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Food Chem Toxicol. 2007 Dec;45(12):2397-401. Epub 2007 Jun 16.

The effect of aspartame metabolites on the suckling rat frontal cortex acetylcholinesterase. An in vitro study.

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  • 1Department of Experimental Physiology, Medical School, University of Athens, P.O. Box 65257, GR 15401 Athens, Greece.


Aspartame (ASP) consumption is suggested to be implicated with muscarinic dysfunction. The aim of this work was to evaluate the effect of ASP and its metabolites on acetylcholinesterase (AChE) activity in rat frontal cortex and pure enzyme. Rat frontal cortex homogenate or pure enzyme AChE (eel E. Electricus) were incubated with ASP and each of ASP components, phenylalanine (Phe), aspartic acid (asp), and methanol (MeOH) for 1 h at 37 degrees C. AChE was measured spectrophotometrically. The results showed that incubation of rat tissue or pure enzyme with the sum of ASP metabolites, as reported to be found in the CSF after 150 or 200 mg/kg ASP consumption, inhibited frontal cortex and pure AChE about -11% to -29% (p<0.001). Asp, Phe or MeOH concentrations related to their CSF levels after ingestion of abuse or toxic ASP doses, when separately incubated with frontal cortex or pure AChE, resulted in a significant decrease of the enzyme activities.


ASP compounds may directly and/or indirectly act on the frontal cortex AChE. High or toxic doses of the sweetener remarkably decreased the enzyme activity. If this in vitro finding comes into human reality, it may be suggested that cholinergic symptoms are related to the consumption of the above ASP doses.

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