The study showed that the result remained the same even after taking into account physical activity and total calorie intake.
Researchers at University of North Carolina at Chapel Hill School of Public Health and in China studied more than 750 Chinese men and women, aged between 40 and 59, in three rural villages in north and south China.
The majority of study participants prepared their meals at home without commercially processed foods. About 82 percent of the participants used MSG in their food.
Those users were divided into three groups, based on the amount of MSG they used.
The researchers found that the group, which used the most MSG, were nearly three times more likely to be overweight than non-users.
"Animal studies have indicated for years that MSG might be associated with weight gain. Ours is the first study to show a link between MSG use and weight in humans," said Ka He, M.D., assistant professor of nutrition and epidemiology at the UNC School of Public Health.
Because MSG is used as a flavour enhancer in many processed foods, studying its potential effect on humans has been difficult.
He and his colleagues chose study participants living in rural Chinese villages because they used very little commercially processed food, but many regularly used MSG in food preparation.
"We found that prevalence of overweight was significantly higher in MSG users than in non-users. We saw this risk even when we controlled for physical activity, total calorie intake and other possible explanations for the difference in body mass. The positive associations between MSG intake and overweight were consistent with data from animal studies," he said.
The study is published in the journal Obesity.