HOW TO LOWER YOUR GLUTAMATE LEVEL (FOR A BETTER SLEEP)
from Nancy Mullan MD
“If you keep the total amount of glutamate in your body under control, you can prevent neurologic symptoms. One way you can do this is by eliminating gluten and casein from your diet. You also want to eliminate glutamate and anything that sounds like that, and aspartate and anything that sounds like that, from your supplements.
Glutamine is a frequently recommended supplement, but glutamate and glutamine change back and forth into each other. This means that the administration of glutamine, say for gastro intestinal support, actually increases the level of glutamate.
There is a neurotransmitter, which opposes glutamate, which has a calming effect. This is GABA, gamma amino butyric acid. It is an inhibitory neurotransmitter. Glutamate should be able to convert into GABA.
Glutamate is acted on by the enzyme glutamic acid decarboxylase (GAD), but several factors may interfere with this conversion, and you get stuck at glutamate.
GABA is the neurotransmitter involved with this function. GABA is very prominently involved with the neuronal connections of language. It actually puts the gaps between words. Decreased GABA leads to increased anxiety, increased aggressive behavior, decreased social behavior, decreased eye contact, and decreased bowel function. GABA is necessary to stimulate bowel contraction.
Decreased GABA also causes eye-focusing problems, like both eyes focused in toward the nose or vertical or horizontal eye wavering.
Calcium is another factor in the glutamate GABA story. If glutamate is like a gun, then calcium is the bullet. Glutamate creates the scenario for excitotoxicity to happen, but the agent that actually destroys the nerve cell is the influx of calcium. The combination of excessive glutamate from any source and too much calcium is major.
Evaluate calcium levels using a urine essential elements test. Vitamin D and Vitamin K are fat-soluble vitamins and are important for re-establishing calcium balance. Your body can store Vitamin D, but Vitamin K may need to be supplemented on a daily basis unless you are eating dark leafy green organic vegetables.
Supplementing calcium may be done by using chamomile and/or nettle rather than by taking calcium directly. Increasing magnesium relative to calcium, using zinc to limit glutamate damage, and monitoring lithium, iodine and boron levels will all aid in reducing glutamate levels and reversing the flow of calcium into the neurons and back to the bones and teeth.
A common issue is taking too many supplements too soon. The more sick you are, the more carefully you need to add supplements. You should add them one at a time, starting with really tiny amounts.”
WHAT IS GABA?
from Novus Medical Detox Center
“GABA is a chemical messenger that is widely distributed in the brain. GABA’s natural function is to reduce the activity of the neurons to which it binds. Some researchers believe that one of the purposes that GABA serves is to control the fear or anxiety experienced when neurons are overexcited.
GABA receptors are probably the most common kind in the mammalian nervous system. It is estimated that close to 40% of the synapses in the human brain work with GABA and therefore have GABA receptors.
GABA receptors are channel receptors. This means that when GABA binds to them, they change shape slightly to allow ions to pass through their central channel. This channel mainly allows negatively charged chloride ions to enter the neuron, thus reducing its excitability.
Because of this property of the GABA channel receptor, GABA is classified as an inhibitory neurotransmitter, as opposed to excitatory neurotransmitters, such as glutamate, which augment the nerve impulses in the neuron.
When GABA binds to a nerve cell receptor, it opens the nerve cell so that chloride ions which are present in the brain are allowed to move into the nerve cell and slow the activity of the cell, and the person normally experiences a calming feeling.
For example, if our brain produces more excitatory neurotransmitters like norepinephrine or epinephrine (adrenaline) than normal, we can become anxious or have more stress than normal.
If our brain is working normally, it will produce more GABA and this will slow down the actions in the brain and thus have a calming and relaxing effect on us.
Because of our unique DNA and the way that each of us metabolize drugs, each of us may have different amounts of GABA in the brain but we are still considered to be operating “normally.” Unfortunately, there are no accepted medical tests to determine if we have too much or too little GABA activity.
In addition, it appears that people who are nutritionally deficit and dehydrated often have problems with the operation of GABA in their brains.
It is widely believed that caffeine produces its stimulant effects by inhibiting the release of GABA and thereby allowing the increase of excitatory neurotransmitters.
Research is indicating that a major factor in people who suffer from anxiety disorders or panic attacks and in people who have become addicted or dependent to street drugs, prescription drugs and alcohol is that they are likely to be suffering from low GABA activity.”
THE GLUTAMATE-GLUTAMINE CYCLE
During all the research I’ve done over the last few years, researching EVERY area of RLS, from the scientific to the emotional, to the outrageous … I’ve never been as confused and overwhelmed as I have been in trying to decipher all the information that’s available on how to naturally boost your GABA level.
One thing that is unanimous, is that the “supplement” GABA is essentially useless. So that option is eliminated.
The really confusing area (the part that hurt my brain) is whether or not to take L-Glutamine to help boost your GABA level.
To understand the relationship between GABA, glutamine and glutamate, you have to understand a bit about the intimate cycle they are involved with. This cycle determines whether more GABA or more glutamate is produced.
Here are a couple of explanations.
from Wikipedia, Glutamate-glutamine cycle
“In biochemistry, the glutamate-glutamine cycle is a sequence of events by which an adequate supply of the neurotransmitter glutamate is maintained in the central nervous system. Neurons are not able to perform new synthesis of the neurotransmitter glutamate and y-aminobutyric acid (GABA) from glucose. Discoveries of glutamine and glutamate pools within intercellular compartments led to suggestions of the glutamate-glutamine cycle working between neurons and astrocytes. The glutamate/GABA-glutamine cycle is a metabolic pathway that describes the release of glutamate or GABA from neurons and then taken up into astrocytes (star shaped glial cells). In return, astrocytes release glutamine to be taken up into neurons for use as a precursor to the synthesis of glutamate or GABA.”
from Natural Stresscare
“Think of glutamic acid (GA), glutamine (GAM) and gamma-aminobutyric acid (GABA) as three members of a close-knit family with three very different personalities. Glutamic acid is a non-essential amino acid (the body can manufacture it when things are working right) that’s also an excitatory neurotransmitter.
Its cousin GABA has an opposite personality – it calms our nerves and relaxes us. Glutamine is the source for both of them – the body can make either glutamic acid or GABA from glutamine. This is a special family … the members can change into each other from time to time.”
As I understand it, the glutamine in your body is used to either build your GABA level, in turn lowering your glutamate level … or vice versa – depending on which way they are out of balance at that time.
Glutamine is essentially a manager, determining what needs to be produced in order to keep the GABA and glutamate levels in balance.
For restless legs sufferers, that have some inflammation going on, and in most cases, a racing mind at night … it’s seems logical that the l-glutamine that you intake is going to be used to raise your GABA level, which will in turn lower your glutamate level, and help calm down that racing mind of yours.
But, there’s a catch. Because you have a higher than normal amount of inflammation in your body, this can affect the transport and monitoring that are part of the Glutamate-glutamine cycle.
As you may have read in some of the scientific studies posted on my website regarding inflammation and glutamate, inflammation can affect how the cycle behaves … which is often badly.
It’s kind of like how your keyboard behaves after you spill a cup of coffee on it. It will probably still work, but with a few quirks.
I sent an e-mail to Dr. Mullan asking her to clarify this confusing area for me. Here is her response.
“Be careful when you read studies. You never know what the author’s motive may be or who may be backing the study. Dr Amy Yasko does not recommend l-glutamine because it can turn into glutamate, especially if the GAD gene or enzyme is affected in any way.
And certainly be aware of any dietary influences, especially MSG (it goes without saying). Peas, mushrooms and Parmesan cheese are also on the high glutamate avoid list.”
After taking everything I’ve learned into consideration, my recommendation is to take neither the supplement GABA or L-Glutamine.
Because of the inflammation in your body, their behavior in the delicate Glutamate-glutamine cycle is unpredictable. My suggestion is to take L-Theanine or Taurine and to also consider some of the other natural GABA boosters you’ll read about below.
NATURAL REMEDIES TO INCREASE GABA AND LOWER GLUTAMATE LEVELS
from The Wellspring School for Healing Arts
“L-Theanine is a free (non-protein) amino acid found primarily in tea leaves, (Camilla Sinensis).
L-Theanine, otherwise know as gamma-ethylamino-L-glutamic acid, is thought to be the key to tea’s subtle but calming effects despite the caffeine content in tea. L-Theanine is thought to counter the stimulating effects of caffeine by increasing the production of alpha brain waves. Alpha waves are associated with a state of deep relaxation while being mentally alert. In studies, subjects on L-Theanine exhibited alpha brain wave patterns similar to the state achieved by those during meditation.
Additionally, L-Theanine easily crosses the blood brain barrier, and is thought to play a role in increasing and regulating several neurotransmitters, most notably GABA (gamma amino butyric acid), which is an important inhibitory neurotransmitter in the brain. GABA promotes a pleasant calm without the drowsiness. L-Theanine is thought to interact with dopamine and serotonin as well, resulting in increased focus, improved memory and learning ability.”
from Natural Stresscare
“Rather than GABA or l-glutamine, one can take the amino acid l-theanine instead. L-theanine is converted to several useful calming and mood-elevating substances in the brain, including GABA.3,4 So one can use theanine as a kind of “bank shot” to get around the blood brain barrier issue with respect to GABA.”
“Theanine and glutamate transporter inhibitors enhance the antitumor efficacy of chemotherapeutic agents.”
Sugiyama T, Sadzuka Y. Biochim Biophys Acta. 2003 Dec 5;1653(2):47-59. School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, 422-8526 Shizuoka, Japan.
“The combined effects of theanine, a specific amino acid in green tea, and glutamate transporter inhibitors on the antitumor activity of doxorubicin (DOX), were investigated and we clarified the biochemical mechanisms of action of these modulators.
We revealed the novel mechanism of enhancement of antitumor efficacy of DOX via the inhibition of glutamate transporters. Similarly, theanine enhanced the antitumor activities of other anthracyclines, cisplatin and irinotecan. Consequently, the modulating effect of theanine on the efficacy of antitumor agents is expected to be applicable in clinical cancer chemotherapy.”
from Integrative Psychiatry
“Taurine is an amino acid that is present at significant levels in the CNS and is positive modulator of GABA that does not have any adverse side-effects. Taurine also potentiates glycine – the inhibitory neurotransmitter in the spinal cord.
The role of taurine as an inhibitory amino acid has been confirmed in many studies. Not surprisingly, brain tissue and cardiac tissue, which are susceptible to high levels of neurotransmitter stimulation, maintain high levels of taurine. Taurine has been shown to prevent the neuronal damage that can occur when there is an exposure to increased levels of the excitatory neurotransmitter glutamate. Over stimulation by excitatory neurotransmitters is the primary cause of neuron death in ischemic stroke. Taurine has been found to significantly reduce neuron death caused by over stimulation.
The calming effects of taurine have been well studied. Other studies of taurine have found that it can reduce epileptic seizures and that low taurine levels are associated with anxiety.”
from Charles Poliquin on Poliquin Inc.
“I call taurine the amino acid of anxiety control and stress management because it will lower cortisol and helps people be less anxious. The benefits of taurine don’t stop there. It also improves athletic performance and reaction time, supports insulin health, can prevent diabetes, elevates energy production, is a potent brain nutrient, increases work capacity and time to exhaustion from intense exercise, lowers blood pressure, protects the heart, helps with detoxification, and fights inflammation.
It’s best to lay the building blocks for success before you start taking taurine because this amino acid is an excellent addition to a protein-rich diet and supplement plan that ensures you aren’t deficient in any of the essential nutrients. For example, be sure you are getting a nice therapeutic dose of omega-3 fats, and have your fat intake balanced because this will help taurine work its magic.
Taurine is an amino acid that calms the nervous system by facilitating the production of the neurotransmitter GABA, which stands for gamma-aminobutyric acid. By helping to raise GABA levels, taurine will allow your body to manage anxiety so that your thoughts don’t go spiraling out of control and you don’t get the associated cortisol and adrenaline spikes that go with anxiety and stress.
Research shows that taurine supplementation can lower anxiety in stress-producing situations, thereby allowing for greater work output and performance. One study in Advances in Experimental Medicines and Biology found that giving rats a taurine treatment prior to an anxiety-inducing exercise maze resulted in less anxious behavior and better speed through the maze a rat group that were given a placebo.
Take taurine for better sleep, but make sure you are getting a magnesium supplement that your body can absorb as well. Together these nutrients are the answer to abolish stress, calm the nervous system, and help you sleep better. You’ll also have a better overall mood. People who are deficient in either magnesium or taurine are at greater risk for depression and poor motivation.
Magnesium is well known to calm the nervous system, while countering fatigue. Similarly, taurine raises GABA levels, calming the nervous system and lowering anxiety and stress hormones that hinder rest. I suggest magnesium taurate, a form of taurine that is bound to magnesium for best results.”
“Taurine prevents the neurotoxicity of beta-amyloid and glutamate receptor agonists: activation of GABA receptors and possible implications for Alzheimer’s disease and other neurological disorders.”
Louzada PR, Paula Lima AC, Mendonca-Silva DL, Noël F, De Mello FG, Ferreira ST. Departamento de Bioquímica Medica, Instituto de Ciencias Biomedicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ 21941-590, Brasil. FASEB J. 2004 Mar;18(3):511-8.
“Alzheimer’s disease (AD) and several other neurological disorders have been linked to the overactivation of glutamatergic transmission and excitotoxicity as a common pathway of neuronal injury. The beta-amyloid peptide (Abeta) is centrally related to the pathogenesis of AD, and previous reports have demonstrated that the blockade of glutamate receptors prevents Abeta-induced neuronal death. We show that taurine, a beta-amino acid found at high concentrations in the brain, protects chick retinal neurons in culture against the neurotoxicity of Abeta and glutamate receptor agonists. The protective effect of taurine is not mediated by interaction with glutamate receptors, as demonstrated by binding studies using radiolabeled glutamate receptor ligands. The neuroprotective action of taurine is blocked by picrotoxin, an antagonist of GABA(A) receptors. GABA and the GABA(A) receptor agonists phenobarbital and melatonin also protect neurons against Abeta-induced neurotoxicity. These results suggest that activation of GABA receptors decreases neuronal vulnerability to excitotoxic damage and that pharmacological manipulation of the excitatory and inhibitory neurotransmitter tonus may protect neurons against a variety of insults. GABAergic transmission may represent a promising target for the treatment of AD and other neurological disorders in which excitotoxicity plays a relevant role.”
from Wikipedia – Valerian (herb)
“Valerian has been used as a medicinal herb since at least the time of ancient Greece and Rome. Hippocrates described its properties, and Galen later prescribed it as a remedy for insomnia. Valerian root has sedative and anxiolytic effects. These effects are suspected to be mediated through the GABA receptor. The amino acid valine is named after this plant.”
“The University of Maryland Medical Center says valerian root might increase the concentration of GABA within your brain. Because of this action, valerian is often prescribed as a natural remedy for anxiety and those affected by insomnia. It might take up to three weeks of consistent use for its effects to be felt.”
“Synaptosomal GABA release as influenced by valerian root extract–involvement of the GABA carrier.”
Santos MS, Ferreira F, Cunha AP, Carvalho AP, Ribeiro CF, Macedo T. Department of Zoology, Faculty of Medicine, University of Coimbra, Portugal. Arch Int Pharmacodyn Ther. 1994 Mar-Apr;327(2):220-31.
“The effect of an aqueous extract obtained from the roots of Valeriana officinalis was investigated on the uptake and release of GABA in synaptosomes. It is concluded that valerian extract releases [3H]GABA by reversal of the GABA carrier, which is Na(+)-dependent and Ca(2+)-independent.”
OTHER NATURAL REMEDIES
by Dr. Mike Dow, The Dr. OZ Show
“You know that feeling you get in the middle of a frantic workday with 3 deadlines approaching while your kids keep texting you about dinner? If we were to take a look inside your brain, the chemicals that act like your car’s accelerator pedal – dopamine, adrenaline, norepinephrine – are surging. And GABA, the chemical that acts like your car’s brakes, is in short supply.
While there are several drugs that help to boost GABA, there are also some natural ways to get the peace and calm your brain needs. Finding natural solutions have a few benefits. First, they’re not addictive like many of the prescription medications. Also, they won’t leave you feeling groggy, so you’ll still be able to be productive at work and at home.
Here are 4 ways to get the GABA your brain is craving:
Swap your afternoon coffee for a cup of oolong tea.
When we feel overworked and worn out, coffee is a natural go-to. But its high levels of caffeine send the activating brain chemical dopamine soaring. The tradeoff for short-term productivity is a jittery feeling and insomnia hours later. Try oolong tea instead. It contains GABA, and sipping it may provide you with the break your brain and body needs. The break you’ll get may provide you with the stamina to get everything done without feeling worn out.
Swap the candy bar for cherry tomatoes and hummus.
The high levels of fat in that candy bar are not only bad for your waistline, it’s bad for your brain! High levels of unhealthy fat also increase dopamine levels. But cherry tomatoes are rich in GABA, and the olive oil in hummus helps to balance your omega-3 versus omega-6 ratio. This ratio can help balance all of your brain chemicals over the long-term which will leave you feeling peaceful and happy.
Swap the soda for a glass of kefir, a probiotic drink.
Soda is not only associated with obesity; a new study showed an association with soda (and diet soda) and depression. Kefir contains GABA, and the carbohydrates boost serotonin – your other main feel-good, peaceful brain chemical. Talk about a double whammy!
Swap orange chicken and fried rice for grilled shrimp and brown rice. The high fat in orange chicken and fried rice flood your brain with dopamine which can even set you up for food addiction. But the shrimp contains a healthy dose of GABA, and the high-fiber brown rice gives you nice, healthy release of serotonin.”
from Science Daily “Yoga May Elevate Brain GABA Levels, Suggesting Possible Treatment For Depression”
“Researchers at Boston University School of Medicine (BUSM) and McLean Hospital have found that practicing yoga may elevate brain gamma-aminobutyric (GABA) levels, the brain’s primary inhibitory neurotransmitter. The findings, which appear in the May issue of the Journal of Alternative and Complementary Medicine, suggest that the practice of yoga be explored as a possible treatment for depression and anxiety, disorders associated with low GABA levels.
Using magnetic resonance spectroscopic imaging, the researchers compared the GABA levels of eight subjects prior to and after one hour of yoga, with 11 subjects who did no yoga but instead read for one hour. The researchers found a twenty-seven percent increase in GABA levels in the yoga practitioner group after their session, but no change in the comparison subject group after their reading session. The acquisition of the GABA levels was done using a magnetic resonance spectroscopy technique developed by J. Eric Jensen, PhD, an assistant professor of psychiatry at Harvard Medical School and an associate physicist at McLean Hospital.
According to the researchers, yoga has shown promise in improving symptoms associated with depression, anxiety and epilepsy. “Our findings clearly demonstrate that in experienced yoga practitioners, brain GABA levels increase after a session of yoga,” said lead author Chris Streeter, MD, an assistant professor of psychiatry and neurology at BUSM and a research associate at McLean Hospital.
“This study contributes to the understanding of how the GABA system is affected by both pharmacologic and behavioral interventions and will help to guide the development of new treatments for low GABA states,” said co-author Domenic Ciraulo, MD, professor and chairman of the department of psychiatry at BUSM.
“The development of an inexpensive, widely available intervention such as yoga that has no side effects but is effective in alleviating the symptoms of disorders associated with low GABA levels has clear public health advantage,” added senior author Perry Renshaw, MD, PhD, director of the Brain Imaging Center at Harvard-affiliated McLean Hospital.”
“Consume 150 to 300 mg of kava kava standardized extract one to three times per day. Make sure the extract contains 30 to 70 percent kavalactones, which are this herb’s primary active compound. It is suggested that this herb increases the number of attachment sites for GABA in the brain. By creating more attachment sites, it is believed the effects of GABA might be more profound, which results in a mild sedated state. Use extreme caution when supplementing with kava kava, as this herb might have detrimental effects on the liver if consumed in excess. Thus, discuss the use of kava kava with your physician to ensure its safety.”
from Paleo for Women
“Foods rich in B-complex vitamins, particularly inositol, prompt GABA production. In fact, B-vitamins are necessary for the functioning of nearly all brain processes and chemicals. Foods containing B-vitamins comprise a rich and varied list. They include: fruits such as bananas, figs, cantaloupe oranges and figs, and vegetables, particularly cruciferous vegetables, such as beets, broccoli, kale, and spinach, and nuts, and seafood, and beef and beef liver, chicken liver, all organ meats, and all game/ruminant meats.”