11 Medical Conditions Associated With Glutamate Imbalance

Glutamate is the most abundant excitatory neurotransmitter in our brains and central nervous systems. It regulates the central nervous system, learning, and memory and plays a role in regulating GABA levels.

Until recently, glutamate has often been mentioned only as a sidenote to the more well-known neurotransmitters such as serotonin and norepinephrine. But recently, glutamate has staked its claim in the limelight, and neuroscience is obsessed with its role in regulating mood, memory, cognition, and learning.

This article will explain why glutamate deserves this newfound attention, how to test for glutamate and a functional medicine approach to balancing its levels.

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What is Glutamate?

Glutamate is our body's most abundant amino acid (building blocks of protein and is made and stored in muscle tissue. It is also made by glial cells in the brain and is necessary for making GABA  (1, 2). GABA is the "calming" neurotransmitter involved in sleep, relaxation, anxiety regulation, and muscle function.

Glutamate acts as an energy source in the brain, which helps regulate the body's energy homeostasis (4, 5). It is essential for proper brain function, can bind to multiple receptors in the central nervous system, and is involved in more than 90% of all excitatory functions in the brain (3, 2).

*Note: An excitatory neurotransmitter excites or stimulates a nerve cell, making it more likely that the chemical message will continue to move from nerve cell to nerve cell and not be stopped.

What Causes Low Glutamate?

Lower levels of glutamate can often be seen in relation to imbalances in other neurotransmitters, partially GABA, as they work together to balance neurotransmitters' excitatory and inhibitory effects. The blood-brain barrier does help to maintain healthy glutamate levels and keeps the glutamate circulating in the bloodstream from entering the brain (8). The enzyme glutamic acid decarboxylase (GAD) turns glutamate into GABA, which requires amino acids such as Taurine synthesis, and vitamin B6 is an essential cofactor for converting glutamate into GABA, therefore having lower levels of these two nutrients could play a role in having imbalanced levels of glutamate (9, 20).

Low Glutamate Levels Signs & Symptoms

Much of the research on glutamate is around excessive amounts; however, glutamate deficiency has been linked to the below symptoms (2).

• Issues concentrating
• Low energy
• Feeling mentally exhausted
  

5 Medical Conditions Associated with Low Glutamate

Low levels of glutamate have been linked to:

• Learning and memory issues
• Low concentration
• Mental exhaustion
• General low energy  
• ADHD symptoms of inability to focus and feelings of restlessness
  

What Causes High Glutamate?

Since GABA and Glutamate have a homeostatic relationship (and it is the precursor to GABA), having too little GABA can lead to elevated glutamate levels.

Other Ways that Too Much Glutamate Can Be in Your Brain Include:

• Glutamate, directly released from glial cells, adds to the total amount in your brain.
• Excess glutamate remains in the space between nerve cells (the synapse), which can lead to too many glutamate receptors being continuously activated and nerve cells being continuously excited.
• Nerve cell receptors have become oversensitive to glutamate, meaning fewer glutamate molecules are needed to excite them.
  

6 Medical Conditions Associated with High Glutamate

Glutamate can become excitotoxin at excessive levels, which can overstimulate brain cells. Balance of glutamate levels is essential, as too much can lead to nerve cell (brain cell) damage and death, resulting in a host of neurological and neurodegenerative diseases such as: (6)(19)(21).

• Parkinson's
• Alzheimer's
• Huntington's disease
• Anxiety
• OCD
• Schizophrenia

Functional Medicine Lab Test to Test Glutamate Levels

The Neurotransmitters + Micronutrients test can assess glutamate levels, which is one of the most comprehensive tests to evaluate neurotransmitter function and levels.

This test analyzes the status of neurotransmitters, their precursors, and their derivatives, which allows the patient and the practitioner to take a more holistic approach to treating imbalances.

How to Balance Low Glutamate Levels?

There are no supplements to raise glutamate levels; therefore, focusing on lifestyle, diet, and glutamate precursors can be a natural approach to supporting healthy levels. Exercise has been shown to help the body make more glutamate. Increasing GABA levels can help to increase glutamate levels; therefore, focusing on GABA precursors such as 5-HTP and theanine can be promising therapies (11, 12).

Foods that naturally contain glutamate include cheese, beets, asparagus, sea vegetables, eggs, mushrooms, fermented soy products, and bone broth; increasing your consumption of these foods may help increase glutamate levels (13).

How to Balance High Glutamate Levels?

Conventional treatments for lowering glutamate levels would include using antidepressants, as they can regulate glutamate receptor expression and function (14). Other glutamate blockers include Riluzole, which inhibits the release of glutamic acid from neurons (15).

Certain foods contain glutamate (both artificial and naturally), such as MSG (the sodium salt of glutamate), which is made from fermented starches and sugars and is used to add flavor to sauces, dressings, and soups, therefore monitoring your intake of MSG foods can be a natural approach towards modulating glutamate levels (10).

Magnesium can reduce the stimulatory effects of glutamate and can protect against glutamate damage, as magnesium sits on NMDA glutamate receptors, which helps to calm excitatory cells and raise GABA levels (16).

It could also be theorized that supporting mitochondrial health can be an indirect way to support glutamate levels. Glutamate in excess can damage brain cells to the point of mitochondrial dysfunction, leading to an accumulation of ROS and free radical damage. When mitochondria experience excessive amounts of free radical damage, nerve cell death can occur, and having too much glutamate can lead to nerve cell damage.  

The mitochondria influence and regulate the transport of cell energy and influence oxidative stress (which having excessive amounts of excitatory neurotransmitters can lead to excessive amounts of oxidative stress). In particular to this conversation, mitochondrial glutamate regulates the transport of glutamate across the mitochondrial membrane.  

Glial cells (which produce glutamate) depend on mitochondrial function. Therefore supporting the mitochondria with CoQ10 can be important for balancing glutamate levels and protecting against free radical accumulation in the brain, which can further damage brain cells (17, 18, 21).

PQQ (pyrroloquinoline quinone ) can also support mitochondrial health and has been shown to protect the brain from glutamate-induced neurotoxicity (19).

Summary

Glutamate is the most common neurotransmitter in the central nervous system and the most abundant excitatory neurotransmitter, which can be more stimulating and energizing in nature. It regulates the central nervous system, learning, and memory and plays a role in regulating GABA levels. Glutamate acts as an energy source in the brain, which helps regulate the body's energy homeostasis.