Glutamate benefit and side effects, risk and danger
October 24 2015 by
Ray Sahelian, M.D.


Glutamate is an amino acid, found in protein-containing foods. It is one of the most abundant and important components of proteins. Glutamate occurs naturally in cheese, milk, meat, fish, and many vegetables. Glutamate is also produced by the human body and is vital for metabolism and brain function.


Glutamate in the nervous system, brain

Glutamate is the principle excitatory amino acid in the central nervous system and is widely distributed. Regions in which glutamate seems particularly important include the granular cells of the cerebellum, the pyramidal cells of the hippocampus, the Betz cells of the motor strip, and the projections of the frontal lobe to the basal ganglia. One of the major difficulties in recognizing the role of glutamate as a neurotransmitter was the fact that there is only a small percentage of the glutamate present in synaptic vesicles. The vast majority of glutamate is present as part of intermediary metabolism. There are four glutamate receptor subtypes of importance: the NMDA receptor, the quisqualte receptor (also called the AMPA receptor), the kainate receptor, and the metabotropic receptor.


Protection by vitamin E?
Int J Vitam Nutr Res. 2014. Cytoprotective Effect of Tocotrienol-Rich Fraction and α-Tocopherol Vitamin E Isoforms Against Glutamate-Induced Cell Death in Neuronal Cells.


Monosodium glutamate (MSG)

This substance is used as a flavor enhancer in a variety of foods. Its use has become controversial because of reports of adverse reactions in people who've eaten foods that contain MSG. Research on the role of glutamate -- a group of chemicals that includes MSG -- in the nervous system also has raised questions about the chemical's safety. Studies have shown that the body uses glutamate as a nerve impulse transmitter in the brain and that there are glutamate-responsive tissues in other parts of the body, as well. Abnormal function of glutamate receptors has been linked with certain neurological diseases, such as Alzheimer's disease and Huntington's chorea. Injections of glutamate in laboratory animals have resulted in damage to nerve cells in the brain. Consumption of glutamate in food, however, does not cause this effect. While people normally consume dietary glutamate in large amounts and the body can make and metabolize glutamate efficiently, the results of animal studies conducted in the 1980s raised a significant question: Can MSG and possibly some other glutamates harm the nervous system?


Food Chem Toxicol. 2014 Feb 17. Protective effects of N-acetylcysteine against monosodium glutamate-induced astrocytic cell death.


In 1956 a direct fermentation method to produce glutamate was introduced. The advantages of the fermentation method, such as reduction of production costs and environmental load, were large enough to cause all glutamate manufacturers to shift to fermentation. As of 2009, total world production of MSG by fermentation is estimated to be 2 million tons/year (2 billion kg/year).


Glutamate Receptor changes after Radiation Therapy
Changes in hippocampal glutamate receptors may help explain the dementia that often occurs after whole-brain radiotherapy. Up to one half of the patients who receive whole-brain radiation to prevent brain tumor recurrence or the metastasis of other malignancies will display progressive memory problems at 1 year. Dr. Lei Shi and colleagues, from Wake Forest University School of Medicine in Winston-Salem, North Carolina, used a rat model of whole-brain radiation and focused on changes occurring in the hippocampus, an area critical for memory and learning. At 1 year, rats treated with radiation showed impaired learning and memory on a water maze compared with the animals given sham therapy. Further analysis showed that the hippocampal regions of radiation-treated rats contained a different composition of glutamate receptor than did the regions in control animals.


In the brain
Front Endocrinol (Lausanne). Dec 16  2013. Glutamate Pays Its Own Way in Astrocytes. In vitro and in vivo studies have shown that glutamate can be oxidized for energy by brain astrocytes. The ability to harvest the energy from glutamate provides astrocytes with a mechanism to offset the high ATP cost of the uptake of glutamate from the synaptic cleft.



Q. I just finished reading your book, "Mind Boosting Secrets, Natural Supplements That Enhance Your Mind, Memory and Mood". Can you tell me the difference between Glutamate and Glutamine? Which one do I take for anxiety and stress and also as a precursor to GABA? I was reading somewhere else that Glutamate is a toxin to the brain, specifically MSG.
   A. Glutamate or glutamine are not the best supplements to take for anxiety. Kava, 5-HTP, and passion flower are better options.


I would be grateful if you're able to clarify an important point, regarding "essential components of effective cognitive enhancement". Glutamic acid serves as a neurotransmitter vital to the transmission of nerve impulses, but apparently it also functions as a neurotoxin, causing neuron degeneration and cell death which I understand is linked to its "overstimulation" of these neurons - itself a main reason for the controversy surrounding the use of monosodium glutamate which unnaturally elevates free glutamate levels in the body. The same can be said of aspartic acid (found in the toxic sweetener aspartame) and phenylalanine. As various preparations (including the one I take) containing potentially "neurotoxic" elements are on sale as cognitive "enhancers", I am not confident I understand what - if anything - separates 'good' from 'bad' glutamic acid in the making of such preparations. How does anyone know an "enhancement" supplement containing, for example, glutamic acid (or aspartic acid) is safe, when we are warned not to take substances like MSG and aspartame?
   There is much yet to be learned regarding the benefits and side effects and potential neurotoxicity of glutamate and glutamic acid when ingested as supplements or in brain formulas that include a number of other herbs and nutrients. For the time being, it is a good idea to avoid supplements containing glutamic acid. There are many effective brain boosters that do not contain glutamic acid.


Iím confused about a few supplements that are similar or at least have similar sounding names. Even though I have tried to research them and know a little about them, I am confused about the safe use of them in regards to the possible excitotoxic effects of them. For instance, if I see l-glutamic acid as part of a formula containing other items for a particular health concern, should I be concerned about it being excitotoxic if taken this way? I will list a few others Iím confused about and if you donít mind, could you give a little information about each one regarding their safe or unsafe use in this regard? L-Glutamic Acid ( I believe this is supposed to be the safer one) D-Glutamic Acid, Glutamine ( I know this is good for stomach lining, ulcers, etc., Glutathione ( I understand that our bodies can make this antioxidant and may be better off with the precursors) I have read Dr. Russell Blaylockís books so try to be careful of excitotoxins. I would just like to know how to avoid excess glutamate accumulating in my brain besides the obvious culprit, msg and all Itís alias names it hides behind.
   Glutathione is an endogenous antioxidant.