Deciphering the MSG controversy.

Monosodium glutamate (MSG), a common flavor enhancer in various canned food and stereotypically associated with food in Chinese restaurants, has been claimed and tested to have side effects including headache and dizziness. However, the mechanism behind MSG-induced headache was not clear. Using dissociated mouse neuronal culture and cell injury assays, we determined whether incubation of neurons with clinically relevant concentrations of MSG induces cell swelling or death, and whether any measure can be taken to prevent or reduce MSG effects. We demonstrated that (1) Treatment with MSG induces a dose-dependent swelling and death of mature neurons (12-14 days in culture) with little effect on young immature neurons (<1 week in culture). The threshold concentration of MSG for neuronal injury is 3 microM; (2) MSG only injures neurons with little effect on glial cells; (3) Boiling MSG does not affect its toxicity but the addition of Vitamin C provides significant protection against MSG toxicity; (4) Pretreatment of neurons with a low dose of MSG reduces subsequent injury by a large dose of MSG. Together, our studies suggest that the side effect of MSG may be mediated, at least in part, by its toxic effect on brain neurons. Pre-exposure to low doses of MSG or the use of Vitamin C may prevent or reduce the side effects of MSG.