Glutamate and GABA Balance

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.

It was initially thought that autistic children had fewer glutamate receptors, but subsequent studies, including one from the prestigious journal Neurology published in 2001, showed that autistic children, in fact, have more glutamate receptors than normal controls. Furthermore, they are genetically predisposed to have more. So autism is another hyper-glutamate condition.

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.

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.

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. See Figure 1.

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.

One of the things that interferes with the activity of the GAD enzyme is the rubella virus. This is the same virus as is in the MMR vaccination. It has been shown in the type 1 diabetes that the rubella virus can cause the GAD enzyme to stop functioning. The body makes antibodies against it. In some studies, enzyme activity was decreased by 50%.

This connects back to methylation. If you are making too few methyl groups and you cannot methylate virus to silence or kill it, and you can’t make T-cells to deal with the infection because you have too few methyl groups, then you are more likely to wind up with chronic infection when you do something like inject live virus into an immune compromised body.

When someone speaks to you and you are not quite attending, you may turn to them and say, “What did you say?” but before they can answer you, your mind replays it, and you can recover what they said.

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.

Evaluate glutamate and GABA levels first by noting if you have the symptoms I mentioned and doing a urine amino acids test (UAA). The UAA has both of these neurotransmitters on it. You can supplement GABA directly and it is in Dr. Amy’s supplement for glutamate GABA balancing called Be Calm. Dr. Amy also has a workbook that lists supplements you can use to balance these neurotransmitters.

Still feel like you need help? The areas of optimizing glutamate and GABA balance and enhancing methylation function, are not kitchen medicine. You may need help. It’s not always easy to know when you are going forward or backwards.

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. Keep your eye on this blog for more tips on how to get through the supplementation and healing process.

Glutamate_diagram

For more information: www.nancymullanmd.com

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About Nancy Mullan, MD

Some people call Dr. Nancy Mullan the MTHFR genetic medicine expert. Dr. Mullan works with people who are struggling with chronic disease or other significant illness, who are willing to use diet and genetics-based nutritional supplementation, and who want to increase wellbeing and energy, enhance immunity, lift mood, fine-tune genetic function, and get their lives back. Dr. Mullan has studied at a number of exceptional institutions: the University of Pennsylvania, Tufts University School of Medicine, and the University of Chicago Hospitals and Clinics. She excels at integrating the results of biochemical and genetic testing into sustained clinical improvement for you. She has succeeded with patients who confounded the specialists at Massachusetts General Hospital, the Mayo Clinic, the Cleveland Clinic, Stanford, and many well-known integrative medical doctors. When recommending her, her patients say, “This is the woman you need to talk to. She really knows how to handle tough clinical problems.” Dr. Mullan's specialty areas are MTHFR+, methylation genetics, and genetics-based nutritional supplementation. Within this context, she most often works with Chronic Fatigue Syndrome, Lyme Disease, Psychiatric Disorders, Autism Spectrum Disorders, Women’s Health Issues, Thyroid Disorder, Gastrointestinal Disorder, and Heavy Metal Toxicity.
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