What is Glutamate?

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When you hear the word "glutamate," you may think of monosodium glutamate (MSG), the food additive often associated with Americanized Chinese food. But did you know that glutamate is the most abundant amino acid in your brain? There, glutamate's role is primarily to excite other neurons so that they'll carry out their functions.^[1] Read on to learn everything you need to know about glutamate, including what happens if you have too much or too little of this amino acid.

What is glutamate?

Glutamate is an amino acid that acts as a neurotransmitter in your brain. As a neurotransmitter, glutamate's job is to send a message. Glutamate receptors on the surface of most brain cells take in glutamate. Glutamate, in turn, tells that cell to perform its function (whatever that may be—it varies from cell to cell).^[2]

You might think of glutamate as a neurotransmitter's neurotransmitter—its message primarily excites other neurons to release their neurotransmitters, which results in something happening. For example, if glutamate triggers a motor neuron, it might cause a muscle to contract.

What's the difference between glutamate and MSG?

Monosodium glutamate (MSG) is a food additive that contains glutamate. Your body processes MSG the same way it processes natural glutamate. The US FDA considers MSG safe for use as a food additive.^[3]

Some people have claimed to suffer headaches or nausea after consuming MSG, but research hasn't confirmed that MSG itself causes those symptoms.

Glutamate in your blood is separate from the glutamate in your brain. The blood-brain barrier (BBB) is a semi-permeable border of cells that separates the fluid in your brain and central nervous system from your circulating blood. This barrier is highly selective about what can go through it and glutamate doesn't make the cut.^[4]

Because glutamate can't cross the BBB, the amount of glutamate you eat doesn't affect the levels of glutamate in your brain at all.
All glutamate in your brain is synthesized by the neurons in your brain and central nervous system, then held for later release.

What foods naturally contain glutamate?

Tomatoes, cheese, and mushrooms contain high amounts of glutamate.^[5]The high levels of glutamate in these foods are responsible for their unique taste—the flavor known as umami. Umami is the 5th basic taste humans recognize, along with sweet, salty, bitter, and sour.^[6]

Parmesan cheese contains the highest amount of glutamate, with 1680mg of glutamate for every 100g of cheese.^[7]
Chicken and beef, as well as seafood such as scallops and shrimp, are also relatively high in glutamate.
The food flavor additive MSG is created using a fermentation process similar to that used for making vinegar or beer.

Glutamate's Functions

Maintenance of neural communication. Glutamate triggers various neurons to release neurotransmitters to other receptors. All of these different neurotransmitters communicate different messages, but glutamate's role remains the same—to tell the neuron to release the neurotransmitters it holds.^[8]

Because of this particular function, glutamate plays at least a small role in everything that occurs in your body. Thanks to glutamate, the neurons in your nervous system are able to react to various stimuli and communicate with each other.

Learning and memory. Neurons release glutamate in response to an experience or any kind of new information. That glutamate is transported to glutamate receptors in different regions of the brain to trigger the encoding of that new information so that you can learn from it.^[9]

Glutamate plays a particular role in associative learning—essentially learning through repetition or conditioning. With each repeated exposure, glutamate stimulates the same neurons, which reinforces the same neural pathways and helps you retain the information you've been exposed to.
Glutamate's role in the maintenance of neural communication also helps to encode memories in your brain, both for short-term working memory and long-term memory.^[10]

Brain and neural plasticity. Your nervous system has the ability to constantly modify itself in response to injury, trauma, or experience. Through this process, your neural network effectively "rewires" itself so that you can continue to function despite one neural pathway or connection being damaged or destroyed.^[11]

Glutamate helps regulate this process by provoking new neurons to fire.^[12]

Pain sensitivity.Generally, higher levels of glutamate correspond to a higher degree of pain sensitivity.^[13] Glutamate transmits pain across your nervous system to your brain.^[14] Chronic, severe, or persistent pain triggers a continuous release of glutamate.^[15]

For example, the knee joints of arthritis patients have elevated levels of glutamate, indicating the prolonged pain resulted in the release of more glutamate.^[16]

Stimulation of taste receptors. Glutamate is one of 3 substances that provide the umami taste. There are 3 umami receptors on your tongue that communicate this taste to your brain.^[17]

Glutamate and GABA

Glutamate is a precursor for GABA. Your nervous system uses glutamate to make its own gamma-aminobutyric acid (GABA). Therefore, your glutamate levels directly affect your GABA levels.^[18]

Glutamate and GABA perform opposing functions. Glutamate excites neurons to act while GABA blocks or stops them from acting. In a neurotypical brain, these neurotransmitters are balanced.^[19]

A shortage of GABA relative to glutamate could result in hyperactive and asocial behavior, similar to symptoms of autism spectrum disorder (ASD). Too much GABA relative to glutamate, on the other hand, can lead to depressive symptoms.

Medical Conditions Associated with Low Glutamate

Major depressive disorder. Research consistently shows that people with depression have lower glutamate levels in their brains than healthy people.^[20] On top of that, people with chronic depression might also have less sensitive glutamate receptors—meaning that even if they got more glutamate, the receptors would have trouble taking it in.^[21]

Schizophrenia. In people with schizophrenia, glutamate receptors aren't able to do their jobs. In a 2020 study, healthy test subjects developed schizophrenia-like symptoms when they were given drugs that prevented specific glutamate receptors from receiving glutamate. This result leads scientists to believe that schizophrenia may somehow block or damage glutamate receptors, causing an increase in the incidence and severity of symptoms of the disease. However, more research is needed to confirm this hypothesis.^[22]

Historically, schizophrenia studies have focused on dopamine. Scientists don't believe glutamate receptors alone account for schizophrenia's symptoms. Rather, research focuses on how the glutamate and dopamine systems work together.
While schizophrenia is caused by both genetic and environmental factors, the 2020 study recognizes that glutamate dysfunction is caused by genetic factors.

Glutamate formiminotransferase deficiency. In this rare genetic disorder, low glutamate results in mental and physical developmental delays. People with the severe form of this disorder typically have profound intellectual disabilities and difficulty developing basic motor skills that allow them to sit, stand, or walk.^[23]

As of 2021, there are no known treatments for this disorder that will prevent or delay its signs and symptoms.^[24]

Medical Conditions Associated with Excess Glutamate

Anxiety disorders. Many anxiety disorders, including post-traumatic stress disorder (PTSD) and phobias, are characterized by heightened anxiousness or a panic response when you're exposed to a certain thing that you associate with fear. Because glutamate plays a role in that associational learning, researchers believe that lowering glutamate levels can help ease anxiety symptoms.^[25]

Current therapy for phobias and similar anxiety disorders focuses on gradually exposing you to the thing you're afraid of in safe circumstances. Experiencing safety in response to that thing gradually "overwrites" your fear association.
Glutamate's roles in learning, neural communication, and neural plasticity make it a prime candidate to focus on when looking for new anxiety disorder treatments.

Autistic Spectrum Disorder (ASD). Impaired social interaction is a hallmark symptom of ASD. Research suggests this symptom might be a function of an imbalance of glutamate and GABA in the brain. Having more glutamate than GABA can result in more hyperactivity and an inability to focus.^[26]

Researchers looked specifically at the ratio of glutamate to GABA in the prefrontal cortex, the area of your brain responsible for executive functions, such as planning, organization, prediction, and attention.

Neurodegenerative diseases. Neurodegenerative diseases, such as Alzheimer's disease and Huntington's disease, are often associated with excess glutamate release. Excess glutamate is toxic and can result in nerve cell death (excitotoxicity). That cell death is, in turn, responsible for progressive dysfunction.^[27]

Scientists believe that if there were a way to control and reduce the excess glutamate in the brain, there would be a way to prevent nerve cell death and slow (if not stop) the progression of these diseases.

Amyotrophic lateral sclerosis (ALS). ALS attacks motor neurons in the brain and spinal cord. When these neurons die, they release a flood of glutamate, which in turn can damage or kill other neurons in the vicinity. In this way, excess glutamate contributes to the progressive degeneration of people with ALS.^[28]

Riluzole, a drug that modulates glutamate, was the first approved treatment specifically for ALS. This drug helps reduce excess glutamate to slow the progressive degeneration of the disease.

Human immunodeficiency virus (HIV). Researchers believe that neurocognitive disorders caused by HIV infection may be due to excess glutamate released in the brain. Studies show nervous system trauma brought about by HIV infection causes increased sensitivity of glutamate receptors, leading to over-stimulation.^[29]

This over-stimulation can result in nerve cell death (excitotoxicity) in people infected with HIV. For the affected person, the result is progressive dysfunction, similar to that experienced by people with multiple sclerosis (MS) or Alzheimer's disease.^[30]

Stroke/Traumatic brain injury (TBI). A sudden trauma can result in neurons flooding the brain with glutamate. This massive release kills surrounding nerve cells and causes dysfunction for the affected person, depending on the specific cells killed.

This can result in a cascading effect as the dead nerve cells dump the glutamate they were holding as well, triggering the death of other surrounding nerve cells.
By enhancing a natural cellular process that pumps excess glutamate out of the brain and into the blood, scientists hope to prevent or stop further brain damage after stroke or TBI.
A similar process is likely at work in epilepsy, which causes trauma to the brain and central nervous system leading to the release of excess glutamate.^[32]

Chronic pain. Diseases and disorders that cause chronic pain result in continuous releases of glutamate. These releases mean you end up with more glutamate pooling around the site of the pain. That excess glutamate can render you more sensitive to pain than you were before the surrounding tissue was damaged.^[33]

Researchers believe that removing excess glutamate might have the effect of making chronic pain patients less sensitive to pain than they would be otherwise.

Boosting Glutamate Levels

Exercise at 80% of your predicted max heart rate. Research shows that just 10-15 minutes of vigorous exercise can significantly increase the glutamate levels in your brain. Glutamate levels continued to rise for 15-20 minutes after the exercise session.^[34]

Leading a generally active lifestyle improves your health and fitness, but research also shows that at least 75-150 minutes a week of vigorous exercise is better for your overall health than regular, moderate exercise.^[35]

Drink coffee or other caffeinated beverages. Caffeine briefly stimulates your brain to produce and release more glutamate. This is why a cup of coffee in the morning makes you feel more alert.^[36]

Too much caffeine can leave you feeling jittery and frazzled. Medical experts recommend no more than 400mg of caffeine per day for healthy adults—that's about 2 grande (16-ounce) cups of brewed coffee or 10 cans of soda.^[37]

Avoid drinking alcohol. Alcohol slows the production of glutamate as well as the release of the neurotransmitter. If you already have low levels of glutamate, keep in mind that alcohol use will likely exacerbate your related symptoms.^[38]

Lowering Glutamate Levels

Practice yoga and meditation to increase your GABA levels. Research has shown that just a single 60-minute yoga session can increase the levels of GABA in your brain.^[39] Both yoga and meditation practice stimulate GABA production, which has a calming effect to counterbalance the effect of excess glutamate.^[40]

Additionally, since neurons need glutamate to make GABA, increased GABA production also lowers your overall glutamate levels.

Take a taurine supplement to prevent damage from excess glutamate. Taurine acts similarly to GABA and blocks excitability in neurons. If you have excess glutamate, taurine can calm your nervous system down to prevent further damage.^[41]

Taurine has been studied and determined safe at doses from 1 to 6 grams per day. It doesn't have any major side effects, but could slightly increase your blood pressure temporarily.^[42]

Try a GABA supplement to improve your GABA/glutamate balance. There hasn't been a lot of research on GABA supplements, but they're generally considered safe. If you have excess glutamate in your brain, increasing GABA can offset it. Just make sure you talk to your doctor first. While these supplements have minimal side effects, they might interact with other medications you're on or interfere with other conditions you have.^[43]

Researchers haven't arrived at a recommended dosage for GABA supplements. Start with the lowest dosage listed on the bottle, which is usually 100mg spread out over several doses.^[44]

Go on a ketogenic diet to improve your brain's handling of glutamate. Although more famous for its weight-loss effects, the ketogenic diet was originally proposed as a treatment for epilepsy. As epilepsy symptoms occur as a result of excess glutamate, scientists believe that the state of ketosis prompts the more efficient disposal of excess glutamate.^[45]

Talk to your doctor before starting this diet. There are short-term side effects you should be aware of, including nausea, vomiting, headache, and fatigue.
While the short-term (up to 2 years) effects of the ketogenic diet have been studied extensively, less is known about the potential long-term effects. Work closely with your doctor if you plan on maintaining the ketogenic diet for more than 2 years.
The keto diet is not recommended if you have diabetes, pancreatitis, liver disease, or any disorder that prevents your body from using fat for energy.^[46]

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