Effects of Non-Nutritive Sweeteners on Energy Intake, Body Weight and Postprandial Glycemia in Healthy and with Altered Glycemic Response Rats.
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ABSTRACT:
SUBMITTER: Ramos-Garcia M
PROVIDER: S-EPMC8146401 | biostudies-literature |
REPOSITORIES: biostudies-literature
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| S-EPMC7387865 | biostudies-literature
Project description:Recent studies suggest that preferences are conditioned by nutritive (sucrose) but not by non-nutritive (sucralose) sweeteners in mice. Here we compared the effectiveness of nutritive and non-nutritive sweeteners to condition flavor preferences in three mouse strains. Isopreferred sucrose and sucralose solutions both conditioned flavor preferences in C57BL/6J (B6) mice but sucrose was more effective, consistent with its post-oral appetition action. Subsequent experiments compared flavor conditioning by fructose, which has no post-oral appetition effect in B6 mice, and a sucralose+saccharin mixture (SS) which is highly preferred to fructose in 24-h choice tests. Both sweeteners conditioned flavor preferences but fructose induced stronger preferences than SS. Training B6 mice to drink a flavored SS solution paired with intragastric fructose infusions did not enhance the SS-conditioned preference. Thus, the post-oral nutritive actions of fructose do not explain the sugar's stronger preference conditioning effect. Training B6 mice to drink a flavored fructose solution containing SS did not reduce the sugar-conditioned preference, indicating that SS does not have an off-taste that attenuates conditioning. Although B6 mice strongly preferred flavored SS to flavored fructose in a direct choice test, they preferred the fructose-paired flavor to the SS-paired flavor when these were presented in water. Fructose conditioned a stronger flavor preference than an isopreferred saccharin solution, indicating that sucralose is not responsible for the limited SS conditioning actions. SS is highly preferred by FVB/NJ and CAST/EiJ inbred mice, yet conditioned only weak flavor preferences. It is unclear why highly or equally preferred non-nutritive sweeteners condition weaker preferences than fructose, when all stimulate the same T1r2/T1r3 sweet receptor. Recent findings support the existence of non-T1r2/T1r3 glucose taste sensors; however, there is no evidence for receptors that respond to fructose but not to non-nutritive sweeteners.
| S-EPMC5357161 | biostudies-literature
Project description:IntroductionThis study aimed to explore the knowledge, attitude, and practice (KAP) toward non-nutritive sweeteners among a population with reduced sugar intake requirements.MethodsThis cross-sectional study used self-developed questionnaires to collect demographic characteristics and KAP towards non-nutritive sweeteners among respondents with reduced sugar intake requirements, i.e., overweight or obese individuals and patients with pre-diabetes or diabetes.ResultsA total of 639 valid questionnaires were collected, and 51.64% of participants were male. The KAP scores were 7.63 ± 3.58 (range: 0-11), 34.28 ± 7.47 (range: 12-60), and 15.48 ± 3.97 (range: 7-35), respectively. Pearson's correlation analysis showed that knowledge score was positively correlated with attitude (r = 0.229, p < 0.001) and practice score (r = 0.467, p < 0.001), while attitude was positively correlated with practice (r = 0.312, p < 0.001). The structural equation model showed that knowledge was directly and positively associated with attitude (path coefficient = 0.48, p < 0.001) and practice (path coefficient = 0.46, p < 0.001). In addition, the attitude was directly and positively associated with practice (path coefficient = 0.12, p < 0.001). Besides, diabetes was associated with lower knowledge (path coefficient = -0.81, p = 0.038) and practice (path coefficient = -0.42, p < 0.041).DiscussionPopulation with the reduced sugar intake requirement showed poor knowledge, negative attitudes, and suboptimal practices toward non-nutritive sweeteners. To optimize the utilization of non-nutritive sweeteners in accordance with medical prescriptions, especially for individuals with diabetes, tailored educational interventions may be designed for participants with lower KAP.
| S-EPMC10796998 | biostudies-literature
Project description:ObjectiveExcessive consumption of added sugars has been linked to the rise in obesity and associated metabolic abnormalities. Non-nutritive sweeteners (NNSs) offer a potential solution to reduce sugar intake, yet their metabolic safety remains debated. This study aimed to systematically assess the long-term metabolic effects of commonly used NNSs under both normal and obesogenic conditions.MethodsTo ensure consistent sweetness level and controlling for the acceptable daily intake (ADI), eight weeks old C57BL/6 male mice were administered with acesulfame K (ace K, 535.25 mg/L), aspartame (411.75 mg/L), sucralose (179.5 mg/L), saccharin (80 mg/L), or steviol glycoside (Reb M, 536.25 mg/L) in the drinking water, on the background of either regular or high-fat diets (in high fat diet 60% of calories from fat). Water or fructose-sweetened water (82.3.gr/L), were used as controls. Anthropometric and metabolic parameters, as well as microbiome composition, were analyzed following 20-weeks of exposure.ResultsUnder a regular chow diet, chronic NNS consumption did not significantly affect body weight, fat mass, or glucose metabolism as compared to water consumption, with aspartame demonstrating decreased glucose tolerance. In diet-induced obesity, NNS exposure did not increase body weight or alter food intake. Exposure to sucralose and Reb M led to improved insulin sensitivity and decreased weight gain. Reb M specifically was associated with increased prevalence of colonic Lachnospiracea bacteria.ConclusionsLong-term consumption of commonly used NNSs does not induce adverse metabolic effects, with Reb M demonstrating a mild improvement in metabolic abnormalities. These findings provide valuable insights into the metabolic impact of different NNSs, aiding in the development of strategies to combat obesity and related metabolic disorders.
| S-EPMC11347859 | biostudies-literature
Project description:Background: There has been an emerging concern that non-nutritive sweeteners (NNS) can increase the risk of cardiometabolic disease. Much of the attention has focused on acute metabolic and endocrine responses to NNS. To examine whether these mechanisms are operational under real-world scenarios, we conducted a systematic review and network meta-analysis of acute trials comparing the effects of non-nutritive sweetened beverages (NNS beverages) with water and sugar-sweetened beverages (SSBs) in humans. Methods: MEDLINE, EMBASE, and The Cochrane Library were searched through to January 15, 2022. We included acute, single-exposure, randomized, and non-randomized, clinical trials in humans, regardless of health status. Three patterns of intake were examined: (1) uncoupling interventions, where NNS beverages were consumed alone without added energy or nutrients; (2) coupling interventions, where NNS beverages were consumed together with added energy and nutrients as carbohydrates; and (3) delayed coupling interventions, where NNS beverages were consumed as a preload prior to added energy and nutrients as carbohydrates. The primary outcome was a 2 h incremental area under the curve (iAUC) for blood glucose concentration. Secondary outcomes included 2 h iAUC for insulin, glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), peptide YY (PYY), ghrelin, leptin, and glucagon concentrations. Network meta-analysis and confidence in the network meta-analysis (CINeMA) were conducted in R-studio and CINeMA, respectively. Results: Thirty-six trials involving 472 predominantly healthy participants were included. Trials examined a variety of single NNS (acesulfame potassium, aspartame, cyclamate, saccharin, stevia, and sucralose) and NNS blends (acesulfame potassium + aspartame, acesulfame potassium + sucralose, acesulfame potassium + aspartame + cyclamate, and acesulfame potassium + aspartame + sucralose), along with matched water/unsweetened controls and SSBs sweetened with various caloric sugars (glucose, sucrose, and fructose). In uncoupling interventions, NNS beverages (single or blends) had no effect on postprandial glucose, insulin, GLP-1, GIP, PYY, ghrelin, and glucagon responses similar to water controls (generally, low to moderate confidence), whereas SSBs sweetened with caloric sugars (glucose and sucrose) increased postprandial glucose, insulin, GLP-1, and GIP responses with no differences in postprandial ghrelin and glucagon responses (generally, low to moderate confidence). In coupling and delayed coupling interventions, NNS beverages had no postprandial glucose and endocrine effects similar to controls (generally, low to moderate confidence). Conclusions: The available evidence suggests that NNS beverages sweetened with single or blends of NNS have no acute metabolic and endocrine effects, similar to water. These findings provide support for NNS beverages as an alternative replacement strategy for SSBs in the acute postprandial setting.
| S-EPMC9965414 | biostudies-literature
Project description:BACKGROUND:Non-nutritive sweeteners (NNS), especially in form of diet soda, have been linked to metabolic derangements (e.g. obesity and diabetes) in epidemiologic studies. We aimed to test acute metabolic effects of NNS in isolation (water or seltzer) and in diet sodas. METHODS:We conducted a four-period, cross-over study at the National Institutes of Health Clinical Center (Bethesda, Maryland). Thirty healthy adults consumed 355 mL water with 0 mg, 68 mg, 170 mg, and 250 mg sucralose, and 31 individuals consumed 355 mL caffeine-free Diet Rite Cola™, Diet Mountain Dew™ (18 mg sucralose, 18 mg acesulfame-potassium, 57 mg aspartame), and seltzer water with NNS (68 mg sucralose and 41 mg acesulfame-potassium, equivalent to Diet Rite Cola™) in randomized order, prior to oral glucose tolerance tests. Blood samples were collected serially for 130 min. Measures included GLP-1, GIP, glucose, insulin, C-peptide, glucose absorption, gastric emptying, and subjective hunger and satiety ratings. RESULTS:Diet sodas augmented active GLP-1 (Diet Rite Cola™ vs. seltzer water, AUC, p?=?0.039; Diet Mountain Dew™ vs. seltzer water, AUC, p?=?0.07), but gastric emptying and satiety were unaffected. Insulin concentrations were nominally higher following all NNS conditions without altering glycemia. Sucralose alone (at any concentration) did not affect metabolic outcomes. CONCLUSIONS:Diet sodas but not NNS in water augmented GLP-1 responses to oral glucose. Whether the trends toward higher insulin concentrations after NNS are of clinical importance remains to be determined. Our findings emphasize the need to test metabolic effects of NNS after chronic consumption. TRIAL REGISTRATION:The data for this manuscript were gathered from clinical trial #NCT01200940.
| S-EPMC5073441 | biostudies-literature
Project description:With the prevalence of obesity, non-nutritive sweeteners (NNS) have been widely used as sugar substitutes as they deliver a sweet taste without excessive caloric load. However, it is increasingly recognized that NNS are not inert compounds and may cause long-term metabolic perturbations. Endoplasmic reticulum (ER) stress has emerged as a critical link in the development of obesity and type 2 diabetes. In this study, we investigated the effects of NNS found in common diet beverages (i.e., sucralose, aspartame, acesulfame potassium) and a natural sweetener (i.e., rebaudioside A) on ER stress in the hypothalamic cell line mHypoE-N43/5 in vivo and on axonal outgrowth ex vivo. Sucralose, aspartame, and acesulfame potassium caused elevated ER stress gene expression in mHypoE-N43/5 cells, with sucralose and acesulfame potassium having the most potent effect. Moreover, acesulfame potassium treatment reduced axon outgrowth from arcuate nucleus explants and this effect was attenuated with the ER stress-relieving drug tauroursodeoxycholic acid. Furthermore, sucralose induced cytotoxicity and acesulfame potassium increases caspase3/7 activity at high concentrations in mHypoE-N43/5 cells. In contrast, rebaudioside A only had moderate effects on hypothalamic ER stress and no adverse effects on axon outgrowth, cytotoxicity, or caspase3/7 activity. Together, our data reveal that commonly consumed NNS cause cellular stress in hypothalamic cells disrupting axon outgrowth and that these biological alterations are not seen with rebaudioside A. These data provide biological plausibility for some NNS to adversely impact metabolic health and identifies rebaudioside A as a sweetener with lower detrimental biological impact on hypothalamic cells.
| S-EPMC6928131 | biostudies-literature
Project description:Non-nutritive sweeteners (NNS) are marketed as sugar alternatives providing sweet taste with few or no calories. Yet their consumption has been linked to metabolic dysfunction and changes in the gut microbiome. NNS exposure mostly originates from diet beverages and sweetener packages in adults or breastmilk in infants. Consequences of early life exposure remain largely unknown. We exposed pregnant and lactating mice to NNS (sucralose, acesulfame-K) at doses relevant for human consumption. While the pups' exposure was low, metabolic changes were drastic, indicating extensive downregulation of hepatic detoxification mechanisms and changes in bacterial metabolites. Microbiome profiling confirmed a significant increase in firmicutes and a striking decrease of Akkermansia muciniphila. Similar microbiome alterations in humans have been linked to metabolic disease and obesity. While our findings need to be reproduced in humans, they suggest that NNS consumption during pregnancy and lactation may have adverse effects on infant metabolism.
| S-EPMC6595049 | biostudies-literature
Project description:Understanding how to modulate appetite in humans is key to developing successful weight loss interventions. Here, we showed that postprandial glucose dips 2-3 h after a meal are a better predictor of postprandial self-reported hunger and subsequent energy intake than peak glucose at 0-2 h and glucose incremental area under the blood glucose curve at 0-2 h. We explore the links among postprandial glucose, appetite and subsequent energy intake in 1,070 participants from a UK exploratory and US validation cohort, who consumed 8,624 standardized meals followed by 71,715 ad libitum meals, using continuous glucose monitors to record postprandial glycaemia. For participants eating each of the standardized meals, the average postprandial glucose dip at 2-3 h relative to baseline level predicted an increase in hunger at 2-3 h (r = 0.16, P < 0.001), shorter time until next meal (r = -0.14, P < 0.001), greater energy intake at 3-4 h (r = 0.19, P < 0.001) and greater energy intake at 24 h (r = 0.27, P < 0.001). Results were directionally consistent in the US validation cohort. These data provide a quantitative assessment of the relevance of postprandial glycaemia in appetite and energy intake modulation.
| S-EPMC7610681 | biostudies-literature
Project description:Sweet flavorants enhance palatability and intake of alcohol in adolescent humans. We asked whether sweet flavorants have similar effects in adolescent rats. The inherent flavor of ethanol in adolescent rats is thought to consist of an aversive odor, bitter/sweet taste, and burning sensation. In Experiment 1, we compared ingestive responses of adolescent rats to 10% ethanol solutions with or without added flavorants using brief-access lick tests. We used 4 flavorants, which contained mixtures of saccharin and sucrose or saccharin, sucrose, and maltodextrin. The rats approached (and initiated licking from) the flavored ethanol solutions more quickly than they did unflavored ethanol, indicating that the flavorants attenuated the aversive odor of ethanol. The rats also licked at higher rates for the flavored than unflavored ethanol solutions, indicating that the flavorants increased the naso-oral acceptability of ethanol. In Experiment 2, we offered rats chow, water, and a flavored or unflavored ethanol solution every other day for 8 days. The rats consistently consumed substantially more of the flavored ethanol solutions than unflavored ethanol across the 8 days. When we switched the rats from the flavored to unflavored ethanol for 3 days, daily intake of ethanol plummeted. We conclude that sweet and sweet/maltodextrin flavorants promote high daily intake of ethanol in adolescent rats (i.e., 6-10 g/kg) and that they do so in large part by improving the naso-oral sensory attributes of ethanol.
| S-EPMC7648650 | biostudies-literature