Balancing the levels of the neurotransmitter glutamate — and its counterpart GABA — is crucial for modulating overall brain function.
When most people hear the word glutamate, they think of the flavor enhancer MSG (monosodium glutamate).
And while glutamate is found in MSG, it also naturally occurs throughout your body where it performs many vital functions.
Its most important role by far is as a neurotransmitter — a chemical messenger in your brain.
It is one of the most recently discovered neurotransmitters and there is still much we don’t know about it.
But one of the most intriguing discoveries is that glutamate acts as both a beneficial neurotransmitter and a dangerous neurotoxin.
What Is Glutamate? What Does It Do?
Glutamate is the most common amino acid in the body.
It’s estimated that each of us contains over 4 pounds of it! (1)
You can readily get all you need from food since it’s common in most plant and animal sources of protein.
Additionally, your body can synthesize it when necessary since it’s a non-essential amino acid.
Glutamate is the most abundant neurotransmitter in the brain and central nervous system.
Of all the neurotransmitters, glutamate is considered the most critical for healthy brain function.
Ironically, because glutamate performs so many functions, it was not immediately recognized as a neurotransmitter.
It wasn’t considered a neurotransmitter until the early 1980s, decades after the other major neurotransmitters such as dopamine, serotonin, and acetylcholine were discovered. (6)
One way of classifying neurotransmitters is whether they are excitatory or inhibitory.
Glutamate is your main excitatory neurotransmitter.
Excitatory neurotransmitters increase the likelihood that a nerve impulse will fire.
Glutamate system dysfunction has been linked to numerous psychological and neurodegenerative disorders.
The term glutamate is often used interchangeably with glutamic acid.
They have slightly different chemical structures but, for all intents and purposes, they are the same thing as glutamic acid readily converts to glutamate.
The Relationship Between Glutamate and GABA
You really can’t discuss glutamate without mentioning GABA (gamma-aminobutyric acid), another abundant neurotransmitter. (7)
Glutamate and GABA are integrally related in both form and function.
They have a complex, homeostatic relationship that brings balance to the level of brain activity.
While glutamate is your main excitatory neurotransmitter, GABA is your main inhibitory neurotransmitter.
Inhibitory neurotransmitters decrease the likelihood that a nerve impulse will fire.
GABA normally inhibits brain activity, enabling you to relax.
But when you’re low in GABA, your mind gets stuck in the “on” position and you’ll find yourself anxious, overstimulated, and overwhelmed.
Much as the gas pedal and brakes in your car work together to control speed, GABA puts the brakes on brain activity to counter glutamate’s gas pedal effects.
There is an additional connection between these two neurotransmitters — glutamate is the precursor of GABA. (8)
An enzyme called glutamic acid decarboxylase (GAD) triggers the production of GABA from glutamate.
Conversely, GABA can turn back into glutamate as needed. (9)
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The Dangers of Too Much Glutamate
Glutamate is essential for a healthy brain, but “the dose makes the poison.” (10)
In excess, glutamate becomes a potent excitotoxin that overstimulates brain cells, sometimes to death. (11)
There are two main causes of excess glutamate and its resulting excitotoxicity:
- Too much glutamate has accumulated in the brain.
- Glutamate receptors have become overly sensitive and thus are easily overstimulated.
Receptor oversensitivity sometimes occurs in patients with neurodegenerative disorders even when glutamate levels are not particularly high. (12)
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Symptoms indicative of a high level of glutamate include anxiety, depression, restlessness, inability to concentrate, headaches, insomnia, fatigue, and increased sensitivity to pain. (13)
- Alzheimer’s disease
- amyotrophic lateral sclerosis
- anxiety disorders (19)
- autism (20)
- bipolar disorder
- chronic fatigue syndrome
- Huntington’s disease (21)
- migraines (22)
- multiple sclerosis
- obsessive-compulsive disorder
- Parkinson’s disease
- post-traumatic stress disorder
- restless leg syndrome
- schizophrenia (23)
- seizure disorders
- traumatic brain injury
Causes of Excess Glutamate
The brain has a remarkable ability to accumulate glutamate, but normally there are safeguards to keep excess glutamate from building up to dangerous levels in the brain. (24)
As the authors of one study write, “neurons eat glutamate to stay alive” which usually keeps glutamate from reaching toxic levels. (25)
Numerous protein transporter molecules can bind to glutamate and move it out of the brain. (26)
The blood-brain barrier keeps glutamate that’s circulating in the bloodstream from entering the brain.
And finally, when all works right, excess glutamate is “supposed” to get turned into GABA.
But even with all these checks and balances, there are still times the glutamate system goes awry.
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Here are some of the things that can go wrong.
Glutamic acid decarboxylase (GAD) is the enzyme used to turn glutamate into its calming partner GABA.
But it’s possible to develop an autoimmune reaction to the GAD enzyme leading to poor conversion into GABA. (27)
Gluten intolerance, celiac disease, Hashimoto’s disease, type 1 diabetes, and other autoimmune diseases are linked to GAD autoimmunity. (28)
Since vitamin B6 (pyridoxine) is an essential cofactor in this conversion process, lack of it results in diminished GABA synthesis and a buildup of glutamate. (29)
It’s also possible to have a genetic tendency for glutamate oversensitivity and imbalances between glutamate and GABA. (30)
Traumatic stress can elevate glutamate to abnormally high levels. (31)
Many mood-altering substances disrupt the glutamate-GABA balance. (32)
Caffeine, the most widely used stimulant, increases glutamate activity at the expense of GABA.
A brain injury or stroke causes glutamate to flood the injured area.
This counter-productively causes brain damage by overexciting damaged neurons to death. (33)
Glutamate in Foods and Additives
There are numerous foods that contain glutamate, both naturally and unnaturally.
Can eating glutamate-rich foods impact your glutamate neurotransmitters levels?
There’s a lot of controversy surrounding this topic, so let’s try to clear up the confusion!
Foods That Naturally Contain Glutamate
Glutamate is responsible for giving foods their umami taste.
Umami is a meaty or brothy taste that is a little harder to recognize than sweet, sour, salty, or bitter.
The average person eats about 20 grams of glutamate every day and, for most people, these foods pose no problem. (34)
Foods that naturally contain glutamate include:
- bone broth
- green tea
- sea vegetables
- soybeans, especially fermented soy products
You’ll find comprehensive information on umami, including foods that contain glutamate, at the Umami Information Center.
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Bound vs Free Glutamate
There are two ways glutamate naturally occurs in foods.
Glutamate can either be bound to other amino acids (bound glutamate) or not (free glutamate). (35)
Bound glutamate is absorbed slowly whereas free glutamate is rapidly digested, leading to spikes in the bloodstream.
Bound glutamate has no flavor — it’s only when it’s been broken down into the free form that you can taste it. (36)
When foods that contain glutamate are cured or fermented, free glutamate is released.
This is why we find foods like cured ham, aged cheese, and fermented miso so delicious!
MSG: Pure Glutamate
MSG (monosodium glutamate) is a highly controversial food additive used as a flavor enhancer.
It is pure glutamate.
It is found mainly in salty foods such as canned soups, condiments, snacks, ramen noodles, and refined soy products like veggie burgers.
The international scientific consensus is that MSG is safe. (37)
One human trial found that MSG caused headaches, muscle tightness, numbness, tingling, general weakness, and flushing in study participants. (42)
Some researchers posit that MSG may cross the blood-brain barrier leading to raised glutamate levels, but we don’t know this for sure.
It’s notoriously difficult to study neurotransmitter levels in the human brain.
While you can measure levels in blood, saliva, or urine, these results have little-to-no correlation with levels in the brain.
MSG Side Effects and Toxicity Symptoms
But it’s not hard to find lists of reported MSG side effects, even on prestigious websites like Mayo Clinic. (43)
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Reported side effects of MSG include asthma, headache, flushing, sweating, psychiatric disorders, convulsions, migraines, nausea, fuzzy thinking, diarrhea, heart palpitations, mood swings, burning or tingling, muscle weakness, numbness, chest pain, and back pain. (44, 45)
The US National Library of Medicine lists symptoms of Chinese restaurant syndrome ranging from mild to serious. (47)
Symptoms that could be life-threatening and demand immediate medical attention include chest pain, heart palpitations, shortness of breath, and swelling of the throat.
This is surprising considering that most medical institutions deny the existence of Chinese restaurant syndrome and purport that MSG is perfectly safe!
Complications of a Leaky Blood-Brain Barrier
Researchers contend glutamate brain levels are not affected by MSG unless there is a disruption of the blood-brain barrier. (48)
But having a compromised blood-brain barrier is a problem for many people.
Additionally, people who have an autoimmune reaction to the glutamic acid decarboxylase (GAD) enzyme often have strong reactions to MSG and other high glutamate foods.
It seems that generous doses of MSG do not affect brain glutamate levels under normal circumstances.
But if you have a compromised blood-brain barrier, MSG allergy or sensitivity, or autoimmune reaction to the GAD enzyme, you may be among those that react badly to MSG.
If you suspect you have any of these conditions, it’s only prudent to avoid MSG and minimize high-glutamate food consumption.
How to Balance Glutamate Naturally
When it comes to neurotransmitters, you want to have the proper balance — not too much and not too little.
If you experience problems with mood, sleep, focus, and energy, you may be producing too much glutamate.
If you are easily stressed out, overwhelmed, and overstimulated, it’s likely you’re producing too little GABA.
Here are some things you can take and do to optimize glutamate levels and restore the glutamate-GABA balance:
Taurine acts amazingly like GABA in the brain.
It has a similar structure to GABA and binds to GABA receptors. (49)
Taurine excels at protecting the brain against toxic levels of glutamate. (50)
Eat more ginger or take a ginger supplement.
Ginger protects the brain from MSG-induced excitotoxicity. (53)
The prominence in some Asian cuisines of ginger, seafood, and nori may offset the effect of the consumption of high-glutamate foods and MSG.
Coenzyme Q10 exhibits potent anti-glutamate properties. (56)
CoQ10 is also a powerful antioxidant that protects vulnerable brain cells from free radical damage.
The herbal remedy valerian interacts with glutamate receptors to deliver relief from anxiety. (57)
L-theanine, a relaxing compound found in tea, is structurally similar to both glutamate and GABA.
It has been found to enter the brain to stimulate GABA production and modestly lower glutamate levels. (58)
PQQ (pyrroloquinoline quinone) is a little-known supplement that protects the brain from glutamate toxicity. (59)
Vitamin B6 (pyridoxine) is an essential cofactor required to synthesize GABA from glutamate. (60)
Inadequate B6 intake not only diminishes GABA synthesis, it also leads to a buildup of glutamate. (61)
Physical exercise optimizes the balance between glutamate and GABA. (62)
And one final tip: Chronic inflammation increases glutamate so take active steps to reduce it. (63)
Balance Glutamate by Increasing GABA
Another way to offset excess glutamate is by restoring its balance with GABA.
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You’ll find more ways to increase GABA naturally in our comprehensive article GABA Supplements for Stress and Anxiety (& which work best).
Look for probiotics that contain either Lactobacillus brevis or Bifidobacterium dentium which so far have been found to be the best GABA producers. (72)
You can get similar benefits from traditionally fermented foods such as unpasteurized sauerkraut, kimchi, kefir, and yogurt. (73)
All exercise is good for GABA production, but yoga stands out as a proven GABA booster.
Just a single one-hour session of yoga can increase GABA levels by an impressive 27%. (74)
The Neurotransmitter Glutamate: Take the Next Step
Glutamate is the most abundant and important neurotransmitter.
It works in partnership with the relaxing neurotransmitter GABA to modulate brain activity.
But the dose makes the poison.
When too much glutamate accumulates in the brain, it becomes an excitotoxin — a substance that literally stimulates brain cells to death.
Glutamate system dysfunction is linked to numerous psychological disorders and neurodegenerative diseases.
There are many foods that naturally contain glutamate, but these do not usually contribute to excess glutamate.
MSG, however, is a food additive that is pure glutamate.
And while the scientific consensus is that MSG is safe and usually does not cross into the brain, under some circumstances it may.
This highly controversial food additive comes with a long list of reported side effects and it’s best to avoid it if you suspect you are sensitive to it.
The right supplements and healthy lifestyle habits can optimize glutamate levels and restore the balance between glutamate and GABA.
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