MfG: The ingredient in protein supplements and flavor enhancers such as MSG that can cause brain damage
Most everyone has heard of MSG. Spelled out that’s monosodium glutamate, a widely used and advertised flavor enhancer and salt substitute. What isn’t advertised is the fact that the manufactured free glutamic acid (MfG) component of MSG could be killing brain cells in the arcuate nucleus of the hypothalamus and killing or damaging other brain cells while it is giving the food with which it is eaten a “bigger, more robust taste.
You may know glutamic acid (a.k.a. glutamate) from high school biology or study of neuroscience. It’s one of approximately 20 amino acids that make up life. It’s an acidic amino acid which when present in protein or released from protein in a regulated fashion (through routine digestion) is vital for normal body function. It is the principal neurotransmitter in humans, carrying nerve impulses from glutamate stimuli to glutamate receptors throughout the body.
Following ingestion of protein and during the course of normal digestion, glutamic acid is released from ingested protein becoming free glutamic acid. If sufficient amounts of free glutamic acid are not available for normal body function, the body can create glutamic acid from other amino acids. Humans do not need to eat glutamic acid or eat protein that contains glutamic acid in order to supply the body with the glutamic acid that it needs. For that reason, glutamic acid is referred to as a “non-essential” amino acid.
In addition to being released from ingested protein during digestion or created in the body from other amino acids, glutamic acid can be freed from protein prior to ingestion and be ingested as a free amino acid. Fermentation, enzymolysis, use of acids, or other manufacturing processes are all ways to create free glutamic acid.
When present outside of protein in amounts that exceed what the healthy human body was designed to accommodate, glutamate becomes an excitotoxic neurotransmitter, firing repeatedly, damaging targeted glutamate-receptors and/or causing neuronal and non-neuronal death by over exciting those glutamate receptors until their host cells die. In 1969, neuroscientist Dr. John Olney coined the word “excitotoxin” to describe this phenomenon.
The potentially excitotoxic amino acid glutamate becomes actively excitotoxic only when there is an accumulation of glutamate (or glutamate plus other excitotoxic amino acids) that exceeds what the human body requires for normal functioning.
To repeat: In controlled quantities, glutamate does not express excitotoxicity. Yet, when present outside of protein in excess (amounts that exceed what the healthy human body was designed to accommodate) glutamate becomes an excitotoxic neurotransmitter, firing repeatedly, damaging targeted glutamate-receptors and/or causing neuronal and non-neuronal death by over exciting those glutamate receptors until their host cells die.
The first study to address the possibility that glutamate from exogenous sources (such as eating) might cause brain damage followed by obesity and reproductive dysfunction was published by Olney in 1969. At the time, researchers were administering glutamate to laboratory animals subcutaneously using Accent brand MSG because it had been observed that MSG was as effective for inflicting brain damage as the more expensive pharmaceutical grade L-glutamate.
In the decade that followed, research confirmed that glutamate given as monosodium glutamate to neonatal animals causes hypothalamic damage, endocrine disruption, and behavior disorders when delivered to immature animals either subcutaneously or orally.
In the 1980s, researchers focused on identifying and understanding abnormalities
associated with free glutamate, often for the purpose of finding drugs that would mitigate glutamate’s adverse effects.
It is well documented that free glutamate is implicated in kidney and liver disorders, neurodegenerative disease, and more. By 1980, glutamate-associated disorders such as headaches, asthma, diabetes, muscle pain, atrial fibrillation, ischemia, trauma, seizures, stroke, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), multiple sclerosis, Huntington’s disease, Parkinson’s disease, depression, schizophrenia, obsessive-compulsive disorder (OCD), epilepsy, addiction, attention-deficit/hyperactivity disorder (ADHD), frontotemporal dementia and autism were on the rise, and evidence of the toxic effects of glutamate were generally accepted by the scientific community. A July 4, 2021 search of the National Library of Medicine using PubMed.gov returned 3971 citations for “glutamate-induced.”
Glutamic acid found in unprocessed, unadulterated, and/or unfermented food and in the human body is composed of one form of a single amino acid, L-glutamic acid, and nothing more. In contrast, MfG, the glutamic acid that is freed from protein through a manufacturing process or through fermentation is always accompanied by D-glutamic acid and a variety of other by-products of L-glutamic acid production (impurities). This remains true regardless of the method used to produce L-glutamate, be it through use of genetically modified bacteria that feed on various nutrients and excrete L-glutamate and impurities through their cell walls or though extraction of glutamate from protein using hydrolysis or autolysis. Thus, the glutamic acid that is used as a flavor enhancer or protein substitute is always composed of L-glutamic acid, D-glutamic acid and impurities that inevitably appear during fermentation or other modes of glutamic acid manufacture or processing. In addition to the inevitable production of D-glutamic acid, impurities may include, but are not limited to, pyroglutamic acid, mono and dichloro propanols, and heterocyclic amines. Mono and dichloro propanols and heterocyclic amines are carcinogenic. The consequences of the interactions of these various chemicals with other chemicals and/or with the digestive processes are unknown.
There is no reason to believe that the glutamic acid in monosodium glutamate or any other product of glutamate manufacture will be functionally equivalent to pure, unadulterated, L-glutamic acid. There is no reason to believe that the processed and the unprocessed chemicals will behave identically.
For purposed of clarification
Free glutamic acid is glutamic acid that has been released from protein. Just as humans have two hands, glutamic acid has two enantiomers (chemically identical molecules with the L-enantiomer being the mirror image of the D-enantiomer). Just like most other alpha-amino acids, glutamic acid contains a stereogenic center and exists as the L- and D-enantiomers.
- “The word chiral, from the Greek word for hand, alludes to molecules that exist in mirror-image versions — right-handed or left-handed. Although they appear to be identical twins, chiralmolecules are fundamentally different. One molecular twin cannot be substituted for the other because they are asymmetrical. The difference is comparable to asymmetry between your right and left hand: One is a mirror image of the other, but you cannot fit your right hand into a left-hand glove.” (1)
- “Although it has been generally accepted that the free amino acids and proteins found in higher organisms are composed exclusively of the L-enantiomers of amino acids, the mirror image D-forms are known to be present in some naturally occurring peptide antibiotics and in the cell walls of bacteria.” (2)
Naturally freed glutamic acid is glutamic acid that has been freed from ingested protein during digestion, or glutamic acid that has been transaminated (created) from other amino acids. It is also possible that there are some minute amounts of naturally freed glutamic acid associated with some intact, unadulterated, unprocessed, unfermented protein. Naturally freed glutamic acid found in higher organisms is made of L-glutamic acid only.
- “Natural food protein, as well as protein in the human body, contains only L-forms of amino acids.” (3)
- “Unlike amino acids derived from natural protein, which possess only the structure (S)-12, synthetic amino acids are composed of equal mixtures of (S)-12 and (R)-12.” (4)
Note: In this paper, (S)-12 refers to the L-amino acids and (R)-12 refers to the D-amino acids.
- “There were contrasting views expressed on the use of the various isometric forms (the natural L-form or the commercially available mixtures of DL-forms) of amino acids.” (5)
- “The chemical structure of L-glutamic acid and related compounds and the chemical composition of MSG are represented in Figure 1….Two possible stereoisomeric forms of glutamic acid exist, D and L. According to Maga (1983) the L form (dextrorotary form with the L-configuration) is the predominant natural form….” (6,7)
- “Because D-amino acids are rare in higher animals…” (8)
Manufactured free glutamic acid (MfG) is glutamic acid that has been freed from protein through a manufacturing process or fermentation prior to ingestion, or glutamic acid that has been grown from selected bacteria that secrete glutamic acid through their cell walls. There are over 40 ingredients in which MfGwill be found. “Monosodium glutamate,” “autolyzed yeast,” and “natural flavoring” are names of some of those ingredients. (In the first FDA classification of such ingredients, the FDA called them “monosodium glutamate and other hydrolyzed proteins.”) The amount of free glutamic acid (MfG) that will be found in each is dependent on the method used to produce it, the protein source used (if bacterial fermentation was not used), and the extent of the processing.
Manufactured free glutamic acid is made up of L-glutamic acid and D-glutamic acid, and may bring with it pyroglutamic acid, mono and dichloro propanols (which are carcinogenic), heterocyclic amines (which are carcinogenic), and other unwanted byproducts (impurities).
- “Foods contain a large assortment of xenobiotics (foreign, unnatural substances) that can have both positive and negative nutritional implications. One example is the occurrence of the uncommon D-stereoisomers of amino acids in some dietary proteins. These D-amino acids are produced from the common L-stereoisomers during food preparation and processing.” (9)
- In table 1 of a research report by Rundlett and Armstrong, the authors present a list of all of the processed foods analyzed by them for L and D-glutamate (glutamic acid) content. Every one of the 38 processed foods evaluated contained D-glutamate. Three of those analyzed and found to have D-glutamate content were three brands of monosodium glutamate, including Ac’cent Flavor Enhancer, once marketed by Pet Incorporated. (10)
- “hydrolysis of proteins in 6 N HCl at 110 degrees centigrade for 24 h inevitably causes racemization of amino acids….Even under milder conditions of hydrolysis using lower temperatures and shorter exposure time, racemization of amino acids occurs.” (11)
- “Savory ingredients like hydrolyzed vegetable protein… have…been produced by….extreme conditions….[that] promote a variety of chemical reactions, thus a range of unwanted by-products are produced as well.” (12)
- “The chemical hydrolysis with hydrochloric acid is efficient, but almost any organic substance in the raw material is hydrolyzed, resulting in desired reactions such as hydrolysis of proteins, carbohydrates, fats (triglycerides), and the unwanted formation of mono and dichloro propanols (MCP and DCP).” (12)
- “Pyroglutamic acid…occurs as a breakdown product of glutamate that can accumulate in foods during storage and processing.” (13)
- “I have been asked to give testimony on the chemical nature of glutamates in food. The parent compound in the glutamate family is glutamic acid, an amino acid and normal component of the human body….Glutamic acid exists in two forms: (L)-glutamic acid and (D)-glutamic acid. The L and D designations indicate different spatial arrangements of the atoms of the two forms. (D)- and (L)- glutamic acid molecules are mirror images, relating to each other in the same way as a glove for the right hand relates to its mate for the left hand. Just as certain properties of the left-hand glove differ from those of the right-hand glove (e.g., the left-hand glove cannot be worn on the right hand, and vice versa), so (L)-glutamic acid and (D)-glutamic acid differ from each other in certain other properties. For example, in the body, (D)-glutamic acid is not broken down (metabolized) in the same way as the (L) form because the enzymes that recognize and work on the (L) form do not recognize, and, therefore, ‘ignore,’ the (D) form. Nearly all naturally occurring glutamic acid is in the (L) form.” (14)
1. Bruce V. Bigelow, staff writer, San Diego Union-Tribune. October 4, 1995. (Source K. Barry Sharpless)
2. Rundlett, K.L. and Armstrong, D.W.. Evaluation of free D-glutamate in processed foods. Chirality. 1994;6:277-282.
3. Hunter, B.T. The Great Nutrition Robbery. New York, NY: Charles Scribner’s Sons, 1978, page 135.
4. Cram, D.J. and Cram, J.M. Host-Guest Chemistry: Complexes between organic compounds simulate the substrate selectivity of enzymes. Science. 1974;183:803-809.
5. Federal Register. Vol 38, No. 143–Thursday, July 26, 1973, page 20037
6. Maga, J.A.. Flavor potentiators. Critical Rev. Food Sci. Nutr. 1983;18:231-312.
7. Life Sciences Research Office of the Federation of American Societies for Experimental Biology. Analysis of adverse reactions to monosodium glutamate (MSG). July, 1995. Prepared for the Center for Food Safety and Applied Nutrition, Food and Drug Administration. Page 9.
8. Konno, R. et al. Origin of D-alanine present in urine of mutant mice lacking D-amino-acid oxidase activity. American Journal of Physiology, 1993, 265:G699-703.
9. Man, E.H. and Bada, J.L. Dietary D-Amino Acids. Ann. Rev. Nutr. 1987;7:209-25.
10. Rundlett, K.L. and Armstrong, D.W. Evaluation of free D-glutamate in processed foods. Chirality. 1994;6:277-282.
11. Konno, R. et al. Origin of D-alanine present in urine of mutant mice lacking D-amino-acid oxidase activity. American Journal of Physiology, 1993, 265:G699-703.
12. Pommer, K. (Novo Nordisk BioChem Inc., Franklinton, NC) Cereal Foods World. October, 1995 Vol 40. No 10. Page 745.
13. Life Sciences Research Office of the Federation of American Societies for Experimental Biology. Analysis of adverse reactions to monosodium glutamate (MSG). July, 1995. Prepared for the Center for Food Safety and Applied Nutrition, Food and Drug Administration. Page 31.
14. Expert Report of Paul M. Kuznesof, Ph.D., Chief of the Chemistry Review Branch in the Division of Product Manufacture and Use, Office of Premarket Approval, Center for Food Safety and Applied Nutrition, FDA. The Report was submitted on September 3, 1996 to the Federal Court in the Eastern District of Missouri re: Truth in Labeling Campaign, et al., vs. Shalala et al., pages 1-3.