The Effects of Chronic Aspartame Administration on the Kidney of Albino Rat
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Abstract:
Background: Aspartame is a widely employed synthetic sweetener used in diet control and by diabetic patients. Its safety based on the findings of the previous studies showed controversy. Aim of the Work: The aim of this study was to demonstrate the chronic effect of aspartame on the structure of the kidney in the newborn, adult and old albino rats. Materials and Methods: In this work, 60 albino rats were used, 40 of which were three month old, while the remaining 20 rats were twelve month old at the beginning of the study. They were divided into 3 groups: A, B, C and every group was subdivided into 2 subgroups; control and treated. Group A included 20 female albino rats aged three months. The treated subgroup A received aspartame in a dose of 20 mg/kg/day dissolved in tap water through an intragastric tube for three months pregestational and during the gestational period. The offspring numbers, body and kidney weights were estimated and statistically analyzed and their kidneys were examined histopathologically. Group B included 20 adult albino rats aged three months. Group C included 20 albino rats aged twelve months. The treated animals of groups B and C were given aspartame in the same dose and by the same route as in group A for six months. The kidney specimens from all groups were processed for light microscopic examination using Haematoxylin and Eosin stain. Toluidine blue stain was used for the semithin sections of the adult rat's kidney specimens. Electron microscopic study of the proximal convoluted tubules of the adult kidney was done. Results: The results of this study revealed a delayed development of the kidney of the newborn rat with the maternal aspartame administration in addition to degenerative changes in the renal corpuscles and tubules. The statistical analysis of the newborns' body and kidney weights showed significant reduction. The kidneys of aspartame-treated adult rats showed degenerative changes affecting the renal corpuscles and tubules. The renal corpuscles had shrunken glomerular capillary tuft and widened Bowman`s space. Some of which revealed irregularity of Bowman`s capsule. The renal tubules showed dilatation of the tubular lumen, dense nuclei and vacuolated cytoplasm with sloughed epithelial lining cells. Congested and dilated blood vessels were also observed. The ultrastructural study of the proximal convoluted tubular lining cells revealed an extensive damage of the cytoplasmic organelles and the brush border. Aspartame-treated aged rat's kidney showed massive degenerative changes in comparison to the other treated groups. All the renal tubules showed thinning of their lining epithelium with dilated lumen. Some of which had destructed or thickened basement membrane. Others showed accumulation of dense acidophilic casts inside the lumen. Dilated and congested blood vessels with vacuolated cytoplasm were noticed. Conclusion: It was concluded from this study that aspartame had nephrotoxic effects on the newborn, adult and aged ratsKeywords:
Aspartame
Aspartame
Strain (injury)
Degradation
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Aspartame
Saccharin
Artificial Sweetener
Sweet Taste
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With the recommendation of the World Health Organization (WHO) to reduce the sugar consumption of children and adults to less than 10% of the total energy intake, many people turned to sweeteners. Aspartame (E951), an artificial sweetener, is synthesized from L-phenylalanine or methyl ester of L-phenylalanine with L-aspartic acid. It is an amphoteric dipeptide composed of aspartic acid and phenylalanine. Apart from chemical peptide synthesis, aspartame can also be synthesized enzymatically commercially. 1 gr of it gives 4 Kcal energy. The taste perception of aspartame appears delayed and lasts a long time. Since it is not heat resistant during cooking, it can only be used as a sweetener in cold drinks and food, coffee, tea. Although there were some scientific objections after the introduction of aspartame to the market, animal and human experiments and investigations started to increase. In another study; Consumption of 40, 75, 500 mg/kg/day aspartame have increased oxidative stress parameters and has been reported to damage liver antioxidant capacity. Also, in some other studies in which negative effects on experimental animals were discussed, 250, 500, 1000 mg/kg/day aspartame consumption was found to significantly increase the liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST). Besides, studies showing that aspartame does not have negative effects on health, 240 mg/kg/day aspartame consumption did not make a significant difference in alanine aminotransferase (ALT) value, and there was no significant difference between the groups in fasting blood glucose with 4% aspartame solution daily consumption. On the other hand, studies on aspartame toxicity also have conflicting results. Some studies using in vivo and in vitro tests have shown that aspartame does not cause genotoxicity, DNA damage, and mutagenesis, but does stimulate chromosome aberrations and micronucleus formation. Many studies have been done to show the safety of aspartame. The European Food Safety Authority stated in its 2013 re-evaluation that aspartame is safe for human consumption at current exposure levels. In a review evaluating the data obtained from aspartame studies, it is supported that aspartame is a safe sweetener when used within the recommended dose limits. For aspartame, this value (ADI) has been recommended as 40 mg/kg body weight/day. Considering its association with age, gender, personal metabolism, and metabolic diseases, it was concluded that the use of aspartame is safe, with the fact that it has some harmful effects depending on the exposure time and dose.
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Acceptable daily intake
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Consumption of the artificial sweetener aspartame raises plasma phenylalanine levels, thereby increasing brain phenylalanine and, conceivably, affecting the syntheses of monoaminergic brain neurotransmitters known to underlie various types of behavior. We have thus assessed the effects of single aspartame doses on certain types of behavior, particularly those relating to mood and performance. In a double-blind, placebo-controlled, crossover study, a single dose of aspartame (60 mg/kg), or the same dose in combination with 37 g of carbohydrate, was administered to 20 male volunteers. [Carbohydrates enhance the entry of circulating phenylalanine into the brain by lowering plasma levels of competing large neutral amino acids (LNAA)]. A lower dose of aspartame (20 mg/kg) was also tested. Aspartame alone, or in combination with carbohydrate, did not alter any aspect of behavior that we assessed, nor did it produce detectable side effects. The ratios of plasma phenylalanine and tyrosine concentrations to those of the other LNAA were significantly increased by administration of aspartame. Since anecdotal reports of aspartame-associated neurological or behavioral side effects almost always describe effects as occurring after multiple aspartame exposures, it would be important to repeat our study using a protocol involving repeated aspartame administration.
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Almost all dietetic products now contain aspartame, a sweetener consisting of phenylalanine and aspartic acid. Recently, three pilot studies have proposed that the addition of products containing aspartame to the diets of migraine headache sufferers may produce a significant increase in the frequency of their migraines. The present study was a controlled thirteen-week, double-blind, randomized cross-over study comparing the effect of aspartame to that of a matched placebo on the frequency and intensity of migraine headache. The results of this study indicated that the ingestion of aspartame by migraineurs caused a significant increase in headache frequency for some subjects. The possible biochemical bases of these findings and their implications for research are discussed.
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In aqueous solutions, L‐aspartyl‐L‐phenylalanine methyl ester (aspartame) was 182 times sweeter than 2% sucrose but only 43 times sweeter than 30% sucrose according to rank analyses of scores from 20 judges. In buffer solutions (pH 3.2), pH was elevated by 0.025% and 0.12% aspartame and not by 4% or 12% sucrose, but no effect on sweetness equivalents or sourness was detected. Sweetness of 0.025% aspartame was enhanced by gelatin (1.5%) and methocel (1%). Enhancement also occurred when gelatin was combined with 0.12% aspartame. Sweetness ranks were not significantly affected by 1% carboxymethylcellulose or gum arabic. Viscosity was not a reliable indicator of differences in sensory response for thickness.
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Gelatin
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Sucralose
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From its discovery in 1965 till today, aspartame has caused numerous dilemmas and its descriptions vary from ideal sweetener to dangerous and poisonous substance that is being used for food production. Aspartame, (L-α-aspartyl-L-phenylalanine-1-methyl ester) was authorized by FDA (Food and Drug Administration) in 1981, when its ADI (Acceptable Daily Intake) was defined. Aspartame is unique intensive sweetener that is nowadays used in production of many kinds of food, and in digestive tract it is broken down by esterases and peptidases into aspartic acid, phenylalanine and small amount of methanol. Impact of aspartame on human health has
been widely investigated during last few decades, whereat two opposite opinions were represented: one arguing in favor of its toxicity and carcinogenicity, and the other (primarily expressed by food industry, i.e. sweetener industry) trying to prove complete absence of aspartame toxicity if used in approved doses. The aim of this work was to perform aspartame
risk assessment on the national level. The two-phase method for data collection was used in order to carry out this risk assessment,. It included survey on consumer habits concerning consumption of foods containing non-nutritive sweeteners, and chemical analysis of foods that contain aspartame. The results of the questionnaire,on consumption of aspartame containing foods, assumed and determined amounts of additives in tested foods, were presented based on calculations of the acceptable daily intakes using five different approaches in assessment of aspartame intake: (a) minimalistic for the total population, (b) including only consumers of foods
which contain aspartame, (c) based on the evaluation of daily intakes according to the maximum permitted use levels defined by the Ordinance on Food Additives O.G.173/4, (d) combining intake in the population of consumers with maximum permitted use, and (e) combining theoretical intake of foods which contain aspartame with maximum permitted use levels in particular food group. Risk characterization was carried out by comparison of EDI with ADI (EFSA, JECFA, Codex Alimentarius Commission). The determined estimated daily intake is much lower than the acceptable daily intake both for total population, as well as for consumers of aspartame containing foods. The acceptable daily intake was exceeded when theoretical intakes of foods which contain aspartame were combined with maximum permitted use level (EDI teor. / ADI, 107%). The present results were compared to similar reports from the EU and
other countries and they were in accordance with the results obtained in developed European countries. Based on the results of this work, it can be undoubtedly concluded that application of aspartame in food production should closely follow the regulations on maximum permitted use levels in foods thus maintaining the intake of the additive, especially in susceptible groups of consumers, within acceptable range.
Aspartame
Acceptable daily intake
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Artificial Sweetener
Sweetening
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