Aspartame and Susceptibility to Headache

We performed a double-blind crossover trial of challenges with 30 mg of aspartame per kilogram of body weight or placebo in 40 subjects who reported having headaches repeatedly after consuming products containing aspartame. The incidence rate of headache after aspartame (35 percent) was not significantly different from that after placebo (45 percent) (P<0.50). No serious reactions were observed, and the incidence of symptoms other than headache following aspartame was also equivalent to that after placebo. No treatment-related effects were detected in vital signs, blood pressure, or plasma concentrations of cortisol, insulin, glucagon, histamine, epinephrine, or norepinephrine. Most of the subjects were well educated and overweight and had a family or personal history of allergic reactions. The subjects who had headaches had lower plasma concentrations of norepinephrine (P<0.0002) and epinephrine (P<0.02) just before the development of headache. We conclude that in this population, aspartame is no more likely to produce headache than placebo. (N Engl J Med 1987; 317:1181–5.) ASPARTAME is a dipeptide sweetener (L-aspartyl-L-phenylalanine methyl ester^1,2) that is 180 to 200 times sweeter by weight than sugar. The Food and Drug Administration approved the use of aspartame as a table-top sweetener and an ingredient in dry foods in 1981³ and approved its use in carbonated beverages in 1983.⁴ The widespread use of aspartame provoked reports of various reactions attributed to sensitivity to the sweetener.^{5 6 7} The Centers for Disease Control (CDC) investigated 517 consumer complaints and found that 67 percent involved neurologic or behavioral symptoms, especially headaches.^6,7 Other case reports of adverse reactions to the sweetener have included.