Food contains aspartic acid as an amino acid bound to proteins. Approximately 40% of aspartame (by mass) is broken down into aspartic acid. Because aspartame is metabolized and absorbed very quickly (unlike aspartic acid-containing proteins in foods), it is known that aspartame can spike blood plasma levels of aspartate to very high levels.^[23][35] Large spikes in blood plasma aspartate levels have not been seen when ingesting natural foods.

Aspartic acid belongs to a class of chemicals that in high concentrations act as an excitotoxin, inflicting damage on brain and nerve cells. High levels of excitotoxins have been shown in hundreds of animal studies to cause damage to areas of the brain unprotected by the blood-brain barrier and a variety of chronic diseases arising out of this neurotoxicity.^[36][37] The debate among scientists has been raging since the early 1970s, when Dr. John Olney found that high levels of aspartic acid caused damage to the brains of infant mice.^[38] Dr. Olney and consumer attorney, James Turner filed a protest with the FDA to block the approval of aspartame. The debate is complex and has focused on several areas: (a) whether the increase in plasma aspartate levels from typical ingestion levels of aspartame is enough to cause neurotoxicity in one dose or over time, (b) whether humans are susceptible to the neurotoxicity from aspartic acid seen in some animal experiments, (c) whether aspartic acid increases the toxicity of formaldehyde, (d) whether neurotoxicity from excitotoxins should consider the combined effect of aspartic acid and other excitotoxins such as glutamic acid from monosodium glutamate. The neuroscientists at a 1990 meeting of the Society for Neuroscience had a split of opinion on the issues related to neurotoxic effects from excitotoxic amino acids found in some additives such as aspartame.^[39]

Some scientists think that humans and other primates are not as susceptible to excitotoxins as rodents and therefore there is little concern with aspartic acid from aspartame.^[40][41] While they agree that the combined effects of all food-based excitotoxins should be considered,^[42] their measurements of the blood plasma levels of aspartic acid after ingestion of aspartame and monosodium glutamate demonstrate that there is not a cause for concern.^[43][44] Other scientists think that primates are susceptible to excitotoxic damage^[45] and that humans concentrate excitotoxins in the blood more than other animals.^[46] Based on these findings, they think that humans are approximately 5-6 times more susceptible to the effects of excitotoxins than are rodents.^[47] While they agree that typical use of aspartame does not spike aspartic acid to extremely high levels in adults, they are particularly concerned with potential effects in infants and young children,^[48] the potential long-term neurodegenerative effects of small-to-moderate spikes on plasma excitotoxin levels,^[49] and the potential dangers of combining formaldehyde exposure from aspartame with excitotoxins given that chronic methanol exposure increases excitoxin levels in susceptible areas of the brain^[50][51] and that excitotoxins may potentiate formaldehyde damage.^[52]

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