Glutamate is a non-essential amino acid and can either be bound in protein as found in whole commercially unprocessed foods (glutamic acid) or unbound as a free amino acid found in food additives or resulting from processing or manufacturing processes, commonly known as free glutamate. Monosodium Glutamate is a manufactured ingredient that contains free glutamate. Amino acids are the molecular building blocks of proteins, and as these proteins are degraded, the result is the free amino acids, including the neurotoxin/excitotoxin-free glutamate. Glutamate is also the most abundant neurotransmitter, regulating over 50% of the nervous and sensory systems.

What is the Importance of Glutamate?

Glutamate is considered to be an excitatory neurotransmitter, which means it excites or stimulates nerve cells located throughout the nervous system. The excitatory pathway is responsible for a wide variety of functions like releasing adrenaline, controlling movement and motor systems, learning, memory, and expressing thought. It works in tandem with the inhibitory neurotransmitter GABA (gamma-aminobutyric acid), which calms and relaxes nerve cells. GABA is also imperative for sensory integration, sleep, speech, and language.  Glutamate and GABA have a relationship similar to a seesaw. When glutamate is high, GABA is low, and vice versa.  Children with autism and related disorders tend to lean towards excess glutamate and low GABA, but a balance must be maintained for their bodies and nervous system to function correctly. Supplementing with GABA is not suggested as it can be converted back to glutamate.

Glutamate is highly toxic to the brain and nervous system when in excess. It can become so excitatory it is considered an excitotoxin, which means that it overstimulates brain cells to the point of killing them or damaging them enough to cause severe mitochondrial dysfunction (associated with low muscle tone) and neurological inflammation.  This neural damage can essentially change how the brain is “wired.” Beyond the nervous system, glutamate is involved in nitrogen balance, energy balance, and a vast host of cell functions like regulating insulin secretion.

Excess glutamate is believed to be involved in a variety of neurological and neurodegenerative disorders, including autism, obsessive-compulsive disorders, hyperactivity disorders, complex motor stereotypes, tics, insomnia, anxiety disorders, seizures, sensory processing disorder, addiction, depression, chronic fatigue, PANS, PANDAS, Alzheimer’s, and so on. Elevated levels of glutamate trigger the brain to release endorphins (the nervous system’s natural opioids) to protect the brain from damage, which can result in feelings of spaciness and eventually contribute to the depletion of your natural opioids. Excess glutamate also impairs methylation and depletes glutathione levels, which are vital for detoxification, inflammation, and gut health.

What Would Cause Someone to be More Sensitive to Glutamate?

Chronic inflammation, microglial activation, autoimmune disorders, neurological damage, poor detoxification pathways, GAD mutations, toxins, glyphosate, aluminum, mercury, etc., all increase glutamate and signaling.  Even various microbes/parasites promote an environment for glutamate metabolism, increasing glutamate signaling. Glutamate initiates the inflammatory response and vice versa. Inflammation causes the cells to signal additional glutamate.

For example, glutamate receptors reside on many different cell types throughout the body, and the number and function of these receptors are dependent on the environment and stress.  For example, one of the functions of the cells in our nervous system and our digestive tract is to report about their environment to our brain and the rest of the body. These cells (glial cells) report on the gut environment by releasing signals from their cells, and one of these signals is glutamate. So, if it senses a stress response, like inflammation from glutamate, it releases more glutamate to send the stress signal throughout the body. Then the glial cells, which are also the cells that are responsible for protecting the intestinal barrier, start to die off.  As these glial cells start to die off, it leads to intestinal permeability, aka leaky gut, due to the inflammation associated with excess glutamate levels.

Similarly, microglia are a type of glial cell located in the brain and the spinal cord. They act as the first and foremost* form of immune defense in protection against foreign invaders in the central nervous system (CNS). When the microglia are chronically activated (either from single stimuli or multiple stimuli such as vaccines, physical injuries, or chronic underlying infections), they disrupt brain function and neuronal loss due to their surge of damaging cytokines and excitotoxic levels of glutamate.  For example, exposure to a prolonged viral infection can increase glutamate signaling in our body’s response to fighting that infection. This prolonged increased glutamate signaling can make cells sensitive to glutamate, where it takes less glutamate to induce a response, compared to an individual with a ‘non-stress’ glutamate signaling response. As a result, some can regulate back to ‘normal’ once a perceived invader is gone. However, some cells can take a long time not to be sensitive (chronically in stress response) once a stressor is gone.

Diet and Glutamate

Several studies have concluded those with autism, and many of the disorders listed above tend to lean towards excess glutamate signaling.  Many see behavioral improvements by following a gluten and casein (class of proteins found in dairy) free diet, likely because they inadvertently lower glutamate levels and inflammation.   Gluten, casein, and to a lesser extent, soy and corn contain roughly 25% glutamic acid as part of their protein structure.  In the bound protein, raw and unprocessed form, this amount of glutamate should rarely cause an issue.  The issues arise when these proteins are degraded. Some examples are pasteurization, fat removal, fermentation, and acid hydrolysis, which even occurs to a lesser extent as foods are digested. The protein degradation breaks down the amino acids, freeing up glutamate, leading to a high amount of unbound glutamic acid (MSG), an excitotoxin/neurotoxin wreaking havoc on the nervous system.  This can especially be problematic if you have a leaky gut, allowing free glutamate to cause damage directly.  However, one doesn’t need a leaky gut to be sensitive to free glutamate, as our digestive system has glutamate receptors that can signal additional glutamate.

Gluten and casein are not the only concern.  The FDA only requires ingredients over 99% free glutamate to be listed as MSG.  Therefore, anything under 99% free glutamate must not be identified as MSG and can be hidden or disguised in over 50 different names.  MSG and its various names are added to our foods to provide a competitive edge over other manufacturers by making food taste better and more addictive.  Unfortunately, these names can be as innocuous and deceptive as “natural flavors” or “spices,” leaving consumers utterly unaware of their neurotoxic properties.