*Corresponding Author Address: Dr. Tushar Kanti Bera,, Assistant Professor, Department of Physiology, Universal College of Medical
Sciences, Bhairahawa, Lumbini Zone, Nepal; Email: firstname.lastname@example.org
World Journal of Pharmaceutical Sciences
ISSN (Print): 2321-3310; ISSN (Online): 2321-3086
Published by Atom and Cell Publishers © All Rights Reserved
Available online at: http://www.wjpsonline.org/
Effects of monosodium glutamate on human health: A systematic review
Tushar Kanti Bera*, Sanjit Kumar Kar, Prem Kumar Yadav, Prithwiraj Mukherjee, Shankar Yadav, Bishal
Department of Physiology, Universal College of Medical Sciences, Bhairahawa, Lumbini Zone, Nepal
Received: 03-03-2017 / Revised: 30-03-2017 / Accepted: 17-04-2017 / Published: 26-04-2017
Monosodium glutamate (MSG) is one of several forms of glutamic acid found in foods, in large part because
glutamic acid (an amino acid) is pervasive in nature. MSG is used in the food industry as a flavor enhancer with
an umami taste that intensifies the meaty, savory flavor of food, as naturally occurring glutamate does in foods
such as stews and meat soups. MSG has been used for more than 100 years to season food, with a number of
studies conducted on its safety. Under normal conditions, humans can metabolize relatively large quantities of
glutamate, which is naturally produced in the gut by exopeptidase enzymes in the course of protein hydrolysis.
The median lethal dose (LD50) is between 15 and 18 g/kg body weight in mice and rats, respectively, five times
greater than the LD50 of salt (3 g/kg in rats). The use of MSG as a food additive and the natural level of glutamic
acid in foods are not toxicological concerns in humans. The U.S. Food and Drug Administration have given
MSG it’s generally recognized as safe (GRAS) designation. A popular belief is that large doses of MSG can
cause headaches and other feelings of discomfort, known as ‘Chinese Restaurant Syndrome’ (CRS), but double-
blind tests fail to find evidence of such a reaction. The European Union classifies it as a food additive permitted
in certain foods and subject to quantitative limits.
Keywords: MSG, Chinese restaurant syndrome, oxidative stress, appetite enhancer, oral care
Foods have two main functions, i.e. they provide
nutrition and an occasion for a pleasurable social
event. Both functions are fulfilled only if a food is
actually consumed. A food composed of the
nutritional elements required for an optimal diet
that is unattractive and thus not consumed provides
no nutrition. Flavouring systems are of vital
importance in savoury food manufacturing. Many
industrially prepared foods are particularly
attractive to potential consumers primarily because
of their typical flavours. Therefore it's no surprise
that the food industry dealing with these product
segments shows great interest in the use of food or
food ingredients carrying the typical umami taste
and flavour enhancement systems. Flavourings can
play an important nutritional role, particularly in
foods that are not very flavourful, by providing the
needed appeal. Monosodium glutamate (MSG) is
the sodium salt of the amino acid glutamic acid.
Glutamic acid or glutamate is one of the most
common amino acids found in nature. It is the main
component of many proteins and peptides, and is
present in most tissues. It is made commercially by
the fermentation of molasses, but exists in many
products made from fermented proteins, such as
soy sauce and hydrolyzed vegetable protein.
Glutamate is also produced in the body and plays
an essential role in human metabolism . It is a
major component of many protein-rich food
products such as meat, fish, milk and some
vegetables. However, only the free form of
glutamic acid or glutamates has an effect on the
glutamate receptors. When bound to other amino
acids in a protein, it does not stimulate glutamate
receptors. They become partially free during
processing, thereby accentuating their characteristic
flavor properties [2, 3]. The two isomers of
monosodium glutamate are L-glutamate
enantiomer and D-glutamate enantiomer. Only the
L-glutamate enantiomer has flavor-enhancing
properties. Manufactured monosodium glutamate
contains over 99.6% of the naturally predominant
L-glutamate form, which is a higher proportion of
L-glutamate than found in the free glutamate ions
of naturally occurring foods .
Glutamic acid was discovered and identified in
1866 by the German chemist Karl Heinrich
Bera et al., World J Pharm Sci 2017; 5(5): 139-144
Ritthausen, who treated wheat gluten with
sulphuric acid . Kikunae Ikeda of Tokyo
Imperial University isolated glutamic acid as a taste
substance in 1908 from the seaweed Laminaria
japonica (Kombu) by aqueous extraction and
crystallization, calling its taste umami. Ikeda
noticed that dashi, the Japanese broth of
katsuobushi and kombu, had a unique taste not yet
scientifically described (not sweet, salty, sour, or
bitter) . To verify that ionized glutamate was
responsible for umami, he studied the taste
properties of glutamate salts: calcium, potassium,
ammonium, and magnesium glutamate. All these
salts elicited umami and a metallic taste due to the
other minerals. Of them, sodium glutamate was the
most soluble and palatable and the easiest to
crystallize. Ikeda called his product ‘monosodium
glutamate’, and submitted a patent to produce
MSG; the Suzuki brothers began commercial
production of MSG in 1909 as Aji-no-moto
(essence of taste) [5, 7]. The level of glutamates
and free amino acids increases considerably after
ripening or seasoning of certain foods. Especially
certain cheeses due their taste and texture to long
ripening, which increases the presence of amino
acids. These products are often used to enhance the
flavor of meat dishes (Table-1).
Table 1: Natural glutamate content of fresh food -the values is expressed in mg/100g food .
Types of Foods
PROPERTIES OF MSG
Monosodium glutamate (MSG, also known as
sodium glutamate; IUPAC name- Sodium 2-
aminopentanedioate) is the sodium salt of glutamic
acid, one of the most abundant naturally occurring
non-essential amino acids (Fig. 1). The tongue is
sensitive to five flavors- salt, sweet, bitter, sour,
and umami in the Japanese language, the taste of
MSG. ‘Umami’ is used by the Japanese to describe
the taste of MSG as well as the meaty taste of
certain fish and broth . The substances which
constitute the umami taste can be divided in two
One is the -amino acid group, represented
by monosodium glutamate.
5'-nucleotid group, represented by inosine
5'-monophosphate (IMP) and guanosine mono
phosphate (GMP) and their derivatives .
Figure 1: Chemical structure of
Bera et al., World J Pharm Sci 2017; 5(5): 139-144
Food palatability increases with appropriate
concentrations of MSG . The basic sensory
function of MSG is attributed to its ability to
enhance the presence of other taste-active
compounds. Ideal serum levels of Glutamine to
Glutamate appear to be 9 parts Glutamine to 1 part
Glutamate, which is mediated by enzymatic
conversion in various parts of the body as required
by fluctuating levels. When enzyme function is
depressed or electrolytes are deficiency-stressed in
the presence of too much glutamate to too little
glutamine the optimal ratio fails to support aerobic
metabolism. This is the reason why athletes need to
read the labels and consider reducing MSG from
their diet. ‘Monosodium Glutamate’ appears on
labels as "MSG", ‘contains glutamate’,
‘hydrosolated’, or simply a processed protein that
contains "Glutamate", should be limited. Simplified
summary of glutamic acid, glutamate, and
glutamine pathway .
AMMONIA + GLUTAMINE
GLUTAMINE SYNTHASE ENZYME
GLUTAMATE GLUTAMINE (BRAIN) CONVERSION
GABA or GLUTAMATE
ENERGY + GLUTATHIONE + NIACIN GLUTAMINE SYNTHASE
GLUTAMATE OR GABA
GLUTAMINE [SCAVENGES AMMONIA]
EFFECTS OF MONOSODIUM GLUTAMATE
MSG on oxidative stress: More recent studies
have examined other metabolic and toxic effects of
MSG, with a number of the reports showing that
showing the induction of oxidative stress in
different tissues of experimental animals after
administration of chronic doses of MSG [12-14].
Glutamic acid has been suggested as one of the
amino acids utilized by the kidney during
gluconeogenesis since the net uptake of important
gluconeogenic precursors such as lactate, glycerol,
glutamate, glutamine and other amino acids by the
kidney accounts for the turnover of glucose by the
kidney . Increased influx of substances into the
kidney has been associated with various changes
and oxidative stress . This has been
corroborated in more recent reports in which
hyperglycemia caused oxidative stress in the
kidney via the formation of free radicals and altered
the antioxidant reactions catalyzed by ROS
scavenging enzymes . Hyperglycemia is also
known to increase glucose auto-oxidation and
labile glycation or intracellular activation of the
polyol pathway, with the subsequent oxidative
degradation of the glycated protein enhancing the
production of reactive oxygen species .
Monosodium glutamate causes obesity: MSG
may influence you to overeat, leading to obesity.
Researchers from the University of North Carolina
did a study among people in rural China to examine
the effects of MSG. They chose that region because
most people there prepare their meals at home
without processed foods but still use a lot of MSG.
Those who used the most MSG were also the most
likely to be overweight, regardless of how their
total calories and levels of physical activity
Bera et al., World J Pharm Sci 2017; 5(5): 139-144
compared with those who used the least. In other
studies, mice are injected with MSG for the very
purpose of causing them to become obese.
Scientists think MSG causes lesions in the brain
and interferes with its processing leptin [17, 18].
Leptin is a hormone that signals to the brain that
you have had enough to eat, and it shuts off your
appetite and increases your calorie-burning.
Problems with leptin signaling, called leptin
resistance, are factors in obesity.
Monosodium glutamate and cancer: According
to the American Institute for Cancer Research,
studies to uncover MSG's potential ill effects began
in the late 1960s. At that time, some people began
to believe that the additive in dishes they ate at
Chinese restaurants made them sick. Since that
time, scientists have looked and have not found a
link between monosodium glutamate and cancer
. Katherine Zeratsky, a registered and licensed
dietitian with Mayo Clinic, says that people's
complaints about monosodium glutamate vary.
Some say they develop headaches or nausea while
others feel flushed after eating it. Accelerated
heartbeat, chest pain and weakness also are some of
the reactions individuals associate with MSG.
There also are those who say they begin to sweat or
feel a certain pressure or numbness in the face
when exposed to the food additive. The U.S. Food
and Drug Administration requires manufacturers to
indicate on the label that a product has MSG. Read
the list of ingredients before buying canned and
other processed goods. If you have a history of
reacting to monosodium glutamate, do not buy
anything that lists it as an ingredient.
Monosodium glutamate poisoning: Other terms
for MSG are Chinese restaurant syndrome,
glutamate-induced asthma, hot dog headache and
MSG syndrome. The term ‘Chinese restaurant
syndrome’ was first used in the 1960s to describe
the symptoms experienced by some people after
eating in Chinese restaurants. Monosodium
glutamate poisoning refers to a cluster of symptoms
recognized as an adverse reaction to MSG. The
symptoms include headache, sweating, flushing,
heart palpitations, weakness, chest pain and nausea
. Other symptoms are tightness in the face and
burning, numbness and tingling in the face and
MSG on pregnant and lactating women: It is
common practice for expectant women to eat a
varied and well-balanced diet and consume enough
calories to ensure a healthy pregnancy. To facilitate
fetal growth and development, most amino acids
are actively transported across the placenta.
Research indicates that amino acid concentrations
are higher in the fetus, regardless of what the
mother consumes . Both the placenta and fetal
liver play important roles in amino acid (and
specifically glutamate) transport and metabolism
important for fetal development . In rodent
studies, researchers investigated effects of dietary
intake of MSG on reproduction and birth. The
study looked at three generations of mice that were
fed a daily intake of up to 7.2 g/kg of MSG. No
adverse effect was observed in each generation, nor
was there evidence of any incident of brain lesions
in the neonates.
Besides research on the fetus, scientists also
investigated the effect of MSG ingestion on
lactation and breast-fed infants. Upon examination
of lactating women who consumed MSG at 100
mg/kg of body weight, researchers noticed no
increase in the level of glutamate in human milk,
and no effect on the infant’s intake of glutamate.
According to Baker and colleagues, a newborn
infant, through breastfeeding, ingests more free
glutamate per kilogram of body weight than during
any other period of its life. American Academy of
Pediatrics Committee stated that MSG has no effect
on lactation and poses no risk to the consuming
MSG on children: It has been speculated that
children would metabolize oral MSG more slowly
than adults. However, research conducted by
Stegink and colleagues at the University of Iowa
showed that children as young as one year old
metabolize glutamate as effectively as adults. In the
study, infants were fed beef consommé providing
MSG at various dosage levels of 0, 25 and 50
mg/kg of body weight. Researchers measured the
infant’s plasma glutamate levels and, after
comparing the children’s plasma levels to those of
adults, found no higher plasma glutamate values
for children . Additionally, scientific evidence
has not implicated MSG in attention deficit
hyperactivity disorder or other behavioral problems
in children. For the general population, MSG does
not pose a health risk . Based on the scientific
evidence upholding the safety and efficacy of
MSG, the Select Committee on GRAS Substances
(SCOGS) concluded in 1980 that there is no
evidence that demonstrates reasonable grounds to
suspect a hazard to the public when glutamic acid
or its salts are used at current levels and manners
now practiced .
MSG and neurological effects: MSG is a well-
known compound in research circles used to fatten
up rats for experimentation, because it dramatically
increases insulin production. According to
‘Contemporary Nutrition,’ the food additive
industry readily admits that MSG has addictive
properties and can cause people to gain weight, but
Bera et al., World J Pharm Sci 2017; 5(5): 139-144
they justify its use by claiming that this can be
beneficial to elderly persons who are sometimes
malnourished. Glutamate, the main component of
MSG, is the primary excitatory neurotransmitter in
the brain, and it has been linked to neurological
symptoms when taken in excess [27, 28].
Neurotransmitters, such as glutamate, are important
for chemical communication in the brain, where
they are very carefully balanced and managed.
Excessive quantities of a neurotransmitter,
however, can cause it to become an excitotoxin, a
substance that over-excites cells to the point of
damage, when the balance of glutamate is upset
this substance can become neurotoxic, leading to
enzymatic cascades resulting in cell death .
Neurological conditions that some researchers
claim may be associated with MSG include
migraines, seizures, autism, attention deficit
disorder, hyperactivity, Alzheimer's disease, Lou
Gehrig's disease, multiple sclerosis and Parkinson's
disease. However, according to a 2007 issue of the
‘European Journal of Clinical Nutrition,’ an
international team of experts concluded that MSG
was "harmless for the whole population." They
declared that 16 mg/kg of body weight per day was
the safe limit for MSG consumption .
MSG as an appetite enhancer: MSG is used
extensively throughout the world as a flavor
enhancer. It improves such specific flavor
characteristics of food as continuity, mouth
fullness, mildness, and thickness of food. It also
improves the overall preference for food. In the
elderly, there is a general decrease in the sensitivity
of the senses, including taste. Several such reports
have described the taste threshold to MSG in
elderly people in Western countries; however, few
data have evaluated changes in elderly people in
Asian countries . A recent study reported the
sensitivity and preference for L-glutamate (umami
taste) in middle-aged and elderly Japanese women.
Similar to findings in Western individuals, the
threshold and preferred concentrations of L-
glutamate were significantly higher in elderly
Japanese women than in middle aged Japanese
women . L-Glutamate (umami taste) preference
varies under different physiologic conditions. The
preference for umami is affected by nutritional
status. For example, poorly nourished subjects
prefer foods with a higher MSG concentration than
do well-nourished subjects . It was reported
that umami taste sensitivity is correlated with the
protein preference score, suggesting that the taste
threshold for umami predicts one’s liking as well as
preference for high-protein foods.
Oral care effect of MSG: Eating is one of the
great pleasures in life. Optimal nutrition, appetite
satisfactions are of paramount importance in the
elderly. When food is ingested, saliva acts not only
as a solvent that allows tastants to be extracted
from foods but also as a glue and lubricant for
masticated foods that permits safe swallowing.
Furthermore, saliva is important for the dental
health (lubrication and mineralization), immune
function, and prevention of microbial growth .
Salivary secretion is provoked by mechanical
(mastication and speech) and gustatory stimuli, as
well as the autonomic nerves . Kawamura et al
and Horio and Kawamura reported that umami
taste stimuli increase salivary flow in healthy adult
subjects. According to one study, next to sour taste,
umami taste is the most potent taste stimulus of
saliva secretion from the parotid gland. In addition,
of the 5 basic tastes, the increase in salivary
secretion produced by umami is the most long
lasting . Schiffman and Miletic have measured
the influence of umami taste on the amount of
immunoglobulin A in the saliva (sIgA) secreted by
elderly subjects ingesting food. The ingestion of a
food containing added MSG was observed to
produce significantly more saliva secretion than
occurred after ingesting the same food with no
added MSG. Salivary sIgA concentration was not
different; hence, the oral cavity experienced a
greater total exposure to secreted sIgA when MSG
was present in the food . The ability of umami
to increase salivary flow may therefore have
clinical potential in the elderly, who frequently
experience dry mouth and its complications.
It is apparent that there is no shortage of research
conducted on this ubiquitous ingredient and its
potential health effects. Because MSG is one of the
most intensely studied food ingredients in the food
supply and has been found safe, the Joint Expert
Committee on Food Additives of the United
Nations Food and Agriculture Organization and
World Health Organization placed it in the safest
category for food additives. United States food and
drug administration (FDA) concluded that MSG is
safe when ‘eaten at customary levels’ and, although
a subgroup of otherwise healthy individuals
develop an MSG symptom complex when exposed
to 3 g of MSG in the absence of food, MSG as a
cause has not been established because the
symptom reports are anecdotal. International and
national bodies governing food additives currently
consider MSG safe for human consumption as a
Bera et al., World J Pharm Sci 2017; 5(5): 139-144
1. Kurihara K. Glutamate: from discovery as a food flavor to role as a basic taste (umami). Am J Clin Nutri 2009; 90: 719S-22S.
2. Loliger J. Function and importance of glutamate for savory foods. J Nutri 2000; 130: 915-20.
3. Yamaguchi S. Basic properties of umami and effects on humans. Physiol Behavior 1991; 49: 833-41.
4. Halpern BP. Glutamate and the flavor of food. J Nutri 2000; 130: 910S-4S.
5. Sano C. History of glutamate production. Am J Clin Nutri 2009; 90: 728-32.
6. Yamaguch S. Technical committee, umami manufacturers association of Japan. What is umami?. Food Reviews Int 1998; 14:
7. Accent flavor enhancer. Accent flavor com. B&G Foods, Inc. Retrieved August 11, 2014.
8. Institute of Food Technologists. Expert panel on food safety and nutrition. Monosodium Glutamate. Food Technol 1987; 41: 143-
9. Schiffman SS. Intensification of sensory properties of foods for the elderly. J Nutri 2000; 130: 927S-930S.
10. Mojet J et al. Taste perception with age: generic or specific losses in threshold sensitivity to the five basic tastes. Chem Senses
11. Bellisle F et al. Monosodium glutamate affects mealtime food selection in diabetic patients. Appetite 2003; 26: 267-76.
12. Onyema OO et al. Effect of vitamin E on monosodium glutamate induced hepatoxicity and oxidative stress in rats. Ind J Biochem
Biophys 2006; 43: 20-4.
13. Farombi EO, Onyema OO. Monosodium glutamate induced oxidative damage and genotoxicity in rat: Modulatory role of
vitamin C, vitamin E and quercetin. Human Experi Toxicol 2006; 25: 251-9.
14. Diniz YS et al. Toxicity of hyper caloric diet and monosodium glutamate: Oxidative stress and metabolic shifting in hepatic
tissue. Food Chem Toxicol 2004; 42: 319-25.
15. Singh P et al. Prolonged glutamate excitotoxicity effects on mitochondrial antioxidants and antioxidant enzymes. Mol Cell
Biochem 2003; 243: 139-45.
16. Koya D et al. Effects of antioxidants in diabetes-induced oxidative stress in the glomeruli of diabetic rats. J Am Soc Nephrol
2003; 14: S250-S3.
17. Shi Z et al. Monosodium glutamate is not associated with obesity or a greater prevalence of weight gain over 5 years: Findings
from the Jiangsu nutrition study of Chinese adults. Bri J Nutri 2010; 104: 457-63.
18. Nicholas B. Consumption of monosodium glutamate, the widely used food additive, may increase the likelihood of being
overweight, a new study says. New York Times. Retrieved 2010-11-10.
19. Shi HB et al. Irradiation impairment of umami taste in patients with head and neck cancer. Auris Nasus Larynx 2004; 31:401-6.
20. Geha RS et al. Review of alleged reaction to monosodium glutamate and outcome of a multi center double-blind placebo
controlled study J Nutri 2000; 130: 1058S-62S.
21. Filer LJ, Public Forum: Analysis of adverse reactions to monosodium glutamate. Paper presented at open meeting of the
Federation of American Societies for Experimental Biol. April 1993.
22. Battaglia FC. Glutamine and glutamate exchange between the fetal liver and the placenta. J Nutri 2000; 130: 974S-7S.
23. American Academy of Pediatrics’ Committee on Drugs. The transfer of drugs and other chemicals into human milk. Pediatrics
24. Ball P et al. Calcium di-glutamate improves taste characteristics of lower salt soup. Eur J Clin Nutri 2002; 56:519-23.
25. Selvakumar E et al. Chemoprotective effect of lipoic acid against cyclophosphamide-induced changes in the rat sperm. Toxicol
2006; 217: 71-8.
26. SCOGS (Select Committee on GRAS Substances). Evaluation of the health aspects of certain glutamates as a food ingredient
(SCOGS-37a.-Suppl.). Paper presented to U.S. Food and Drug Administration, 1980.
27. Nicholas J et al. Glutamate transporters in neurologic disease. J Nutri Health 2001; 58: 365-70.
28. Rivera MC et al. NMDA and AMPA receptor expression and cortical neuronal death are associated with p38 in glutamate-
induced excitotoxicity in vivo. J Neurosci Res 2004; 76: 678-85.
29. Pelaez B. Lectin histochemistry and ultra-structure of microglial response to monosodium glutamate-mediated neurotoxicity in
the arcuate nucleus. Arch Neurol 2001; 14: 165-74.
30. Husarova V, Ostatnikov D. Monosodium glutamate toxic effects and their implications for human intake: A review. Euro J Clin
Nutri 2007; 34: 758-65.
31. Hayakawa Y et al. Umami sensitivity of the elderly females-comparison with middle-aged females. Jap J Taste Smell Res 2007;
32. Schiffman SS, Miletic ID. Effect of taste and smell on secretion rate of salivary IgA in elderly and young persons. J Nutri Health
Aging 1999; 3: 158-64.
33. Gupta A et al. Hyposalivation in elderly patients. J Can Dent Assoc 2006; 72:841-6.
34. Proctor GB, Carpenter GH. Regulation of salivary gland functions by autonomic nerves. Auton Neurosci 2007; 133:3-18.
35. Hayakawa Y et al. The effect of umami taste on saliva secretion. Japn J Taste Smell Res 2008; 15:367-70.
36. Schiffman SS. Intensification of sensory properties of foods for the elderly. J Nutri 2000; 130: 927S-30S.