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Is Dietary Aspartame Dangerous?

Lisa B.'s picture

Marketed under the trade names "Equal" and "NutraSweet," aspartame has met the Food and Drug Administration (FDA) requirements as a food additive for the past thirty years, yet the artificial sweetener continues to be a subject of public controversy.  Recent concerns have focused on potential neurotoxicity in humans, since its metabolic byproducts are phenylalanine, known to cause brain damage in humans with an inborn inability to metabolize this amino acid, and aspartic acid, an excitatory neurotransmitter (Stegink et al., 1837).

Aspartame, or L-aspartyl-L-phenylalanyl-methyl ester, was discovered in 1965 by James Schlatter in a failed attempt to isolate an anti-ulcer drug. The dipeptide has a sweetening potential 180 to 200 times that of sucrose (Stegink et al., 1837).  At the temperatures found in the intestinal mucosa, aspartame breaks down into the amino acids aspartate and phenylalanine. Stegink and Filer (Stegink et al., 47) have raised concerns about interactions between glutamate and aspartame when aspartame is added to foods already containing monosodium L-glutamate.

Aspartame and Glutamate enter the metabolic pathways in similar manners. Glutamate enters the mitochondrion by two processes, either transamination or enzyme glutamate dehydrogenase. Transamination converts glutamate into a carbon skeleton by removing the α-amino group from most of the amino acids. During metabolism the carbon structure of glutamate produces carbon dioxide and energy (ATP) for the cell.

The second mechanism, enzyme glutamate dehydrogenase, functions in the cytoplasmic and mitochondrial fractions of the cell. The two products of enzyme glutamate dehydrogenase, a α-ketoglutarate and ammonium ions, continue to react and generate carbon dioxide and water with the generation of ATP. The accumulation of ATP and NADH from transamination and glutamate dehydrogenase increases the concentration of citrate and malate. The malate is oxidized to carbon dioxide or gluconeogenesis. Citrate cleavage enzymes convert citrate into oxaloacetate and acetyl-coenzyme A (acetyl-CoA), where acetyl-CoA forms fatty acids and triglycerides for further processing in the liver. The oxaloacetate is metabolized into either glucose or fatty acids.  

Aspartate enters metabolism by transamination with other α-ketoacids to form oxaloacetate. However, oxaloacetate produced outside of the mitochondria is oxidized to carbon dioxide or gluconeogenesis. Aspartate that enters mitochondria is transaminated to yield oxaloacetate, which is oxidized in the mitochondrion or converted to citrate or malate. The citrate and malate are then metabolized in a similar manner as glutamate.  

A rare metabolic disorder in humans, phenylkenonuria (PKU), can result in elevated serum levels of phenylalanine and brain damage.  PKU is the most common inherited autosomal recessive disorder involving amino acid metabolism, and is caused by a deficiency of the liver enzyme phenylalanine hydroxylase.  The disorder is incurable, and brain damage is irreversible, so treatment of PKU is focused on avoiding foods with high concentrations of phenylalanine.  A specialized PKU diet includes higher levels of other amino acids, and daily monitoring of serum levels of phenylalanine. However, even those affected with this disorder require substantial levels of plasma aspartate and phenylalanine to develop signs of toxicity (NIH). Consequently, humans with normal metabolisms should be able to effectively metabolize even large amounts of aspartame if delivered over a long period of time.

Aspartate, an excitatory neurotransmitter and excitotoxin, has been shown to cause brain damage in high doses (Mercola and Pearsall, 53). Patients who experience seizures and strokes have increased levels of aspartic acid. Olney (Mercola and Pearsall, 54) showed that excitotoxins caused certain nerve cells in the brain to die. Although the FDA has not required food manufactures to remove free-form amino acids acting as excitotoxins in food, excitotoxicity could lead to neurodegenerative diseases such as Parkinson's and Alzheimer's.

Natural phenylalanine and aspartic acid are required for the nervous system to function, but when ingested on their own they have toxicities. The toxic effects of aspartame vary by species, subject age, and amount ingested. Stegink et al. (1977) found that older mice were less susceptible to aspartame toxicity, presumably because of a more fully developed metabolism. While the neonatal mouse reached a threshold effect between 50 and 70 μmoles/100 ml, PKU children must reach 180 μmoles/100 ml before any signs of neuronal necrosis are noted (Stegink et al., 1837-38). Stegink et al. have shown that there are no changes in either plasma or erythrocyte asparate levels with an Aspartame dosage of 34 mg/kg (Stegink et al. 1837). To reach this dosage, a 140-pound woman would need to drink about seven cans of diet soda (CBS).

Ed Klein, the vice president of Diet Coke for Coca-Cola North America once stated, "Diet Coke drinkers live an effervescent life, and the effervescent lift of Diet Coke is an important part of it." Klein describes my afternoon craving for Diet Coke, but I hope that "effervescent lift" is from pure refreshment and not from an abundance of excitotoxins.


Mercola, J., and K.D. Pearsall. Sweet Deception: Why Splenda®, Nutrasweet®, and the FDA May Be Hazardous to Your Health. Nashville, TN: Thomas Nelson, 2006.

"Phenylketonuria." 8 April 2009. NIH.

Stegink, L.D., et al. "Effect of Aspartame and Aspartate Loading Upon Plasma and Erythrocyte Free Amino Acid Levels in Normal Adult Volunteers." JN 107.10 (1977): 1837-1845.

De Vries, Lloyd. "Study Links Aspartame to Cancer." 28 July 2005. CBS News.


Rachel 's picture

I hate the fact that people

I hate the fact that people of these big wig corporations think that aspartame and artificial sugars are the best . To be honest I feel they are are all telling lies I was born with PKU and have had it ever since. I can't give blood &I get take any blood from anyone because of it. The reason is it could make my count go crazy and possibly kill me I used take in aspartame in the beginning on a normal basis it acted like a diet supplement but even then you have to be very careful not to raise your levels because it is your health that can change, you have to make sure at all times what your count is and know what it is that has aspartame and other additives that will trigger or raise your enzyme count . If you do not pay attention , It could very well be life threatening for you. I have learned since having my children that now I can't drink it without a reaction to it I get extremely tired and end up sleeping for a long period of time & end up extremely pale which is not very good. And for the people or doctor slash psychologist that think we are supposed to be mentally retarded I was so bored in school because they were to slow.. I needed alot of information and they just couldn't keep up kept giving old things I learned before. I am not stupid or retarded I need more then any teacher or person can give .. I am like a computer always needing more input. If that makes me mentally retarded then someone needs there head check and it isn't me

Sincerely Rachel Moffit

Rachel 's picture


I was born February 3rd 1973 with pku and I used to drink tab daily and never gained weight and never felt like i do now when i Intake it. I hate the fact that people think that i am suppose to be retarded,I am not by any means i am very smart and always look for more information and get bored with the same stuff that is why i left school yes I had a problem with authority but that was nothing . In everything I read I hear i am suppose to be a problem but I am not.... The only problems I have is aspartame and anything that has the phenylalanine in it .. it wasn't so bad before I got pregnant with my first and I made sure I didn't take it in due to make sure her health was ok.. however I got pregnant may of 92 with her sister and still didn't want to take any chances so I still didn't put any in body. Since when I was younger my body somehow had adapted by itself's with no help from doctors or meds and when my brother was born they still couldn't figure out how my blood did it with no help. However now since there was such a gap in me feeding it to my body that when i do drink or eat it i end up very tired and very pale. PKU has not had enough research done on it I know that I can not give blood because of it nor can I take anyone else's due to this ... but does that make me a freak or mentally retarded???? To be honest I think I am smarter then someone that doesn't have it. YOU NEED TO DO MORE RESEARCH ON THINGS THAT PEOPLE HAVE TO LIVE WITH EVERYDAY.

Sincerely Rachel Lynne Moffit Tranello Fackelman

Paul Grobstein's picture

Effervescence and aspartame

Maybe effervescence, like other things in life, has a price, one worth paying for some people, less so for others?