REVIEW

Reconsidering the effects of monosodium glutamate: Aliterature reviewMatthew Freeman, CNP, MPH (Adult Nurse Practitioner)

OhioHealth, Columbus, Ohio

Keywords

Monosodium glutamate; food allergy;

headache.

Correspondence

Matthew Freeman, CNP, MPH, Clinical

Instructor, The Ohio State University College of

Nursing, Newton Hall. 1585 Neil Avenue,

Columbus, OH 43210.

Tel: (614) 292-4041; Fax: (614) 292-4535;

Email: freeman.224@osu.edu

Received: October 2005; accepted: March

2006

doi:10.1111/j.1745-7599.2006.00160.x

Abstract

Purpose: This article reviews the literature from the past 40 years of research

related to monosodium glutamate (MSG) and its ability to trigger a migraine

headache, induce an asthma exacerbation, or evoke a constellation of symptoms

described as the ‘‘Chinese restaurant syndrome.’’

Data sources: Literature retrieved by a search using PubMed, Medline, Lexis-

Nexus, and Infotrac to review articles from the past 40 years.

Conclusions: MSG has a widespread reputation for eliciting a variety of

symptoms, ranging from headache to dry mouth to flushing. Since the first

report of the so-called Chinese restaurant syndrome 40 years ago, clinical trials

have failed to identify a consistent relationship between the consumption of

MSG and the constellation of symptoms that comprise the syndrome. Further-

more, MSG has been described as a trigger for asthma and migraine headache

exacerbations, but there are no consistent data to support this relationship.

Although there have been reports of an MSG-sensitive subset of the population,

this has not been demonstrated in placebo-controlled trials.

Implications for practice: Despite a widespread belief that MSG can elicit

a headache, among other symptoms, there are no consistent clinical data to

support this claim. Findings from the literature indicate that there is no

consistent evidence to suggest that individuals may be uniquely sensitive

to MSG. Nurse practitioners should therefore concentrate their efforts on

advising patients of the nutritional pitfalls of some Chinese restaurant meals

and to seek more consistently documented etiologies for symptoms such as

headache, xerostomia, or flushing.

Introduction

Chinese cuisine has been a part of American culture since

the mid-19th century. Beginning with the first restaurant

in San Francisco in 1949, there are now more than 40,000

Chinese restaurants in the United States. Chinese cuisine

boomed after 1965, when the United States loosened

immigration laws, permitting more Asian immigrants.

As immigrants arrived, restaurants proliferated (Shute,

2005).

In 1968, a report appeared in the New England Journal of

Medicine,describing a constellation of symptoms in patients

who dined in one of the growing number of Chinese

restaurants. The symptoms of the so-called Chinese

restaurant syndrome (CRS) included numbness, radi-

ating to the back, arms, and neck; weakness; and pal-

pitations (Kwok, 1968). Later reports included other

symptoms, such as tightness, flushing, tearing, dizziness,

syncope, and facial pressure (Geha et al., 2000a). The orig-

inal author suggested several possible culprits for these

symptoms, including cooking wine, sodium content, and

the seasoning monosodium glutamate (MSG) (Kwok).

MSG attracted the most attention as a possible source of

CRS symptoms. MSG, known by its chemical name, was

previously unknown in American culinary vocabulary,

and thus lacked the familiarity of common food additives

like wine or salt.

482 Journal of the American Academy of Nurse Practitioners 18 (2006) 482–486 ª 2006 The Author(s)Journal compilation ª 2006 American Academy of Nurse Practitioners

What is MSG?

MSG is a salt of glutamic acid, one of the most abundant

amino acids.Althoughglutamic acid isnaturally occurring, it

is produced commercially through molasses, sugar cane, and

sugarbeet fermentation. Glutamate is not an essential amino

acid in its own right; instead, it supplies an amino group for

the synthesis of other amino acids. Glutamate serves other

functions in the body as well, serving as an energy source for

certain tissues and as a substrate for glutathione synthesis

(Food Standards Australia New Zealand, 2003).

Although MSG is naturally occurring in many foods, it is

frequently added as a flavor enhancer. MSG produces

a unique flavor that cannot be provided by other foods.

Sometimes referred toasa ‘‘sixthflavor,’’ MSGelicits a taste

described in Japanese as umami, which translates to

‘‘savory’’ (Birks, 2005). This property was first described

in 1909 with respect to the glutamine content of konbu

seaweed (Federation of American Societies for Experi-

mental Biology, 1995).

Umami is a fundamental component of Japanese cook-

ing. Japanese food scientists and psychologists emphasize

that glutamate and the umami taste do not necessarily

evoke a flavor themselves; instead, umami enhances other

flavors. Saki, for example, has a significant glutamate

content; hence, the Japanese belief that Saki compliments

and enhances a meal (Birks, 2005).

Despite its association with East Asian cuisine, gluta-

mate-rich foods are common in the West. In 2003, a joint

inquiry by the governments of Australia and New Zealand

reviewed previous research exploring the glutamate con-

tent of common foods. According to this research, a typical

Chinese restaurant meal contains between 10 and 1500 mg

of MSG per 100 g. A condensed soup typically contains

between 0 and 480 mg, Parmesan cheese contains 1200 mg,

and packaged sauces or seasonings contain 20 to 1900 mg.

A meal in a Chinese restaurant is therefore likely to contain

more MSG than one might typically consume in a Western

restaurant, but does this difference carry a clinical

significance?

A ‘‘China’’ syndrome?

Initial studies of the so-called Chinese restaurant syn-

drome were plagued with problems. The first study, by

Schaumburg, Byck, Gerstl, and Mashman (1969), dem-

onstrated dose-dependent reactions to MSG in a variety of

delivery methods (soup, water, broth, and intravenous

administration). Although almost all of the subjects

responded, the tests were not all blinded, and there were

only six subjects in the entire study.

Concerns about MSG became more vocal after a cross-

sectional study in 1977 by Reif-Lehrer (1977) of the

Harvard Medical School. The study revealed that perhaps

25% of the population experiences CRS. Few questioned

the study’s validity of a simple cross-section survey despite

the obvious methodological flaws. In the Reif-Lehrer

study, subjects were asked, ‘‘Do you think you get Chinese

restaurant syndrome?’’ and included a description of the

potential symptoms. Consequently, demand bias and

recall bias interfered with the study’s validity. Reif-

Lehrer’s study did not address causality; it merely sug-

gested a correlation between the consumption of Chinese

food and a constellation of symptoms in a population

subset.

Although subsequent studies were incriminating at first

glance, a closer read unveiled methodological flaws,

thereby negating any indictment against MSG. Ghadimi,

Kumar, and Abaci (1971) hypothesized that CRS was

secondary to acetylcholinosis. The symptoms of CRS are

similar to acetylcholinosis: flushing, chest pain, feelings of

warmth; furthermore, glutamate is converted to acetyl-

choline via the tricarboxylic acid cycle. In order to dem-

onstrate his theory, Ghadimi et al. (1971) administered

MSG alone to one test group and administered prophy-

lactic atropine to other test groups. Those who received

atropine in advance did not experience the character-

istic CRS symptoms. Despite the biologic plausibility of

Ghadimi et al.’s study, one must consider that the study

only included 14 subjects.

Other researchers posited differing theories on the origin

of CRS. Folkers et al. (1981) suggested CRS symptoms

were a result of a vitamin B6 deficiency. Although sup-

plemental B6 appeared to prevent CRS symptoms, the

study was small and has not been replicated since. Another

study by Kenney (1986) suggested that esophageal irrita-

tion from MSG was the mechanism that produced MSG

symptoms. Kenney’s study, however, does not explain

why MSG capsules caused symptoms in other studies.

Expanding upon Ghadimi et al.’s (1971) preliminary

findings, Morselli and Garattini (1970) experimented by

administering 3 g of MSG masked in beef broth. This was

a double-blind, placebo-controlled crossover study of 17

subjects. Morselli and Garattini found no significant differ-

ences in symptoms between the test and placebo groups,

thereby raising one’s suspicion about the validity of the

prior smaller studies.

Tarasoff and Kelly (1993) raised serious questions about

the validity of prior studies. There are significant measure-

ment issues that affect one’s ability to evaluate MSG with

a robust experimental design. For example, MSG is not

routinely consumed on its own; instead, it is served with

food. A researcher must therefore separate the confound-

ing effects of each food substance consumed with MSG.

But studies in the absence of food perhaps cannot be

extrapolated to the general population because one does

M. Freeman Reconsidering the effects of MSG

483

not routinely consume MSG in significant quantities

without food.

Tarasoff and Kelly (1993) also questioned other aspects

of previous experimental designs, such as the lack of both

randomization and adequate sample size, thus reducing

the power of standard statistical analyses. Furthermore,

‘‘demand bias’’ may have increased the high placebo

response to prior studies. In these instances, subjects

consumed MSG or a placebo and were then asked if they

experienced any of several CRS symptoms. The power of

suggestion may have led subjects to feel symptoms that

they might not have considered.

Researchers at the University of Western Sydney

attempted to create a more robust study design. Without

mentioning MSG, the researchers recruited 71 fasting

subjects to consume 5 g of MSG followed by a standardized

breakfast. The subjects then had to answer open-ended

questions that reduced demand bias, such as ‘‘did you taste

anything unusual after breakfast?’’ The most common

response—for the placebo or for MSG—was nothing.

One subject claimed to be ‘‘MSG sensitive’’ but only had

a strong reaction to the placebo and not to MSG (Tarasoff &

Kelly, 1993).

Further studies were similarly unconvincing. Yang

(1997) administered 5 g of MSG on an empty stomach

to 61 subjects with a self-reported history of MSG sensi-

tivity. There was some evidence that subjects began to

experience headache and flushing above a threshold of 2.5

g of MSG—the equivalent of 200 g of Parmesan cheese on

an empty stomach. Conventional wisdom argues that one

would not ordinarily consume so much MSG without

food, but Yang suggested that MSG could be consumed

at the beginningof a meal, essentially on an empty stomach.

But one must still consider that the MSG would soon be

accompanied by food and would be metabolized more

slowly with food than without.

In 2000, a combined research team from Boston Uni-

versity, Harvard University, Northwestern University, and

the University of California at Los Angeles conducted the

largest study to date of MSG and its potential side effects.

This study, by Geha et al. (2000b), specifically included

subjects who reported a history of MSG sensitivity. The

study was organized to test subjects for any reaction to

MSG, followed by subsequent rechallenges of those

subjects who demonstrated a response. Subjects were

questioned about ‘‘general weakness,’’ ‘‘muscle tightness,’’

flushing, burning, and headache.

In order to control for food intake, the Geha et al.

(2000b) study required subjects to fast for 8 h and state

that they had no symptoms at the beginning of the study.

Tests were double-blind, placebo-controlled, and random-

ized. One of the goals of the study was to identify subjects

with two or more symptoms of MSG sensitivity on multiple

occasions with no demonstrable response to the placebo.

Subjects received 5 g of MSG in the first protocol and were

rechallenged with 0, 1.25, 2.5, and 5 g. The administration

of MSG or placebo followed an 8-h fast, and subjects were

given a standardized breakfast after consuming the test

drink.

In total, 130 subjects were tested at multiple centers,

but only two maintained consistent responses to MSG.

The researchers concluded that there were no reproduc-

ible responses. Despite claims that MSG might cause

headache or other symptoms, the Geha et al. (2000b)

study failed to produce any reproducible symptoms with

no food at all. Furthermore, all of the subjects in the Geha

et al. (2000b) study claimed to have a history of MSG

hypersensitivity.

MSG as an asthma trigger

At least seven studies have explored the possibility that

MSG can serve as a trigger for asthma exacerbations.

Unfortunately, these studies have suffered from small size

and questionable study design.

Allen, Delohery, and Baker (1987) recruited 32 sub-

jects, 14 of whom reported a history of asthmatic

symptoms after eating Chinese food. The researchers

administered escalating doses of MSG (from 0.5 to 2.5

g) on a single-blind basis. The researchers then conducted

pulmonary function tests 12 h after the subjects received

MSG. In order to minimize confounders, subjects were

required to follow a glutamate-restricted diet and certain

asthma medications were withheld. Thirteen of the sub-

jects experienced a reduction of 20% or greater in their

peak expiratory flow. Despite these alarming results, the

study has been criticized for its inadequate measurement

of baseline data. Furthermore, subjects who withheld

regular asthma medications may have merely been expe-

riencing reduced peak flow because of medication with-

drawal. Peak flow is a somewhat subjective response

because it requires effort on behalf of the subject and

encouragement by the researcher (Food Standards Aus-

tralia New Zealand, 2003).

Allen et al.’s (1987) findings were not replicated

in a similar study by Moneret-Vautrin (1987) in the

same year. Only 2 of 30 asthmatic subjects experienced

reducedpulmonary function test results 12hafter aplacebo-

controlled challenge of 2.5 g of MSG. Like Allen et al.’s

study, the design fell into question. Subjects withheld

corticosteroids for 3 weeks prior to the study and with-

held theophylline for 3 days. Like Allen et al.’s study,

the procedure was not double blind and the issue of sub-

jective effort in pulmonary function tests also may have

confounded the results (Food Standards Australia

New Zealand, 2003).

Reconsidering the effects of MSG M. Freeman

484

Studies by Schwartzstein, Kelleher, Weinberger, Weiss,

and Drazen (1987) and Germano, Cohen, Hahn, and

Metcalfe (1991) followed similar protocols. None of the

subjects in Schwartzstein et al.’s (1987) study had a pos-

itive response (i.e. reduction in pulmonary function test

results); one subject responded in the Germano et al.

(1991) study, but the subject did not reproduce this result

in subsequent trials. Woods, Weiner, Thien, Abramson,

and Walters (1998) found no change in forced expiratory

volume in 1 s (FEV1) after 1 and 5 g MSG challenges.

Woessner, Simon, and Stevenson (1999) had one subject

experience a 20% drop in FEV1 after an MSG challenge,

but this finding was not replicated.

Altman, Fitzgerald, and Chiaramonte (1994) found that

11 of the 26 subjects in the trial experienced reduction in

pulmonary function test results. But in two cases, subjects

had a positive result with 3 g of MSG but not with 6 g,

thereby negating any suspicion of a dose-response rela-

tionship between MSG and asthma symptoms.

Although flawed study designs make interpretation of

these studies difficult, it is evident that there is no consis-

tent evidence that MSG can trigger an asthma exacerba-

tion. Although one could argue that broader-scale studies

would be beneficial, the data from these small pilot studies

suggest that an MSG/asthma correlation is unlikely and

that a larger study would not be easily justified.

MSG as a migraine trigger

Radnitz (1990) suggested that MSG causes a ‘‘general-

ized vasomotor reaction,’’ which causes ‘‘throbbing pain at

the temples and a throbbing sensation across the fore-

head.’’ Radnitz’s claim derived not from a clinical trial but

from an ‘‘advice from the Diamond Headache Clinic.’’ She

also argued that those who experience migraine head-

aches are more susceptible to headache triggered by MSG,

but this suggestion is not substantiated by any clinical data.

Leira and Rodrıguez (1995) described how MSG can

trigger a migraine headache because of interference with

acetylcholine synthesis. Leira and Rodrıguez cites the

Radnitz (1990) assertion, which, as described above,

was not derived from a clinical study.

In the absence of clinical data, it is premature to make

any conclusions about MSG as a potential trigger for

migraine headaches. With no consistent data to suggest

that MSG causes any type of headache, much more exten-

sive clinical research would be required to establish a link

between MSG and migraine headaches.

Can Chinese food give you a headache?

With or without MSG, the nutritional makeup of Chi-

nese food leads one to question if the fat or sodium content

might give rise to a headache or other symptoms. Chinese

food is exceptionally high in both sodium and fat. Hurley

and Schmidt (1993) found that an average serving of Kung

Pao chicken contained 76 g of fat; a dish of lo mein noodles

contained 3460 mg of sodium. Sensitive to MSG or not,

one would most certainly be thirsty after consuming 3.5 g

of sodium, and most would probably have an uneasy

stomach after 76 g of fat.

Implications for clinical practice

As Reif-Lehrer (1977) first identified 28 years ago, there

is a widely held belief that MSG causes a variety of symp-

toms. Given the pervasive belief in a ‘‘sensitive’’ subset of

the population, it is difficult for healthcare providers to

educate patients and the public about their beliefs regard-

ing MSG.

Although it is within the realm of biological plausibility

that certain individuals experience a hypersensitivity to

MSG, there are no data to substantiate this claim. Clini-

cians therefore have the responsibility to advise patients

that although it is prudent to monitor one’s diet for

potential headache, migraine, and asthma triggers, MSG

is not likely to be the cause for these symptoms. As with

other food hypersensitivities, patients should avoid placing

unwarranted limits on their diets.

In the case of Chinese food and the so-called Chinese

restaurant syndrome, clinicians have the responsibility to

remind or inform their patients that typical Chinese res-

taurant meals contain high concentrations of fat and

sodium, characteristics that may be of greater concern

than MSG.

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