PRACTICA MEDICAL

CERCETARE TIINIFIC

The addictive behaviour induced by food

monosodium glutamate. Experimental study
Anca BUZESCU, Aurelia Nicoleta CRISTEA, Luminia AVRAM, Cornel CHIRI
Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy,
Carol Davila University of Medicine and Pharmacy, Bucharest

ABSTRACT
Introduction. Glutamic acid under the form of monosodium salt (monosodium glutamate) is regulated
in the EU as a food additive (E 621), a flavoring agent, to give the so-called umami taste. Endogen glutamic acid is the major excitatory neurotransmitter of the central nervous system. Cortico-striatal glutamatergic transmission has been implicated in both the initiation and expression of addiction-related behaviors.
In this paper, we have proposed to examine the extent to which food addictive behavior manifests itself in
experimental animals, after repeated consumption of monosodium glutamate (MSG).
Materials and methods. We have experimented on NMRI adult mice. Monosodium glutamate (MSG)
was given daily, dissolved in water in the drinking bottles, for three weeks. Three doses of MSG were tested.
Each lot of mice had two identical drinking bottles, one with MSG solution, another with plain water. The
consumption of MSG solution was measured daily, together with the consumption of water, for all working
groups.
Results. The mice consumed preferentially the solution of monosodium glutamate (MSG), not the plain
water. The greatest increase in MSG solution consumption, 71,02% (p<0.0001), was noticed in the group
receiveing the highest dose (=1/10 DL50/mice).
Conclusions. We experimentally demonstrated that monosodium glutamate (MSG) may induce an addictive alimentary behavior.
Key words: monosodium salt of glutamic acid (MSG, E 621), addictive behaviour, NMRI mice

INTRODUCTION
Glutamic acid (Glu) is regulated in the EU as
a food additive, flavor enhancer, because it gives
the so-called umami taste (etim. jap. = delicious). It can be used by itself (E 620), or as salts:
monosodium glutamate (MSG - E621), monopotassium glutamate (E 622), calcium diglutamate
(E 623), ammonium glutamate (E 624), magnesium diglutamate (E 625) (1). These additives
are extensively used in Chinese and Japanese

cuisine and in fast food. The glutamic acids

most frequently used salt is MSG (E 621). Romanian legislation on food safety, harmonized with
EU legislation, including EC Regulation 178/2002
on Food Additives For Use In Foods For Human
Consumption No 438/295 of July 2002, published in the Ocial Gazette, Part 1 No. 722, of
October 3 2002, allowes the addition of no
more than 10 g/kg food (= 1 g%) of MSG (E621).
In spices, MSG can be added quantum satis (in
the amount which is needed). The use of MSG

Adres de coresponden:
Aurelia Nicoleta Cristea, MD, PhD, Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, Carol Davila University of Medicine
and Pharmacy, 6 Traian Vuia St., Bucharest, Romania
e-mail: [email protected]

PRACTICA MEDICAL VOL. VIII, NR. 4(32), AN 2013

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PRACTICA MEDICAL VOL. VIII, NR. 4(32), AN 2013

(E621) is not legally permitted in foods for infants and young children.
Since there are no ocial reports of severe
adverse eects, glutamic acid and its salts are
considered safe additives by the Joint Committee of WHO experts and F.A.Q. However, there
have been people who have accused a number
of symptoms associated with MSG consumption
such as: dizziness, headache, weakness, numbness, tremors, palpitations (known as Chinese
restaurant syndrome), or nausea, respiratory
problems, excessive sweating, hyperactivity, sudden mood changes, panic attacks (1,2). But, to
date, a clear relationship between MSG ingestion
and the development of these conditions hasnt
been established (3). Yet a double-blind, placebocontrolled, crossover study with the purpose to
examine the eect of a single intake and repeated monosodium glutamate (MSG) intake revealed that a single intake of MSG may cause
headache and increased muscle sensitivity and
repeated intake of MSG induced mechanical
sensitization in masseter muscle and adverse effects such as headache and short-lasting blood
pressure elevation for which tolerance did not
develop over 5 days of MSG intake (4).
In animal experiments, administration of
monoglutamate sodium in rat pups resulted in
neurotoxicity aecting certain brain areas, such
as arcuate nucleus, together with endocrine and
behavioural dysfunctions (5,6) and also in retinotoxicity (7,8).
Given these informations, the consequences
of chronic consumption of glutamic acid salts
due to their frequent use as food additive,
should be further investigated. The fact that glutamate, associated with food, may lead to a
consumer loyalty due to the umami taste,
generating an addictive alimentary behavior,
should be considered.
Furthermore, in a diet with a high number of
products containing MSG as additive (meat,
poultry, processed food, sauces, soups, marinades, juice, refreshing drinks, etc.), it is possible for an individual to reach and even surpass a
MSG dose of maximum 150 mg/kg/day. In this
situation, of unintentional abuse, the major
problem arises from the fact that glutamic acid
(Glu) is the major neurotransmitter of the glutamatergic transmission, the main central excitatory aminoacidergic transmission (9-11). It has
a large number of physiological roles such as:
trophic role during ontogenesis of CNS, involvement in memory and learning; but also the role
in stimulating the release of dopamine in the
striatum, with implication in addiction (9,12).
230

The excitatory role of the glutamic acid is essential from the early development of the brain,
but an excessive activation of this transmission
can lead to neural degeneration and death. The
overstimulation of glutamatergic receptors determines pathological neurotoxicity, probably
through a high increase of calcium influx into
the neurons and an excesive intraneuronal calcium build-up (13,14) and formation of a large
number of free radicals. Death through ischemia arises, phenomenon which is considered
to be the underlying cause of neurodegenerative ilnesses such as Alzheimer disease, Parkinsons disease, Huntington chorea, Lateral Amiotrophic Sclerosis (9,12).
Glutamic acid homeostasis imbalance generates neuroplasticity changes, especially in the
dopaminergic neurons. This aects communication between the prefrontal cortex and nucleus
accumbens (15,16). Neuroplasticity in corticostriatal circuits is associated with dependence,
and it is an important phenomenon for addictive behavior (17,18).
Given the above-mentioned data on the involvement of glutamatergic transmission in addiction and the enhanced use of glutamic acid
and its salts as food additives (E620-E625), the
aim of this research is focused on investigating
the addictive potential behaviour of MSG. MSG
was dissolved into the drinkining water, at experimental animals.

MATERIALS AND METHODS

Reagents
Monosodium glutamate (MSG = E 621) was
purchased from Sigma-Aldrich.
Experimental animals
48 NMRI mice, adults weighing 20-25 g from
UMF biobase, Bucharest, were used. The mice
were housed in plastic cages, in an air-conditioned animal room, with free access to water
and granulated food. The temperature was between 20oC and 22oC and the relative humidity
was maintained at 35-45%.
All procedures were carried out in accordance with the Directive 86/609/EEC of 24th
November 1986 and The Romanian Government Ordinance 37/30.01.2002, regarding the
protection of animals used for experimental
and other scientific purposes.
Experimental protocol
The animals were divided in four groups of
12 mice, weighting 32 5 g/group. During the 7

RESULTS
The average liquid consumption/group for 25
days, from each bottle, is presented in Table 1.
The percentage dierences in the liquid consumption between bottle A and B are ilustrated
in Figures 1 and 2.
Percentual change in average liquid consumption from both bottles (A + B), compared
to group I is presented in Table 2.

20%

Group I

10%

2.95%

Group II

Group III

Group IV

-30.26%
***

-29.35%
***

0%
-10%
-20%
-30%
-40%

-40.48%
***

-50%
-60%

FIGURE 1. Percentual change of the liquid consumption

bottle B compared with bottle A
Group I

% consumption
bottle B vs. bottle A

100%
80%

Group II Group III

71.02%
***
43.39%
***

60%

Group IV

43.68%
***

40%
20%
0%

-2.87%

-20%

FIGURE 2. Percentual change of the liquid consumption

bottle A compared with bottle B

The percentual change in average liquid consumption from each of the bottles A and B compared to group I (control), is illustrated in Figure 3.
Bottle A Bottle B

30%
Percentualdierence in liquid
consumption vs. control group

days accomodation period, the average water

consumption was evaluted for each group as
150 ml/day. During the experiment, for 25 days,
the mice from every cage received daily 2 bottles of liquid A and B, each bottle containing 200
ml (to ensure a possible increase in liquid consumption over 150 ml), as it follows:
Group I: two bottles, A and B, each
containing 200 ml water;
Groups II, III, IV: two bottles, one A
containing 200 ml of MSG solution and
one B, containing 200 ml water.
Taking into account of the DL50 for MSG in
mice (DL50 = 15,000 mg/kg = 15 g/kg), the concentration of MSG solution from the bottles A
was calculated to ensure the administration of
MSG daily doses of maximum:
Group II: D1= 1/10 DL50/animal;
Group III: D2= 1/20 DL50/animal;
Group IV: D3= 1/40 DL50/animal.
The liquid consumption was determined every day, at an exact interval of 23 hours and 30
minutes, using precise measuring instruments.
The bottles, type A and B, were kept the same
for each group and they always had the same position (left or right) and the same type of content
(water or glutamate solution), in order to mantain the specific odour of the group, to ensure
freedom of rapid acces, without fear and for creating a conditioned reflex regarding the location
of the bottle with glutamate solution.
Statistic analysis was made using the soft
GraphPad Prism vers. 5 (Graphpad Software,
San Diego California USA).

% consumption
bottle B vs. bottle A

PRACTICA MEDICAL VOL. VIII, NR. 4(32), AN 2013

24.18%
*

24.00%
**

21.25%
**

20%
10%
0%
-10%
-20%

-29.47%
***

-16.03%
**

-18.03%
***

-30%

FIGURE 3. Percentual change of the liquid consumption

from bottles A and B, compared with group I

TABLE 1. Medium liquid consumption/bottle/group in 25 days of exposure

Liquid consumption (average volume/bottle/group)
Group I (control)
Group II
Group III
Group IV
Bottle A (ml) Bottle B (ml) Bottle A (ml) Bottle B (ml) Bottle A (ml) Bottle B (ml) Bottle A (ml) Bottle B (ml)
AverageDS 74.11 31.46 76.30 21.79 92.03 21.84 53.81 26.52 91.89 18.93 64.08 22.99 89.86 12.37 62.54 23.89
SEM
5.15
3.58
3.26
4.36
3.16
3.78
1.75
3.93
Dn
DAgostino
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Yes
Pearson
DS standard deviation; Dn normal distribution; SE standard medium error

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PRACTICA MEDICAL VOL. VIII, NR. 4(32), AN 2013

TABLE 2. Total average liquid consumption (bottle A+B) during 25 days of
study

AverageDS
SEM
Dn DAgostino
Pearson test
% vs.
control group
p

Liquid consumption
(average volume/bottles A+B/group)
Group I
Group II
Group III
Group IV
150.4 40.79 145.8 30.52 157.4 28.10 152.4 27.18
6,71
5.02
4.62
4.47
Yes
Yes
Yes
Yes
- 3.03%

4.65%

1.32%

0.3049 ns

0.1103 ns

0.6728 ns

DS standard deviation; SEM standard medium error; Dn normal distribution change; * statistically significant, ** with high statistical significance, *** with extremely
high statistical significance, ns with no statistical significance

DISCUSSIONS
The consumption of water form bottle B decreased statistically significant (p < 0.0001), while
the consumption of monosodium glutamate (MSG)
solution from bottle A increased statistically significant (p < 0.0001), for all three test groups (II, III,
IV), as seen in Figures 1 and 2. The intensity of the
eect is in a direct relation with the concentration
of the solution of MSG given (the greatest increase
in MSG consumption, 71.02%, is noticed in the group receiveing the highest MSG dose (corresponding at 1/10 DL50/mice). For the control group,
group I, the dierence of consumption between
the two bottles is minimum, having no statistical
significance (p > 0.05). On what concerns the total average liquid consumption, the variations
between all four groups have no statistical dierence (as showed in Table 2). In comparison
with the control group, the consumption of water form bottle B decreased statistically significant, while the consumption of MSG solution from
bottle A increased statistically significant for all
three test groups (II, III, IV), illustrated in Figure 3.
Again, a direct relation between the intensity of
the eect and the concentration of the given MSG
solution can be observed (the greatest variations,
a 24,18% increase of MSG solution consumption
and a 29.47% decrease in water consumption,
are noticed between control group I and group II,
the group receiveing the most concentrate solution of glutamate equal to 1/10 DL50/mice).
These results indicate that monosodium glutamat (MSG), used as food additive (E 621), may
influence eating behavior, inducing a loyalty
for glutamate enriched-food and an addictive
behavior. One of the underlying causes of this
phenomenon may be the fact that MSG activates chorda tympani (CT) neurons, by stimulating
separate receptors for Na+, sugars and glutamate, in taste bud cells (2). The specific savoury
232

taste (umami) is elicited by both components

of MSG: glutamate anion and Na+ cation (17). It
must be remembered also that glutamatergic
plasticity in the nucleus accumbens is critical for
the expression of the behaviors related to addiction (18,19). Desensibilization of D2 receptors and sensibilization of glutamatergic pathways are linked at cellular level and are
considered to be molecular mechanisms of conditioning and drug addiction (20-22). Primary
rewards like food and water, when presented in
an unexpected manner, are among the most effective stimuli for dopamine neurons in the ventral tegmental area (VTA) (23) which receive a
major excitatory response from the prefrontal
cortex, and also other brain regions (24), the
major neurotransmission involved being the
glutamatergic transmission (25). The evidence
supports the hypothesis that VTA neural cells
are involved in reward based learning, like the
one involved in drug-addiction (25).

CONCLUSIONS
The purpose of this experimental research
was to investigate the hypothesis that sodium
monoglutamate (MSG), used as food additive
(E621), may influence eating behavior, inducing
a loyalty for glutamate enriched-food and an
addictive behavior.
Statistically significant increase in the consumption of aqueous solution of MSG from
bottles A, accompanied by a significant decrease in water consumption from bottles B, for the
three groups exposed to MSG, but not for the
control group, and also a similar daily total fluid
intake for all 4 groups, verified the working hypothesis of an addictive eect of MSG used as
additive in food.
This conclusion resulting from this animal
experimental research, together with the re-

PRACTICA MEDICAL VOL. VIII, NR. 4(32), AN 2013

search presented in the introduction and in discussions of the paper, highlighting the involvement of endogenous glutamatergic system in
the phenomenon of addiction, raises the question of obvious negative report financial-benefit/
adverse eects cumulative time for MSG as a
food additive.

ACKNOWLEDGEMENT
This paper is supported by the Sectoral Operational Programme Human Resources Development (SOP HRD) 2007-2013, financed from
the European Social Fund and by the Romanian
Government under the contract number
POSDRU/107/1.5/S/82839.

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