When ingested, aspartame is broken down into its constituent amino acids, L-aspartic acid and L-phenylalanine. Further metabolism of these products produces methanol, formaldehyde, and formic acid in small quantities These chemicals can cause adverse effects in large doses and may, therefore, be implicated in some of the reported adverse effects of aspartame. However, the precise modes of action and fates of these metabolites in the body are not completely understood.[1][2][3][4]
Like all nonnutritive artificial sweeteners, aspartame has a sweet taste because it activates taste receptors on the tongue.[5] This mechanism might influence sweet taste behavior and increase motivation for sweet foods, but the evidence is mixed and further work is needed to make a firm conclusion.[6][7] Some studies have also shown that a single dose of aspartame can acutely decrease food intake at the next meal.[8][9][10] The current evidence shows that this effect is not driven by changes in the secretion of appetite-regulating gut hormones,[11] but it has been suggested that the increase in blood phenylalanine concentrations following aspartame ingestion may regulate appetite because phenylalanine can cross the blood-brain barrier and can influence neurotransmitter synthesis.[12]
Although a direct causal effect of aspartame on cancer in humans is unlikely at the current exposure levels, it has been associated with cancer in some observational studies, so it is important to explore the plausible mechanistic bases for a causal link. One possibility is that L-aspartic acid and L-phenylalanine (breakdown products of aspartame) could enter cellular protein synthesis pathways and affect mTOR signaling, which is known to regulate cell growth.[13] L-aspartic acid (aka aspartate) has also been shown to directly regulate cancer cell growth.[14][15] However, these are speculations, and evidence for this comes mainly from in vitro cell experiments.[14][15] Furthermore, humans are exposed to L-aspartic acid and L-phenylalanine every time protein is eaten, and cancer cell metabolism is also regulated by many other metabolites — other amino acids, glucose, etc. — that are essential for life.[13][14][15] This does not mean that such metabolites cause cancer.