Consumption of Low-Calorie Sweeteners among Children Aged 6 Months to 5 Years in the United States, NHANES 2017-2020.

BACKGROUND: Although the American Academy of Pediatrics advises against low-calorie sweeteners (LCS) consumption by children <5 y due to potential health and development concerns, the extent of this consumption among these children is unknown. OBJECTIVES: The objective of this study was to describe the intake, sources, and dietary patterns associated with LCS consumption among United States infants and preschoolers. METHODS: We used cross-sectional 24-h dietary recall data (day 1) among 1497 children aged 6 mo to 5 y from the National Health and Nutrition Examination Survey 2017-2020 prepandemic. Complex survey procedures and sampling weights were applied to compare LCS consumption patterns (prevalence and frequency [times/day] of any LCS, any LCS-containing beverages [LCSBs], and any LCS-containing foods [LCSFs], with each occurrence of consumption = 1 "serving") across demographic subgroups and to assess the associated nutrients and % of total energy intake (TEI). RESULTS: Thirty-one percent of children aged 6 mo to 5 y consumed ≥1 LCSB and/or LCSF on a given day. The prevalence of LCS consumption increased with age, 10.5% (6 to <12 mo) to 34.3% (2-5 y). Among LCS consumers, mean serving frequency was 1.4 times/d, with no differences by age or sex. Of all LCSBs servings consumed, 64.0% were fruit drinks; 57.8% of all LCSFs servings were non-Greek yogurt. As consumption levels increased from no LCS to >1 serving/d, intake of the following also increased: total sugar (+1.8% TEI, P-trend = 0.04), added sugar (+1.1%, P-trend = 0.048), sodium (+304 mg, P-trend = 0.04), and fiber (+0.8 g, P-trend = 0.01). In contrast, protein intake was lower (-0.7% TEI, P-trend = 0.02). Those consuming 1 LCS serving/d consumed more total energy than LCS nonconsumers (1606 compared with 1401 kcal), but TEI did not increase further with >1 LCS serving/d (1607 kcal). LCS consumption was not associated with carbohydrate or fat intake. CONCLUSIONS: LCS consumption, primarily from fruit drinks and non-Greek yogurt, is prevalent among United States preschoolers, and this consumption is associated with greater intake of total sugar, added sugar, and sodium.

Assessing the relationship between low-calorie sweetener use and quality of life measures in adults with type 1 diabetes.

BACKGROUND: To evaluate use of low-calorie sweeteners (LCS) among adults with type 1 diabetes (T1D) and its impact on quality of life (QOL). METHODS: In this single center, cross-sectional survey study with 532 adults with T1D, Food related QOL (FRQOL), LCS specific questionnaire (LCSSQ), Diabetes Self-Management Questionnaire (DSMQ), Food Frequency Questionnaire (FFQ), Audit of Diabetes-Dependent QOL (AddQOL), Type 1 Diabetes and Life (T1DAL) questionnaires were administered through RedCAP, a secure, HIPAA-compliant web-based application. Demographics and scores of adults who used LCS in last month (recent users) and others (non-users) were compared. Results were adjusted for age, sex, diabetes duration and other parameters. RESULTS: Of 532 participants (mean age 36 ± 13, 69% female), 99% heard LCS before, 68% used them in the last month, 73% reported better glucose control with LCS use and 63% reported no health concerns about LCS use. Recent LCS users were older and had a longer diabetes duration and more complications (hypertension, or any complication) than non-users. However, A1c, AddQOL, T1DAL, FRQOL scores did not differ significantly between recent LCS users and non-users. DSMQ scores, DSMQ management, diet, health care scores did not differ between two groups; however, recent LCS users had lower physical activity score than non-users (p = 0.001). CONCLUSIONS: Most of the adults with T1D have used LCS and perceived that LCS use improved their QOL and glycemic control; however, these were not verified with questionnaires. There was no difference in QOL questionnaires except DSMQ physical activity between recent LCS users and not users with T1D. However, more patients in need to increase their QOL may be using LCS; therefore, associations between the exposure and outcome can be bi-directional.

Consumption of low-calorie sweetened drinks is associated with 'sweet satiation', but not with 'sweet-taste confusion': A virtual study.

Originating from studies on rats, the 'taste confusion' hypothesis predicts that exposure to low-calorie sweeteners (LCS) will impair compensatory responses to sugar intake, resulting in increased overall calorie intake. We conducted a virtual study in which young adult human participants (n = 332), who differed in their history of exposure to sweet drinks (e.g., drank 'diet' (LCS) soft drinks or 'regular' (sugar-sweetened) soft drinks), imagined consuming a cheese sandwich and two-thirds of a 500 ml drink (still water, sparkling water, diet Coca Cola, regular Coca Cola, or semi-skimmed milk), or no drink, as a hypothetical lunch-time meal. They then used a screen-based tool to select the amount of a sweet snack (chocolate M&M's) or savoury snack (salted peanuts) that they would eat immediately with the remaining third of their drink (i.e., a total of 12 drink and snack combinations per participant). The results were inconsistent with the predictions of the taste confusion hypothesis; specifically, the extent to which consumption of sugar cola compared with water (still or sparkling) reduced snack intake did not differ between habitual diet (LCS) and habitual sugar soft-drink consumers. Other results showed a 'sweet satiation' effect (i.e., lower sweet versus savoury snack intake when the drink accompanying the meal was sweet compared with when it was water), and negligible compensation in snack food intake for the difference in the energy content of diet versus sugar cola.

Rare mono- and disaccharides as healthy alternative for traditional sugars and sweeteners?

Obesity and type 2 diabetes are major health problems affecting hundreds of millions of people. Caloric overfeeding with calorie-dense food ingredients like sugars may contribute to these chronic diseases. Sugar research has also identified mechanisms via which conventional sugars like sucrose and fructose can adversely influence metabolic health. To replace these sugars, numerous sugar replacers including artificial sweeteners and sugar alcohols have been developed. Rare sugars became new candidates to replace conventional sugars and their health effects are already reported in individual studies, but overviews and critical appraisals of their health effects are missing. This is the first paper to provide a detailed review of the metabolic health effects of rare sugars as a group. Especially allulose has a wide range of health effects. Tagatose and isomaltulose have several health effects as well, while other rare sugars mainly provide health benefits in mechanistic studies. Hardly any health claims have been approved for rare sugars due to a lack of evidence from human trials. Human trials with direct measures for disease risk factors are needed to allow a final appraisal of promising rare sugars. Mechanistic cell culture studies and animal models are required to enlarge our knowledge on understudied rare sugars.

Low-calorie sweeteners cause only limited metabolic effects in mice.

There are widespread concerns that low-calorie sweeteners (LCSs) cause metabolic derangement. These concerns stem in part from prior studies linking LCS consumption to impaired glucose tolerance in humans and rodents. Here, we examined this linkage in mice. In experiment 1, we provided mice with chow, water, and an LCS-sweetened solution (saccharin, sucralose, or acesulfame K) for 28 days and measured glucose tolerance and body weight across the exposure period. Exposure to the LCS solutions did not impair glucose tolerance or alter weight gain. In experiment 2, we provided mice with chow, water, and a solution containing saccharin, glucose, or a mixture of both for 28 days, and tested for metabolic changes. Exposure to the saccharin solution increased the insulinemic response of mice to the glucose challenge, and exposure to the saccharin + glucose solution increased the rate of glucose uptake during the glucose challenge. However, neither of these test solutions altered glucose tolerance, insulin sensitivity, plasma triglycerides, or percent body fat. In contrast, exposure to the glucose solution increased glucose tolerance, early insulin response, insulin sensitivity, and percent body fat. We conclude that whereas the LCS-containing solutions induced a few metabolic changes, they were modest compared with those induced by the glucose solution.

A Novel Urinary Biomarker Approach Reveals Widespread Exposure to Multiple Low-Calorie Sweeteners in Adults.

BACKGROUND: Observational investigations into the health impacts of low-calorie sweeteners (LCSs) in humans fail to adequately identify or fully characterize LCS consumption. OBJECTIVES: We aimed to utilize a novel biomarker approach to investigate exposure to 5 LCSs and to test whether reported low-calorie sweetened beverage (LCSB) consumption effectively identifies exposure to LCSs in adults. METHODS: In this cross-sectional analysis, 2 population studies were conducted in adults. Urinary excretions of 5 LCSs, namely acesulfame-K, saccharin, cyclamate, sucralose, and steviol glycosides, were simultaneously determined using LC tandem-MS. In Study 1, previously collected 24-h urine samples (n = 357) were analyzed. In Study 2, previously collected 24-h urine samples (n = 79) were analyzed to compare urinary excretions of LCSs with self-reported LCSB consumption for identifying LCS exposure. Exposure to LCSs was characterized using descriptive statistics and chi-square tests were performed to assess associations between age-groups and LCS excretion, and to assess the proportion of individuals identified as LCS consumers using biomarker data or reported LCSB consumption. RESULTS: A total of 341 adults (45% men) and 79 adults (39% men) were included in the final analysis of Studies 1 and 2, respectively. In Study 1, >96% of samples contained ≥1 LCS and almost 60% contained ≥3 LCSs. A greater proportion of younger adults (<40 y old) excreted ≥3 LCSs than older adults (>40 y old) (P < 0.001). In Study 2, a much higher prevalence of LCS consumption was observed using biomarker data (92%) than reported LCSB consumption (6%) (P < 0.001). CONCLUSIONS: This work indicates widespread exposure to LCSs, suggesting that population-based research to date into LCS exposure and health may be flawed. Therefore, a urinary biomarker approach offers considerable potential for more robust investigations in this area.

Expert consensus on low-calorie sweeteners: facts, research gaps and suggested actions.

A consensus workshop on low-calorie sweeteners (LCS) was held in November 2018 where seventeen experts (the panel) discussed three themes identified as key to the science and policy of LCS: (1) weight management and glucose control; (2) consumption, safety and perception; (3) nutrition policy. The aims were to identify the reliable facts on LCS, suggest research gaps and propose future actions. The panel agreed that the safety of LCS is demonstrated by a substantial body of evidence reviewed by regulatory experts and current levels of consumption, even for high users, are within agreed safety margins. However, better risk communication is needed. More emphasis is required on the role of LCS in helping individuals reduce their sugar and energy intake, which is a public health priority. Based on reviews of clinical evidence to date, the panel concluded that LCS can be beneficial for weight management when they are used to replace sugar in products consumed in the diet (without energy substitution). The available evidence suggests no grounds for concerns about adverse effects of LCS on sweet preference, appetite or glucose control; indeed, LCS may improve diabetic control and dietary compliance. Regarding effects on the human gut microbiota, data are limited and do not provide adequate evidence that LCS affect gut health at doses relevant to human use. The panel identified research priorities, including collation of the totality of evidence on LCS and body weight control, monitoring and modelling of LCS intakes, impacts on sugar reduction and diet quality and developing effective communication strategies to foster informed choice. There is also a need to reconcile policy discrepancies between organisations and reduce regulatory hurdles that impede low-energy product development and reformulation.

Sweet satiation: Acute effects of consumption of sweet drinks on appetite for and intake of sweet and non-sweet foods.

Sensory-specific satiety (SSS) describes a reduction in the pleasantness of the taste of (momentary liking) and desire to consume a food that occurs with eating, compared with the relative preservation of liking and desire for uneaten foods. We conducted three studies in healthy female and male participants to test whether SSS generalises from sweet drinks to sweet foods. Studies 1 (n = 40) and 2 (n = 64) used a two-condition cross-over design. Participants consumed non-carbonated, fruit squash drinks sweetened with low-calorie sweeteners (LCS) versus water and evaluated various food and drink samples (stimuli). Generalisation of SSS was evident across all sweet stimuli, without having an effect on non-sweet (savoury) stimuli. These SSS effects were present when measured shortly after consumption of the sweet drink, but not 2 h later. There was no evidence of a 'rebound' increase above baseline in liking or desire to consume sweet foods 2 h after the sweet drink versus water. In study 3, 51 participants consumed labelled and branded 500 ml cola and water drinks (4 conditions, cross-over design) immediately before and during ad libitum consumption of sweet and non-sweet snack foods. Compared with still water, 'diet' (LCS-sweetened) cola reduced sweet food intake, but not total ad libitum intake. Carbonated water decreased hunger and increased fullness compared with still water, without differentially affecting thirst. Energy compensation from the ad libitum snacks for consumption of sugar-containing cola averaged only 20%. Together, these results demonstrate that consumption of LCS drinks acutely decreases desire for sweet foods, which supports their use in place of sugar-sweetened drinks. Further studies on the effects of carbonation of appetite are warranted.

Artificial sweeteners in food and beverage products at school.

OBJECTIVE: Experts recommend that products containing artificial sweeteners are not marketed to children or sold at schools. The present study aimed to provide a baseline assessment of the extent to which state laws and local school district wellness policies (LWP) address restrictions on the use of artificial sweeteners in competitive foods and beverages (CF&B) sold at schools. DESIGN: A descriptive, cross-sectional study of policies in place for the 2014-15 school year. SETTING: Data were collected on laws in all fifty states and Washington, DC. LWP were compiled for 496/518 school food authorities (SFA) for which data were collected as part of the US Department of Agriculture's School Nutrition and Meal Cost Study. SUBJECTS: State laws and LWP respectively were coded on a 0-3 ordinal scale for the strength of their restrictions on artificial sweeteners in CF&B sold in each of five CF&B venues, separately by grade level. Prevalence of state laws and LWP for SFA nationwide was computed. RESULTS: Thirteen states addressed the use of artificial sweeteners. Six states addressed the use of artificial sweeteners in both CF&B. District-level artificial sweetener policies were most frequently addressed for beverages in elementary schools' vending machines. District policies also were more likely to address artificial sweeteners in states with laws addressing artificial sweeteners. CONCLUSIONS: Most state laws and LWP do not address artificial sweeteners in CF&B. This is not surprising given the Food and Drug Administration has approved eight artificial sweeteners for consumption and the Smart Snacks regulation does not limit artificial sweeteners for CF&B.

High-level production of single chain monellin mutants with enhanced sweetness and stability in tobacco chloroplasts.

MAIN CONCLUSION: Plastid-based MNEI protein mutants retain the structure, stability and sweetness of their bacterial counterparts, confirming the attractiveness of the plastid transformation technology for high-yield production of recombinant proteins. The prevalence of obesity and diabetes has dramatically increased the industrial demand for the development and use of alternatives to sugar and traditional sweeteners. Sweet proteins, such as MNEI, a single chain derivative of monellin, are the most promising candidates for industrial applications. In this work, we describe the use of tobacco chloroplasts as a stable plant expression platform to produce three MNEI protein mutants with improved taste profile and stability. All plant-based proteins were correctly expressed in tobacco chloroplasts, purified and subjected to in-depth chemical and sensory analyses. Recombinant MNEI mutants showed a protein yield ranging from 5% to more than 50% of total soluble proteins, which, to date, represents the highest accumulation level of MNEI mutants in plants. Comparative analyses demonstrated the high similarity, in terms of structure, stability and function, of the proteins produced in plant chloroplasts and bacteria. The high yield and the extreme sweetness perceived for the plant-derived proteins prove that plastid transformation technology is a safe, stable and cost-effective production platform for low-calorie sweeteners, with an estimated production of up to 25-30 mg of pure protein/plant.

Where are the low-calorie sweeteners? An analysis of the presence and types of low-calorie sweeteners in packaged foods sold in Brazil from food labelling.

OBJECTIVE: Studies have shown that consumption of low-calorie sweeteners (LCS) may be associated with harmful health effects. The current study investigated the presence and types of LCS added to packaged foods. DESIGN: Cross-sectional study analysing the presence and types of LCS in the ingredients lists of packaged foods sold at a major Brazilian supermarket. To identify types of LCS allowed for use in foods in Brazil, current legislation was consulted. Data were organised and analysed through descriptive statistics, presenting simple and relative frequencies of LCS presence categorised by food group. SETTING: Supermarket in Florianópolis, southern Brazil. SUBJECTS: Packaged food products (n 4539) from eight food groups. RESULTS: One or more LCS were found in 602 (13·3 %) of the packaged foods analysed. There were 1329 citations of LCS among these foods, with a mean of 2·2 sweeteners per food. Groups with the highest frequency of foods containing LCS were: products with energy derived from carbohydrates and fats (25·0 %); milk and dairy products (11·7 %); bakery products, cereals, legumes, roots and tubers (11·2 %); and fruits, juices, nectars and fruit drinks (8·3 %). CONCLUSIONS: There was high prevalence of packaged foods with LCS, especially in food groups that form the basis of the Brazilian diet. The study was the first to extensively analyse the presence and types of LCS in packaged foods available for sale in a Brazilian supermarket and can be useful to monitor the use of LCS in these foods, as well as to support future changes in legislation to label sugars.

TM0416, a Hyperthermophilic Promiscuous Nonphosphorylated Sugar Isomerase, Catalyzes Various C5 and C6 Epimerization Reactions.

There is currently little information on nonphosphorylated sugar epimerases, which are of potential interest for producing rare sugars. We found a gene (the TM0416 gene) encoding a putative d-tagatose-3-epimerase-related protein from the hyperthermophilic bacterium Thermotoga maritima We overexpressed the TM0416 gene in Escherichia coli and purified the resulting recombinant protein for detailed characterization. Amino acid sequence alignment and a structural similarity search revealed that TM0416 is a putative nonphosphorylated sugar epimerase. The recombinant enzyme exhibited maximal C-3 epimerization of l-ribulose to l-xylulose at ∼80°C and pH 7 in the presence of 1 mM Mn2+ In addition, this enzyme showed unusually high activity for the epimerization of d-tagatose to d-sorbose, with a conversion yield of 20% after 6 h at 80°C. Remarkably, the enzyme catalyzed the isomerization of d-erythrose or d-threose to d-erythrulose significantly, with conversion yields of 71% and 54.5%, respectively, after 6 h at 80°C at pH 7. To further investigate the substrate specificity of TM0416, we determined its crystal structures in complex with divalent metal ions and l-erythrulose at resolutions of 1.5 and 1.6 Å. Detailed inspection of the structural features and biochemical data clearly demonstrated that this metalloenzyme, with a freely accessible substrate-binding site and neighboring hydrophobic residues, exhibits different and promiscuous substrate preferences, compared with its mesophilic counterparts. Therefore, this study suggests that TM0416 can be functionally classified as a novel type of l-ribulose 3-epimerase (R3E) with d-erythrose isomerase activity.IMPORTANCE Rare sugars, which occur naturally in small amounts, have attracted considerable attention in the food and drug industries. However, there is little information on nonphosphorylated sugar epimerases, which might potentially be applied for the production of rare sugars. This study describes the characterization and functional annotation of a putative nonphosphorylated sugar 3-epimerase from a hyperthermophilic bacterium. Furthermore, we determined its crystal structures in complex with divalent metal ions and l-erythrulose, highlighting its metal-dependent, bifunctional, sugar-isomerizing activity. This hyperthermophilic R3E exhibited d-erythrose/d-threose isomerase activity, with structural features near the substrate-binding site distinct from those of its mesophilic counterparts. Moreover, this metalloenzyme showed unusually high activity for the epimerization of d-tagatose to d-sorbose at 70°C. Therefore, TM0416 can be functionally classified as a novel type of promiscuous R3E with a potential for the production of rare sugars for the food and pharmaceutical industries.

Understanding the metabolic and health effects of low-calorie sweeteners: methodological considerations and implications for future research.

Consumption of foods, beverages, and packets containing low-calorie sweeteners (LCS) has increased markedly across gender, age, race/ethnicity, weight status, and socio-economic subgroups. However, well-controlled intervention studies rigorously evaluating the health effects of LCS in humans are limited. One of the key questions is whether LCS are indeed a beneficial strategy for weight management and prevention of obesity. The current review discusses several methodological considerations in the design and interpretation of these studies. Specifically, we focus on the selection of study participants, inclusion of an appropriate control, importance of considering habitual LCS exposure, selection of specific LCS, dose and route of LCS administration, choice of study outcomes, and the context and generalizability of the study findings. These critical considerations will guide the design of future studies and thus assist in understanding the health effects of LCS.

[Effects of low calorie sweeteners based on data from clinical trials, in vitro and animal studies]. / Az energiamentes édesítoszerek alkalmazásának hatása klinikai vizsgálatok, in vitro és állatkísérletek eredményei alapján.

Low calorie sweeteners are used by many consumers as they can provide the sweet taste without calories and, therefore, they may have a beneficial effect on weight management. These positive outcomes are often questioned and accused of keeping up or increasing a liking for sweetness and leading to overconsumption of sugar containing food and beverages. The most recent studies failed to find any positive correlation between usage of low calorie sweeteners and craving for sweet taste. In randomized controlled trials consumption of low calorie sweeteners have accompanied with lower intake of sugar containing food, higher healthy eating index and better weight management. Several laboratory trials on cell cultures and animal studies found a link between the usage of low calorie sweeteners and positive metabolic effects, e.g. smaller ectopic fat deposits in the fat and liver tissue versus controll group. In addition, increased adipogenesis and reduction of lipolysis were also observed. Orv. Hetil., 2016, 157(Suppl. 1), 3-7.

A dynamic panel model of the associations of sweetened beverage purchases with dietary quality and food-purchasing patterns.

Investigating the association between consumption of sweetened beverages and dietary quality is challenging because issues such as reverse causality and unmeasured confounding might result in biased and inconsistent estimates. Using a dynamic panel model with instrumental variables to address those issues, we examined the independent associations of beverages sweetened with caloric and low-calorie sweeteners with dietary quality and food-purchasing patterns. We analyzed purchase data from the Homescan survey, an ongoing, longitudinal, nationally representative US survey, from 2000 to 2010 (n = 34,294). Our model included lagged measures of dietary quality and beverage purchases (servings/day in the previous year) as exposures to predict the outcomes (macronutrient (kilocalories per capita per day; %), total energy, and food purchases) in the next year after adjustment for other sociodemographic covariates. Despite secular declines in purchases (kilocalories per capita per day) from all sources, each 1-serving/day increase in consumption of either beverage type resulted in higher purchases of total daily kilocalories and kilocalories from food, carbohydrates, total sugar, and total fat. Each 1-serving/day increase in consumption of either beverage was associated with more purchases of caloric-sweetened desserts or sweeteners, which accounted for a substantial proportion of the increase in total kilocalories. We concluded that consumers of both beverages sweetened with low-calorie sweeteners and beverages sweetened with caloric sweeteners had poorer dietary quality, exhibited higher energy from all purchases, sugar, and fat, and purchased more caloric-sweetened desserts/caloric sweeteners compared with nonconsumers.

Consumption of sucralose- and acesulfame-potassium-containing diet soda alters the relative abundance of microbial taxa at the species level: findings of two pilot studies.

Sucralose and acesulfame-potassium consumption alters gut microbiota in rodents, with unclear effects in humans. We examined effects of three-times daily sucralose- and acesulfame-potassium-containing diet soda consumption for 1 (n = 17) or 8 (n = 8) weeks on gut microbiota composition in young adults. After 8 weeks of diet soda consumption, the relative abundance of Proteobacteria, specifically Enterobacteriaceae, increased; and, increased abundance of two Proteobacteria taxa was also observed after 1 week of diet soda consumption compared with sparkling water. In addition, three taxa in the Bacteroides genus increased following 1 week of diet soda consumption compared with sparkling water. The clinical relevance of these findings and effects of sucralose and acesulfame-potassium consumption on human gut microbiota warrant further investigation in larger studies. Clinical trial registration: NCT02877186 and NCT03125356.

Intergenerational transmission of sucralose and acesulfame-potassium from mothers to their infants via human milk: a pharmacokinetic study.

BACKGROUND: Low-calorie sweetener (LCS) consumption is prevalent among lactating mothers, yet infants' exposure to LCS in human milk is not well-characterized. OBJECTIVES: Conduct a pharmacokinetic study of sucralose and acesulfame-potassium (ace-K) in mothers' milk and plasma over 72 h and in infants' plasma. METHODS: Following baseline blood and milk collection, mothers (n = 40) consumed 20 oz of diet cranberry juice containing sucralose and ace-K. Blood samples were collected from the mother 0.5, 1, 1.5, 2, 3, 4, 6, 8, 12, 24, 48, and 72 h after beverage ingestion, and milk was expressed at 1, 2, 3, 4, 6, 8, 12, and 24 h postingestion. One blood sample was collected from each infant, the timing of which was determined using pharmacokinetics model-based simulation. Concentration-time profiles of LCS from the mother's plasma and milk were analyzed using noncompartmental methods. RESULTS: Ace-K rapidly entered human milk with the largest observed concentration of 373.0 (coefficient of variation 69%) ng/mL first detected 4 h following diet beverage ingestion. Sucralose appeared in human milk 1-2 h after diet beverage ingestion with the largest observed concentration of 7.2 (coefficient of variation 63%) ng/mL first detected 7 h postingestion. The mean 24-h milk to plasma ratio of ace-K was 1.75 [standard deviation (SD) 1.37] with a mean relative infant dose of 1.59% (SD 1.72%). Ace-K was detected in all infants' plasma with an mean concentration of 9.2 (SD% 14.8) ng/mL ∼6 h after maternal beverage ingestion. The mean 24-h milk to plasma ratio of sucralose was 0.15 (SD 0.06) with a mean relative infant dose of 0.04% (SD 0.02%). Sucralose was detected in only 15 infants' plasma, and the mean concentration was 5.0 (SD% 7.1) ng/mL ∼5 h after diet beverage ingestion. CONCLUSIONS: Ace-K rapidly transfers from human milk into infants' circulation whereas sucralose was detected at much lower concentrations and in some but not all infants. Future research should investigate the effects of early-life sucralose and ace-K exposure via human milk on infants' health. This trial was registered at clinicaltrials.gov as NCT05379270.

Non-Sugar-Sweetened Beverages and Risk of Chronic Diseases: An Umbrella Review of Meta-analyses of Prospective Cohort Studies.

CONTEXT: Several effects of non-sugar-sweetened beverage (NSSBs) intake on health outcomes have been reported; however, the evidence on the association between NSSBs intake and chronic diseases and mortality risk is still inconclusive. OBJECTIVE: This umbrella review aimed to summarize the evidence on the association between NSSBs intake and the risk of chronic diseases and mortality. DATA SOURCES: Embase, ISI Web of Science, Cochrane Central, and PubMed were searched up to September 2023 for relevant meta-analyses of observational prospective cohort studies. DATA EXTRACTION: Two groups of researchers independently extracted study data and assessed the risk of bias for meta-analyses and primary studies. DATA ANALYSIS: Six meta-analyses, reporting 74 summary hazard ratios (HRs) for different outcomes obtained from 50 primary studies, were included. The summary HRs, 95% CIs, and certainty of evidence on the association of NSSBs intake with risk of chronic diseases and mortality were as follows: all-cause mortality (per 355 mL/d: 1.06 [1.01 to 1.10]; moderate certainty); stroke (per 250 mL/d: 1.09 [1.04 to 1.13]; high certainty); coronary heart disease (CHD) (per 250 mL/d: 1.06 [1.02 to 1.11]; high certainty); hypertension (HTN) (high vs low intake: 1.14 [1.09 to 1.18]; moderate certainty); type 2 diabetes (T2D) (high vs low intake: 1.16 [1.08 to 1.26]; low certainty); metabolic syndrome (MetS) (high vs low intake: 1.32 [1.22 to 1.43]; low certainty); colorectal cancer (high vs low intake: 0.78 [0.62 to 0.99]; moderate certainty); and leukemia (high vs low intake: 1.35 [1.03 to 1.77]; moderate certainty). For other outcomes, including the risk of cardiovascular and cancer mortality, chronic kidney diseases, breast cancer, prostate cancer, endometrial cancer, pancreatic cancer, multiple myeloma, and non-Hodgkin lymphoma, no association was found. CONCLUSION: This study provides further evidence that NSSBs are associated with increased risk of all-cause mortality, stroke, CHD, HTN, T2D, MetS, and leukemia. Moreover, a higher intake of NSSBs was associated with a lower risk of colorectal cancer. However, it should be noted that the magnitudes of the associations are not large. Further studies are needed to clarify the long-term effects of different NSSBs intakes on health. SYSTEMATIC REVIEW REGISTRATION: PROSPERO no. CRD42023429981.

Substituting Low-Calorie Sweetened Beverages for Sugar-Sweetened Beverages to Prevent Obesity and Cardiometabolic Diseases: Still a Good Idea?

Low-calorie sweeteners (LCSs) and LCS-containing beverages have been proposed as appropriate substitutes for caloric sugars in recent years. In this Perspective, we highlight the recent findings from observational and interventional studies, focusing on obesity, gut microbiome, and cardiometabolic health. We provide public health actors and health care professionals with an insightful overview of recent evidence to bridge the gap between research and practice.

Determination of sweetener specificity of horse gut-expressed sweet taste receptor T1R2-T1R3 and its significance for energy provision and hydration.

Studies carried out in several species have demonstrated that detection of low-calorie sweeteners in the lumen of the intestine, by the sweet receptor, T1R2-T1R3, initiates a signaling pathway leading to enhanced expression and activity of intestinal Na+/glucose cotransporter 1, SGLT1. This results in an increased gut capacity to absorb glucose, sodium chloride and water, the basis for oral rehydration therapy. Horses express T1R2, T1R3 and downstream signaling elements in the intestinal tissue. As such, the potential of sweetener-stimulation of T1R2-T1R3 leading to upregulation of SGLT1 allows the provision of more glucose (energy) and hydration for horses. This is especially important when the need for glucose increases during strenuous exercise, pregnancy, and lactation. There are significant differences among species in the ability to detect sweeteners. Amino acid substitutions and pseudogenization of taste receptor genes underlie these variations. Nothing is known about the sweetener specificity of horse T1R2-T1R3. Using heterologous expression methodology, we demonstrate that sweeteners sucralose, stevia and neohesperidin dihydrochalcone (NHDC) activate horse T1R2-T1R3, but cyclamate does not. Determination of sweetener specificity of equine sweet receptor is crucial for developing suitable dietary additives to optimize glucose absorption, hydration and avoiding the intestinal disease brought about by microbial fermentation of unabsorbed carbohydrate reaching the large intestine.