Low- and no-calorie sweeteners (LNCS), also known as non-nutritive sweeteners (NNS), are sugar substitutes that provide a sweet taste with little to no energy contribution. Examples include aspartame, sucralose, saccharin, and stevia. LNCS are found in a wide range of packaged foods, beverages, and non-food products, including sugar-free or low-calorie drinks, flavored dairy products, protein supplements, baked goods, medications, vitamins, chewing gum, and oral care products. [1] [1] Adminstration. UFaD. How Sweet It Is: All About Sweeteners. Accessed 6/15/2026, 2026. https://www.fda.gov/consumers/consumer-updates/how-sweet-it-all-about-sweeteners LNCS are commonly incorporated into dietary strategies aimed at reducing energy and added sugar intake while maintaining palatability, particularly in the context of weight management, diabetes care, and cardiometabolic health.1
Regulation of Low- and No-Calorie Sweeteners
In the United States, sweeteners are regulated under the Federal Food, Drug, and Cosmetic Act and must be demonstrated to be safe for their intended use. The U.S. Food and Drug Administration (FDA) evaluates scientific evidence to approve food additives and establish acceptable daily intake (ADI) levels considered safe for lifetime consumption. [1] [1] Adminstration. UFaD. How Sweet It Is: All About Sweeteners. Accessed 6/15/2026, 2026. https://www.fda.gov/consumers/consumer-updates/how-sweet-it-all-about-sweeteners Some sweeteners may instead be marketed as "generally recognized as safe" (GRAS) if qualified experts determine they meet the same safety standards as FDA-approved additives. Sweeteners that have been approved for use by the FDA include Acesulfame potassium (ACE-K), Aspartame, Neotame, Saccharin, Sucralose, and Advantame. Three plant- and fruit-derived sweeteners are classified as GRAS in the United States: certain stevia extracts, monk fruit (Luo han guo), and thaumatin. All of these sweeteners provide intense sweetness at levels much greater than sugar but with fewer calories. [1] [1] Adminstration. UFaD. How Sweet It Is: All About Sweeteners. Accessed 6/15/2026, 2026. https://www.fda.gov/consumers/consumer-updates/how-sweet-it-all-about-sweeteners, [2] [2] Ayoub-Charette S, Nguyen M, Chiavaroli L, et al. Low- and no-calorie sweeteners and health: unravelling the evidence and controversy. Applied Physiology, Nutrition, and Metabolism. 2026;51:1–11. doi:10.1139/apnm-2025-0440 %M 41990199
The safety of LNCS is reviewed not only by the FDA but also by leading international food safety organizations, including the Food and Agriculture Organization of the United Nations (FAO) and the World Health Organization (WHO). Internationally, approved sweeteners have been rigorously evaluated by food safety authorities, such as the Joint FAO/WHO Expert Committee on Food Additives (JECFA) and European Food Safety Authority (EFSA). [2] [2] Ayoub-Charette S, Nguyen M, Chiavaroli L, et al. Low- and no-calorie sweeteners and health: unravelling the evidence and controversy. Applied Physiology, Nutrition, and Metabolism. 2026;51:1–11. doi:10.1139/apnm-2025-0440 %M 41990199 LNCS differ in their absorption, distribution, metabolism, and excretion characteristics, leading to distinct ADI levels, despite frequently being considered as one collective group. [2] [2] Ayoub-Charette S, Nguyen M, Chiavaroli L, et al. Low- and no-calorie sweeteners and health: unravelling the evidence and controversy. Applied Physiology, Nutrition, and Metabolism. 2026;51:1–11. doi:10.1139/apnm-2025-0440 %M 41990199
While the LNCS listed above have been recognized as safe when used within their acceptable daily intake levels by the FDA, the long-term health implications of LNCS remain an area of ongoing investigation, particularly regarding their role in weight management and the potential effects of sweet taste exposure independent of energy intake. The inconsistency or mixed evidence as reported by different study designs has led to this debate and hence, has caused public confusion.
Summary of Evidence on Low- and No-Calorie Sweeteners
In recent years, numerous umbrella reviews, systematic reviews, and meta-analyses have been conducted to evaluate the effects of LNCS on health outcomes. Randomized controlled trials have consistently linked LNCS consumption with favorable weight-related outcomes, whereas observational studies (cohorts) have consistently associated higher LNCS consumption with increased risk for obesity, all-cause mortality, cardiovascular mortality (CVD) and Type 2 diabetes (T2DM). Evidence synthesis for this report identified seven recently published umbrella reviews that based their findings on 65 systematic reviews and meta-analyses. [3] [3] Ayoub-Charette S, Kavanagh M, Khan T, Sievenpiper J. Reconciling conflicting evidence on low- and no-calorie sweeteners and cardiometabolic outcomes: an umbrella review using naïve and bias-adjusted methods. Appl Physiol Nutr Metab. Jan 1 2025;50:1–26. doi:10.1139/apnm-2025-0068, [4] [4] Choi JH, Song S, Kim SK, et al. Health Effects of Sugar-Sweetened and Artificially Sweetened Beverages: Umbrella Review and Evidence-Based Consensus Statement of the Korean Diabetes Association and the Korean Nutrition Society. Diabetes Metab J. Jan 2026;50(1):32–46. doi:10.4093/dmj.2025.0848, [5] [5] Higgins KA, Rawal R, Kramer M, Baer DJ, Yerke A, Klurfeld DM. An Overview of Reviews on the Association of Low Calorie Sweetener Consumption With Body Weight and Adiposity. Adv Nutr. Dec 2024;15(12):100239. doi:10.1016/j.advnut.2024.100239, [6] [6] Jeong J, Cho J, Jo Y, et al. Low- and no-calorie sweeteners and beverages and their associated health outcomes: an umbrella review of systematic reviews and meta-analyses. Nutr Res Pract. Jun 2026;20(3):382–397. doi:10.4162/nrp.2026.20.3.382, [7] [7] Abu-Zaid A, Kutbi E, Alshammari N, et al. The association of artificial sweeteners intake and risk of cancer: an umbrella meta-analysis. Front Med (Lausanne). 2025;12:1647178. doi:10.3389/fmed.2025.1647178, [8] [8] Beigrezaei S, Raeisi-Dehkordi H, Hernández Vargas JA, et al. Non-Sugar-Sweetened Beverages and Risk of Chronic Diseases: An Umbrella Review of Meta-analyses of Prospective Cohort Studies. Nutr Rev. Apr 1 2025;83(4):663–674. doi:10.1093/nutrit/nuae135, [9] [9] Diaz C, Rezende LFM, Sabag A, et al. Artificially Sweetened Beverages and Health Outcomes: An Umbrella Review. Adv Nutr. Jul 2023;14(4):710–717. doi:10.1016/j.advnut.2023.05.010 (Table 1)
The summarized evidence includes variation in study populations (e.g., healthy individuals, people with overweight or obesity, diabetes, or children), the comparator used (e.g., sugar-sweetened beverages, water, placebo, or no intervention), and the analytical approach. These differences can influence the interpretation of findings and should be carefully considered when reviewing the evidence.
References
Factors to Consider when Interpreting Evidence
The evidence on LNCS is derived from both randomized controlled trials (RCTs) and observational studies, each with distinct strengths and limitations. RCTs provide the strongest evidence for causal effects because randomization minimizes confounding and directly evaluates the replacement of added sugars or sugar-sweetened beverages with LNCS. However, most RCTs are relatively short, include modest sample sizes, and primarily assess intermediate outcomes such as body weight rather than long-term outcomes, including cardiovascular disease, cancer, or mortality.
Observational studies provide important evidence on long-term consumption patterns and health outcomes but are more susceptible to bias, including residual confounding, reverse causality, and measurement error from self-reported dietary intake. Individuals with overweight, obesity, diabetes, or other cardiometabolic conditions may preferentially consume LNCS, potentially contributing to observed associations with adverse health outcomes. These methodological limitations may partly explain why observational studies often report less favorable associations than RCTs.
Interpretation of the evidence is further complicated by substantial heterogeneity across studies, including differences in study populations, types and amounts of LNCS, comparator groups, outcome definitions, and follow-up duration. Many studies also group different sweeteners together despite differences in their metabolism and physiological effects. Consequently, findings should be interpreted within the context of study design, risk of bias, and the specific dietary comparison being evaluated rather than as evidence of causal effects.
Most of the available evidence has been generated in mixed adult populations, particularly among individuals with overweight, obesity, or elevated cardiometabolic risk. Comparatively fewer studies have examined the effects of LNCS in children, adolescents, pregnant individuals, and older adults, limiting the ability to draw firm conclusions for these groups. Differences in age, health status, baseline dietary habits, and reasons for consuming LNCS may influence observed outcomes and contribute to variability across studies. As a result, findings from one population may not be directly generalizable to others.
The interpretation of LNCS research is strongly influenced by the analytical approach used.
- Prevalent analyses typically compare individuals with higher versus lower LNCS intake measured at a single point in time and often do not account for the dietary component being replaced. These analyses may be particularly vulnerable to reverse causality because individuals with overweight or who are at increased risk of chronic disease may be more likely to choose LNCS products.
- In contrast, substitution analyses explicitly evaluate the effects of replacing sugar-sweetened beverages or added sugars with LNCS alternatives and may better reflect real-world dietary choices.
- Across umbrella reviews, prevalent analyses frequently suggest modest adverse associations, whereas substitution analyses generally indicate neutral or beneficial effects, particularly for body weight and some cardiovascular outcomes.
The health effects of LNCS depend largely on the comparator used. When compared with water, some LNCS may show neutral or less favorable effects. However, from a public health perspective, the most relevant comparison is often sugar-sweetened beverages (SSBs) or added sugars. Evidence consistently indicates that replacing SSBs with LNCS beverages reduces added sugars and energy intake and is associated with modest improvements in body weight, body mass index (BMI), and some cardiometabolic outcomes. Similarly, substituting added sugars with LNCS can improve postprandial glycemic responses. These findings suggest that the potential benefits of LNCS are most apparent when they are used to replace caloric sweeteners rather than when they are compared with water.
Evidence regarding adverse effects of LNCS remains limited and inconsistent. Regulatory agencies have determined that approved LNCS are safe when consumed within established acceptable daily intake levels, and systematic reviews have generally not identified consistent evidence of serious harms. However, uncertainty remains regarding potential long-term effects on cardiometabolic health, cancer risk, appetite regulation, and the gut microbiome. Many reported adverse associations are small in magnitude and are primarily derived from observational studies, making it difficult to determine whether these relationships are causal. Furthermore, adverse events are often not systematically assessed as primary outcomes in clinical trials.
Weight-Related Outcomes
Evidence from randomized controlled trials has consistently shown that consumption of LNCS compared to all-comparators reduced body weight and body mass index. [3] [3] Ayoub-Charette S, Kavanagh M, Khan T, Sievenpiper J. Reconciling conflicting evidence on low- and no-calorie sweeteners and cardiometabolic outcomes: an umbrella review using naïve and bias-adjusted methods. Appl Physiol Nutr Metab. Jan 1 2025;50:1–26. doi:10.1139/apnm-2025-0068, [4] [4] Choi JH, Song S, Kim SK, et al. Health Effects of Sugar-Sweetened and Artificially Sweetened Beverages: Umbrella Review and Evidence-Based Consensus Statement of the Korean Diabetes Association and the Korean Nutrition Society. Diabetes Metab J. Jan 2026;50(1):32–46. doi:10.4093/dmj.2025.0848, [5] [5] Higgins KA, Rawal R, Kramer M, Baer DJ, Yerke A, Klurfeld DM. An Overview of Reviews on the Association of Low Calorie Sweetener Consumption With Body Weight and Adiposity. Adv Nutr. Dec 2024;15(12):100239. doi:10.1016/j.advnut.2024.100239, [6] [6] Jeong J, Cho J, Jo Y, et al. Low- and no-calorie sweeteners and beverages and their associated health outcomes: an umbrella review of systematic reviews and meta-analyses. Nutr Res Pract. Jun 2026;20(3):382–397. doi:10.4162/nrp.2026.20.3.382 When LNCS consumption was compared to water intake, randomized controlled trials indicated no effect on weight outcomes. Results from prospective cohort studies have reported mixed associations between LNCS and body weight, with most relying on prevalent analyses that assess intake at a single time point and are vulnerable to reverse causation. In contrast, a recent systematic review [10] [10] Lee JJ, Khan TA, McGlynn N, et al. Relation of Change or Substitution of Low- and No-Calorie Sweetened Beverages With Cardiometabolic Outcomes: A Systematic Review and Meta-analysis of Prospective Cohort Studies. Diabetes Care. Aug 1 2022;45(8):1917–1930. doi:10.2337/dc21-2130 and umbrella review [3] [3] Ayoub-Charette S, Kavanagh M, Khan T, Sievenpiper J. Reconciling conflicting evidence on low- and no-calorie sweeteners and cardiometabolic outcomes: an umbrella review using naïve and bias-adjusted methods. Appl Physiol Nutr Metab. Jan 1 2025;50:1–26. doi:10.1139/apnm-2025-0068 of cohort studies using substitution analysis found that replacing sugar-sweetened beverages with LNCS beverages was associated with lower body weight.
Type 2 Diabetes and HbA1c
Evidence from systematic reviews of randomized controlled trials on hemoglobin A1c (HbA1c) levels is inconsistent. [3] [3] Ayoub-Charette S, Kavanagh M, Khan T, Sievenpiper J. Reconciling conflicting evidence on low- and no-calorie sweeteners and cardiometabolic outcomes: an umbrella review using naïve and bias-adjusted methods. Appl Physiol Nutr Metab. Jan 1 2025;50:1–26. doi:10.1139/apnm-2025-0068, [4] [4] Choi JH, Song S, Kim SK, et al. Health Effects of Sugar-Sweetened and Artificially Sweetened Beverages: Umbrella Review and Evidence-Based Consensus Statement of the Korean Diabetes Association and the Korean Nutrition Society. Diabetes Metab J. Jan 2026;50(1):32–46. doi:10.4093/dmj.2025.0848 Evidence from one systematic review of six RCTs indicated no effect on HbA1c values in prevalent analysis or substitution analysis for sugar-sweetened beverages (SSB). [3] [3] Ayoub-Charette S, Kavanagh M, Khan T, Sievenpiper J. Reconciling conflicting evidence on low- and no-calorie sweeteners and cardiometabolic outcomes: an umbrella review using naïve and bias-adjusted methods. Appl Physiol Nutr Metab. Jan 1 2025;50:1–26. doi:10.1139/apnm-2025-0068 However, when comparing LNCS substitution for water or placebo, a trivial increase on HbA1c was noticed. [3] [3] Ayoub-Charette S, Kavanagh M, Khan T, Sievenpiper J. Reconciling conflicting evidence on low- and no-calorie sweeteners and cardiometabolic outcomes: an umbrella review using naïve and bias-adjusted methods. Appl Physiol Nutr Metab. Jan 1 2025;50:1–26. doi:10.1139/apnm-2025-0068 A 2026 systematic review of 14 primary studies, and prevalent analysis of LNCS consumption compared to SSB indicated a modest reduction in HbA1c. [4] [4] Choi JH, Song S, Kim SK, et al. Health Effects of Sugar-Sweetened and Artificially Sweetened Beverages: Umbrella Review and Evidence-Based Consensus Statement of the Korean Diabetes Association and the Korean Nutrition Society. Diabetes Metab J. Jan 2026;50(1):32–46. doi:10.4093/dmj.2025.0848
Evidence from prevalent analysis of four umbrella reviews of cohort studies consistently indicated an association of LNCS and risk of T2DM. [3] [3] Ayoub-Charette S, Kavanagh M, Khan T, Sievenpiper J. Reconciling conflicting evidence on low- and no-calorie sweeteners and cardiometabolic outcomes: an umbrella review using naïve and bias-adjusted methods. Appl Physiol Nutr Metab. Jan 1 2025;50:1–26. doi:10.1139/apnm-2025-0068, [4] [4] Choi JH, Song S, Kim SK, et al. Health Effects of Sugar-Sweetened and Artificially Sweetened Beverages: Umbrella Review and Evidence-Based Consensus Statement of the Korean Diabetes Association and the Korean Nutrition Society. Diabetes Metab J. Jan 2026;50(1):32–46. doi:10.4093/dmj.2025.0848, [8] [8] Beigrezaei S, Raeisi-Dehkordi H, Hernández Vargas JA, et al. Non-Sugar-Sweetened Beverages and Risk of Chronic Diseases: An Umbrella Review of Meta-analyses of Prospective Cohort Studies. Nutr Rev. Apr 1 2025;83(4):663–674. doi:10.1093/nutrit/nuae135, [9] [9] Diaz C, Rezende LFM, Sabag A, et al. Artificially Sweetened Beverages and Health Outcomes: An Umbrella Review. Adv Nutr. Jul 2023;14(4):710–717. doi:10.1016/j.advnut.2023.05.010 However, results from substitution analysis (biased-adjusted) indicated no effect of LNCS on T2DM incidence risk. [3] [3] Ayoub-Charette S, Kavanagh M, Khan T, Sievenpiper J. Reconciling conflicting evidence on low- and no-calorie sweeteners and cardiometabolic outcomes: an umbrella review using naïve and bias-adjusted methods. Appl Physiol Nutr Metab. Jan 1 2025;50:1–26. doi:10.1139/apnm-2025-0068
All-Cause Mortality
Prevalent analyses from five umbrella reviews of cohort studies indicate that higher LNCS intake compared to lower LNCS intake was associated with a relatively small increase in all-cause mortality risk or a risk comparable to that associated with SSB intake. [3] [3] Ayoub-Charette S, Kavanagh M, Khan T, Sievenpiper J. Reconciling conflicting evidence on low- and no-calorie sweeteners and cardiometabolic outcomes: an umbrella review using naïve and bias-adjusted methods. Appl Physiol Nutr Metab. Jan 1 2025;50:1–26. doi:10.1139/apnm-2025-0068, [4] [4] Choi JH, Song S, Kim SK, et al. Health Effects of Sugar-Sweetened and Artificially Sweetened Beverages: Umbrella Review and Evidence-Based Consensus Statement of the Korean Diabetes Association and the Korean Nutrition Society. Diabetes Metab J. Jan 2026;50(1):32–46. doi:10.4093/dmj.2025.0848, [6] [6] Jeong J, Cho J, Jo Y, et al. Low- and no-calorie sweeteners and beverages and their associated health outcomes: an umbrella review of systematic reviews and meta-analyses. Nutr Res Pract. Jun 2026;20(3):382–397. doi:10.4162/nrp.2026.20.3.382, [8] [8] Beigrezaei S, Raeisi-Dehkordi H, Hernández Vargas JA, et al. Non-Sugar-Sweetened Beverages and Risk of Chronic Diseases: An Umbrella Review of Meta-analyses of Prospective Cohort Studies. Nutr Rev. Apr 1 2025;83(4):663–674. doi:10.1093/nutrit/nuae135, [9] [9] Diaz C, Rezende LFM, Sabag A, et al. Artificially Sweetened Beverages and Health Outcomes: An Umbrella Review. Adv Nutr. Jul 2023;14(4):710–717. doi:10.1016/j.advnut.2023.05.010 However, substitution analysis (LNCS for SSB) of cohort studies indicated lower all cause-mortality risk. [3] [3] Ayoub-Charette S, Kavanagh M, Khan T, Sievenpiper J. Reconciling conflicting evidence on low- and no-calorie sweeteners and cardiometabolic outcomes: an umbrella review using naïve and bias-adjusted methods. Appl Physiol Nutr Metab. Jan 1 2025;50:1–26. doi:10.1139/apnm-2025-0068
Cardiovascular Outcomes
Across five umbrella reviews of cohort studies, findings on cardiovascular (CVD) outcomes were mixed and largely derived from prevalent analyses. [3] [3] Ayoub-Charette S, Kavanagh M, Khan T, Sievenpiper J. Reconciling conflicting evidence on low- and no-calorie sweeteners and cardiometabolic outcomes: an umbrella review using naïve and bias-adjusted methods. Appl Physiol Nutr Metab. Jan 1 2025;50:1–26. doi:10.1139/apnm-2025-0068, [4] [4] Choi JH, Song S, Kim SK, et al. Health Effects of Sugar-Sweetened and Artificially Sweetened Beverages: Umbrella Review and Evidence-Based Consensus Statement of the Korean Diabetes Association and the Korean Nutrition Society. Diabetes Metab J. Jan 2026;50(1):32–46. doi:10.4093/dmj.2025.0848, [6] [6] Jeong J, Cho J, Jo Y, et al. Low- and no-calorie sweeteners and beverages and their associated health outcomes: an umbrella review of systematic reviews and meta-analyses. Nutr Res Pract. Jun 2026;20(3):382–397. doi:10.4162/nrp.2026.20.3.382, [8] [8] Beigrezaei S, Raeisi-Dehkordi H, Hernández Vargas JA, et al. Non-Sugar-Sweetened Beverages and Risk of Chronic Diseases: An Umbrella Review of Meta-analyses of Prospective Cohort Studies. Nutr Rev. Apr 1 2025;83(4):663–674. doi:10.1093/nutrit/nuae135, [9] [9] Diaz C, Rezende LFM, Sabag A, et al. Artificially Sweetened Beverages and Health Outcomes: An Umbrella Review. Adv Nutr. Jul 2023;14(4):710–717. doi:10.1016/j.advnut.2023.05.010 Higher LNCS vs. lower intake was generally associated with a small increase in CVD incidence, including coronary heart disease and stroke, and some reviews reported that the risks of CVD incidence and CVD mortality were similar to those observed with higher SSB consumption. Higher intake of NNS beverages was also associated with an increased risk of CVD. [4] [4] Choi JH, Song S, Kim SK, et al. Health Effects of Sugar-Sweetened and Artificially Sweetened Beverages: Umbrella Review and Evidence-Based Consensus Statement of the Korean Diabetes Association and the Korean Nutrition Society. Diabetes Metab J. Jan 2026;50(1):32–46. doi:10.4093/dmj.2025.0848 In contrast, analyses that evaluated substitution of SSBs with LNCS beverages and adjusted for potential biases suggested potential benefits, including lower cardiovascular mortality risk (RR 0.94, 95% CI 0.90–0.99) and lower coronary heart disease risk (RR 0.89, 95% CI 0.81–0.98). [3] [3] Ayoub-Charette S, Kavanagh M, Khan T, Sievenpiper J. Reconciling conflicting evidence on low- and no-calorie sweeteners and cardiometabolic outcomes: an umbrella review using naïve and bias-adjusted methods. Appl Physiol Nutr Metab. Jan 1 2025;50:1–26. doi:10.1139/apnm-2025-0068 Overall, prevalent analyses tended to suggest modest adverse associations, whereas substitution analyses indicated potential cardiovascular benefits when LNCS beverages replaced SSBs.
Cancer
Across three umbrella reviews of cohort studies, evidence linking higher LNCS intake compared to lower LNCS intake and cancer outcomes was generally limited and inconsistent. [4] [4] Choi JH, Song S, Kim SK, et al. Health Effects of Sugar-Sweetened and Artificially Sweetened Beverages: Umbrella Review and Evidence-Based Consensus Statement of the Korean Diabetes Association and the Korean Nutrition Society. Diabetes Metab J. Jan 2026;50(1):32–46. doi:10.4093/dmj.2025.0848, [8] [8] Beigrezaei S, Raeisi-Dehkordi H, Hernández Vargas JA, et al. Non-Sugar-Sweetened Beverages and Risk of Chronic Diseases: An Umbrella Review of Meta-analyses of Prospective Cohort Studies. Nutr Rev. Apr 1 2025;83(4):663–674. doi:10.1093/nutrit/nuae135, [9] [9] Diaz C, Rezende LFM, Sabag A, et al. Artificially Sweetened Beverages and Health Outcomes: An Umbrella Review. Adv Nutr. Jul 2023;14(4):710–717. doi:10.1016/j.advnut.2023.05.010Most associations were null or very small, with cancer mortality estimates close to no effect4 and no significant associations observed for several site-specific cancers. [8] [8] Beigrezaei S, Raeisi-Dehkordi H, Hernández Vargas JA, et al. Non-Sugar-Sweetened Beverages and Risk of Chronic Diseases: An Umbrella Review of Meta-analyses of Prospective Cohort Studies. Nutr Rev. Apr 1 2025;83(4):663–674. doi:10.1093/nutrit/nuae135 Some findings suggested that higher LNCS intake compared to lower was associated with a small increase in leukemia risk, while higher LNCS consumption was associated with a lower risk of colorectal cancer. [8] [8] Beigrezaei S, Raeisi-Dehkordi H, Hernández Vargas JA, et al. Non-Sugar-Sweetened Beverages and Risk of Chronic Diseases: An Umbrella Review of Meta-analyses of Prospective Cohort Studies. Nutr Rev. Apr 1 2025;83(4):663–674. doi:10.1093/nutrit/nuae135 One umbrella review reported weak evidence that high LNCS intake compared to lower was associated with an increased risk of overall cancer based on prevalent analyses. [9] [9] Diaz C, Rezende LFM, Sabag A, et al. Artificially Sweetened Beverages and Health Outcomes: An Umbrella Review. Adv Nutr. Jul 2023;14(4):710–717. doi:10.1016/j.advnut.2023.05.010
A 2025 umbrella review found no consistent evidence that LNCS consumption is associated with overall cancer incidence or mortality. [7] [7] Abu-Zaid A, Kutbi E, Alshammari N, et al. The association of artificial sweeteners intake and risk of cancer: an umbrella meta-analysis. Front Med (Lausanne). 2025;12:1647178. doi:10.3389/fmed.2025.1647178 Most site-specific cancer analyses were also null, although associations varied by cancer type, with limited evidence suggesting a lower risk of gynecological cancers. Overall, the findings do not support a consistent relationship between LNCS intake and cancer outcomes.
Energy Intake
A study published in 2026 synthesized evidence from both randomized controlled trials and observational studies examining various types of LNCS intake. [6] [6] Jeong J, Cho J, Jo Y, et al. Low- and no-calorie sweeteners and beverages and their associated health outcomes: an umbrella review of systematic reviews and meta-analyses. Nutr Res Pract. Jun 2026;20(3):382–397. doi:10.4162/nrp.2026.20.3.382 Observational evidence indicated that, compared with water or placebo, consumption of LNCS was associated with a small increase in energy intake (SMD 0.24; 95% CI 0.08–0.40), while also being associated with a small reduction in daily sugar intake (SMD −0.09; 95% CI −0.17 to −0.01). The certainty of evidence was rated as very low.
Gastrointestinal Outcomes
Research examining gastrointestinal effects of LNCS has focused on changes in the gut microbiome and gastrointestinal symptoms. The impact of LNCS on gut microbiota is inconsistent, with some intervention studies reporting a dysbiotic effect and others finding no effects, even at high doses. [11] [11] Conz A, Salmona M, Diomede L. Effect of Non-Nutritive Sweeteners on the Gut Microbiota. Nutrients. Apr 13 2023;15(8 doi:10.3390/nu15081869, [12] [12] Gauthier 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. Jan 2024;117:112237. doi:10.1016/j.nut.2023.112237 Differences in study design, LNCS dose and duration, and participant characteristics may contribute to variability in findings, while individualized microbiome responses may further limit the generalizability of results.
Cognition
A 2025 systematic review of prospective cohort studies found an association between higher artificially sweetened beverage intake and an increased risk of Alzheimer's disease, based on two studies representing 208,090 participants. [13] [13] Jouni N, Torabinasab K, Amiri SM, et al. The association between sugar- and artificially sweetened beverages and risk of Alzheimer's disease: systematic review and dose-response meta-analysis of prospective cohort studies. Aging Ment Health. Oct 2025;29(10):1845–1855. doi:10.1080/13607863.2025.2512215 In both studies, the association between Alzheimer's disease and LNCS consumption existed at the highest level of consumption (>/= 1 beverage/day or >2 beverages/day, respectively) and was slightly attenuated when controlling for diabetes status among other cardiometabolic confounders (e.g., lipoproteins, blood pressure). [14] [14] Chen Y, Zhang Y, Yang H, et al. Associations of sugar-sweetened, artificially sweetened, and naturally sweet juices with Alzheimer's disease: a prospective cohort study. Geroscience. Feb 2024;46(1):1229–1240. doi:10.1007/s11357-023-00889-0, [15] [15] Pase MP, Himali JJ, Beiser AS, et al. Sugar- and Artificially Sweetened Beverages and the Risks of Incident Stroke and Dementia: A Prospective Cohort Study. Stroke. May 2017;48(5):1139–1146. doi:10.1161/strokeaha.116.016027 A multicohort study of U.S. adults (n=10,974) aged 65 and older did not find an association between LNCS beverage consumption and dementia risk. [16] [16] Chen H, Ding Y, Dhana K, et al. Sweetened Beverages and Incident All-Cause Dementia Among Older Adults. JAMA Psychiatry. Aug 1 2025;82(8):801–809. doi:10.1001/jamapsychiatry.2025.1230
Evidence Synthesis for Children and Adolescents
A 2024 systematic review and meta-analysis evaluated the association between nonnutritive sweetener consumption and body mass index (BMI) among children and adolescents, incorporating evidence from four randomized controlled trials (n=1,372) and eight prospective cohort studies (n=35,340). [17] [17] Espinosa A, Mendoza K, Laviada-Molina H, et al. Effects of Nonnutritive Sweeteners on the BMI of Children and Adolescents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Prospective Cohort Studies. Adv Nutr. Dec 2024;15(12):100292. doi:10.1016/j.advnut.2024.100292 Evidence from randomized controlled trials suggested that replacing SSBs with beverages containing LNCS was associated with modest reductions in BMI among children and adolescents. However, evidence from prospective cohorts was less consistent and generally showed no clear association between habitual LNCS intake and long-term BMI changes. The overall certainty of evidence ranged from low to moderate for most outcomes, reflecting the limited number of trials and variability across studies. [17] [17] Espinosa A, Mendoza K, Laviada-Molina H, et al. Effects of Nonnutritive Sweeteners on the BMI of Children and Adolescents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials and Prospective Cohort Studies. Adv Nutr. Dec 2024;15(12):100292. doi:10.1016/j.advnut.2024.100292
A 2022 systematic review found limited evidence on LNCS use in children, with no consistent effects on health outcomes. [18] [18] Rios-Leyvraz MM, Jason. World Health Organization. Health effects of the use of non-sugar sweeteners: a systematic review and meta-analysis. 2022 One randomized controlled trial included in this systematic review reported reductions in body weight, waist circumference, and body fat mass when SSB were replaced with LNCS-beverages, whereas, prospective cohort studies generally found no significant associations with adiposity. [18] [18] Rios-Leyvraz MM, Jason. World Health Organization. Health effects of the use of non-sugar sweeteners: a systematic review and meta-analysis. 2022 Two trials also reported improvements in dental caries with stevia, but most other studies found no significant associations between LNCS consumption and the health outcomes evaluated. [18] [18] Rios-Leyvraz MM, Jason. World Health Organization. Health effects of the use of non-sugar sweeteners: a systematic review and meta-analysis. 2022
Evidence Synthesis for Pregnant Individuals
Evidence on LNCS use during pregnancy was limited and generally of low certainty. [18] [18] Rios-Leyvraz MM, Jason. World Health Organization. Health effects of the use of non-sugar sweeteners: a systematic review and meta-analysis. 2022 Meta-analysis of prospective cohort studies found that higher LNCS intake compared to lower intake was associated with a modest increase in the risk of preterm birth, particularly late preterm delivery. Findings related to birth weight and offspring adiposity were inconsistent, with some studies reporting higher body fatness in childhood and others finding no association. Limited evidence also suggested possible links between prenatal LNCS exposure and childhood asthma, allergies, or cognitive outcomes, while no association was observed with gestational diabetes. Overall, the certainty of the evidence was rated as very low, highlighting the need for further research.
A 2025 systematic review and meta-analysis examined whether maternal consumption of LNCS before conception, during pregnancy, or while breastfeeding affects child health outcomes, including birth weight, growth, overweight/obesity risk, cognition, and behavior. [19] [19] Gebremichael B, Lassi ZS, Begum M, Zhou SJ. Association between low-calorie sweetener consumption during pregnancy and child health: A systematic review and meta-analysis. Matern Child Nutr. Jan 2025;21(1):e13737. doi:10.1111/mcn.13737 Most studies were observational cohort studies. Evidence from included studies does not support a clear association between maternal LNCS consumption during pregnancy and adverse child health outcomes. While frequent intake may be associated with modest increases in birth weight and childhood overweight risk, the evidence is inconsistent and of low certainty.
Evidence Synthesis for Individuals with Diabetes
Among individuals with diabetes, systematic reviews indicate that the health effects of LNCS remain uncertain due to limited and heterogeneous evidence. A 2026 systematic review which included 22 studies across multiple study designs, found inconsistent associations between sweetener intake and metabolic outcomes, with meta-analyses suggesting possible increases in insulin and HbA1c levels, although results were not robust across statistical models and showed substantial heterogeneity. [20] [20] Lück A, Standl F, Stich H. Artificial sweeteners and their implications for patients with diabetes: a systematic review and meta-analysis. J Med Life. Jan 2026;19(1):33–42. doi:10.25122/jml-2025-0135 Similarly, a 2020 systematic review of nine randomized controlled trials involving 979 individuals with Type 1 or Type 2 diabetes found no consistent differences between LNCS and sugar, placebo, or other low-calorie sweeteners for HbA1c, body weight, or adverse events, and rated the overall certainty of evidence as very low because of small sample sizes and methodological limitations. [21] [21] Lohner S, Kuellenberg de Gaudry D, Toews I, Ferenci T, Meerpohl JJ. Non-nutritive sweeteners for diabetes mellitus. Cochrane Database Syst Rev. May 25 2020;5(5):Cd012885. doi:10.1002/14651858.CD012885.pub2 While a 2024 meta-analysis reported that replacing sugar with LNCS was associated with lower energy and carbohydrate intake in adults, including some individuals with diabetes, these findings were not observed when LNCS were compared with water, and the certainty of evidence was low to moderate. [22] [22] Rostampour K, Moghtaderi F, Najafi A, Seyedjafari B, Salehi-Abargouei A. The effects of non-nutritive sweeteners on energy and macronutrients intake in adults: a grade-assessed systematic review and meta-analyses of randomized controlled trials. Systematic Review. Frontiers in Nutrition. 2024–November–13 2024;Volume 11 - 2024doi:10.3389/fnut.2024.1475962 Overall, current evidence suggests that LNCS may reduce energy and carbohydrate intake, particularly relative to sugar-sweetened products, but current evidence does not support clear metabolic benefits or harms, highlighting the need for higher-quality long-term studies in people with diabetes.
Translating Evidence into Public Health
The divergence between findings from randomized controlled trials and observational studies is also reflected in clinical guidelines and public health recommendations. While short-term randomized trials generally demonstrate that replacing SSBs with LNCS can reduce intake of added sugars and lead to modest improvements in body weight and adiposity, long-term observational studies frequently report associations between higher LNCS consumption and increased risks of obesity, Type 2 diabetes, cardiovascular disease, and mortality. As a result, most contemporary guidelines acknowledge that LNCS may have a role as a temporary or transitional strategy for reducing added sugar intake, particularly among individuals at elevated metabolic risk, but stop short of recommending their routine long-term use.
Several organizations and guidelines, including the World Health Organization (WHO), the Korean Society of Obesity, the British Dietetic Association, and the Dietary Guidelines for Americans emphasize that water and unsweetened beverages should be the preferred alternatives to sugar-sweetened beverages. [4] [4] Choi JH, Song S, Kim SK, et al. Health Effects of Sugar-Sweetened and Artificially Sweetened Beverages: Umbrella Review and Evidence-Based Consensus Statement of the Korean Diabetes Association and the Korean Nutrition Society. Diabetes Metab J. Jan 2026;50(1):32–46. doi:10.4093/dmj.2025.0848, [23] [23] Organization. WH. Use of non-sugar sweeteners: WHO guideline. Geneva: World Health Organization; 2023. Licence: CC BY-NC-SA 3.0 IGO. 2023, [24] [24] British Dietetic Association (BDA) BNF, Diabetes UK. Joint position statement on the use of low or no calorie sweeteners (LNCS). 2025, [25] [25] Dietary Guidelines for Americans (2025). These groups generally recommend focusing on improving overall diet quality and reducing intake of added sugars rather than relying on LNCS as a primary strategy for weight management or chronic disease prevention. Similarly, diabetes-focused organizations, including the American Diabetes Association, Diabetes Canada, [25] [25] Dietary Guidelines for Americans (2025). Diabetes Australia, and Diabetes UK, recognize that LNCS can be used in moderation as a substitute for sugar-sweetened products when they help reduce overall calorie and carbohydrate intake. [24] [24] British Dietetic Association (BDA) BNF, Diabetes UK. Joint position statement on the use of low or no calorie sweeteners (LNCS). 2025, [26] [26] American Diabetes Association Professional Practice Committee for Diabetes*; 5. Facilitating Positive Health Behaviors and Well-being to Improve Health Outcomes: Standards of Care in Diabetes—2026. Diabetes Care 1 January 2026; 49 (Supplement_1): S89–S131. https://doi.org/10.2337/dc26-S005, [27] [27] Canada. D. Sugar and Diabetes. Accessed 6/15/2026, 2026. https://www.diabetes.ca/advocacy---policies/our-policy-positions/sugar---diabetes., [28] [28] Australia. D. Alternative Sweeteners—Can They Help Manage Diabetes? . Diabetes Australia. Accessed 6/15/26, 2026. https://www.diabetesaustralia.com.au/blog/alternative-sweeteners-diabetes However, these recommendations consistently emphasize that LNCS should be considered one tool within a broader dietary approach rather than a stand-alone solution. For pediatric populations, both the Healthy Eating Research (HER) [29] [29] Lott M CE, Welker Duffy E, Story M, Daniels S. Healthy Beverage Consumption in Early Childhood: Recommendations from Key National Health and Nutrition Organizations. Technical Scientific Report. 2019. Healthy Eating Research, 2019. https://healthyeatingresearch.org/ Healthy Beverage Consensus Statement (0-5 years of age) and the American Academy of Pediatrics (AAP) [30] [30] Baker-Smith CM, de Ferranti SD, Cochran WJ, et al. The Use of Nonnutritive Sweeteners in Children. Pediatrics. 2019;144(5) doi:10.1542/peds.2019-2765 (0-2 years of age) do not recommend beverages containing LNCS because evidence regarding their long-term health and developmental effects during early childhood remains insufficient. (Table 2)
Conclusion
Evidence suggests that LNCS may be useful tools for reducing added sugar intake and supporting short-term weight management when they replace caloric sweeteners, particularly SSBs. However, interpretation of findings should consider study design, population characteristics, and analytical approaches, as outcomes appear more favorable when LNCS replace SSBs rather than water or no consumption. Consequently, current guidelines generally support cautious, context-specific use of LNCS while emphasizing dietary patterns centered on water, minimally processed foods, and reduced added sugar intake. Additional long-term research using substitution-based approaches, particularly in understudied populations, is needed to clarify their role in chronic disease prevention and overall health.
References
Join the Academy
Members of the Academy of Nutrition and Dietetics receive exciting benefits including complimentary continuing professional education opportunities, discounts on events and products in eatrightSTORE.org, invitations to exclusive members-only events and more!