N Engl J Med. 1987 Nov 5;317(19):1181-5.

Aspartame and susceptibility to headache.

Schiffman SS, Buckley CE 3rd, Sampson HA, Massey EW, Baraniuk JN, Follett JV, Warwick ZS.

Department of Psychiatry, Duke University, Durham, N.C. 27710.

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 less than 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 less than 0.0002) and epinephrine (P less than 0.02) just before the development of headache. We conclude that in this population, aspartame is no more likely to produce headache than placebo.