to educate people on artificial sweeteners and its implication as one can use them by being aware of their properties.

Long-term intake of aspartame-induced cardiovascular toxicity is reflected in altered histochemical parameters, evokes oxidative stress, and trigger P53-dependent apoptosis in a mouse model.

Aspartame (ASP) is probably the best known artificial sugar substitute that is used widely in food. Many experimental studies have reported the toxicity of long-term administration of ASP in various organ tissues. However, there is little evidence available about the nature and mechanisms of the adverse effects of long-term consumption of ASP on the cardiovascular system. This study was conducted to evaluate the possible effects of ASP on heart tissue. For this study 36 mature male mice were divided into one control group and three groups which received respectively 40 mg/kg, 80 mg/kg and 160 mg/kg ASP orally, for 90 days. ASP at the doses of 80 and 160 mg/kg increased the serum content of malondialdehyde (MDA), but decreased serum nitric oxide (NO), creatine kinase (CK) and CK-MB, as well as blood superoxide dismutase (SOD) levels. Serum level of total anti-oxidant capacity (TAC) in blood was also reduced in serum at the dose of 80 mg/kg. Histochemical staining, including Periodic acid-Schiff, Masson's trichrome and Verhoeff-van Gieson staining, indicated that ASP at doses of 80 and 160 mg/kg reduced glycogen deposition and decreased the number of collagen and elastic fibres in the cardiac tissue. The cardiac expression of pro-apoptotic genes, including P53, Bax, Bcl-2 and Caspase-3, was modulated at the dose of 160 mg/kg. Moreover, transcription of Caspase-3 was up-regulated at the dose of 80 mg/kg. In conclusion, long-term consumption of ASP any higher than the acceptable daily intake (40 mg/kg) appears to act by promoting oxidative stress, has the potential to alter both histopathological and biochemical parameters, and induces P53-dependent apoptosis in cardiac tissue.

The impact of nutritive and non-nutritive sweeteners on the central nervous system: preliminary study.

BACKGROUND: Human consumption of food and beverages containing added nutritive or non-nutritive sweeteners has increased worldwide. OBJECTIVE: The present study evaluated the possible impact of frequent sweetener consumption on human CNS activity and functions through neuropsychological testing and EEG/qEEG analysis. METHODS: A sample of 23 women and 16 men, aged 18-35, with a body mass index between 18 and 24.9 kg/m2 was evaluated. Participants underwent a 1-week washout period in which food with added sugars or sweeteners was restricted from their diet. Initial assessment of cognitive functions was performed with a validated neuropsychological test and EEG/qEEG analysis, prior to supplementation. Sucrose, sucralose, or steviol glycosides, in commercially available presentations, were randomly assigned to three experimental groups of 13 participants each. Sweeteners were supplemented in fixed amounts, daily, for six weeks. After supplementation, neurological tests were repeated and the initial and final results were compared. RESULTS: The results show no significant changes between final and initial measures in the steviol glycosides group. However, a significant decrease in encoding memory was found in the sucrose group in the final evaluation. Strikingly, the sucralose group showed a significant decrease in overall memory, encoding memory, and executive functions after supplementation. Furthermore, qEEG analysis showed an increase in theta wave absolute and relative power at the final evaluation in the same group. CONCLUSION: These data show that frequent consumption of specific sweeteners is accompanied by measurable changes in EEG/qEEG activity and neuropsychological test performance in humans.

What are the benefits and risks of nutrition policy actions to reduce added sugar consumption? An Australian case study.

OBJECTIVE: This study aimed to critically analyse Australia's current and proposed policy actions to reduce added sugar consumption. Over-consumption of added sugar is a significant public health nutrition issue. The competing interests, values and beliefs among stakeholders mean they have disparate views regarding which policy actions are preferable to reduce added sugar consumption. DESIGN: Semi-structured interviews using purposive, snowball sampling and policy mapping. Policy actions were classified by two frameworks: NOURISHING (e.g. behaviour change communication, food environment and food system) and the Orders of Change (e.g. first order: technical adjustments, second order: reforming the system, third order: transforming the system). SETTING: Australia. PARTICIPANTS: Twenty-two stakeholders from the food industry, food regulation, government, public health groups and academia. RESULTS: All proposed and existing policy actions targeted the food environment/behaviour change; most were assessed as first-order changes, and reductionist (nutrient specific) in nature. Influences on policy actions included industry power, stakeholder fragmentation, government ideology/political will and public pressure. Few stakeholders considered potential risks of policy actions, particularly of non-nutritive sweetener substitution or opportunity costs for other policies. CONCLUSIONS: Most of Australia's policy actions to reduce added sugar consumption are reductionist. Preferencing nutrient specific, first-order policy actions could reflect the influence of vested interests, a historically dominant reductionist orientation to nutrition science and policy, and the perceived difficulty of pursuing second- or third-order changes. Pursuing only first-order policy actions could lead to 'regrettable' substitutions and creates an opportunity cost for more comprehensive policy aimed at adjusting the broader food system.

Non-nutritive sweetener activation of the pig sweet taste receptor T1R2-T1R3 in vitro mirrors sweetener stimulation of the gut-expressed receptor in vivo.

The perception of sweet is mediated by the sweet taste receptor T1R2-T1R3 expressed in taste cells of the lingual epithelium. This receptor is also expressed in intestinal enteroendocrine cells and is required for sensing luminal sugars and sweeteners to regulate expression of intestinal Na+-glucose cotransporter 1 (SGLT1). There are some notable differences amongst species in the ability to detect certain non-nutritive (artificial) sweeteners. Amino acid substitutions and pseudogenization of taste receptor genes are responsible for these disparities. Using heterologous expression, we demonstrate that the commonly used non-nutritive sweeteners sucralose, saccharin and acesulfame K activate pig T1R2-T1R3, but that aspartame and cyclamate do not. Furthermore, we show that in vitro sweetener activation of pig T1R2-T1R3 mirrors the sweetener stimulation of the gut-expressed receptor in vivo. Considering that sweeteners are included in animal feed worldwide, determination of taste receptor specificities in different species is essential for the development of scientifically-based dietary formulations.

Consumption of Non-nutritive Sweeteners and Risk for Type 2 Diabetes: What Do We Know, and Not?

PURPOSE OF REVIEW: The article explores the relationship between non-nutritive sweetener consumption and the risk of developing type 2 diabetes through reviewing meta-analyses and systematic reviews, as well as clinical trials and observational studies. RECENT FINDINGS: The data overall has yet to show a strong and clear link between consumption of non-nutritive sweeteners and the development of type 2 diabetes. However, several observational studies have shown a positive relationship between these two variables, with a stronger association found among women. Regarding non-nutritive sweeteners that are currently commercially available, there is not one specific non-nutritive sweetener that appears to be more strongly associated with the development of type 2 diabetes than other non-nutritive sweeteners. There is still much to be learned regarding non-nutritive sweeteners and their potential link to metabolic disorders. Further research is needed to identify the long-term impacts of non-nutritive sweetener consumption and identify the nuances in terms of risk of developing type 2 diabetes concerning specific non-nutritive sweeteners.

Sucralose can improve glucose tolerance and upregulate expression of sweet taste receptors and glucose transporters in an obese rat model.

OBJECTIVES: Non-nutritive sweeteners (NNS) are widely used as replacements for table sugar in beverages and dessert. However, the metabolic effects of NNS remain controversial. This study aimed to investigate the effects of various sucralose loads on glucose metabolism and expression of sweet taste receptors (STR) and glucose transporters in a high-fat diet (HFD) rats. METHODS: Four-week-old male Sprague Dawley rats were fed a HFD for 8 weeks, then randomly divided into eight groups (6 in each group). All were gavaged with either saline, sucralose (0.54 mM or 0.78 mM), or sucrose (324 mM) with/without gurmarin, a sweet taste inhibitor, for 4 weeks, followed by an intragastric glucose tolerance test (IGGTT) with blood glucose, and plasma insulin, GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) measurements. In the following week, the rats were sacrificed and the small intestine was removed for measurement of sweet taste receptor and glucose transporter expression by quantitative Reverse Transcription-Polymerase Chain Reaction. RESULTS: In HFD rats, blood glucose levels were decreased at 30, 60, and 120 min during the IGGTT after 4 weeks supplementation with 0.78 mM sucralose. TIR3 expression was increased in the duodenum and TIR2 was increased in the ileum after 324 mM sucrose supplementation. T1R3 expression was increased after 0.54 mM and 0.78 mM sucralose in the ileum, but there was no change in the expression of TIRs in the duodenum after sucralose treatments. SGLT-1 expression was increased after both 0.78 mM sucralose and 324 mM sucrose in the ileum, and only increased in the duodenum after 324 mM sucrose supplementation. CONCLUSIONS: The effects of sucralose on glucose metabolism in HFD rats are dose-dependent and related to enhanced expression of sweet taste receptors and glucose transporters. Further studies are needed to clarify the molecular mechanisms involved.

Brain activity and connectivity changes in response to nutritive natural sugars, non-nutritive natural sugar replacements and artificial sweeteners.

INTRODUCTION: The brain plays an important regulatory role in directing energy homeostasis and eating behavior. The increased ingestion of sugars and sweeteners over the last decades makes investigating the effects of these substances on the regulatory function of the brain of particular interest. We investigated whole brain functional response to the ingestion of nutrient shakes sweetened with either the nutritive natural sugars glucose and fructose, the low- nutritive natural sugar replacement allulose or the non-nutritive artificial sweetener sucralose. METHODS: Twenty healthy, normal weight, adult males underwent functional MRI on four separate visits. In a double-blind randomized study setup, participants received shakes sweetened with glucose, fructose, allulose or sucralose. Resting state functional MRI was performed before and after ingestion. Changes in Blood Oxygen Level Dependent (BOLD) signal, functional network connectivity and voxel based connectivity by Eigenvector Centrality Mapping (ECM) were measured. RESULTS: Glucose and fructose led to significant decreased BOLD signal in the cingulate cortex, insula and the basal ganglia. Glucose led to a significant increase in eigen vector centrality throughout the brain and a significant decrease in eigen vector centrality in the midbrain. Sucralose and allulose had no effect on BOLD signal or network connectivity but sucralose did lead to a significant increase in eigen vector centrality values in the cingulate cortex, central gyri and temporal lobe. DISCUSSION: Taken together our findings show that even in a shake containing fat and protein, the type of sweetener can affect brain responses and might thus affect reward and satiety responses and feeding behavior. The sweet taste without the corresponding energy content of the non-nutritive sweeteners appeared to have only small effects on the brain. Indicating that the while ingestion of nutritive sugars could have a strong effect on feeding behavior, both in a satiety aspect as well as rewarding aspects, non-nutritive sweeteners appear to not have these effects. TRIAL REGISTRATION: This study is registered at clinicaltrials.gov under number NCT02745730.