The following studies are presented in order by year published. They are connected by hyperlink to their abstracts in MedLine. Last update - 7/16/2000
Comments on the purported generation of formaldehyde and adduct formation from the sweetener aspartame. , Tephly TR, Life Sci 1999;65(13):PL157-60
"A recent paper by Trocho et al. (1) describes experiments meant to show that formaldehyde adducts are formed when rats are administered the sweetener aspartame. ... In this letter, studies which have been published previously and which were not cited by these authors are reviewed in order to put into perspective the disposition of methanol and formaldehyde in monkeys and humans, species relevant to the toxicity of methanol and its toxic metabolite, formic acid."Formaldehyde derived from dietary aspartame binds to tissue components in vivo. , Trocho C, et al., Life Sci 1998;63(5):337-49
"Adult male rats were given an oral dose of 10 mg/kg aspartame 14C-labelled in the methanol carbon. At timed intervals of up to 6 hours, the radioactivity in plasma and several organs was investigated. ... The specific radioactivity of tissue protein, RNA and DNA was quite uniform. The protein label was concentrated in amino acids, different from methionine, and largely coincident with the result of protein exposure to labelled formaldehyde. ... It is concluded that aspartame consumption may constitute a hazard because of its contribution to the formation of formaldehyde adducts."Erythema nodosum: 112 cases. Epidemiology, clinical aspects and histopathology, Bohn S, Buchner S, Itin P, Schweiz Med Wochenschr 1997 Jul 8;127(27-28):1168-76
"... The commonest cause of erythema nodosum [multiple, tender nodules most often occurring on the shins] was infection. Other etiologic factors were adverse drug reactions, sarcoidosis, Crohn's disease, non-Hodgkin lymphoma, pregnancy, discoid lupus erythematosus, Sharp syndrome and aspartame..."
Increasing brain tumor rates: is there a link to aspartame? , Olney JW, Farber NB, Spitznagel E, Robins LN. J Neuropathol Exp Neurol 1996 Nov;55(11):1115-23" ... we analyzed these data from 1975 to 1992 and found that the brain tumor increases in the United States occurred in two distinct phases, an early modest increase that may primarily reflect improved diagnostic technology, and a more recent sustained increase in the incidence and shift toward greater malignancy that must be explained by some other factor(s). ... Evidence potentially implicating aspartame includes an early animal study revealing an exceedingly high incidence of brain tumors in aspartame-fed rats compared to no brain tumors in concurrent controls, the recent finding that the aspartame molecule has mutagenic potential, and the close temporal association (aspartame was introduced into US food and beverage markets several years prior to the sharp increase in brain tumor incidence and malignancy). We conclude that there is need for reassessing the carcinogenic potential of aspartame. "Aspartame ingestion and headaches: a randomized crossover trial. Van den Eeden SK, Koepsell TD, Longstreth WT Jr, van Belle G, Daling JR, McKnight B, Neurology 1994 Oct;44(10):1787-93
"...It appears that some people are particularly susceptible to headaches caused by aspartame and may want to limit their consumption."
Neuropharmacological evaluation of movement disorders that are adverse reactions to specific foods. Gerrard JW, Richardson JS, Donat J, Int J Neurosci 1994 May;76(1-2):61-9Three cases are reported of patients who had episodic movement disorders triggered by foods or components of the diet. [aspartame was one] ... These observations suggest that, in susceptible individuals, foods can trigger movement disorders through an action on dopamine and other neurotransmitter pathways in the brain."
Adverse reactions to aspartame: double-blind challenge in patients from a vulnerable population. Walton RG, Hudak R, Green-Waite RJ, Biological Psychiatry 1993 Jul 1-15;34(1-2):13-7"...there was a significant difference between aspartame and placebo in number and severity of symptoms for patients with a history of depression, whereas for individuals without such a history there was not. We conclude that individuals with mood disorders are particularly sensitive to this artificial sweetener and its use in this population should be discouraged."
Aspartame exacerbates EEG spike-wave discharge in children with generalized absence epilepsy: a double-blind controlled study., Camfield PR, Camfield CS, Dooley JM, Gordon K, Jollymore S, Weaver DF. Neurology 1992 May;42(5):1000-3" Following aspartame compared with sucrose, the number of spike-wave discharges per hour and mean length of spike-wave discharges increased but not to a statistically significant degree. However, the total duration of spike-wave discharge per hour was significantly increased after aspartame (p = 0.028), with a 40% +/- 17% (SEM) increase in the number of seconds per hour of EEG recording that the children spent in spike-wave discharge. Aspartame appears to exacerbate the amount of EEG spike wave in children with absence seizures..."Oral administration of aspartame is not proconvulsant in rats. Tilson HA, Thai L, Zhao D, Sobotka TJ, Hong JS. Neurotoxicology 1989 Summer;10(2):229-38
" These experiments examined the potential for single or repeated doses of aspartame to exacerbate or facilitate the production of seizures in Fischer-344 rats. ... In a second series of studies, young male and female rats were dosed with 1,000 mg/kg of aspartame on day 3-13 or 21-35 of age. Prior exposure to aspartame had no significant effect on the rate of kindling at 90 days of age. These experiments indicate that aspartame does not act a pro-convulsant in rats. "Effect of aspartame on seizures in various models of experimental epilepsy. Guiso G, Caccia S, Vezzani A, Stasi MA, Salmona M, Romano M, Garattini S. Toxicol Appl Pharmacol 1988 Dec;96(3):485-93
" ... Aspartame (0.75-1.0 g/kg), given orally as a single bolus to 16-hr fasted animals 60 min before metrazol, significantly increased the number of animals showing clonic-tonic seizures. ... A similar increase in seizure susceptibility was observed with 0.25-0.5 g/kg of the aspartame's metabolite phenylalanine.... Plasma and brain levels of phenylalanine and tyrosine significantly raised after both 1 g/kg aspartame as a single bolus ... or in three divided doses ... "Administration of aspartame potentiates pentylenetetrazole- and fluorothyl-induced seizures in mice. Pinto JM, Maher TJ. Neuropharmacology 1988 Jan;27(1):51-5
" ... Doses of aspartame were used which increased phenylalanine more than tyrosine in brain, as occurs in humans after the consumption of any dose of aspartame. Pretreatment with aspartame significantly increased the percentage of animals convulsing after administration of pentylenetetrazole and significantly lowered the CD50 for this convulsant. ... The seizure-promoting effect of aspartame could be demonstrated 30, 60 or 120 min after the 1000 mg/kg dose. The seizures induced by either convulsant were potentiated by equimolar amounts of phenylalanine, a major endogenous metabolite of aspartame, while the other metabolites, aspartic acid and methanol, were without effect. ..."Possible neurologic effects of aspartame, a widely used food additive, Maher TJ, Wurtman RJ, Environmental Health Perspectives 1987 Nov;75:53-7
"... Since phenylalanine can be neurotoxic and can affect the synthesis of inhibitory monoamine neurotransmitters, the phenylalanine in aspartame could conceiveably mediate neurologic effects. If mice are given aspartame in doses that elevate plasma phenylalanine levels more than those of tyrosine . . . the frequency of seizures . . . is enhanced. ... Perhaps regulations concerning the sale of food additives should be modified to require the reporting of adverse reactions and the continuing conduct of mandated safety research."TOP
