Glutamic acid (flavor)
Encyclopedia
Glutamic acid and its ion
Ion
An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...

s and salt
Salt
In chemistry, salts are ionic compounds that result from the neutralization reaction of an acid and a base. They are composed of cations and anions so that the product is electrically neutral...

s, called glutamates, are flavor-enhancing compounds which provide an umami
Umami
Umami , popularly referred to as savoriness, is one of the five basic tastes together with sweet, sour, bitter, and salty.-Etymology:Umami is a loanword from the Japanese meaning "pleasant savory taste". This particular writing was chosen by Professor Kikunae Ikeda from umai "delicious" and mi ...

 (savory) taste to food. Glutamic acid is a natural constituent of many fermented
Fermentation (food)
Fermentation in food processing typically is the conversion of carbohydrates to alcohols and carbon dioxide or organic acids using yeasts, bacteria, or a combination thereof, under anaerobic conditions. Fermentation in simple terms is the chemical conversion of sugars into ethanol...

 or aged foods, including soy sauce
Soy sauce
Soy sauce is a condiment produced by fermenting soybeans with Aspergillus oryzae or Aspergillus sojae molds, along with water and salt...

, fermented bean paste
Fermented bean paste
Fermented bean paste is a category of fermented foods typically made from ground soybeans, which are indigenous to the cuisines of East and Southeast Asia...

, and cheese
Cheese
Cheese is a generic term for a diverse group of milk-based food products. Cheese is produced throughout the world in wide-ranging flavors, textures, and forms....

, and is also a component of hydrolyzed protein
Hydrolyzed protein
Hydrolyzed protein is protein that has been hydrolyzed or broken down into its component amino acids. While there are many means of achieving this, two of the most common are prolonged boiling in a strong acid or strong base or using an enzyme such as the pancreatic protease enzyme to stimulate...

 such as yeast extract
Yeast extract
Yeast extract is the common name for various forms of processed yeast products made by extracting the cell contents ; they are used as food additives or flavourings, or as nutrients for bacterial culture media. They are often used to create savory flavors and umami taste sensations. Monosodium...

. The sodium salt of glutamic acid, monosodium glutamate
Monosodium glutamate
Monosodium glutamate, also known as sodium glutamate or MSG, is the sodium salt of glutamic acid, one of the most abundant naturally occurring non-essential amino acids....

 (MSG), is a widely used additive in the food industry
Food industry
The food production is a complex, global collective of diverse businesses that together supply much of the food energy consumed by the world population...

.

Glutamic acid versus glutamate

When glutamic acid or one of its salts is dissolved in aqueous solution
Solution
In chemistry, a solution is a homogeneous mixture composed of only one phase. In such a mixture, a solute is dissolved in another substance, known as a solvent. The solvent does the dissolving.- Types of solutions :...

s, a pH
PH
In chemistry, pH is a measure of the acidity or basicity of an aqueous solution. Pure water is said to be neutral, with a pH close to 7.0 at . Solutions with a pH less than 7 are said to be acidic and solutions with a pH greater than 7 are basic or alkaline...

-dependent instantaneous chemical equilibrium
Chemical equilibrium
In a chemical reaction, chemical equilibrium is the state in which the concentrations of the reactants and products have not yet changed with time. It occurs only in reversible reactions, and not in irreversible reactions. Usually, this state results when the forward reaction proceeds at the same...

 of the amino acid's ionized forms, including zwitterion
Zwitterion
In chemistry, a zwitterion is a neutral molecule with a positive and a negative electrical charge at different locations within that molecule. Zwitterions are sometimes also called inner salts.-Examples:...

ic forms, will result. These ions are called glutamates. Salts exist only in a dry and crystallized form. The form ultimately responsible for the taste is the glutamate ion, and the form of glutamic acid at the time of the addition is not important. However, crystalline glutamic acid salts such as monosodium glutamate dissolve much better and faster than crystalline glutamic acid, a property important for use as a flavor enhancer.

Discovery

Although they occur naturally in many foods, the flavor contributions made by glutamic acid and other amino acids were only scientifically identified early in the twentieth century. The substance was discovered and identified in the year 1866, by the German chemist Karl Heinrich Leopold Ritthausen. In 1907 Japanese researcher Kikunae Ikeda
Kikunae Ikeda
was a Japanese chemist and Tokyo Imperial University professor in Chemistry who, in 1908, uncovered the chemical root behind a taste he named umami. He discovered the common component that produced the flavor of meat, seaweed and tomatoes was glutamate, which produces the sensation of umami.He also...

 of the Tokyo Imperial University identified brown crystals left behind after the evaporation of a large amount of kombu
Kombu
Kombu or konbu , also called dashima or haidai , is edible kelp from the family Laminariaceae widely eaten in East Asia....

 broth as glutamic acid. These crystals, when tasted, reproduced the ineffable but undeniable flavor he detected in many foods, most especially in seaweed. Professor Ikeda termed this flavor umami
Umami
Umami , popularly referred to as savoriness, is one of the five basic tastes together with sweet, sour, bitter, and salty.-Etymology:Umami is a loanword from the Japanese meaning "pleasant savory taste". This particular writing was chosen by Professor Kikunae Ikeda from umai "delicious" and mi ...

. He then patented a method of mass-producing a crystalline salt of glutamic acid, monosodium glutamate.

Isomers

Only the L-glutamate enantiomer
Enantiomer
In chemistry, an enantiomer is one of two stereoisomers that are mirror images of each other that are non-superposable , much as one's left and right hands are the same except for opposite orientation. It can be clearly understood if you try to place your hands one over the other without...

 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. Fermented products such as soy sauce
Soy sauce
Soy sauce is a condiment produced by fermenting soybeans with Aspergillus oryzae or Aspergillus sojae molds, along with water and salt...

, steak sauce
Steak sauce
Steak sauce —brown sauce —is a generic term for a dark brown sauce commonly served as a condiment for meat.The two terms are similar but not identical...

, and Worcestershire sauce
Worcestershire sauce
Worcestershire sauce , or Worcester sauce is a fermented liquid condiment; primarily used to flavour meat or fish dishes.First made at 60 Broad Street, Worcester, England, by two dispensing chemists, John Wheeley Lea and William Henry Perrins, the Lea & Perrins brand was commercialised in 1837 and...

 have levels of glutamate similar to foods with added monosodium glutamate. However, 5% or more of the glutamate may be the D-enantiomer.

Taste perception

Glutamic acid stimulates specific receptors located in taste bud
Taste bud
Taste buds contain the receptors for taste. They are located around the small structures on the upper surface of the tongue, soft palate, upper esophagus and epiglottis, which are called papillae. These structures are involved in detecting the five elements of taste perception: salty, sour,...

s such as the amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 receptor T1R1/T1R3 or other glutamate receptor
Glutamate receptor
Glutamate receptors are synaptic receptors located primarily on the membranes of neuronal cells. Glutamate is one of the 20 amino acids used to assemble proteins and as a result is abundant in many areas of the body, but it also functions as a neurotransmitter and is particularly abundant in the...

s like the metabotropic receptors (mGluR4
Metabotropic glutamate receptor 4
Metabotropic glutamate receptor 4 is a protein that in humans is encoded by the GRM4 gene.Together with GRM6, GRM7 and GRM8 it belongs to group III of the metabotropic glutamate receptor family. Group III receptors are linked to the inhibition of the cyclic AMP cascade.Activation of GRM4 has...

 and mGluR1
Metabotropic glutamate receptor 1
The glutamate receptor, metabotropic 1, also known as GRM1, is a human gene which encodes the metabotropic glutamate receptor 1 protein.-Function:...

) which induce the taste known as umami
Umami
Umami , popularly referred to as savoriness, is one of the five basic tastes together with sweet, sour, bitter, and salty.-Etymology:Umami is a loanword from the Japanese meaning "pleasant savory taste". This particular writing was chosen by Professor Kikunae Ikeda from umai "delicious" and mi ...

, one of the five basic tastes (the word umami
Umami
Umami , popularly referred to as savoriness, is one of the five basic tastes together with sweet, sour, bitter, and salty.-Etymology:Umami is a loanword from the Japanese meaning "pleasant savory taste". This particular writing was chosen by Professor Kikunae Ikeda from umai "delicious" and mi ...

 is a loanword
Loanword
A loanword is a word borrowed from a donor language and incorporated into a recipient language. By contrast, a calque or loan translation is a related concept where the meaning or idiom is borrowed rather than the lexical item itself. The word loanword is itself a calque of the German Lehnwort,...

 from Japanese
Japanese language
is a language spoken by over 130 million people in Japan and in Japanese emigrant communities. It is a member of the Japonic language family, which has a number of proposed relationships with other languages, none of which has gained wide acceptance among historical linguists .Japanese is an...

; it is also referred to as "savory" or "meaty").

Natural occurrence

Glutamate itself is a widespread amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

. It is found naturally in all living cells, primarily in the bound form as part of protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

s. Only a fraction of the glutamate in foods is in its "free" form, and only free glutamate can enhance the flavor of foods. Part of the flavor-enhancing effect of tomato
Tomato
The word "tomato" may refer to the plant or the edible, typically red, fruit which it bears. Originating in South America, the tomato was spread around the world following the Spanish colonization of the Americas, and its many varieties are now widely grown, often in greenhouses in cooler...

es, fermented soy products, yeast extract
Yeast extract
Yeast extract is the common name for various forms of processed yeast products made by extracting the cell contents ; they are used as food additives or flavourings, or as nutrients for bacterial culture media. They are often used to create savory flavors and umami taste sensations. Monosodium...

s, certain sharp cheeses, and fermented or hydrolyzed protein
Hydrolyzed protein
Hydrolyzed protein is protein that has been hydrolyzed or broken down into its component amino acids. While there are many means of achieving this, two of the most common are prolonged boiling in a strong acid or strong base or using an enzyme such as the pancreatic protease enzyme to stimulate...

 products (such as soy sauce
Soy sauce
Soy sauce is a condiment produced by fermenting soybeans with Aspergillus oryzae or Aspergillus sojae molds, along with water and salt...

 and fermented bean paste
Fermented bean paste
Fermented bean paste is a category of fermented foods typically made from ground soybeans, which are indigenous to the cuisines of East and Southeast Asia...

) is due to the presence of free glutamate ions.

Asia

Japanese cuisine originally used broth
Dashi
Dashi is a class of soup and cooking stock, considered fundamental to Japanese cooking. In 1980, Shizuo Tsuji wrote: "Many substitutes for dashi are possible, but without dashi, dishes are merely à la japonaise and lack the authentic flavor." Dashi forms the base for miso soup, clear broth, noodle...

 made from kombu
Kombu
Kombu or konbu , also called dashima or haidai , is edible kelp from the family Laminariaceae widely eaten in East Asia....

 (kelp
Kelp
Kelps are large seaweeds belonging to the brown algae in the order Laminariales. There are about 30 different genera....

) to bring up the umami
Umami
Umami , popularly referred to as savoriness, is one of the five basic tastes together with sweet, sour, bitter, and salty.-Etymology:Umami is a loanword from the Japanese meaning "pleasant savory taste". This particular writing was chosen by Professor Kikunae Ikeda from umai "delicious" and mi ...

 taste in soups. Manufacturers, such as Ajinomoto
Ajinomoto
Ajinomoto Co. Inc. , is a Japanese food and chemical corporation which produces seasonings, cooking oils, TV dinners, sweeteners, amino acids and pharmaceuticals...

, use selected strains of Micrococcus glutamicus
Micrococcus
Micrococcus is a genus of bacteria in the Micrococcaceae family. Micrococcus occurs in a wide range of environments, including water, dust, and soil. Micrococci have Gram-positive spherical cells ranging from about 0.5 to 3 micrometers in diameter and are typically appear in tetrads...

 bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

 in a nutrient-rich medium. The bacteria are selected for their ability to excrete glutamic acid, which is then separated from the nutrient medium and processed into its sodium salt, monosodium glutamate.

Rome

In the Roman Empire
Roman Empire
The Roman Empire was the post-Republican period of the ancient Roman civilization, characterised by an autocratic form of government and large territorial holdings in Europe and around the Mediterranean....

 glutamic acid was found in a sauce called "Garum
Garum
Garum, similar to liquamen, was a type of fermented fish sauce condiment that was an essential flavour in Ancient Roman cooking, the supreme condiment....

", made from fermenting fish in saltwater. It was used so widely that it has been called "the ketchup
Ketchup
Ketchup is a sweet-and-tangy condiment typically made from tomatoes, vinegar, sugar or high-fructose corn syrup and an assortment of...

 of the ancient Romans." The flavor enhancing properties of glutamic acid allowed Romans to reduce the use of expensive salt.

Concentration in foods

The following table illustrates the glutamate content of some selected common foods. Free glutamate is metabolized differently from glutamate bound in protein, so they are listed separately.
Food Free glutamate (mg/100 g) Protein glutamate (mg/100 g)
Marmite
Marmite
Marmite is the name given to two similar food spreads: the original British version, first produced in the United Kingdom and later South Africa, and a version produced in New Zealand...

 
1960
Vegemite
Vegemite
Vegemite is a dark brown Australian food paste made from yeast extract. It is a spread for sandwiches, toast, crumpets and cracker biscuits, and filling for pastries...

 
1431
Roquefort cheese  1280
Parmesan cheese  1200 9847
Chinese soy sauce  1090
Japanese soy sauce  782
Grape juice
Grape juice
Grape juice is obtained from crushing and blending grapes into a liquid. The juice is often sold in stores or fermented and made into wine, brandy, or vinegar. In the wine industry, grape juice that contains 7-23 percent of pulp, skins, stems and seeds is often referred to as "must"...

 
258
Peas
PEAS
P.E.A.S. is an acronym in artificial intelligence that stands for Performance, Environment, Actuators, Sensors.-Performance:Performance is a function that measures the quality of the actions the agent did....

 
200 5583
Tomatoes  140 238
Corn
Maize
Maize known in many English-speaking countries as corn or mielie/mealie, is a grain domesticated by indigenous peoples in Mesoamerica in prehistoric times. The leafy stalk produces ears which contain seeds called kernels. Though technically a grain, maize kernels are used in cooking as a vegetable...

 
130 1765
Cow milk  2 819
Human milk  22 229
Eggs
Egg (food)
Eggs are laid by females of many different species, including birds, reptiles, amphibians, and fish, and have probably been eaten by mankind for millennia. Bird and reptile eggs consist of a protective eggshell, albumen , and vitellus , contained within various thin membranes...

 
23 1583
Chicken
Chicken
The chicken is a domesticated fowl, a subspecies of the Red Junglefowl. As one of the most common and widespread domestic animals, and with a population of more than 24 billion in 2003, there are more chickens in the world than any other species of bird...

 
44 3309
Duck
Duck
Duck is the common name for a large number of species in the Anatidae family of birds, which also includes swans and geese. The ducks are divided among several subfamilies in the Anatidae family; they do not represent a monophyletic group but a form taxon, since swans and geese are not considered...

 
69 3636
Beef
Beef
Beef is the culinary name for meat from bovines, especially domestic cattle. Beef can be harvested from cows, bulls, heifers or steers. It is one of the principal meats used in the cuisine of the Middle East , Australia, Argentina, Brazil, Europe and the United States, and is also important in...

 
33 2846
Pork
Pork
Pork is the culinary name for meat from the domestic pig , which is eaten in many countries. It is one of the most commonly consumed meats worldwide, with evidence of pig husbandry dating back to 5000 BC....

 
23 2325
Salmon
Salmon
Salmon is the common name for several species of fish in the family Salmonidae. Several other fish in the same family are called trout; the difference is often said to be that salmon migrate and trout are resident, but this distinction does not strictly hold true...

 
20 2216

Hydrolyzed protein

Hydrolyzed protein
Hydrolyzed protein
Hydrolyzed protein is protein that has been hydrolyzed or broken down into its component amino acids. While there are many means of achieving this, two of the most common are prolonged boiling in a strong acid or strong base or using an enzyme such as the pancreatic protease enzyme to stimulate...

s, or protein hydrolysates, are acid- or enzymatically treated proteins from certain foods. One example is yeast extract
Yeast extract
Yeast extract is the common name for various forms of processed yeast products made by extracting the cell contents ; they are used as food additives or flavourings, or as nutrients for bacterial culture media. They are often used to create savory flavors and umami taste sensations. Monosodium...

. Hydrolyzed protein contains free amino acids, such as glutamate, at levels of 5% to 20%. Hydrolyzed protein is used in the same manner as monosodium glutamate in many foods, such as canned vegetables, soups, and processed meats.

Safety as a flavor enhancer

In April 1968, Robert Ho Man Kwok wrote a letter to the New England Journal of Medicine
New England Journal of Medicine
The New England Journal of Medicine is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It describes itself as the oldest continuously published medical journal in the world.-History:...

, coining the term "Chinese restaurant syndrome". In this letter he claimed:

I have experienced a strange syndrome whenever I have eaten out in a Chinese restaurant
Chinese cuisine
Chinese cuisine is any of several styles originating in the regions of China, some of which have become highly popular in other parts of the world – from Asia to the Americas, Australia, Western Europe and Southern Africa...

, especially one that served northern Chinese food. The syndrome, which usually begins 15 to 20 minutes after I have eaten the first dish, lasts for about two hours, without hangover effect. The most prominent symptoms are numbness at the back of the neck, gradually radiating to both arms and the back, general weakness and palpitations...


In 1969 the "Chinese restaurant syndrome" was attributed to the flavor enhancer glutamate largely due to the widely-cited article "Monosodium L-glutamate: its pharmacology and role in the Chinese Restaurant Syndrome" published in the journal Science
Science (journal)
Science is the academic journal of the American Association for the Advancement of Science and is one of the world's top scientific journals....

. The syndrome
Syndrome
In medicine and psychology, a syndrome is the association of several clinically recognizable features, signs , symptoms , phenomena or characteristics that often occur together, so that the presence of one or more features alerts the physician to the possible presence of the others...

 is often abbreviated as CRS and also became known under the names "Chinese food syndrome" and "monosodium glutamate symptom complex."

Symptoms attributed to the Chinese restaurant syndrome are rather common and unspecific. They have included burning sensations, numbness, tingling, feelings of warmth, facial pressure or tightness, chest pain
Chest pain
Chest pain may be a symptom of a number of serious conditions and is generally considered a medical emergency. Even though it may be determined that the pain is non-cardiac in origin, this is often a diagnosis of exclusion made after ruling out more serious causes of the pain.-Differential...

, headache
Headache
A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...

, nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...

, rapid heartbeat
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...

, bronchospasm
Bronchospasm
Bronchospasm or a bronchial spasm is a sudden constriction of the muscles in the walls of the bronchioles. It is caused by the release of substances from mast cells or basophils under the influence of anaphylatoxins...

 in people with asthma, drowsiness, and weakness
Weakness
Weakness is a symptom represented, medically, by a number of different conditions, including: lack of muscle strength, malaise, dizziness, or fatigue. The causes are many and can be divided into conditions that have true or perceived muscle weakness. True muscle weakness is a primary symptom of a...

.

While many people believe that monosodium glutamate
Monosodium glutamate
Monosodium glutamate, also known as sodium glutamate or MSG, is the sodium salt of glutamic acid, one of the most abundant naturally occurring non-essential amino acids....

 (MSG) is the cause of these symptoms, an association has never been demonstrated under rigorously controlled conditions, even in studies with people who were convinced that they were sensitive to the compound. Adequately controlling for experimental bias includes a placebo-controlled
Placebo-controlled studies
A Placebo-controlled study is a way of testing a medical therapy in which, in addition to a group of subjects that receives the treatment to be evaluated, a separate control group receives a sham "placebo" treatment which is specifically designed to have no real effect...

 double-blinded experimental design and the application in capsules because of the strong and unique after-taste of glutamates.

A 2002 study found that rats fed on diets supplemented with 10% and 20% pure monosodium glutamate suffered retina
Retina
The vertebrate retina is a light-sensitive tissue lining the inner surface of the eye. The optics of the eye create an image of the visual world on the retina, which serves much the same function as the film in a camera. Light striking the retina initiates a cascade of chemical and electrical...

 degeneration, possibly through glutamate accumulation in the vitreous humor
Vitreous humour
The vitreous humour or vitreous humor is the clear gel that fills the space between the lens and the retina of the eyeball of humans and other vertebrates...


. However, such extreme amounts are more than 10 times higher than those used for flavoring or found in foods and would not be possible to replicate in a meal for human consumption.

Timeline

In 1959, the U.S. Food and Drug Administration (FDA) classified monosodium glutamate as generally recognized as safe
Generally recognized as safe
Generally recognized as safe is an American Food and Drug Administration designation that a chemical or substance added to food is considered safe by experts, and so is exempted from the usual Federal Food, Drug, and Cosmetic Act food additive tolerance requirements.-History:On January 1, 1958,...

 (GRAS). This action stemmed from the 1958 Food Additives Amendment to the Federal Food, Drug, and Cosmetic Act
Federal Food, Drug, and Cosmetic Act
The United States Federal Food, Drug, and Cosmetic Act , is a set of laws passed by Congress in 1938 giving authority to the U.S. Food and Drug Administration to oversee the safety of food, drugs, and cosmetics. A principal author of this law was Royal S. Copeland, a three-term U.S. Senator from...

 that required premarket approval for new food additives and led the FDA to promulgate regulations listing substances, such as monosodium glutamate, which have a history of safe use or are otherwise GRAS.

Since 1970, FDA has sponsored extensive reviews on the safety of monosodium glutamate, other glutamates, and hydrolyzed proteins, as part of an ongoing review of safety data on GRAS substances used in processed foods. One such review was by the Federation of American Societies for Experimental Biology
Federation of American Societies for Experimental Biology
The Federation of American Societies for Experimental Biology, abbreviated FASEB, is a non-profit organization that is the principal umbrella organization of U.S. societies in the field of biological and medical research. FASEB organizes academic conferences and publishes scientific literature...

 (FASEB) Select Committee on GRAS Substances. In 1980, the committee concluded that monosodium glutamate was safe at current levels of use but recommended additional evaluation to determine monosodium glutamate's safety at significantly higher levels of consumption. Additional reports attempted to look at this.

In 1986, FDA's Advisory Committee on Hypersensitivity
Hypersensitivity
Hypersensitivity refers to undesirable reactions produced by the normal immune system, including allergies and autoimmunity. These reactions may be damaging, uncomfortable, or occasionally fatal. Hypersensitivity reactions require a pre-sensitized state of the host. The four-group classification...

 to Food Constituents concluded that monosodium glutamate poses no threat to the general public but that reactions of brief duration might occur in some people. Other reports have given the following findings:
  • The 1987 Joint Expert Committee on Food Additives of the United Nations Food and Agriculture Organization
    Food and Agriculture Organization
    The Food and Agriculture Organization of the United Nations is a specialised agency of the United Nations that leads international efforts to defeat hunger. Serving both developed and developing countries, FAO acts as a neutral forum where all nations meet as equals to negotiate agreements and...

     and the World Health Organization
    World Health Organization
    The World Health Organization is a specialized agency of the United Nations that acts as a coordinating authority on international public health. Established on 7 April 1948, with headquarters in Geneva, Switzerland, the agency inherited the mandate and resources of its predecessor, the Health...

     placed monosodium glutamate in the safest category of food ingredients.
  • A 1991 report by the European Community's
    European Commission
    The European Commission is the executive body of the European Union. The body is responsible for proposing legislation, implementing decisions, upholding the Union's treaties and the general day-to-day running of the Union....

     (EC) Scientific Committee for Foods
    Directorate-General of the Joint Research Centre (European Commission)
    The Joint Research Centre , located in Brussels, Belgium, is a Directorate-General of the European Commission. Its current Commissioner is Máire Geoghegan-Quinn, and the Director General is Dominique Ristori....

     reaffirmed monosodium glutamate's safety and classified its "acceptable daily intake" as "not specified", the most favorable designation for a food ingredient. In addition, the EC Committee said, "Infants, including prematures, have been shown to metabolize glutamate as efficiently as adults and therefore do not display any special susceptibility to elevated oral intakes of glutamate."
  • A 1992 report from the Council on Scientific Affairs of the American Medical Association
    American Medical Association
    The American Medical Association , founded in 1847 and incorporated in 1897, is the largest association of medical doctors and medical students in the United States.-Scope and operations:...

     stated that glutamate in any form has not been shown to be a "significant health hazard".
  • A 1995 FDA-commissioned report by the FASEB confirmed the safety assessments of the aforementioned Committees, but stated that an unknown percentage of the population may react to monosodium glutamate and develop a monosodium glutamate symptom complex when consuming more than 3 grams of monosodium glutamate alone. The report compiled several, mostly very non-specific and common, symptoms from anecdotal reports, including burning sensation in the back of the neck, forearms and chest, numbness in the back of the neck, radiating to the arms and back, tingling, warmth and weakness in the face, temples, upper back, neck and arms, facial pressure or tightness, chest pain
    Chest pain
    Chest pain may be a symptom of a number of serious conditions and is generally considered a medical emergency. Even though it may be determined that the pain is non-cardiac in origin, this is often a diagnosis of exclusion made after ruling out more serious causes of the pain.-Differential...

    , headache, nausea, rapid heartbeat, bronchospasm
    Bronchospasm
    Bronchospasm or a bronchial spasm is a sudden constriction of the muscles in the walls of the bronchioles. It is caused by the release of substances from mast cells or basophils under the influence of anaphylatoxins...

    , drowsiness, weakness.
  • A 2000 review found that large doses of MSG given without food may elicit more symptoms than a placebo in individuals who believe that they react adversely to MSG. However, the frequency of the responses was low and the responses reported were inconsistent and were not reproducible. The responses were not observed when MSG was given with food.

Excitotoxicity

Because glutamate is absorbed very quickly in the gastrointestinal tract
Gastrointestinal tract
The human gastrointestinal tract refers to the stomach and intestine, and sometimes to all the structures from the mouth to the anus. ....

 (unlike glutamic acid-containing proteins in foods), glutamate could spike blood plasma
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...

 levels of glutamate. Glutamic acid is in a class of chemicals known as excitotoxins, high levels of which have been shown in animal studies
Animal testing
Animal testing, also known as animal experimentation, animal research, and in vivo testing, is the use of non-human animals in experiments. Worldwide it is estimated that the number of vertebrate animals—from zebrafish to non-human primates—ranges from the tens of millions to more than 100 million...

 to cause damage to areas of the brain unprotected by the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...

 and that a variety of chronic diseases
Chronic (medicine)
A chronic disease is a disease or other human health condition that is persistent or long-lasting in nature. The term chronic is usually applied when the course of the disease lasts for more than three months. Common chronic diseases include asthma, cancer, diabetes and HIV/AIDS.In medicine, the...

 can arise out of this neurotoxicity
Neurotoxicity
Neurotoxicity occurs when the exposure to natural or artificial toxic substances, which are called neurotoxins, alters the normal activity of the nervous system in such a way as to cause damage to nervous tissue. This can eventually disrupt or even kill neurons, key cells that transmit and process...

. There has been debate among scientists on the significance of these findings since the early 1970s, when John Olney found that high levels of glutamic acid caused damage to the brains of infant mice. The debate is complex and has focused mainly on whether the increase in plasma glutamate levels from typical ingestion levels of glutamate is enough to cause neurotoxicity and on whether humans are susceptible to the neurotoxicity from glutamic acid seen in some animal experiments.

At a meeting of the Society for Neuroscience
Society for Neuroscience
The Society for Neuroscience is a professional society, headquartered in Washington, D.C., for basic scientists and physicians around the world whose research is focused on the study of the brain and nervous system.-History:...

 in 1990, the delegates had a split opinion on the issues related to neurotoxic effects from excitotoxic amino acids found in some additives such as monosodium glutamate.

Some scientists believe that humans and other primates are not as susceptible to excitotoxins as rodents and therefore there is little concern with glutamic acid as a food additive. While they agree that the combined effects of all food-based excitotoxins should be considered, their measurements of the blood plasma levels of glutamic acid after ingestion of monosodium glutamate and aspartame
Aspartame
Aspartame is an artificial, non-saccharide sweetener used as a sugar substitute in some foods and beverages. In the European Union, it is codified as E951. Aspartame is a methyl ester of the aspartic acid/phenylalanine dipeptide. It was first sold under the brand name NutraSweet; since 2009 it...

 demonstrate that there is not a cause for concern.

Other scientists around John Olney felt that primates are susceptible to excitotoxic damage and that humans concentrate excitotoxins in the blood more than other animals. Based on these findings, they feel that humans are approximately 5-6 times more susceptible to the effects of excitotoxins than rodents are. While they agree that typical use of monosodium glutamate does not spike glutamic acid to extremely high levels in adults, they are particularly concerned with potential effects in infants and young children and the potential long-term neurodegenerative effects of small-to-moderate spikes on plasma excitotoxin levels.

Obesity

In 2008, a collaboration between American and Chinese
China
Chinese civilization may refer to:* China for more general discussion of the country.* Chinese culture* Greater China, the transnational community of ethnic Chinese.* History of China* Sinosphere, the area historically affected by Chinese culture...

 researchers found a positive statistical association between MSG intake and obesity in humans: Prevalence of overweight was significantly higher in MSG users than in non-users. The population in this study was 752 healthy rural Chinese villagers between the ages of 40 and 59, of whom 48.7% were women. The results of this study, however, were challenged in another Chinese study released in April 2010. The new study took two measurements, one in 2002, and one in 2007. By comparing weights of 1282 Chinese men and women and controlling for other food intake, the researchers showed that there was no correlation between MSG and weight gain over a five year period.

Previously, monosodium glutamate has been shown to indirectly cause obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...

 in lab rats by downregulating hypothalamic
Hypothalamus
The Hypothalamus is a portion of the brain that contains a number of small nuclei with a variety of functions...

 appetite suppression and, thus, increasing the amount of food the lab rats consumed. However, at least one study (1978) found that this obesity effect (widely used in obesity research using rats and mice, and also observed in Chinese hamster
Chinese hamster
The Chinese hamster , is a species of hamster originating from the deserts of northern China and Mongolia.- Description :...

s) was not dependent on additional food intake. Animal research demonstrating an inverse relationship between increased glutamate intake via maternal feeding and serum levels of growth hormone, combined with an epidemiological survey of 2,239,960 German adults demonstrating an inverse relationship between height and morbid obesity, compels some researchers to theorize (2006) that monosodium glutamate has a role in the occurrence of obesity in humans. In contrast, a 2008 Japanese study sponsored by a MSG manufacturer found that rats lost body fat when allowed to freely drink a solution of MSG and water.

However, an earlier study (1973) did not find a similar effect in humans. The epidemiological survey of 4,938 ethnically Japanese
Japanese people
The are an ethnic group originating in the Japanese archipelago and are the predominant ethnic group of Japan. Worldwide, approximately 130 million people are of Japanese descent; of these, approximately 127 million are residents of Japan. People of Japanese ancestry who live in other countries...

 men drawn from the Honolulu heart program in Hawaii found that self-reported dietary monosodium glutamate consumption was not statistically linked with obesity. Researchers furthermore found that frequent monosodium glutamate consumption did not significantly affect blood sugar
Blood sugar
The blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. Normally in mammals, the body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mM , or 64.8 and 104.4 mg/dL...

 or serum cholesterol
Cholesterol
Cholesterol is a complex isoprenoid. Specifically, it is a waxy steroid of fat that is produced in the liver or intestines. It is used to produce hormones and cell membranes and is transported in the blood plasma of all mammals. It is an essential structural component of mammalian cell membranes...

 levels among the participants.

Monosodium glutamate may worsen non-alcoholic fatty liver disease
Non-alcoholic fatty liver disease
Non-alcoholic fatty liver disease is one cause of a fatty liver, occurring when fat is deposited in the liver not due to excessive alcohol use. It is related to insulin resistance and the metabolic syndrome and may respond to treatments originally developed for other insulin-resistant states...

 caused by trans fat
Trans fat
Trans fat is the common name for unsaturated fat with trans-isomer fatty acid. Because the term refers to the configuration of a double carbon-carbon bond, trans fats are sometimes monounsaturated or polyunsaturated, but never saturated....

s.

European Union

Following the compulsory EU-food labeling law the use of glutamic acid and its salts has to be declared, and the name or E number
E number
E numbers are number codes for food additives that have been assessed for use within the European Union . They are commonly found on food labels throughout the European Union. Safety assessment and approval are the responsibility of the European Food Safety Authority...

 of the salt has to be listed. Glutamic acid and its salts as food additives have the following E numbers: glutamic acid
Glutamic acid
Glutamic acid is one of the 20 proteinogenic amino acids, and its codons are GAA and GAG. It is a non-essential amino acid. The carboxylate anions and salts of glutamic acid are known as glutamates...

: E620, monosodium glutamate
Monosodium glutamate
Monosodium glutamate, also known as sodium glutamate or MSG, is the sodium salt of glutamic acid, one of the most abundant naturally occurring non-essential amino acids....

: E621, monopotassium glutamate
Monopotassium glutamate
Monopotassium glutamate is a compound with formula KC5H8NO4. It is a potassium acid salt of glutamic acid.It has the E number E622 and is used in foods as a flavor enhancer. It is a non-sodium MSG alternative....

: E622, calcium diglutamate
Calcium diglutamate
Calcium diglutamate, sometimes abbreviated CDG and also called calcium glutamate, is a compound with formula Ca2. It is a calcium acid salt of glutamic acid. CDG is a flavor enhancer — it is the calcium analog of monosodium glutamate...

: E623, monoammonium glutamate
Monoammonium glutamate
Monoammonium glutamate is a compound with formula NH4C5H8NO4. It is an ammonium acid salt of glutamic acid.It has the E number E624 and is used as a flavor enhancer....

: E624, and magnesium diglutamate
Magnesium diglutamate
Magnesium diglutamate is a compound with formula Mg2. It is a magnesium acid salt of glutamic acid.It has the E number E625 and is used in foods as a flavor enhancer....

: E625. In the European Union, these enhancers are not allowed to be added to milk, emulsified fat and oil, pasta, cocoa/chocolate products and fruit juice. The EU did not yet publish an official NOAEL (no observable adverse effect level) for glutamate, but a 2006 consensus statement of a group of German experts drawing from animal studies was that a daily intake of glutamic acid of 6 grams per kilogram of body weight (6 g/kg/day) is safe. From human studies, the experts noted that doses as high as 147 g/day produced no adverse effects in males when given for 30 days; in a 70 kg male that corresponds to 2.1 g per kg of body weight.

United States

In 1959, the Food and Drug Administration classified MSG as a "generally recognized as safe" (GRAS
Gras
Gras is a commune in the Ardèche department in southern France.-Population:-References:*...

) food ingredient under the Federal Food, Drug, and Cosmetic Act
Federal Food, Drug, and Cosmetic Act
The United States Federal Food, Drug, and Cosmetic Act , is a set of laws passed by Congress in 1938 giving authority to the U.S. Food and Drug Administration to oversee the safety of food, drugs, and cosmetics. A principal author of this law was Royal S. Copeland, a three-term U.S. Senator from...

. In 1986, FDA's Advisory Committee on Hypersensitivity to Food Constituents also found that MSG was generally safe, but that short-term reactions may occur in some people. To further investigate this matter, in 1992 the FDA contracted the Federation of American Societies for Experimental Biology
Federation of American Societies for Experimental Biology
The Federation of American Societies for Experimental Biology, abbreviated FASEB, is a non-profit organization that is the principal umbrella organization of U.S. societies in the field of biological and medical research. FASEB organizes academic conferences and publishes scientific literature...

 (FASEB) to produce a detailed report, which was published in 1995. The FASEB report reaffirmed the safety of MSG when it is consumed at usual levels by the general population, and found no evidence of any connection between MSG and any serious long-term reactions.

Under 2003 U.S. Food and Drug Administration regulations, when monosodium glutamate is added to a food, it must be identified as "monosodium glutamate" in the label's ingredient list. Because glutamate is commonly found in food, primarily from protein sources, the FDA does not require foods and ingredients that contain glutamate as an inherent component to list it on the label. Examples include tomatoes, cheeses, meats, hydrolyzed protein
Hydrolyzed protein
Hydrolyzed protein is protein that has been hydrolyzed or broken down into its component amino acids. While there are many means of achieving this, two of the most common are prolonged boiling in a strong acid or strong base or using an enzyme such as the pancreatic protease enzyme to stimulate...

 products such as soy sauce, and autolyzed yeast extracts. These ingredients are to be declared on the label by their common or usual names. The term 'natural flavor' is now used by the food industry when using glutamic acid. Due to lack of regulation, it is impossible to determine what percentage of 'natural flavor' is actually glutamic acid.

The food additives disodium inosinate
Disodium inosinate
Disodium inosinate is the disodium salt of inosinic acid with the chemical formula C10H11N4Na2O8P. It is used as a food additive and often found in instant noodles, potato chips, and a variety of other snacks.-Use as a food additive:...

 and disodium guanylate
Disodium guanylate
Disodium guanylate, also known as sodium 5'-guanylate and disodium 5'-guanylate, is a natural disodium salt of the flavor enhancer guanosine monophosphate . Disodium guanylate is a food additive with the E number E627...

 are usually used in synergy with monosodium glutamate-containing ingredients, and provide a likely indicator of the addition of glutamate to a product. For this reason, FDA considers labels such as "No MSG" or "No Added MSG" to be misleading if the food contains ingredients that are sources of free glutamate, such as hydrolyzed protein
Hydrolyzed protein
Hydrolyzed protein is protein that has been hydrolyzed or broken down into its component amino acids. While there are many means of achieving this, two of the most common are prolonged boiling in a strong acid or strong base or using an enzyme such as the pancreatic protease enzyme to stimulate...

.

As of 2002 the National Academy of Sciences
United States National Academy of Sciences
The National Academy of Sciences is a corporation in the United States whose members serve pro bono as "advisers to the nation on science, engineering, and medicine." As a national academy, new members of the organization are elected annually by current members, based on their distinguished and...

 Committee on Dietary Reference Intakes had not set a NOAEL or LOAEL for glutamate.

Australia and New Zealand

Standard 1.2.4 of the Australia New Zealand
New Zealand
New Zealand is an island country in the south-western Pacific Ocean comprising two main landmasses and numerous smaller islands. The country is situated some east of Australia across the Tasman Sea, and roughly south of the Pacific island nations of New Caledonia, Fiji, and Tonga...

 Food Standards Code requires the presence of monosodium glutamate as a food additive to be labeled. The label must bear the food additive class name (e.g. flavor enhancer), followed by either the name of the food additive (e.g. MSG) or its International Numbering System (INS) number (e.g. 621)

Canada

The Canada Food Inspection Agency considers claims of "no MSG" or "MSG free" to be misleading and deceptive when other sources of free glutamates are present.

See also

  • Umami
    Umami
    Umami , popularly referred to as savoriness, is one of the five basic tastes together with sweet, sour, bitter, and salty.-Etymology:Umami is a loanword from the Japanese meaning "pleasant savory taste". This particular writing was chosen by Professor Kikunae Ikeda from umai "delicious" and mi ...

  • Flavor enhancer
    Flavour enhancer
    Flavour enhancers are food additives commonly added to food and designed to enhance the existing flavours of products. In western cultures, the 5th taste or umami went unrecognized for a long time. It was believed that flavour enhancers did not add any new taste of their own...

  • List of food additives
  • Disodium glutamate
    Disodium glutamate
    Disodium glutamate, abbreviated DSG, is a sodium salt of glutamic acid.-Formation:Disodium glutamate can be produced by neutralizing glutamic acid with two molar equivalents of sodium hydroxide ....

  • Monosodium glutamate
    Monosodium glutamate
    Monosodium glutamate, also known as sodium glutamate or MSG, is the sodium salt of glutamic acid, one of the most abundant naturally occurring non-essential amino acids....


General

  • Jordan Sand, "A Short History of MSG: Good Science, Bad Science, and Taste Cultures", Gastronomica '5:4 (Fall 2005). History of MSG and its marketing in Japan, Taiwan (under the Japanese), China, and the U.S.
  • Federal Register, Dec. 4, 1992 (FR 57467)
  • Federal Register, Jan. 6, 1993 (FR 2950)
  • FDA Consumer, December 1993, "Food Allergies: When Eating is Risky."

External links

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