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, aspartylphenylalanine 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). Conclusion: 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.