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Department of Pharmacology, Faculty of Medicine, Gadjah Mada University, Yogyakarta, Indonesia and * Department of Mathematical Sciences, Faculty of Business and Technology, University of Western Sydney, Australia
2To whom correspondence should be addressed.
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ABSTRACT |
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 TOP ABSTRACT INTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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KEY WORDS: • monosodium glutamate • randomized double-blind challenge • adverse reactions • humans
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INTRODUCTION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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). Since the
first reports of adverse effects of MSG (Kwok 1968
),
numerous studies have been conducted and have yielded no consistent
results. In South East Asia, only one Thai group (Tanphaichitr et al. 1983
) has studied symptomology after MSG ingestion in
local foods (despite the common use of MSG in this region).
The occurrence of psychosomatic symptoms is well known (Shorter 1993
). For example, it is known that many more people believe
they are "allergic" to foods and food additives than are actually
identified on objective examination (Altman and Chiaramonte 1996
). For example, the importance of familiarity and
beliefs in the generation of psychosomatic symptoms has been described
previously for odors; perceived intensity (Dalton 1996
)
and adverse symptoms (Lees-Haley and Brown 1992
) have
been found to be influenced by a subject’s familiarity with an odor
stimulus and beliefs regarding its effect on health.
Because MSG is an effective flavor enhancer, it is questionable that
its taste can really be masked by food. In the earlier Thai study
(Tanphaichitr et al. 1983
), although the ability of
subjects to identify the MSG taste in food was controlled, and no
adverse symptoms were reported after the ingestion of
MSG-containing meals, it could be argued that the subjects tasted
the MSG, and because it was an accepted flavor, elaborated or reported
no symptomology. In the one study that used a combination of a food and
encapsulated MSG [to prevent tasting the MSG (Tarasoff and Kelly 1993
)], the subjects were mainly Caucasian, and the food
was a Western style light snack, not a full breakfast as is consumed
frequently by Asians.
Hence, because it prevented the taste of MSG in the mouth, we decided
to use the design employed by Tarasoff and Kelly (1993)
in a group of healthy Indonesian subjects to evaluate the prevalence of
adverse symptomology in response to the ingestion of MSG in combination
with a typical Indonesian meal.
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SUBJECTS AND METHODS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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Subjects were recruited through advertisements in three subdistricts of
Yogyakarta municipality. To avoid demand bias, suggestive wordings such
as "MSG," "Chinese Restaurant Syndrome" and "adverse
effect" were not used in advertisements (Kerr et al. 1979
). The incentive for healthy volunteers, who were not
self-identified MSG responders, to participate in a 3-d study was
the provision of a small fee. They were registered by a representative
of each subdistrict and were then referred to the Department of
Pharmacology, Faculty of Medicine, Gadjah Mada University for further
examination.
Candidate subjects were excluded from the study if they were pregnant
or had a history of any of the following conditions: bronchial asthma,
general allergy syndromes, epilepsy, diabetes mellitus, moderate or
severe hypertension, gastric or duodenal ulcer, alcoholism, drug
dependence or psychiatric disease. They were also excluded if they had
been taking prescription drugs 
1 wk before the study began. Otherwise
healthy subjects of either sex, between the ages of 18 and 65 y,
were recruited into the study.
The aim and design of the study were explained, and informed consent forms were signed by the subjects before their participation. Medical histories and physical examinations were completed before study commencement. Healthy volunteers (n = 52) were selected (mean age 29.6 ± 6.5 y; mean mass 53.4 ± 7.4 kg; mean height 159.9 ± 7.7 cm).
Experimental protocol.
Opaque capsules were filled with food-grade MSG (P. T. Ajinomoto Indonesia, Jakarta, Indonesia) or pharmaceutical grade lactose (supplied by Faculty of Pharmacy, Yogyakarta, Indonesia). Each capsule contained one of the following: 1) 1.0 g lactose, 2) 0.5 g of MSG and 0.5g of lactose powder, or 3) 1.0 g MSG. Treatment packages containing either placebo or MSG capsules were prepared by the Faculty of Pharmacy of the University. A random table was used to code the packages. The master code was stored with confidentiality in a sealed envelope and was opened only after completion of the study.
A double-blind, randomized, controlled protocol was used. Participants were allocated randomly to each of three treatments successively on each day; i.e., capsules with 1.5 g MSG, 3 g MSG or placebo (lactose). The list for assigning subjects to treatment was generated using simple randomization with crossover, to ensure an equal number of subjects in each treatment.
Subjects arrived in the morning at the Department of Pharmacology after
fasting for 10 h. Blood pressure, and pulse and respiratory rates
were measured (in triplicate), and the subjects then ingested three
capsules containing MSG or placebo. A standardized breakfast was
provided and consumed immediately after capsule ingestion. Thereafter,
blood pressure, and pulse and respiratory rates were again measured,
and the subjects were asked to go about their normal activities (but to
refrain from eating, except for bread and snacks that did not contain
added MSG). Standardized lunches and dinners were also provided during
test days. All standardized meals were prepared without added MSG at
the Department of Pharmacology. Lunch and dinner were delivered to the
subjects by research assistants (Table 1
).
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Treatment and statistical analysis of results.
Reported symptoms were grouped by the investigators into 10 standard
symptom headings, as listed in Table 2
. The Friedman test, which is the nonparametric equivalent of the
two-way ANOVA procedure, was conducted using MINITAB (Version 8.1,
Minitab, State College, PA). Differences in period effect were tested
separately for the three challenge days. If the probability level was
< 0.05 (P < 0.05), the statistical tests
were considered significant.
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RESULTS |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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; although the number is too small for convincing
statistical analysis, there was generally no difference among the
groups. The incidence of nausea at 1.5 g MSG was higher than
placebo, but was also higher than that at 3.0 g MSG.
Because the incidence of each symptom was low, the intensities of the
symptoms (symptom score) were summed for further statistical analysis
to maximize the chance of detecting possible responses. The Friedman
test for the sum of symptom values, factored by three MSG levels,
revealed no significant difference among the three treatment groups
(Table 3
). The Friedman test of the results shows that the P-value
was always > 0.05 and that consequently, the symptoms after MSG
ingestion were not different from symptoms after placebo ingestion.
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|
DISCUSSION |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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In this study, there were no differences in the symptoms reported
between MSG and placebo. A higher incidence of nausea was seen at 1.5g
MSG (vs. placebo), but because there was no dose response, this effect
was probably not MSG-related. Headache has been reported by some to
be a typical adverse effect of MSG ingestion (Kenney and Tidball 1972
, Schaumberg 1968
). However, it should be
noted that when MSG taste is successfully masked, as in our study, no
difference in the incidence of headache is observed between MSG and
placebo test days. For subjective symptoms such as headache, the
importance of successfully masking the sensory (taste) properties of
the presumed active substance in a double-blind trial cannot be
overemphasized.
MSG has been subjected to repeated regulatory review over the past
decade (Commission of the European Communities 1991
,
Joint FAO/WHO Expert Committee on Food Additives 1988
,
Life Sciences Research Office 1995
) and has been deemed
safe for the general population. Our results in healthy Indonesian
subjects, suggesting that adverse effects are not elicited by MSG (at
doses up to 3 g), support this conclusion.
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FOOTNOTES |
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REFERENCES |
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TOPABSTRACTINTRODUCTIONSUBJECTS AND METHODSRESULTSDISCUSSIONREFERENCES |
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1. Altman D. R., Chiaramonte L. T. Public perception of food allergy. J. Allergy Clin. Immunol. 1996;97:1247-1251[Medline]
2. Commission of the European Communities Food-science and techniques. First series of food additives of various technical functions. Reports of the Scientific Committee for Food (25th series) 1991 Luxembourg.
3.
Dalton P. Odor perception and beliefs about risk. Chem. Senses 1996;21:447-458
4. Joint FAO/WHO Expert Committee on Food Additives Toxicological Evaluation of Certain Food Additives, WHO Food Additives Series No. 22 1988: IPCS Cambridge University Press Cambridge, UK.
5. Kenney R. A., Tidball C. S. Human susceptibility to oral monosodium L-glutamate. Am. J. Clin. Nutr. 1972;25:140-146[Medline]
6. Kerr G. R., Wu-Lee M., El-Lozy M., McGandy R., Stare F. J. Food-symptomatology questionnaires: risks of demand-bias questions and population-biased surveys. Filer L. J., Jret al eds. Glutamic Acid: Advances in Biochemistry and Physiology 1979:375-387 Raven Press New York. NY.
7. Kwok R.H.M. Chinese-restaurant syndrome. N. Engl. J. Med. 1968;278:296
8. Lees-Haley P. R., Brown R. S. Biases in perception and reporting following a perceived toxic exposure. Percept. Mot. Skills 1992;75:531-544[Medline]
9. Life Sciences Research Office Analysis of Adverse Reactions to Monosodium Glutamate (MSG) 1995 Federation of American Societies for Experimental Biology. American Institute of Nutrition Publication Bethesda, MD.
10. Muhilal T., Tarwotjo I. G. The prospect of remedying vitamin A deficiency through certain food stuff fortification. Gizi Indonesia 1986;11:7-12
11. Nicholas P. G., Jones S. M. Monosodium glutamate in Western Australian foods. Chem. Aust. 1991;58:556-558
12. Schaumburg H.H.Y., Byck R., Gerstel R., Mashman J. H. Monosodium L-glutamate: its pharmacology and role in the Chinese restaurant syndrome. Science (Washington DC) 1968;163:826-828
13. Shorter E. From Paralysis to Fatigue: A History of Psychosomatic Illness in the Modern Era 1993 Free Press
14. Tanphaichitr V., Srianujata S., Pothisiri P., Sammasut R., Kulapongse S. Post prandial responses to Thai foods with and without added monosodium L-glutamate. Nutr. Rep. Int. 1983;28:783-792
15. Tarasoff L., Kelly M. F. Monosodium L-glutamate: a double-blind study and review. Food Chem. Toxicicol. 1993;31:1019-1035
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