Glutamic acid (flavor)
Glutamic acid and its ions and salts called glutamates, are flavor compounds that provide umami or savory taste to food. Glutamic acid is a natural constituent of many fermented or aged foods, including soy sauce, fermented bean paste, and cheese, as well as of hydrolyzed protein such as yeast extract. Glutamic acid in its sodium salt form monosodium glutamate (MSG) is a widely used flavor enhancer used in the food industry.

# Glutamic acid versus glutamate
When glutamic acid or one of its salts is dissolved in aqueous solutions, a pH-dependent instantaneous chemical equilibrium of the amino acid's ionized forms, including zwitterionic forms, will result. These ions are called glutamates. Only in a dry and crystallized form do defined salts exist. 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 have a much better and faster solubility compared to crystalline glutamic acid, a property important for its 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 of the Tokyo Imperial University identified brown crystals left behind after the evaporation of a large amount of kombu 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. He then patented a method of mass-producing a crystalline salt of glutamic acid, monosodium glutamate.

# Isomers
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. Fermented products like soy sauce, steak sauce, and worcestershire sauce have comparable levels of glutamate as foods with added monosodium glutamate. However, glutamate in these brewed products may be composed 5% or more of the D-enantiomer.

# Taste perception
Glutamic acid stimulates specific receptors located in taste buds such as the amino acid receptor T1R1/T1R3 or other glutamate receptors like the metabotropic receptors (mGluR4 and mGluR1) which induce the taste known as umami, one of the five basic tastes (the word umami is a loanword from Japanese; it is also referred to as "savoury" or "meaty").

# Sources

## Natural occurrence
Glutamate itself is a widespread amino acid. It is found naturally in all living cells, primarily in the bound form as part of proteins. 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 tomatoes, fermented soy products, yeast extracts, certain sharp cheeses, and fermented or hydrolyzed protein products (such as soy sauce and fermented bean paste) is due to the presence of free glutamate ions.
Asian cuisine originally used a natural seaweed broth, such as kelp, to bring up the umami taste in soups. Manufacturers, such as Ajinomoto, use selected strains of Micrococcus glutamicus bacteria 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.

## 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. 

## Hydrolyzed protein
Hydrolyzed proteins, or protein hydrolysates, are acid- or enzymatically treated proteins from certain foods. One example is yeast extract. 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.

# Health concerns
In April 1968, Ho Man Kwok wrote an article for the New England Journal of Medicine where he said, "I have experienced a strange syndrome whenever I have eaten out in a Chinese restaurant, 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...". This comment began a global health scare about monosodium glutamate and "Chinese restaurant syndrome" was born. Research has failed to prove that monosodium glutamate affects a large percentage of the population, and Chinese restaurant syndrome is largely resigned to urban legend status. However, monosodium glutamate is still thought of as suspect by a large proportion of the general public, and many foods continue to be labeled "MSG free".
In 1959, the FDA classified monosodium glutamate as a "generally recognized as safe", or GRAS, substance. This action stemmed from the 1958 Food Additives Amendment to the Federal Food, Drug, and Cosmetic Act, which 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 (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 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 and the World Health Organization placed monosodium glutamate in the safest category of food ingredients.
- A 1991 report by the European Community's (EC) Scientific Committee for Foods reaffirmed monosodium glutamate's safety and classified its "acceptable daily intake" as "not specified", the most favourable 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 stated that glutamate in any form has not been shown to be a "significant health hazard".
- A 1995 FDA-commissioned report by the FASEB stated that an unknown percentage of the population may react to monosodium glutamate and develop a monosodium glutamate symptom complex. 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, headache, nausea, rapid heartbeat, bronchospasm, drowsiness, weakness, and sweating.
- A 2002 report found that rats fed on diets supplemented with 10% and 20% pure monosodium glutamate suffered retina degeneration, possibly through glutamate accumulation in the vitreous humour. However, such extreme amounts are more than one order of magnitude higher than those used for flavoring or found in foods.

## Excitotoxicity
Because glutamate is absorbed very quickly in the gastrointestinal tract (unlike glutamic acid-containing proteins in foods), glutamate could spike blood plasma levels of glutamate. Glutamic acid is in a class of chemicals known as excitotoxins, high levels of which have been shown in animal studies to cause damage to areas of the brain unprotected by the blood-brain barrier and that a variety of chronic diseases can arise out of this neurotoxicity. The debate among scientists on the significance of these findings has been raging since the early 1970s, when John Olney found that high levels of glutamic acid caused damage to the brains of infant mice ("Olney's lesions"). 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 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 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
Monosodium glutamate has been shown to indirectly cause obesity in lab rats by downregulating hypothalamic 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 utilized in obesity research using rats and mice, and also observed in Chinese hamsters) 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.
However, an earlier study (1973) did not find a similar effect in humans. The epidemiological survey of 4938 ethnically Japanese 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 or serum cholesterol levels among the participants.

# Regulations

## United States
Under current FDA regulations, when monosodium glutamate is added to a food, it must be identified as "monosodium glutamate" in the label's ingredient list. If MSG is part of a spice mix that is purchased from another company, the manufacturer is still required to list the ingredients of that spice mix including monosodium glutamate. Some companies whether intentionally or unknowingly may simply use the words "flavorings" or "spices" even if other ingredients including monosodium glutamate are present. This is technically against the regulation and should the company be questioned about it, would be required to update labels.
Also, monosodium glutamate is only one of several forms of free glutamate used in foods. Free glutamate may also be present in a wide variety of other additives, including: hydrolyzed vegetable proteins, autolyzed yeast, hydrolyzed yeast, yeast extract, soy extracts, protein isolate, "spices" and "natural flavorings." The food additives disodium inosinate and disodium guanylate are useful only in synergy with monosodium glutamate-containing ingredients, and provide a likely indicator of the addition of monosodium 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.
In 1993, FDA proposed adding the phrase "(contains glutamate)" to the common or usual names of certain protein hydrolysates that contain substantial amounts of glutamate. For example, if the proposal were adopted, hydrolyzed soy protein would have to be declared on food labels as "hydrolyzed soy protein (contains glutamate)."
In 1994, FDA received a citizen's petition requesting changes in labeling requirements for foods that contain MSG or related substances.  The petition asks for mandatory listing of MSG as an ingredient on labels of manufactured and processed foods that contain manufactured free glutamic acid. It further asks that the amount of free glutamic acid or MSG in such products be stated on the label, along with a warning that MSG may be harmful to certain groups of people. FDA has not yet taken action on the petition.

## Europe
Monosodium glutamate has the E number E621.

## Australia and New Zealand
Standard 1.2.4 of the Australia New Zealand 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 (eg. flavor enhancer), followed by either the name of the food additive (e.g. MSG) or its International Numbering System (INS) number (e.g. 621)