REVIEW

Reconsidering the effects of monosodium glutamate: A

literature review
Matthew 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, LexisNexus, 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. Furthermore, 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
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restaurant syndrome (CRS) included numbness, radiating to the back, arms, and neck; weakness; and palpitations (Kwok, 1968). Later reports included other
symptoms, such as tightness, flushing, tearing, dizziness,
syncope, and facial pressure (Geha et al., 2000a). The original 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.

Journal of the American Academy of Nurse Practitioners 18 (2006) 482486 2006 The Author(s)
Journal compilation 2006 American Academy of Nurse Practitioners

M. Freeman

What is MSG?
MSG is a salt of glutamic acid, one of the most abundant
amino acids. Although glutamic acid is naturally occurring, it
is produced commercially through molasses, sugar cane, and
sugar beet 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 to as a sixth flavor, MSG elicits 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 Experimental Biology, 1995).
Umami is a fundamental component of Japanese cooking. 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, glutamate-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 content 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 syndrome were plagued with problems. The first study, by
Schaumburg, Byck, Gerstl, and Mashman (1969), demonstrated 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 crosssectional study in 1977 by Reif-Lehrer (1977) of the

Reconsidering the effects of MSG

Harvard Medical School. The study revealed that perhaps

25% of the population experiences CRS. Few questioned
the studys 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 studys validity. ReifLehrers study did not address causality; it merely suggested 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 acetylcholine via the tricarboxylic acid cycle. In order to demonstrate his theory, Ghadimi et al. (1971) administered
MSG alone to one test group and administered prophylactic atropine to other test groups. Those who received
atropine in advance did not experience the characteristic 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 supplemental B6 appeared to prevent CRS symptoms, the
study was small and has not been replicated since. Another
study by Kenney (1986) suggested that esophageal irritation from MSG was the mechanism that produced MSG
symptoms. Kenneys 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 differences in symptoms between the test and placebo groups,
thereby raising ones 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 measurement issues that affect ones 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 confounding 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
483

Reconsidering the effects of MSG

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
responsefor the placebo or for MSGwas 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 sensitivity. There was some evidence that subjects began to
experience headache and flushing above a threshold of 2.5
g of MSGthe 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 beginning of 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 University, 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 randomized. One of the goals of the study was to identify subjects
with two or more symptoms of MSG sensitivity on multiple
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M. Freeman

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 reproducible 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 subjects, 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 subjects 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 experiencing reduced peak flow because of medication withdrawal. Peak flow is a somewhat subjective response
because it requires effort on behalf of the subject and
encouragement by the researcher (Food Standards Australia 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
reduced pulmonary function test results 12 h after a placebocontrolled 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 withheld theophylline for 3 days. Like Allen et al.s study,
the procedure was not double blind and the issue of subjective effort in pulmonary function tests also may have
confounded the results (Food Standards Australia
New Zealand, 2003).

Reconsidering the effects of MSG

M. Freeman

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 positive 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 relationship between MSG and asthma symptoms.
Although flawed study designs make interpretation of
these studies difficult, it is evident that there is no consistent evidence that MSG can trigger an asthma exacerbation. 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 generalized vasomotor reaction, which causes throbbing pain at
the temples and a throbbing sensation across the forehead. Radnitzs claim derived not from a clinical trial but
from an advice from the Diamond Headache Clinic. She
also argued that those who experience migraine headaches are more susceptible to headache triggered by MSG,
but this suggestion is not substantiated by any clinical data.
Leira and Rodrguez (1995) described how MSG can
trigger a migraine headache because of interference with
acetylcholine synthesis. Leira and Rodrguez 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 extensive 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 Chinese 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 symptoms. 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 regarding 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. Clinicians therefore have the responsibility to advise patients
that although it is prudent to monitor ones 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 restaurant meals contain high concentrations of fat and
sodium, characteristics that may be of greater concern
than MSG.

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