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.
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.