{"v":1,"ledgerId":"aspartame-acesulfame","generatedAt":"2026-11-05T21:54:51.831Z","query":"(TITLE:(\"Aspartame\" OR \"ASPARTAME\" OR \"E951\" OR \"ACESULFAME POTASSIUM\" OR \"22839-47-0\") OR ABSTRACT:(\"Aspartame\" OR \"ASPARTAME\" OR \"E951\" OR \"ACESULFAME POTASSIUM\" OR \"22839-47-0\")) AND (TOXICITY OR EXPOSURE OR \"ENDOCRINE\" OR \"REPRODUCTIVE\" OR CARCINOGEN* OR \"BIOMONITORING\" OR \"SYSTEMATIC REVIEW\") AND SRC:MED AND LANG:eng","totalPapers":606,"lastYearPapers":75,"analysed":35,"byFunding":{"independent":17,"industry":0,"mixed":0,"none_declared":0,"unclear":18},"byDesign":{"human":4,"animal":11,"in_vitro":4,"review":2,"other":14},"byFinding":{"concern":25,"no_effect":7,"mixed":3},"gap":{"independent":{"concern":11,"total":17},"industry":{"concern":0,"total":0}},"fundingSources":{"full_text":7,"grant_metadata":15,"abstract":0,"none":13},"newestPublished":"2026-10-03","papers":[{"id":"pmid:42829191","pmid":"42829191","pmcid":"","doi":"10.1016/j.fct.2026.116424","title":"Low- and no-calorie sweeteners lack shared target organs or modes of action required for cumulative risk assessment.","journal":"Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association","published":"2026-10-03","design":"other","finding":"no_effect","summary":"Low- and no-calorie sweeteners, including aspartame and acesulfame-K, lack shared structural or toxicological features, showing no cumulative effects at typical intake levels.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"none","verified":false},{"id":"pmid:42772194","pmid":"42772194","pmcid":"","doi":"10.1016/j.tice.2026.103972","title":"Acute high-dose acesulfame exposure induces developmental and neurobehavioral toxicity.","journal":"Tissue & cell","published":"2026-09-19","design":"animal","finding":"concern","summary":"Acute high-dose acesulfame potassium exposure in zebrafish larvae was associated with developmental abnormalities, altered motor neuron morphology, impaired locomotor and sensorimotor behavior, and apoptosis-related gene expression changes.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"none","verified":false},{"id":"pmid:42796941","pmid":"42796941","pmcid":"PMC13609978","doi":"10.3390/nu18182958","title":"Urinary Concentrations of Non-Nutritive Sweeteners and Breast Cancer: A Case-Cohort Analysis of the Moli-sani Study.","journal":"Nutrients","published":"2026-09-09","design":"human_cohort","finding":"no_effect","summary":"Urinary concentrations of non-nutritive sweeteners, including aspartame and acesulfame, were not associated with overall breast cancer risk in a case-cohort analysis of the Moli-sani Study.","funding":"independent","conflictOfInterest":true,"fundingEvidence":["public: \"Ministry of\"","COI: \"employed by\""],"fundingSource":"full_text","verified":false},{"id":"pmid:42739035","pmid":"42739035","pmcid":"PMC13567529","doi":"10.3390/nu18172863","title":"Acute and Prolonged Effects of Sweeteners and Sweetness Enhancers on Postprandial Substrate Oxidation, Energy Expenditure, Glucose, and Insulin in Humans-A SWEET Sub-Study.","journal":"Nutrients","published":"2026-09-02","design":"human_rct","finding":"no_effect","summary":"Acesulfame potassium and cyclamate showed no significant acute or prolonged effects on postprandial fat oxidation, carbohydrate oxidation, energy expenditure, glucose, or insulin compared to water in humans.","funding":"independent","conflictOfInterest":true,"fundingEvidence":["public: \"Horizon 2020\"","COI: \"received honoraria from\""],"fundingSource":"full_text","verified":false},{"id":"pmid:42660440","pmid":"42660440","pmcid":"","doi":"10.1016/j.cbi.2026.112319","title":"Assessing the cardiovascular toxicity of aspartame: An integrated approach from computational prediction to experimental validation.","journal":"Chemico-biological interactions","published":"2026-08-27","design":"other","finding":"concern","summary":"Computational, in vivo mouse, and in vitro studies showed aspartame promotes cardiovascular toxicity by modulating inflammatory responses, impairing endothelium-dependent vasodilation, and increasing vascular adhesion molecules.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"National Natural Science Foundation of China\""],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:42648381","pmid":"42648381","pmcid":"","doi":"10.1016/j.biortech.2026.135720","title":"Aspartame induces hormesis-toxicity switch in microalgal‑bacterial granular sludge: Community assembly and functional gene responses.","journal":"Bioresource technology","published":"2026-08-26","design":"in_vitro","finding":"mixed","summary":"Low concentrations of aspartame stimulated microalgal-bacterial granular sludge performance, while high concentrations induced oxidative stress and impaired treatment efficiency.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"National Natural Science Foundation of China\""],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:42648040","pmid":"42648040","pmcid":"","doi":"10.1016/j.ecoenv.2026.120705","title":"Risk and mechanisms of artificial sweetener-induced metabolic dysfunction-associated steatotic liver disease: Insights from multi-level bioinformatics and in vitro assays.","journal":"Ecotoxicology and environmental safety","published":"2026-08-26","design":"in_vitro","finding":"concern","summary":"Bioinformatics and in vitro HepG2 assays showed artificial sweeteners, including aspartame and acesulfame, target MASLD-related pathways, inhibit NR4A1 and THBS1 expression, and induce intracellular lipid accumulation.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"National Natural Science Foundation of China\""],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:42655918","pmid":"42655918","pmcid":"PMC13691406","doi":"10.1002/adhm.202505777","title":"Hydrogels Augmented With Artificial Sweeteners can Inhibit Multidrug-Resistant Acinetobacter baumannii Growth and Biofilm Formation While Demonstrating Safety in Pre-Clinical Pilot Human Trials.","journal":"Advanced healthcare materials","published":"2026-08-26","design":"other","finding":"no_effect","summary":"Hydrogels augmented with acesulfame potassium inhibited multidrug-resistant bacteria and biofilms while showing non-cytotoxicity and no adverse irritancy effects in a human pilot study.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"Medical Research Council\""],"fundingSource":"full_text","verified":false},{"id":"pmid:42604715","pmid":"42604715","pmcid":"","doi":"10.1016/j.bbadis.2026.168425","title":"Aspartame triggers premature ovarian failure via SIRT1-dependent suppression of the PI3K/AKT/mTOR pathway and induction of oxidative stress and apoptosis.","journal":"Biochimica et biophysica acta. Molecular basis of disease","published":"2026-08-17","design":"animal","finding":"concern","summary":"Aspartame exposure in rats and human ovarian cells caused premature ovarian failure, oxidative stress, apoptosis, and disruption of the SIRT1 and PI3K/AKT/mTOR pathways.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"none","verified":false},{"id":"pmid:41951359","pmid":"41951359","pmcid":"PMC13479683","doi":"10.1136/gutjnl-2024-333999","title":"Quantifying artificial sweeteners and emulsifiers in Crohn's disease and its relationship with disease activity: the ENIGMA study - a novel and targeted approach.","journal":"Gut","published":"2026-08-06","design":"human_case_control","finding":"concern","summary":"Patients with Crohn's disease had higher levels of artificial sweeteners than controls, and sweetener levels correlated significantly with disease activity.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"National Natural Science Foundation of China\""],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:42544845","pmid":"42544845","pmcid":"","doi":"10.1093/inteam/vjag122","title":"A Review of the Fate and Effects of Selected Low- and No-Calorie Sweeteners and Their Probabilistic Risk to Aquatic Organisms.","journal":"Integrated environmental assessment and management","published":"2026-08-03","design":"other","finding":"no_effect","summary":"Predicted environmental concentrations of aspartame were significantly lower than predicted no-effect concentrations, indicating high margins of safety and minimal ecological risk for aquatic organisms.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"none","verified":false},{"id":"pmid:42537333","pmid":"42537333","pmcid":"","doi":"10.1016/j.compbiolchem.2026.109290","title":"A comprehensive analysis reveals the potential risks and molecular connections between aspartame and polycystic ovary syndrome.","journal":"Computational biology and chemistry","published":"2026-07-29","design":"other","finding":"concern","summary":"Network toxicology and molecular docking analyses suggest aspartame may contribute to polycystic ovary syndrome pathogenesis by modulating FOS- and JUN-mediated endocrine and inflammatory pathways.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"none","verified":false},{"id":"pmid:42514471","pmid":"42514471","pmcid":"PMC13415452","doi":"10.3390/nu18142402","title":"Effects of Non-Nutritive Artificial Sweeteners on Gut Microbiota and Host Metabolism and Health-Related Outcomes: A Review.","journal":"Nutrients","published":"2026-07-22","design":"other","finding":"mixed","summary":"A review indicates current evidence does not support a class-wide conclusion that non-nutritive artificial sweeteners, including aspartame and acesulfame potassium, are uniformly harmful or safe.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"National Key Research and Development Program\""],"fundingSource":"full_text","verified":false},{"id":"pmid:42480151","pmid":"42480151","pmcid":"","doi":"10.1016/j.biopha.2026.119788","title":"Investigation of the healing effects of phenylboronic acid and exosome on the TGF-β-Smad/REDD1 pathway in aspartame-induced liver damage in BALB/c type mice.","journal":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","published":"2026-07-21","design":"animal","finding":"concern","summary":"Chronic aspartame administration induced hepatocellular degeneration, inflammation, and pro-fibrotic signaling in male BALB/c mice, which was attenuated by phenylboronic acid and exosome treatments.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:42464261","pmid":"42464261","pmcid":"PMC13656438","doi":"10.1186/s12931-026-03820-1","title":"Aspartame and asthma: immunomodulatory effects on airway inflammation.","journal":"Respiratory research","published":"2026-07-17","design":"other","finding":"concern","summary":"Aspartame intake was associated with increased asthma odds in adolescents and exacerbated airway inflammation, IgE levels, and histological changes in sensitized mice.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"University Hospital 112TMU-TMUH-02-1 and 113TMU-TMUH-01 Chen Yang-Ching This study was supported by grants from the National Science and Technology Council, Taiwan (grant number 113-2628-B-038-006-MY3) and from Taipei Medical University Hospital (grant\""],"fundingSource":"full_text","verified":false},{"id":"pmid:42393139","pmid":"42393139","pmcid":"","doi":"10.1038/s41598-026-58464-4","title":"In silico exploration of potential associations between aspartame and cardiometabolic disease networks: a network toxicology study.","journal":"Scientific reports","published":"2026-07-02","design":"other","finding":"concern","summary":"An in silico study identified 45 overlapping targets between aspartame and cardiometabolic diseases, showing stable binding to AGT and enrichment in inflammation and RAAS signaling pathways.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"none","verified":false},{"id":"pmid:42504496","pmid":"42504496","pmcid":"PMC13402976","doi":"10.1002/mnfr.70563","title":"Chronic Aspartame Exposure Leading to Hypertension in Mice may be Related to the Activation of the Wnt/β-Catenin Signaling Pathway in the Hypothalamus.","journal":"Molecular nutrition & food research","published":"2026-07-01","design":"animal","finding":"concern","summary":"Chronic aspartame exposure in mice significantly increased blood pressure, induced hypothalamic neuronal necrosis, and activated the Wnt/β-catenin signaling pathway.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"none","verified":false},{"id":"pmid:42385372","pmid":"42385372","pmcid":"","doi":"10.1016/j.ecoenv.2026.120456","title":"Aspartame exposure promotes endometriosis progression through PTGS2-mediated oxidative stress and mitochondrial dysfunction.","journal":"Ecotoxicology and environmental safety","published":"2026-07-01","design":"animal","finding":"concern","summary":"Aspartame exposure promoted endometriosis progression in cellular and mouse models through PTGS2-mediated oxidative stress and mitochondrial dysfunction.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"National Natural Science Foundation of China\""],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:42371361","pmid":"42371361","pmcid":"","doi":"10.1007/s12672-026-05503-1","title":"Aspartame drives the continuous progression from MASLD to HCC.","journal":"Discover oncology","published":"2026-06-29","design":"other","finding":"concern","summary":"Network toxicology, RNA-seq, and docking analyses indicate aspartame binds EGR1 and PTGS2, potentially driving the continuous progression from MASLD to hepatocellular carcinoma.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"Natural Science Foundation\""],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:42629092","pmid":"42629092","pmcid":"","doi":"10.1016/j.foodres.2026.119872","title":"Non-nutritive sweeteners in hand-shaken beverages: Occurrence, consumption patterns, and dietary risk assessment.","journal":"Food research international (Ottawa, Ont.)","published":"2026-06-27","design":"other","finding":"no_effect","summary":"Analysis of Taiwanese hand-shaken beverages found acesulfame potassium and other sweeteners resulted in dietary exposures well below acceptable daily intake thresholds, indicating minimal toxicological concern.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"none","verified":false},{"id":"pmid:42450069","pmid":"42450069","pmcid":"PMC13361535","doi":"10.3390/ijms27135798","title":"Integrative Network Toxicology, Machine Learning, Single-Cell Analysis, scTenifoldKnk-Based Virtual Knockout, and Molecular Docking Suggest a Potential Molecular Link Between Aspartame and Rheumatoid Arthritis Involving <i>HLA-DRB1</i>.","journal":"International journal of molecular sciences","published":"2026-06-26","design":"other","finding":"concern","summary":"Computational network toxicology and molecular docking identified a potential molecular link between predicted aspartame targets and rheumatoid arthritis networks involving HLA-DRB1.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"National Natural Science Foundation of China\""],"fundingSource":"full_text","verified":false},{"id":"pmid:42319418","pmid":"42319418","pmcid":"","doi":"10.1007/s00210-026-05591-4","title":"Integrated network toxicology and experimental validation to investigate potential mechanisms associated with aspartame-induced malignant phenotypic changes in colorectal cancer.","journal":"Naunyn-Schmiedeberg's archives of pharmacology","published":"2026-06-19","design":"in_vitro","finding":"concern","summary":"Aspartame increased colorectal cancer cell proliferation, elevated reactive oxygen species, and promoted epithelial-mesenchymal transition-related molecular alterations in HCT116 and SW480 cells.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"none","verified":false},{"id":"pmid:42314871","pmid":"42314871","pmcid":"","doi":"10.1016/j.tjnut.2026.101680","title":"Aspartame and Obesity: A Comprehensive Review of Mechanisms of Action, Transgenerational Effects, and Health Implications.","journal":"The Journal of nutrition","published":"2026-06-18","design":"other","finding":"mixed","summary":"This review evaluates potential mechanisms linking aspartame intake to obesity, metabolic and neurobehavioral risks, and transgenerational effects alongside established safety thresholds.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"none","verified":false},{"id":"pmid:42308903","pmid":"42308903","pmcid":"","doi":"10.1016/j.marenvres.2026.108181","title":"Chronic exposure of the model organism Aurelia coerulea (Scyphozoa, Cnidaria) to \"first generation\" artificial sweeteners.","journal":"Marine environmental research","published":"2026-06-12","design":"animal","finding":"concern","summary":"Chronic exposure to aspartame temporarily arrested growth and asexual reproduction and triggered regression in Aurelia coerulea polyps, followed by full regeneration and acclimatization.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"European Commission\""],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:42242077","pmid":"42242077","pmcid":"","doi":"10.1016/j.jhazmat.2026.142583","title":"Aspartame promotes intestinal tumor progression via Akkermansia muciniphila -mediated 5-hydroxytryptophan production.","journal":"Journal of hazardous materials","published":"2026-06-02","design":"animal","finding":"concern","summary":"Subchronic aspartame exposure in drinking water promoted intestinal tumor progression in Apc min/+ mice via Akkermansia muciniphila-mediated 5-hydroxytryptophan production.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"National Natural Science Foundation of China\""],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:42142239","pmid":"42142239","pmcid":"","doi":"10.1007/s13668-026-00768-y","title":"Artificial Sweeteners and Gut Microbiota: Mechanistic Insights and Implications for Metabolic Health.","journal":"Current nutrition reports","published":"2026-05-16","design":"other","finding":"concern","summary":"Review indicates artificial sweeteners like aspartame and acesulfame-K alter gut microbiota, short-chain fatty acid production, and barrier integrity, influencing glucose homeostasis and insulin sensitivity.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"none","verified":false},{"id":"pmid:42010990","pmid":"42010990","pmcid":"","doi":"10.1080/15376516.2026.2662931","title":"Neurotoxic and metabolic effects of chronic aspartame consumption in rodent models: a systematic review and meta-analysis.","journal":"Toxicology mechanisms and methods","published":"2026-05-14","design":"systematic_review","finding":"concern","summary":"A systematic review and meta-analysis of rodent studies found chronic aspartame exposure was associated with increased oxidative stress, neurobehavioural deficits, and metabolic dysfunction.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:40608001","pmid":"40608001","pmcid":"","doi":"10.1093/nutrit/nuaf103","title":"Aspartame and Its Potential Neurocognitive Effects in Humans.","journal":"Nutrition reviews","published":"2026-05-01","design":"systematic_review","finding":"concern","summary":"A scoping review found that multiple studies associate aspartame exposure with potential neurotoxic effects, histopathological brain changes, memory and learning impairments, and mood disorders in animals and humans.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"none","verified":false},{"id":"pmid:42012419","pmid":"42012419","pmcid":"","doi":"10.1177/02601060261443466","title":"Long-term aspartame consumption affects global levels of DNA methylation in different types of rat tissues.","journal":"Nutrition and health","published":"2026-04-21","design":"animal","finding":"concern","summary":"Long-term consumption of aspartame in rats altered global DNA methylation levels in the liver, kidney, pancreas, and brain cortex.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:42041924","pmid":"42041924","pmcid":"PMC13113027","doi":"10.3390/biology15080646","title":"High-Sugar Consumption Induces Anxiety-Like Behavior via Activating the Glutamatergic Neurons in the Nucleus of the Solitary Tract in Mice.","journal":"Biology","published":"2026-04-19","design":"animal","finding":"no_effect","summary":"Two-week consumption of acesulfame potassium did not induce anxiety-like behavior or activate nucleus of the solitary tract glutamatergic neurons in mice.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"National Natural Science Foundation of China\""],"fundingSource":"full_text","verified":false},{"id":"pmid:42002150","pmid":"42002150","pmcid":"","doi":"10.1016/j.taap.2026.117827","title":"Nanoencapsulation modulates aspartame metabolite exposure: Toxicokinetic, mechanistic, and pharmacological evaluation in a glucocorticoid dysfunction model.","journal":"Toxicology and applied pharmacology","published":"2026-04-17","design":"animal","finding":"concern","summary":"Nanoencapsulation of aspartame reduced peak phenylalanine exposure and attenuated oxidative stress, inflammatory cytokines, and metabolic dysfunction in a rat model compared to free aspartame.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:42004387","pmid":"42004387","pmcid":"PMC13084496","doi":"10.1021/acsomega.5c06005","title":"In Vitro Testing of Artificial Sweeteners with Apple and Chokeberry Fruit Juice Extracts for Intestinal Permeability and Glucose Uptake.","journal":"ACS omega","published":"2026-03-31","design":"in_vitro","finding":"concern","summary":"In human intestinal cell models, aspartame significantly reduced TEER values, though it did not alter permeability or glucose uptake, and the reduction was prevented by apple polyphenols.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"none","verified":false},{"id":"pmid:41879845","pmid":"41879845","pmcid":"","doi":"10.1007/s00210-026-05241-9","title":"Long-term artificial sweetener exposure increases the risk of atherosclerosis.","journal":"Naunyn-Schmiedeberg's archives of pharmacology","published":"2026-03-25","design":"other","finding":"concern","summary":"Computational analyses and Mendelian randomization suggest artificial sweeteners, including aspartame and acesulfame, may promote atherosclerosis via interactions with SCARB1 and ST14 targets.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"Education Department\""],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:41765137","pmid":"41765137","pmcid":"","doi":"10.1016/j.tjnut.2026.101460","title":"Association between Aspartame Consumption and Cancer Risk: Evidence from a Large Prospective Cohort.","journal":"The Journal of nutrition","published":"2026-02-28","design":"human_cohort","finding":"concern","summary":"In a prospective cohort of 100,004 U.S. adults, aspartame consumption was associated with higher risks of all cancers combined, obesity-related cancers, and non-obesity-related cancers.","funding":"unclear","conflictOfInterest":false,"fundingEvidence":[],"fundingSource":"grant_metadata","verified":false},{"id":"pmid:41688030","pmid":"41688030","pmcid":"","doi":"10.1016/j.jnutbio.2026.110309","title":"The protective role of Astaxanthin against the central and peripheral detrimental effects for chronic administration of sweeteners in a rat model: Involvement of multiple signaling axes.","journal":"The Journal of nutritional biochemistry","published":"2026-02-11","design":"animal","finding":"concern","summary":"Chronic aspartame intake in rats induced hyperglycemia, oxidative stress, inflammation, and organ dysfunction in the liver, heart, and brain, which were alleviated by astaxanthin.","funding":"independent","conflictOfInterest":false,"fundingEvidence":["public: \"University\""],"fundingSource":"grant_metadata","verified":false}],"model":"gemini-3.8-flash","run":{"aiCalls":39,"cachedPapers":0,"offTopic":4,"inputTokens":27032,"outputTokens":5413}}