A double-blind crossover study in 32 subjects with self-identified aspartame-induced headache is reported from the University of Washington School of Medicine, Seattle, WA. Volunteers were randomized to receive aspartame (30 mg/kg/d) and placebo in a 2-treatment, 4-period crossover design. Each period was 7 days. Subjects reported significantly more headaches during aspartame treatment (on 33% of the days) compared with placebo (24%). Headache triggered by aspartame was particularly frequent [p < 0.001] in subjects who were “very sure” that aspartame had caused them headaches previously. One-fourth of the subjects withdrew from the study, complaining of too frequent or severe headaches or sleep disturbance. A number of individuals had declined inclusion in the study because of the severity of their reaction to aspartame. 
COMMENT. The authors conclude that aspartame causes headaches in a subset of adults with self-identified aspartame-induced headaches. An underestimation of the adverse effect of aspartame in some studies may reflect differences in subject susceptibility, exclusion of specific responders, and concomitant ingestion of other food or drink. Children with migraine may be more responsive to dietary triggers than adults. (Progress in Pediatric Neurology I & II, Chicago, PNB Publ, 1991, 1994).