Aspartame Consumption Research Articles

Long-term consumption of aspartame & cancer risk

Artificial sweeteners, specifically aspartame, are present in everyday modern diets due to their low-calorie content and high level of sweetness. They are often used as sugar substitutes to promote weight loss and manage diabetes. Despite their widespread use and approval by regulatory bodies such as the U.S. Food and Drug Administration (FDA), concerns about the safety and potential carcinogenicity of artificial sweeteners persist. This research paper delves into the controversy surrounding aspartame, which was classified as possibly carcinogenic to humans by the International Agency for Research on Cancer (IARC) in 2023. By reviewing literature and analyzing studies published between 2000 and 2024, this paper explores aspartame’s metabolism in the human body, its by-products, and its biological effects. The article also delves into a notable experimental study involving male Wistar albino rats that demonstrated significant biochemical changes, histological liver damage, and gene expression alterations at high doses of aspartame, indicating potential cancer risks. The findings underscore the need for further research to clarify the biochemical and molecular mechanisms linking artificial sweeteners to cancer while emphasizing cautious consumption and reevaluation of safety guidelines.

Consumption of aspartame and risk of breast cancer in the Nurses' Health Studies.

Debate persists regarding the potential carcinogenicity of aspartame as suggested by experimental studies. Therefore, we prospectively evaluated whether aspartame consumption is associated with breast cancer risk in the Nurses' Health Study (NHS) and Nurses' Health study II (NHSII). We used Cox models to calculate HRs and 95% CIs. During up to 30 years of follow-up with 4-yearly assessments of intake, we documented 10,814 invasive breast cancer cases. Overall, there was no association between aspartame consumption and invasive breast cancer risk (HR per 200 mg/day [approximately one 12 oz serving of diet soda] = 1.00 (95% CI 0.98, 1.03). We observed similar lack of associations after excluding cases occurring in the first 10 years of follow-up (n = 3,125) (HR per 200 mg/day 1.00, 95% CI 0.97, 1.03). In these cohorts, aspartame consumption did not increase breast cancer risk.

Aspartame Intake Delayed Puberty Onset in Female Offspring Rats and Girls.

The disturbance of the hypothalamic-pituitary-gonadal (HPG) axis, gut microbiota (GM) community, and short-chain fatty acids (SCFAs) is a triggering factor for pubertal onset. The study investigates the effects of the long-term intake of aspartame on puberty and GM in animals and humans. Aspartame-fed female offspring rats result in vaginal opening time prolongation, serum estrogen reduction, and serum luteinizing hormone elevation. , 60mgkg-1 aspartame treatment decreases the mRNA levels of gonadotropin-releasing hormone (GnRH), Kiss1, and G protein-coupled receptor 54 (GPR54), increases the mRNA level of RFamide-related peptide-3 (RFRP-3), and decreases the expression of GnRH neurons in the hypothalamus. Significant differences in relative bacterial abundance at the genus levels and decreased fecal SCFA levels are noted by 60mgkg-1 aspartame treatment. Among which, Escherichia-Shigella is negatively correlated with several SCFAs. In girls, high-dose aspartame consumption decreases the risk of precocious puberty. Aspartame reduces the chance of puberty occurring earlier than usual in female offspring and girls. Particularly, 60mgkg-1 aspartame-fed female offspring delays pubertal onset through the dysregulation of HPG axis and GM composition by inhibiting the Kiss1/GPR54 system and inducing the RFRP-3. An acceptable dose of aspartame should be recommended during childhood.

Differential Alterations of Expression of the Serotoninergic System Genes and Mood-Related Behavior by Consumption of Aspartame or Potassium Acesulfame in Rats.

The use of aspartame (ASP) and potassium acesulfame (ACK) to reduce weight gain is growing; however, contradictory effects in body mass index control and neurobiological alterations resulting from artificial sweeteners consumption have been reported. This study aimed to evaluate the impact of the chronic consumption of ASP and ACK on mood-related behavior and the brain expression of serotonin genes in male Wistar rats. Mood-related behaviors were evaluated using the swim-forced test and defensive burying at two time points: 45 days (juvenile) and 95 days (adult) postweaning. Additionally, the mRNA expression of three serotoninergic genes (Slc6a4, Htr1a, and Htr2c) was measured in the brain areas (prefrontal cortex, hippocampus, and hypothalamus) involved in controlling mood-related behaviors. In terms of mood-related behaviors, rats consuming ACK exhibited anxiety-like behavior only during the juvenile stage. In contrast, rats consuming ASP showed a reduction in depressive-like behavior during the juvenile stage but an increase in the adult stage. The expression of Slc6a4 mRNA increased in the hippocampus of rats consuming artificial sweeteners during the juvenile stage. In the adult stage, there was an upregulation in the relative expression of Slc6a4 and Htr1a in the hypothalamus, while Htr2c expression decreased in the hippocampus of rats consuming ASP. Chronic consumption of ASP and ACK appears to have differential effects during neurodevelopmental stages in mood-related behavior, potentially mediated by alterations in serotoninergic gene expression.

Aspartame and diet soda impact on blood sugar and insulin in Wistar rat

Research reports on the safety of Aspartame as a sugar substitute which was intended to reduce the prevalence of metabolic disorders has been inconclusive. Thus, this study is aimed at investigating the effects of aspartame and diet soda on body weight, blood sugar and insulin levels. Thirty seven Wistar rats were divided into: Group 1 (5): control group and administered 5ml of distilled water daily. Groups 2 and 3 (8 each) received high and low doses of diet soda respectively. Groups 4 and 5 (8 each) received high (45 mg/ kg b.w) and low (22.5 mg/kg b.w) doses of aspartame respectively. After 10 weeks, the rats were subjected to an overnight fast for the determination of fasting blood sugar test after which they were sacrificed. Blood samples were collected and the pancreas harvested and put in formal saline for histological analysis. Insulin level was measured using ELISA technique. Results show various morphological changes in the pancreas of all experimental groups, including hypoplastic islet, vascular congestion and ulceration, nerve hypertrophy, amongst others. Body weight was significantly increased in groups given high diet soda (114 ± 0.12g) and aspartame (121 ± 0.17g) when compared with the control (85 ± 0.21g). However, there was no significant difference in fasting blood sugar and insulin levels in all treated groups compared to control. In conclusion, this study has shown that chronic consumption of aspartame and diet soda increased body weight, but no effect on blood sugar and insulin levels. The adverse effects on pancreas morphology suggest impending health implications.

Relationship between Aspartame-Induced Cerebral Cortex Injury and Oxidative Stress, Inflammation, Mitochondrial Dysfunction, and Apoptosis in Sprague Dawley Rats.

There are emerging concerns about the potential cerebral cortex injury from aspartame due to the accumulation of the various neurotoxic metabolic components in the central nervous system after long-term dietary exposure. The aim of this study was to evaluate the effect of oral aspartame consumption on cerebral cortex injury in the rat brain, and further evaluate the various underlying molecular mechanisms, with a special focus on oxidative stress, inflammation, mitochondrial dysfunction, and apoptosis pathways. Sprague Dawley rats (nineteen, female) were randomly sub-divided into three groups: (i) normal diet with vehicle: control group (five rats), (ii) low dose of aspartame group (LA): seven rats received 30 mg/kg body weight (bw) daily doses of aspartame, (iii) high dose of aspartame group (HA): seven rats received 60 mg/kg bw daily doses of aspartame. After 8 weeks, the LA and HA groups showed lower expression levels of brain-derived neurotrophic factor (BDNF), antioxidant enzyme activity (SOD2, CAT), antioxidant marker (Nrf2), inflammatory response (IκB), mitochondrial biogenesis (Sirt1, PGC1α, Nrf1, TFAM), mitochondrial DNA (mtDNA) copy number, and apoptosis-related proteins (Bax, Caspase-3) expressions. Aspartame administration also elevated oxidative stress levels (Malondialdehyde, MDA), 8-hydroxy-2-deoxy guanosine (8-OHdG), PGE2 and COX-2 expressions, pro-inflammatory cytokines (TNFα, IL6, IL1β), antioxidant marker expression (Keap1), inflammatory responses (iNOS, NFκB), and glial fibrillary acidic protein (GFAP) levels in the cerebral cortex of the rats, thereby contributing to the reduced survival of pyramidal cells and astrocyte glial cells of the cerebral cortex. Therefore, these findings imply that aspartame-induced neurotoxicity in rats' cerebral cortex could be regulated through four mechanisms: inflammation, enhanced oxidant stress, decreased mitochondrial biogenesis, and apoptosis pathways.

Aspartame induced dyslipidemia and plasma hyperviscosity in Albino Wistar rats

Aspartame is a low-calorie sweetener that has been used for decades in place of sugar. However, there has been conflicting reports on the use and safety profile of aspartame associated with several diseases especially cancer and cardiovascular diseases. This study therefore aims to determine the effects of aspartame on some cardiovascular indices. Thirty seven (37) young Albino Wistar rats weighing between 110g-140g were used for this study. The rats were divided into five groups; control (5) received 5 ml of distilled water. Group 1 (n=8) received 5 ml of diet soda, group 2 (n=8) received 5 ml diluted (1:1) diet soda, Group 3 (n=8) received 5 ml aspartame 45 mg/kg b.w, Group 4 (n=8) received 5 ml of aspartame 22.5 mg/kg b.w. The various doses of aspartame and diet soda were administered orally daily for ten weeks. Weight of the rats were taken weekly, at the end of the experimental period, the rats were sacrificed and blood samples collected into plain sample bottles and tri sodium citrate bottles. Lipid profile (total cholesterol, HDL-C, LDL-C &.triglyceride) were analyzed spectrophotometrically, fibrinogen and blood viscosity were also measured. Results showed that the aspartame and diet soda significantly increased total cholesterol, triglyceride, LDL-C, fibrinogen and plasma viscosity and significantly decreased HDL cholesterol. In conclusion, consumption of aspartame as a sweetener can impact negatively on cardiovascular haemodymic factors. Therefore, its intake should be discouraged.

Learning and memory deficits produced by aspartame are heritable via the paternal lineage

Environmental exposures produce heritable traits that can linger in the population for one or two generations. Millions of individuals consume substances such as artificial sweeteners daily that are declared safe by regulatory agencies without evaluation of their potential heritable effects. We show that consumption of aspartame, an FDA-approved artificial sweetener, daily for up to 16-weeks at doses equivalent to only 7–15% of the FDA recommended maximum daily intake value (equivalent to 2–4 small, 8 oz diet soda drinks per day) produces significant spatial learning and memory deficits in mice. Moreover, the cognitive deficits are transmitted to male and female descendants along the paternal lineage suggesting that aspartame’s adverse cognitive effects are heritable, and that they are more pervasive than current estimates, which consider effects in the directly exposed individuals only. Traditionally, deleterious environmental exposures of pregnant and nursing women are viewed as risk factors for the health of future generations. Environmental exposures of men are not considered to pose similar risks. Our findings suggest that environmental exposures of men can produce adverse impact on cognitive function in future generations and demonstrate the need for considering heritable effects via the paternal lineage as part of the regulatory evaluations of artificial sweeteners.

Daily Early-Life Exposures to Diet Soda and Aspartame Are Associated with Autism in Males: A Case-Control Study.

Since its introduction, aspartame-the leading sweetener in U.S. diet sodas (DS)-has been reported to cause neurological problems in some users. In prospective studies, the offspring of mothers who consumed diet sodas/beverages (DSB) daily during pregnancy experienced increased health problems. We hypothesized that gestational/early-life exposure to ≥1 DS/day (DSearly) or equivalent aspartame (ASPearly: ≥177 mg/day) increases autism risk. The case-control Autism Tooth Fairy Study obtained retrospective dietary recalls for DSB and aspartame consumption during pregnancy/breastfeeding from the mothers of 235 offspring with autism spectrum disorder (ASD: cases) and 121 neurotypically developing offspring (controls). The exposure odds ratios (ORs) for DSearly and ASPearly were computed for autism, ASD, and the non-regressive conditions of each. Among males, the DSearly odds were tripled for autism (OR = 3.1; 95% CI: 1.02, 9.7) and non-regressive autism (OR = 3.5; 95% CI: 1.1, 11.1); the ASPearly odds were even higher: OR = 3.4 (95% CI: 1.1, 10.4) and 3.7 (95% CI: 1.2, 11.8), respectively (p < 0.05 for each). The ORs for non-regressive ASD in males were almost tripled but were not statistically significant: DSearly OR = 2.7 (95% CI: 0.9, 8.4); ASPearly OR = 2.9 (95% CI: 0.9, 8.8). No statistically significant associations were found in females. Our findings contribute to the growing literature raising concerns about potential offspring harm from maternal DSB/aspartame intake in pregnancy.

Investigation of the toxic effects of aspartame as an artificial sweetener in food: effect on redox and inflammatory biomarkers in rat

Aspartame (L-aspartyl-L-phenylalanine methyl ester) is a widely used synthetic sweetener. The safety of aspartame consumption remains controversial due to its widespread and sometimes indiscriminate use above the FDA-recommended level. The study focused on investigating the toxic effects of aspartame administration at high doses on redox and inflammatory biomarkers in male Wistar rats. Rats were divided into two groups: Group I was given normal saline (0.9%) orally and Group II was administered with aspartame (100 mg/kg body weight) for 30 days. Administration of aspartame significantly (p&lt;0.05) increased the levels of Malondialdehyde (MDA), protein carbonyl (PCO), and Advanced Oxidation Protein Products (AOPP) content which are prominent markers of oxidative stress. The assessment of antioxidant defenses in both the groups denoted a significant (p&lt;0.05) decrease in levels of Ferric Reducing Ability of Plasma (FRAP), Superoxide Dismutase (SOD), and Catalase in the aspartame-treated group in comparison to the control. The proinflammatory markers Tumour Necrosis Factor -α (TNF-α), Interleukin-6 (IL-6) and C - reactive protein (CRP) were also significantly (p&lt;0.05) increased in the treated group. These results suggest that aspartame intake of 100 mg/kg body weight contributes to oxidative stress in erythrocytes which in turn may play a role in predisposing an individual to obesity, cardiovascular disease, and cancer. Aspartame should be strictly limited to the FDA-recommended levels since its indiscriminate use causes severe toxic effects.

Consumption of aspartame and other artificial sweeteners and risk of cancer in the Spanish multicase-control study (MCC-Spain).

Use of artificial sweeteners (AS) such as aspartame, cyclamate, saccharin and sucralose is widespread. We evaluated the association of use of aspartame and other AS with cancer. In total 1881 colorectal, 1510 breast, 972 prostate and 351 stomach cancer and 109 chronic lymphocytic leukaemia (CLL) cases and 3629 population controls from the Spanish Multicase-Control (MCC-Spain) study were recruited (2008-2013). The consumption of AS, from table-top sweeteners and artificially sweetened beverages, was assessed through a self-administered and validated food frequency questionnaire (FFQ). Sex-specific quartiles among controls were determined to compare moderate consumers (<third quartile) and high consumers (≥ third quartile) vs non consumers (reference category), distinguishing aspartame-containing products and other AS. Unconditional logistic regression models were used to estimate adjusted OR and 95%CI, and results were stratified by diabetes status. Overall, we found no associations between the consumption of aspartame or other AS and cancer. Among participants with diabetes, high consumption of other AS was associated with colorectal cancer (OR = 1.58, 95% CI 1.05-2.41, P trend = .03) and stomach cancer (OR = 2.27 [0.99-5.44], P trend = .06). High consumption of aspartame, was associated with stomach cancer (OR = 2.04 [0.7-5.4], P trend = .05), while a lower risk was observed for breast cancer (OR = 0.28 [0.08-0.83], P trend = .03). In some cancers, the number of cases in participants with diabetes were small and results should be interpreted cautiously. We did not find associations between use of AS and cancer, but found associations between high consumption of aspartame and other AS and different cancer types among participants with diabetes.

Aspartame induced dyslipidemia and plasma hyperviscosity in Albino Wistar Rats

Aspartame is a low-calorie sweetener that has been used for decades in place of sugar. However, there has been conflicting reports on the use and safety profile of aspartame associated with several diseases especially cancer and cardiovascular diseases. This study therefore aims to determine the effects of aspartame on some cardiovascular indices. Thirty seven (37) young Albino Wistar rats weighing between 110g-140g were used for this study. The rats were divided into five groups; control (5) received 5 ml of distilled water. Group 1 (n=8) received 5 ml of diet soda, group 2 (n=8) received 5 ml diluted (1:1) diet soda, Group 3 (n=8) received 5 ml aspartame 45 mg/kg b.w, Group 4 (n=8) received 5 ml of aspartame 22.5 mg/kg b.w. The various doses of aspartame and diet soda were administered orally daily for ten weeks. Weight of the rats were taken weekly, at the end of the experimental period, the rats were sacrificed and blood samples collected into plain sample bottles and tri sodium citrate bottles. Lipid profile (total cholesterol, HDL-C, LDL-C and triglyceride) were analyzed spectrophotometrically, fibrinogen and blood viscosity were also measured. Results showed that the aspartame and diet soda significantly increased total cholesterol, triglyceride, LDL-C, fibrinogen and plasma viscosity and significantly decreased HDL cholesterol. In conclusion, consumption of aspartame as a sweetener can impact negatively on cardiovascular haemodymic factors. Therefore, its intake should be discouraged.

Aspartame and Phenylketonuria: an analysis of the daily phenylalanine intake of aspartame-containing drugs marketed in France

BackgroundPhenylketonuria (PKU) is a rare genetic metabolic disorder in which especially high phenylalanine (Phe) concentrations cause brain dysfunction. If untreated, this brain dysfunction results in severe microcephaly, intellectual disability, and behavioral problems. Dietary restriction of Phe is the mainstay of PKU treatment, with long-term successful outcomes. Aspartame, an artificial sweetener sometimes added into medications, is metabolized in the gut into Phe. Then, patients suffering from PKU on a Phe-restricted diet should avoid consumption of aspartame. The aim of our study was to evaluate the number of drugs containing aspartame and/or Phe as an excipient, and to quantify their corresponding Phe intake.MethodsThe list of drugs marketed in France containing aspartame and/or Phe was established using a national medication database called “Theriaque”. For each drug, the corresponding daily Phe intake was calculated according to age and weight and was distributed into 3 categories: high (> 40 mg/d), medium (10 to 40 mg/d) and low (< 10 mg/d) Phe intake.ResultsThe number of drugs containing Phe or its precursor aspartame remained very limited (n = 401). Among the aspartame containing drugs, Phe intakes were significant (medium or high) for only half of them whereas there were negligible for the others. Furthermore, these medications with a significant Phe intake were limited to few pharmaceutical classes (mainly antiinfectives agents, analgesics, and drugs for nervous system), and within these classes the drugs were limited to a small number of molecules, including principally amoxicillin, amoxicillin + clavulanic acid and paracetamol/ acetaminophen.DiscussionIn situations requiring the use of these molecules, we propose as an alternative, the use of an aspartame-free form of these molecules or a form with a low Phe intake. If it is not possible, we propose as second-line the use of another antibiotics or analgesics. Finally, we have to remember the benefits-risk balance to use medications containing significant Phe intake in PKU patients. Indeed, it may be better to use a Phe containing medication in the absence of an aspartame-free form of this drug rather than to leave a person with PKU without treatment.

Assessment of Aspartame (E951) Occurrence in Selected Foods and Beverages on the German Market 2000-2022.

This study examines the occurrence of the artificial sweetener aspartame (E951) in foods and beverages sampled by food control authorities in Germany between 2000 and 2022. The dataset was obtained through the Consumer Information Act. Out of 53,116 samples analyzed, aspartame was present in 7331 samples (14%), of which 5703 samples (11%) in nine major food groups were further evaluated. The results showed that aspartame was most commonly found in powdered drink bases (84%), flavored milk drinks (78%), chewing gum (77%), and diet soft drinks (72%). In the solid food groups, the highest mean aspartame content was detected in chewing gum (1543 mg/kg, n = 241), followed by sports foods (1453 mg/kg, n = 125), fiber supplements (1248 mg/kg, n = 11), powdered drink bases (1068 mg/kg, n = 162), and candies (437 mg/kg, n = 339). Liquid products generally had the highest aspartame content in diet soft drinks (91 mg/L, n = 2021), followed by regular soft drinks (59 mg/L, n = 574), flavored milk drinks (48 mg/kg, n = 207), and mixed beer drinks (24 mg/L, n = 40). These results suggest that aspartame is commonly used in some foods and beverages in Germany. The levels of aspartame found were generally within the legal limits set by the European Union. These findings provide the first comprehensive overview of aspartame in the German food market and may be particularly useful in informing the forthcoming working groups of the WHO International Agency for Research on Cancer (IARC) and the WHO/FAO Joint Expert Committee on Food Additives (JECFA), which are in the process of evaluating the human health hazards and risks associated with the consumption of aspartame.

Effects of Nonnutritive Sweeteners on Body Composition Changes during Pubertal Growth.

The effects of consuming specific types of nonnutritive sweeteners (NNSs) on adiposity changes in children have remained inconsistent. In this study, we aimed to investigate the effects of the intake of different kinds of NNSs on long-term adiposity changes during pubertal growth. Furthermore, we examined the above relationships among different sexes, pubertal stages, and levels of obesity. A total of 1893 6-15-year-old adults were recruited and followed-up every 3 months. The NNS-FFQ (Food Frequency Questionnaire) was conducted and urine samples were collected to investigate the effects of the selected sweeteners, which included acesulfame potassium, aspartame, sucralose, glycyrrhizin, steviol glycosides, and sorbitol. Multivariate linear mixed-effects models were used to examine the relationship between NNS intake and body composition. The consumption of aspartame, sucralose, glycyrrhizin, stevioside, and sorbitol was associated with decreased fat mass and increased fat-free mass. In the highest tertile group, the effects of NNS consumption on fat mass corresponded to values of -1.21 (95% CI: -2.04 to -0.38) for aspartame, -0.62 (95% CI: -1.42 to 0.19) for sucralose, -1.26 (95% CI: -2.05 to -0.47) for glycyrrhizin, -0.90 (95% CI: -2.28 to 0.48) for stevioside, and -0.87 (95% CI: -1.67 to -0.08) for sorbitol, while the effects on fat-free mass corresponded to values of 1.20 (95% CI: 0.36 to -0.38) for aspartame, 0.62 (95% CI: -0.19 to 1.43) for sucralose, 1.27 (95% CI: 0.48 to 2.06) for glycyrrhizin, 0.85 (95% CI: -0.53 to 2.23) for stevioside, and 0.87 (95% CI: 0.08 to 1.67) for sorbitol. Particularly, aspartame and sorbitol revealed a dose-responsiveness effect. The above finding was more prominent among girls than boys. Moreover, fat mass was significantly reduced in normal-weight children who consumed a moderate amount of aspartame and a large amount of glycyrrhizin and sorbitol compared with obese children. In conclusion, the NNS-specific and sex-specific effects of long-term NNS consumption revealed associations of decreasing fat mass and increasing fat-free mass for children undergoing pubertal growth.

Abstract 542: Short Term High Consumption Of Aspartame Does Not Increase Infarct Volume And Stroke Mortality In Mouse Models Of Focal Ischemic Stroke

Background: Aspartame is an artificial sweetener that has been widely used in beverages and foods. Recently, higher intake of artificially sweetened beverages was shown to be associated with increased risk of stroke. Objective: To investigate if short-term high consumption of aspartame could increase cerebral infarct volume and mortality in mouse models of focal ischemic stroke. Methods: Eleven-week-old male C57BL/6N mice (n=90) received one of the following three treatments for 7 days: phosphate-buffered saline (PBS), aspartame 200 mg/kg in PBS, and aspartame in Zero Coke (with the final dose of aspartame being 200 mg/kg). Thereafter, either transient middle cerebral artery occlusion for 1 hour (1h-tMCAO; n=27, 9/group) or common carotid artery occlusion (CCAO)-related hemispheric ischemia with cerebral autoregulatory dysfunction (CCAO+CAD; n=63, 21/group) was induced. To measure the infarct volume, 2,3,5-Triphenyltetrazolium chloride staining was performed at 24 hours after tMCAO and 6 days after CCAO+CAD. Results: 1h-tMCAO-related 24-hour mortality and infarct volume (of survived animals) did not differ significantly among the three groups (both p&gt;0.05): PBS (5/9 death and 93.7±30.0mm 3 ), aspartame in PBS (2/9 death and 102±50.0mm 3 ), and aspartame in Zero Coke (4/9 death and 111.4±17.4mm 3 ). CCAO+CAD-related mortality 6-day mortality did not show inter-group differences (p&gt;0.05): PBS (n=9/21, 42.9 %), aspartame in PBS (n=12/21, 57.1 %), and aspartame in Zero Coke (n=8/21, 38 %). Among the survived, infarct volume did not significantly differ, either (p&gt;0.05): PBS (60.8±68.0mm 3 ), aspartame in PBS (58.5±68.0mm 3 ), and aspartame in Zero Coke (54.2±48.3mm 3 ). Conclusions: Short-term high consumption of aspartame did not increase cerebral infarct volume and stroke-related mortality in our experimental setting. Category: Peripheral Artery Disease, Carotid Artery Disease and Stroke

The role of study quality in aspartame and cancer epidemiology study reviews

Toews et al. [1] and the World Health Organization (WHO) [2] reviewed observational epidemiology studies of non-sugar sweeteners (NSSs) and various health effects. The former used the Risk of Bias in Non-randomised Studies – of Interventions (ROBINS-I) tool and the latter used both the ROBINS-I tool and the Newcastle-Ottawa Scale to evaluate study quality. Both reviews concluded that there were no associations between NSS or aspartame consumption and cancer (except possibly between saccharin and bladder cancer) but indicated that the certainty of the evidence for all cancer types was “very low.” While we agree with this conclusion, the support for the confidence in the evidence generally was not transparently documented, as the results of the study quality assessment were only provided in scores or ratings. An examination of illustrative case studies shows that some important aspects of study quality domains specific for NSSs generally or aspartame specifically (i.e., issues with the exposure and outcome assessments, the consideration of confounding/covariates, and selection bias) may have been overlooked or not given appropriate consideration, while other aspects that were less likely to have a large impact on overall study quality dominated the results in the two assessments. Our review of other studies published after the WHO [2] review further demonstrates this point. While this may not seem important given the overall lack of associations, it impacts the degree to which evidence supports a lack of effects as opposed to not being adequate to evaluate associations. In the future, aspartame and cancer outcome reviews should focus on those study quality domains that are most likely to impact the interpretation of results and discuss them in a transparent, systematic manner. If there is very low certainty in the evidence as a result of low study quality, reviewers should conclude the evidence is inadequate for making a causal determination.

Aspartame consumption causes cognitive impairment in streptozotocin-induced diabetic Wistar rats

Aspartame consumption causes cognitive impairment in streptozotocin-induced diabetic Wistar rats

Updated systematic assessment of human, animal and mechanistic evidence demonstrates lack of human carcinogenicity with consumption of aspartame.

Aspartame has been studied extensively and evaluated for its safety in foods and beverages yet concerns for its potential carcinogenicity have persisted, driven primarily by animal studies conducted at the Ramazzini Institute (RI). To address this controversy, an updated systematic review of available human, animal, and mechanistic data was conducted leveraging critical assessment tools to consider the quality and reliability of data. The evidence base includes 12 animal studies and >40 epidemiological studies reviewed by the World Health Organization which collectively demonstrate a lack of carcinogenic effect associated with any tumor type. Assessment of >1360 mechanistic endpoints, including many guideline-based genotoxicity studies, demonstrate a lack of activity associated with endpoints grouped to key characteristics of carcinogens. Other non-specific mechanistic data (e.g., mixed findings of oxidative stress across study models, tissues, and species) do not provide evidence of a biologically plausible carcinogenic pathway associated with aspartame. Taken together, available evidence supports that aspartame consumption is not carcinogenic in humans and that the inconsistent findings of the RI studies may be explained by flaws in study design and conduct (despite additional analyses to address study limitations), as acknowledged by authoritative bodies.

Pathologists' perspective on the study design, analysis, and interpretation of proliferative lesions in lifetime and prenatal rodent carcinogenicity bioassays of aspartame.

Aspartame, an artificial sweetener commonly used as a sugar substitute, is currently authorized for use in more than 100 countries. Hundreds of studies, conducted in various countries dating back to the 1970s, have shown that aspartame is safe at real-world exposure levels. Furthermore, multiple human epidemiology studies have provided no indication that consumption of aspartame induces cancer. Given the continued controversy surrounding the Ramazzini Institute's (RI) studies suggesting that aspartame is a carcinogenic hazard in rodents and evaluation by the International Agency for Research on Cancer, this report aims to provide the perspective of experienced pathologists on publicly available pathology data regarding purported proliferative lesions in liver, lung, lymphoid organs, and mammary gland as well as their implications for human risk assessment as reported for three lifetime rodent carcinogenicity bioassays of aspartame conducted at the RI. In the authors' view, flaws in the design, methodology and reporting of the RI aspartame studies limit the utility of the data sets as evidence that this agent represents a carcinogenic hazard. Therefore, all three RI studies, and particularly the accuracy of their pathology diagnoses and interpretations, should be rigorously reviewed by qualified and experienced veterinary toxicologic pathologists in assessing aspartame's carcinogenic risk.