Background: Considerable debate swirls about the validity of symptoms described by many people after ingestion of monosodium glutamate (MSG), and the question has remained unresolved largely because of a paucity of well-designed challenge studies.

Methods: We conducted oral challenge studies in self-identified MSG-sensitive subjects to determine whether they had a statistically significant difference in the incidence of their specific symptoms after ingestion of MSG compared with placebo. First, 5 gm MSG or placebo was administered in random sequence in a double-blind fashion. Subjects who reacted only to a single test agent then underwent rechallenge in random sequence in a double-blind fashion with placebo and 1.25, 2.5, and 5 gm MSG. A positive response to challenge was defined as the reproduction of ≥2 of the specific symptoms in a subject ascertained on prechallenge interview.

Results: Sixty-one subjects entered the study. On initial challenge, 18 (29.5%) responded to neither MSG nor placebo, 6 (9.8%) to both, 15 (24.6%) to placebo, and 22 (36.1%) to MSG (p=0.324). Total and average severity of symptoms after ingestion of MSG (374 and 80) were greater than respective values after placebo ingestion (232 and 56; p=0.026 and 0.018, respectively). Rechallenge revealed an apparent threshold dose for reactivity of 2.5 gm MSG. Headache (p<0.023), muscle tightness (p<0.004), numbness/tingling (p<0.007), general weakness (p<0.040), and flushing (p<0.016) occurred more frequently after MSG than placebo ingestion.

Conclusions: Oral challenge with MSG reproduced symptoms in alleged sensitive persons. The mechanism of the reaction remains unknown, but symptom characteristics do not support an IgE-mediated mechanism. According to Food and Drug Administration recommendations, the symptoms, originally called the Chinese restaurant syndrome, are better referred to as the MSG symptom complex. (J Allergy Clin Immunol 1997;99:757-62.)