Metabolism of aspartame and its l-phenylalanine methyl ester decomposition product by the porcine gut

Burgert, Stephen L.; Andersen, Dean W.; Stegink, Lewis D.; Takeuchi, Hisanao; Schedl, Harold P.

doi:10.1016/0026-0495(91)90052-x

Cited by 30 publications

(21 citation statements)

References 18 publications

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“…27 Methanol is oxidized in the tissues by alcohol dehydrogenase to formaldehyde, which is a highly reactive intermediate product. Aspartame is a dipeptide methyl ester, which is hydrolyzed by pancreatic chymotrypsin in the upper part of the small intestine to yield phenylalanine, aspartic acid, and methanol.…”

Section: Discussionmentioning

confidence: 99%

Impact of aspartame and saccharin on the rat liver: Biochemical, molecular, and histological approach

Alkafafy

Ibrahim

Ahmed

et al. 2015

Int J Immunopathol Pharmacol

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The current work was undertaken to settle the debate about the toxicity of artificial sweeteners (AS), particularly aspartame and saccharin. Twenty-five, 7-week-old male Wistar albino rats with an average body weight of 101 ± 4.8 g were divided into a control group and four experimental groups (n = 5 rats). The first and second experimental groups received daily doses equivalent to the acceptable daily intake (ADI) of aspartame (250 mg/Kg BW) and four-fold ADI of aspartame (1000 mg/Kg BW). The third and fourth experimental groups received daily doses equivalent to ADI of saccharin (25 mg/Kg BW) and four-fold ADI of saccharin (100 mg/Kg BW). The experimental groups received the corresponding sweetener dissolved in water by oral route for 8 weeks. The activities of enzymes relevant to liver functions and antioxidants were measured in the blood plasma. Histological studies were used for the evaluation of the changes in the hepatic tissues. The gene expression levels of the key oncogene (h-Ras) and the tumor suppressor gene (P27) were also evaluated. In addition to a significant reduction in the body weight, the AS-treated groups displayed elevated enzymes activities, lowered antioxidants values, and histological changes reflecting the hepatotoxic effect of aspartame and saccharin. Moreover, the overexpression of the key oncogene (h-Ras) and the downregulation of the tumor suppressor gene (P27) in all treated rat groups may indicate a potential risk of liver carcinogenesis, particularly on long-term exposure.

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Section: Discussionmentioning

confidence: 99%

Impact of aspartame and saccharin on the rat liver: Biochemical, molecular, and histological approach

Alkafafy

Ibrahim

Ahmed

et al. 2015

Int J Immunopathol Pharmacol

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“…Its peptide nature, aspartyl-phenylalanine methyl ester facilitates its intestinal hydrolysis and absorption of innocuous amino acids together with small amounts of free methanol (Burgert et al, 1991;Lipton et al, 1991). Phenylalanine and aspartic acid are both amino acids which are found in natural proteins and under normal circumstances are beneficial, if not essential, for health (Woodrow, 1984).…”

Section: Introductionmentioning

confidence: 99%

Effect of aspartame on some oxidative stress parameters in liver and kidney of rats

Iman¹

2011

Afr. J. Pharm. Pharmacol.

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Aspartame is one of the most widely used artificial sweeteners in over 90 countries worldwide. It is a highly intensity sweetener added to a large variety of food, most commonly found in low calorie beverages, desserts and table top sweeteners added to tea or coffee. The present study examined whether the daily oral administration of ASP (40 mg/kg) for 2, 4 and 6 weeks induce oxidative stress in the liver and kidney of male albino rats. Lipid peroxidation (LPO), glutathione reduced (GSH) levels as well as the activities of superoxide dismutase (SOD), glutathione-S-transferase (GST) and catalase (CAT) enzymes were determined. A significant increase in LPO levels was obtained in the liver tissue after 4 and 6 weeks of ASP administration while there was a significant decrease in LPO level after 2 weeks followed by a significant increase in the renal tissue at the end of the 6 weeks. SOD activity significantly decreased in the liver tissue after 2, 4 and 6 weeks of treatment. Also, there was a significant decrease in SOD activity after 2 and 4 weeks in the renal tissue. CAT activity significantly decreased in the liver tissue after 2 and 4 weeks of ASP administration. Regarding to GSH content, there was a significant decrease in the liver tissue after 2, 4 and 6 weeks which was accompanied by a significant increase in GST activity after 4 and 6 weeks of ASP administration. In conclusion, ASP may induce an oxidative stress in the liver and kidney of male albino rats.

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“…The products that result from these reactions are MeOH and the amino acids aspartic acid (Asp) and phenylalanine (Phe) (see figure 1). Hydrolysis is very efficient; the amount of aspartame that enters the bloodstream has been reported as undetectable in several studies (Oppermann, 1984;Burgert et al, 1991). A single report has suggested that around up to about 10% of the dose might be absorbed as aspartame (Creppy et al, 1998), but this observation has not been mentioned in other reviews and would need confirmation.…”

Section: Hydrolysismentioning

confidence: 99%

“…Some data on kinetics are available in monkeys and dogs given aspartame at half the ADI (Oppermann, 1984). A study in pigs (Burgert et al, 1991) has been done at fairly high dose levels (up to ca. 18 times the ADI).…”

Section: Introductionmentioning

confidence: 99%

Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) related to a new long‐term carcinogenicity study on aspartame

2006

EFS2

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Aspartame has undergone extensive testing in animals and studies in humans, including four animal carcinogenicity studies conducted during the 1970s and early 1980s. These studies, together with studies on genotoxicity, were evaluated by regulatory bodies worldwide and it was concluded that they did not show evidence of genotoxic or carcinogenic potential for aspartame. Since its approval, however, the safety of aspartame has been repeatedly questioned, with discussions focusing not only on the safety of aspartame itself, but also on the safety of its breakdown products, aspartic acid, phenylalanine and methanol. All these substances occur naturally in the body. In response to such questions, the SCF undertook a further review of all the data on aspartame in 2002 and concluded that there was no need to revise the outcome of their earlier risk assessment or the previously established Acceptable Daily Intake (ADI) for aspartame, of 40 mg/kg body weight (bw).The AFC Panel has assessed the new carcinogenicity study, using not only the ERF publications but also a more extensive report provided to EFSA by the ERF at the end of 2005 and further data from the same study provided by ERF in April 2006. The Panel noted that this lifetime study, using more dose groups and more animals per group than conventional carcinogenicity studies, represented a substantial effort and had the potential to be more sensitive to low incidence effects. After its evaluation the Panel considers that the study has flaws which bring into question the validity of the findings, as interpreted by the ERF. In particular, the high background incidence of chronic inflammatory changes in the lungs and other vital organs and tissues and the uncertainty about the correctness of the diagnoses of some tumour types were major confounding factors in the interpretation of the findings of the study.The Panel's conclusions on the findings of the ERF study include the following:• The increased incidence of lymphomas/leukaemias reported in treated rats was unrelated to aspartame, given the high background incidence of chronic inflammatory changes in the lungs and the lack of a positive dose-response relationship. It is wellknown that such tumours can arise as a result of abundant lymphoid hyperplasia in the lungs of rats suffering from chronic respiratory disease. The most plausible explanation of the findings in this study with respect to lymphomas/leukaemias is that they have developed in a colony suffering from chronic respiratory disease. The slight increase in incidence of these tumours in rats fed aspartame is considered to be an incidental finding of the ERF study and can therefore be dismissed.• The preneoplastic and neoplastic lesions of the renal pelvis, ureter and bladder occurring primarily in female rats along with renal calcification were most probably treatment-related, at least at the higher doses. It is widely accepted that the effect is a high dose effect of irritant chemicals or chemicals producing renal pelvic calcification as a result of im...

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Metabolism of aspartame and its l-phenylalanine methyl ester decomposition product by the porcine gut

Cited by 30 publications

References 18 publications

Impact of aspartame and saccharin on the rat liver: Biochemical, molecular, and histological approach

Impact of aspartame and saccharin on the rat liver: Biochemical, molecular, and histological approach

Effect of aspartame on some oxidative stress parameters in liver and kidney of rats

Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) related to a new long‐term carcinogenicity study on aspartame

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