What does gaba do

What Is GABA?

Some prescription drugs can mimic the effects of GABA, an important neurotransmitter.

Gamma-aminobutyric acid, or GABA, is a neurotransmitter that sends chemical messages through the brain and the nervous system, and is involved in regulating communication between brain cells.

The role of GABA is to inhibit or reduce the activity of the neurons or nerve cells.

GABA plays an important role in behavior, cognition, and the body’s response to stress.

Research suggests that GABA helps to control fear and anxiety when neurons become overexcited.

Lower-than-normal levels of GABA in the brain have been linked to schizophrenia, depression, anxiety, and sleep disorders.

GABA Receptors

GABA receptors on nerve cells receive the chemical messages that help to inhibit or reduce nerve impulses.

Prescription medications called benzodiazepines bind to the same receptors as GABA. They mimic GABA’s natural calming effects.

Diazepam (Valium) and lorazepam (Ativan), are among the most widely prescribed benzodiazepinesfor insomnia and anxiety disorders. They slow down the body’s central nervous system and cause sleepiness.

Benzodiazepines should be used only as prescribed. Taking too much can lead to shallow breathing, clammy skin, dilated pupils, weak pulse, coma, and death.

Medications used to treat insomnia, including zolpidem (Ambien) and eszopiclone (Lunesta), work by improving the ability of GABA to bind to GABA receptors in the brain.

GABA Supplements

GABA supplements, taken alone or in combination with other ingredients, are marketed widely for use in treating depression, anxiety, and insomnia.

While a few small studies have suggested that GABA supplements may help to lower anxiety levels, there is little scientific evidence to support these overall claims.

GABA supplements may increase levels of the chemical circulating in the blood, but there is little evidence to suggest that circulating GABA can pass through the blood-brain barrier and increase GABA levels in the brain.

Talk to your doctor or a qualified healthcare professional before taking GABA supplements (or any other supplements).

What Does Gamma Aminobutyric Acid (GABA) Do?

Not much is known about the effectiveness of GABA supplements. In fact, experts don’t know how much GABA actually reaches the brain when consumed as a supplement or food. But some research suggests that it’s only small amounts.

Here’s a look at some of the research behind GABA’s more popular uses.

Anxiety

According to a 2006 article, two very small studies found that participants who took a GABA supplement had increased feelings of relaxation during a stressful event than those who took a placebo or L-theanine, another popular supplement. The article also notes that the relaxing effects were felt within an hour of taking the supplement.

High blood pressure

Some small, older studies have evaluated the use of GABA-containing products for lowering blood pressure.

In one study from 2003, daily consumption of a fermented milk product that contained GABA reduced blood pressure in people with slighted elevated blood pressure after two to four weeks. This was compared with a placebo.

A 2009 study found that taking a GABA-containing Chlorella supplement twice a day reduced blood pressure in those with borderline hypertension.

Insomnia

In a small 2018 study, participants who took 300 milligrams (mg) of GABA an hour before going to bed feel asleep faster than those taking a placebo. They also reported improved sleep quality four weeks after starting treatment.

Like many other studies looking at the effects of GABA supplements in humans, this study was very small, with only 40 participants.

Stress and fatigue

A 2011 study in Japan examined the effects of a beverage containing either 25 mg or 50 mg of GABA on 30 participants. Both beverages were linked to reduced measures of mental and physical fatigue while doing a problem-solving task. But the beverage containing 50 mg appeared to be slightly more effective.

Another study from 2009 found that eating chocolate containing 28 mg of GABA reduced stress in participants performing a problem-solving task. In another study, taking capsules containing 100 mg of GABA reduced measures of stress in people completing an experimental mental task.

The results of all of these studies sound promising. But most of these studies were very small and many are out of date. Larger, more long-term studies are needed to fully understand the benefits of GABA supplements.

GABA, GABA, GABA, what does it actually do in the brain?

May 16, 2018 by John Hewitt, Medical Xpress GABA molecular structure. Credit: Wikipedia

Gamma-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain. It is the control knob of all control knobs. But why GABA? What, if anything, might be so special about the molecule?

To look at it, there is nothing inherently peculiar about the small four-carbon backbone structure of GABA. Solvation effects in solution allow GABA to take on five different possible conformations, some compact, and others more extended. At the receptor level, this flexibility means that GABA is a highly ‘druggable’ target. In other words, pharmaceutical analogs of GABA are more rigidly pocketable in select receptor subsets, and therefore potentially very specific.

If GABA itself is completely ordinary, does it, perhaps by chance, sit in some prized location within metabolism? Some of the apex positions in metabolic cycles are occupied by molecules like Acetyl-CoA and ATP. Acetyl-CoA sits right at the intersection of glycolysis, the TCA cycle, ketone production, β-oxidation of lipids, and fatty acid elongation. It even plugs directly into synthesis of the neurotransmitter acetylcholine. Curiously, there are no major receptor systems associated with this complex molecule that might otherwise keynote its position inside the cell.

ATP has a more condensed footprint than Acetyl-CoA, but it is certainly no slouch. It directly links oxidative phosphorylation with nucleotide metabolism, and is piloted by its own special set of membrane receptors. Like the GABA ecosystem, ATP comes with the full-service suite containing all the expected ionotropic and metabotropic receptor functions. In the case of GABA, these receptor effects have traditionally been neatly grouped into GABAA receptors, which act as channels for chloride ions, and GABAB receptors, which signal through G-protein bound to their undercarriage.

This tidy picture was recently shaken up with reports of GABA directly gating potassium (K) channels. K channels respond to voltage and normally act to hyperpolarize a neuron, or repolarize a it after a spike. The authors of a paper just published in Nature found that the KCNQ receptor family has an evolutionarily conserved spot set aside just for GABA. When GABA is present there, the voltage set point of these channels is shifted to a more polarized state.

KCNQ channels carry the so-called ‘M’ current, which can be triggered by the agonist muscarine. Because of this receptor-like action, lack of inactivation, and voltage range of operation, these M channels are said to be regulators of neuronal excitability. Often, this just means they convert a neuron from a phasic to a tonic firing pattern. In some cases, neurons with strong M currents might be idealized as voltage controlled oscillators (VCOs). Such a device takes an analog voltage input and generates a variable frequency output. A variation of the VCO, pulse-code modulation, is now the general method of encoding used for uncompressed audio.

While this newfound ability of K ion channel sensitivity is undoubtedly big news in the electrophysiology world, I am going to go out a limb and suggest that the secret of GABA is probably not doing digital audio in your brain. In this void, I think we must dig deeper into what those other kinds of receptors, the slow and roundabout GABAB metabotropic receptors, might be doing. For that matter, we need to break out of the GABA bubble and ask what any G-protein coupled receptor is really doing for the cell.

One clue is that all of these receptors invariably provide for some external control of GTP nucleotide hydrolysis. In that capacity, they are also acting as ‘honest signalers’ of GTP and GDP status. Furthermore, depending on whether the G protein alpha subunit is itself excitatory or inhibitory, the next second messenger down the line (in this case, adenylate or guanylate cyclase), also deals in nucleotides. Namely, they each cleave a double phosphate from their respective namesake trinucleotide, and then lock the remaining molecule up in a knot until phosphodiesterases eventually cleave it.

Who in the cell would be interested in nucleotides? Neurons are generally stuck in the senescence G0 phase of their cell cycle and aren’t worried about having enough nucleotide for the next cell division. There is none coming. Their nuclei only need to maintain a small but steady deoxynucleotide reserve to meet the requirements of DNA repair. In humans, this amount to about 10,000 oxidative lesions per nucleus per day. Therefore, neurons are at liberty to downregulate de-novo nucleotide synthesis enzymes, as well as some of their high-end replication-linked repair pathways.

Mitochondria, on the other hand, are extremely interested in nucleotides. While they have various nucleotide salvage and repair pathways on hand, demand is high—mitochondrial DNA is constantly subjected to mutations and partial deletions, it must be continually refreshed as mitochondria replicate themselves and their nucleoids.

Is there any evidence that GABA signaling and metabolism are directly involved with nucleotide status?

The ‘GABA shunt’ is a detour on the TCA cycle that figures prominently in the nervous system. The cortex in particular is literally one big fat GABA shunt. The detailed molecular structure of the cortex is what you get when you blow up this particular region of metabolism and build an entire higher brain lobe around it. What I mean by this is that our most refined neural wetware runs a relatively simple GABA-glutamate-glutamine metabolic cycle on an elaborate tripartite synaptic hardware; it is a co-op where three different kinds of mitochondria, those optimized by interneuron, pyramidal cell, and astrocyte, exist in mutual communication with each other across a continually fluctuating membranous border.

The take-off point for the GABA shunt lies at alpha-ketoglutarate in the TCA cycle, and the re-entry point connects up at the succinate. A major branch point, succinate is another apex molecule with a hand in everything. Like acetyl-CoA, it links to all major energy pathways, and even contributes to special orders like cholesterol and heme. Similarly, succinate also comes in an acetylated version, and it sits right between succinate and alpha-KG on the TCA cycle.

GABA-glutamate-glutamine cycle at cortical synapses. Credit: studyblue.com

The key observation here is that the enzyme that converts it into succinate, succinyl-CoA ligase (aka. succinyl-CoA synthase), has one very important feature: When it is operating in the forward direction of the cycle, it also generates purine nucleotides as part of the deal. Different tissues in the body build slightly different versions of this enzyme by substituting in alternate secondary subunits. The SUCLG2 version makes GTP in anabolic tissue like the liver and kidneys, while and the SULCA2 version makes ATP for catabolic tissue like brain and muscle. When either of these subunits are mutated, you end with mitochondrial disorder. The exact symptoms depend on which variants you have, and in which tissues.

It is worth mentioning here that some of the most puzzling mental phenomena in all annals of medicine occur when there are genetic defects in the enzymes needed in nucleotide metabolism, particularly in those that localize to mitochondria. Cases in point are the bizarre symptomatology of purine-salvage pathways linked to Lesch-Nyhan syndrome, or to stiff-person syndrome, as well as several unique forms of seizure.

On the far side of succinate on the TCA is fumarate. Fumarate can also enter the cycle by way of a reserve purine cycle that kicks into gear in active tissue when metabolic demand is high. Normal operation of the TCA cycle generates fumarate from succinate via succinate dehydrogenase in the inner mitochondrial membrane. This enzyme simultaneously functions as in respiratory chain electron transport as Complex II.

The GABA shunt. Credit: frontiers.org

We can see from the diagram above that the GABA shunt appears to bypass this critical nucleotide-generating step of succinyl-CoA synthase. However, researchers have previously found that a GABA transaminase (ABAT) shunt enzyme operates in a complex with the SulcA2 subunit and may also act in the final steps of purine salvage. They also believe that a nucleoside diphosphate kinase (NME4) that posses a mitochondrial localization sequence is part of the complex, although there is still some question as to actual levels of this enzyme in the brain.

Some additional insight into what exactly might be going on was recently provided by the discovery of a new mechanism for generating GABA in the brain without the GABA shunt. Normally, only neurons make GABA from glutamate because only they have the GAD enzyme to do it. But glia can also generate GABA by degrading putrescine via monoamine oxidase B (MAOB) in the mitochondrial outer membrane. This is particularly useful in the cerebellum, where glial Bergman cells, which are responsible for generating and maintaining its highly organized architexture, are abundant. Bergmann glia form palisades aligned with the long axis of the cerebellar folium at a ratio of eight glia to one Purkinje cell, and each glia coordinates around 5000 synapses per Purkinje cell.

Cerebellar ataxias and retinal problems are two common issues that regularly arise across the spectrum of mitochondrial disorders. Since MAOB is coded on the X chromosome, males (who get their X from mom) would inherit it as a package deal together with their mtDNA. This is because we all get our mitochondria exclusively from our mothers. Looking at these kinds of co-inherited linkages is an important tool for probing mitochondrial disease. This information is also important to determine what kinds of drugs should be used in treatments.

For example, vigabatrin is a roundly horrific medicine that causes visual field defects in almost half of the kids who are treated with it. Unfortunately, this is often the only drug that works against some kinds of equally horrible seizures. The researchers mentioned above used vigabatrin experimentally to demonstrate the nucleotide synthesis pathways involved with ABAT. While it is a close structural analog of GABA, vigabatrin acts as a potent suicide inhibitor of ABAT, but it won’t bind all to GABA receptors. GABA levels, mitochondrial levels, and mtDNA levels are all been proven to be very sensitive to precise amounts of vigabatrin given. Undesirable effects of vigabatrin might be expected if given to individuals with pre-existing mitochondrial disease.

It was also recently found that a molecule called torin 1 can at least partially correct for some of the primary and incidental effects of vigabatrin. The mechanism involves the ability of GABA to activate mTOR (mechanistic target of rapamycin), which, in turn, blocks elimination of spent or superfluous mitochondria through mitophagy. This also means that more mitochondria with damaged mtDNA will persist. Torin, an inhibitor or mTor (similar to rapamycin), may therefore be a useful tool for dealing with some of the negative effects of vigabatrin in active tissue like the eye and brain.

The authors of the torin study observed some seemingly paradoxical effects in different parts of the brain. For example, they lacked a satisfying explanation for why torin 1 normalized mitochondrial accumulation in the hippocampus, but not in the eye, liver, or parietal cortex, and also why hippocampal mitochondria were increased with vigabatrin, but not in the parietal cortex.

One thing that distinguishes the nervous system from all other non-thinking organs—perhaps its single most defining feature—is its massive, and largely polarized, intracellular conduction of mitochondria. When required, this activity leads to transcellular conduction of mitochondria, often followed by mitophagy, as is well known to be important in the optic nerve.

Such transexudation circuits, perhaps locally between the hippocampus and associated cortical regions, or even more peripherally from the nervous system to other organs, would naturally compensate for metabolic shortfalls that invariably arise in single cells that lack specific enzymes as a result of their genetic differentiation. The GABA shunt is one nice example of this.

Mitochondria are not uniform and faceless like electrons. They age, albeit differentially, sometimes reversibly, and are sorted accordingly in cells and tissues. Spiking in the brain is the direct result of metabolic activity, and seizing the result when things are too far off kilter. We know spikes control mitochondria, their activities, and more visibly, their movements. Now, we also know that one way spikes achieve this control is by manipulating nucleotide metabolism in mitochondria.

More information: Rían W. Manville et al. Direct neurotransmitter activation of voltage-gated potassium channels, Nature Communications (2018). DOI: 10.1038/s41467-018-04266-w

Journal information: Nature , Nature Communications

© 2018 Phys.org

Critical Reviews in Plant Sciences

4-aminobutyrate (GABA) is a non-protein amino acid that is widely distributed throughout the biological world. In animals, GABA functions as the predominant inhibitory neurotransmitter in the central nervous system by acting through the GABA receptors. The neuromuscular system enables animals to escape from environmental stresses. Being nonmotile, plants have evolved chemical responses to mitigate stress. Mechanisms by which GABA may facilitate these responses are discussed in this review. Environmental stresses increase GABA accumulation through two different mechanisms. Stresses causing metabolic and/or mechanical disruptions, resulting in cytosolic acidification, induce an acidic pH-dependent activation of glutamate decarboxylase and GABA synthesis. Extremely marked declines in cytosolic pH occur under oxygen deprivation, which is the primary stress factor in flooded soils, and this stress induces the greatest accumulation of GABA. Other stresses, including cold, heat, salt, and mild or transient environmental factors, such as touch, wind, rain, etc. rapidly increase cellular levels of Ca2+. Increased cytosolic Ca2+ stimulates calmodulin-dependent glutamate decarboxylase activity and GABA synthesis. A review of the kinetics of GABA accumulation in plants reveals a stress-specific pattern of accumulation that is consistent with a physiological role for GABA in stress mitigation. Recent physiological and genetic evidence indicates that plants may possess GAB A-like receptors that have features in common with the animal receptors. The mechanism of action of animal GABA receptors suggests a model for rapid amplification of ion-mediated signals and GABA accumulation in response to stress. Metabolic pathways that link GABA to stress-related metabolism and plant hormones are identified. The survival value of stress-related metabolism is dependent on metabolic changes occurring before stress causes irreversible damage to plant tissue. Rapid accumulation of GABA in stressed tissue may provide a critical link in the chain of events leading from perception of environmental stresses to timely physiological responses.

Understanding GABA

What you need to know about this popular supplement for sleep, stress and anxiety

GABA is one of the supplements I get asked a lot by patients, often with looks of confusion on their faces. I think the confusion comes from the fact that GABA is both a chemical produced within body AND a supplement that’s made for ingestion. Unlike melatonin, which is also produced within the body and as a supplement, GABA isn’t nearly as well known—nor has it received nearly the amount of scientific attention as melatonin supplement. Given the interest and popularity of GABA—and the importance of the body’s own GABA to sleep, mood, and health—it’s definitely worth spending some time talking about.

What is GABA?

GABA (full name, Gamma-Aminobutyric acid) is an amino acid produced naturally in the brain. GABA functions as a neurotransmitter, facilitating communication among brain cells. GABA’s big role in the body is to reduce the activity of neurons in the brain and central nervous system, which in turn has a broad range of effects on the body and mind, including increased relaxation, reduced stress, a more calm, balanced mood, alleviation of pain, and a boost to sleep.

Many medications interact with GABA and GABA receptors in the brain, altering their function to achieve certain effects, often relaxation, pain relief, stress and anxiety reduction, lowering blood pressure, and improving sleep. Barbiturates, anesthetics, benzodiazepines, anti-depressants and anti-seizure medications are some of the medications that target GABA.

In addition, a number of natural supplements affect GABA activity, to help relieve stress and anxiety, promote a balanced mood, and help with sleep. I’ve written about valerian and hops, magnesium, and L-theanine, all of which have an effect on the brain’s GABA activity. Other natural supplements that may affect the brain’s GABA activity include L-arginine, kava, passionflower, American ginseng and others.

GABA is found naturally in varieties of green, black, and oolong tea, as well as in fermented foods including kefir, yogurt and tempeh. Other foods contain GABA or may boost its production in the body, including whole grains, fava, soy, lentils and other beans, nuts including walnuts, almonds and sunflower seeds, fish, including shrimp and halibut, citrus, tomatoes, berries, spinach, broccoli, potatoes, and cocoa.

GABA is also available as a supplement. GABA supplements are often used to treat high blood pressure, stress and anxiety, and sleep, as well as to stimulate the body’s natural growth hormone, often by athletes.

How does GABA work?

I call GABA the brakes of the brain. GABA is the body’s most important inhibitory neurotransmitter, which means it lowers the activity of neural cells in the brain and central nervous system, having the effect of moving the brain and the body into lower gear. By inhibiting neural activity, GABA facilitates sleep, reduces mental and physical stress, lowers anxiety, and creates a calmness of mood. GABA also plays an important role in regulating muscle tone. In combination with glutamate, the body’s most important excitatory neurotransmitter, GABA is an important contributor to the body’s overall mental and physical homeostasis, or balance.

GABA plays a role in the healthy functioning of the body’s immune and endocrine systems, as well as in the regulation of appetite and metabolism. There’s also interesting emerging research about GABA’s role in gut health and gastrointestinal function, where it may work to support motility, control inflammation and support immune system function, and help to regulate hormone activity.

Low GABA activity in the body can result in:

  • Anxiety
  • Chronic stress
  • Depression
  • Difficulty concentrating and memory problems
  • Muscle pain and headaches
  • Insomnia and other sleep problems

Low GABA activity is also associated with substance use disorders.

There is ongoing investigation and debate about how GABA supplements work in the body, and how their mechanisms of action may differ from the body’s own internally-produced GABA. Specifically, scientists have not reached consensus about whether, or how effectively, supplemental GABA crosses what’s known as the blood-brain barrier—meaning, how well it moves from the bloodstream directly into the brain. There remains real need for additional research into the effects of supplemental GABA, including how GABA may affect the nervous system via the gut. Below, I’ll talk about what science tells us today about the potential effectiveness of GABA supplements for sleep and other conditions.

Benefits of GABA

For sleep: The body’s own GABA activity is important for sleep. GABA enables the body and mind to relax and fall asleep, and sleep soundly throughout the night. Low GABA activity is linked to insomnia and disrupted sleep. In one study, GABA levels in people with insomnia were almost 30 percent lower than in people without the sleep disorder. And these low GABA levels also corresponded to more restless, wakeful sleep. Big-pharma sleep medications including those with zolpidem (Ambien and others) and eszopiclone (Lunesta and others) target the body’s GABA system to increase sedation and sleep. Research indicates that one negative side effect of these sleep medications—hallucinations—may result from their alterations to GABA activity.)

There’s relatively limited research that investigates the direct benefits of supplemental GABA for sleep. Some recent research suggests that GABA produced in fermented food may increase sleep time and decrease the time it takes to fall asleep. Another recent study showed a combination of GABA and 5-HTP may together improve sleep quality and increase sleep time. (I’ve written before about the sleep and relaxation benefits of 5-HTP, here.) Given the importance of GABA to the body’s sleep patterns, more research into the effects of GABA supplements on sleep is sorely needed!

For stress and anxiety: As a natural chemical the body produces, GABA’s primary role is to diminish the activity of neurons in the brain and central nervous system, which puts the body in a greater state of relaxation, and alleviates stress and anxiety. Supplemental GABA may benefit sleep by aiding relaxation and providing relief from anxiety and stress. There remains debate among scientists about supplemental GABA’s effectiveness in reducing anxiety and stress, because of longstanding questions over supplemental GABA’s ability to enter the brain from the bloodstream. (It’s important to note that GABA, in supplement form, may have other ways of relaxing the body and relieving, including possibly through GABA’s activity in the gut microbiome.)

While that scientific debate goes on, some studies have shown GABA to be effective in lowering anxiety and boosting relaxation. One small study of a group of 13 adults showed GABA effective as a relaxant and anxiety reliever, with slowed brain waves seen within an hour of taking the supplement. This study also found a boost to immune system also occurred with GABA, suggesting supplemental GABA may enhance immunity in people who are undergoing mental stress.

Another larger study investigated the effects of 100 milligrams of GABA among a group of people who’d recently undertaken a stressful mental task. Scientists measured a slowing down of brain waves in the people who’d taken GABA, pointing to an alleviation of mental stress. Another study tested the effects of GABA in people who were about to take a stressful math test. People who ate chocolate infused with GABA rebounded more quickly from the test-related stress, including stress-lowering changes to heart-rate variability.

For high blood pressure: GABA supplements are sometimes used by people as a natural way to lower blood pressure. There is scientific evidence indicating that GABA may work to reduce high blood pressure. In one study of people with borderline high blood pressure, 12 weeks of use of the supplement chlorella, a type of algae that is rich in GABA, significantly lowered blood pressure. In addition to being important on its own, maintaining a healthy blood pressure can also help protect your sleep. A natural drop in blood pressure at night is one part of the body’s progression into sleep. High blood pressure can be a sign of hyper-arousal, a state of physical alertness and vigilance that can make it difficult to fall asleep and stay asleep. Poor sleep and sleep disorders, particularly sleep apnea, contribute to high blood pressure, and can lead to the kind of hypertension that is difficult to treat.

GABA: what to know

Always consult your doctor before you begin taking a supplement or make any changes to your existing medication and supplement routine. This is not medical advice, but it is information you can use as a conversation-starter with your physician at your next appointment.

GABA dosing

The following doses are based on amounts that have been investigated in scientific studies. In general, it is recommended that users begin with the lowest suggested dose, and gradually increase as needed.

For sleep, stress and anxiety: 100-200 mg and higher doses, in scientific studies. Individual dosing and length of use will vary.

For high blood pressure: 10-20 mg, in scientific studies.

Possible side effects of GABA

GABA oral supplements are generally well tolerated by healthy adults. Some people may experience negative side effects, including:

  • Gastric distress
  • Nausea
  • Diminished appetite
  • Constipation
  • Burning throat
  • Drowsiness and fatigue
  • Muscle weakness
  • Shortness of breath, at very high doses

GABA interactions

These are commonly used medications and supplements that have scientifically-identified interactions with GABA. People who take these or any other medications and supplements should consult with a physician before beginning to use GABA as a supplement.

Interactions with medications

High blood pressure medications. GABA can lower blood pressure. If you take GABA in addition to taking blood pressure medication, your blood pressure may drop too low.

Anti-depressant medications. People taking anti-depressant medications should consult with their physicians before taking GABA.

Neurally-active medications. People taking medications that affect brain activity should consult their physicians before taking GABA.

Interactions with other supplements

Herbs and supplements that may lower blood pressure. Because GABA may lower your blood pressure, if you take GABA along with other herbs or supplements that also may lower blood pressure, the combination may lead to your blood pressure dropping too low.

Herbs and supplements that lower blood pressure include, but are not limited to:

  • Cocoa
  • Alpha-linolenic acid
  • Blond psyllium, and other fiber supplements
  • Cod liver oil
  • Magnesium
  • Calcium
  • Potassium
  • Folic acid
  • Coenzyme Q10
  • L-arginine
  • Garlic
  • Omega-3 fatty acids

I’ve seen patients experience relief from anxiety, reduced stress, and improved sleep via the relaxing impact of supplemental GABA. I don’t think we’ve seen nearly enough research to have a sufficient understanding of how GABA supplements might affect stress, mood, and sleep, or other ways GABA as a supplement may benefit emotional, cognitive, and physical health. As we learn more—which I hope we do, soon—I’ll be sure to update you.

Sweet Dreams,

Michael J. Breus, PhD, DABSM

The Sleep Doctor™

GABA (gamma-aminobutyric acid)

What Is It?

Popularly referred to as the body’s natural tranquilizer, GABA (gamma-aminobutyric acid) is an amino acid produced in the brain. It acts as a Neurotransmitter–a chemical that fosters communication between nerve cells–and helps to keep stress-related nerve impulses at bay.

Normally, the brain pumps out all the GABA we need. Unfortunately, due to a poor diet, exposure to environmental toxins, or other factors, levels of GABA may become depleted. Too little of this important compound may result in anxiety, irritability, and insomnia. A deficiency of GABA has also been linked to depression.

Because various safety issues have recently surfaced concerning the use of the popular tranquilizing Herb kava, nutritionally oriented physicians have begun recommending GABA more frequently. Basically, the clinical effect of both GABA and kava appears to be the same, namely they’re both gentle and nonsedating tranquilizers. GABA is now available as a supplement in pill and powder form.

Health Benefits

GABA supplements appear to promote relaxation and sleep. They may also have a role to play in preventing seizures and allaying chronic pain.

While GABA has been tested for improving exercise tolerance, decreasing body Fat, and stabilizing blood pressure, research on the supplement’s effectiveness and safety for these purposes has been mixed at best. GABA supplements have also been proposed for improving concentration in attention deficit hyperactivity disorder (ADHD) and promoting prostate health, although it remains untested for these purposes.

Specifically, GABA supplements may help to:

  • Promote sound sleep. GABA participates in promoting relaxation, which explains why many well-known anxiety medications–Valium among them–target GABA receptors in the brain. But unlike many prescription tranquilizers, GABA is not habit-forming.

GABA itself does not cause drowsiness. Instead, by easing anxiety, it simply makes it easier to fall asleep. Some research indicates that the popular insomnia-fighting herb, valerian, boosts GABA levels too. When specifically treating sleep disorders, some people like to rotate GABA with valerian or melatonin, the popular Hormone-based sleep supplement.

  • Allay stress. GABA may be taken to calm the mind and body. In this respect, it is much like better-known prescription tranquilizers, such as Xanax and Valium, but doesn’t carry the fear of addiction. Persistent stress may also contribute to depression, and some evidence suggests that GABA may have mood-elevating properties.
  • Combat chronic pain. Stress can aggravate pain, making you feel worse. As a natural stress-reducer, GABA supplements can help to relieve the intensity of pain. They may also lessen pain-related nerve impulses.
  • Treat epilepsy. While the specific cause of epilepsy often remains a mystery from individual to individual, a link has been made to naturally low GABA levels and seizures in some cases. Like a pistol lock, GABA appears to inhibit nerve cells in the brain from firing and setting off seizures. Interestingly, many standard epilepsy drugs, such as benzodiazepines and phenobarbital, serve to enhance GABA levels in the brain.

Clinical study findings have been mixed, however. In a 1994 pilot study, for example, GABA supplementation had no benefit in people with epilepsy whose seizures were set off by exposure to flashes of light. Still, in that study, only a single oral dose of GABA was used. The researchers speculate that GABA may have cumulative benefits when taken over the long term. Earlier studies had reported that GABA helped people with various types of epilepsy who did not respond to conventional medicines. Clearly, more research is needed.

So while GABA should never be used as a substitute for conventional epilepsy drugs, it could possibly compensate for nutritional deficiencies that are contributing to seizures and be a useful adjunct to standard treatments. It may also allow you to take lower doses of conventional medicines. Always check with your doctor before taking GABA, however, and never change your dose on your own.

Forms

  • tablet
  • powder
  • capsule

Dosage Information

Special tips:

–GABA is usually found in the amino acid section of the supplement aisle.

–For those who don’t like swallowing tablets, capsules can be opened and added to juice or water, as can powders. A Sublingual tablet, which is placed under the tongue until it slowly dissolves, is also available.

For insomnia: Take 500 to 1,000 mg an hour or so before bedtime. It will have a calming effect that can help you fall asleep. If anxiety is contributing to your sleep problems, combine GABA with other natural tranquilizers, such as the herb valerian.

For stress: Take 250 mg three times a day.

For chronic pain: Take 250 to 500 mg three times a day.

For epilepsy: Take 250 to 500 mg three times a day.

Guidelines for Use

  • If the mood swings of PMS are causing you to lose sleep, try taking GABA for a week to 10 days before and during your period.
  • Like other Amino acids, GABA may best be taken between meals for best absorption (one hour before or two hours after eating).
  • Store in a cool, dry place, away from light, heat, and moisture.

General Interaction

* Many well-known prescription anxiety medications, including alprazolam (Xanax) and diazepam (Valium), target GABA receptors in the brain. Using GABA with prescription anti-anxiety agents may produce a dangerous additive effect. Always let your doctor know if you are taking GABA or other supplements.

* GABA may produce excessive drowsiness when taken with other medications that have a tranquilizing effect, including codeine and other narcotic pain relievers, antidepressants, sedatives, and muscle relaxants. Combine with extreme caution.

Possible Side Effects

* GABA appears to be safe at recommended doses. In research studies, some mild gastric upset and nausea were reported, and some participants reported drowsiness.

* At high doses, GABA can actually increase anxiety and insomnia. It may also cause numbness around the mouth and tingling in the extremities.

Cautions

* There is limited information on the safety of GABA supplements.

* Don’t drive or operative heavy machinery until you know how GABA affects you.

* When treating a serious condition such as epilepsy, never alter a prescription medication dosage or add GABA to your regimen without consulting your doctor first.

  • Like many supplements, GABA has not been tested in pregnant or breast-feeding women, children, or people with liver or kidney disease. The proper dose in these groups is unknown.

Ailments

Epilepsy – 250-500 mg 3 times a day

Fibromyalgia – 250-500 mg 3 times a day, as needed

Insomnia – 500-1,000 mg at bedtime

Stress – 250 mg 3 times a day or 750 mg once a day

Tobacco dependence – 250 mg 3 times a day, or 750 mg at bedtime

For product recommendations and orders click here for the Natural Apothecary or call 773-296-6700, ext. 2001.

GABA (Gamma-Aminobutyric Acid)

GABA—gamma-aminobutyric acid—is an inhibitory neurotransmitter that also plays a role in muscle tone.

What Does GABA Do?
GABA, like all neurotransmitters, helps to carry nerve signals across a synapse. GABA is an inhibitory neurotransmitter, which means that it weakens or slows down signals. Because of its inhibitory function, GABA plays an important role in anxiety. When nerve signals fire too quickly and carry anxiety-inducing signals, GABA acts to slow the signals down, reducing overwhelming feelings of anxiety. However, in people with anxiety disorders–including posttraumatic stress, generalized anxiety, and panic disorder–GABA may not work as it should, thus increasing anxiety.

GABA’s Role in Psychology
Different people produce GABA in different quantities, and there is no test that can reliably determine the amount of GABA a person is producing. However, when a person has an anxiety disorder, GABA deficiency is a common factor.

Benzodiazepines are anti-anxiety medications such as Ativan, Xanax,and Valium. These medications work on GABA receptors, and can help GABA to slow down anxiety-producing nerve signals.

GABA can also play a role in substance abuse, particularly during the detox process. Dehydration and malnutrition can decrease a person’s GABA production. People with substance abuse often suffer from nutritional deficiencies, and the detox process itself can reduce available GABA. The result can be extreme anxiety. Many doctors prescribe patients anti-anxiety medications during detox. However, substance abuse patients must be carefully monitored when using these drugs, as benzodiazepines can quickly become addictive.

Last Updated: 08-7-2015

GABA occurs in 30-40% of all synapses-only glutamate is more widely distributed. Neurons in every region of the brain use GABA to fine-tune neurotransmission. Increasing GABA at the neuronal synapse inhibits the generation of the action potential of the neuron, thereby making it less likely to excite nearby neurons. A single neuron may have thousands of other neurons synapsing onto it. Some of these release activating (or depolarizing) neurotransmitters; others release inhibitory (or hyperpolarizing) neurotransmitters. GABA is the primary inhibitory neurotransmitter, which means it decreases the neuron’s action potential. When the action potential drops below a certain level, known as the threshold potential, the neuron will not generate action potentials and thus not excite nearby neurons. The nucleus of a neuron is located in the cell body. Extending out from the cell body are dendrites and axons. Dendrites conduct impulses toward the cell body, Axons conducting impulses away from the cell body. A recording electrode has been attached to a voltmeter to record the charge across the cell membrane, the thin layer that controls movement in and out of the neuron. The resting potential in excitable neurons is usually around -65 to -70 millivolts (mV), which can be seen on the voltmeter. Excitatory synapses reduce the membrane potential: The synapses labeled A, B, and C are excitatory (e.g. glutamate ACH). These synapses release activating neurotransmitters, which reduce the resting potential of the neuron. If the voltage reaches the threshold potential, typically around -50 mv, an action potential is generated, which will travel down the axon, where it will communicate with a nearby cell. The strength of the stimuli that produce an action potential is important only insomuch as it reaches threshold potential. The resultant action potential is always the same, whether it was created by relatively strong or relatively weak stimuli. action potential is a constant. Decreasing the action potential: GABA is the primary inhibitory neurotransmitter, which means it decreases the neuron�€™s action potential. When the action potential drops below the threshold potential, the neuron will not excite nearby neurons. Exitatory PostSynaptic Potential (EPSP): The Exitatory PostSynaptic Potential (EPSP) of a single excitatory synapse is not sufficient to reach the threshold of the neuron. Rather, when a number of EPSPs are created in quick succession, their charges sum together. It is the combined sum of these EPSPs that creates an action potential Activation of inhibitory synapses such as GABA, on the other hand, makes resting potential more negative. This hyperpolarization is called an inhibitory postsynaptic potential (IPSP). Activation of inhibitory synapses (D and E) makes the resting potential of the neuron more negative. The resulting IPSP may also prevent what would otherwise have been effective EPSPs from triggering an action potential. It is the total summation of the EPSPs and IPSPs that determines whether a neuron�€™s charge is sufficient to cross the potential threshold.

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