Extensive scientific studies conducted across the globe have collectively demonstrated that MSG and glutamate are generally safe for human consumption.

Key findings indicate that typical dietary doses of MSG do not have adverse health effects. They also showcase that the global regulatory bodies such as JECFA and EFSA support the safety of MSG.

The Safety Evaluation of Monosodium Glutamate

Author: Ronald Walker, School of Biological Sciences, University of Surrey, UK; John R. Lupien, Food and Nutrition Division, FAO, Roma, Italy

Year: 2000

Summary: This review discusses the safety evaluation of MSG by various regulatory bodies. It was found that regulatory evaluations by JECFA, SCF, and other bodies have found MSG safe for consumption. No adverse effects have been observed in conventional toxicity, reproduction, or teratology studies. Despite some concerns about potential central nervous system lesions in neonates, human studies have not linked MSG to “Chinese Restaurant Syndrome” or other intolerances. Overall, MSG has been deemed safe with an “acceptable daily intake not specified,” confirming its safety for all age groups.

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Monosodium Glutamate a Safety Assessment

Author: Food Standards Australia New Zealand

Year: 2003

Summary: This safety assessment found that there is no convincing evidence that MSG is a significant factor in causing systemic reactions resulting in severe illness or mortality. The studies conducted to date on CRS have largely failed to demonstrate a causal association with MSG. Symptoms resembling those of CRS may be provoked in a clinical setting in small numbers of individuals by the administration of large doses of MSG without food. However, such effects are neither persistent nor serious and are likely to be attenuated when MSG is consumed with food. In terms of more serious adverse effects such as the triggering of bronchospasm in asthmatic individuals, the evidence does not indicate that MSG is a significant trigger factor.

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Understanding safety of glutamate in food and brain

Author: H. N. MALLICK, Department of Physiology, All India Institute of Medical Sciences, New Delhi

Year: 2007
Summary:  There are important species differences and differences with age and routes of administration in the glutamate sensitivity of CNS. The brain in general is a net exporter of glutamate and the presence of the blood brain barrier prevents exogenous glutamate from acting on the brain.

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A Test of Dietary Monosodium Glutamate Developmental Neurotoxicity in Rats: A Reappraisal

Author: Charles V. Vorhees, Department of Pediatrics, University of Cincinnati College of Medicine and Division of Neurology, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA.
Year: 2018
Summary: The study revisited a 1979 experiment that evaluated the potential developmental neurotoxicity (DN) of dietary monosodium glutamate (MSG) in rats. The study found four statistically significant effects out of 36 measured variables, none of which were consistent or biologically meaningful. The study concluded that the 1979 findings should not be used as a basis for regulatory changes regarding MSG without further contemporary studies.
 

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Glutamate: A Safe Nutrient, Not Just a Simple Additive

Authors: Cécile Loïa, CITRAGE, Boissy St Léger, France, Luc Cynoberb, Laboratoire de Biologie de la Nutrition, Faculté de Pharmacie

Year: 2022

Summary:The review was conducted to assess the contribution of different dietary sources of glutamate, impact of glutamate form (free or protein-bound) and its safety. The review found no compelling evidence to indicate any ADI, stating that Glutamate should be considered as a safe nutrient before being considered as an additive. 

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Evaluation of certain food additives and contaminants: JECFA

Author: Joint FAO/WHO Expert Committee on Food Additives (JECFA)

Year: 1987

Summary: The committee concluded, based on the analysis of blood levels of glutamic acid in human subjects associated with various dietary regimens, that peak plasma levels are dependent on the food vehicles in which the compound is incorporated and that infants metabolise monosodium glutamate in a similar way to adults. In the light of all data, the committee allocated an ADI “not specified” to monosodium glutamate when incorporated into food or used as a condiment; this ADI applies to all glutamates, alone and in combination.

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Toxicological evaluation of certain food additives with a review of general principles and of specifications: JECFA

Author: Joint FAO/WHO Expert Committee on Food Additives (JECFA)
Year: 1974
Summary: An Acceptable Daily Intake (ADI) of 0–120 mg/kg body weight was allocated,
encompassing the L-glutamic acid equivalents of the salts; this was considered additional to the intake from all nonadditive dietary sources. In the absence of human infant data at that time, and in view of the observation that neonatal rodents appeared to be more sensitive than adults to the neurologic effects of high blood levels of glutamate, it was stated that the ADI did not apply to infants 12 wk of age.
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A Review of the Alleged Health Hazards of Monosodium Glutamate

Author: Anca Zanfirescu, Anca Ungurianu, Aristides M Tsatsakis, George M Nițulescu, Demetrios Kouretas, Aris Veskoukis, Dimitrios Tsoukalas, Ayse B Engin, Michael Aschner, Denisa Margină

Year: 2019

Summary: The study provides a comprehensive examination of the potential health risks associated with MSG consumption. It surveys existing literature, focusing on preclinical studies and clinical trials. The review highlights various reported adverse effects, such as cardiotoxicity, hepatotoxicity, neurotoxicity, metabolic disorders, and behavioral changes.
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Risk Assessment Paradigm for Glutamate

Authors: Ashley Roberts & Barry Lyncha, Intertek Scientific and Regulatory Consultancy Health, Environmental and Regulatory Services (HERS), Mississauga,ON, Canada, Barry Lyncha and Ivonne M.C.M. Rietjens, Division of Toxicology, Wageningen University, Wageningen, The Netherlands
Year: 2018

Summary: The study was conducted to re-evaluate the safety of glutamate (MSG) consumption, and the ADI levels defined by EFSA in 2017. In conclusion, the study called for a revision of the current ADI for glutamate, arguing that the EFSA’s assessment does not align with the extensive body of scientific evidence supporting the safety of glutamate at higher levels of consumption.
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Review of Glutamate Intake from Both Food Additive and Non-Additive Sources in the European Union

Author: David R. Tennant, Independent Scientific Adviser, Food Chemical Risk Analysis, East Sussex, East Dean, UK

Year: 2018

Summary: Intakes of glutamate can be derived from its natural occurrence as a constituent of proteins, from the presence of free glutamate in certain fermented foods, and from the addition of glutamic acid and glutamates to foods as flavor-enhancing additives. Findings: Intakes of glutamate following hydrolysis of dietary proteins can be as high as 440 mg/kg bw/day for toddlers and small children.
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Effects of monosodium glutamate on human health: A systematic review

Authors: Tushar Kanti Bera, Sanjit Kumar Kar, Prem Kumar Yadav, Prithwiraj Mukherjee, Shankar Yadav, Bishal Joshi from Department of Physiology, Universal College of Medical Sciences, Bhairahawa, Lumbini Zone, Nepal

Year: 2017

Summary: 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.

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Update on food safety of monosodium l-glutamate (MSG)

Author: Helen Nonye Henry-Unaeze, Department of Human Nutrition and Dietetics, College of Applied Food Sciences and Tourism, Michael Okpara University of Agriculture, Umudike, Nigeria

Year: 2017

Summary: An evidence-based safety review of the flavor enhancer monosodium l-glutamate (MSG) was triggered by its global use and recent studies expressing some safety concerns.

It was found that the human body processes glutamate from both food and added MSG in the same way, without ethnic differences, and metabolizes it entirely within the gut and liver. Normal dietary levels of MSG are safe and well-regulated, with recent studies showing no consistent adverse reactions even in sensitive individuals.

It was concluded that high quality MSG is safe for all life-cycle stages without respect to ethnic origin or culinary background.

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Does monosodium glutamate really cause headache? a systematic review of human studies

Authors: Yoko Obayashi, IGTC and Yoichi Nagamura, Faculty of Health Science, Department of Clinical Nurition, Suzuka University of Medical Science, Japan

Year: 2016

Summary: Based on the systematic review, it was found that human studies are not consistent, and it was assumed that most studies used beverages as a vehicle were not properly blinded. It is suggested that a causal relationship between MSG and headache has not been proven. In addition, statistically significant differences in the incidence of headache were not observed when MSG was administered with food, except in one case of the female group where the blind integrity was questionable. It would seem premature to conclude that the MSG present in food causes headaches.
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Consensus meeting: monosodium glutamate – an update

Author: K Beyreuther, HK Biesalski, JD Fernstrom, P Grimm, WP Hammes, U Heinemann, O Kempski, P Stehle, H Steinhart and R Walker

Year: 2007

Summary: Glutamate from all sources is mainly used as energy fuel in the body. A maximum intake of 16.000 mg/kg body weight is regarded as safe. The general use of glutamate salts (MSG and others) as food additive can, thus, be regarded as harmless for the whole population.
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Is there a relationship between dietary MSG obesity in animals or humans?

Authors: John T. Brosnan, Department of Biochemistry, Memorial University

of Newfoundland, St. John’s, Canada, Adam Drewnowski, Center for Public Health Nutrition, University of Washington, USA and Mark I. Friedman, Monell Chemical Senses Center, Philadelphia, PA, USA

Year: 2014

Summary: Such studies have been shown to have no relevance to animals or humans under normal or even extreme conditions of MSG ingestion. The fundamental reason is that glutamate is metabolically compartmentalized in the body, and generally does not passively cross biologic membranes. Hence, almost none of the ingested glutamate (including MSG) passes from the gut lumen into the circulation, and essentially none transits the placenta in either direction between maternal and fetal circulations or crosses the blood–brain barrier. Ingesting MSG (glutamate) in food, therefore, does not cause elevations in glutamate concentrations in brain.
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Glutamate - A Multifaceted Molecule: Endogenous Neurotransmitter, Controversial Food Additive, Design Compound for Anti-Cancer Drugs. A Critical Appraisal

Authors: Octavia-Laura Moldovan, Aura Rusu, Corneliu Tanase, Camil-Eugen Vari
Year: 2021
Summary: This review was focused on the long-term toxicity of MSG – with its primary purpose being a survey of the data regarding the consumption of MSG within safe limits. The review, on the basis of scientific studies, stated that MSG, when combined with other compounds, may offer benefits against toxic effects and even serve as a potential anti-
cancer agent.

Intestinal Mucosal Amino Acid Catabolism

Author: Guoyao Wu
Year: 2023
Summary: The study investigated how the small intestine catabolizes dietary amino acids, impacting their availability to extraintestinal tissues and the efficiency of dietary protein utilization. It found that 96% of glutamate delivered enterally is extracted in the first pass by the human splanchnic bed, highlighting that dietary glutamine and glutamate do not significantly enter the portal circulation. Instead, they are metabolized within the intestine, which suggests that these amino acids primarily support intestinal functions rather than being available to other tissues.

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Monosodium Glutamate Induces Limited Modulation in Gut Microbiota

Authors: Qiannan Peng, Dongxue Huo, Chenchen Ma, Shuaiming Jiang, Linsong Wang, Jiachao Zhang

Year: 2018

Summary: The study assessed the effects of MSG consumption on the human intestinal microbiota, particularly focusing on whether MSG alters the microbial community structure and functional features within the gut. It found that while certain bacteria showed variation trends, there were no significant changes in the overall composition of the gut microbiota during the different MSG consumption phases. The results of the study suggest that MSG consumption at typical dietary levels may not significantly alter gut microbiota in healthy individuals.

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Monosodium L-Glutamate and Dietary Fat Differently Modify the Composition of the Intestinal Microbiota in Growing Pigs

Authors: Ze-Meng Feng, Tie-Jun Li, Li Wu, Ding-Fu Xiao, Francois Blachier, Yu-Long Yin

Year: 2015

Summary: This study examined how MSG and dietary fat affect the composition of the intestinal microbiota in growing pigs. The results showed that both MSG and fat increased microbial diversity, particularly in the colon. MSG promoted the colonization of Faecalibacterium prausnitzii and Roseburia, while fat increased the presence of Prevotella. The study suggests that individual or combined dietary changes can modify microbiota composition, which may have implications for preventing obesity.

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Physiological roles of dietary glutamate signalling via gut–brain axis due to efficient digestion and absorption

Author: Kunio Torii, Hisayuki Uneyama, Eiji Nakamura, Institute for Innovation, Ajinomoto Co., Inc

Year: 2013
Summary: The study was conducted to highlight that dietary glutamate (Glu) is more than just an umami flavoring agent; it plays a critical role in the body’s energy metabolism, particularly within the gastrointestinal (GI) tract. In conclusion, the study underscored the integrative role of dietary Glu in digestion, nutrient absorption, and metabolic regulation, highlighting its significance beyond mere flavor enhancement in food.

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Supplementing chicken broth with monosodium glutamate reduces hunger and desire to snack but does not affect energy intake in women

Author: Brett E Carter, Pablo Monsivais, Martine M Perrigue, Adam Drewnowski, Nutritional Sciences Program, School of Public Health, Center for Public Health Nutrition, University of Washington, Seattle
Year: 2011
Summary: The study explored the impact of monosodium glutamate (MSG) on energy intake, specifically in middle-aged healthy women. It involved a controlled experiment where participants were given chicken broth with and without added MSG. The study’s results were significant in indicating a potential dietary strategy for weight management, particularly for those seeking to reduce calorie intake without significantly altering their diet.
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Intestinal glutamate metabolism

Author: Peter J. Reeds,3 Douglas G. Burrin, Barbara Stoll and Farook Jahoor, U.S. Department of Agriculture/Agricultural Research Service, Children’s Nutrition Research Center,Department of Pediatrics, Baylor College of Medicine, Houston, TX
Year: 2000
Summary: The research examined how the gut utilizes dietary and endogenous glutamate, largely directing it towards energy production rather than transporting it in free form into the bloodstream. Findings from the study revealed that glutamate plays a pivotal role in maintaining intestinal integrity and function, while also influencing overall nitrogen metabolism in the body. This research provides insights into how amino acid metabolism in the intestines affects overall physiological functions and may inform nutritional strategies in clinical settings.
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The role of dietary Glutamate in the intestine

Author: Daniel Tomé, UMR PNCA, INRA, AgroParisTech, Université Paris-Saclay, Paris, France

Year: 1998

Summary: The study was conducted to explore the roles of dietary glutamate in the intestine. It found that dietary glutamate plays numerous roles in the intestine, being involved in energy metabolism, in the synthesis of important bioactive molecules, and in sensory and signaling pathways. It also found that most ingested glutamate is metabolized locally, keeping peripheral blood levels low except after high doses. Glutamate also contributes to taste and oral sensations. 

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Free Amino Acids in Human Milk: A Potential Role for Glutamine and Glutamate in the Protection Against Neonatal Allergies and Infections

Author: Joris H. J. van Sadelhoff, Astrid Hogenkamp, Selma P. Johan Garssen

Year: 2020

Summary: The review examined the composition of free amino acids (FAAs) in human milk, particularly glutamate and glutamine, and to explore their potential roles in neonatal immune development and protection against allergies and infections. It found that free glutamine and glutamate, which constitute nearly 70% of the FAA content in human milk, drastically increase in the first 3 months of lactation and their levels have been shown to positively correlate with infant growth, suggestive of important functions in the developing neonate. These FAAs may also influence gut microbiota and help protect neonates against allergic sensitization and infections.

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Glutamate Supply and Metabolism in Infants

Author: Berthold Koletzko, Ludwig-Maximilians-University Munich, Dr. von Hauner Children’s Hospital, University of Munich Medical Center, Munich, Germany
Year: 2018
Summary: The study reviewed the glutamate (Glu) supply and metabolism in infants. It highlighted that glutamate is the most abundant amino acid in human milk, and its metabolism is crucial for infant growth and development. The researchers showed that dietary glutamate is almost entirely metabolized in the splanchnic organs (gut and liver), with little to no effect on plasma glutamate levels. It concluded that there is no evidence suggesting that high glutamate intake from breast milk or certain formulas is harmful to infants.
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Free glutamic acid content of milk in Indian mothers

Authors: Poonam Singh, Department of Obstt. and Gynaecology, Majeedia Hospital, Hamdard Nagar, New Delhi, S. K. SAXENA, Food and Research Analysis Centre, Federation House, Tansen Marg, New Delhi and H. N. MALLICK, Department of Physiology, All India Institute of Medical Sciences, New Delhi

Year: 2004

Summary: The study was conducted to determine the relative concentrations of glutamic acid and glutamine in the milk of healthy Indian mothers. It found that glutamic acid is the most abundant free amino acid in the milk of Indian mothers. It also stated that high levels of free glutamic acid in human milk are significant for neonatal physiology. Glutamate is rapidly metabolized in the gut for energy and serves as a key substrate in the citric acid cycle. It supports intestinal cell energy needs and may be crucial for synaptogenesis in nervous tissue during early development. 

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Glutamate-induced brain damage in infant primates. Reports of the Scientific Committee for Food on a First Series of Food Additives of Various Technological Functions

Author: Commission of the European Communities

Year: 1991

Summary: The review found that L-Glutamic acid is a component of animal and plant proteins and represents some 20% of ingested protein. It concluded that no acute, subchronic and chronic toxicity was found in mice, rats and dogs. Also, there was no evidence of carcinogenic or genotoxic potential. The Committee established a group ADI not specified based on the available data and evidence. 

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