Multicenter, double-blind, placebo-controlled, multiple-challenge evaluation of reported reactions to monosodium glutamate

Background: The frequency of reactions reported to occur after the consumpt ion of monosodium glutamate (MSG) is the subject of controversy. Objective: We conducted a multicenter, multiphase, double-blind, placebo-co ntrolled study with a crossover design to evaluate reactions reportedly cau sed by MSG. Methods: In 3 of 4 protocols (A, B, acid C), MSG was administered without F ood. A positive response was scored if the subject reported 2 or more sympt oms from a list of 10 symptoms reported to occur after ingestion of MSG-con taining foods within 2 hours. In protocol A 130 self-selected reportedly MS G-reactive volunteers were challenged with 5 g of MSG and with placebo on s eparate days (days 1 and 2), Of the 86 subjects who reacted to MSG, placebo , or both in protocol A, 69 completed protocol B to determine whether the r esponse was consistent and dose dependent. To further examine the consisten cy and reproducibility of reactions to MSG, 12 of the 19 subjects who respo nded to 5 g of MSG but not to placebo in both protocols A and B were given, in protocol C, 2 challenges, each consisting of 5 g of MSG versus placebo. Results: Of 130 subjects in protocol A, 50 (38.5%) responded to MSG only, 1 7 (13.1%) responded to placebo only (P <.05), and 19 (14.6%) responded to b oth. Challenge with increasing doses of MSG in protocol B was associated wi th increased response rates. Only half (n = 19) of 37 subjects who reacted to 5 g of MSG but not placebo in protocol A reacted similarly in protocol B , suggesting inconsistency in the response. Two of the 19 subjects responde d in both challenges to MSG but not placebo in protocol C; however, their s ymptoms were not reproducible in protocols A through C. These 2 subjects we re challenged in protocol D 3 times with placebo and 3 times with 5 g of MS G in the presence of food. Both responded to only one of the MSG challenges in protocol D. Conclusion: The results suggest that large doses of MSG given without food may elicit more symptoms than a placebo in individuals who believe that the y react adversely to MSG. However, neither persistent nor serious effects f rom MSG ingestion are observed, and the responses were not consistent on re testing.