Combined intake of caffeine and low-dose glucose to reduce exercise-related hypoglycaemia in individuals with type 1 diabetes on ultra-long-acting insulin degludec: A randomized, controlled, double-blind, cross-over trial.

AIM: To evaluate whether caffeine combined with a moderate amount of glucose reduces the risk for exercise-related hypoglycaemia compared with glucose alone or control in adult people with type 1 diabetes using ultra-long-acting insulin degludec. MATERIALS AND METHODS: Sixteen participants conducted three aerobic exercise sessions (maximum 75 min) in a randomized, double-blind, cross-over design. Thirty minutes before exercise, participants ingested a drink containing either 250 mg of caffeine + 10 g of glucose + aspartame (CAF), 10 g of glucose + aspartame (GLU), or aspartame alone (ASP). The primary outcome was time to hypoglycaemia. RESULTS: There was a significant effect of the condition on time to hypoglycaemia (χ2 = 7.674, p = .0216). Pairwise comparisons revealed an 85.7% risk reduction of hypoglycaemia for CAF compared with ASP (p = .044). No difference was observed between GLU and ASP (p = .104) or between CAF and GLU (p = .77). While CAF increased glucose levels during exercise compared with GLU and ASP (8.3 ± 1.9 mmol/L vs. 7.7 ± 2.2 mmol/L vs. 5.8 ± 1.4 mmol/L; p < .001), peak plasma glucose levels during exercise did not differ between CAF and GLU (9.3 ± 1.4 mmol/L and 9.1 ± 1.6 mmol/L, p = .80), but were higher than in ASP (6.6 ± 1.1 mmol/L; p < .001). The difference in glucose levels between CAF and GLU was largest during the last 15 min of exercise (p = .002). Compared with GLU, CAF lowered perceived exertion (p = .023). CONCLUSIONS: Pre-exercise caffeine ingestion combined with a low dose of glucose reduced exercise-related hypoglycaemia compared with control while avoiding hyperglycaemia.

Insight into the mechanism of aspartame-induced toxicity in male reproductive system following long-term consumption in mice model.

Aspartame is one of the most common consumed artificial sweeteners utilized in many food products and beverages. It has been indicated that long-term consumption of aspartame leads to reproductive toxicity but its mechanism is not well-clear. In this study we investigated mechanism of aspartame-induced reproductive toxicity in male mice. For this purpose, 36 NMRI mature male mice received three doses of 40, 80, and 160 mg/kg body weight of aspartame, respectively per day by gavage for 90 days and also a control group was considered which received 0.5 mL of normal saline as the same route. The results revealed that long-term administration of aspartame at high doses significantly (P < .05) reduced gonadosomatic index, serum concentration of pituitary-testicular axis hormones (FSH, LH, and testosterone). It also decreased sperm parameters and total antioxidant capacity, antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase), while it caused increase in nitric oxide and malondialdehyde levels in testis tissue and sperm samples. Also, it decreased attenuated testicular histomorphometric indices (tubular differentiation index, spermiogenesis index, and repopulation index), and steroidogenic foci, while increased mRNA damages and apoptosis rate, downregulated antiapoptotic (Bcl-2) and upregulated proapoptotic (P53, BAX, and caspase-3) mediators respectively in testis. These findings indicated that consumption of aspartame for a long period results in male reproductive toxicity by decrease in serum concentration of pituitary-testis axis hormones and induction of oxidative stress and apoptosis in testis.

Artificial Sweeteners Negatively Regulate Pathogenic Characteristics of Two Model Gut Bacteria, E. coli and E. faecalis.

Artificial sweeteners (AS) are synthetic sugar substitutes that are commonly consumed in the diet. Recent studies have indicated considerable health risks which links the consumption of AS with metabolic derangements and gut microbiota perturbations. Despite these studies, there is still limited data on how AS impacts the commensal microbiota to cause pathogenicity. The present study sought to investigate the role of commonly consumed AS on gut bacterial pathogenicity and gut epithelium-microbiota interactions, using models of microbiota (Escherichia coli NCTC10418 and Enterococcus faecalis ATCC19433) and the intestinal epithelium (Caco-2 cells). Model gut bacteria were exposed to different concentrations of the AS saccharin, sucralose, and aspartame, and their pathogenicity and changes in interactions with Caco-2 cells were measured using in vitro studies. Findings show that sweeteners differentially increase the ability of bacteria to form a biofilm. Co-culture with human intestinal epithelial cells shows an increase in the ability of model gut bacteria to adhere to, invade and kill the host epithelium. The pan-sweet taste inhibitor, zinc sulphate, effectively blocked these negative impacts. Since AS consumption in the diet continues to increase, understanding how this food additive affects gut microbiota and how these damaging effects can be ameliorated is vital.

Amoxicillin chewable tablets intended for pediatric use: formulation development, stability evaluation and taste assessment.

To cover the unpleasant taste of amoxicillin (250 mg), maize starch (baby food) and milk chocolate were co-formulated. The raw materials and the final formulations were characterized by means of Dynamic Light Scattering (DLS), Differential Scanning Calorimetry (DSC) and Fourier-Transform Infrared (FT-IR) spectroscopy. To evaluate the taste masking two different groups of volunteers were used, according to the Ethical Research Committee of the Aristotle University of Thessaloniki. The optimization of excipients' content in the tablet was determined by experimental design methodology (crossed D-optimal). Due to the matrix complexity, amoxicillin was extracted using liquid extraction and analyzed isocratically by HPLC. The developed chromatographic method was validated (%Recovery 98.7-101.3, %RSD = 1.3, LOD and LOQ 0.15 and 0.45 µg mL-1 respectively) according to the International Conference on Harmonization (ICH) guidelines. The physicochemical properties of the tablets were also examined demonstrating satisfactory quality characteristics (diameter: 15 mm, thickness: 6 mm, hardness <98 Newton, loss of mass <1.0%, disintegration time ∼25min). Additionally, dissolution (%Recovery >90) and in vitro digestion tests (%Recovery >95) were carried out. Stability experiments indicated that amoxicillin is stable in the prepared formulations for at least one year (%Recovery <91).

Systematic review and evaluation of aspartame carcinogenicity bioassays using quality criteria.

The current review assessed cancer studies of aspartame based on a quality appraisal using the Klimisch grading system. Nine studies having complete histopathology were included: three 2-year studies by Searle; three transgenic mice studies by the NTP; three lifetime studies by the Ramazzini Institute. A tenth study limited to brain tumors was not rated. None were determined as Klimisch Code 1 (reliable without restrictions). The Searle studies predated GLP standards but their methodology was comparable; transgenic mouse models are not validated, but are accepted as supporting data. These studies were rated Klimisch Code 2 (reliable with restrictions). The Ramazzini Institute used a lifetime model of their own design that has been questioned due to high rates of spontaneous tumors, issues with tumor type diagnosis and concerns about the impact of chronic infections. As many of these problems could be attributed to using animals that died or were terminated near end of life, along with the other problems noted, these studies were rated Klimisch Code 3 (not reliable). As the Klimisch Code 2 studies demonstrated a lack of carcinogenic potential, and as aspartame is hydrolyzed to common components and lacks genotoxic activity, a conclusion that aspartame is not carcinogenic is supported.

Mutagenicity and genotoxicity studies of aspartame.

Two studies were conducted to further assess its mutagenic and genotoxic potential. In a bacterial reverse mutation pre-incubation study, Salmonella typhimurium strains TA100, TA1535, TA98, and TA1537 and Escherichia coli WP2 uvrA were treated with aspartame at concentrations of up to 5000 µg/plate with or without metabolic activation and showed no mutagenic potential. Similarly, in vivo micronucleus testing of aspartame following gavage administration (500-2000 mg/kg body weight) to Crlj:CD1(ICR) strain SPF male mice showed no increase in the proportion of micronucleated polychromatic erythrocytes in bone marrow cells collected and evaluated 24 or 48 h post administration. Overall, aspartame had no potential for mutagenic or genotoxic activity.

Aspartame supplementation in starter accelerates small intestinal epithelial cell cycle and stimulates secretion of glucagon-like peptide-2 in pre-weaned lambs.

The objective of this study was to test the hypothesis that aspartame supplementation in starter diet accelerates small intestinal cell cycle by stimulating secretion and expression of glucagon-like peptide -2 (GLP-2) in pre-weaned lambs using animal and cell culture experiments. In vivo, twelve 14-day-old lambs were selected and allocated randomly to two groups; one was treated with plain starter diet (Con, n = 6) and the other was treated with starter supplemented with 200 mg of aspartame/kg starter (APM, n = 6). Results showed that the lambs received APM treatment for 35 d had higher (p < .05) GLP-2 concentration in the plasma and greater jejunum weight/live body weight (BW) and jejunal crypt depth. Furthermore, APM treatment significantly upregulated (p < .05) the mRNA expression of cyclin D1 in duodenum; and cyclin A2, cyclin D1, cyclin-dependent kinases 6 (CDK6) in jejunum; and cyclin A2, cyclin D1, CDK4 in ileum. Moreover, APM treatment increased (p < .05) the mRNA expression of glucagon (GCG), insulin-like growth factor 1 (IGF-1) in the jejunum and ileum and mRNA expression of GLP-2 receptor (GLP-2R) in the jejunum. In vitro, when jejunal cells were treated with GLP-2 for 2 hr, the 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) OD, IGF-1 concentration, and the mRNA expression of IGF-1, cyclin D1 and CDK6 were increased (p < .05). Furthermore, IGF-1 receptor (IGF-1R) inhibitor decreased (p < .05) the mRNA expression of IGF-1, cyclin A2, cyclin D1 and CDK6 in GLP-2 treatment jejunal cells. These results suggest that aspartame supplementation in starter accelerates small intestinal cell cycle that may, in part, be related to stimulate secretion and expression of GLP-2 in pre-weaning lambs. Furthermore, GLP-2 can indirectly promote the proliferation of jejunal cells mainly through the IGF-1 pathway. These findings provide new insights into nutritional interventions that promote the development of small intestines in young ruminants.

Neurophysiological symptoms and aspartame: What is the connection?

Aspartame (α-aspartyl-l-phenylalanine-o-methyl ester), an artificial sweetener, has been linked to behavioral and cognitive problems. Possible neurophysiological symptoms include learning problems, headache, seizure, migraines, irritable moods, anxiety, depression, and insomnia. The consumption of aspartame, unlike dietary protein, can elevate the levels of phenylalanine and aspartic acid in the brain. These compounds can inhibit the synthesis and release of neurotransmitters, dopamine, norepinephrine, and serotonin, which are known regulators of neurophysiological activity. Aspartame acts as a chemical stressor by elevating plasma cortisol levels and causing the production of excess free radicals. High cortisol levels and excess free radicals may increase the brains vulnerability to oxidative stress which may have adverse effects on neurobehavioral health. We reviewed studies linking neurophysiological symptoms to aspartame usage and conclude that aspartame may be responsible for adverse neurobehavioral health outcomes. Aspartame consumption needs to be approached with caution due to the possible effects on neurobehavioral health. Whether aspartame and its metabolites are safe for general consumption is still debatable due to a lack of consistent data. More research evaluating the neurobehavioral effects of aspartame are required.

Astrogliosis and decreased neural viability as consequences of early consumption of aspartame and acesulfame potassium in male Wistar rats.

Artificial sweeteners are mainly used as substitutes for sucrose derivates. In this study, we analyzed if the chronic consumption of aspartame or acesulfame potassium at an early age, produces histological alterations, astrogliosis and decreased neuronal viability, in hippocampus, prefrontal cortex, amygdala and hypothalamus of male Wistar rats. A histological analysis was performed on male Wistar rats that consumed aspartame or acesulfame potassium during 90 days, initiating the consumption of sweeteners immediately after weaning. The evaluation of neuronal morphology in different areas of the brain was performed with hematoxylin - eosin staining. To measure astrogliosis and neuronal viability, we used the immunohistochemical technique, with the glial fibrillary acidic protein immunomodulators (GFAP) and with neuronal-specific enolase (NSE). The consumption of aspartame or acesulfame potassium promoted morphological changes of neurons including increased pyknotic nuclei and vacuolization in all the brain areas studied. In hippocampus, prefrontal cortex, amygdala and hypothalamus, astrogliosis and reduction of neural viability were observed in sweeteners consumers in comparison with the control group. Chronic consumption of ASP and ACK from early stages of development and during long periods, may promote neural modifications, astrogliosis and decrease neuronal viability in prefrontal cortex, amygdala, hippocampus, and hypothalamus.

Aspartame and the hippocampus: Revealing a bi-directional, dose/time-dependent behavioural and morphological shift in mice.

Changes, in behaviour, oxidative markers of stress and hippocampal morphology were evaluated following aspartame administration. Mice, (20-22g each) were given vehicle (10ml/kg) or aspartame (20, 40, 80 and 160mg/kg) daily for 28days. They were tested in the Y-maze, radial-arm maze and elevated plus-maze (EPM) after the first and last dose of vehicle or aspartame; and then sacrificed. Hippocampal slices were analysed for aspartic acid, nitric oxide (NO) and superoxide dismutase (SOD); and processed for general histology and neuritic plaques. Glial fibrillary-acid protein (GFAP) expression and neuron-specific enolase (NSE) activities were determined. Radial-arm maze scores increased significantly after acute administration at 80 and 160mg/kg. Repeated administration at 20 and 40mg/kg (Y-maze) and at 40mg/kg (radial-arm maze) was also associated with increased scores, however, performance decreased at higher doses. EPM tests revealed anxiogenic responses following both acute and repeated administration. Significant increase in SOD and NO activities were observed at 40, 80 and 160mg/kg. Neuron counts reduced at higher doses of aspartame. At 40, 80 and 160mg/kg, fewer GFAP-reactive astrocytes were observed in the cornus ammonis, but increased GFAP-reactivity was observed in the dentate gyrus subgranular zone. NSE-positive neurons were readily identifiable within the dentate gyrus at the lower doses of aspartame; but at 160mg/kg, there was marked neuron loss and reduction in NSE-positive neurons. Oral aspartame significantly altered behaviour, anti-oxidant status and morphology of the hippocampus in mice; also, it may probably trigger hippocampal adult neurogenesis.

The Influence of Mixers Containing Artificial Sweetener or Different Doses of Carbohydrate on Breath Alcohol Responses in Females.

BACKGROUND: Breath alcohol responses may be affected by the presence of carbohydrate (CHO) in a beverage. This study investigated the impact of consuming alcohol with mixers containing various doses of CHO or an artificial sweetener on breath alcohol concentration (BrAC), ratings of intoxication and impairment, and cognitive performance in females. METHODS: Twenty-six females (age 25.1 ± 0.7 years, mean ± standard deviation) completed a crossover study involving 4 trials. A dose of alcohol was consumed in each trial mixed with water (W), artificial sweetener (150 ± 1 mg aspartame [AS]), or CHO (15 g sucrose [15CHO] and 50 g sucrose [50CHO]). BrAC was sampled for 210 minutes following beverage ingestion and analyzed for peak BrAC and other parameters using WinNonlin noncompartmental pharmacokinetic modeling (cmax , tmax , area under the curve to the last measured time point [AUClast ]). An objective measure of cognitive performance was assessed using a 4-choice reaction time (CRT) task. Estimation of BrAC, self-reported ratings of intoxication, and willingness to drive were recorded. RESULTS: Mean peak BrAC was reduced in a dose-response manner when alcohol was consumed with CHO compared to both W and AS treatments (W: 0.054 ± 0.015%, AS: 0.052 ± 0.011%, 15CHO: 0.049 ± 0.008%, 50CHO: 0.038 ± 0.007%). No difference in peak BrAC was observed between W and AS treatments. WinNonlin parameters revealed significant differences in cmax and AUClast (W: 4.80 ± 1.12 g/dl/h, AS: 4.61 ± 0.92 g/dl/h, 15CHO: 4.10 ± 0.86 g/dl/h, 50CHO: 3.11 ± 0.58 g/dL/h) when CHO-containing beverages were consumed compared to W and AS treatments. No difference in tmax or CRT was observed between treatments. Participants were able to detect subtle differences in peak BrAC and reported greater ability to drive after consuming 50CHO compared to W. However, participant's willingness to drive and CRT did not differ between treatments. CONCLUSIONS: Consuming alcohol with CHO-containing mixers attenuates peak BrAC and reduces total alcohol exposure in a dose-response manner compared to drinks containing artificial sweetener or no additives. The effect of adding CHO to alcoholic beverages may translate to reduced risk of alcohol-related harms.

Effect of exclusion of frequently consumed dietary triggers in a cohort of children with chronic primary headache.

BACKGROUND: Although dietary factors are known to trigger headaches, the relationship between food and headache in children remains unclear. This prospective, observational case series aimed to evaluate the effect of exclusion of frequently-consumed foods in a cohort of children with headache. METHODS: One hundred and fifteen children aged 3-15 (mean 10.5) years with primary headache were followed in a paediatric outpatient clinic. Patients who frequently consumed foods or food additives known to trigger headaches were advised to exclude them for six weeks and to return for follow-up with headache and food diary. RESULTS: One hundred patients attended follow-up. Of these 13 (13%) did not respond to dietary exclusion; 87 (87%) achieved complete resolution of headaches by exclusion of 1-3 of the identified food(s). Caffeine was the most common implicated trigger (28), followed by monosodium glutamate (25), cocoa (22), aspartame (13), cheese (13), citrus (10) and nitrites (six). One patient was sensitive to tomatoes. CONCLUSIONS: This study demonstrates the potential scale and significance of seven frequently consumed foods or food additives as triggers for primary headache in children. Also this is the first study to show that headaches can be triggered by the cumulative effect of a food that is frequently consumed, rather than by single time ingestion.

A common genetic influence on human intensity ratings of sugars and high-potency sweeteners.

The perception of sweetness varies among individuals but the sources of this variation are not fully understood. Here, in a sample of 1,901 adolescent and young adults (53.8% female; 243 MZ and 452 DZ twin pairs, 511 unpaired individuals; mean age 16.2±2.8, range 12­26 years), we studied the variation in the perception of sweetness intensity of two monosaccharides and two high-potency sweeteners: glucose, fructose, neohesperidine dihydrochalcone (NHDC), and aspartame. Perceived intensity for all sweeteners decreased with age (2­5% per year) and increased with the history of otitis media (6­9%). Males rated aspartame slightly stronger than females (7%). We found similar heritabilities for sugars (glucose: h2=0.31, fructose: h2=0.34) and high-potency sweeteners (NHDC: h2=0.31, aspartame: h2=0.30); all were in the modest range. Multivariate modeling showed that a common genetic factor accounted for >75% of the genetic variance in the four sweeteners, suggesting that individual differences in perceived sweet intensity, which are partly due to genetic factors, may be attributed to a single set of genes. This study provided evidence of the shared genetic pathways between the perception of sugars and high-potency sweeteners.

The protective effect of N-acetylcysteine on oxidative stress in the brain caused by the long-term intake of aspartame by rats.

Long-term intake of aspartame at the acceptable daily dose causes oxidative stress in rodent brain mainly due to the dysregulation of glutathione (GSH) homeostasis. N-Acetylcysteine provides the cysteine that is required for the production of GSH, being effective in treating disorders associated with oxidative stress. We investigated the effects of N-acetylcysteine treatment (150 mg kg(-1), i.p.) on oxidative stress biomarkers in rat brain after chronic aspartame administration by gavage (40 mg kg(-1)). N-Acetylcysteine led to a reduction in the thiobarbituric acid reactive substances, lipid hydroperoxides, and carbonyl protein levels, which were increased due to aspartame administration. N-Acetylcysteine also resulted in an elevation of superoxide dismutase, glutathione peroxidase, glutathione reductase activities, as well as non-protein thiols, and total reactive antioxidant potential levels, which were decreased after aspartame exposure. However, N-acetylcysteine was unable to reduce serum glucose levels, which were increased as a result of aspartame administration. Furthermore, catalase and glutathione S-transferase, whose activities were reduced due to aspartame treatment, remained decreased even after N-acetylcysteine exposure. In conclusion, N-acetylcysteine treatment may exert a protective effect against the oxidative damage in the brain, which was caused by the long-term consumption of the acceptable daily dose of aspartame by rats.

Very low calorie diet without aspartame in obese subjects: improved metabolic control after 4 weeks treatment.

BACKGROUND: Very low calorie diet (VLCD) is routinely used in programs for treatment of obesity and before bariatric surgery in order to reduce risk of postoperative complications. Aspartame, an artificial sweetener, is commonly used in VLCD and is well approved as a food additive without any adverse effects. The development of a new fructose containing VLCD formula without aspartame raises questions as to effects on glucose and lipid control. METHODS: As part of an ongoing study of a novel bariatric surgery procedure, twenty-five obese subjects with mean body mass index (BMI) 39.8 kg/m2 and mean age of 48.8 years enrolled in a single center observational study. Seven subjects presented with type 2 diabetes mellitus. The subjects underwent four weeks dietary treatment with VLCD Slanka (Slanka). Blood samples including fasting plasma glucose, HbA1c, cholesterol and triglycerides were performed at start and after four weeks of diet. Blood pressure and weight were noted. RESULTS: All subjects completed the diet without any adverse events. Mean weight reduction was 8.2 kg with 95% confidence interval 7.1-9.2 kg (p = 0.001). Excess weight (i.e. proportion of weight exceeding BMI 25) loss decreased by median 19.5% (inter quartile range (IQR) 16,8-24,2). Median fasting plasma glucose was at inclusion 5,6 mmol/l (IQR 5,3-6,8) and after diet 4.8 mmol/l (IQR 4,6-5,2) (p = 0.001). Median HbA1c changed from 39 mmol/mol (IQR 37-44) to 37 mmol/mol (IQR 35-43) (p = 0.001). There was also significant reduction in cholesterol and triglyceride levels as well as in systolic blood pressure. Changes in other monitored blood chemistry values were without clinical importance. CONCLUSION: Four weeks treatment with fructose containing VLCD of obese subjects preparing for bariatric surgery gave a substantial weight reduction without any significant negative metabolic effects.

Monosodium glutamate and aspartame in perceived pain in fibromyalgia.

Our aim was to assess the effect of dietary elimination of monosodium glutamate (MSG) and aspartame on perceived pain in fibromyalgia. A total of 72 female patients with fibromyalgia were randomized to discontinuation of dietary MSG and aspartame (n = 36) or waiting list (n = 36). Patients were requested to rate their pain using a seven-point scale. Comparisons between both groups showed no significant differences on pain referred during the baseline or after the elimination of dietary MSG and aspartame. The discontinuation of dietary MSG and aspartame did not improve the symptoms of fibromyalgia.

Chronic Effect of Aspartame on Ionic Homeostasis and Monoamine Neurotransmitters in the Rat Brain.

Aspartame is one of the most widely used artificial sweeteners globally. Data concerning acute neurotoxicity of aspartame is controversial, and knowledge on its chronic effect is limited. In the current study, we investigated the chronic effects of aspartame on ionic homeostasis and regional monoamine neurotransmitter concentrations in the brain. Our results showed that aspartame at high dose caused a disturbance in ionic homeostasis and induced apoptosis in the brain. We also investigated the effects of aspartame on brain regional monoamine synthesis, and the results revealed that there was a significant decrease of dopamine in corpus striatum and cerebral cortex and of serotonin in corpus striatum. Moreover, aspartame treatment significantly alters the tyrosine hydroxylase activity and amino acids levels in the brain. Our data suggest that chronic use of aspartame may affect electrolyte homeostasis and monoamine neurotransmitter synthesis dose dependently, and this might have a possible effect on cognitive functions.

Saccharin and aspartame, compared with sucrose, induce greater weight gain in adult Wistar rats, at similar total caloric intake levels.

It has been suggested that the use of nonnutritive sweeteners (NNSs) can lead to weight gain, but evidence regarding their real effect in body weight and satiety is still inconclusive. Using a rat model, the present study compares the effect of saccharin and aspartame to sucrose in body weight gain and in caloric intake. Twenty-nine male Wistar rats received plain yogurt sweetened with 20% sucrose, 0.3% sodium saccharin or 0.4% aspartame, in addition to chow and water ad libitum, while physical activity was restrained. Measurements of cumulative body weight gain, total caloric intake, caloric intake of chow and caloric intake of sweetened yogurt were performed weekly for 12 weeks. Results showed that addition of either saccharin or aspartame to yogurt resulted in increased weight gain compared to addition of sucrose, however total caloric intake was similar among groups. In conclusion, greater weight gain was promoted by the use of saccharin or aspartame, compared with sucrose, and this weight gain was unrelated to caloric intake. We speculate that a decrease in energy expenditure or increase in fluid retention might be involved.

Long-term consumption of aspartame and brain antioxidant defense status.

The present study investigated the effect of long-term intake of aspartame, a widely used artificial sweetener, on antioxidant defense status in the rat brain. Male Wistar rats weighing 150-175 g were randomly divided into three groups as follows: The first group was given aspartame at a dose of 500 mg/kg body weight (b.w.); the second group was given aspartame at dose of 1,000 mg/kg b.w., respectively, in a total volume of 3 mL of water; and the control rats received 3 mL of distilled water. Oral intubations were done in the morning, daily for 180 days. The concentration of reduced glutathione (GSH) and the activity of glutathione reductase (GR) were significantly reduced in the brain of rats that had received the dose of 1,000 mg/kg b.w. of aspartame, whereas only a significant reduction in GSH concentration was observed in the 500-mg/kg b.w. aspartame-treated group. Histopathological examination revealed mild vascular congestion in the 1,000 mg/kg b.w. group of aspartame-treated rats. The results of this experiment indicate that long-term consumption of aspartame leads to an imbalance in the antioxidant/pro-oxidant status in the brain, mainly through the mechanism involving the glutathione-dependent system.

Dietary aspartyl-phenylalanine-1-methyl ester delays osteoarthritis and prevents associated bone loss in STR/ORT mice.

OBJECTIVE: STR/ORT mice provide a well-known model for murine idiopathic OA, with histological joint lesions resembling those of human OA. This model was used to investigate protective effects of the dipeptide aspartyl-phenylalanine-1-methyl ester (Asp-Phe-OMe or aspartame) via the oral route vs a regular diet. METHODS: STR/ORT mice were housed individually and fed diets with or without Asp-Phe-OMe (4 mg/kg), after weaning at the age of 3 weeks, until 15 months of age (average of 20 animals per group). The study groups were kept blinded to the investigators, who measured food consumption and body weight and performed gait mobility tests. Radiographic scans were also performed at regular time intervals to evaluate differential radiographic anomalies associated with progress of OA in response to oral Asp-Phe-OMe therapy. RESULTS: The Asp-Phe-OMe-fed animals presented a pattern of significantly delayed disease onset. In addition, their muscle and bone mass were highly preserved, even at later time points after OA was established. Moreover, control animals presented a higher variability in gait motility in comparison with the Asp-Phe-OMe-fed animals, suggesting a protective effect from movement limitations associated with advanced OA. CONCLUSION: Asp-Phe-OMe, given orally, delays OA in the spontaneous STR/ORT model, improves bone cortical density and muscle mass, and may contribute to a better quality of life for these diseased animals.