Is Dietary Aspartame Dangerous?
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. http://www.nlm.nih.gov/medlineplus/phenylketonuria.html#cat1.
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. http://www.cbsnews.com/stories/2005/07/28/health/webmd/main712605.shtml