The MSG Files, Part IV: Chinese Restaurant Syndrome

Hi everyone! The weekend may be over, but The MSG Files are back! Today we’ll finally be delving into “Chinese Restaurant Syndrome”, the three words that dealt a serious blow to the MSG industry. The term “Chinese Restaurant Syndrome” has taken up a great deal of space in popular and scientific literature alike. For decades, people have wondered about its symptoms, mechanisms, prevalence, and legitimacy.

Dr. Robert Ho Man Kwok coined the term “Chinese restaurant syndrome” after noticing that he experienced discomfort whenever he would eat at Chinese restaurants.

The words “Chinese restaurant syndrome” (CRS) were first used by a Chinese-American doctor from Maryland in 1968, the same year scientists warned the public that artificial sweeteners potentially caused cancer. The doctor, Robert Ho Man Kwok, wrote a letter to the New England Journal of Medicine describing the discomfort he experienced after eating at Chinese restaurants. In his letter, he explained:

I have experienced a strange syndrome whenever I have eaten out in a Chinese restaurant … which usually begins 15 to 20 minutes after I have eaten the first dish, lasts for two hours, without any hangover effect. The most prominent symptoms are numbness at the back of the neck, gradually radiating to both arms and the back, general weakness and palpitation.

Dr. Kwok went on to suggest some possible causes, including allergies to soy sauce ingredients; effects associated with high sodium intake, such as dehydration and low blood potassium; and even mild intoxication from Chinese restaurants’ generous use of cooking wine.

A year later, in 1969, the publication of an article in Science, entitled “Monosodium L-glutamate: its pharmacology and role in the Chinese Restaurant Syndrome“, threw MSG into the spotlight as the cause of CRS. The study, authored by Herbert Schaumburg et al., found that consumption of MSG could elicit burning sensations, facial pressure, and chest pain. The article achieved wide circulation, and before long, Chinese restaurant syndrome had captured the public’s attention. People began to complain of varied symptoms including headache, numbness, tingling, heart palpitations, nausea, weakness, flushing, sweating, and drowsiness, in addition to the responses observed by Schaumburg and colleagues.

However, shortly thereafter, a study published in a 1970 issue of Nature asserted that prior investigations of CRS had failed to include any “experimental condition which can be used to assess the significance of subjective reactions”. In other words, claimed authors Morselli and Garattini, there was no way of knowing whether participant or experimenter bias skewed the results of Schaumburg et al.’s 1969 study.

In response, Morselli and Garattini carried out their own study using research techniques designed to eliminate any subjective biases of both the researchers and their subjects. These included double-blind trials, in which treatment assignments were withheld from both the experimenters and the study participants until the end of the study. Morselli and Garattini also used a crossover technique, in which each participant received both the control treatment (beef broth) and the experimental treatment (beef broth with MSG). This had the advantage of reducing any confounding variables that would result from comparing two different subjects against one another. Ultimately, Morselli and Garattini found no significant difference between participant reactions to 3 grams of MSG and the placebo treatment. This was the first of several studies over the next few decades to conclude that, if measures were taken to minimize researcher and participant bias, MSG consumption would not elicit any objective changes in health.

That being said, minimizing bias was not the easiest of tasks, and scientists questioned the validity of early experimental designs. Some were concerned about the distinct taste of MSG, worrying that the tastes of MSG and control treatments were different enough to distort participant reactions and nullify the placebo effect. There were also criticisms regarding participant pools. Several early studies used subjects who identified as MSG-sensitive, which probably skewed results in favor of CRS prevalence. In fact, Dr. George Kerr and colleagues found that individuals who simply knew of CRS were 10 times more likely to report CRS-like symptoms in questionnaires than the general population. Given that scientists would inform their subjects about CRS and its symptoms before conducting their studies, it was likely that their results overestimated the effects of CRS. Furthermore, some studies used the same participants over multiple trials, which potentially “trained” these individuals to distinguish the taste of MSG.

A 1993 study found that, when subjects believed they were participating in a study to evaluate a new soft drink, they showed no significant differences in response to MSG and placebo treatments.

In 1993, Tarasoff and Kelley conducted a study that they believed addressed these potential flaws in previous experiments. They incorporated MSG in capsules and a soft drink to eliminate any taste bias, performed more stringent statistical analyses, and perhaps most critically, took out any mention of MSG or CRS by publicizing the study as an “evaluation of a new soft drink”. In their study of 71 subjects who were given MSG in doses of 1 to 3.15 grams, the scientists found no significant difference between participant reactions to the experimental and control treatments.

In 2000, scientists found that, for individuals who identify as MSG-sensitive, large doses of MSG intake without food may induce more CRS-like symptoms than a placebo treatment. They could not, however, draw any definitive conclusions because participant responses were infrequent and inconsistent. The researchers did not observe similar responses when MSG was delivered with food.

More recently, a 2009 literature review of decades of research on Chinese restaurant syndrome concluded that there is no reason to believe that the MSG found in typical diets causes any of the symptoms attributed to CRS. While studies have suggested that large doses of MSG (>3 g) might elicit some responses when ingested without food on an empty stomach, these situations are unrealistic. Moreover, claims that MSG might cause other conditions such as asthma, hives, angioedema, or rhinitis are largely unfounded.

You will often hear MSG critics citing studies that show MSG toxicity in animals, particularly rodents. As early as 1969, a year after Dr. Kwok first penned the words “Chinese restaurant syndrome”, a study found that MSG caused lesions in the hypothalamus region of the brain in neonatal mice. Furthermore, in adulthood these same mice had higher incidence of obesity and sterility. Scientists also found that MSG injections decreased the levels of key hormones and caused size reduction of gonads, adrenal glands, and thyroid glands in rats.

These results are sobering, but not particularly relevant to informing our usage of MSG as a food additive. In studies involving newborn mice, MSG was delivered via injection or tube, without the presence of food, and at a level of 500 mg/ kg. Even with an extreme MSG dose of 60 mg/kg (which is 30 times greater than our average daily intake and a dosage high enough to actually make food taste more unpleasant), humans plasma levels of glutamate are 57 times less than the levels that achieved damage in mice. When the same concentration of MSG is delivered with other nutrients, such as in tomato juice, plasma levels decrease to 110 times less than neurotoxic levels.

Studies on animals other than rodents have been even less convincing. Though some studies have reported minor brain lesions in infant monkeys treated with high dosages of MSG, others have refuted such findings. Ultimately, there just aren’t enough available data to draw conclusions about the effects of MSG on non-human primates.

All things considered, these studies reveal that MSG is highly unlikely to cause serious health problems in humans. Though high amounts of MSG have elicited symptoms in rodents, there is nothing to suggest that these pathways also manifest themselves in humans. Furthermore, MSG studies with animal subjects have all involved delivery quantities and methods, such as subcutaneous injections, that far exceed the severity of human usage of MSG as a food additive. In fact, a multigenerational study found that, when MSG is delivered to rodents in food, they no longer experience brain lesions, obesity, sterility, or for that matter, any observable deleterious effects. Science has consistently shown that, when MSG is administered as a food additive, it does no harm.

So then, what, short of mass hysteria, might account for CRS?

Some other proposed mechanisms of CRS include acetylcholine imbalance, vitamin deficiency, vasospasm, gastric reflux, and histamine toxicity.

There have been numerous proposed mechanisms for Chinese restaurant syndrome, one of which suggests that consumption of MSG increases acetylcholine levels in the body. However, these explanations are not backed by much evidence, and require follow-up studies to substantiate their claims.

Acetylcholine is a neurotransmitter like glutamate. In 1971, scientists observed that consumption of large doses of MSG can cause a 28% decrease in the enzyme that processes acetylcholine, presumably in response to an increase in acetylcholine. Given that injection of acetylcholine can cause flushing, heating, head throbbing, palpitation, and tightness in the chest, the scientists suggested that CRS was the result of a surge in acetylcholine levels. However, there’s been little subsequent evidence to support this story in the literature.

Some folks have found that vitamin B6 can prevent CRS symptoms in MSG-sensitive individuals, and propose that CRS is a result of vitamin B6 deficiency. One study suggested that  MSG irritates the esophagus and causes gastric reflux. Still others believe that naturally-occurring histamine can reach levels high enough in Chinese foods to cause symptoms similar to that of scombroid poisoning. Though these studies present compelling explanations of CRS, they are limited in scope and have not received much follow-up research to support their claims.

In the end, Chinese restaurant syndrome may arise from any number of pathways. Certainly, Chinese take-out can be greasy and not all that dissimilar from other unhealthy fast foods. Moreover, overeating of any sort can cause feelings of discomfort. Another possibility is that people may have adverse reactions to other ingredients in Chinese food, such as peanuts, shellfish, or cooking wine. At present, there is still no definitive answer to what causes the mysterious ailment.

We do know, however, that MSG does not seem to be the culprit. Decades of scientific research have proved, time and again, that dietary MSG is not a hazard to human health for the general population. It is possible that an extremely small portion of the population (Food Standards Australia New Zealand puts the statistic at less than 1%) may experience short-term side effects in response to high levels of MSG consumption, but no study has been able to show that MSG causes anything more severe than these transient, mild symptoms.

In fact, scientific studies have been so unsuccessful at demonstrating any dangers associated with dietary MSG that no governmental entities have banned or placed limits on MSG consumption. The FDA recognizes MSG as GRAS, or “generally recognized as safe”, and requires that it be labeled when present in foods. (See Part III‘s list of commonly used names for glutamic acid-derived food additives.) Therefore, if you do believe you are sensitive to MSG, it is simple enough to avoid it by reading the fine print on your groceries, or asking restaurants if they add MSG to their food. Meanwhile, there’s no need to spoil the fun for the majority of people who can enjoy some casual MSG in their diets.

Keep your eyes peeled for Part V, which will focus on the cultural perceptions surrounding MSG, and a run-down of the pro-/con- MSG campaigns that continue to be waged today…