Non-nutritive Sweeteners: Beneficial or Detrimental to Health?

Non-nutritive Sweeteners: Beneficial or Detrimental to Health?

Added sugars are used in food and beverage processing to impart sweetness and taste; to adjust the viscosity, volume, texture and appearance of foods; and for preservation and fermentation purposes.1Davis E. Functionality of sugars: Physicochemical interactions in foods. Am J Clin Nutr 1995;62(Suppl):170S-7S. ^,2Fitch C, Keim KS; Academy of Nutrition and Dietetics. Position of the Academy of Nutrition and Dietetics: use of nutritive and nonnutritive sweeteners. J Acad Nutr Diet 2012;112(5):739-58.^,3Al Humaid J. Sweetener content and cariogenic potential of pediatric oral medications: A literature. Int J Health Sci (Qassim) 2018;12(3):75-82. However, added sugars are a risk factor for dental caries, and high intake is associated with obesity, diabetes mellitus (DM), metabolic syndrome, cardiovascular disease, and an increased risk of all-cause mortality.2Fitch C, Keim KS; Academy of Nutrition and Dietetics. Position of the Academy of Nutrition and Dietetics: use of nutritive and nonnutritive sweeteners. J Acad Nutr Diet 2012;112(5):739-58.^,4Roberts MW, Wright JT. Nonnutritive, low caloric substitutes for food sugars: Clinical implications for addressing the incidence of dental caries and overweight/obesity. Int J Dent 2012;Article ID 625701.^,5Gardener H, Moon YP, Rundek T et al. Diet Soda and Sugar-Sweetened Soda Consumption in Relation to Incident Diabetes in the Northern Manhattan Study. Curr Dev Nutr 2018;2(5).^,6Malik VS, Li Y, Pan A, De Koning L et al. Long-term consumption of sugar-sweetened and artificially sweetened beverages and risk of mortality in US adults. Circulation 2019;139:2113-25. ^,7Johnson RK, Lichtenstein AH, Anderson CAM et al. Low-calorie sweetened beverages and cardiometabolic health: a science advisory from the American Heart Association. Circulation 2018;138:e126-40. Sugar substitutes are used by food processors as a cost-efficient method to obtain sweetness and in some cases to bulk food, and are also used by individuals to reduce caloric intake, improve glycemic control, and to help prevent and manage dental caries and systemic disease.2Fitch C, Keim KS; Academy of Nutrition and Dietetics. Position of the Academy of Nutrition and Dietetics: use of nutritive and nonnutritive sweeteners. J Acad Nutr Diet 2012;112(5):739-58.^,8Wee M, Tan V, Forde C. A comparison of psychophysical dose-response behaviour across 16 sweeteners. Nutrients 2018;10(11):pii E1632.^,9Sylvetsky AC, Chandran A, Talegawkar SA et al. Consumption of Beverages Containing Low-Calorie Sweeteners, Diet, and Cardiometabolic Health in Youth With Type 2 Diabetes. J Acad Nutr Diet 2020;120(8):1348-58. doi:10.1016/j.jand.2020.04.005. Sugar substitutes include non-nutritive sweeteners (NNS) and nutritive sweeteners. NNS available in the US include artificial sweeteners (AS) that are FDA-approved as food additives, and low-calorie natural sweeteners that are ‘generally recognized as safe’ (GRAS).4Roberts MW, Wright JT. Nonnutritive, low caloric substitutes for food sugars: Clinical implications for addressing the incidence of dental caries and overweight/obesity. Int J Dent 2012;Article ID 625701.^,10United States Food & Drug Administration. Aspartame and Other Sweeteners in Food. (content current as of 2/27/2025) https://www.fda.gov/food/food-additives-petitions/aspartame-and-other-sweeteners-food. (Figure 1) NNS are also referred to as low-calorie sweeteners (LCS), and beverages sweetened with NNS are typically referred to as low calorie-sweetened beverages (LCSB).

Categories and Sweetness of NNS

All NNS offer greater sweetness than sugar, and are variously used in foods, beverages, table sweeteners, chewing gums, cosmetics, and pharmaceuticals. AS include advantame, aspartame, neotame, acesulfame-K, saccharin and sucralose, are manufactured chemically, and are all calorie free with the exception of aspartame and advantame which each contain 4 kilocalories.2Fitch C, Keim KS; Academy of Nutrition and Dietetics. Position of the Academy of Nutrition and Dietetics: use of nutritive and nonnutritive sweeteners. J Acad Nutr Diet 2012;112(5):739-58.^,11Mayo Clinic. Healthy Lifestyle. Nutrition and healthy eating. Available at: https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/ex pert-answers/phenylalanine/faq-20058361. Chemically, acesulfame-K combines an organic acid and potassium, offering a clean taste and flavor extension.2Fitch C, Keim KS; Academy of Nutrition and Dietetics. Position of the Academy of Nutrition and Dietetics: use of nutritive and nonnutritive sweeteners. J Acad Nutr Diet 2012;112(5):739-58.^,12Calorie Control Council. Statements on sweetener safety. Available at: www.caloriecontrolcouncil.org. Aspartame is created through a complex process that includes two amino acids - phenylalanine and aspartic acid, while Advantame is derived from aspartame and vanillin, and Neotame through N-alkylation of aspartame.12Calorie Control Council. Statements on sweetener safety. Available at: www.caloriecontrolcouncil.org. Youth born with phenylketonuria need to avoid such foods and drinks as they cannot metabolize phenylalanine, as should pregnant women. Therefore, aspartame and phenylalanine-containing foods and drinks must carry a warning that they contain phenylalanine.2Fitch C, Keim KS; Academy of Nutrition and Dietetics. Position of the Academy of Nutrition and Dietetics: use of nutritive and nonnutritive sweeteners. J Acad Nutr Diet 2012;112(5):739-58. Caution is also advised in certain other individuals, including but not limited to those with tardive dyskinesia, sleep or anxiety disorders, or taking certain medications.13Lindseth GN, Coolahan SE, Petros TV, Lindseth PD. Neurobehavioral effects of aspartame consumption. Res Nurs Health 2014;37(3):185-93. Saccharin is derived from an organic sulfa-based molecule; cross-sensitivity reactions may occur in children with sulfonamide allergy.3Al Humaid J. Sweetener content and cariogenic potential of pediatric oral medications: A literature. Int J Health Sci (Qassim) 2018;12(3):75-82.^,11Mayo Clinic. Healthy Lifestyle. Nutrition and healthy eating. Available at: https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/ex pert-answers/phenylalanine/faq-20058361.

All AS are free of fermentable carbohydrates and therefore not a risk factor for dental caries. Sucralose is the only AS derived from sugar, and in 2006 the FDA permitted a noncariogenic claim for sucralose, supported by studies on bacterial metabolism, experimental caries and in situ plaque pH.14Food and Drug Administration, HHS. Food labeling: health claims; dietary noncariogenic carbohydrate sweeteners and dental caries. Final rule. Fed Regist 2006;71(60):15559-64.^,15McNutt K. Sugar replacers and the FDA noncariogenicity claim. J Dent Hyg 2000;74(1):36-40.^,16Mandel ID, Grotz VL. Dental considerations in sucralose use. J Clin Dent 2002;13(3):116-8. However, bulking agents used for sucralose-based granular table sweeteners consist of either dextrose (a fermentable carbohydrate) and/or maltodextrin (a starch with cariogenic potential), and sucralose is also available in a 50:50 mix with sugar.16Mandel ID, Grotz VL. Dental considerations in sucralose use. J Clin Dent 2002;13(3):116-8.^,17Touger-Decker R, van Loveren C. Sugars and dental caries. Am J Clin Nutr 2003;78(4):881S-92S.^,18Rezende G, Hashizume LN. Maltodextrin and dental caries: a literature review. Rev Gaúch Odontol 2018;66(3):257-62.

Until recently, non-nutritive natural sweeteners with GRAS status consisted of refined stevia and monk fruit extract (luo han guo). A third NNS with GRAS status, thaumatin, is now also available as a natural sweetener. (Table 1) All three are calorie-free.7Johnson RK, Lichtenstein AH, Anderson CAM et al. Low-calorie sweetened beverages and cardiometabolic health: a science advisory from the American Heart Association. Circulation 2018;138:e126-40.^,19Brown MJ. What to know about monk fruit sweetener. Healthline, updated May12, 2025. https://www.healthline.com/nutrition/monk-fruit-sweetener.

Table 1. NNS, sweetness and uses10United States Food & Drug Administration. Aspartame and Other Sweeteners in Food. (content current as of 2/27/2025) https://www.fda.gov/food/food-additives-petitions/aspartame-and-other-sweeteners-food.^,20Sugar and sweetener guide. https://www.sugar-and-sweetener-guide.com/thaumatin/.

Acceptable Daily Intakes (ADI)

ADI are established by a joint FAO/WHO Expert Committee on Food Additives and often confirmed or updated by the FDA and other regulatory bodies.21Calorie Council. Understanding ADI. https://caloriecontrol.org/understanding-the-adi/. ADI are based on body weight, and actual NNS intake is generally found to be well within these limits.2Fitch C, Keim KS; Academy of Nutrition and Dietetics. Position of the Academy of Nutrition and Dietetics: use of nutritive and nonnutritive sweeteners. J Acad Nutr Diet 2012;112(5):739-58.^,22Martyn D, Darch M, Roberts A et al. Low-/no-calorie sweeteners: A review of global intakes. Nutrients 2018;10:357. (Table 2)

Table 2. ADI and equivalent # packets for a person weighing 132 lb. (60 kg)10United States Food & Drug Administration. Aspartame and Other Sweeteners in Food. (content current as of 2/27/2025) https://www.fda.gov/food/food-additives-petitions/aspartame-and-other-sweeteners-food.

Prevalence of AS intake

In a recent study in children up to five years-of-age, using NHANES data from between 2017 and 2020, it was reported that 31% of children in this age group consume foods and beverages containing NNS (AS or refined stevia) at least once daily, largely from sweetened fruit beverages and non-Greek yogurt.23Zhu X, Sylvetsky AC, Luo H et al. Consumption of Low-Calorie Sweeteners among Children Aged 6 Months to 5 Years in the United States, NHANES 2017-2020. J Nutr 2024;154(11):3416-23. doi:10.1016/j.tjnut.2024.08.028. In contrast, 7% of children were reported to consume LCSB based on the 2007-2008 NHANES dataset, and >1% in 1999-2000.24Sylvetsky AC, Welsh JA, Brown RJ, Vos MB. Low-calorie sweetener consumption is increasing in the United States. Am J Clin Nutr 2012;96(3):640-6. Among adults, for the same periods, the reported prevalence for LCSB consumption was 24% and 19%.24Sylvetsky AC, Welsh JA, Brown RJ, Vos MB. Low-calorie sweetener consumption is increasing in the United States. Am J Clin Nutr 2012;96(3):640-6. In addition, in 2014 artificially sweetened beverages (ASB) were consumed by an estimated 18.3% of pregnant women.25Sylvetsky AC, Jin Y, Clark EJ et al. Consumption of low-calorie sweeteners among children and adults in the United States. J Acad Nutr Diet 2017;117:441.e2-448. ^,26Sylvetsky AC, Figueroa J, Rother KI et al. Trends in low-calorie sweetener consumption among pregnant women in the United States. Curr Dev Nutr 2019;3(4):nzz004. ASB are the primary dietary source of NNS globally, with their consumption increasing over time.7Johnson RK, Lichtenstein AH, Anderson CAM et al. Low-calorie sweetened beverages and cardiometabolic health: a science advisory from the American Heart Association. Circulation 2018;138:e126-40.^,27Malek AM, Hunt KJ, DellaValle DM et al. Reported consumption of low-calorie sweetener in foods, beverages, and food and beverage additions by US adults: NHANES 2007–2012. Curr Dev Nutr 2018;2:nzy054.

Systemic Health and Outcomes on Use of NNS

Numerous systematic reviews and studies have been conducted on NNS intake and outcomes, with conflicting results. In this section we will review more recent systematic reviews and studies on overall outcomes, dietary intake and weight management, and DM-related outcomes. In one systematic review and meta-analysis, 37 studies published prior to 2025 with more than 3.5 million subjects were included.28Kim M, JJ Lee, Kumar S et al. Association of Artificial Sweetener Intake With Cardiometabolic Outcomes: A Systematic Review and Meta-Analysis. Curr Dev Nutr 2025;9(Suppl 2):107038. Greater intake of AS was found to increase risk for Type 2 DM, heart failure, cardiovascular death, hypertension, stroke and coronary artery disease by 26%, 26%, 18%, 13%, 12% and 11%, respectively. The researchers concluded that cautious intake of AS was called for as well as further research on the long-term effects of AS.

NNS, dietary intake and weight management

Results of studies on NNS intake, diet and weight management outcomes are conflicting, as noted in a recent review (2025) in which some studies showed potential benefits for weight management.29Sun Y, Xu B. A critical review on effects of artificial sweeteners on gut microbiota and gastrointestinal health. J Sci Food Agric 2025;105(5):2737-47. doi: 10.1002/jsfa.14148. In a 2023 review of systematic reviews and meta-analyses of RCT and other studies, conflicting outcomes and conclusions were reached for differing study populations regarding NNS intake, body weight and adipose tissue, exposure, and other factors.30Higgins K, Rawal R, Kramer M et al. An Overview of Reviews on the Association of Low Calorie Sweetener Consumption With Body Weight and Adiposity. Curr Dev Nutr 2023;7(Suppl 1):P31-025-23. In a cross-sectional study with >600 adults, after adjusting for confounders, higher NNS intake was found to be significantly associated with a higher body mass index (BMI), and less so with WC and C-reactive protein levels after adjusting for BMI.31Allison C, Sylvetsky AC, Reddy A, Wang Y. Associations Between Non-nutritive Sweetener Consumption, Metabolic Risk Factors, and Inflammatory Biomarkers Among U.S. Adults. Curr Dev Nutr 2024;8(Suppl 2):103305. AS represented in the study included acesulfame-K, aspartame, saccharin and sucralose. In one 12-week RCT, the impact of daily consumption of 1.25 to 1.75 liters of SSB by overweight and obese adults was compared to consumption of LCSB containing aspartame, saccharin, sucralose or refined stevia.32Higgins KA, Mattes RD. A randomized controlled trial contrasting the effects of 4 low-calorie sweeteners and sucrose on body weight in adults with overweight or obesity. Am J Clin Nutr 2019;109(5):1288-301. doi: 10.1093/ajcn/nqy381. Similar moderate increases in body weight were observed from baseline to the study’s endpoint for individuals consuming sucrose or saccharin, while body weight and frequency of ingestion decreased for those consuming sucralose. In an earlier 10-week parallel single-blind study (n=22), overweight subjects consumed sucrose- or AS-sweetened foods and beverages, with no dietary restrictions during the study.33Sørensen LB, Vasilaras TH, Astrup A, Raben A. Sucrose compared with artificial sweeteners: a clinical intervention study of effects on energy intake, appetite, and energy expenditure after 10 wk of supplementation in overweight subjects. Am J Clin Nutr 2014;100(1):36-45. doi:10.3945/ajcn.113.081554. Compared to baseline, no changes in calories expended during the study were reported, while sucrose consumption was associated with increased weight and appetite and AS consumption with decreased weight. Additionally, in another study with more than nine hundred adults with no history of DM, after adjusting for lifestyle and sociodemographic factors, greater protein intake and reduced caloric intake was found for individuals consuming NNS at least once daily compared to individuals not consuming NNS.34Moreira TKB, Mendes FD, Santos HCD et al. Exploring the Relationship Between Nonnutritive Sweeteners and Nutrient Intake: Findings from the ELSA-Brasil Baseline Study. Nutrients 2025;17(11):1778. doi: 10.3390/nu17111778.

Outcomes in children
Utilizing 24-hour dietary recall information from the 2017-2020 NHANES datasets for almost 1500 young children, NNS intake more than once per day was found to increase consumption of fibers, total sugars, added sugars and sodium, while protein levels were lower.23Zhu X, Sylvetsky AC, Luo H et al. Consumption of Low-Calorie Sweeteners among Children Aged 6 Months to 5 Years in the United States, NHANES 2017-2020. J Nutr 2024;154(11):3416-23. doi:10.1016/j.tjnut.2024.08.028. In a Chilean study with 450 toddlers (kindergartners), dietary sugar and NNS intakes were analyzed based on 24-hour recalls for dietary information.35Arevalo PA, Rebolledo N, Reyes M et al. Non-Nutritive Sweeteners Intake and Its Association With Sugars Intake Among Chilean Toddlers. Curr Dev Nutrit 2024;8(Suppl 2):103031. Among the outcomes, significantly higher added sugar intake was observed in the children who also received sucralose and was not observed for children who received acesulfame-K, aspartame, steviol glycosides, saccharin, or cyclamate (which is not FDA-accepted). In an earlier review (2014) of prospective cohort studies, no clear association was found for weight gain/obesity and ASB, and weak evidence was reported for an association with sugar-sweetened beverages (SSB).36Pereira MA. Sugar-sweetened and artificially-sweetened beverages in relation to obesity risk 1–3. Adv Nutr 2014;5:797-808.

Taste and appetite
Sweet substances activate sweet-taste receptors, with their intense sweetness proposed to stimulate appetite or promote dependency, and the hypothalamus plays a key role in controlling hunger, food intake and glucose regulation.11Mayo Clinic. Healthy Lifestyle. Nutrition and healthy eating. Available at: https://www.mayoclinic.org/healthy-lifestyle/nutrition-and-healthy-eating/ex pert-answers/phenylalanine/faq-20058361.^,36Pereira MA. Sugar-sweetened and artificially-sweetened beverages in relation to obesity risk 1–3. Adv Nutr 2014;5:797-808.^,37Smeets PA, Weijzen P, de Graaf C, Viergever MA. Consumption of caloric and non-caloric versions of a soft drink differentially affects brain activation during tasting. Neuroimage 2011;54(2):1367-74.^,38Bouret SG. Metabolic hormones, artificial sweeteners and the development of hypothalamic circuits controlling appetite. Ann d'Endocrinol 2025;86(3):101767. https://doi.org/10.1016/j.ando.2025.101767.^,39Chakravartti SP, Jann K, Veit R et al. Non-caloric sweetener effects on brain appetite regulation in individuals across varying body weights. Nat Metab 2025;7(3):574-85. doi: 10.1038/s42255-025-01227-8. Conflicting outcomes have been reported for the association between NNS intake and changes in appetite, with some studies reporting increased appetite while others reported no change.40Romo-Romo A, Aguilar-Salinas CA, Brito-Córdova GX et al. Effects of the non-nutritive sweeteners on glucose metabolism and appetite regulating hormones: Systematic review of observational prospective studies and clinical trials. PLoS ONE 2016;11(8):e0161264. ^,41Ford HE, Peters V, Martin NM et al. Effects of oral ingestion of sucralose on gut hormone response and appetite in healthy normal-weight subjects. Eur J Clin Nutr 2011;65(4):508-13.^,42Maersk M, Belza A, Holst JJ et al. Satiety scores and satiety hormone response after sucrose-sweetened soft drink compared with isocaloric semi-skimmed milk and with non-caloric soft drink: a controlled trial. Eur J Clin Nutr 2012;66(4):523-9.^,43Hall WL, Millward DJ, Rogers PJ, Morgan LM. Physiological mechanisms mediating aspartame induced satiety. Physiol Behavior 2003;78(4-5):557-62.^,44Anton SD, Martin CK, Han H et al. Effects of stevia, aspartame, and sucrose on food intake, satiety, and postprandial glucose and insulin levels. Appetite 2010;55(1):37-43.^,45Higgins KA, Considine RV, Mattes RD. Aspartame consumption for 12 weeks does not affect glycemia, appetite, or body weight of healthy, lean adults in a randomized controlled trial. J Nutr 2018;148(4):650-7. In one study with healthy, overweight and obese individuals, SSB consumption increased peripheral glucose levels and reduced medial hypothalamic blood flow which decreases hunger.39Chakravartti SP, Jann K, Veit R et al. Non-caloric sweetener effects on brain appetite regulation in individuals across varying body weights. Nat Metab 2025;7(3):574-85. doi: 10.1038/s42255-025-01227-8. In contrast, consumption of sucralose-sweetened beverages with a similar sweetness profile had the opposite effect, proposed to be due to a lack of post-ingestion feedback. Additionally, in an RCT of one year’s duration with approximately 200 individuals, subjects’ preferred sweetness levels decreased with unsweetened beverage intake while increasing with LCSB intake more than with SSB.46Ebbeling CB, Feldman HA, Steltz SK et al. Effects of Sugar-Sweetened, Artificially Sweetened, and Unsweetened Beverages on Cardiometabolic Risk Factors, Body Composition, and Sweet Taste Preference: A Randomized Controlled Trial. J Am Heart Assoc 2020;9(15):e015668. doi:10.1161/JAHA.119.015668. Furthermore, among the 33% with the greatest trunk fat at baseline, less weight gain was observed for those consuming ASB or unsweetened beverages compared to those consuming SSB. Results from an earlier study (n=115) indicated that individuals consuming LCSB preferred sweeter snacks than those consuming SSB or mineral water.47Hill SE, Prokosch ML, Morin A, Rodeheffer CD. The effect of non-caloric sweeteners on cognition, choice, and post-consumption satisfaction. Appetite 2014;83:82-8. doi: 10.1016/j.appet.2014.08.003.

Studies related to DM

Studies have been conducted on the potential impact of NNS intake on incident diabetes and glycemic control in individuals with DM. In the Coronary Artery Risk Development in Young Adults study with more than 4,500 individuals (mean age 24.9 years at enrolment) and a median follow-up of 30 years, a more than two-fold risk for incident diabetes was found for the 20% of individuals consuming the most diet beverages, and for those consuming saccharin.48Hejingzi Jia H, Steffen LM, Yi S-Y et al. Association Between Artificial Sweetener Consumption and Risk of Incident Diabetes: The CARDIA study. Curr Dev Nutr 2025;9:Suppl 2107034. In contrast, no significant association with incident diabetes was found for total intake of AS, aspartame and sucralose. In addition, in a web-based study with more than 100,000 participants and a follow-up of 9.1 years, high consumption of AS was found to increase risk for DM by 69% compared to no consumption.49Debras C, Deschasaux-Tanguy M, Chazelas E et al. Artificial Sweeteners and Risk of Type 2 Diabetes in the Prospective NutriNet-Santé Cohort. Diabetes Care 2023;46(9):1681-90. doi: 10.2337/dc23-0206. Further, risk for DM was found to increase by 63%, 42% and 34% when evaluating aspartame, acesulfame-K and sucralose separately. In an earlier study, diet sodas containing NNS were associated with incident DM, particularly for individuals who were overweight/obese including after adjusting for BMI as a confounder. The researchers concluded that it was possible that NNS may be a risk factor for DM.5Gardener H, Moon YP, Rundek T et al. Diet Soda and Sugar-Sweetened Soda Consumption in Relation to Incident Diabetes in the Northern Manhattan Study. Curr Dev Nutr 2018;2(5).

In one meta-analysis, a relative risk for DM of 1.13 was found with an intake of 330 ml/day of ASB and a greater risk with SSB intake, while no association was found in another meta-analysis.40Romo-Romo A, Aguilar-Salinas CA, Brito-Córdova GX et al. Effects of the non-nutritive sweeteners on glucose metabolism and appetite regulating hormones: Systematic review of observational prospective studies and clinical trials. PLoS ONE 2016;11(8):e0161264. An association for ASB and metabolic disease was, however, found in >50% of observational studies. In longitudinal studies with approximately 40,000, >340,000 and >70,000 individuals, respectively, no association for ASB and risk for DM was found after adjusting for BMI in one study and for BMI and energy intake in 2 other studies.40Romo-Romo A, Aguilar-Salinas CA, Brito-Córdova GX et al. Effects of the non-nutritive sweeteners on glucose metabolism and appetite regulating hormones: Systematic review of observational prospective studies and clinical trials. PLoS ONE 2016;11(8):e0161264.

Studies on NNS in individuals with DM

In a systematic review and meta-analysis (2020) of 9 RCT published up to May 2019 (n=979), the effect of consumption of NNS, sugar or placebo over a period of 4 to 10 months was evaluated.50Lohner S, Kuellenberg de Gaudry D, Toews I et al. Non-nutritive sweeteners for diabetes mellitus. Cochrane Database Syst Rev 2020;5(5):CD012885. doi:10.1002/14651858.CD012885.pub2. No significant differences in weight change or glycosylated hemoglobin A1c (HbA1c) levels were found when comparing NNS and sugar intake (3 RCT), nor when comparing NNS with placebo.

In a more recent RCT in patients with Type 1 DM (n=37), the immediate/short-term effects of white bread (control group) or breakfasts containing 50 g of carbohydrates with or without the addition of a combination of sucralose/stevia were investigated, with 24 subjects completing the study.51Sambra V, Duarte L, González G et al. Influence of Breakfast With/Without Non-nutritive Sweeteners on Glycemic Response and Appetite-Satiety in Adults With Type 1 Diabetes 2025;9:Suppl 2107251. Elevated capillary glucose levels were observed at 15 minutes for the group consuming only carbohydrates (mean 8.0 mmol/L), while glucose levels were elevated for the group consuming NNS at 15, 30, 45 and 60 minutes and were higher than for the control group.

The ‘Treatment Option for Type 2 Diabetes in Adolescents and Youth’ (TODAY) multi-center study conducted between 2004 and 2012 researched the effect of LCSB intake over a 2-year period among almost 500 youth with Type 2 DM who were ages 10 to 17 years.9Sylvetsky AC, Chandran A, Talegawkar SA et al. Consumption of Beverages Containing Low-Calorie Sweeteners, Diet, and Cardiometabolic Health in Youth With Type 2 Diabetes. J Acad Nutr Diet 2020;120(8):1348-58. doi:10.1016/j.jand.2020.04.005. Energy intake was found to be higher for all youth consuming LCSB than for non-consumers of LCSB, and highest for youth with the highest intake level of LCSB (at least 12 servings per week). In addition, no significant differences were found in energy intake or cardiometabolic risk factors as a result of reductions or increases in LCSB intake from baseline. Furthermore, when LCSB intake was reduced, individuals were likely to increase sugar intake.

NNS and the gut microbiome

In a review published in 2025 that included in vitro, animal and clinical trials, it was concluded that AS can alter the composition and diversity of the gut microbiota and impact systemic health by changing the production of bacterial metabolites.29Sun Y, Xu B. A critical review on effects of artificial sweeteners on gut microbiota and gastrointestinal health. J Sci Food Agric 2025;105(5):2737-47. doi: 10.1002/jsfa.14148. Other reviews corroborate these findings, including a review published in 2024 in which AS was found to be associated with significant changes in gut microflora in two of five clinical trials and three of four cross-sectional studies.52Gauthier E, Milagro FI, Navas-Carretero S. Effect of low-and non-calorie sweeteners on the gut microbiota: A review of clinical trials and cross-sectional studies. Nutrition 2024;117:112237. doi: 10.1016/j.nut.2023.112237. In other recent reviews, saccharin and sucralose were found to alter the gut microbiota and diversity, while aspartame and acesulfame-K were found to have a limited or no effect, and no changes in the gut microbiota composition were observed with intake of neotame or advantame.53Plaza-Diaz J, Pastor-Villaescusa B, Rueda-Robles A et al. Plausible Biological Interactions of Low- and Non-Calorie Sweeteners with the Intestinal Microbiota: An Update of Recent Studies. Nutrients 2020;12(4):1153. doi:10.3390/nu12041153.^,54Ruiz-Ojeda FJ, Plaza-Díaz J, Sáez-Lara MJ, Gil A. Effects of Sweeteners on the Gut Microbiota: A Review of Experimental Studies and Clinical Trials. Adv Nutr 2019;10(suppl 1):S31-S48. doi: 10.1093/advances/nmy037. Erratum in: Adv Nutr 2020;11(2):468. doi:10.1093/advances/nmz112. In addition, in an in vitro study using fecal samples in bioreactors with AS supplementation over a 35-day period, saccharin and sucralose reduced microbial diversity and sucralose increased the proportion of pathogens, while Acesulfame-K increased microbial diversity but disrupted its structure.55Kidangathazhe A, Amponsah T, Maji A et al. Synthetic vs. non-synthetic sweeteners: their differential effects on gut microbiome diversity and function. Front Microbiol 2025;16:1531131. doi:10.3389/fmicb.2025.1531131. It has been proposed that aspartame, sucralose and saccharin may inhibit quorum sensing responsible for microbial communication and activity, thereby altering the gut’s microbial composition.56Markus V, Share O, Shagan M et al. Inhibitory Effects of Artificial Sweeteners on Bacterial Quorum Sensing. Int J Mol Sci 2021;22(18):9863. doi:10.3390/ijms22189863. The gut microbiome is believed to influence risk for DM, warranting further research in this area and on NNS.7Johnson RK, Lichtenstein AH, Anderson CAM et al. Low-calorie sweetened beverages and cardiometabolic health: a science advisory from the American Heart Association. Circulation 2018;138:e126-40.

Guidelines and Recommendations on the use of AS

In a policy statement developed by the American Heart Association Scientific Advisory Group, it is advised that consuming LCSB instead of SSB may help to prevent large spikes in glucose levels, and may also be a helpful substitute for SSB for adults whose intake of SSB is high and for children with DM with a balanced diet.7Johnson RK, Lichtenstein AH, Anderson CAM et al. Low-calorie sweetened beverages and cardiometabolic health: a science advisory from the American Heart Association. Circulation 2018;138:e126-40. It was noted that there is an absence of safety data on NNS intake in children >2 years-of-age and on the long-term effects in children, and therefore no advice was given for this age group. The American Academy of Pediatrics policy statement on the use of NNS in children notes that the lack of data on their use in children under 2 years-of-age precludes providing advice for this age group; and, that although a modest weight loss of around 1 kg or reduced weight gain can be achieved by substituting NNS for nutritive sweetener in foods or beverages, robust weight loss is not likely.57Baker-Smith CM, de Ferranti SD, Cochran WJ et al. The Use of Nonnutritive Sweeteners in Children. Pediatrics 2019;144 (5): e20192765. Meanwhile, the UK Scientific Advisory Committee on Nutrition (SACN) recommends minimizing NNS intake as a precaution due to conflicting outcomes in studies, while also recognizing that they may be beneficial in combatting short-term weight gain.58Larkin M. Medical News Report on Non-Sugar Sweeteners Challenges WHO Guideline. Medscape, April 17, 2025. https://www.medscape.com/viewarticle/report-non-sugar-sweeteners-challenges-who-guidance-2025a100095f?ecd=WNL_mdpls_250425_mscpedit_wir_etid7383850&uac=116821EY&spon=17&impID=7383850. SACN further recommends to avoid SSB and LCSB in younger children and, for older children and adults, advises that NSS as sugar substitutes my reduce sugar intake and help adults lose a small amount of weight in the short term. However, following an Ibero-American consensus meeting on NNS, it was concluded in 2018 that AS had been extensively evaluated and their safety confirmed by multiple global regulatory bodies.59Serra-Majem L, Raposo A, Aranceta-Bartrina J et al. Ibero–American consensus on low- and no-calorie sweeteners: Safety, nutritional aspects and benefits in food and beverages. Nutrients 2018;10:818. doi:10.3390/nu10070818.

In 2023, the World Health Organization issued an updated guideline conditionally recommending against the use of non-sugar sweeteners to control body weight or reduce the risk of noncommunicable diseases in individuals without pre-existing DM.60World Health Organization. WHO Advises Not to Use Nonsugar Sweeteners for Weight Control in Newly Released Guideline. https://www.who.int/news/item/15-05-2023-who-advises-not-to-use-non-sugar-sweeteners-for-weight-control-in-newly-released-guideline. This was based on outcomes of a systematic review that no long-term benefit accrued from their use for weight loss, and their potential negative effects with respect to risk for DM. These recommendations have been challenged by the UK SACN, which notes that the WHO recommendations were conditional because of the low quality of evidence and applicability to differing populations and that less weight was given to the more robust data (RCT) compared to observational studies.59Serra-Majem L, Raposo A, Aranceta-Bartrina J et al. Ibero–American consensus on low- and no-calorie sweeteners: Safety, nutritional aspects and benefits in food and beverages. Nutrients 2018;10:818. doi:10.3390/nu10070818.

Conclusions

Obesity and DM are already at epidemic levels globally with 589 million adults living with DM, while dental caries continues to be the most prevalent chronic disease in children and adults.61International Diabetes Federation. The Diabetes Atlas. https://diabetesatlas.org/.^,62National Institute of Dental and Craniofacial Research. Dental Caries (Tooth Decay). https://www.nidcr.nih.gov/research/data-statistics/dental-caries. Against this background, NNS are one of the methods used to help prevent and manage these diseases.9Sylvetsky AC, Chandran A, Talegawkar SA et al. Consumption of Beverages Containing Low-Calorie Sweeteners, Diet, and Cardiometabolic Health in Youth With Type 2 Diabetes. J Acad Nutr Diet 2020;120(8):1348-58. doi:10.1016/j.jand.2020.04.005.^,48Hejingzi Jia H, Steffen LM, Yi S-Y et al. Association Between Artificial Sweetener Consumption and Risk of Incident Diabetes: The CARDIA study. Curr Dev Nutr 2025;9:Suppl 2107034.^,50Lohner S, Kuellenberg de Gaudry D, Toews I et al. Non-nutritive sweeteners for diabetes mellitus. Cochrane Database Syst Rev 2020;5(5):CD012885. doi:10.1002/14651858.CD012885.pub2.^,51Sambra V, Duarte L, González G et al. Influence of Breakfast With/Without Non-nutritive Sweeteners on Glycemic Response and Appetite-Satiety in Adults With Type 1 Diabetes 2025;9:Suppl 2107251. However, data on the benefits and risks of NNS intake, and LCSB specifically, is reported to be limited, and robust studies and data on individual AS are lacking.7Johnson RK, Lichtenstein AH, Anderson CAM et al. Low-calorie sweetened beverages and cardiometabolic health: a science advisory from the American Heart Association. Circulation 2018;138:e126-40. Existing studies are also heterogeneous in design methodology and include numerous biases, including varying consideration of confounders.3Al Humaid J. Sweetener content and cariogenic potential of pediatric oral medications: A literature. Int J Health Sci (Qassim) 2018;12(3):75-82.^,36Pereira MA. Sugar-sweetened and artificially-sweetened beverages in relation to obesity risk 1–3. Adv Nutr 2014;5:797-808.^,40Romo-Romo A, Aguilar-Salinas CA, Brito-Córdova GX et al. Effects of the non-nutritive sweeteners on glucose metabolism and appetite regulating hormones: Systematic review of observational prospective studies and clinical trials. PLoS ONE 2016;11(8):e0161264. ^,63Toews I, Lohner S, Küllenberg de Gaudry D et al. Association between intake of non-sugar sweeteners and health outcomes: systematic review and meta-analyses of randomised and non-randomised controlled trials and observational studies. Br Med J 2019;364:k4718. doi: https://doi. org/10.1136/bmj. Further research and robust studies in children and adults with and without DM have been recommended, and studies on the long-term effects of NNS on diet management, glucose intolerance, cardiometabolic health, gut health, sweetness receptors, appetite and satiety.9Sylvetsky AC, Chandran A, Talegawkar SA et al. Consumption of Beverages Containing Low-Calorie Sweeteners, Diet, and Cardiometabolic Health in Youth With Type 2 Diabetes. J Acad Nutr Diet 2020;120(8):1348-58. doi:10.1016/j.jand.2020.04.005.^,29Sun Y, Xu B. A critical review on effects of artificial sweeteners on gut microbiota and gastrointestinal health. J Sci Food Agric 2025;105(5):2737-47. doi: 10.1002/jsfa.14148.^,47Hill SE, Prokosch ML, Morin A, Rodeheffer CD. The effect of non-caloric sweeteners on cognition, choice, and post-consumption satisfaction. Appetite 2014;83:82-8. doi: 10.1016/j.appet.2014.08.003. ^,49Debras C, Deschasaux-Tanguy M, Chazelas E et al. Artificial Sweeteners and Risk of Type 2 Diabetes in the Prospective NutriNet-Santé Cohort. Diabetes Care 2023;46(9):1681-90. doi: 10.2337/dc23-0206.^,50Lohner S, Kuellenberg de Gaudry D, Toews I et al. Non-nutritive sweeteners for diabetes mellitus. Cochrane Database Syst Rev 2020;5(5):CD012885. doi:10.1002/14651858.CD012885.pub2.^,56Markus V, Share O, Shagan M et al. Inhibitory Effects of Artificial Sweeteners on Bacterial Quorum Sensing. Int J Mol Sci 2021;22(18):9863. doi:10.3390/ijms22189863.

Dental and other healthcare professionals should stay abreast of developments on the use of NNS and nutrition. In the meantime, dental professionals can advise patients and parents on weight management and caries control, and the need to limit intake of added sugars.13Lindseth GN, Coolahan SE, Petros TV, Lindseth PD. Neurobehavioral effects of aspartame consumption. Res Nurs Health 2014;37(3):185-93.^,64American Dental Association. Policies and recommendations on diet and nutrition. Available at: https://www.ada.org/en/advocacy/current-policies/diet-and-nutrition. Individualized evaluation and advice should be provided based on current recommendations, considering the patient’s age, risk for oral and systemic disease, and suitability of NNS as part of a program to reduce added sugars and energy intake.

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