L-Glutamine is all the hype when it comes to leaky gut and sleep but why is everyone ignoring the fact that there are just as many paradoxical reactions? Some people who try L-glutamine or products that contain L-Glutamine like whey protein, hydrolyzed collagen and many others experience extreme reactions and suffer from insomnia. Why is no one talking?
L-Glutamine caused me lots of grief and left me suffering from a nasty insomnia for weeks. In this article I will share my story, making some educated guesses as to what could have gone wrong and will caution you against taking L-Glutamine so indiscriminately.
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The L-Glutamine Hype
The reason I decided to try L-Glutamine is because a few studies out there which claim that:
1. It is said to have a calming effect on the brain, and
2. Regular use of glutamine supplements leads to a more restful sleep;
3. Helpful in repairing the intestinal wall for those of us with the so called leaky gut.
4. L-glutamine (especially in combo with Glycine) has a proven ability to elevate glutathione levels.
5. Can lower ammonia levels.
The hyped up version from the so called Amino Acid Alliance sounds like this:
“L-glutamine’s main role in the body is to stabilize the immune system. Adequate levels of L-glutamine promote good health, optimization of sleep cycle behavior, a calm mind, and reduced anxiety. The function of L-glutamine is also related to gut health, tissue healing, brain and muscle functions, as well as regulate appetite. In terms of sleep, L-glutamine helps with increased dopamine production. Low levels of dopamine are also associated with sleep disorders. Good deep sleep supplements should always contain L-Glutamine.”
This same “Alliance” claims that L-Glutamine is helpful in “eliminating toxic ammonia.” “If blood levels of ammonia increase, the body uses glutamine to reduce ammonia levels in the brain.” If any of you have studied ammonia’s role in our sleep you know that this is a serious issue so anything that can help reduce ammonia is awesome. So a big Yeh! to L-Glutamine… Found a winner, right?
My L-Glutamine Experiment Gone Bad
Once I took a dose of L-Glutamine powder I initially felt very relaxed and sleepy. This was a very welcome reaction but towards the evening I felt something was seriously off. I started experiencing increased ear ringing, felt even more stimulated and at night I was unable to sleep. Intense reaction lasted a week and it started tapering off only two weeks into it. I was really upset, angry, defeated, AGAIN. Another experiment had gone sour.
Untangling all this is quite a challenge but I found three potential actions at play here. It could be one of them or the combination that caused such a bad insomnia. One factor is related to excess glutamate and ammonia toxicity, second to Glutamate-GABA imbalance and third to mast cell activation (MCAS). All of these seem to be impacted by poor liver and gut function.
What is Glutamate and How it’s Related to L-glutamine?
You’ll notice that I will mostly focus on the action of glutamate here. The latter and L-Glutamine are technically two different amino acids but our bodies convert L-Glutamine into Glutamate and vice versa.
The key thing to remember is that glutamate is one of your primary excitatory neurotransmitters or brain signalers. It has many important roles like stimulating your brain cells so you can talk, think, process information, learn, remember. It animates us!
Although glutamate is one of the most abundant neurotransmitters found in the brain, it exists in very small concentrations. If the concentration level rises, then neurons become too excited and don’t fire in a “normal” manner. Science says glutamate becomes an excitotoxin when it is in excess; it overstimulates brain cells and nerves and results in neurological inflammation and cell death. An excess of glutamate is a primary contributing factor to a variety of neurological disorders of which one is insomnia. In short – we want to avoid excess glutamate circulating in our system.
Liver, Gut and High Ammonia
Safe to say that many of us chronic insomniacs have issues with toxicity and suffer from some sort of liver dysfunction which means that not only our detox pathways are not working properly we might be failing to process (eliminating or converting) certain nutrients. In some cases we might even be producing toxins to our brain. Some studies call L-Glutamine the Trojan Horse of ammonia toxicity.
We propose a mechanism by which glutamine executes its toxic effects in astrocytes, the “Trojan horse” hypothesis. Much of the newly synthesized glutamine is subsequently metabolized in mitochondria by phosphate-activated glutaminase, yielding glutamate and ammonia. In this manner, glutamine (the Trojan horse) is transported in excess from the cytoplasm to mitochondria serving as a carrier of ammonia. We propose that it is the glutamine-derived ammonia within mitochondria that interferes with mitochondrial function giving rise to excessive production of free radicals and induction of the mitochondrial permeability transition, two phenomena known to bring about astrocyte dysfunction, including cell swelling.
Normally it is said that “The liver assumes a major role in regulating glutamine metabolism in the body; it synthesizes extra glutamine when needed, and breaks down glutamine when there is excess.” But what if one’s liver function is impaired in any way? Apparently, liver can convert L-Glutamine to ammonia! Excess ammonia becomes toxic to CNS and produces symptoms. According to studies:
Ammonia toxicity occurs when the ammonia content in the blood supersedes the liver’s capacity to eliminate it. Ammonia is very toxic to the brain. When excessive amounts of ammonia enter the central nervous system, the brain’s defenses are severely challenged.
Besides impaired liver function, one’s gut health can be a major source of additional ammonia. Parasites, “bad” bacteria, and candida yeast overgrowth in the intestinal tract, can produce more ammonia than the body is equipped to deal with. This adds to overall ammonia burden. Some studies show that the ammonia produced in the gut can further damage the liver leading to a vicious cycle and compromise an immune system, damaged mitochondria, which is what i feel happened to me.
Most importantly, this study explains why therapies targeted to intestinal bacteria have only a limited effect on ammonia levels in patients with liver failure and indicate the need for new strategies focused on addressing both the liver and gut.
Glutamate – GABA Imbalance
GABA, which is short for gamma-aminobutyric acid, is your primary inhibitory neurotransmitter. Its primary role is to calm the brain, slow things down and relax you. In this respect, it is the complete opposite of glutamate.
Thus, depletion of GABA can be a major contributing factor to autonomic nervous system disorders like adrenal fatigue, insomnia, chemical sensitivities, chronic fatigue, panic attacks, etc.
This is Where it Gets Interesting!
Glutamine coverts glutamate which becomes a precursor to GABA. Any excess glutamate should technically automatically convert into GABA and increase GABA. This is why many people actually report sleeping better when supplementing with L-Glutamine.
However, sometimes the body cannot regulate glutamate properly. While L-Glutamine should technically increase GABA, it first increases glutamate, and if for some reason you aren’t converting your glutamate to GABA then you end up with excess glutamate which builds up to high levels causing excitotoxicity and INSOMNIA.
Additionally, glutamate receptors also pull other excitatory substances into the cell: aspartate, aspartame, aspartic, MSG, cysteine, and homocysteine. Each of these can bind with glutamate receptors and result in excessive stimulation contributing to the imbalance in GABA and glutamate. This way a wide array of symptoms can be generated. The more glutamate receptors you have the more excitatory substances that will be pulled in. Too much glutamate can also lead to too much acetylcholine (another neurotransmiter), which will also promote a stimulating effect and stress our nervous system with high levels of anxiety, fear, insomnia, restlessness, nervousness etc.
Is this getting complicated already? Trust me, for me too! This is why insomnia is so much more complicated than most of the advice we hear about it on the net. But don’t let me leave you stranded here on the confusion island. Here’s more!
What Else Can Cause High Glutamate Levels?
Mast Cell Activation Syndrome can leave you with excess glutamate.
Genetic variants that can contribute to high glutamate levels – like GAD1, and GRIA3. Our bodies can recycle glutamate into GABA, however, to some people these genetic variants can disrupt conversion pathways.
Methylation issues – again various genetic variations like MTHFR and CBS and COMT can play a role here. I, for example, have a COMT (++) gene polymorphism which is implicated for poorly breaking down neurochemicals. Dysfunctional methylation is slowly being recognized by the medical community as a major cause of a whole range of chronic health conditions.
People with brain injuries – research is out there. Brain injury can leave one with excess glutamate for life.
Heavy metal toxicity – this would me closer to direct cause and a more overarching root cause.
Mold toxicity – can overwhelm our drainage and detox pathways, mess with methylation and wreak havoc in our bodies. Look up mold symptoms and see if anything else matches up.
Lyme disease – chronic Lyme is another major dis-regulator. Check for other symptoms.
Shortage in GAD enzyme – An enzyme called glutamic acid decarboxylase (GAD) is needed for glutamate to make the conversion to GABA, but there are several factors that may interfere with this enzyme. An impaired GAD enzyme may be the primary underlying issue that results in too much glutamate.
B6 deficiency – for Glutamate to be broken down, it requires vitamin B6 through an enzyme glutamate decarboxylase. B6 (pyridoxine) is an essential cofactor in the conversion of glutamate to GABA. Lack of this vitamin can result in diminished GABA synthesis and a buildup of glutamate. One must be very careful here as supplementing too much could lead you towards another perilous path. B6 toxicity is a real thing.
Doses too high – I might have taken too much and overburdened my system. Some of us can eat small amounts glutamate rich foods (but if we drink a protein shake (free and unbound glutamate), have a beer, some aged sausage and cheese we might produce a glutamate storm right away. (FYI: other major food sources of glutamate in food are wheat, barley, oats, cow dairy, various beans, soy, peanuts, processed foods, etc.)
Stress – The demand for glutamine increases with physical and mental stress so your body will produce more. Insomnia is very stressful and this is why it can be such a vicious cycle.
Remember, Glutamine/Glutamate sensitivity is only one piece of a chain reaction. IT IS NOT a direct cause of your health issues.
In any case, once you’ve been “glutamated” it is very difficult to shake the excess. I have a feeling this happens because glutamate plays a role in mast cells and those need days to calm down. Perhaps this why I initially felt very relaxed (increased GABA) and then suffered for weeks because ammonia levels kept circulating, activating mast cells, brain and nervous system.
Neither L-Glutamine, nor glutamate are an enemy if our bodies are able to convert things properly and flush the excess out. Problem is that for many of us the underlying issues in our gut and liver do not allow for this to happen. Whether it is high levels of ammonia that become toxic to liver, brain and the nervous system or some other mechanism that causes symptoms one thing is clear – we should learn how to manage our condition in order to function better.
For a start, anyone who has an issue with excess glutamate should avoid supplementation with glutamine or any other supplements like Glycine (also implicated in restless sleep and high ammonia) and foods that contain high glutamate. Once the root cause is rectified you can potentially shake your insomnia or at least improve sleep to tolerable levels, which is what happened to me.
There are a few things we can do to lower glutamine and ammonia. One beneficial supplement could be bentonite clay. It is said to have an affinity for ammonia ions and absorb toxins out of the intestinal tract. I’ve been using it for a couple of months and feel subtle benefits.
As of today, the only remedy (that I’ve heard of) to reduce glutamate levels is suppose to be taking Niacin. I haven’t tried it yet but the next time I get “glutamated” I will try a small dose like 50gm and see if it helps. Meanwhile, if you have experienced insomnia from taking L-Glutamine or aware of any tricks to neutralize it please let me know in the comments below.
Have you tried L- Ornithine to remove excess ammonia? It’s an amino acid.
Hi Patricia, yes I did but even that felt too much for my liver. Is it helping you?
Yes! I’m so glad you wrote this. I thought maybe I was imagining it. I see this is over a year old. Can you update us as to your progress? Also, for anyone else just finding this, I found a helpful article on web md called “ten food high in glutamate” that also lists some herbs that can help balance glutamate with GABA: (lemon balm, chamomile, passion).
Hi Leah, by detoxing mercury I’m finding that my glutamate and histamine issues are mostly related to my liver function (methylation) and also general inflammation. Our bodies should have no problem braking down glutamate unless there’s something blocking that process or “overloading the pathways” so to speak. I’ll update you more as I get down to the bottom of this.
Thanks for this post. I’ve had insomnia for 19 years. 4 keys to healing, for me so far have been, 20 mg melatonin before bed (no headaches or problems when taking the right brand), transdermal magnesium (can’t take internally because digestion is weak), no alcohol/meds, high quality diet. I still haven’t got all the pieces but one step at a time… I’d love to hear any improvements you’ve had.
Hi. I’m so glad you wrote this as well! I couldn’t figure out what was causing my insomnia to be SO wickedly intense after taking high doses of l-glutamine for my leaky gut/celiac disease inflammation. Your research has given me hope and helped me find this path of liver/inflammation to be the possible missing link for my chronic insomnia. (I’ve tried so many, many different things with zero luck) Please send updates as you progress and I can also share my progress if you’re interested. And thank you again so very much!
Thank you Cambria. I’ll update this post with new discoveries. Have you ever done a genetic test to look into your methylation profile? There’re are many answers there in how our liver processes nutrients and why some of us are really sensitive to glutamate. Please stay in touch and perhaps we can share some of our experiences.
I have not done a genetic test for methylation. I will bring this up with my doctor. I am very curious. Through further research I’m trying to understand the potential link between my histamine issues and glutamate as well. My understanding thus far is that they seem to hang out together but having high histamine doesn’t seem to mean high glutamate. Both are excitatory. Histamine doesn’t seem to have as intense an effect as the glutamate. It took me over a week to start getting any sleep again after this last time I took l-glutamine. I was recently diagnosed with celiac disease and a thermogram scan shows the inflammation in my body. So I’m assuming that the inflammation is causing or at least part of the issue with the inability to flush the histamine and glutamate..? Maybe the genetic test will help resolve this. I started taking NAC to see if it helped at all but studies show it also can cause a histamine flood as well. I’m considering a liver detox as well. Thank you so much I really appreciate being able to toss this back and forth!
I’m so glad to see this. My Sister told me I should be taking L Glutamine for gut issues but since taking it I have had wrestles sleep and overly active brain and anxiety all day long each day. I read you above sleep issues and mine are good by taking GABA at night before sleep and I also take a liquid Melatonin that is fermented. Just a mere 8 drops and you sleep really great. I was the queen of insomnia before I found this Quantum Nutritional Labs brand of liquid Melatonin. I’ve been taking it for years. I’m not affiliated in any way with this company. Also no nightmares with this melatonin and you don’t feel groggy.
Thank you sooo much for writing this, now I know why I’m having these symptoms.
Thank you for this article and website. I so appreciate you sharing your experiences and educated guesses.
I wonder if you can provide insight about my situation. I deal with anxiety and major depression. I recently noticed that certain Asian meals, likely high in ingredients meant to replace MSG (therefore having a similar result in the body), were helping to calm my mind and nervous system as well if not better than Xanax, which I know raises GABA temporarily. And I’ve had full relief from depression with motivation I have lacked for months and haven’t had continuously in a very long time.
I began consuming these Asian foods as a replacement for medications. It’s been great to slow my overactive mind. However, after buying MSG to use at home, I noticed it is causing alertness, which is making my insomnia return. Yet I still slur my words and have memory issues as though my GABA is high. It’s embarrassing, but preferable to a mind that won’t stop.
So, I believe the ingredients in these dishes that were working for me as a sedative are not MSG, but the sort of copycats. I guess. And maybe a combo effect is occurring. It’s things like autolyzied yeast extract and disodium inosinate, and I don’t know what role DMSO may play in this, but I don’t feel good about that in my food.
It interests me that you mention mitochondrial function and I wonder what role a lack of sunlight plays in this for all of us. I do already supplement with D3 and K2. I also take B12 and B6 regularly. All of these I take sublingually.
Anyhow, I’m a thin individual and I don’t feel I have liver issues, though genetic testing showed I cannot tolerate most SSRIs. I also may have had a mast cell issue in the past, but I don’t feel I do right now. Insomnia is destroying me though and I wondered what suggestions you have apart from the typical stuff. CBD oil did nothing for me.
Side note-I read elsewhere that you can immediately neutralize MSG with ginger.
Also, I believe occasional fasting is the solution to restoring the body’s equilibrium.
Wow, what a story.. MSG laden meals actually make you feel better? I wonder if there is something else going on here, like you say. When you say you put MSG in your meals you actually put MSG or you supplemented with L-Glutamine? Your question is very vast and difficult to answer here but I would look into methylation issues, liver phases and heavy metal toxicity. By the way, all of your supplements you mentioned can trigger insomnia. I would stop all of them, especially Vit D and B12 and give it some time.
Could you please comment on this article?
“ Here’s the cool deal on absorption. 95% of glutamate, free or bound – is actually NEVER absorbed in the intestines, but is actually utilized by the gut where it gets converted within the cells that line the GI tract into energy or other amino acids. In other words, there is no scientific evidence to suggest that dietary glutamate reduces absorption of other amino acids.”
I would assume it gets utilized in the gut ONLY if the gut is able to do so. Some of us with compromised glutamate decarboxylase/GABA shunt pathway will feel like hell after large doses of glutamate due to NMDA receptor excitation and inability to counteract glutamate load. In simple terms, the observation of the article is probably correct IF the gut functions properly. Do you agree?
Great article, thank you
I was thinking of supplementing with Glutathione
Have you heard of any issues with this interrupting sleep?
Hi Ryan, glutathione is a whole different animal but the general idea I’ve developed so far is to be very careful with supplementation. Instead it would be wise to encourage endogenous production with necessary co-factors or else it can backfire rather quickly.
After taking L glutamine. My energy was so high… was hard for me to get a good nights sleep.
yes, this is what they call a glutamate/GABA imbalance. Body is not fast to convert because of some underlying issue like liver congestion.
I suppose that taking a benzodiazepine to sleep increases GABA. I wonder what type of connection there might be between this and glutamate, or how it can be regulated. I haven’t had any reaction from taking glutamine, but I cannot assure that it has helped me in any way. Thank you Tadas
I believe that Benzos are targeting GABA receptors directly while Glutamine has to be converted through Kreb’s cycle before GABA is produced. If you had no issues with L-Glutamine then that is a good sign that your conversion process to GABA is solid but the question remains whether you are still flushing enough ammonia which could be the real culprit behind L-Glutamine.