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.


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

    1. Glutathione is often confused with glutamate, but they are very different. Glutathione is generally safe for most people, but I would check with your practitioner first.

      1. Latisha D Lomax-Harris

        I agree, I’m lost and scared my Functional Dr just prescribe this for me to heal Gut Dysbosis but I’m dealing with alot of depression and anxiety do to being I’ll.

    2. Recently I began using L Glutamine to help suppress sugar cravings. Within a few weeks of taking it occasionally, I began having trouble thinking and remembering simple things. I can only assume it was the L Glutamine since I’m already taking GABA and combined, I believe it has affected my thinking faculties. This is the only thing new in my vitamin and supplements. Decided to stop taking to see if this indeed is the issue.

  1. Albeit glutamine having repercussions for those with mental health imbalances, I have documented no real negative effect at randomized doses under 5g. Glutamine, from what I’ve read, takes a week or so to build up in our system (hence the “loading” phase in athletes), therefore I seem to be having sucess taking it during shorter periods of time; allowing my body to receive the gut healing and muscle repair benefits. It can be a wonderful supplement to administer where slow muscle recover is predominate, or other gut healing protocols are seemingly not working. It was the one nutrient that gave me relief of intense post exercise muscle pain 🙂

    1. I agree it is a great nutrient, but even at lower doses, it can create significant negative reactions. I’m glad it worked well for you!

    1. I started taking L glutamine a five days ago. I’m using 5g of powder in a shake once a day. Suddenly I find I’m in a state of excessive worry and feeling depressed and anxious about the future. I was hoping it would help with some gut issues and lack of motivation, after reading a lot of positive reviews. It was not until today that I searched for a list of negative side effects, after experiencing these systems. Goes to show that we see and hear what we want to. Natural supplements are not always for everyone. I’m going to stop using it.

  2. Hi Sami
    I had blood test done and noticed that copper and zinc were also tested.
    I’ve read that the copper/zinc ratio is as important as each level by itself and also the ceruloplasmin is also significant. When I try to determine the ratio it doesn’t come out to match and any reference that I read of so I think I’m figuring it wrong.
    If my copper is 114 (mcg/dL) and zinc is 71 (mcg/dL), ceruloplasmin is 28 (mg/dl), can you tell me how to determine the ration?
    Thank you

    1. You just divide the copper value by the zinc. Your ratio is 1.6,too high right now (just like my daughter’s 🙂

  3. I remember taking L-glutamine many years ago after reading the Mood Cure by Julia Ross. I instantly felt very good. However, I think that taking it over the years may have contributed to problems down the road. Now I know I’m an overmethylator. I’m really thankful I did the biochemistry testing and that you are sharing this information.

  4. Can you tell me how do I know if a collagen powder or protein powder contain glutamine,since, as you stated it can be hidden?

    1. All protein powders contain free glutamates, which most aren’t a problem for most people. What you need to look out for is the addition of l-glutamine to their formula. It will be listed under ingredients on the nutrition label.

    1. I am so glad I read this information today regarding l-Glutamine. I was diagnosed with leaky gut syndrome may years ago
      by my holistic doctor prescribed this supplement. I tried many time on and off. Every time I started, I had to discontinue it because I did not feel good. I felt nausea, stomach discomfort and headaches.

    2. I’m really worried. My functional dr had me taking a lot to heal leaky gut. Now I can’t think straight- have anxiety and panic. Is this permanent?

      1. Hi Kathleen – the negative effects of the l-glutamine will wear off over time after you stop taking it.

  5. I’ve recently been taking approximately 15g of l-glutamine to heal leaky gut. I’ve noticed that after taking it my body temperature increases dramatically and can lead to sweating (I am normally run cold in temperature).

    Would this be a negative side-effect related to the brain? I can’t seem to find much information on the temperature side-effect.

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