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Do You Have Too Much Glutamate? What Happens When Neurotransmitters are Imbalanced

Glutamate in the brain functions as an excitatory neurotransmitter. This means glutamate helps the neurons in your brain talk to each other and the rest of your body. It also means glutamate is the energizing force in your brain. And it plays a vital role in helping you learn and remember things. Glutamate is also a key component in the production of Gamma-aminobutyric acid (GABA) and glutathione (a key antioxidant). GABA is the calming presence to glutamate’s energetic presence.

But too much glutamate can cause problems in the body.

Experts point to excess glutamate as the culprit in the development of neurodegenerative diseases and mood disorders like depression and anxiety.

What Is Glutamate?

Glutamate is an amino acid found in the brain and spinal cord. Glutamate is a non-essential amino acid — which means that the body can make it. Glutamate is considered your primary excitatory neurotransmitter.[1]https://www.ncbi.nlm.nih.gov/books/NBK62187/#:~:text=Glutamate%20is%20the%20major%20excitatory,cord%20in%20neurons%20and%20glia.

Glutamate plays many crucial roles in the brain. It sends signals between neurons. And it is essential for the brain’s development and for memory and learning.[2]https://link.springer.com/article/10.1007/s11033-010-0128-9 Glutamate is also important for amino acid metabolism.[3]https://pubmed.ncbi.nlm.nih.gov/22526238/#:~:text=Glutamate%20is%20one%20of%20the,in%20nutrition%2C%20metabolism%20and%20signaling.

Glutamate Synthesis

Glutamate is made in the central nervous system from glutamine by glutaminase, a mitochondrial enzyme. This process is known as the glutamate-glutamine cycle.[4]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4133642/​​ Glutamate is also synthesized by transfer of 2-oxoglutarate.[5]https://www.ncbi.nlm.nih.gov/books/NBK10807/

Glutamate Vs. GABA

Glutamate is considered excitatory, which means it’s exactly like it sounds — an arousing presence in the brain. Gamma-aminobutyric acid, also known as GABA, is the primary inhibitory transmitter in the brain. That means it’s the calming force.

Glutamate in the brain should ideally be balanced by levels of GABA. When the glutamate to GABA ratio leans too far one way or the other, problems can start. Too much glutamate is suspected to be a factor in the development of neurodegenerative disease and is implicated in mood disorders like depression.[6]https://www.nature.com/articles/s41380-018-0252-9#:~:text=Both%20animal%20and%20clinical%20studies,glutamatergic%20system%20alterations%20%5B19%5D.

Interestingly, GABA is actually synthesized from glutamate. As is glutathione, the body’s master antioxidant.[7]https://pubmed.ncbi.nlm.nih.gov/19587091/

Glutamate Vs Gluten

Since glutamate and gluten sound so very similar, they are often confused with one another. However, glutamate and gluten are actually two different things. One has no relation to the other. So when you wonder if glutamate is gluten-free — the answer is yes, but glutamate has nothing to do with gluten. Gluten is a protein found in wheat that’s responsible for its elasticity.[8]https://www.ncbi.nlm.nih.gov/books/NBK538505/

Glutamate In Food

Glutamate is found naturally in many foods. It is estimated adults consume about 10-20 grams per day.[9]https://pubmed.ncbi.nlm.nih.gov/30508814/

Some common foods with higher levels of glutamate include:

  • Parmesan cheese
  • Tomatoes
  • Walnuts
  • Soy sauce
  • Mushrooms
  • Peas

However, glutamate foods may not actually affect levels of glutamate in the brain, as it is believed dietary glutamate does not cross the blood-brain barrier.[10]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5192417/[11]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2813370/[12]https://academic.oup.com/ajcn/article/90/3/867S/4597370?login=true[13]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3136011/#:~:text=Early%20studies%20that%20used%20very,receptors%20(29%E2%80%9331).

Other research suggests that dietary glutamate could possibly be related to depressive symptoms in patients with schizophrenia.[14]https://www.frontiersin.org/articles/10.3389/fpsyt.2020.620097/full

Glutamate Vs. Monosodium Glutamate (MSG)

Monosodium glutamate (MSG) is a food additive that is made from glutamate. The FDA considers MSG to be generally regarded as safe (GRAS). It appears as though the body metabolizes MSG in the same way it does dietary glutamate.[15]https://www.fda.gov/food/food-additives-petitions/questions-and-answers-monosodium-glutamate-msg While many concerns over the safety of MSG have been raised, it seems as though MSG does not cross the blood-brain barrier in the same way that natural sources of glutamate don’t.[16]https://www.karger.com/Article/Fulltext/494782

Glutamate Excess

When levels of glutamate in the brain increase or the glutamate receptors in the brain become oversensitive, that’s when certain symptoms can crop up.

Too much glutamate, which is also known as glutamate toxicity, can lead to damaged neurons and is believed to be correlated with mood disorders and neurodegenerative diseases like Alzheimer’s disease and Parkinson’s.[17]https://www.frontiersin.org/articles/10.3389/fnins.2020.585584/full#:~:text=Too%20much%20glutamate%20induces%20excessive,the%20effects%20of%20glutamate%20excitotoxicity.[18]https://www.frontiersin.org/articles/10.3389/fnins.2015.00469/full

Glutamate Schizophrenia

Glutamate and dopamine and schizophrenia also appear to be interrelated.[19]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4902122/[20]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6953551/[21]https://www.frontiersin.org/articles/10.3389/fpsyt.2018.00544/full#:~:text=According%20to%20the%20glutamate%20hypothesis,and%20negative%20symptoms%20of%20schizophrenia. Research suggests that changes in glutamate levels may appear before the onset of the psychosis which is a symptom of schizophrenia.[22]https://www.sciencedirect.com/science/article/pii/S0920996420304710

Glutamate And Depression

Glutamate is also thought to play a role in the development of mood disorders like anxiety.[23]https://www.sciencedirect.com/science/article/abs/pii/S0091305711001201[24] … Continue reading

But while glutamate, anxiety, and depression have been linked in studies, scientists are still trying to figure out how to target the glutamatergic system to treat mood disorders.[25]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984954/[26]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3439647/[27]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8311508/[28]https://www.frontiersin.org/articles/10.3389/fpsyt.2021.637863/full[29]https://www.nature.com/articles/mp2015114

Glutamate Inhibitors

Since excess glutamate is linked to mood disorders and neurodegenerative diseases, it makes sense that you may want to find ways to block glutamate. There are several medications that work as glutamate blockers. These are known as glutamate antagonists.[30] … Continue reading

Some natural substances that have a reputation for inhibiting glutamate include[31]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3307240/:

  • Curcumin (which is part of turmeric root)
  • Magnesium (found in dark leafy greens and whole grains)
  • Omega-3 fatty acids (found in fatty fish)
  • Foods that increase GABA (like germinated brown rice, potatoes, and cruciferous veggies)[32]https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5986471/

Glutamate Deficiency

On the other side of the coin, it is possible, albeit very rare, to have a glutamate deficiency. A glutamate deficiency is known as Glutamate formiminotransferase deficiency. This is a disorder that is inherited. It can cause delays in mental and physical development.[33] … Continue reading

Glutamate Supplements

There aren’t really any glutamate supplements, per se. Remember, it’s likely that dietary glutamate doesn’t readily cross the blood-brain barrier, so supplementation would probably not be of much help.

If your doctor has told you that you need to increase glutamate levels, you can always try exercising. Studies show workouts are great for increasing levels of both glutamine and GABA.[34]https://www.jneurosci.org/content/36/8/2449

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