Glutamic acid and its ions and salts, called glutamates, are flavor-enhancing compounds which provide an umami (savory) taste to food. Glutamic acid is a natural constituent of many fermented or aged foods, including soy sauce, fermented bean paste, and cheese, and is also a component of hydrolyzed protein such as yeast extract. The sodium salt of glutamic acid, monosodium glutamate (MSG), is a widely used additive in the food industry.
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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. 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.
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.[1][2]
Only the L-glutamate enantiomer has flavor-enhancing properties.[3] 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, steak sauce, and Worcestershire sauce have levels of glutamate similar to foods with added monosodium glutamate. However, 5% or more of the glutamate may be the D-enantiomer.[3]
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 "savory" or "meaty").
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.
Japanese cuisine originally used broth made from kombu (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.
In the Roman Empire glutamic acid was found in a sauce called "Garum", made from fermenting fish in saltwater. It was used so widely that it has been called "the ketchup of the ancient Romans." The flavor enhancing properties of glutamic acid allowed Romans to reduce the use of expensive salt.[4][5]
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.[6]
| Food | Free glutamate (mg/100 g) | Protein glutamate (mg/100 g) |
|---|---|---|
| Marmite | 1960 | |
| Vegemite | 1431 | |
| Roquefort cheese | 1280 | |
| Parmesan cheese | 1200 | 9847 |
| Chinese soy sauce | 1090 | |
| Japanese soy sauce | 782 | |
| Grape juice | 258 | |
| Peas | 200 | 5583 |
| Tomatoes | 140 | 238 |
| Corn | 130 | 1765 |
| Cow milk | 2 | 819 |
| Human milk | 22 | 229 |
| Eggs | 23 | 1583 |
| Chicken | 44 | 3309 |
| Duck | 69 | 3636 |
| Beef | 33 | 2846 |
| Pork | 23 | 2325 |
| Salmon | 20 | 2216 |
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.
In April 1968, Robert Ho Man Kwok wrote a letter to the New England Journal of Medicine, 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, 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...[7]
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.[8] The syndrome 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, headache, nausea, rapid heartbeat, bronchospasm in people with asthma, drowsiness, and weakness.[9]
While many people believe that monosodium glutamate (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.[10][11][12][13] Adequately controlling for experimental bias includes a placebo-controlled double-blinded experimental design and the application in capsules because of the strong and unique after-taste of glutamates.[10]
A 2002 study found that rats fed on diets supplemented with 10% and 20% pure monosodium glutamate suffered retina degeneration, possibly through glutamate accumulation in the vitreous humor[14] . 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.[15]
In 1959, the U.S. Food and Drug Administration (FDA) classified monosodium glutamate as generally recognized as safe (GRAS).[16] This action stemmed from the 1958 Food Additives Amendment to the Federal Food, Drug, and Cosmetic Act 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 (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:
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.[17][18][19] 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.[20][21] 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.[22] 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.[23]
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.[24][25] While they agree that the combined effects of all food-based excitotoxins should be considered,[26] 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.[27]
Other scientists around John Olney felt that primates are susceptible to excitotoxic damage[28] and that humans concentrate excitotoxins in the blood more than other animals.[29] Based on these findings, they feel that humans are approximately 5-6 times more susceptible to the effects of excitotoxins than rodents are.[30] 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[31] and the potential long-term neurodegenerative effects of small-to-moderate spikes on plasma excitotoxin levels.[32]
In 2008, a collaboration between American and Chinese 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.[33][34][35] 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.[36]
Previously, 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 used in obesity research using rats and mice, and also observed in Chinese hamsters) was not dependent on additional food intake.[37] 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.[38] 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.[39]
However, an earlier study (1973) did not find a similar effect in humans. The epidemiological survey of 4,938 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.[40][41] Researchers furthermore found that frequent monosodium glutamate consumption did not significantly affect blood sugar or serum cholesterol levels among the participants.
Monosodium glutamate may worsen non-alcoholic fatty liver disease caused by trans fats.[42]
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 of the salt has to be listed. Glutamic acid and its salts as food additives have the following E numbers: glutamic acid: E620, monosodium glutamate: E621, monopotassium glutamate: E622, calcium diglutamate: E623, monoammonium glutamate: E624, and magnesium diglutamate: 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.[43]
In 1959, the Food and Drug Administration classified MSG as a "generally recognized as safe" (GRAS) food ingredient under the Federal Food, Drug, and Cosmetic Act. 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 (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.[44]
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 products such as soy sauce, and autolyzed yeast extracts. These ingredients are to be declared on the label by their common or usual names.[44] 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 and disodium guanylate 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.[9]
As of 2002 the National Academy of Sciences Committee on Dietary Reference Intakes had not set a NOAEL or LOAEL for glutamate.[43][45]
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 (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)
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.[46]