Glutamate, Inflammation, Restless Legs and Insomnia: PART 1 of 2

ImageIn April of 2013 results of a scientific study were released showing that the presence of glutamate was much higher in Restless Legs patients than in the normal population. As you’ll read below, excessive glutamate makes your brain race uncontrollably. Not helpful if you’re trying to fall asleep at night before your legs start acting up.

This (as well as the presence of increased histamine levels in RLS patients) is hard evidence of why so many RLS sufferers have a racing mind at night when they are trying to sleep. 

I remember so many night, lying in bed exhausted, but unable to sleep. It didn’t make any sense? Now it makes perfect sense.

Fortunately, there are remedies to help lessen your glutamate level and slow the brain down. I’ll touch on those in the next post.

from Johns Hopkins Medicine
“The small new study, headed by Richard P. Allen, Ph.D., an associate professor of neurology at the Johns Hopkins University School of Medicine, used MRI to image the brain and found glutamate — a neurotransmitter involved in arousal – in abnormally high levels in people with RLS. The more glutamate the researchers found in the brains of those with RLS, the worse their sleep.

For the study, Allen and his colleagues examined MRI images and recorded glutamate activity in the thalamus, the part of the brain involved with the regulation of consciousness, sleep and alertness. They looked at images of 28 people with RLS and 20 people without. The RLS patients included in the study had symptoms six to seven nights a week persisting for at least six months, with an average of 20 involuntary movements a night or more.

The researchers then conducted two-day sleep studies in the same individuals to measure how much rest each person was getting. In those with RLS, they found that the higher the glutamate level in the thalamus, the less sleep the subject got. They found no such association in the control group without RLS.

Previous studies have shown that even though RLS patients average less than 5.5 hours of sleep per night, they rarely report problems with excessive daytime sleepiness. Allen says the lack of daytime sleepiness is likely related to the role of glutamate, too much of which can put the brain in a state of hyperarousal — day or night.”


from the Vitality & Wellness Centre
“Your body has two sorts of neurotransmitters; one that excites you (keeps you awake) called Glutamate and one that relaxes you called GABA.

GABA is your body’s main relaxing neurotransmitter. Your body’s main excitatory neurotransmitter (Glutamate) is most active during your waking hours. So when you fall asleep your brain Glutamate levels should drop and your brain GABA levels should rise. This facilitates a great restful nights sleep.

People who have trouble sleeping, or more specifically are unable to switch their minds off, generally have lower than normal levels of GABA with elevated Glutamate levels. These people generally make the comment that their minds are always racing and that they are unable to fall asleep or when they wake up they are always thinking and are unable to get back to sleep.”

Below is an excerpt from a highly informative article by Dr. Nancy Mullan that gives a great overview of glutamate. 

from Nancy Mullan MD
“Glutamate is an excitatory neurotransmitter. While I am thinking, talking, processing and sharing with you, the glutamate receptors in my neurons are functioning actively to take glutamate into the cell.

You need glutamate for learning, attending, and functioning. In fact, the more intelligent you are, the more glutamate receptors you have on your cells. But too much glutamate being taken in to your nerve cells will burn them out. It would be like turning a light switch on and off continuously until it breaks.

A number of other substances related to glutamate will also act as excitatory neurotransmitters at glutamate receptor sites. They include glutamate, glutamic acid, glutamine, alpha ketoglutarate, and monosodium glutamate or MSG. The aspartate family of molecules will do this also. They include aspartate, aspartic acid, and aspartame, commonly known as NutraSweet.

For the aficionados among you, cysteine can also act as a mild excitatory neurotransmitter, but N-acetyl cysteine does not. However, N-acetyl cysteine contains an acetyl and a sulfur group and so must be used thoughtfully.

Glycine is also a special case neurotransmitter. If the balance in your body is towards glutamate, glycine will be excitatory. If the balance is toward GABA, it will be inhibitory. So if you tend toward glutamate excess, avoid glycine.

The number of glutamate receptor sites on your neuron surfaces are an important determinant of the level of glutamate in your cells. The more glutamate receptor sites you have, the more glutamate you take in. Your resting level of glutamate is higher. Your balance tips to favor excitotoxicity. Glutamate excitotoxicity produces nerve damage or death. It does this by setting off inflammation.

Increased numbers of glutamate receptors have been associated with certain neurologic disorders. Lou Gehrig’s Disease or Amyotrophic Lateral Sclerosis (ALS), Fragile X, schizophrenia, and seizure disorder are among them.

Increased glutamate produces insomnia, decreased eye contact and may lead to too much acetyl-choline which can lead to bladder contraction and abnormal eye movements called strabismus. And increased glutamate causes an increase in self-stimulatory behavior (stims).

One of the ways your brain deals with excitotoxin damage is to increase the level of opioids that are produced. Opioids are opium-like substances. Obviously they will interfere with your ability to function.

Elevated levels of glutamate deplete your levels of glutathione (GSH). GSH is a central antioxidant and metal detox agent in your body. Depleted GSH leads to increased inflammatory mediators, including TNF alpha, and helps to exacerbate leaky gut.”


from Wikipedia – Excitotoxicity
“Excitotoxicity is the pathological process by which nerve cells are damaged and killed by excessive stimulation by neurotransmitters such as glutamate and similar substances. This occurs when receptors for the excitatory neurotransmitter glutamate (glutamate receptors) such as the NMDA receptor and AMPA receptor are overactivated by Glutamatergic Storm.”

Pictorial Review of Glutamate Excitotoxicity: Fundamental Concepts for Neuroimaging.”
Leighton P. Marka, Robert W. Prosta, John L. Ulmera, Michelle M. Smitha, David L. Danielsa, James M. Strottmanna, W. Douglas Browna and Lotfi Hacein-Beya. From the Neuroradiology Section, Department of Diagnostic Radiology, Medical College of Wisconsin, Froedtert Hospital, 9200 W Wisconsin Ave, Milwaukee, WI 53226. AJNR 2001 22: 1813-1824

“There is a growing list of neurologic disorders are now understood to share a final common destructive metabolic pathway called excitotoxicity, which has been the focus of intense investigative efforts in the neurosciences over the past several decades (3–31). Excitotoxicity refers to an excessive activation of neuronal amino acid receptors. The specific type of excitotoxicity triggered by the amino acid glutamate is the key mechanism implicated in the mediation of neuronal death in many disorders.

Glutamate excitotoxicity is the final common pathway resulting in neuronal injury for many seemingly unrelated disorders, including ischemia, trauma, seizures, hypoglycemia, hypoxia, and even some neural degenerative disorders. Familiarity with this process is important for neuroradiologists because of its central position in many of the disorders encountered in daily practice. This area has been one of the most intensely investigated fields in the neurosciences over the past several decades, and the information generated from this work will clearly influence our basic understanding of many neurologic disorders.”


When I see a report like results of the John Hopkins study, I am 100% certain that if I do a bit of digging, there will be an undeniable bond between whatever the agent happens to be (in this case glutamate) and inflammation.

Sure enough, the evidence is OVERWHELMING that inflammation is directly involved with the excessive glutamate levels.

Below are some studies that identify this connection. I’m only posting a few here. You can read the results from several other studies at my website.

from Russell L. Blaylock, M.D. on the Vaccine Risk Awareness Network

“Neuroscientists have known for sme time that inflammatory cytokines cause the brain to release higher levels of glutamate — the more intense the inflammation, the higher the brain glutamate level. The highest levels are found in the prefrontal lobes and limbic system, the areas most related to mood control. MSG also increases brain inflammation.”

from Emily Deans, M.D. in Evolutionary Psychiatry
“Inflammatory cytokines interfere with the regulation ofthe neurotransmitter, glutamate. Glutamate is an excitatory neurotransmitter that, if left to go wild, can pound our NMDA receptors in the brain and wreak major havoc. No one wants overexcited NMDA receptors, and clinical depression is one among many nasty brain issues that can be caused by overexcitement. Astrocytes, little clean-up cells in the brain, are supposed to mop up excess glutamate to keep it from going nutso on the NMDA. Turns out inflammatory cytokines interfere with the clean-up process. The horse tranquilizer (and club drug) ketamine, when administered IV, can eliminate symptoms of severe depression pretty much immediately in some cases (do NOT try this at home) (2). Ketamine helps the astrocytes mop up glutamate, and it is assumed that this is how ketamine instantly cures depression. Unfortunately, the effects of ketamine don’t last, otherwise it would be a nifty tool, indeed.”

“Effect of glutamate on inflammatory responses of intestine and brain after focal cerebral ischemia.”
Xu L, Sun J, Lu R, Ji Q, Xu JG. Department of Anesthesiology, Jinling Hospital, 305 East Zhongshan Road, Nanjing 210002, Jiangsu Province, China.

“Glutamate is involved in the mechanism of intestinal and cerebral inflammation responses. The effects of glutamate on cerebral and intestinal inflammatory responses after ischemia are up-regulated at the transcriptional level, through the NF-kappaB signal transduction pathway.”

Don’t worry, it may seem bleak, but the news gets better. In the second post of this series I’ll feature some natural methods for lowering your glutamate level –  hopefully opening the doorway to a better sleep.


  1. ken osborn said

    OK, glutamates (glutamic acid, glutamine, et al) are cytotoxic and glutathione is an antioxidant that protects against cytotoxicity. Now I read that cysteine and glycine can also be cytotoxic but they are also precursors of glutathione. So if glutathione stores are depleted should one avoid taking the precursors as supplements?

  2. rlsottawa said

    Hi Ken
    Sorry, I have no idea. If a scientist reads this comment maybe they can answer your question.
    I would recommend you hop on Google and find if there’s a safe way to restore your glutathione level. Did you have some sort of test done to find that your glutathione level was low?

  3. ken osborn said

    Thanks for the response. I haven’t done any blood tests to determine if my glutathione level is low, but I know my stress level is pretty high and as a consequence glutathione levels could very well be diminished. I’m also in that age range where glutathione levels typically decline (

    I did find an article on oxidative stress in aging (The American Journal of Clinical Nutrition, July 27, 2011: that concludes: “Glutathione deficiency in elderly humans occurs because of a marked reduction in synthesis. Dietary supplementation with the glutathione precursors cysteine and glycine fully restores glutathione synthesis and concentrations and lowers levels of oxidative stress and oxidant damages. These findings suggest a practical and effective approach to decreasing oxidative stress in aging”.

  4. rlsottawa said

    I did a quick search and found this website.

    Even though this guy is pushing his supplement, there’s some great info on his website, including a short video of the Dr. Oz Show where an expert explains the importance of glutathione

    According to Dr. Oz’s guest (and you) glutathione is absolutely crucial, and lacking in most people.

    I’ll do more research in the near future.


  5. Thank you so much for this wonderful article. It’s the best I’ve read. After 15 years of insomnia, racing mind and RLS I finally feel I’ve discovered what’s wrong. What a relief. It would be helpful to have some info on how much of these supplements to take and the best time to take them.

    • rlsottawa said

      Hi Claire Glad you enjoyed it! As far as the dosage, just follow the instructions on the bottle for the supplements, and I would try to integrate some of the recommended foods into your diet as well.

  6. Gisele said

    Please know that the information in this article has given me lots of hope. Thank you, thank you, thank you!

  7. Shankar said

    Where is part 2??

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