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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., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Over the past few decades, the scientific community has been highly concerned about the obesity epidemic. Artificial sweeteners are compounds that mimic the sweet taste of sugar but have no calories or carbohydrates; hence, they are very popular among patients suffering from diabetes or obesity, aiming to achieve glycemic and/or weight control. There are four different types of sweeteners: artificial, natural, rare sugars, and polyols. Artificial and natural sweeteners are characterized as non-nutritional sweeteners (NNSs) since they do not contain calories. The extended use of sweeteners has been reported to have a favorable impact on body weight and glycemic control in patients with type 2 diabetes (T2DM) and on tooth decay prevention. However, there is concern regarding their side effects. Several studies have associated artificial sweeteners' consumption with the development of insulin resistance, nonalcoholic fatty liver disease (NAFLD), gastrointestinal symptoms, and certain types of cancer. The present review focuses on the description of different types of sweeteners and the benefits and possible deleterious effects of the chronic consumption of NNSs on children's health. Additionally, possible underlying mechanisms of the unfavorable effects of NNSs on human health are described.

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., Competing Interests: S.L. Hazen and Z. Wang report being named as coinventors on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics, all unrelated to the subject and contents of this article. S.L. Hazen and Z. Wang also report having received royalty payments for inventions or discoveries related to cardiovascular diagnostics or therapeutics from Procter & Gamble and Cleveland HeartLab, Inc, a fully owned subsidiary of Quest Diagnostics. S.L. Hazen is a paid consultant at Zehna Therapeutics, has received research funds from Zehna Therapeutics, and is eligible to receive royalty payments for inventions or discoveries related to cardiovascular diagnostics and therapeutics from Zehna Therapeutics. W.H.W. Tang reports being a consult at Sequana Medical A.G., Cardiol Therapeutics, Zehna Therapeutics, Genomics plc, Boston Scientific, WhiteSwell, Bristol Myers Squibb, Intellia Therapeutics, Alexion Pharmaceuticals, Alleviant Medical, CardiaTec Biosciences, Salubris Biotherapeutics, BioCardia, and has received honoraria from American Board of Internal Medicine, Belvoir Media Group, and Springer Nature. The other authors report no conflicts.

Background: Artificial sweeteners are widely popular worldwide as substitutes for sugar or caloric sweeteners, but there are still several important unknowns and controversies regarding their associations with cardiovascular disease (CVD). We aimed to extensively assess the association and subgroup variability between artificial sweeteners and CVD and CVD mortality in the UK Biobank cohort, and further investigate the modification effects of genetic susceptibility and the mediation role of type 2 diabetes mellitus (T2DM)., Methods: This study included 133,285 participants in the UK Biobank who were free of CVD and diabetes at recruitment. Artificial sweetener intake was obtained from repeated 24-hour diet recalls. Cox proportional hazard models were used to estimate HRs. Genetic predisposition was estimated using the polygenic risk score (PRS). Furthermore, time-dependent mediation was performed., Results: In our study, artificial sweetener intake (each teaspoon increase) was significantly associated with an increased risk of incident overall CVD (HR1.012, 95%CI: 1.008,1.017), coronary artery disease (CAD) (HR: 1.018, 95%CI: 1.001,1.035), peripheral arterial disease (PAD) (HR: 1.035, 95%CI: 1.010,1.061), and marginally significantly associated with heart failure (HF) risk (HR: 1.018, 95%CI: 0.999,1.038). In stratified analyses, non-whites were at greater risk of incident overall CVD from artificial sweetener. People with no obesity (BMI < 30 kg/m 2 ) also tended to be at greater risk of incident CVD from artificial sweetener, although the obesity interaction is not significant. Meanwhile, the CVD risk associated with artificial sweeteners is independent of genetic susceptibility, and no significant interaction exists between genetic susceptibility and artificial sweeteners in terms of either additive or multiplicative effects. Furthermore, our study revealed that the relationship between artificial sweetener intake and overall CVD is significantly mediated, in large part, by prior T2DM (proportion of indirect effect: 70.0%). In specific CVD subtypes (CAD, PAD, and HF), the proportion of indirect effects ranges from 68.2 to 79.9%., Conclusions: Our findings suggest significant or marginally significant associations between artificial sweeteners and CVD and its subtypes (CAD, PAD, and HF). The associations are independent of genetic predisposition and are mediated primarily by T2DM. Therefore, the large-scale application of artificial sweeteners should be prudent, and the responses of individuals with different characteristics to artificial sweeteners should be better characterized to guide consumers' artificial sweeteners consumption behavior., (© 2024. The Author(s).)

The purpose of this study is to further investigate the relationship between sweetener exposure and the risk of endometrial cancer (EC). Up until December 2022, a literature search in an electronic database was carried out utilizing PubMed, Web of Science, Ovid, and Scopus. The odds ratio (OR) and 95 % confidence interval (CI) were used to evaluate the results. Sweeteners were divided into nutritional sweeteners (generally refers to sugar, such as sucrose and glucose) and non-nutritional sweeteners (generally refers to artificial sweeteners, such saccharin and aspartame). Ten cohort studies and two case-control studies were eventually included. The study found that in 12 studies, compared with the non-exposed group, the incidence rate of EC in the sweetener exposed group was higher (OR = 1·15, 95 % CI = [1·07, 1·24]). Subgroup analysis showed that in 11 studies, the incidence rate of EC in the nutritional sweetener exposed group was higher than that in the non-exposed group (OR = 1·25, 95 % CI = [1·14, 1·38]). In 4 studies, there was no difference in the incidence rate of EC between individuals exposed to non-nutritional sweeteners and those who were not exposed to non-nutritional sweeteners (OR = 0·90, 95 % CI = [0·81, 1·01]). This study reported that the consumption of nutritional sweeteners may increase the risk of EC, whereas there was no significant relationship between the exposure of non-nutritional sweeteners and the incidence of EC. Based on the results of this study, it is recommended to reduce the intake of nutritional sweeteners, but it is uncertain whether use of on-nutritional sweeteners instead of nutritional sweetener.

Metformin, a frontline therapy for type 2 diabetes and related metabolic diseases, results in variable outcomes. This study aimed to investigate whether sweetened beverages (caloric or non-caloric) affect the therapeutic benefits of metformin on glucose, food intake, and weight loss in diet-induced obesity. Mice were given a high-fat diet and sweetened water for 8 weeks to induce obesity and glucose intolerance. Then, mice were randomized to receive metformin in either water, high-fructose corn syrup (HFCS), or the non-nutritive sweetener saccharin for 6 weeks. After 6 weeks of metformin treatment, all groups had improved glucose tolerance compared to pretreatment. However, saccharin resulted in worse glucose tolerance and weight gain outcomes than the water or HFCS groups and correlated with lower plasma growth differentiation factor 15 levels. In conclusion, reducing non-nutritive sweetener consumption during metformin therapy is recommended to avoid impairing the therapeutic effects of metformin on body weight and glucose homeostasis.

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<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.

The relationship between the consumption of maternal non-nutritive sweeteners (NNS) during pregnancy and the risk of obesity in offspring remains inconsistent. We aimed to systematically evaluate and clarify the relationship between NNS intake during pregnancy and weight gain in offspring based on evidence from population and clinical research. Databases including PubMed (via Medline), EMBASE, and the Cochrane Library were systematically searched for eligible human studies. The primary outcome was the differences in body mass index (BMI) z-scores between offspring at 1 year of age who were with and without NNS intake during pregnancy or between offspring with different NNS intake levels during pregnancy. A random-effects meta-analysis was conducted for data synthesis to calculate the weighted mean difference (WMD). A total of six prospective cohort studies were eligible for inclusion, among which three were used for pooled analysis of the BMI z-score. A significant increase was found in an offspring's weight at 1 year of age in the NNS group when compared with the control group: WMD in BMI z-score = 0.19 (95% CI: 0.07, 0.31), p -value = 0.002. Results from the dose-response analysis showed a linear relationship between NNS intake during pregnancy and WMD at 1 year of age: beta = 0.02 (95% CI: 0.001, 0.04) for per serving/week increase in NNS consumption. The whole body of evidence for the review was rated as low quality. In summary, maternal NNS intake during pregnancy was found to be associated with increased weight gain in offspring based on evidence from human studies. Further well-designed and adequately powered studies are needed to confirm this relationship.

This study evaluated the effects of long-term intake of nutritive sweeteners (NSs) and non-nutritive sweeteners (NNSs) on body weight, food and energy intake, blood pressure, metabolic parameters, and memory retention in rats. Sixty male Sprague-Dawley rats were randomly divided into six groups ( n  = 10 per group): control (water),10% sucrose (SUC), aspartame (ASP), sucralose (SCA), stevia (STV), and 5% xylitol (XYL). Pure NSs (SUC and XYL) and NNSs were added to the drinking water for 18 weeks. ASP, SCA, and STV dosage was based on the estimated daily intake limit: 4.1, 2.0, and 3.4 mg/kg/day, respectively. Chronic access to NNSs did not result in any difference in total weight gain of the rats, while it was significantly elevated in the SUC group compared with the control and NNSs groups. Food intake was significantly lower in all NNSs groups compared with SUC and control groups. Sweetened beverage intake volumes were significantly diminished in all NNSs groups compared with intake in SUC and control groups. Total calories consumed were lower for the STV and XYL groups compared with all other groups. Blood pressure and glucose metabolism did not differ significantly between the groups. All sweeteners increased total cholesterol, low-density lipoprotein, and triglyceride levels. Short-term memory was significantly impaired in the ASP group in the novel object recognition task, while long-term memory was impaired in SUC and STV groups. These metabolic and behavioral results suggest that the long-term intake of NSs or NNSs can be associated with peripheral and central effects.

Introduction: Introduction: the consumption of non-nutritive sweeteners (NNS) has increased. Recent studies have reported possible metabolic effects of NNS, and this may influence the perception regarding their consumption in the general population and health professionals. Objective: to describe and compare the beliefs about NNS in consumers, non-consumers, and health professionals; and to explore the reasons and opinions of health professionals for recommending or not their consumption. Methods: surveys were applied to 100 consumers, 100 non-consumers and 100 health professionals (dietitians and physicians) to evaluate a positive, negative, or neutral attitude towards certain beliefs regarding NNS, including the information they have, safety, price, side effects and taste. In addition, the opinion of health professionals for recommending or not the consumption of NNS and the related reasons was evaluated. Results: statistically significant differences regarding the safety, side effects and taste of NNS were found between the three groups (p < 0.01). The most frequent opinion of health professionals (48 %) is that NNS should be limited, used as a transition and in certain patients. Consumers tend to have a more positive opinion about NNS except for the price, non-consumers have a more neutral position except for taste, and health professionals have a more negative perception of NNS in all aspects. Conclusions: the beliefs regarding NNS differed among the studied groups, which might influence their consumption or recommendation of its use.

Non-nutritive sweeteners are increasingly consumed to satisfy cravings for sweet taste without the associated calories. Paradoxically, non-nutritive sweeteners have been linked to metabolic risks, but the underlying mechanisms are not understood. In this issue of Cell, Suez and colleagues pinpoint changes in the gut microbiome as a mechanism for non-nutritive sweetener-induced glycemic impairments in healthy adults., Competing Interests: Declaration of interests The author declares no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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.

Obesity is associated with the risk of cardiovascular disease, and non-nutritive sweetener, such as acesulfame potassium (AceK) has been used to combat obesity. However, the effects of AceK on cardiovascular disease are still unclear. In this study, high cholesterol diet (HCD)-fed ApoE -/- mice had dysregulated plasma lipid profile, and developed atherosclerosis, determined by atherosclerotic plaque in the aorta. Supplement of AceK in HCD worsened the dyslipidemia and increased atherosclerotic plaque, as compared with HCD-fed ApoE -/- mice. Since treatment of AceK in RAW264.7 macrophages showed no significant effects on inflammatory cytokine expressions, we then investigated the impacts of AceK on lipid metabolism. We found that AceK consumption enhanced hepatic lipogenesis and decreased β-oxidation in ApoE -/- mice. In addition, AceK directly increased lipogenesis and decreased β-oxidation in HepG2 cells. Taken together, a concurrent consumption of AceK exacerbated HCD-induced dyslipidemia and atherosclerotic lesion in ApoE -/- mice, and AceK might increase the risk of atherosclerosis under HCD.

The excess consumption of added sugar is consistently found to be associated with weight gain, and a higher risk of type 2 diabetes mellitus, coronary heart disease, and stroke. In an effort to reduce the risk of cardiometabolic disease, sugar is frequently replaced by low- and null-calorie sweeteners (LCSs). Alarmingly, though, emerging evidence indicates that the consumption of LCSs is associated with an increase in cardiovascular mortality risk that is amplified in those who are overweight or obese. Sucralose, a null-caloric high-intensity sweetener, is the most commonly used LCS worldwide, which is regularly consumed by healthy individuals and patients with metabolic disease. To explore a potential causal role for sucralose in increased cardiovascular risk, this present review summarizes the preclinical and clinical data from current research detailing the effects of sucralose on systems controlling food intake, glucose homeostasis, and gut microbiota., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition.)

Background: Products sweetened with non-nutritive sweeteners (NNS) are widely available. Many people with type 1 or type 2 diabetes use NNS as a replacement for nutritive sweeteners to control their carbohydrate and energy intake. Health outcomes associated with NNS use in diabetes are unknown., Objectives: To assess the effects of non-nutritive sweeteners in people with diabetes mellitus., Search Methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE Ovid, Scopus, the WHO ICTRP, and ClinicalTrials.gov. The date of the last search of all databases (except for Scopus) was May 2019. We last searched Scopus in January 2019. We did not apply any language restrictions., Selection Criteria: We included randomised controlled trials (RCTs) with a duration of four weeks or more comparing any type of NNS with usual diet, no intervention, placebo, water, a different NNS, or a nutritive sweetener in individuals with type 1 or type 2 diabetes. Trials with concomitant behaviour-changing interventions, such as diet, exercise, or both, were eligible for inclusion, given that the concomitant interventions were the same in the intervention and comparator groups., Data Collection and Analysis: Two review authors independently screened abstracts, full texts, and records retrieved from trials registries, assessed the certainty of the evidence, and extracted data. We used a random-effects model to perform meta-analysis, and calculated effect estimates as risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs). We assessed risk of bias using the Cochrane 'Risk of bias' tool and the certainty of evidence using the GRADE approach., Main Results: We included nine RCTs that randomised a total of 979 people with type 1 or type 2 diabetes. The intervention duration ranged from 4 to 10 months. We judged none of these trials as at low risk of bias for all 'Risk of bias' domains; most of the included trials did not report the method of randomisation. Three trials compared the effects of a dietary supplement containing NNS with sugar: glycosylated haemoglobin A1c (HbA1c) was 0.4% higher in the NNS group (95% CI -0.5 to 1.2; P = 0.44; 3 trials; 72 participants; very low-certainty evidence). The MD in weight change was -0.1 kg (95% CI -2.7 to 2.6; P = 0.96; 3 trials; 72 participants; very low-certainty evidence). None of the trials with sugar as comparator reported on adverse events. Five trials compared NNS with placebo. The MD for HbA1c was 0%, 95% CI -0.1 to 0.1; P = 0.99; 4 trials; 360 participants; very low-certainty evidence. The 95% prediction interval ranged between -0.3% and 0.3%. The comparison of NNS versus placebo showed a MD in body weight of -0.2 kg, 95% CI -1 to 0.6; P = 0.64; 2 trials; 184 participants; very low-certainty evidence. Three trials reported the numbers of participants experiencing at least one non-serious adverse event: 36/113 participants (31.9%) in the NNS group versus 42/118 participants (35.6%) in the placebo group (RR 0.78, 95% CI 0.39 to 1.56; P = 0.48; 3 trials; 231 participants; very low-certainty evidence). One trial compared NNS with a nutritive low-calorie sweetener (tagatose). HbA1c was 0.3% higher in the NNS group (95% CI 0.1 to 0.4; P = 0.01; 1 trial; 354 participants; very low-certainty evidence). This trial did not report body weight data and adverse events. The included trials did not report data on health-related quality of life, diabetes complications, all-cause mortality, or socioeconomic effects., Authors' Conclusions: There is inconclusive evidence of very low certainty regarding the effects of NNS consumption compared with either sugar, placebo, or nutritive low-calorie sweetener consumption on clinically relevant benefit or harm for HbA1c, body weight, and adverse events in people with type 1 or type 2 diabetes. Data on health-related quality of life, diabetes complications, all-cause mortality, and socioeconomic effects are lacking., (Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Introduction: Non-nutritive sweeteners (NNS) are food additives that have been used as a possible tool to reduce energy and sugar intake. There is a scientific debate around the real benefits of their use. NNS are substances widely evaluated in the scientific literature. Their safety is reviewed by international regulatory health agencies. Health professionals and consumers often lack education and objective information about food additives based on the best scientific evidence. NNS have been used as a substitute for sucrose, especially by people with diabetes mellitus and obesity. However, concerns related to their possible association with preterm birth have been raised, and also with their use during pregnancy and lactation because of the possibility of metabolic or other consequences in both the mother and offspring. This analysis of the evidence in gynecology and obstetrics presents a review of the most commonly asked questions regarding this matter by health professionals and their patients. This document evaluates a diversity of scientific publications under the sieve of evidence-based medicine and the regulatory framework for food additives to elucidate whether the use of NNS in women in these critical stages of pregnancy and breastfeeding represents a potential risk.

Obesity has been associated with changes in the gut microbiota and its metabolites. The study explored changes in the faecal microbiota and short-chain fatty acids (SCFA) associated with the diet (including nonnutritive sweeteners (NNSs)) and evaluated metabolic consequences in subjects with morbid obesity. The diet was assessed with a validated food frequency questionnaire. One unit of NNSs was 100 mL beverage with NNSs or 2 tablets/teaspoons of NNSs. The faecal microbiota was assessed with GA-map® dysbiosis test and SCFA with gas chromatography and flame ionisation detection. Fourteen men and 75 women with a mean age of 44.6 (SD 8.7) years, BMI 41.8 (SD 3.6) kg/m 2 , and intake of NNSs 7.5 units/day (SD 3.2; range 0-43) were included. Faecal butyric acid was positively and negatively associated with the intake of starch (partial correlation = 0.264; p =0.015) and NNSs (partial correlation = -0.274; p =0.011), respectively. NNSs were associated with changes in four out of 39 bacterial groups. Butyric acid has antiobesogenic effects, reduces insulin resistance, and improves dyslipidaemia. Since the weight-reducing effect of NNSs on obese adults trying to lose weight is dubious, it seems imprudent to use NNSs that might counteract the favourable effects of butyric acid., Competing Interests: The authors declare that they have no conflicts of interest regarding the publication of this article., (Copyright © 2019 Per G. Farup et al.)

Many pregnancies have a weight gain that is higher than recommended, situation that carries several risks for the mother and her child. As a strategy to achieve a lower weight gain, the replacement of sugar-sweetened foods and beverages by those with non-caloric sweeteners could be a choice for pregnant or puerperal mothers. The objective of this article is to review the available evidence regarding the use of non-caloric sweeteners during pregnancy and lactation. Pregnancy is not a period to lose weight, so it would not be advisable to perform hypocaloric diets. However, to achieve an adequate weight gain during pregnancy, many women choose to consume food and beverages with non-caloric sweeteners. During pregnancy, the consumption of cyclamate, saccharin and crude stevia leaf should be avoided, as well as that of stevia infusions or extracts of the whole leaf. Regarding the rest of the approved non-caloric sweeteners, their consumption during pregnancy and lactation is considered to be safe, as long as they are consumed in moderation, adhering to their admissible daily intake levels. Aspartame does not reach breast milk. While saccharin, sucralose, and acesulfame-K are detectable in breast milk, their concentration is several orders of magnitude below their admissible daily intake levels.

Postprandial hypotension (PPH) is under-recognised, but common, particularly in the elderly, and is of clear clinical importance due to both the independent association between PPH and an increase in mortality and lack of effective management for this condition. Following health concerns surrounding excessive consumption of sugar, there has been a trend in the use of low- or non-nutritive sweeteners as an alternative. Due to the lack of literature in this area, we conducted a systematic search to identify studies relevant to the effects of different types of sweeteners on postprandial blood pressure (BP). The BP response to ingestion of sweeteners is generally unaffected in healthy young subjects, however in elderly subjects, glucose induces the greatest decrease in postprandial BP, while the response to sucrose is less pronounced. The limited studies investigating other nutritive and non-nutritive sweeteners have demonstrated minimal or no effect on postprandial BP. Dietary modification by replacing high nutritive sweeteners (glucose, fructose, and sucrose) with low nutritive (d-xylose, xylitol, erythritol, maltose, maltodextrin, and tagatose) and non-nutritive sweeteners may be a simple and effective management strategy for PPH., Competing Interests: The authors declare no conflict of interest.

Here's what's known about the safety of these sweeteners and their effect on weight, appetite, and the risk for type 2 diabetes.

Individuals widely use non-nutritive sweeteners (NNS) in attempts to lower their overall daily caloric intake, lose weight, and sustain a healthy diet. There are insufficient scientific data that support the safety of consuming NNS. However, recent studies have suggested that NNS consumption can induce gut microbiota dysbiosis and promote glucose intolerance in healthy individuals that may result in the development of type 2 diabetes mellitus (T2DM). This sequence of events may result in changes in the gut microbiota composition through microRNA (miRNA)-mediated changes. The mechanism(s) by which miRNAs alter gene expression of different bacterial species provides a link between the consumption of NNS and the development of metabolic changes. Another potential mechanism that connects NNS to metabolic changes is the molecular crosstalk between the insulin receptor (IR) and G protein-coupled receptors (GPCRs). Here, we aim to highlight the role of NNS in obesity and discuss IR-GPCR crosstalk and miRNA-mediated changes, in the manipulation of the gut microbiota composition and T2DM pathogenesis.

Objective: The aim of this study is to review the control of energy balance and outline some causes of and remedies for excessive energy intake., Methods: A narrative review was conducted., Results: There is negative feedback control of energy intake and body weight, but, nonetheless, energy intake is only loosely coupled with energy expenditure. Consequently, we are vulnerable to eating in excess of energy requirements. In this context, energy density, portion size, and habitual meal patterns have strong influences on energy intake and, accordingly, can be targeted to reduce energy intake. For example, energy density can be reduced without much affecting food reward (approximately the pleasure gained from eating) because their relationship is such that reward value is affected relatively little by increments in energy density above 1.5 kcal/g. This and other strategies that increase reward per calorie eaten may be superior to increasing the satiety effect of products because fullness is not inherently rewarding. Low-calorie sweeteners provide a means to reduce energy density while largely preserving food or beverage reward value. Consistent with this, consumption of low-calorie sweeteners compared with consumption of sugars has been found to reduce energy intake and body weight., Conclusions: Understanding what causes excessive eating also provides insights into how to combat this problem., (© 2018 The Obesity Society.)

Low-calorie sweeteners (LCS) are found in a variety of foods and beverages, yet their role in diet, weight, and obesity-related chronic disease is controversial. This article summarizes proceedings from one of four presentations during a preconference session entitled "Low-Calorie Sweeteners and Weight Management," which took place at the 2017 Obesity Society Annual Meeting in Washington, District of Columbia. The objective of this brief review is to summarize findings of observational and interventional studies of LCS effects on weight and metabolic health and to provide potential explanations for their discrepant results. Key research priorities for advancing the understanding of the role of LCS in weight and chronic disease are also discussed. The existing literature suggests that LCS consumption is consistently associated with obesity, diabetes, and related cardiometabolic conditions in observational studies. Although several plausible mechanisms have been proposed to explain these associations and have received considerable support in cellular and rodent models, the relevance of these mechanisms to humans has yet to be confirmed. Meanwhile, randomized controlled trials demonstrate that NNS may benefit weight loss and weight maintenance. This is the case particularly when LCS are administered in the context of behavioral weight loss support and are consumed knowingly by habitual LCS consumers. Although these findings suggest that LCS may be useful for weight control among those cognitively engaged in weight loss and who are aware of their LCS consumption, LCS administration in these studies does not reflect typical consumption. Furthermore, few interventional studies have assessed the role of LCS on metabolic outcomes other than body weight. Additional factors must be considered before recommending LCS for weight management and chronic disease prevention and further study of LCS effects on a variety of cardiometabolic outcomes, including visceral adiposity and glucose homeostasis is warranted., (© 2018 The Obesity Society.)

Objective: Many scientists and laypeople alike have concerns about low-calorie sweeteners (LCSs). These concerns stem from both a dissatisfaction with the taste of LCSs and reports that they cause metabolic disruptions (e.g., weight gain, glucose intolerance)., Methods: This article provides a critical review of the literature on LCSs from the standpoint of their taste, gastrointestinal, and metabolic effects; biological fate in the body; and impact on ingestion and glucose homeostasis., Results and Conclusions: Mammals can readily discriminate between LCSs and sugars because both types of sweetener activate distinct oral and post-oral sensory pathways. LCSs differ in their ability to access post-oral tissues, but few studies have incorporated this observation into their design. It is difficult to extrapolate results between mice, rats, and humans because of interspecies differences in the taste and post-oral actions of LCSs and the fact that investigators often use different response measures in rodents and humans. There is confounding in the experimental design of some of the most widely cited studies of LCS-induced metabolic disruptions. The uncritical acceptance of these studies has generated considerable controversy. More work is needed to obtain a clearer understanding of the metabolic effects of LCSs., (© 2018 The Obesity Society.)

The use and impact of low-calorie sweeteners (LCS) in relation to the national challenges of overweight and obesity are complex and controversial. Most research on LCS have focused on the prevalence of consumption of LCS in beverages. The 2015 Dietary Guidelines Advisory Committee emphasized dietary patterns and health rather than a focus on specific nutrients or foods. The committee took this approach to shift the national emphasis onto the context of total rather than individual nutrient consumption. A broader research paradigm is needed to elucidate the actual exposure to LCS and how they are consumed within dietary patterns in the US population. National-level databases exist that can be used to broaden scientific understanding of the effects of LCS and health outcomes. These databases are underutilized, and they provide potential tools for grasping a fuller picture of LCS in the US diet., (© 2018 The Obesity Society.)

By virtue of reducing dietary energy density, low-calorie sweeteners (LCS) can be expected to decrease overall energy intake and thereby decrease body weight. Such effects will be limited by the amount of sugar replaced by LCS, and the dynamics of appetite and weight control (e.g., acute compensatory eating, and an increase in appetite and decrease in energy expenditure accompanying weight loss). Consistent with these predictions, short-term intervention studies show incomplete compensation for the consumption of LCS v. sugar, and longer-term intervention studies (from 4 weeks to 40 months duration) show small decreases in energy intake and body weight with LCS v. sugar. Despite this evidence, there are claims that LCS undermine weight management. Three claims are that: (1) LCS disrupt the learned control of energy intake (sweet taste confusion hypothesis); (2) exposure to sweetness increases desire for sweetness (sweet tooth hypothesis); (3) consumers might consciously overcompensate for 'calories saved' when they know they are consuming LCS (conscious overcompensation hypothesis). None of these claims stands up to close examination. In any case, the results of the intervention studies comparing LCS v. sugar indicate that the effect of energy dilution outweighs any tendency LCS might conceivably have to increase energy intake.

Non-nutritive sweeteners (NNSs) are widely used in various food products and soft drinks. There is growing evidence that NNSs contribute to metabolic dysfunction and can affect body weight, glucose tolerance, appetite, and taste sensitivity. Several NNSs have also been shown to have major impacts on bacterial growth both in vitro and in vivo. Here we studied the effects of various NNSs on the growth of the intestinal bacterium, E. coli, as well as the gut bacterial phyla Bacteroidetes and Firmicutes, the balance between which is associated with gut health. We found that the synthetic sweeteners acesulfame potassium, saccharin and sucralose all exerted strong bacteriostatic effects. We found that rebaudioside A, the active ingredient in the natural NNS stevia, also had similar bacteriostatic properties, and the bacteriostatic effects of NNSs varied among different Escherichia coli strains. In mice fed a chow diet, sucralose increased Firmicutes, and we observed a synergistic effect on Firmicutes when sucralose was provided in the context of a high-fat diet. In summary, our data show that NNSs have direct bacteriostatic effects and can change the intestinal microbiota in vivo., Competing Interests: The authors declare that they have no competing interests.

Non-nutritive sweeteners (NNS) are used in the food supply to replace sugar and/or to reduce dietary energy intake. The aim of this research was to assess the consumption prevalence and food sources of NNS in the Australian population. Food group and nutrient intakes were assessed to compare diet quality of NNS consumers and non-consumers. Secondary analysis of the Australian National Nutrition and Physical Activity Survey, 2011/12 was conducted ( n = 12,435) after identifying all NNS products consumed in the population. The proportion of participants that reported intake of NNS per day was 18.2% for adults (19+ years), and 8.5% for children (2⁻18 years), with the most common food sources being carbonated soft drinks, tabletop sweeteners, and yoghurt. Characteristics associated with NNS consumption in adults included being female, higher body mass index (BMI), self-reported diabetes status, and being on a weight-loss diet. For adults, NNS consumers had lower free sugar intake but energy intake did not differ from non-consumers. However, for children, no differences in free sugar or energy intake were observed between consumers and non-consumers. While these results support the use of NNS in reducing sugar intake, these data suggest compensatory increases in energy intake may occur.

International scientific experts in food, nutrition, dietetics, endocrinology, physical activity, paediatrics, nursing, toxicology and public health met in Lisbon on 2⁻4 July 2017 to develop a Consensus on the use of low- and no-calorie sweeteners (LNCS) as substitutes for sugars and other caloric sweeteners. LNCS are food additives that are broadly used as sugar substitutes to sweeten foods and beverages with the addition of fewer or no calories. They are also used in medicines, health-care products, such as toothpaste, and food supplements. The goal of this Consensus was to provide a useful, evidence-based, point of reference to assist in efforts to reduce free sugars consumption in line with current international public health recommendations. Participating experts in the Lisbon Consensus analysed and evaluated the evidence in relation to the role of LNCS in food safety, their regulation and the nutritional and dietary aspects of their use in foods and beverages. The conclusions of this Consensus were: (1) LNCS are some of the most extensively evaluated dietary constituents, and their safety has been reviewed and confirmed by regulatory bodies globally including the World Health Organisation, the US Food and Drug Administration and the European Food Safety Authority; (2) Consumer education, which is based on the most robust scientific evidence and regulatory processes, on the use of products containing LNCS should be strengthened in a comprehensive and objective way; (3) The use of LNCS in weight reduction programmes that involve replacing caloric sweeteners with LNCS in the context of structured diet plans may favour sustainable weight reduction. Furthermore, their use in diabetes management programmes may contribute to a better glycaemic control in patients, albeit with modest results. LNCS also provide dental health benefits when used in place of free sugars; (4) It is proposed that foods and beverages with LNCS could be included in dietary guidelines as alternative options to products sweetened with free sugars; (5) Continued education of health professionals is required, since they are a key source of information on issues related to food and health for both the general population and patients. With this in mind, the publication of position statements and consensus documents in the academic literature are extremely desirable.

Background: The effect of sugar-sweetened beverages (SSBs) on satiety and short-term food intake (FI) regulation in girls has received little attention. The objective of the present study was to compare the effect of pre-meal consumption of commercially available SSBs on subjective appetite and short-term FI in 9-14-year-old girls. The methods we used include using a randomized crossover design in which 28 girls consumed isovolumetric amounts (350 mL) of a fruit drink (154 kcal), cola (158 kcal), 1% chocolate milk (224 kcal), or water (control; 0 kcal) on four separate mornings. Subjective appetite and thirst were measured at regular intervals via visual analogue scales (VAS) and FI was assessed at 60 min post-beverage consumption. The results show that subjective appetite and thirst decreased after all beverages, but did not differ among beverages. Short-term FI was suppressed following consumption of chocolate milk (15%; p < 0.001) and cola (11%; p = 0.02) compared to the water control. However, cumulative energy intake (beverage (kcal) + test meal (kcal)) was not affected by beverage type. In conclusion, chocolate milk and cola, but not fruit drink, suppressed FI in girls while cumulative FI did not differ among treatments., Competing Interests: The authors declare no conflict of interest.

The current review examined published data on the intake of all major low-/no-calorie sweeteners-aspartame, acesulfame-K, saccharin, sucralose, cyclamate, thaumatin and steviol glycosides-globally over the last decade. The most detailed and complex exposure assessments were conducted in Europe, following a standardized approach. Japan and Korea similarly had up-to-date and regular intake data available. The data for other Asian countries, Latin America, Australia/New Zealand and global estimates, evaluated by the Joint FAO/WHO Expert Committee on Food Additives (JECFA), while available, were shown to be more limited in terms of design. Overall, the studies conducted since 2008 raised no concerns with respect to exceedance of individual sweetener acceptable daily intake (ADIs) among the general population globally. The data identified do not suggest a shift in exposure over time, with several studies indicating a reduction in intake. However, some data suggest there may have been an increase in the numbers of consumers of low-/no-calorie-sweetened products. Future research should consider a more standardized approach to allow the monitoring of potential changes in exposure based upon events such as sugar reduction recommendations, to ensure there is no shift in intake, particularly for high-risk individuals, including diabetics and children with specific dietary requirements, and to ensure risk management decisions are based on quality intake analyses., Competing Interests: The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Recent data indicate that artificial sweeteners (AS) may have deleterious effects on glucose metabolism. The purpose of this study was to compare the effects of AS and the effects of a high fructose diet (HFrD) on glucose metabolism and insulin resistance (IR) in Sprague-Dawley (SD) rats. SD rats were fed either regular chow, chow with saccharin (Sac) (0.1 mg/mL) placed in their water, or HFrD for seven weeks. Glucose, insulin, and triglycerides (Tg) levels were measured upon completion. A homeostatic model assessment (HOMA)-IR index was used to determine insulin resistance. The liver was stained to detect signs of a fatty liver. Hepatic mRNA expression of glucose metabolism regulation genes, Srepb-1c (sterol regulatory element binding protein) and ChREB (α & β) (carbohydrate response element binding protein), as well as other glycolytic and lipogenic genes including glucose-6-phosphatase (G6pc), were considered IR markers. Both HFrD and Sac significantly increased fasting blood glucose levels compare to the control (140 ± 5 and 137 ± 6 vs. 118 ± 3 mg/dL, respectively, p < 0.05). However, only HFrD increased insulin secretion (0.99 ± 0.12 vs. 0.7 ± 0.1 and 0.6 ± 0.1 ug/L), Tg levels (420 ± 43 vs. 152 ± 20 and 127 ± 13 mg/dL), and the HOMA-IR index (3.4 ± 0.4 vs. 2.3 ± 0.36 and 2.13 ± 0.3) (HFrD vs. control and sac, p < 0.05). Fatty liver changes were only observed in HFrD fed rats. The expression of ChREB β, Srepb-1c, and G6pc mRNA were only significantly elevated (between 2-10 times folds, p < 0.05) in HFrD fed rats. Sac may increase fasting blood glucose but has no effect on liver insulin resistance., Competing Interests: The authors declare no conflict of interest.

Sweeteners are found in all types of foods, and their high consumption is associated with chronic degenerative diseases, such as diabetes and obesity, among others. A characterization was carried out of food products with sweeteners from the three biggest supermarkets at a national level; they were identified by the list of ingredients and classified according to caloric or non-caloric intake, and pursuant to their country of origin. A statistical interpretation of results was made using descriptive measures such as the number of times the sweeteners were found in the formulation of the products and how many of them were found in a product at the same time. In total, 341 products were evaluated and classified according to the processed food categories of the Pan American Health Organization (PAHO) nutrient profile. The category of beverages had the highest quantity of products with sweeteners, and their consumption by the inhabitants represents a high exposure. Overall, 60.1% of the products evaluated were of US origin; these US exports have a significant impact on the Honduran market. A high-fructose corn syrup caloric sweetener was the one most frequently found in these products; at least 51% are combined with additional sweeteners to increase the sweetening effect., Competing Interests: The authors declare no conflict of interest.

Few studies have evaluated the relationships between intake of sugar-sweetened beverages (SSB) and intermediate biomarkers of cardiometabolic risk. Associations between artificially sweetened beverages (ASB) and fruit juice with cardiometabolic biomarkers are also unclear. We investigated habitual SSB, ASB and fruit juice intake in relation to biomarkers of hepatic function, lipid metabolism, inflammation and glucose metabolism. We analysed cross-sectional data from 8492 participants in the Nurses' Health Study who were free of diabetes and CVD. Multivariate linear regression was used to assess the associations of SSB, ASB and fruit juice intake with concentrations of fetuin-A, alanine transaminase, γ-glutamyl transferase, TAG, HDL-cholesterol, LDL-cholesterol, total cholesterol, C-reactive protein (CRP), intracellular adhesion molecule 1 (ICAM-1), vascular cell adhesion protein 1, adiponectin, insulin and HbA1c as well as total cholesterol:HDL-cholesterol ratio. More frequent intake of SSB was significantly associated with higher concentrations of fetuin-A, TAG, CRP, ICAM-1, adiponectin and insulin, a higher total cholesterol:HDL-cholesterol ratio, and a lower concentration of HDL-cholesterol (P trend ranges from <0·0001 to 0·04) after adjusting for demographic, medical, dietary and lifestyle variables. ASB intake was marginally associated with increased concentrations of CRP (P trend=0·04) and adiponectin (P trend=0·01). Fruit juice intake was associated with increased concentrations of TAG and HbA1c and a lower concentration of adiponectin (P trend ranges from <0·0001 to 0·01). In conclusion, habitual intake of SSB was associated with adverse levels of multiple cardiometabolic biomarkers. Associations between ASB and fruit juice with cardiometabolic risk markers warrant further exploration.

Non-nutritive sweeteners (NNS) are increasingly consumed by children and pregnant women around the world, yet their long-term health impact is unclear. Here, we review an emerging body of evidence suggesting that early-life exposure to NNS may adversely affect body composition and cardio-metabolic health. Some observational studies suggest that children consuming NNS are at increased risk for obesity-related outcomes; however, others find no association or provide evidence of confounding. Fewer studies have examined prenatal NNS exposure, with mixed results from different analytical approaches. There is a paucity of RCTs evaluating NNS in children, yielding inconsistent results that can be difficult to interpret due to study design limitations (e.g., choice of comparator, multifaceted interventions). The majority of this research has been conducted in high-income countries. Some rodent studies demonstrate adverse metabolic effects from NNS, but most have used extreme doses that are not relevant to humans, and few have distinguished prenatal from postnatal exposure. Most studies focus on synthetic NNS in beverages, with few examining plant-derived NNS or NNS in foods. Overall, there is limited and inconsistent evidence regarding the impact of early-life NNS exposure on the developmental programming of obesity and cardio-metabolic health. Further research and mechanistic studies are needed to elucidate these effects and inform dietary recommendations for expectant mothers and children worldwide., Competing Interests: The authors declare no conflict of interest.

Background: Food products containing non-nutritive sweeteners (NNSs) instead of sugar have become increasingly popular in the last decades. Their appeal is obviously related to their calorie-free sweet taste. However, with the dramatic increase in their consumption, it is reasonable and timely to evaluate their potential health benefits and, more importantly, potential adverse effects. The main aim of this scoping review was to map the evidence about health outcomes possibly associated with regular NNS consumption by examining the extent, range, and nature of research activity in this area., Methods: We systematically searched Ovid MEDLINE, EMBASE and the Cochrane CENTRAL databases for studies on NNSs (artificial sweeteners or natural, non-caloric sweeteners, either used individually or in combination) using text terms with appropriate truncation and relevant indexing terms. All human studies investigating any health outcomes of a NNS intervention or exposure were eligible for inclusion. No studies were excluded based on language, study design or methodological quality. Data for each health outcome were summarized in tabular form and were discussed narratively., Results: Finally, we included 372 studies in our scoping review, comprising 15 systematic reviews, 155 randomized controlled trials (RCTs), 23 non-randomized controlled trials, 57 cohort studies, 52 case-control studies, 28 cross sectional studies and 42 case series/case reports. In healthy subjects, appetite and short term food intake, risk of cancer, risk of diabetes, risk of dental caries, weight gain and risk of obesity are the most investigated health outcomes. Overall there is no conclusive evidence for beneficial and harmful effects on those outcomes. Numerous health outcomes including headaches, depression, behavioral and cognitive effects, neurological effects, risk of preterm delivery, cardiovascular effects or risk of chronic kidney disease were investigated in fewer studies and further research is needed. In subjects with diabetes and hypertension, the evidence regarding health outcomes of NNS use is also inconsistent., Conclusions: This scoping review identifies the needs for future research to address the numerous evidence gaps related to health effects of NNSs use.It also specifies the research questions and areas where a systematic review with meta-analyses is required for the proper evaluation of health outcomes associated to regular NNSs consumption.

Objective: Long-term effects of diet beverage consumption on the regulation of caloric intake is unclear. The goal of this study was to investigate whether the chronic intake of a liquid diet with nonnutritive sweeteners (NNS) would lead to greater appetite and weight gain., Methods: Wistar rats were fed a liquid diet (Osmolite) sweetened with nutritive sweetener (NS; sucrose) and NNS (stevia and saccharin) or a nonsweetened control. Intakes and weight gain were measured. Phases 1 and 2 investigated sweetness preference, phase 3 used diets with or without sweeteners, and phase 4 measured the effect on volume of food and caloric intake of alternating between NNS, NS, and control diets., Results: In phase 1, rats preferred: stevia, 0.10%; saccharin, 0.20%; and sucrose, 15%. In phase 2, rats preferred the sweetened diet over the control. In phase 3, rats fed the NS diet consumed less volume and more calories but gained less weight. In phase 4, when altering diet from NNS to NS, no differences were observed in appetite or weight gain., Conclusions: Using sucrose-sweetened diet as a control, increased weight gain with the ingestion of NNS was observed. However, using a nonsweetened control, neither increased caloric intake nor weight gain occurred with NNS intake. Alternating diets between NNS, NS, and control did not affect the appetite., (© 2017 The Obesity Society.)

Background: Nonnutritive sweeteners, such as aspartame, sucralose and stevioside, are widely consumed, yet their long-term health impact is uncertain. We synthesized evidence from prospective studies to determine whether routine consumption of non-nutritive sweeteners was associated with long-term adverse cardiometabolic effects., Methods: We searched MEDLINE, Embase and Cochrane Library (inception to January 2016) for randomized controlled trials (RCTs) that evaluated interventions for nonnutritive sweeteners and prospective cohort studies that reported on consumption of non-nutritive sweeteners among adults and adolescents. The primary outcome was body mass index (BMI). Secondary outcomes included weight, obesity and other cardiometabolic end points., Results: From 11 774 citations, we included 7 trials (1003 participants; median follow-up 6 mo) and 30 cohort studies (405 907 participants; median follow-up 10 yr). In the included RCTs, nonnutritive sweeteners had no significant effect on BMI (mean difference -0.37 kg/m 2 ; 95% confidence interval [CI] -1.10 to 0.36; I 2 9%; 242 participants). In the included cohort studies, consumption of nonnutritive sweeteners was associated with a modest increase in BMI (mean correlation 0.05, 95% CI 0.03 to 0.06; I 2 0%; 21 256 participants). Data from RCTs showed no consistent effects of nonnutritive sweeteners on other measures of body composition and reported no further secondary outcomes. In the cohort studies, consumption of nonnutritive sweeteners was associated with increases in weight and waist circumference, and higher incidence of obesity, hypertension, metabolic syndrome, type 2 diabetes and cardiovascular events. Publication bias was indicated for studies with diabetes as an outcome., Interpretation: Evidence from RCTs does not clearly support the intended benefits of nonnutritive sweeteners for weight management, and observational data suggest that routine intake of nonnutritive sweeteners may be associated with increased BMI and cardiometabolic risk. Further research is needed to fully characterize the long-term risks and benefits of nonnutritive sweeteners. Protocol registration: PROSPERO-CRD42015019749., Competing Interests: Competing interests: Jonthan McGavock has received speaker fees from Medtronic. No other competing interests were declared., (© 2017 Canadian Medical Association or its licensors.)

Background and Purpose: Sugar- and artificially-sweetened beverage intake have been linked to cardiometabolic risk factors, which increase the risk of cerebrovascular disease and dementia. We examined whether sugar- or artificially sweetened beverage consumption was associated with the prospective risks of incident stroke or dementia in the community-based Framingham Heart Study Offspring cohort., Methods: We studied 2888 participants aged >45 years for incident stroke (mean age 62 [SD, 9] years; 45% men) and 1484 participants aged >60 years for incident dementia (mean age 69 [SD, 6] years; 46% men). Beverage intake was quantified using a food-frequency questionnaire at cohort examinations 5 (1991-1995), 6 (1995-1998), and 7 (1998-2001). We quantified recent consumption at examination 7 and cumulative consumption by averaging across examinations. Surveillance for incident events commenced at examination 7 and continued for 10 years. We observed 97 cases of incident stroke (82 ischemic) and 81 cases of incident dementia (63 consistent with Alzheimer's disease)., Results: After adjustments for age, sex, education (for analysis of dementia), caloric intake, diet quality, physical activity, and smoking, higher recent and higher cumulative intake of artificially sweetened soft drinks were associated with an increased risk of ischemic stroke, all-cause dementia, and Alzheimer's disease dementia. When comparing daily cumulative intake to 0 per week (reference), the hazard ratios were 2.96 (95% confidence interval, 1.26-6.97) for ischemic stroke and 2.89 (95% confidence interval, 1.18-7.07) for Alzheimer's disease. Sugar-sweetened beverages were not associated with stroke or dementia., Conclusions: Artificially sweetened soft drink consumption was associated with a higher risk of stroke and dementia., (© 2017 American Heart Association, Inc.)

There is ongoing debate concerning non-nutritive sweeteners, their usage, and their effects on metabolism. The association between non-nutritive sweeteners consumption, development of metabolic diseases, and changes in appetite-regulating hormones is not clear. The aim of this article is to present an overview of non-nutritive sweeteners and to examine the scientific evidence of their effects on glucose metabolism and appetite-regulating hormones. Some observational studies suggest an association between non-nutritive sweeteners consumption and development of metabolic diseases; however, adiposity is a confounder frequently found in these studies. Results of the available clinical trials are heterogeneous and not comparable because of major differences between them. Future controlled studies evaluating specific non-nutritive sweeteners, with an appropriate sample size, including a uniform study group, with sufficient exposure time, and considering adjustment for confounder variables, such as anthropometric characteristics, previous consumption of non-nutritive sweeteners, and coexistence of significant metabolic comorbidities, are needed.

Background: Substituting sweeteners with non-nutritive sweeteners (NNS) may aid in glycaemic control and body weight management. Limited studies have investigated energy compensation, glycaemic and insulinaemic responses to artificial and natural NNS., Objectives: This study compared the effects of consuming NNS (artificial versus natural) and sucrose (65 g) on energy intake, blood glucose and insulin responses., Methods: Thirty healthy male subjects took part in this randomised, crossover study with four treatments: aspartame-, monk fruit-, stevia- and sucrose-sweetened beverages. On each test day, participants were asked to consume a standardised breakfast in the morning, and they were provided with test beverage as a preload in mid-morning and ad libitum lunch was provided an hour after test beverage consumption. Blood glucose and insulin concentrations were measured every 15 min within the first hour of preload consumption and every 30 min for the subsequent 2 h. Participants left the study site 3 h after preload consumption and completed a food diary for the rest of the day., Results: Ad libitum lunch intake was significantly higher for the NNS treatments compared with sucrose (P=0.010). The energy 'saved' from replacing sucrose with NNS was fully compensated for at subsequent meals; hence, no difference in total daily energy intake was found between the treatments (P=0.831). The sucrose-sweetened beverage led to large spikes in blood glucose and insulin responses within the first hour, whereas these responses were higher for all three NNS beverages following the test lunch. Thus, there were no differences in total area under the curve (AUC) for glucose (P=0.960) and insulin (P=0.216) over 3 h between the four test beverages., Conclusions: The consumption of calorie-free beverages sweetened with artificial and natural NNS have minimal influences on total daily energy intake, postprandial glucose and insulin compared with a sucrose-sweetened beverage.

Evidence of an association between added sugars (AS) and the risk of obesity has triggered public health bodies to develop strategies enabling consumers to manage their AS intake. The World Health Organisation (WHO) has strongly recommended a reduction of free sugars to 10% of total dietary energy (TE) and conditionally recommended a reduction to 5% TE to achieve health benefits. Despite food labelling being a policy tool of choice in many countries, there is no consensus on the mandatory addition of AS to the nutrition panel of food labels. An online survey was conducted to explore consumer ability to identify AS on food labels and to investigate consumer awareness of the WHO guidelines in relation to sugar intakes. The questionnaire was tested for participant comprehension using face-to-face interviews prior to conducting the online study. The online survey was conducted in Northern Ireland during May 2015 and was completed by a convenient sample of 445 subjects. Results showed that just 4% of respondents correctly classified 10 or more ingredients from a presented list of 13 items, while 65% of participants were unaware of the WHO guidelines for sugar intake. It may be timely to reopen dialogue on inclusion of AS on food product nutrition panels., Competing Interests: The authors declare no conflict of interest.

This study assessed the effect of carbohydrate intake on self-selected soccer-specific running performance. Sixteen male soccer players (age 23 ± 4 years; body mass 76.9 ± 7.2 kg; predicted VO 2max = 54.2 ± 2.9 mL∙kg -1 ∙min -1 ; soccer experience 13 ± 4 years) completed a progressive multistage fitness test, familiarisation trial and two experimental trials, involving a modified version of the Loughborough Intermittent Shuttle Test (LIST) to simulate a soccer match in a fed state. Subjects completed six 15 min blocks (two halves of 45 min) of intermittent shuttle running, with a 15-min half-time. Blocks 3 and 6, allowed self-selection of running speeds and sprint times, were assessed throughout. Subjects consumed 250 mL of either a 12% carbohydrate solution (CHO) or a non-caloric taste matched placebo (PLA) before and at half-time of the LIST. Sprint times were not different between trials (CHO 2.71 ± 0.15 s, PLA 2.70 ± 0.14 s; p = 0.202). Total distance covered in self-selected blocks (block 3: CHO 2.07 ± 0.06 km; PLA 2.09 ± 0.08 km; block 6: CHO 2.04 ± 0.09 km; PLA 2.06 ± 0.08 km; p = 0.122) was not different between trials. There was no difference between trials for distance covered ( p ≥ 0.297) or mean speed ( p ≥ 0.172) for jogging or cruising. Blood glucose concentration was greater ( p < 0.001) at the end of half-time during the CHO trial. In conclusion, consumption of 250 mL of 12% CHO solution before and at half-time of a simulated soccer match does not affect self-selected running or sprint performance in a fed state., Competing Interests: Ian Rollo is an employee of the Gatorade Sports Science Institute, a division of PepsiCo Inc. The views expressed in this manuscript are those of the authors and do not necessarily reflect the position or policy of PepsiCo Inc.

Background: The effects of non-nutritive sweeteners (NNS) on glucose metabolism and appetite regulating hormones are not clear. There is an ongoing debate concerning NNS use and deleterious changes in metabolism., Objectives: The aim of this review is to analyze the scientific available evidence regarding the effects of NNS on glucose metabolism and appetite regulating hormones., Data Sources and Study Eligibility Criteria: We identified human observational studies evaluating the relation between NNS consumption and obesity, diabetes, and metabolic syndrome, in addition to clinical trials evaluating the effects of NNS in glucose metabolism and appetite regulating hormones., Results: Fourteen observational studies evaluating the association between NNS consumption and the development of metabolic diseases and twenty-eight clinical trials studying the effects of NNS on metabolism were included. Finally, two meta-analyses evaluating the association between the consumption of NNS-containing beverages and the development of type 2 diabetes were identified., Conclusions: Some observational studies suggest an association between NNS consumption and development of metabolic diseases; however, adiposity is a confounder frequently found in observational studies. The effects of the NNS on glucose metabolism are not clear. The results of the identified clinical trials are contradictory and are not comparable because of the major existing differences between them. Studies evaluating specific NNS, with an adequate sample size, including a homogeneous study group, identifying significant comorbidities, with an appropriate control group, with an appropriate exposure time, and considering adjustment for confounder variables such as adiposity are needed.

Background: The relation between the consumption of sweetened beverages and metabolic syndrome (MetS) is controversial., Objective: This analysis evaluated the associations between intakes of sugar-sweetened beverages (SSBs), artificially sweetened beverages, and natural and bottled fruit juices and the incidence of MetS in elderly individuals at high risk of cardiovascular disease (CVD) and without MetS at baseline., Methods: We prospectively examined 1868 participants free of MetS at baseline from the PREDIMED (PREvención con DIeta MEDiterránea) study. MetS was defined by using the updated harmonized criteria of the International Diabetes Federation, the American Heart Association, and National Heart, Lung, and Blood Institute. Energy and nutrient intakes were evaluated at baseline and then yearly by using a validated 137-item food-frequency questionnaire. Multivariable-adjusted HRs for MetS and its components were estimated from mean intakes during follow-up. We compared the 2 highest consumption categories (1-5 and >5 servings/wk) with the lowest category (<1 serving/wk)., Results: A total of 930 incident cases of MetS were documented during a median follow-up of 3.24 y. When we compared consumption of >5 servings/wk with consumption of <1 serving/wk, multivariable HRs (95% CIs) for MetS incidence were 1.43 (1.00, 2.15), 1.74 (1.26, 2.41), 1.30 (1.00, 1.69), and 1.14 (1.04, 1.65) for SSBs, artificially sweetened beverages, natural fruit juices, and bottled fruit juices, respectively., Conclusions: The occasional consumption of SSBs and artificially sweetened beverages (1-5 servings/wk) was not associated with the incidence of MetS in middle-aged and elderly individuals at high risk of CVD. The consumption of >5 servings/wk of all of the types of beverages analyzed was associated with an increased risk of MetS and some of its components. However, for SSBs and bottled fruit juices these associations must be interpreted with caution because of the low frequency of consumption in this population. This trial was registered at clinicaltrials.gov as ISRCTN35739639., (© 2016 American Society for Nutrition.)

Background/objectives: Nonalcoholic fatty liver disease (NAFLD) is the major concern of public health worldwide. The risk of NAFLD in subjects who regularly drink soda is controversial. The aim of this study was to assess the association between consumption of sugar-sweetened soda and NAFLD., Methods: A literature search was performed using MEDLINE, EMBASE, and Cochrane Database of Systematic Reviews from inception through June 2015. Studies that reported relative risks, odd ratios, or hazard ratios comparing the risk of NAFLD in patients consuming a significant amount of either sugar or artificially sweetened soda vs. those who did not consume soda were included. Pooled risk ratios (RRs) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method., Results: Seven observational studies were included in our analysis to assess the association between consumption of sugar-sweetened soda and NAFLD. The pooled RR of NAFLD in patients consuming sugar-sweetened soda was 1.53 (95% CI: 1.34-1.75, I(2) = 0). When meta-analysis was limited only to studies with adjusted analysis, the pooled RR of NAFLD was 1.55 (95% CI: 1.36-1.78, I(2) = 0). The data on association between consumption of artificially sweetened soda and NAFLD were limited; one observational study reported no significant increased risk of NAFLD in artificially sweetened soda consumption., Conclusions: Our study demonstrates statistically significant association between sugar-sweetened soda consumption and NAFLD. This finding may impact clinical management and primary prevention of NAFLD., (© The Author 2015. Published by Oxford University Press on behalf of the Association of Physicians. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background: Increased energy intake is consistently observed in individuals consuming sugar-sweetened beverages (SSBs), likely mainly because of an inadequate satiety response to liquid calories. However, SSBs have a high content of fructose, the consumption of which acutely fails to trigger responses in key signals involved in energy homeostasis. It is unclear whether the fructose content of SSBs contributes to the increased energy intake in individuals drinking SSBs., Objective: We investigated whether the relative amounts of fructose and glucose in SSBs modifies ad libitum energy intake over 8 d in healthy adults without fructose malabsorption., Design: We conducted 2 randomized, controlled, double-blind crossover studies to compare the effects of consuming 4 servings/d of a fructose-, glucose-, or aspartame-sweetened beverage (study A; n = 9) or a fructose-, glucose-, or high-fructose corn syrup (HFCS)-sweetened beverage (study B; n = 24) for 8 d on overall energy intake. SSBs were provided at 25% of estimated energy requirement, or an equivalent volume of the aspartame-sweetened beverage, and consumption was mandatory. All solid foods were provided at 125% of estimated energy requirements and were consumed ad libitum., Results: In study A, ad libitum energy intake was 120% ± 10%, 117% ± 12%, and 102% ± 15% of estimated energy requirements when subjects consumed the fructose-, glucose-, and aspartame-sweetened beverages. Energy intake was significantly higher in the fructose and glucose phases than in the aspartame phase (P < 0.003 for each), with no difference between the fructose and glucose phases (P = 0.462). In study B, total energy intake during the fructose, HFCS, and glucose phases was 116% ± 14%, 116% ± 16%, and 116% ± 16% of the subject's estimated total energy requirements (P = 0.880)., Conclusions: In healthy adults, total 8-d ad libitum energy intake was increased in individuals consuming SSBs compared with aspartame-sweetened beverages. The energy overconsumption observed in individuals consuming SSBs occurred independently of the relative amounts of fructose and glucose in the beverages. These trials were registered at clinicaltrials.gov as NCT00475475 and NCT01424306., (© 2015 American Society for Nutrition.)