Aspartame is no more likely than placebo to cause urticaria/angioedema: results of a multicenter, randomized, double-blind, placebo-controlled, crossover study.
BACKGROUND
Anecdotes and single case reports have suggested that the high-intensity sweetener, aspartame, may be associated with allergic/hypersensitivity-type reactions.


METHODS
We conducted a multicenter, placebo-controlled clinical study to evaluate individuals who had experienced urticaria and/or angioedema allegedly associated with ingestion of an aspartame-containing product. Despite extensive recruiting efforts over 4 years, only 21 subjects could be enrolled. After admission to clinical research units, subjects were given aspartame and placebo in a randomized, double-blind, crossover fashion. Subjects received, on different days, increasing doses (50, 300, 600 mg) of aspartame and placebo at 8:00 AM, 10:00 AM, and noon. Subjects who weighed less than 40 kg received one half of these doses. Conversion products of aspartame, aspartyl-phenylalanine diketopiperazine and beta-aspartame, were also included in the aspartame arm of the study. Positive reactions were defined as urticaria (hives with wheals 4 mm or more in diameter with a collective diameter of at least 15 mm or one or more hives with a wheal of 4 mm or greater with a flare of 8 mm or greater) or as angioedema.


RESULTS
According to these criteria, four reactions were observed; two followed aspartame ingestion and two followed placebo ingestion (p = 1.00). The incidence of other adverse experiences was no different after aspartame versus placebo ingestion (p = 0.289).


CONCLUSIONS
These results indicate that aspartame and its conversion products are no more likely than placebo to cause urticaria and/or angioedema reactions in subjects with a history consistent with hypersensitivity to aspartame.
Geha
R
R
Harvard Medical School, Boston, MA.
Buckley
C E
CE
Greenberger
P
P
Patterson
R
R
Polmar
S
S
Saxon
A
A
Rohr
A
A
Yang
W
W
Drouin
M
M
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000799:Angioedema / Q000139:chemically induced*; D001218:Aspartame / Q000008:administration & dosage / Q000009:adverse effects*; D002214:Capsules; D002648:Child; D004311:Double-Blind Method; D004342:Drug Hypersensitivity / Q000209:etiology*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D010919:Placebos; D014581:Urticaria / Q000139:chemically induced*
D002214:Capsules; D010919:Placebos; D001218:Aspartame