Glutamine Versus Glutamate: Nutrients and Safety

By Samantha Gilbert, FNC, CHNP, CNC     Last updated on December 26th, 2021

In today’s post, I explain what glutamine is, its effect on the brain and body, and why it’s not a safe nutrient for everyone.

Special thanks to Dr. William Walsh of the Walsh Research Institute for his insights into this powerful nutrient. Dr. Walsh’s research in the area of mental health has been accepted by the American Psychiatric Association and has helped thousands (including myself) recover from mental health imbalances.

What is Glutamine?

Glutamine is an amino acid used in the biosynthesis of proteins and is a major player in many biochemical functions including:

  • Protein synthesis, as any other of the 20 proteinogenic amino acids
  • Lipid synthesis, especially by cancer cells
  • Regulation of acid-base balance in the kidney by producing ammonium
  • Cellular energy, as a source, next to glucose
  • Nitrogen donation for many anabolic processes, including the synthesis of purines
  • Carbon donation, as a source, refilling the citric acid cycle
  • Nontoxic transporter of ammonia in the blood circulation
  • Precursor to the neurotransmitter glutamate [1]

Is Glutamine Safe?

As an oral supplement, glutamine is used in catabolic states of injury and illness. It has been used to combat the muscle wasting that occurs in people with advanced cancer and HIV/AIDS, as well as for professional athletes who expend lots of physical energy. People with gut infections and intestinal barrier issues have experienced improvement with glutamine; [2] in general, glutamine is a terrific positive for physical health.

Glutamine and the Brain

Glutamine is the precursor for both glutamate and GABA, the two primary neurotransmitters in the brain. Glutamine is the number one neurotransmitter. As it turns out, glutamate is very excitatory and can be very neurotoxic. On the other hand, GABA, which also comes from glutamine, actually neutralizes excess glutamate. In the brain, the major concern is having too much glutamate.

Is Glutamate Bad for the Brain?

Glutamate is the number one amino acid in the bloodstream, with copious amounts flowing around in the periphery of the body. The process which converts glutamine to glutamate is a straightforward one, primarily occurring in glial brain cells, which support and help nourish brain neurons.

The brain always has lots of glutamate and glutamine present, and glutamine can pass the blood-brain barrier very readily. The problem is that glutamate tends toward neuronal hyperactivity. In other words, it’s excitatory, and too much neuronal activity can kill brain cells. When excessive glutamate is in the vicinity of neurons, it tends to allow too much calcium to enter the neurons and that can kill off mitochondria and therefore brain cells.

Glutamate causes an enormously high percentage of brains to act to fire and have overexcitability. Chronic overexcitability of neurons causes apoptosis (death of brain cells) and is associated with a number of mental health conditions such as mania in bipolar disorder and hyperactivity (to name a few) — and, in addition to being neurotoxic, it can actually kill brain cells.

Some people are more prone to overexcitability than others and this is why testing is essential. Then there are people born without a tendency for neuronal hyperactivity so for them, glutamine is likely safe.

People born with a tendency for neuronal excitability or hyperactivity are most at risk of glutamate complications. Overmethylated individuals or patients who have high copper levels (not able to regulate copper) tend toward high neuronal activity which can cause anxiety, depression, schizophrenia, and bipolar disorder, making glutamine supplements very dangerous.

High glutamate levels have been observed alongside some serious diseases such as Multiple Sclerosis (MS), Lou Gehrig’s disease (ALS), and autism.

GABA Brain Benefits

GABA has to do with brain cell voltage. The brain has about 80 billion neurons (or brain cells) that don’t divide, meaning you’ll basically keep the same neuronal brain cells that you were born with. With respect to neurotransmission and brain function, brain cells have to be firing and communicating with each other by way of voltage.

GABA calms the brain making brain neurons, in general, less hyperactive, whereas glutamate does the exact opposite. There are numerous glutamate and GABA receptors on brain cells; when GABA interacts with a neuron at a receptor, it increases the voltage of that brain cell and has a calming effect.

What do NMDA Receptors Do?

N-methyl-D-aspartate (NMDA) is a glutamate receptor. The NMDA receptor is a peculiar one; it has a lot to do with memory and obsessive-compulsive tendencies. It’s a leading culprit in terms of malfunctioning for schizophrenia. You have to have a simultaneous docking of glutamate at a receptor and at the same time, there’s another receptor that’s a dual receptor system that has to interact with several neurotransmitters.

While glutamate tends to be something that you want to avoid in the brain, you want to increase glutamate activity at the NMDA receptor for people who are in trouble, without affecting the rest of the glutamate receptors, which can be done with advanced nutrient therapy.

What About Free Glutamates from Natural Foods?

My experience with glutamates from healing foods, such as bone broth, is that the foods can be made safely (such as meat stock that’s cooked slow and at a lower temperature with less time, usually 3 hours), therefore producing significantly less glutamic acid while still imparting healing benefits. I have found that the effects ultimately depend on a patient’s chemistry and symptoms, as well as food preparation methods.

Final Thoughts on Glutamine and Glutamate

If you struggle with any kind of mental health issue (even if it’s mild), you’d be wise to steer clear of any form of glutamine supplementation (l-glutamine is the most common). If you are supplementing, I encourage keeping a journal notating any responses. Even if you are an athlete, it’s wise to be aware of any harm it could be causing (be sure to read labels, l-glutamine is hidden in many protein powders).

Also, keep in mind that gut issues often have methylation imbalances, copper toxicity, zinc deficiency, and pyrrole disorder, which can exacerbate SIBO, candida, and other pathogens making testing an important tool in the recovery process.

If you know of someone who struggles with a chronic mental health condition, please share this post. If you are struggling, please share your experience in the comments below. It is through sharing your story that we create community, eliminate guilt and shame, and bring about healing.


71 thoughts on “Glutamine Versus Glutamate: Nutrients and Safety”

  1. Where in Australia in Brisbane noosa and is there a great bio practitioner the one I’ve got at the moment is turning me around in circles
    Makes me,wonder how she is,being trained costing me thousands for a no care attitude

  2. So last year, I was completely healthy, great corporate high paying job, new car, recently married, everything was great, then like a flick of a switch, a rush surged up the back of my head and everything changed. Since that 10 second rush I’ve been in constant Derealization, everyday, all day, like I’m disconnected and in a dream. I have tinnitus, visual disturbance, migraines, occasional vertigo and anxiety. I’ve lost my career and have filed for disability. I was diagnosed with Meniere’s Disease, an inner ear disease and Vestibular Migraines but I sometimes wonder if Glutamine could’ve caused it. About a week before this hit me I started working out and taking BCAA’s which had L Glutamine as a main ingredient, as a pre workout. My first workout I took a full dosage and I was super wired, heart beating fast, I felt completely off so I slowed down to sipping it throughout the day vs all at once. A week later, boom, rush up my head and everything changed. Do you think there could be a connection? I’ve been told by doctors there’s nothing more they can do except prescribe me anxiety meds and am at the end of the road. Please feel free to email.

    1. So glutamine can actually be helpful for treating derealization , some psychologists even prescribe gabapentin (works on GABA receptors). I too have depersonalization/derealization. The most effective treatment though is counseling and getting absorbed in happy things that take up your thoughts. DR/DP gets worse the more that you think about it. You’re going to be alright!

    2. I am having the same thing happening to me. It is awful. I was on 16.5g for 3 weeks and I have not been the same since. This was for leaky gut plus was telling me to drink bone broth and collagen powder. I am so scared I damaged myself and it was extremely negligent of the doctor knowing I already had anxiety and ADD issues.

  3. Samantha,
    I don’t have a primary care physician and I do not have insurance anymore but I do desperately need help with eating disordered and deciding if I’m over methylated or under , I’m homo c677t and currently battling severe anxiety and social anxiety as well as depression and just out of control everything. Anyways I want a consultation with you but was wonder
    How we would go about get testings done and such. Thank you for our insightful website, you are amazing.

    1. My dr knew all this and put me on 16.5g plus telling me to drink bone broth and add collagen powder. Can this cause cell death in this amount of time? I have not been the same and feel really scared. All they can say now is for me to see a psychiatrist. I was completely fine and living a normal life before this. Now my thinking is off and I feel like I cannot function day to day. Will this ever get better?

      1. Hi Kathleen – I’m sorry you’ve had this experience. Testing to determine your biochemical status would help to determine the appropriate nutrients and diet to correct underlying imbalances that caused the reaction, to begin with. So, yes, it will get better.

  4. Hi Sami,

    My Name is Ana. Ive been really sick due to Copper Toxicity because of an IUD I had placed in December of 2015. The one thing I noticed that helped me get unstuck from the obsessive negative thinking, depression and Anxiety was 5g of lglutamine 2x a day. I Know that alot but it was helping me shift my attention and my anxiety and depression has been alot better as well. OF course Im also taking 400 mg of Magnesium and 100 mg of B6. I was just wondering …do you know if there is any connection with Lglutamine and copper toxicity?


  5. I have a leaky gut and my health practitioner told me to take L glutamine , 3 capsules each day. I have been taking 50mg of dosulepin each day to prevent migraines. And have been on them for 4 years Anyway, I’m feeling awful since taking the glutamine, run down, tired, agitated, depressed and have never felt like this before. I’m going to stop taking them!

  6. For people who have been using L-glutamate for gut health but have methylation problems, depression and anxiety, what is a suggestive replacement to help gut health. My son needs his gut health to be better in order to absorb his vitamin/supplements. He has two autoimmune diseases. Gut health is horrible

    1. Man, I wish I knew. I’m in the same boat as your son… At least with the anxiety/autoimmune/leaky gut issue. Most practitioners for dealing with leaky gut/autoimmune (Hashimoto’s in my case) scream from the rooftops that L-Glutamine is indispensable for gut healing, and I have no reason not to believe them. However, taking more than a small amount (nowhere even near the 10-30g a day most places suggest for effectiveness) makes me feel very agitated and unwell. Soooo… when I post asking for alternatives or workarounds to the L-Glutamine problem, I just get silence in response. Frustrating as hell. Perhaps the writer of this article knows of a way to get past this?

  7. I’m a high-mileage runner/athlete in the anxiety/depression, leaky gut, fatigue, brain-fog, gluten sensitivity boat with you all. However, I have had very different results using collagen and l-glutamine. Even months after cleaning up my diet (x-nay the sugars, wheat, and dairy), I was still feeling pretty slow in the head although much better physically. I read that to heal the gut, elimination of the offending foods isn’t enough, that gut-healing supplements are usually needed. I started collagen & glutamine and I only take a half scoop of collagen and 5g of glutamine per day and have noticed my brain fog and fatigue reduced significantly. My memory and mood have improved as well and have realized a general better attitude. I believe the glutamine and/or collagen have been helpful in my case. (Note: I also take fish oil, CoQ10, turmeric, nettle but had taken those before beginning the collagen/glutamine).

  8. I suffer from an anxiety disorder and have a history of having super severe panic attacks.
    I know for a fact that Pheylalnine has caused me to have severe panic attacks.

    I’m fairly certain that I have leaky gut syndrome. I have seen that it is thought by some that L-glutamine may help heal leaky gut syndrome.

    So, might L-glutamine be dangerous for me due to my anxiety-disorder/panic-attacks?

  9. I took glutamine supplement for the first time today due to starting exercising. I couldn’t sleep was actually high and due to me having some issues with life right now I thought I was having a manic episode for the first time. I am bipolar and have a family history of mania. I started reading up on mania and eventually lead me to this site. If this does that for me that has never had mania before I would definitely not recommend someone in same shoes to use the supplement. Thank god it was the supplement because I thought I was having my first manic episode. It’s 4am and feel like I can go another day. Definitely not normal behaviour!!!!!

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