Consumption Of Non-nutritive Sweeteners Research Articles

Long-term metabolic effects of non-nutritive sweeteners

ObjectiveExcessive 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. MethodsTo 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. ResultsUnder 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. ConclusionsLong-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.

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.

Assessment of Knowledge and Perceptions of Pakistani Adults about Non-nutritive Sweeteners

Non-nutritive sweeteners are used as a substitute for sugar and have strong sweetening properties. They can be helpful in weight management, diabetes, and other insulin sensitivity-related metabolic disorders. Objective: This survey intended to analyze the knowledge and risk perceptions related to the safety and benefits of Non-nutritive sweeteners in a population of Pakistani adults. The impact of knowledge dissemination on the consumption of Non-nutritive sweeteners was also assessed. Methods: An online survey was conducted, and 680 responses were received. Results: Results indicated that 55.7% reported Non-nutritive sweeteners consumption, while 44.3% denied any usage. Only 27.4% of respondents showed trust in regulatory bodies while only 26.2% had any idea about the laws surrounding their use. The second part of the study aimed to examine the effect of knowledge dissemination on Non-nutritive sweeteners consumption, but the result showed that the participants were still not convinced about the safety levels of Non-nutritive sweeteners (p < 0.05). The only statement that participants were persuaded by was that Non-nutritive sweeteners does not pose any risk of cancer. The main reason for consumption was attributed to the low caloric properties of Non-nutritive sweeteners. Conclusions: The results showed that effective communication by regulatory authorities and health professionals via the internet, social media and leaflets can be beneficial in educating the public about Non-nutritive sweeteners. The role of health care professionals is also important to assure the public of the safety of Non-nutritive sweeteners.

Cross sectional study on the nonnutritive sweetener consumption and its association with socio-demographic characteristics among Saudi pregnant women

Cross sectional study on the nonnutritive sweetener consumption and its association with socio-demographic characteristics among Saudi pregnant women

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.

Effect of non-nutritive sweeteners on insulin regulation, glycemic response, appetite and weight management: a systematic review

PurposeThe purpose of this study is to collect and assess the evidence available on the effect of non nutritive sweeteners on appetite, weight and glycemic regulation. As a replacement for sugars, non-nutritive sweeteners (NNSs) are widely being used in different food products with the assumption that these would lower calorie intake and help to manage weight and blood sugar levels better. However, studies using animal models have reported that chronic exposure to NNSs leads to increased food consumption, weight gain and insulin resistance.Design/methodology/approachEvidence was acquired from systematic reviews or meta-analyses (2016–2021) of relevant clinical studies, especially randomized control trials using Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines.FindingsThe review showed NNSs exposure did not conclusively induce increased food intake or change in subjective appetite ratings. Appetite biomarkers like ghrelin, gastric inhibitory peptide, C-peptide levels and Peptide YY remained mostly unaffected by NNSs. Meta-analyses of human randomized control studies showed a reduced energy intake and body weight. No significant change was seen in blood glucose levels, post-prandial glycemic or insulin response after consumption of NNSs. Adequate evidence is not available to conclusively say that NNSs influence gut health at doses relevant to human use.Research limitations/implicationsMost studies which are prospective cohort, observational and cross-sectional studies suggest that use of NNSs may promote obesity and metabolic syndrome in adults. Such studies are plagued by confounding variables and reverse causation. Mechanistic evidence is mostly based on in-vitro and in-vivo studies. The same causal pathways may not be operative or relevant in humans.Practical implicationsThis review of available literature concludes that to achieve specific public health and clinical goals, the safe use of NNSs for the reduction of intakes of free sugars and energy should be explored. This would be possible by educating the consumer about energy compensation and understanding the nutritional content of artificially sweetened products in terms of calories coming from fat and complex carbohydrates used in the product.Originality/valueThis study was, thus, designed with the objective of examining the usefulness of NNSs in human population, especially with respect to insulin regulation, glycemic control and weight management. Well-designed randomized control trials which control for confounding variables are needed to generate high quality evidence.

Consumption of the nonnutritive sweetener acesulfame potassium increases central precocious puberty risk

The prevalence of precocious puberty and the consumption of nonnutritive sweeteners (NNS) is rapidly growing worldwide. However, the effects of NNSs on precocious puberty remain unclear. We examined the impact of acesulfame potassium (AceK), one of the most widely used NNS, on central precocious puberty (CPP) development using ex vivo and in vitro studies. 884 girls aged 6–12 were enrolled with complete AceK consumption data and CPP outcome assessment in the Taiwan Pubertal Longitudinal Study from 2018 to 2022. After adjustment for confounders, compared with no AceK consumption, AceK consumption at more than the median dose was associated with higher CPP risk in girls (odds ratio = 1.88, 95% confidence interval = 1.16–3.06; p for trend = 0.003). In rats, AceK consumption from in-utero to post-weaning stages accelerated puberty onset, accompanied by increased brain gonadotropin-releasing hormone (GnRH) expression. Intracerebroventricular AceK injection also induced early puberty onset in rats. In N44 hypothalamic neuron cells, AceK treatment increased reactive oxygen species production, which led to protein kinase A (PKA) activation and increased GnRH expression. These findings suggest that prepubertal girls should consume soft drinks or food products containing AceK more cautiously.

Non-nutritive sweeteners: consumer awareness and inclusion in food and beverage products in South Africa

Background: The widespread use of non-nutritive sweeteners (NNSs) in the food and beverage industry has become a global trend. Objective: A study was undertaken to assess the level of awareness of South Africans of NNSs and to create a scientific product database of NNSs in a sample of packaged products in South Africa. Design: A cross-sectional survey design was chosen. Setting: The study was carried out online in South Africa . Subjects: The study participants were South African adults (n = 388). Outcome measures: A consumer awareness survey on NNSs and a scientific product database were created to identify products formulated with NNSs. Results: A large proportion of participants were unfamiliar with most NNSs by name; however, a significant 61% (n = 238) (p < 0.001) of participants were most aware of xylitol, and 45% (n = 174) were aware of aspartame. Despite this, a significant number of participants consumed products labelled ‘sugar-free’ and/or ‘diet’ (p < 0.001). Participants were aware of health concerns and health benefits associated with the consumption of NNSs. A scientific product database consisting of 419 products containing NNSs was created during the study. A combination of NNSs was used in the formulations of 65% (n = 273) of the products, while 35% (n = 146) of the products were formulated with a single NNS. Conclusion: The outcome of this research highlights key consumer insights into NNSs and their widespread use in product formulations in South Africa. The outcome of this study shows the need for continuous monitoring of the effects of the increasing use of NNSs in product formulation and their impact on health and diet. Consumer education would advance consumer awareness of NNSs.

48-LB: Changes in Plasma Levels of Nonnutritive Sweetener Erythritol Are Related to Two-Year Changes of Insulin Sensitivity in Response to Weight-Loss Diets—The POUNDS Lost trial

Evidence on the benefits of non-nutritive sweeteners for weight management and improving insulin sensitivity and glucose metabolism is inconsistent. Recently, high levels of circulating erythritol, a sugar alcohol used as one of the non-nutritive sweeteners, have been linked to increased risks of type 2 diabetes and its vascular complications. Whether changes in circulating erythritol levels are related to insulin sensitivity and glucose metabolism remains unknown. Here, we investigated whether changes in plasma erythritol induced by weight-loss diet interventions were related to improved insulin sensitivity and glucose metabolism. This study included overweight or obese participants without diabetes or unstable cardiovascular disease from the POUNDS Lost trial with available data on circulating erythritol at baseline (n=805) and its changes from baseline to 6 months (n=670) and 2 years (n=533) during weight-loss diet interventions. At baseline, higher plasma levels of erythritol were related to hyperinsulinemia and greater degrees of insulin resistance assessed by HOMA-IR, even after adjusting for covariates, including BMI (P &amp;lt;0.05 for all). In response to weight-loss dietary interventions, a greater decrease in plasma erythritol was significantly associated with larger reductions of fasting insulin (p= 0.0001) and HOMA-IR (p=0.039) at 6 months, regardless of the initial levels of BMI, erythritol, and the respective outcome. Similarly, we found a significant association between long-term changes in erythritol and a 2-year reduction of fasting insulin (p=0.0027). In conclusion, circulating plasma erythritol, a marker of non-nutritive sweetener consumption, was significantly associated with hyperinsulinemia and insulin sensitivity among adults with overweight or obesity. Weight-loss diet-induced decreases in plasma erythritol were related to improved insulin sensitivity. Disclosure Y. Heianza: None. Q. Xue: None. J. Rood: None. G. Bray: Advisory Panel; Medifast, Inc., Herbalife International of America, Inc. F. Sacks: None. L. Qi: None. Funding National Institutes of Health (DK091718, DK100383, DK115679, 2P20GM109036-06A1-7233)

Maternal consumption and perinatal exposure to non-nutritive sweeteners: should we be concerned?

The context for this review is the rapid increase in the use of non-nutritive sweeteners (NNSs) instead of sugar in foods and beverages, a situation so prevalent in some countries that consumers are finding it increasingly challenging to access foods without NNSs. The benefits of consuming NNSs on obesity and diabetes are now being questioned, and studies have shown that they may exert physiological activities, sometimes independently of sweet taste receptor stimulation. Few studies, limited mainly to North American and European countries, have described the consumption of NNSs by pregnant or lactating women and infants. Most focus on beverages rather than foods, but all agree that consumption levels have increased dramatically. Although some studies report a negative impact of NNSs on the risk of preterm birth, increased birth weight and decreased gestational age, the level of evidence is low. Several studies have also reported increased weight gain in infancy, associated with maternal NNS intake. Interestingly, several NNSs have been detected in amniotic fluid and breast milk, usually (but not always) at concentrations below their established detection limit in humans. Unfortunately, the impact of chronic exposure of the fetus/infant to low levels of multiple NNSs is unknown. In conclusion, there is a stark contrast between the galloping increase in the consumption of NNSs and the small number of studies evaluating their impact in at-risk groups such as pregnant and lactating women and infants. Clearly, more studies are needed, especially in Latin America and Asia, to fill these gaps and update recommendations.

Effects of Nonnutritive Sweeteners on Body Composition Changes during Pubertal Growth.

The effects of consuming specific types of nonnutritive sweeteners (NNSs) on adiposity changes in children have remained inconsistent. In this study, we aimed to investigate the effects of the intake of different kinds of NNSs on long-term adiposity changes during pubertal growth. Furthermore, we examined the above relationships among different sexes, pubertal stages, and levels of obesity. A total of 1893 6-15-year-old adults were recruited and followed-up every 3 months. The NNS-FFQ (Food Frequency Questionnaire) was conducted and urine samples were collected to investigate the effects of the selected sweeteners, which included acesulfame potassium, aspartame, sucralose, glycyrrhizin, steviol glycosides, and sorbitol. Multivariate linear mixed-effects models were used to examine the relationship between NNS intake and body composition. The consumption of aspartame, sucralose, glycyrrhizin, stevioside, and sorbitol was associated with decreased fat mass and increased fat-free mass. In the highest tertile group, the effects of NNS consumption on fat mass corresponded to values of -1.21 (95% CI: -2.04 to -0.38) for aspartame, -0.62 (95% CI: -1.42 to 0.19) for sucralose, -1.26 (95% CI: -2.05 to -0.47) for glycyrrhizin, -0.90 (95% CI: -2.28 to 0.48) for stevioside, and -0.87 (95% CI: -1.67 to -0.08) for sorbitol, while the effects on fat-free mass corresponded to values of 1.20 (95% CI: 0.36 to -0.38) for aspartame, 0.62 (95% CI: -0.19 to 1.43) for sucralose, 1.27 (95% CI: 0.48 to 2.06) for glycyrrhizin, 0.85 (95% CI: -0.53 to 2.23) for stevioside, and 0.87 (95% CI: 0.08 to 1.67) for sorbitol. Particularly, aspartame and sorbitol revealed a dose-responsiveness effect. The above finding was more prominent among girls than boys. Moreover, fat mass was significantly reduced in normal-weight children who consumed a moderate amount of aspartame and a large amount of glycyrrhizin and sorbitol compared with obese children. In conclusion, the NNS-specific and sex-specific effects of long-term NNS consumption revealed associations of decreasing fat mass and increasing fat-free mass for children undergoing pubertal growth.

Artificial non-nutritive sweeteners consumption is able to modulate glycemic control and body composition in healthy or diet-induced obese mice

Non-nutritive sweeteners (NNS) are among the most widely used food additives worldwide. Their substitution to sugar is presented as one of the solutions to prevent cardiometabolic disease, especially as they have a sweet taste but very low-energy content. However, several recent studies have questioned their physiological inactivity, which was the basis for their approval by health authorities. The main objective of this study was to evaluate the acute and chronic effects of artificial NNS consumption on glycemic control in lean and diet-induced mice models. Consequently, we evaluated the acute effects of NNS acesulfame-potassium (aceK) and sucralose on glucose tolerance, insulin sensitivity and insulin secretion measured in blood and at the beta-cells pancreatic level of mice. In another set of mice, we compared the effects of aceK or sucralose supplementations to sugar consumption during a 12 week long high-fat (HF) diet. At the end of the 12 weeks of supplementation, we evaluated the influence of these different conditions on glucose metabolism and body fat distribution. First, we reported, in our mice models, that oral glucose tolerance tests (OGTTs) after acute sucralose gavage were improved significantly compared to AceK gavage and control situation (vehicle). These acute effects on blood glucose levels after sucralose ingestion were not directly explained by a significant increase neither in beta cells insulin secretion nor in insulin sensitivity. Interestingly, we further demonstrated that both NNS chronic consumption were able to attenuate significantly the deleterious effect of HF diet on glycemic control (glucose tolerance and insulin sensitivity), independently of caloric intake. Moreover, we reported in HF mice supplemented with NNS a lower accumulation of adipose tissue in the inguinal and subcutaneous compartments which was associated with a reduction in body mass in these groups. Surprisingly, our results demonstrate that even an acute consumption of widely used NNS sucralose and AceK is able to alter glucose metabolism. When repeated over time, the consumption of these NNS also seems to be able to reduce deleterious effects of HF diet on glycemic control but also on body composition. These results may contribute to a better understanding of the effects of NNS on metabolic health, but further studies are needed to decipher underlying mechanisms.

Associated factors to the consumption of non-nutritive sweeteners in the Mexican adult population

Objective. To identify the associated factors to the consumption of non-nutritive sweeteners (NNS) in the Mexican adult population since its consumption has increased exponentially worldwide. Materials and methods. An online survey was applied to 5 038 Mexican adults to evaluate the frequency of NNS consumption and classify the population in tertiles. The sociodemographic, lifestyle and health status characteristics of the participants were compared by gradient of NNS consumption, and a multiple linear regression analysis was performed to determine the associated factors to the NNS consumption. Results. The variables that showed a positive association (p≤0.01) with the consumption of NNS were economic income, BMI, smoking, physical activity, diet quality, the presence of chronic diseases (diabetes, hypertension, or dyslipidemias), and the consumption of fruit. The age and the consumption of confectionery and sugar-sweetened beverages were negatively associated (p&lt;0.01) with the consumption of NNS. Conclusion. The results of this study help to characterize the target population that is a consumer of NNS since it is recommended not encourage the preference for sweet taste and to promote a decrease in the consumption of both caloric and NNS, preferring the natural flavor of food.

Sweetener System Intervention Shifted Neutrophils from Homeostasis to Priming.

Non-nutritive sweeteners (NNS) are part of personalized nutrition strategies supporting healthy glycemic control. In contrast, the consumption of non-nutritive sweeteners has been related to person-specific and microbiome-dependent glycemic impairments. Reports on the effects of NNS on our highly individual cellular immune system are sparse. The recent identification of taste receptor expression in a variety of immune cells, however, suggested their immune-modulatory relevance. We studied the influence of a beverage-typical NNS system on the transcriptional profiling of sweetener-cognate taste receptors, selected cytokines and their receptors, and on Ca2+ signaling in isolated blood neutrophils. We determined plasma concentrations of saccharin, acesulfame-K, and cyclamate by HPLC-MS/MS, upon ingestion of a soft drink-typical sweetener surrogate. In an open-labeled, randomized intervention study, we determined pre- versus post-intervention transcript levels by RT-qPCR of sweetener-cognate taste receptors and immune factors. Here we show that the consumption of a food-typical sweetener system modulated the gene expression of cognate taste receptors and induced the transcriptional regulation signatures of early homeostasis- and late receptor/signaling- and inflammation-related genes in blood neutrophils, shifting their transcriptional profile from homeostasis to priming. Notably, sweeteners at postprandial plasma concentrations facilitated fMLF (N-formyl-Met-Leu-Phe)-induced Ca2+ signaling. Our results support the notion of sweeteners priming neutrophils to higher alertness towards their adequate stimuli.

Effects of non-nutritive sweeteners on the BMI of children and adolescents: a systematic review and meta-analysis of randomised controlled trials and prospective cohort studies

BackgroundConsidering the biological variation across subgroups during periods of growth, the role of non-nutritive sweeteners in weight-related outcomes among children and adolescents is unclear. We did a systematic review and meta-analysis to summarise the evidence on experimental and habitual consumption of non-nutritive sweeteners and prospective changes in BMI in paediatric populations. MethodsWe searched eligible (ie, lasting a minimum of 4 weeks) randomised controlled trials of the effect of non-nutritive sweeteners versus non-caloric or caloric comparators on BMI change and prospective cohort studies reporting multivariable-adjusted coefficients for non-nutritive sweetener intake and BMI in children (aged 2–9 years) and adolescents (aged 10–24 years). We generated pooled estimates using random effects meta-analysis and did secondary stratified analyses to explore heterogeneity by study-level and subgroup characteristics. We further evaluated the quality of the included evidence and classified industry-funded studies, or those whose authors were related to the food industry, as having potential conflicts of interest. FindingsFrom 2789 results, we included five randomised controlled trials (n=1498 participants; median follow-up 19·0 weeks [IQR 13·0–37·5]); three [60%] with potential conflicts of interest), and eight prospective cohort studies (n=35 340 participants; median follow-up 2·5 years [IQR 1·7–6·3]; two [25%] with potential conflicts of interest). Random allocation to intake of non-nutritive sweeteners (25–2400 mg/day, from food and beverages) suggested less BMI gain (standardised mean difference –0·42 kg/m2 [95% CI –0·79 to –0·06]; I2=89%) compared with intake of sugar from food and beverages. Stratified estimates were significant only in adolescents, participants with obesity at baseline, consumers of a mixture of non-nutritive sweeteners, longer trials, and trials not found to have potential conflicts of interest. No randomised controlled trials tested beverages containing non-nutritive sweeteners versus water. Prospective cohorts reported a non-significant association between consumption of beverages containing non-nutritive sweeteners and BMI gain (0·05 kg/m2 [95% CI –0·02 to 0·12]; I2=67%; per daily serving of 355 mL), which was accentuated for adolescents, boys, and cohorts with longer follow-ups. Removing studies with potential conflicts of interest attenuated the estimates. Evidence was predominantly classified as of low to moderate quality. InterpretationIntake of non-nutritive sweeteners versus sugar in randomised controlled trials resulted in less BMI gain in adolescents and participants with obesity. Better designed studies should contrast beverages containing non-nutritive sweeteners with water. Long-term prospective analyses with changes in repeated measures might clarify the effect of intake of non-nutritive sweeteners on BMI changes in childhood and adolescence. FundingNone.

Association between non-nutritive sweetener consumption and liver enzyme levels in adults: a systematic review and meta-analysis of randomized clinical trials.

The use of non-nutritive sweeteners (NNSs) is dramatically increasing in food commodities, and their effects on biochemical parameters have been the subject of great controversy. Liver enzymes as markers of liver injury may be helpful measures of non-alcoholic fatty liver disease (NAFLD), but the outcomes of randomized controlled trials (RCTs) suggest their associations with NNSs are contentious. The current study was designed to provide a GRADE-assessed systematic review and meta-analysis of RCTs studying the consequences of NNS consumption on ALT, AST, and GGT concentrations (ie, the 3 main liver enzymes in adults). Scopus, PubMed, and EMBASE were searched for relevant studies up to April 2021, with no time and language limitations. Two independent researchers extracted information from qualified studies, and a third researcher rechecked it. Of 3212 studies, 10 studies that enrolled a total of 854 volunteers were included. A random-effects or fixed-effects model was utilized to calculate weighted mean differences (WMDs) and 95% confidence intervals (CIs). Heterogeneity between studies was evaluated using Cochran's Q test and quantified using the I2 statistic. The pooled results demonstrated that, compared with control groups, NNS intake led to nonsignificant reductions in ALT (WMD: -.78, 95% CI: -2.14, .57, P = .25) and GGT (WMD: -.21, 95% CI: -1.46, 1.04, P = .74). Also, a small nonsignificant increasing effect on AST level was found (WMD: .02, 95% CI: -1.26, 1.30, P = .97). NNS significantly reduced AST levels in type 2 diabetes patients when subgroup analyses were performed. Also, in trials with ≥24-week intervention or studies that utilized stevioside for intervention, a significant reducing effect on ALT level was observed. The results of this study showed that NNS intake has no significant effect on liver enzyme levels in adults. PROSPERO registration no. CRD42021250067.

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 2weeks 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.

An Ecological Validity Model for the Prevention of Obesity: Non-Nutritive Sweetener Consumption in Rats and the Effects of Switching from Sugar-Sweetened to Diet Beverages.

Reducing consumption of sugar-sweetened beverages (SSBs) has been encouraged due to its strong association with obesity. In parallel, consumption of “diet” or non-nutritive sweetened (NNS) beverages has significantly increased. This has led to burgeoning numbers of animal studies investigating metabolic consequences of NNS beverage consumption. However, most animal study designs do not reflect the way humans consume NNS drinks, thus reducing translational capacity. The present experiment aimed to find an ecologically valid model of NNS consumption and evidence of metabolic recovery following a switch from sucrose to NNS in female and male Sprague Dawley rats. The main behavioural outcome was consumption of commercially available NNS beverages during preference and acceptance testing, with changes to consumption following chronic sucrose consumption as a secondary outcome. The main metabolic outcome was retroperitoneal fat pad mass at culling, with body weight gain and fasting blood glucose levels (FBGLs) as secondary outcomes. In a two-phase experiment, behavioural tests were performed before and after 4 weeks of ad libitum access to 10% w/v sucrose. During Phase 2, the rats were given ad libitum access to assigned commercial NNS drinks for a further 4 weeks, with controls provided access to water only. FBGLs were measured at the end of Phases 1 and 2. Female and male rats accepted commercially available NNS beverages, although the volumes consumed varied considerably. Following the switch from sucrose to NNS (containing no sucrose), no group difference was observed in retroperitoneal fat mass, body weight change or FBGLs, suggesting both sexes exhibited limited metabolic recovery. These findings demonstrate that an ecologically valid model for NNS consumption can be developed for some commercially available NNS beverages to further enhance translational capacity.

Chronic intake of nutritive sweeteners and saccharin increases levels of glycolytic and lipogenic enzymes in rat liver

There are doubts about the impact of non-nutritive sweeteners consumption on lipogenic and glycolytic metabolism. Therefore, the objective was to determine the effects of chronic consumption of sweeteners on the activity levels of the enzymes glucokinase (GK), phosphofructokinase-1 (PFK-1), pyruvate kinase (PKL), acetyl coenzyme A carboxylase (ACC), and fatty acid synthase (FAS) in livers’ extracts. Groups of male and female Wistar rats drank solutions of sweeteners for 480 days: Sucrose 10%, glucose 14%, fructose 7%, acesulfame K 0.05%, aspartame:acesulfame mixture 1.55%, sucralose 0.017%, saccharin 0.033%, and a control group. The enzymatic activity in livers’ extracts was determined. Likewise, the levels of glucose, triglycerides, insulin, glucagon, and leptin were determined. In both genders, there were significant differences in the levels of enzymatic activity, hormonal, and biochemical parameters due to sweeteners consumption. The highest glycolytic and lipogenic enzyme activity levels were observed in the groups that ingested nutritive sweeteners and saccharin.

A Metagenomics Investigation of Intergenerational Effects of Non-nutritive Sweeteners on Gut Microbiome.

To identify possible mechanisms by which maternal consumption of non-nutritive sweeteners increases obesity risk in offspring, we reconstructed the major alterations in the cecal microbiome of 3-week-old offspring of obese dams consuming high fat/sucrose (HFS) diet with or without aspartame (5–7 mg/kg/day) or stevia (2–3 mg/kg/day) by shotgun metagenomic sequencing (n = 36). High throughput 16S rRNA gene sequencing (n = 105) was performed for dams, 3- and 18-week-old offspring. Maternal consumption of sweeteners altered cecal microbial composition and metabolism of propionate/lactate in their offspring. Offspring daily body weight gain, liver weight and body fat were positively correlated to the relative abundance of key microbes and enzymes involved in succinate/propionate production while negatively correlated to that of lactose degradation and lactate production. The altered propionate/lactate production in the cecum of weanlings from aspartame and stevia consuming dams implicates an altered ratio of dietary carbohydrate digestion, mainly lactose, in the small intestine vs. microbial fermentation in the large intestine. The reconstructed microbiome alterations could explain increased offspring body weight and body fat. This study demonstrates that intense sweet tastants have a lasting and intergenerational effect on gut microbiota, microbial metabolites and host health.