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.

Long-term metabolic effects of non-nutritive sweeteners.

OBJECTIVE: Excessive consumption of added sugars has been linked to the rise in obesity and associated metabolic abnormalities. Non-nutritive sweeteners (NNSs) offer a potential solution to reduce sugar intake, yet their metabolic safety remains debated. This study aimed to systematically assess the long-term metabolic effects of commonly used NNSs under both normal and obesogenic conditions. METHODS: To ensure consistent sweetness level and controlling for the acceptable daily intake (ADI), eight weeks old C57BL/6 male mice were administered with acesulfame K (ace K, 535.25 mg/L), aspartame (411.75 mg/L), sucralose (179.5 mg/L), saccharin (80 mg/L), or steviol glycoside (Reb M, 536.25 mg/L) in the drinking water, on the background of either regular or high-fat diets (in high fat diet 60% of calories from fat). Water or fructose-sweetened water (82.3.gr/L), were used as controls. Anthropometric and metabolic parameters, as well as microbiome composition, were analyzed following 20-weeks of exposure. RESULTS: Under a regular chow diet, chronic NNS consumption did not significantly affect body weight, fat mass, or glucose metabolism as compared to water consumption, with aspartame demonstrating decreased glucose tolerance. In diet-induced obesity, NNS exposure did not increase body weight or alter food intake. Exposure to sucralose and Reb M led to improved insulin sensitivity and decreased weight gain. Reb M specifically was associated with increased prevalence of colonic Lachnospiracea bacteria. CONCLUSIONS: Long-term consumption of commonly used NNSs does not induce adverse metabolic effects, with Reb M demonstrating a mild improvement in metabolic abnormalities. These findings provide valuable insights into the metabolic impact of different NNSs, aiding in the development of strategies to combat obesity and related metabolic disorders.

Could Insulin Be a Better Regulator of Appetite/Satiety Balance and Body Weight Maintenance in Response to Glucose Exposure Compared to Sucrose Substitutes? Unraveling Current Knowledge and Searching for More Appropriate Choices.

BACKGROUND: Insulin exerts a crucial impact on glucose control, cellular growing, function, and metabolism. It is partially modulated by nutrients, especially as a response to the intake of foods, including carbohydrates. Moreover, insulin can exert an anorexigenic effect when inserted into the hypothalamus of the brain, in which a complex network of an appetite/hunger control system occurs. The current literature review aims at thoroughly summarizing and scrutinizing whether insulin release in response to glucose exposure may be a better choice to control body weight gain and related diseases compared to the use of sucrose substitutes (SSs) in combination with a long-term, well-balanced diet. METHODS: This is a comprehensive literature review, which was performed through searching in-depth for the most accurate scientific databases and applying effective and relevant keywords. RESULTS: The insulin action can be inserted into the hypothalamic orexigenic/anorexigenic complex system, activating several anorexigenic peptides, increasing the hedonic aspect of food intake, and effectively controlling the human body weight. In contrast, SSs appear not to affect the orexigenic/anorexigenic complex system, resulting in more cases of uncontrolled body weight maintenance while also increasing the risk of developing related diseases. CONCLUSIONS: Most evidence, mainly derived from in vitro and in vivo animal studies, has reinforced the insulin anorexigenic action in the hypothalamus of the brain. Simultaneously, most available clinical studies showed that SSs during a well-balanced diet either maintain or even increase body weight, which may indirectly be ascribed to the fact that they cannot cover the hedonic aspect of food intake. However, there is a strong demand for long-term longitudinal surveys to effectively specify the impact of SSs on human metabolic health.

Sucralose and stevia consumption leads to intergenerational alterations in body weight and intestinal expression of histone deacetylase 3.

OBJECTIVES: It is unclear whether parental consumption of non-nutritive sweetener (NNS) can affect subsequent generations. The aim of this study was to determine whether chronic parental consumption of sucralose and stevia in mice affects body weight gain and liver and intestinal expression of histone deacetylase 3 (Hdac3) in these animals and in the subsequent first filial (F1) and second filial (F2) generations. METHODS: Male and female mice (n = 47) were divided into three groups to receive water alone or supplemented with sucralose (0.1 mg/mL) or stevia (0.1 mg/mL) for 16 wk (parental [F0] generation). F0 mice were bred to produce the F1 generation; then, F1 mice were bred to produce the F2 generation. F1 and F2 animals did not receive NNSs. After euthanasia, hepatic and intestinal expression of Hdac3 was determined by quantitative reverse transcription polymerase chain reaction. RESULTS: Body weight gain did not differ between the three groups in the F0 generation, but it was greater in the F1 sucralose and stevia groups than in the control group. Consumption of both NNSs in the F0 generation was associated with lower Hdac3 expression in the liver and higher in the intestine. Hepatic Hdac3 expression was normalized to the control values in the F1 and F2 animals of the sucralose and stevia groups. Intestinal expression was still higher in the F1 generations of the sucralose and stevia groups but was partially normalized in the F2 generation of these groups, compared with control. CONCLUSIONS: NNS consumption differentially affects hepatic and intestinal Hdac3 expression. Changes in hepatic expression are not transmitted to the F1 and F2 generations whereas those in intestinal expression are enhanced in the F1 and attenuated in the F2 generations.

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.

Consumption of the Non-Nutritive Sweetener Stevia for 12 Weeks Does Not Alter the Composition of the Human Gut Microbiota.

The use of non-nutritive sweeteners (NNSs) as an alternative to caloric sugars has increased in recent years. Stevia is an NNS that has demonstrated beneficial effects on appetite and energy intake. However, the impact on the gut microbiota is not well understood. Therefore, we investigated how regular consumption of stevia, for up to 12 weeks, impacts the human gut microbiota. Healthy subjects with a normal body mass index participated in our study; the stevia group (n = 14) was asked to consume five drops of stevia twice daily, compared to control participants (n = 13). Faecal samples collected before and after treatment were analysed by 16S rRNA gene sequencing. Stevia did not cause significant changes in the alpha or beta diversity when compared to the control groups. When the relative abundances of taxa were investigated, no clear differences were detected. Conversely, a random forest analysis correctly associated the gut microbiome with the control and stevia groups with an average of 75% accuracy, suggesting that there are intrinsic patterns that could discriminate between control and stevia use. However, large-scale changes in the gut microbiota were not apparent in this study, and, therefore, our data suggest that stevia does not significantly impact the gut microbiota.

Relative validity of habitual sugar and low/no-calorie sweetener consumption assessed by food frequency questionnaire, multiple 24-h dietary recalls and urinary biomarkers: an observational study within the SWEET project.

BACKGROUND: Studies investigating associations between sweeteners and health yield inconsistent results, possibly due to subjective self-report dietary assessment methods. OBJECTIVES: We compared the performance of a food frequency questionnaire (FFQ), multiple 24-h dietary recalls (24hRs), and urinary biomarkers to estimate intake of sugars and low/no-calorie sweeteners (LNCSs). METHODS: Participants (n = 848, age 54 ± 12 y) from a 2-y observational study completed 1 semiquantitative FFQ and ≥ 3 nonconsecutive 24hRs. Both methods assessed intake of sugars (mono- and disaccharides, sucrose, fructose, free and added sugars) and sweetened foods and beverages (sugary foods, fruit juice, and sugar or LNCS-containing beverages [sugar-sweetened beverages and low/no-calorie sweetened beverages (LNCSBs)]); 24hRs also included LNCS-containing foods and tabletop sweeteners (low/no-calorie sweetened foods [LNCSFs]). Urinary excretion of sugars (fructose+sucrose) and LNCSs (acesulfame K+sucralose+steviol glucuronide+cyclamate+saccharin) were simultaneously assessed using ultrapressure liquid chromatography coupled to tandem mass spectrometry in 288 participants with 3 annual 24-h urine samples. Methods were compared using, amongst others, validity coefficients (correlations corrected for measurement error). RESULTS: Median (interquartile range) FFQ intakes ranged from 0 (0-7) g/d for LNCSBs to 94 (73-117) g/d for mono- and disaccharides. LNCSB use was reported by 32% of participants. Median LNCSB+LNCSF intake using 24hRs was 1 (0-50) g/d and reported by 58%. Total sugar excretions were detected in 100% of samples [56 (37-85) mg/d] and LNCSs in 99% of urine samples [3 (1-10) mg/d]. Comparing FFQ against 24hRs showed VCs ranging from 0.38 (fruit juice) to 0.74 (LNCSB). VCs for comparing FFQ with urinary excretions were 0.25 to 0.29 for sugars and 0.39 for LNCSBs; for 24hR they amounted to 0.31-0.38 for sugars, 0.37 for LNCSBs, and 0.45 for LNCSFs. CONCLUSIONS: The validity of the FFQ against 24hRs for the assessment of sugars and LNCSBs ranged from moderate to good. Comparing self-reports and urine excretions showed moderate agreement but highlighted an important underestimation of LNCS exposure using self-reports.

Effect of low-and non-calorie sweeteners on the gut microbiota: A review of clinical trials and cross-sectional studies.

Use of non-nutritive sweeteners (NNSs) has increased worldwide in recent decades. However, evidence from preclinical studies shows that sweetener consumption may induce glucose intolerance through changes in the gut microbiota, which raises public health concerns. As studies conducted on humans are lacking, the aim of this review was to gather and summarize the current evidence on the effects of NNSs on human gut microbiota. Only clinical trials and cross-sectional studies were included in the review. Regarding NNSs (i.e, saccharin, sucralose, aspartame, and stevia), only two of five clinical trials showed significant changes in gut microbiota composition after the intervention protocol. These studies concluded that saccharin and sucralose impair glycemic tolerance. In three of the four cross-sectional studies an association between NNSs and the microbial composition was observed. All three clinical trials on polyols (i.e, xylitol) showed prebiotic effects on gut microbiota, but these studies had multiple limitations (publication date, dosage, duration) that jeopardize their validity. The microbial response to NNSs consumption could be strongly mediated by the gut microbial composition at baseline. Further studies in which the potential personalized microbial response to NNSs consumption is acknowledged, and that include longer intervention protocols, larger cohorts, and more realistic sweetener dosage are needed to broaden these findings.

Maternal Consumption of Non-Nutritive Sweeteners during Pregnancy Is Associated with Alterations in the Colostrum Microbiota.

Non-nutritive sweeteners (NNSs) provide a sweet taste to foods and beverages without significantly adding calories. Still, their consumption has been linked to modifications in adult's and children's gut microbiota and the disruption of blood glucose control. Human milk microbiota are paramount in establishing infants' gut microbiota, but very little is known about whether the consumption of sweeteners can alter it. To address this question, we sequenced DNA extracted colostrum samples from a group of mothers, who had different levels of NNS consumption, using the Ion Torrent Platform. Our results show that the "core" of colostrum microbiota, composed of the genera Bifidobacterium, Blautia, Cutibacteium, Staphylococcus, and Streptococcus, remains practically unchanged with the consumption of NNS during pregnancy, but specific genera display significant alterations, such as Staphylococcus and Streptococcus. A significant increase in the unclassified archaea Methanobrevibacter spp. was observed as the consumption frequency of NNS increased. The increase in the abundance of this archaea has been previously linked to obesity in Mexican children. NNS consumption during pregnancy could be related to changes in colostrum microbiota and may affect infants' gut microbiota seeding and their future health.

Non-nutritive Sweeteners: Weight Loss or Weight Gain?

The consumption of non-nutritive sweeteners (NNS) is on the rise among different populations. In parallel, the debate about their potential health benefits and risks remains inconclusive. Numerous published studies elucidate the impact of NNS on general health, weight control, and the risk of certain diseases. However, no definitive conclusions regarding the effect of chronic NNS use on weight have been reached in humans. This review summarizes current evidence related to the biological role of NNS and their subsequent effects on weight. The mechanisms of action through which NNS impact weight are discussed, including their effect on sweet taste receptors, cognition, metabolic and endocrine functions, intestinal microbiota, and adiposity. Conflicting evidence is hindering the formulation of precise recommendations, but the evidence opposing the use of NNS remains weak, and the ultimate impact on weight largely relies on several other behavioral patterns.

Sweeteners and the Gut Microbiome: Effects on Gastrointestinal Cancers.

Worldwide, the demand for natural and synthetic sweeteners in the food industry as an alternative to refined sugar is increasing. This has prompted more research to be conducted to estimate its safety and effects on health. The gut microbiome is critical in metabolizing selected sweeteners which might affect overall health. Recently, more studies have evaluated the relationship between sweeteners and the gut microbiome. This review summarizes the current knowledge regarding the role played by the gut microbiome in metabolizing selected sweeteners. It also addresses the influence of the five selected sweeteners and their metabolites on GI cancer-related pathways. Overall, the observed positive effects of sweetener consumption on GI cancer pathways, such as apoptosis and cell cycle arrest, require further investigation in order to understand the underlying mechanism.

Daily Early-Life Exposures to Diet Soda and Aspartame Are Associated with Autism in Males: A Case-Control Study.

Since its introduction, aspartame-the leading sweetener in U.S. diet sodas (DS)-has been reported to cause neurological problems in some users. In prospective studies, the offspring of mothers who consumed diet sodas/beverages (DSB) daily during pregnancy experienced increased health problems. We hypothesized that gestational/early-life exposure to ≥1 DS/day (DSearly) or equivalent aspartame (ASPearly: ≥177 mg/day) increases autism risk. The case-control Autism Tooth Fairy Study obtained retrospective dietary recalls for DSB and aspartame consumption during pregnancy/breastfeeding from the mothers of 235 offspring with autism spectrum disorder (ASD: cases) and 121 neurotypically developing offspring (controls). The exposure odds ratios (ORs) for DSearly and ASPearly were computed for autism, ASD, and the non-regressive conditions of each. Among males, the DSearly odds were tripled for autism (OR = 3.1; 95% CI: 1.02, 9.7) and non-regressive autism (OR = 3.5; 95% CI: 1.1, 11.1); the ASPearly odds were even higher: OR = 3.4 (95% CI: 1.1, 10.4) and 3.7 (95% CI: 1.2, 11.8), respectively (p < 0.05 for each). The ORs for non-regressive ASD in males were almost tripled but were not statistically significant: DSearly OR = 2.7 (95% CI: 0.9, 8.4); ASPearly OR = 2.9 (95% CI: 0.9, 8.8). No statistically significant associations were found in females. Our findings contribute to the growing literature raising concerns about potential offspring harm from maternal DSB/aspartame intake in pregnancy.

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.

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.

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.

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.

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.