The monosodium glutamate symptom complex: assessment in a double-blind, placebo-controlled, randomized study

J Allergy Clin Immunol. 1997 Jun;99(6 Pt 1):757-62. doi: 10.1016/s0091-6749(97)80008-5.


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 > 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.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Oral
  • Adult
  • Double-Blind Method
  • Female
  • Flushing / chemically induced
  • Food Additives / adverse effects*
  • Food Hypersensitivity / etiology*
  • Food Hypersensitivity / physiopathology
  • Headache / chemically induced
  • Humans
  • Male
  • Middle Aged
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / physiopathology
  • Severity of Illness Index
  • Sodium Glutamate / administration & dosage
  • Sodium Glutamate / adverse effects*


  • Food Additives
  • Sodium Glutamate