Non-sugar sweeteners
Swapping sweetened for sugar-sweetened drinks lowered body weight about 1 kg in pooled trials. Against water, results were mixed. Cohorts link sweetener use to more type 2 diabetes, heart disease and cancer, links that may reflect who uses them. IARC classed aspartame as possibly carcinogenic. Erythritol raised platelet clotting in small studies.
Add to Bio HackChecked 2026-11-13
- Status
- A food, not a regulated health product. The FDA regulates sweeteners such as aspartame, saccharin and sucralose as food additives, has not questioned GRAS notices for high-purity steviol glycosides, and permits sugar alcohols including erythritol. It states it has no concerns about aspartame used under approved conditions and disagrees with IARC's conclusion on it [3]. In 2023 WHO issued a conditional guideline advising against non-sugar sweeteners to control body weight or reduce the risk of noncommunicable diseases, for everyone except people with existing diabetes, and excluding sugar alcohols [1]. IARC classified aspartame as possibly carcinogenic to humans (Group 2B), and JECFA kept its acceptable daily intake at 0 to 40 mg per kg of body weight [2]. The Dietary Guidelines for Americans, 2025-2030 say no amount of non-nutritive sweeteners is advised and to limit foods and drinks that contain them [4].
- Also called
- artificial sweeteners, non-nutritive sweeteners, low-calorie sweeteners, low-energy sweeteners, sugar substitutes, aspartame, sucralose, saccharin, acesulfame potassium, acesulfame K, stevia, steviol glycosides, erythritol, sugar alcohols, diet soda, diet drinks, zero-sugar drinks
- Studied for
- weight loss, cutting sugar, fewer calories, blood sugar, diabetes, diet drinks in place of soda, and concerns about cancer, heart disease, gut bacteria and insulin
Strong several reviews agree · Moderate one review or consistent trials · Limited one or a few small studies · Untested no study in people, listed with what it rests on
Shown to help1
Reported risks6
- StrongLinked to 25% more type 2 diabetes per daily serving of artificially sweetened drinks, 8% after adjusting for body weight, and to weight gain in cohorts.How often is not known
- ModerateLinked to 9% more cardiovascular disease and 18% more cerebrovascular disease with higher artificial sweetener intake in a French cohort, and to more cardiovascular events in pooled cohorts.How often is not known
- LimitedMixed results: IARC found limited evidence that aspartame causes liver cancer and classed it possibly carcinogenic, while JECFA and the FDA found the evidence not convincing.How often is not known
- LimitedSmall studies found 30 g of erythritol raised platelet clotting responses in healthy volunteers, and cohorts linked high blood erythritol to more heart attacks, strokes and deaths.How often is not known
- LimitedOne trial found saccharin and sucralose for 2 weeks impaired glucose tolerance against controls, with changes in gut bacteria that varied from person to person.How often is not known
- LimitedFDA states people with phenylketonuria, a rare genetic disorder, need to avoid or restrict aspartame, and labels must state that a product contains phenylalanine.How often is not known
What it was studied for, and what was found
Shown to help1
Body weight, in place of sugar
Shown to lower body weight by about 1 kg when sweetened foods or drinks replaced sugar-sweetened ones, in pooled trials of adults.
Compared with sugar-sweetened drinks [5]; sugar-sweetened foods or drinks [6]; the regular-calorie versions of the same foods and drinks [7]
The numbers and sources
- Effect
- Replacing sugar-sweetened drinks with low- and no-calorie sweetened drinks lowered body weight by 1.06 kg (95% CI -1.71 to -0.41), BMI by 0.32 and body fat by 0.60 percentage points, with moderate certainty [5]. In sustained trials of 4 weeks to 40 months, sweeteners against sugar lowered body weight by 1.35 kg (95% CI -2.28 to -0.42), and before a meal cut total energy intake by 94 kcal [6]. Across 15 trials, low-calorie sweeteners lowered weight by 0.80 kg (95% CI -1.17 to -0.43), fat mass by 1.10 kg and waist by 0.83 cm [7]. In children, sweeteners against sugar gave a smaller rise in BMI z score (-0.15, 95% CI -0.17 to -0.12) and no significant difference in weight [8].
- Population
- 601 adults with overweight or obesity, at risk for or with diabetes, in 12 trials [5]. 9 sustained trial comparisons [6]. 15 trials [7]. 528 children in 2 studies [8].
- Sources
- [5], [6], [7], [8]
- Caveats
- The weight differences are small. WHO's 2023 review, the basis of its guideline, found no long-term benefit in reducing body fat [1].
Mixed results2
Body weight, against water or no sweetener
Mixed results: against water, one review found no weight difference and another 1.24 kg less, while trials against no sweetener found little or no change.
Compared with water [5][6]; no or lower sweetener intake [8]; control groups the abstract does not describe [9]
The numbers and sources
- Effect
- Replacing water with sweetened drinks was not associated with body weight, with low certainty [5]. In 3 sustained trial comparisons against water, sweeteners lowered weight by 1.24 kg (95% CI -2.22 to -0.26), and before a meal energy intake did not differ (-2 kcal) [6]. In adults, a small BMI fall (-0.6, 95% CI -1.19 to -0.01) came from 2 studies of 174 people, and no effect was seen in people actively trying to lose weight [8]. In 7 trials, sweeteners did not significantly change BMI (-0.37, 95% CI -1.10 to 0.36) [9].
- Population
- 974 adults in 9 trials of sweetened drinks against water [5]. 3 trial comparisons [6]. Small trials in adults and children [8]. 1,003 participants in 7 trials, median 6 months [9].
- Sources
- [5], [6], [8], [9]
- Caveats
- Few trials, mostly small and short [8][9]. Certainty for the water comparison was low [5].
Blood sugar
Mixed results: sweeteners did not raise blood sugar after intake in pooled trials, while against water, sweetened drinks raised HbA1c 0.21 percentage points in one review.
Compared with blood sugar before intake, in the same people [10]; no or lower sweetener intake [8]; water [5]
The numbers and sources
- Effect
- Across 29 trials of aspartame, saccharin, steviosides and sucralose, blood glucose did not rise after intake and gradually declined over the observation period [10]. In 2 small studies of 52 adults, sweeteners lowered fasting glucose by 0.16 mmol/L (95% CI -0.26 to -0.06) against no sweetener, with very low to low certainty [8]. Replacing water with sweetened drinks was associated with higher HbA1c (0.21 percentage points, 95% CI 0.02 to 0.40) and lower systolic blood pressure (-2.63 mmHg) [5].
- Population
- 741 participants in 29 randomized trials [10]. 52 adults in 2 studies [8]. 974 adults in 9 trials of sweetened drinks against water [5].
- Sources
- [10], [8], [5]
- Caveats
- The glucose trials measured short-term responses [10]. Each finding rests on few or small trials.
Amounts studied
Trials of sweetened drinks lasted at least 2 weeks [5], and sustained trials ran 4 weeks to 40 months [6]. Doses in one review had to be within the acceptable daily intake and given for at least 7 days [8]. JECFA's acceptable daily intake for aspartame is 0 to 40 mg per kg of body weight a day. WHO notes that a 70 kg adult would need more than 9 to 14 cans of a diet soft drink containing 200 to 300 mg of aspartame a day to exceed it [2]. The gut trial gave sachets of saccharin, sucralose, aspartame or stevia below the acceptable daily intake for 2 weeks [16]. The erythritol platelet study gave 30 g in one drink [15]. Cohorts compared people above the median sweetener intake with non-consumers [12][13], or modeled risk per daily serving of sweetened drink [11].
Risks
Reported risks5
Type 2 diabetes and weight gain, in cohorts
Linked to 25% more type 2 diabetes per daily serving of artificially sweetened drinks, 8% after adjusting for body weight, and to weight gain in cohorts.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Each daily serving of artificially sweetened drinks was linked to 25% higher type 2 diabetes (95% CI 18% to 33%) before and 8% (95% CI 2% to 15%) after adjustment for adiposity, with publication bias and residual confounding indicated [11]. In 30 cohorts, sweetener use was linked to a modest rise in BMI and to higher weight, waist size, obesity, hypertension, metabolic syndrome, type 2 diabetes and cardiovascular events [9]. Another review found no link with body weight or fat mass in cohorts and a slightly higher BMI [7]. WHO reported its review found possible undesirable effects from long-term use, including higher risk of type 2 diabetes, cardiovascular disease and death in adults [1].
- Population
- 17 cohorts with 38,253 cases [11]. 405,907 participants in 30 cohorts followed a median 10 years [9]. 9 cohorts [7].
- Sources
- [11], [9], [7], [1]
- Caveats
- Observational. People already gaining weight or at risk of diabetes may switch to sweeteners, which runs the link backward, and WHO rated its recommendation conditional for this reason [1]. Publication bias was found for diabetes [9][11].
Heart disease and stroke, in cohorts
Linked to 9% more cardiovascular disease and 18% more cerebrovascular disease with higher artificial sweetener intake in a French cohort, and to more cardiovascular events in pooled cohorts.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- In 103,388 French adults, total artificial sweetener intake was linked to cardiovascular disease (HR 1.09, 95% CI 1.01 to 1.18), with 346 against 314 cases per 100,000 person-years in higher consumers and non-consumers. It was linked to cerebrovascular disease (HR 1.18, 95% CI 1.06 to 1.31). Aspartame was linked to cerebrovascular events, and acesulfame potassium and sucralose to coronary heart disease [12]. Pooled cohorts linked sweetener use to more cardiovascular events [9], and WHO reported a higher risk of cardiovascular disease in its review [1].
- Population
- 103,388 adults, 79.8% women, mean age 42, 904,206 person-years [12]. 30 cohorts [9].
- Sources
- [12], [9], [1]
- Caveats
- Observational, with possible confounding and reverse causation. The French cohort was web-based and 79.8% women [12].
Erythritol and blood clotting
Small studies found 30 g of erythritol raised platelet clotting responses in healthy volunteers, and cohorts linked high blood erythritol to more heart attacks, strokes and deaths.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- In patients undergoing cardiac evaluation, the top quarter of blood erythritol against the bottom was linked to major adverse cardiovascular events over 3 years (HR 1.80, 95% CI 1.18 to 2.77 in the US, and 2.21, 95% CI 1.20 to 4.07 in Europe). Erythritol ingestion in 8 healthy volunteers raised blood levels above those linked to clotting for over 2 days [14]. In 20 healthy volunteers, 30 g of erythritol raised blood levels more than 1,000-fold and enhanced platelet aggregation in every subject, while 30 g of glucose did not [15]. The FDA reviewed the 2023 paper and determined its observational studies did not establish a causal link [3].
- Population
- 2,149 US and 833 European patients undergoing cardiac evaluation, and 8 healthy volunteers [14]. 10 healthy volunteers per group [15].
- Sources
- [14], [15], [3]
- Caveats
- The cohorts measured erythritol in blood, not how much people ate. The platelet studies measured clotting tests, not clots. WHO's sweetener guideline does not cover sugar alcohols such as erythritol [1].
Glucose tolerance and gut bacteria
One trial found saccharin and sucralose for 2 weeks impaired glucose tolerance against controls, with changes in gut bacteria that varied from person to person.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- Saccharin, sucralose, aspartame and stevia each changed stool and oral bacteria and blood metabolites. Saccharin and sucralose significantly impaired glycemic responses against controls given glucose or nothing. Mice given gut bacteria from the people with the largest and smallest responses reproduced their donors' glucose responses [16].
- Population
- 120 healthy adults in a randomized trial of 2 weeks [16].
- Sources
- [16]
- Caveats
- One trial of 2 weeks, with doses below the acceptable daily intake. The authors say clinical implications still need assessing [16].
Aspartame and phenylketonuria
FDA states people with phenylketonuria, a rare genetic disorder, need to avoid or restrict aspartame, and labels must state that a product contains phenylalanine.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- The FDA states that people who have difficulty metabolizing phenylalanine because of phenylketonuria need to avoid or restrict aspartame, that newborns are routinely tested for it, and that labels of products with aspartame must carry a statement for people with phenylketonuria [3].
- Population
- People with phenylketonuria [3].
- Sources
- [3]
- Caveats
- A regulator statement about one inherited condition. It does not apply to other sweeteners.
Mixed results1
Cancer
Mixed results: IARC found limited evidence that aspartame causes liver cancer and classed it possibly carcinogenic, while JECFA and the FDA found the evidence not convincing.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- IARC classified aspartame in Group 2B on limited evidence for cancer in humans, specifically hepatocellular carcinoma, with limited evidence in animals and for mechanism. JECFA found the evidence of a link between aspartame and cancer in humans not convincing [2]. The FDA disagrees with IARC's classification and cites shortcomings in the studies relied on [3]. In a French cohort, higher consumers of artificial sweeteners had more cancer than non-consumers (HR 1.13, 95% CI 1.03 to 1.25), including aspartame (HR 1.15) and acesulfame potassium (HR 1.13), and breast and obesity-related cancers [13]. A review of trials and observational studies found no differences for cancer between users and non-users [8].
- Population
- 102,865 French adults followed a median 7.8 years, 3,358 cancers [13]. Evidence reviewed by IARC and JECFA [2].
- Sources
- [2], [3], [13], [8]
- Caveats
- An IARC class reflects the strength of evidence that something can cause cancer, not the risk at a given intake [2]. The cohort authors list selection bias, residual confounding and reverse causation as limits [13].
Checked, no increase found1
Saccharin and bladder cancer
Not found in people: FDA states more than 30 human studies did not reproduce the bladder cancer seen in rats, and the warning label was dropped.
The numbers and sources
- How common
- How often is not known: the sources give no rate.
- Effect
- The FDA states that saccharin was linked to bladder cancer in laboratory rats in the early 1970s, that more than 30 human studies since then found the rat results irrelevant to humans, and that in 2000 the National Toxicology Program removed saccharin from its list of potential carcinogens and products no longer carry the warning [3].
- Population
- Human studies summarized by the FDA [3].
- Sources
- [3]
- Caveats
- A regulator's summary. The underlying studies are not cited individually here.
Claims tested and not found
- That sweeteners raise blood sugar right after intake. Across 29 trials, blood glucose did not rise after intake of aspartame, saccharin, steviosides or sucralose [10].
- That sweeteners make people eat more overall. Before a meal, sweeteners cut total energy intake by 94 kcal against sugar and did not differ from water [6].
Related
Sources
- World Health Organization. WHO advises not to use non-sugar sweeteners for weight control in newly released guideline. WHO news. 2023-05-15. https://www.who.int/news/item/15-05-2023-who-advises-not-to-use-non-sugar-sweeteners-for-weight-control-in-newly-released-guideline
- World Health Organization. Aspartame hazard and risk assessment results released. WHO news. 2023-07-14. https://www.who.int/news/item/14-07-2023-aspartame-hazard-and-risk-assessment-results-released
- US Food and Drug Administration. Aspartame and Other Sweeteners in Food. FDA. Content current as of 2025-02-27. https://www.fda.gov/food/food-additives-petitions/aspartame-and-other-sweeteners-food
- US Department of Agriculture and US Department of Health and Human Services. Dietary Guidelines for Americans, 2025-2030. realfood.gov. 2026. https://cdn.realfood.gov/DGA.pdf
- McGlynn ND, Khan TA, Wang L, et al. Association of Low- and No-Calorie Sweetened Beverages as a Replacement for Sugar-Sweetened Beverages With Body Weight and Cardiometabolic Risk: A Systematic Review and Meta-analysis. JAMA Network Open. 2022. https://doi.org/10.1001/jamanetworkopen.2022.2092
- Rogers PJ, Hogenkamp PS, de Graaf C, et al. Does low-energy sweetener consumption affect energy intake and body weight? A systematic review, including meta-analyses, of the evidence from human and animal studies. International Journal of Obesity. 2016. https://doi.org/10.1038/ijo.2015.177
- Miller PE, Perez V. Low-calorie sweeteners and body weight and composition: a meta-analysis of randomized controlled trials and prospective cohort studies. The American Journal of Clinical Nutrition. 2014. https://doi.org/10.3945/ajcn.113.082826
- Toews 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. BMJ. 2019. https://doi.org/10.1136/bmj.k4718
- Azad MB, Abou-Setta AM, Chauhan BF, et al. Nonnutritive sweeteners and cardiometabolic health: a systematic review and meta-analysis of randomized controlled trials and prospective cohort studies. CMAJ. 2017. https://doi.org/10.1503/cmaj.161390
- Nichol AD, Holle MJ, An R. Glycemic impact of non-nutritive sweeteners: a systematic review and meta-analysis of randomized controlled trials. European Journal of Clinical Nutrition. 2018. https://doi.org/10.1038/s41430-018-0170-6
- Imamura F, O'Connor L, Ye Z, et al. Consumption of sugar sweetened beverages, artificially sweetened beverages, and fruit juice and incidence of type 2 diabetes: systematic review, meta-analysis, and estimation of population attributable fraction. BMJ. 2015. https://doi.org/10.1136/bmj.h3576
- Debras C, Chazelas E, Sellem L, et al. Artificial sweeteners and risk of cardiovascular diseases: results from the prospective NutriNet-Santé cohort. BMJ. 2022. https://doi.org/10.1136/bmj-2022-071204
- Debras C, Chazelas E, Srour B, et al. Artificial sweeteners and cancer risk: Results from the NutriNet-Santé population-based cohort study. PLOS Medicine. 2022. https://doi.org/10.1371/journal.pmed.1003950
- Witkowski M, Nemet I, Alamri H, et al. The artificial sweetener erythritol and cardiovascular event risk. Nature Medicine. 2023. https://doi.org/10.1038/s41591-023-02223-9
- Witkowski M, Wilcox J, Province V, et al. Ingestion of the Non-Nutritive Sweetener Erythritol, but Not Glucose, Enhances Platelet Reactivity and Thrombosis Potential in Healthy Volunteers: Brief Report. Arteriosclerosis, Thrombosis, and Vascular Biology. 2024. https://doi.org/10.1161/atvbaha.124.321019
- Suez J, Cohen Y, Valdés-Mas R, et al. Personalized microbiome-driven effects of non-nutritive sweeteners on human glucose tolerance. Cell. 2022. https://doi.org/10.1016/j.cell.2022.07.016