Letter to the Editor

European Journal of Clinical Nutrition (2009) 63, 698–699; doi:10.1038/ejcn.2008.5; published online 30 January 2008

Aspartame effects on the brain

J D Fernstrom1

1Department of Psychiatry and Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

Correspondence: JD Fernstrom, E-mail: fernstromjd@upmc.edu

The following comments relate to the review by Humphries et al. (2007). The premise of the review, that the high-intensity sweetener aspartame is neurotoxic, ignores a very large scientific literature to the contrary, recently comprehensively summarized (Butchko et al., 2002; Magnuson et al., 2007).

The key point about aspartame is that very little is consumed. Because it is 180 times sweeter than sugar, relatively little shows up in products. For example, a 355ml can of diet soda contains 180mg of aspartame, which for a 70kg human is a 2.5mgkg−1 dose (1.25mgkg−1 phenylalanine). After its introduction, its use was monitored for years, revealing that average daily dosing is barely 5mgkg−1day−1 (2.5mgkg−1day−1 phenylalanine), not much. As a comparison, the amount of phenylalanine in a quarter-pound hamburger is about 1000mg, or 14mgkg−1 phenylalanine (70kg individual), or much more. It is important to keep this fact in mind when considering the authors' arguments, which relate to studies in animals involving extremely high aspartame doses (for example, up to 2000mgkg−1 in rats, a huge dose). Such studies have no relevance to human use. And, for aspartame to have effects in animals, blood levels of aspartame constituents (aspartate, phenylalanine, methanol) must increase to very high values. At the levels ingested by humans, such increases in blood do not occur, even at high levels of intake (Butchko et al., 2002; Magnuson et al., 2007).

The errors in this article are too numerous to enumerate in a letter of limited length. I note those most obvious to me. (a) Formate is not converted to diketopiperazine (abstract). (b) The authors are incorrect in stating that tyrosine cannot be synthesized in brain from phenylalanine. (c) Despite the authors' statement, even very large increases in phenylalanine levels produced by aspartame administration to rats do not suppress catecholamine synthesis rate (Fernstrom et al., 1991). (d) Contrary to the authors' statement, my 1983 Life Sciences paper did not find changes in regional brain catecholamine concentrations following aspartame dosing of rats. (e) Maher and Wurtman gave rats aspartame up to 2000mgkg−1, a huge dose. And their results could not be confirmed (see Butchko et al., 2002; Magnuson et al., 2007). (f) Aspartame does not enter the blood from the gut, and thus does not get into brain. Hence, brain glutamate receptors cannot be engaged directly by aspartame, despite the authors' assertions. (g) Despite the authors' statement, my 1994 Journal of the American Dietetic Association article does not state that aspartame increases brain levels of acidic amino acids. (h) There is no such thing as ‘excitotoxic-saturated placental blood flow’ caused by maternal aspartame consumption. (i) Finally, many erroneous statements have been obtained from two websites, one cited as Mehl-Madrona and the other as Bowen and Evangelista. These seem to me to be inappropriate references, as their contents have not been subjected to peer review, and contain unsupported speculation.

While I recognize the need for a continuing dialog on any issue relevant to human nutrition and health, here in relation to aspartame, in my view, the article by Humphries does not make an informed contribution.



  1. Butchko HH, Stargel WW, Comer CP, Mayhew DA, Benninger C, Blackburn GL et al. (2002). Aspartame: review of safety. Regul Toxicol Pharmacol 35, S1–S93. | Article | PubMed |
  2. Fernstrom JD, Fernstrom MH, Massoudi MS (1991). In vivo tyrosine hydroxylation in rat retina: effect of aspartame ingestion in rats pretreated with p-chlorophenylalanine. Am J Clin Nutr 53, 923–929. | PubMed | ChemPort |
  3. Humphries P, Pretorius E, Naude H (2007). Direct and indirect cellular effects of aspartame on the brain. Eur J Clin Nutr; e-pub ahead of print 8 August 2007; doi: 10.1038/sj.ejcn.1602866.
  4. Magnuson BA, Burdock GA, Doull J, Kroes RM, Marsh GM, Pariza MW et al. (2007). Aspartame: a safety evaluation based on current use levels, regulations, and toxicological and epidemiological studies. Crit Rev Toxicol 37, 629–727. | Article | PubMed | ChemPort |


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