Sweeteners

What they are

Sweeteners are food additives that taste sweet, some of them 200 to 500 times more intensely than sugar ¹²³.

Aspartame is L-aspartyl-L-phenylalanine methyl ester, sucralose a trichlorinated sucrose derivative, erythritol a four-carbon polyol, and steviol glycosides constituents of Stevia rebaudiana leaves ⁴⁵⁶⁷.

The sweet receptor is a TAS1R2–TAS1R3 heterodimer; sucralose and aspartame bind the same pocket of its TAS1R2 subunit ⁸.

In the body

Most sweeteners are excreted largely unchanged; aspartame is hydrolysed to two amino acids and methanol ²¹⁵⁶⁴.

Intestinal esterases and peptidases, including aminopeptidase A, hydrolyse aspartame with a half-life of minutes, yielding up to 10% methanol by weight ⁴.

Hydrolysis of aspartame and hydroxylation of its phenylalanineSmall-intestinal brush border and mucosa, then liver

Aspartame
Glutamyl aminopeptidase, aminopeptidase A (ENPEP)Zn2+, H2OReleases L-aspartate; esterases can act first, forming aspartylphenylalanine
L-Phenylalanine methyl ester
Esterases of intestinal mucosa and bloodH2OReleases methanol, at most 10% of aspartame by weight
L-Phenylalanine
Phenylalanine hydroxylase (PAH)Tetrahydrobiopterin to 4a-hydroxytetrahydrobiopterin, O2, Fe2+Deficient in phenylketonuria
L-Tyrosine

In phenylketonuria, an autosomal recessive deficiency of hepatic phenylalanine hydroxylase, phenylalanine from food and aspartame accumulates and, untreated, causes intellectual impairment ⁴.

Acesulfame K, saccharin and, within 24 hours, 78 to 92% of erythritol are excreted unchanged in urine ²¹⁶. Only 8.8 to 21.7% of sucralose is absorbed ⁵. Colonic bacteria release steviol from steviol glycosides; steviol is excreted as glucuronide, mainly in urine ⁷.

What studies show

In trials, sugar-free drinks slowed children’s weight gain, and replacing them with water did not lower blood glucose in type 2 diabetes ⁹¹⁰.

Over 18 months, 641 children given a daily sugar-free or sugar-sweetened drink gained 6.35 and 7.37 kg (difference −1.01 kg, 95% CI −1.54 to −0.48) ⁹. In 181 adults with type 2 diabetes, HbA1c over 24 weeks rose from 7.20% to 7.44% with water and went from 7.19% to 7.14% with habitual sweetened beverages (adjusted difference 0.29 percentage points, P = 0.013) ¹⁰. Without randomisation, 30 g erythritol raised plasma erythritol over 1000-fold and, unlike 30 g glucose, enhanced platelet aggregation in all 10 volunteers ¹¹.

EFSA acceptable daily intakes, mg/kg body weight:

Sweetener	Intake
Aspartame	40 ⁴
Acesulfame K	15 ²
Saccharin	9, as free imide ¹
Sucralose	15 ⁵
Steviol glycosides	4, as steviol ⁷
Erythritol	500; 95th-percentile estimates reach or exceed it ⁶

Regulation

In 2023 JECFA, a United Nations expert committee, kept the aspartame limit at 40 mg per kg body weight a day, above estimated intakes ³.

The limit does not apply in phenylketonuria, and EU labels must declare aspartame a source of phenylalanine ⁴.

References

Regulator
EFSA Panel on Food Additives and Flavourings (FAF), Castle L, Andreassen M, Aquilina G, Bastos ML, Boon P, et al. Re-evaluation of saccharin and its sodium, potassium and calcium salts (E 954) as food additives EFSA Journal, 2024.
doi:10.2903/j.efsa.2024.9044 PubMed 39553702
Funding and finding
Funding
European Food Safety Authority; requestor: European Commission (question numbers EFSA-Q-2011-00736, EFSA-Q-2011-00737, EFSA-Q-2011-00738 and EFSA-Q-2011-00739). Adopted 24 September 2024.
Finding
Saccharin is 1,2-benzisothiazol-3(2H)-one-1,1-dioxide, approximately 300 to 500 times as sweet as sucrose. Most, if not all, of oral doses of 2.2 to 69.3 mg is absorbed; saccharin is not metabolised, has a half-life of approximately 4 h and is excreted primarily in urine; it crosses the placenta and passes into breast milk. ADI 9 mg/kg bw per day expressed as saccharin free imide, with decreased body weight in animal studies as the relevant endpoint; it replaces the SCF ADI of 5 mg/kg bw per day expressed as sodium saccharin, corresponding to 3.8 mg/kg bw per day as free imide. The 95th percentile chronic exposure estimates were below the ADI in all population groups.
Regulator
EFSA Panel on Food Additives and Flavourings (FAF), Castle L, Andreassen M, Aquilina G, Bastos ML, Boon P, et al. Re-evaluation of acesulfame K (E 950) as food additive EFSA Journal, 2025.
doi:10.2903/j.efsa.2025.9317 PubMed 40309404
Funding and finding
Funding
European Food Safety Authority; requestor: European Commission (question number EFSA-Q-2011-00721).
Finding
Acesulfame K is 6-methyl-1,2,3-oxathiazin-4(3H)-one-2,2-dioxide potassium salt, approximately 200 times as sweet as sucrose; it is authorised in 34 food categories (47 uses), many of them restricted to energy-reduced foods or foods with no added sugar. It is almost fully absorbed, is not metabolised, has a half-life of 2 to 4 h and is excreted in urine; it crosses the placenta and passes into breast milk. ADI 15 mg/kg bw per day, from a NOAEL of 1500 mg/kg bw per day, the highest dose tested in a chronic toxicity and carcinogenicity study in rats, with an uncertainty factor of 100; it replaces the ADI of 9 mg/kg bw per day established by the SCF. The 95th percentile exposure estimates were generally below the ADI in all population groups.
Regulator
Joint FAO/WHO Expert Committee on Food Additives (JECFA). Evaluation of certain food additives: ninety-sixth report of the Joint FAO/WHO Expert Committee on Food Additives World Health Organization and Food and Agriculture Organization of the United Nations, Geneva; WHO Technical Report Series, No. 1050, 2023.
https://www.who.int/publications/i/item/9789240083059
Funding and finding
Funding
Not stated. The Joint Secretariat states that all experts participating in the meeting completed declaration-of-interest forms and that no conflicts of interest were identified. Sponsors submitted unpublished toxicity study reports and dietary exposure information.
Finding
Aspartame, approximately 200 times sweeter than sucrose, is fully hydrolysed in the gastrointestinal tract by esterases and peptidases to phenylalanine, aspartic acid and methanol (approximately 50, 40 and 10% by weight); no aspartame enters the systemic circulation. Cohort associations with hepatocellular, breast and haematological cancers were inconsistent, reverse causality, chance, bias and confounding could not be ruled out, and the Committee concluded that the evidence of an association between aspartame consumption and cancer in humans is not convincing; the same conclusion was reached for type 2 diabetes and other non-cancer end-points. The ADI of 0 to 40 mg/kg bw, based on the NOAEL of 4000 mg/kg bw per day in a 104-week rat study and a 100-fold uncertainty factor, was reaffirmed. Dietary exposure estimates of up to 10 mg/kg bw per day for children and 5 mg/kg bw per day for adults at the mean, and up to 20 and 12 mg/kg bw per day for high consumers, do not exceed the ADI.
Regulator
EFSA Panel on Food Additives and Nutrient Sources added to Food (ANS). Scientific Opinion on the re-evaluation of aspartame (E 951) as a food additive EFSA Journal, 2013.
doi:10.2903/j.efsa.2013.3496
Funding and finding
Funding
European Food Safety Authority; on request from the European Commission (question number EFSA-Q-2011-00406).
Finding
Aspartame is rapidly and completely hydrolysed in the gastrointestinal tract to phenylalanine, aspartic acid and methanol. Developmental toxicity in animals was attributed to phenylalanine. The acceptable daily intake of 40 mg/kg bw per day was retained; in normal people and PKU heterozygotes, intakes up to the ADI in addition to dietary phenylalanine would not raise peak plasma phenylalanine above the clinical guideline for preventing adverse effects in fetuses. The ADI is not applicable to PKU patients.
Regulator
EFSA Panel on Food Additives and Flavourings (FAF), Castle L, Andreassen M, Aquilina G, Bastos ML, Boon P, et al. Re-evaluation of sucralose (E 955) as a food additive and evaluation of a new application on extension of use of sucralose (E 955) in fine bakery wares EFSA Journal, 2026.
doi:10.2903/j.efsa.2026.9854 PubMed 41710869
Funding and finding
Funding
European Food Safety Authority; requestor: European Commission (question numbers EFSA-Q-2011-00724 and EFSA-Q-2021-00375). Adopted 10 December 2025.
Finding
Sucralose is 1,6-dichloro-1,6-dideoxy-beta-D-fructofuranosyl-4-chloro-4-deoxy-alpha-D-galactopyranoside, produced by a process that selectively replaces three hydroxyl groups of sucrose with chlorine. Oral absorption in humans varied between 8.8% and 21.7% of the dose; systemically available sucralose is eliminated mainly in urine, with less than 10% of urinary radioactivity in glucuronide-like metabolites; in two volunteers about 85% of a radiolabelled dose was recovered in faeces after 120 h; no 14CO2 was detected in expired air. From human studies, the Panel concluded that sucralose does not adversely affect glucose and insulin homeostasis (moderate level of confidence). Reference point BMDL 55 mg/kg bw per day for decreased body weight in rats; no need to revise the ADI of 15 mg/kg bw per day established by the SCF in 2000; exposure estimates did not exceed the ADI.
Regulator
EFSA Panel on Food Additives and Flavourings (FAF), Younes M, Aquilina G, Castle L, Degen G, Engel KH, et al. Re-evaluation of erythritol (E 968) as a food additive EFSA Journal, 2023.
doi:10.2903/j.efsa.2023.8430 PubMed 38125972
Funding and finding
Funding
European Food Safety Authority; requestor: European Commission (question numbers EFSA-Q-2011-00730 and EFSA-Q-2022-00219). Adopted 25 October 2023.
Finding
Erythritol is 1,2,3,4-butanetetrol (C4H10O4), a polyol obtained by fermentation, with a sweetness of approximately 60% to 80% that of sucrose. It is absorbed dose-dependently, 78% to 92% is excreted unchanged in urine within 24 h, less than 1% of the dose is metabolised to erythronate, the half-life of excretion is about 4 h, and human gut microbiota metabolise it negligibly; in humans erythritol is also formed endogenously through the pentose phosphate pathway. ADI 0.5 g/kg bw per day (500 mg/kg bw per day), the lower bound of the range of NOAELs for diarrhoea in human studies, without uncertainty factors; 95th percentile acute and chronic exposure estimates were at or above the ADI in all populations, and the Panel considered the exposure assessments overestimates. The Panel considered that the cohort associations of circulating erythritol with cardiovascular disease (Witkowski et al. 2023 and others) do not demonstrate a causal relationship with dietary erythritol, that fasting erythritol may be a biomarker of metabolic disturbance, and that no long-term interventional study is available; the in vitro platelet studies provided insufficient basis to predict effects in humans.
Regulator
EFSA Panel on Food Additives and Flavourings (FAF), Castle L, Andreassen M, Aquilina G, Bastos ML, Boon P, et al. Scientific opinion on the extension of the authorisation of use of the food additive steviol glycosides (E 960a–d) and the modification of the acceptable daily intake (ADI) for steviol EFSA Journal, 2024.
doi:10.2903/j.efsa.2024.9045 PubMed 39502654
Funding and finding
Funding
European Food Safety Authority; requestor: European Commission (question number EFSA-Q-2023-00594), following an application to extend uses and modify the ADI. Adopted 25 September 2024.
Finding
Steviol glycosides from stevia (E 960a) are obtained by water extraction of the leaves of Stevia rebaudiana Bertoni and contain not less than 95% steviolbioside, rubusoside, dulcoside A, stevioside and rebaudiosides A, B, C, D, E, F and M. Steviol glycosides are not hydrolysed by digestive enzymes of the upper gastrointestinal tract; colonic microbiota release the aglycone steviol, which is absorbed and glucuronidated, and steviol glucuronide is excreted in urine and partly via bile into faeces. In eight men given rebaudioside A or stevioside, steviol glucuronide in urine accounted for 59% and 62% of the doses. The Panel found insufficient justification to raise the ADI of 4 mg/kg bw per day, expressed as steviol equivalents, to 6 or 16 mg/kg bw per day.
Independent research
Juen Z, Lu Z, Yu R, Chang AN, Wang B, Fitzpatrick AWP, et al. The structure of human sweetness Cell, 2025.
doi:10.1016/j.cell.2025.04.021 PubMed 40339580
Funding and finding
Funding
C.S.Z. is an investigator of the Howard Hughes Medical Institute. The early phase of this project was funded in part by a grant from the Berrie Foundation to Rudy Leibel and C.S.Z.
Finding
Cryo-EM structures of the human sweet receptor, a TAS1R2-TAS1R3 heterodimer, bound to sucralose and to aspartame. Both sweeteners bind the same pocket in the Venus flytrap domain of TAS1R2; alanine substitutions of pocket residues (Y103, D142, S165) markedly reduced responses to sucralose in cell-based assays. TAS1R2 binds the ligand and couples to the G protein, and TAS1R3 is an obligatory partner of TAS1R2 for receptor function. The authors state that this single receptor mediates sweet taste in humans and other mammals.
Independent research
de Ruyter JC, Olthof MR, Seidell JC, Katan MB. A trial of sugar-free or sugar-sweetened beverages and body weight in children New England Journal of Medicine, 2012.
doi:10.1056/NEJMoa1203034 PubMed 22998340
Funding and finding
Registration
NCT00893529
Participants
641
Follow-up
18 months
Funding
Supported by grants from the Netherlands Organization for Health Research and Development (120520010), the Netherlands Heart Foundation (2008B096), and the Royal Netherlands Academy of Arts and Sciences (ISK/741/PAH). The investigators hired Refresco Benelux to produce the beverages; the manufacturer had no role in the design of the study, the accrual or analysis of the data, or the preparation of the manuscript.
Finding
Double-blind; one 250 ml can per day of a sugar-free drink (34 mg sucralose, 12 mg acesulfame potassium) or a matching drink with 26 g sucrose (104 kcal). With imputation for the 26% who stopped drinking the beverages, BMI z score rose by 0.02 SD in the sugar-free group and 0.15 SD in the sugar group (95% CI of the difference -0.21 to -0.05); weight rose by 6.35 kg and 7.37 kg (difference 1.01 kg; 95% CI -1.54 to -0.48).
Independent research
Odegaard AO, Chang J, Jiang L, Rashid S, Rydell S, Mitchell NR, et al. The Effect of Substituting Water for Artificially Sweetened Beverages on Glycemic and Weight Measures in People With Type 2 Diabetes: The Study of Drinks With Artificial Sweeteners (SODAS), a Randomized Trial Diabetes Care, 2026.
doi:10.2337/dc25-1516 PubMed 41369640
Funding and finding
Registration
NCT03944616
Participants
181
Follow-up
24 weeks
Funding
This work was supported by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases (grant R01DK117028). The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Finding
Participants were randomised to 24 oz per day of a commercial artificially sweetened beverage of their choice (n = 91) or unflavoured water (n = 90); 179 provided complete data. HbA1c changed from 7.19% to 7.14% with sweetened beverages and from 7.20% to 7.44% with water; the adjusted mean difference in change was 0.29 percentage points higher with water (SE 0.12; P = 0.013). The difference in change of fasting glucose was 4.71 mg/dL (SE 6.43; P = 0.47), and weight change was 1.11 kg higher with water (SE 0.55; P = 0.045).
Independent research
Witkowski M, Wilcox J, Province V, Wang Z, Nemet I, Tang WHW, 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.
doi:10.1161/ATVBAHA.124.321019 PubMed 39114916
Funding and finding
Registration
NCT04731363
Participants
20
Follow-up
30 minutes after a single dose
Funding
This work was supported by grants from the NIH and Office of Dietary Supplements P01 HL147823, R01 HL167831 and R01 HL103866 (S.L.H.). M.W. was partially supported by an award from the Deutsche Forschungsgemeinschaft WI 5229/1-1 and the Corona Foundation (S0199/10098/2023). Lead sponsor in the registry: The Cleveland Clinic.
Finding
After 30 g erythritol, plasma erythritol rose from a median 3.8 (IQR 3.4 to 3.9) to 6480 (5930 to 7300) umol/L at 30 min, and ADP- and TRAP6-stimulated platelet aggregation increased in every subject; stimulus-dependent release of serotonin rose (P<0.0001 with TRAP6, P=0.004 with ADP), as did release of CXCL4 with TRAP6 (P<0.0001; P=0.064 with ADP). After 30 g glucose, plasma glucose rose from 87 to 127 mg/dL and platelet aggregation and granule release did not increase.
Industry-funded
Harrold JA, Hill S, Radu C, Thomas P, Thorp P, Hardman CA, et al. Non-nutritive sweetened beverages versus water after a 52-week weight management programme: a randomised controlled trial International Journal of Obesity, 2024.
doi:10.1038/s41366-023-01393-3 PubMed 37794246
Funding and finding
Registration
NCT02591134
Participants
493
Follow-up
52 weeks: 12-week weight-loss phase and 40-week weight-maintenance phase
Funding
This trial was funded by the American Beverage Association. The American Beverage Association was not involved in the design, conduct or interpretation of this trial; a representative from the American Beverage Association was provided with the opportunity to review the manuscript. Final decisions regarding the content were retained by the authors. The manuscript was developed with the assistance of a medical writer, funded by the American Beverage Association, under the direction of the authors.
Finding
SWITCH trial: two 330 ml servings per day of non-nutritive sweetened beverages or water within a behavioural weight-management programme. In the 262 completers (53.1%), weight changed by -6.1 kg with water and -7.5 kg with sweetened beverages, a difference of 1.4 kg (90% CI 0.2 to 2.6), non-equivalent and below the 1.5 kg prespecified as clinically significant. With multiple imputation for all 493, the changes were -6.3 and -7.1 kg (difference 0.8 kg, 90% CI -0.1 to 1.7).
Industry-funded
Witkowski M, Nemet I, Alamri H, Wilcox J, Gupta N, Nimer N, et al. The artificial sweetener erythritol and cardiovascular event risk Nature Medicine, 2023.
doi:10.1038/s41591-023-02223-9 PubMed 36849732
Funding and finding
Registration
NCT00590200; DRKS00020915; NCT04731363
Participants
4,139
Follow-up
3 years
Funding
This work is supported by grants from the NIH and Office of Dietary Supplements P01 HL147823, R01 HL103866 (S.L.H.), the Leducq Foundation #17CVD01 (S.L.H., U.L.) and the Deutsche Forschungsgemeinschaft WI 5229/1-1 (M.W.). A.H. is participant in the BIH-Charité Advanced Clinician Scientist Program funded by the Charité - Universitätsmedizin Berlin and the Berlin Institute of Health. The LipidCardio Study was partially funded by the Sanofi-Aventis Deutschland GmbH (I.D., U.L.). P.P.S. was supported in part by an AHA postdoctoral grant 20POST35210937. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Finding
Fourth against first quartile of fasting plasma erythritol, adjusted hazard ratio for 3-year death, non-fatal myocardial infarction or stroke: 2.95 (95% CI 1.70 to 5.12) in the discovery cohort, 1.80 (1.18 to 2.77) in the US and 2.21 (1.20 to 4.07) in the European validation cohort; event counts by quartile not given in the text. In vitro, erythritol enhanced agonist-stimulated activation of human platelets from 4.5 umol/L (GP IIb/IIIa activation) and aggregation from 18 umol/L; in mice it shortened the time to cessation of carotid blood flow after FeCl3 injury. After 30 g erythritol, plasma erythritol in 8 volunteers rose from a median 3.84 umol/L to 5.85 mmol/L at 30 min and remained elevated for more than 2 days. The authors note that the observational studies cannot establish causation and that unmodelled confounding, for example by diet, is possible.
Expert consensus
World Health Organization. Use of non-sugar sweeteners: WHO guideline World Health Organization, Geneva, 2023.
PubMed 37256996
Funding and finding
Funding
WHO gratefully acknowledges the financial support provided by the Ministry of Health, Labour and Welfare of the Government of Japan for the guideline development work, including the systematic reviews, and by Qingdao University in China for hosting the 13th meeting of the WHO Nutrition Guidance Expert Advisory Group - Subgroup on Diet and Health in December 2019.
Finding
WHO suggests that non-sugar sweeteners not be used as a means of achieving weight control or reducing the risk of noncommunicable diseases (conditional recommendation, low certainty evidence overall). The recommendation does not apply to individuals with existing diabetes, or to sugar alcohols and low-calorie sugars. In the systematic review, randomised trials in adults, most lasting 3 months or less, gave body weight MD -0.71 kg (95% CI -1.13 to -0.28; 29 trials, 2433 participants; low certainty) and fasting glucose MD -0.01 mmol/L (-0.05 to 0.04; 16 trials, 1494 participants; moderate certainty). Prospective cohorts associated higher intake with type 2 diabetes (beverages, HR 1.23, 95% CI 1.14 to 1.32; 13 studies, 408,609 participants), cardiovascular diseases (HR 1.32, 1.17 to 1.50; 3 studies, 166,938 participants) and all-cause mortality (HR 1.12, 1.05 to 1.19). Reverse causation and residual confounding were considered possible contributors.
Expert consensus
IARC Working Group on the Identification of Carcinogenic Hazards to Humans. Aspartame, methyleugenol, and isoeugenol IARC Monographs on the Identification of Carcinogenic Hazards to Humans, volume 134, 2024.
PubMed 39715313
Funding and finding
Funding
This programme has been supported since 1982 by Cooperative Agreement U01 CA33193 with the United States National Cancer Institute, Department of Health and Human Services. Additional support has been provided since 1986 by the European Commission Directorate-General for Employment, Social Affairs, and Inclusion, and since 1992 by the United States National Institute of Environmental Health Sciences. The contents of this volume are solely the responsibility of the Working Group.
Finding
Aspartame is possibly carcinogenic to humans (Group 2B): limited evidence in humans, from positive associations of artificially sweetened beverage consumption, used as a proxy for aspartame, with hepatocellular carcinoma in three studies including four cohorts, in which bias or confounding could not be ruled out; limited evidence in experimental animals; limited mechanistic evidence. A minority of the Working Group supported Group 2A. In humans, ingested aspartame is hydrolysed by esterases and peptidases in the gastrointestinal tract to aspartic acid, phenylalanine and methanol; phenylalanine is partly converted to tyrosine in the liver by phenylalanine hydroxylase. The Monographs assess the strength of evidence that an agent is a cancer hazard, which the Preamble distinguishes from a cancer risk, the probability of cancer at a given exposure.

Updated 2026-10-21