Metabolites
Hypotheses of adverse health effects have focused on the three metabolites of aspartame, which are aspartic acid, methanol and phenylalanine. Aspartame is rapidly hydrolyzed in the small intestines. Even with ingestion of very high doses of aspartame (over 200 mg/kg), no aspartame is found in the blood due to the rapid breakdown.[8] These metabolites have been studied in a wide range of populations including infants, children, adolescents, and healthy adults. In healthy adults and children, even enormous doses of aspartame do not lead to plasma levels of metabolites that are a concern for safety.
Aspartate
Aspartic acid (aspartate) is one of the most common amino acids in the typical diet but nevertheless has been implicated as a possible source for neurotoxic effects of aspartame. As with methanol and phenylalanine, intake of aspartic acid from aspartame is less than would be expected from other dietary sources. At the 90th percentile of intake, aspartame provides only between 1% and 2% of the daily intake of aspartic acid. There has been some speculation that aspartame, in conjunction with other amino acids like glutamate, may lead to excitotoxicity, inflicting damage on brain and nerve cells. However, clinical studies have shown no signs of neurotoxic effects,[8] and studies of metabolism suggests it is not possible to ingest enough aspartic acid and glutamate through food and drink to levels that would be expected to be toxic.[61]
Methanol
The methanol produced by the metabolism of aspartame is absorbed and quickly converted into formaldehyde and then completely converted to formic acid, which, due to its long half life, is considered the primary mechanism of toxicity in methanol poisoning. The methanol from aspartame is unlikely to be a safety concern for several reasons. The amount of methanol in aspartame is less than that found in fruit juices and citrus fruits, and there are other dietary sources for methanol such as fermented beverages. Therefore, the amount of methanol produced from aspartame is likely to be less than that from natural sources. With regards to formaldehyde, it is rapidly converted in the body, and the amounts of formaldehyde from the metabolism of aspartame is trivial when compared to the amounts produced routinely by the human body and from other foods and drugs. At the highest expected human doses of consumption of aspartame, there are no increased blood levels of methanol or formic acid,[8] and ingesting aspartame at the 90th percentile of intake would produce 25 times less methanol than would be considered toxic.[61]
Phenylalanine
People with the genetic disorder phenylketonuria are advised to avoid aspartame as they have a decreased ability to metabolize phenylalanine. Common foods such as milk, meat, and fruits provide far greater amounts of these metabolites in a diet than aspartame.[61]
Phenylalanine is one of the essential amino acids and is required for normal growth and maintenance of life. Concerns about the safety of phenylalanine from aspartame center largely around hypothetical changes in neurotransmitter levels as well as ratios of neurotransmitters to each other in the blood and brain that could lead to neurological symptoms. Reviews of the literature have found no consistent findings to support such concerns,[61] and while high doses of aspartame consumption may have some biochemical effects, these effects are not seen in toxicity studies to suggest aspartame can adversely affect neuronal function.[8] Like methanol, the typical diet will lead to ingestion of significantly higher amounts of phenylalanine than would be expected from aspartame consumption.[61]