GABA Supplement information, benefit, side effects, review by Ray Sahelian, M.D. Does it work for anxiety or stress reduction?

GABA or gamma-aminobutyric acid, discovered in 1950, is the most important and widespread inhibitory neurotransmitter in the brain. Excitation in the brain must be balanced with inhibition. Too much excitation can lead to restlessness, irritability, insomnia, and even seizures. GABA is able to induce relaxation, analgesia, and sleep. Barbiturates and benzodiazepines are known to stimulate GABA receptors, and hence induce relaxation. Several neurological disorders, such as epilepsy, sleep disorders, and Parkinson’s disease are affected by this neurotransmitter. This neurotransmitter is made in the brain from the amino acid glutamate with the aid of vitamin B6. Do GABA supplements help induce relaxation?

GABA supplement, 250 mg - Enzymatic Therapy
GABA is an important amino acid neurotransmitter in the brain.
Recommendations: One to four GABA capsules once or twice daily.

Supplement Facts:
Amount per Capsule
GABA (Gamma-aminobutyric acid) -  250 mg *

* GABA daily value not established

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GABA for anxiety
I have come across very little human research regarding the use of GABA supplements for anxiety in humans.

Relaxation and immunity enhancement effects of gamma-aminobutyric acid administration in humans.
Biofactors. 2006;26(3):201-8. Department of Research and Development, Pharma Foods International Co. Ltd., Kyoto, Japan.
The effect of orally administrated gamma-aminobutyric acid on relaxation and immunity during stress has been investigated in humans. Two studies were conducted. The first evaluated the effect of GABA intake by 13 subjects on their brain waves. Electroencephalograms (EEG) were obtained after 3 tests on each volunteer as follows: intake only water, GABA, or L-theanine. After 60 minutes of administration, GABA significantly increases alpha waves and decreases beta waves compared to water or L-theanine. These findings denote that GABA not only induces relaxation but also reduces anxiety. The second study was conducted to see the role of relaxant and anxiolytic effects of GABA intake on immunity in stressed volunteers. Eight acrophobic subjects were divided into 2 groups (placebo and GABA). All subjects were crossing a suspended bridge as a stressful stimulus. Immunoglobulin A (IgA) levels in their saliva were monitored during bridge crossing. Placebo group showed marked decrease of their IgA levels, while GABA group showed significantly higher levels. In conclusion, GABA could work effectively as a natural relaxant and its effects could be seen within 1 hour of its administration to induce relaxation and diminish anxiety. Moreover, GABA administration could enhance immunity under stress conditions.

Do GABA supplements work for anxiety?
GABA is available as a supplement in vitamin stores, but taking it in pill form is not always an effective way to raise brain levels of this neurotransmitter because GABA cannot easily cross the blood-brain barrier. Companies are searching for ways to place GABA in an oil base in order to ease its entry across this barrier. However, some people have noticed better relaxation and sleep from GABA supplements when taking more than one or two grams. One gram equals 1,000 milligrams. However, at these dosages, one wonders whether other herbs and nutrients that have relaxation potential may be more cost effective. Good Night Rx is a much more effective herbal product for sleep.

GABA review summary
As of January 2008, I don't have a strong opinion regarding the effectiveness of GABA supplements. I think GABA may reduce anxiety when used in high doses, or work better when combined with other anti-stress supplements. Other options for anxiety and tension that, in my opinion, are more effective include 5-HTP, valerian herb, kava herb,  and passion flower herb. For tension relief and better sleep at night, Good Night Rx, a product that has a combination of several nutrients and herbs, works very well for sleep problems.

Mind Power Rx - Formulated by Ray Sahelian, M.D.

Research studies
Alcohol effects on gamma-aminobutyric acid type A receptors: are extrasynaptic receptors the answer?
Life Sci. 2004 Nov 19;76(1):1-8.
GABA (A) receptors have long been implicated in mediating at least part of the actions of ethanol in mammalian brain. However, until very recently, reports of the actions of ethanol on recombinant receptors have required very high doses of ethanol and animals lacking receptor subunits shown to be important for ethanol actions in vitro did not support the view that these subunits are crucial in ethanol actions. Recombinant GABA (A) receptors are uniquely sensitive to ethanol, with a dose-response relationship mirroring the well known effects of alcohol consumption on the human brain. Receptors containing the delta subunit are thought to be located extrasynaptically and it will be important to determine if these extrasynaptic GABA (A) receptor subunit combinations mediate low dose alcohol effects in vivo.

GABA inhibits T cell autoimmunity and the development of inflammatory responses in a mouse type 1 diabetes model.
J Immunol. 2004 Oct 15;173(8):5298-304.
Gamma-aminobutyric acid is both a major inhibitory neurotransmitter in the CNS and a product of beta cells of the peripheral islets. Our previous studies, and those of others, have shown that T cells express functional GABA A receptors. However, their subunit composition and physiological relevance are unknown. In this study, we show that a subset of GABA A receptor subunits are expressed by CD4+ T cells, including the delta subunit that confers high affinity for GABA and sensitivity to alcohol. GABA at relatively low concentrations down-regulated effector T cell responses to beta cell Ags ex vivo, and administration of GABA retarded the adoptive transfer of type 1 diabetes in mice. Furthermore, treatment with low dose of GABA dramatically inhibited the development of proinflammatory T cell responses and disease progression in diabetes-prone mice that already had established autoimmunity. Finally, GABA inhibited TCR-mediated T cell cycle progression in vitro, which may underlie GABA's therapeutic effects. The immunoinhibitory effects of GABA on T cells may contribute to the long prodomal period preceding the development of T1D, the immunological privilege of the CNS, and the regulatory effects of alcohol on immune responses. Potentially, pharmacological modulation of GABA A receptors on T cells may provide a new class of therapies for human diabetes as well as other inflammatory diseases.

Effect of a gamma-aminobutyric acid-enriched dairy product on the blood pressure of spontaneously hypertensive and normotensive Wistar-Kyoto rats.
Br J Nutr. 2004 Sep;92(3):411-7.
We investigated the blood-pressure-lowering effects of gamma-aminobutyric acid and a GABA-enriched fermented milk product (FMG) by low-dose oral administration to spontaneously hypertensive (SHR/Izm) and normotensive Wistar-Kyoto (WKY/Izm) rats. FMG was a non-fat fermented milk product produced by lactic acid bacteria, and the GABA contained in FMG was made from the protein of the milk during fermentation. A single oral dose of GABA or FMG (5 ml/kg; 0.5 mg GABA/kg) significantly decreased the blood pressure of SHR/Izm from 4 to 8 h after administration, but did not increase that of WKY/Izm rats. The hypotensive activity of GABA was dose-dependent from 0.05 to 5.00 mg/kg in SHR/Izm. During the chronic administration of experimental diets to SHR/Izm, a significantly slower increase in blood pressure with respect to the control group was observed at 1 or 2 weeks after the start of feeding with the GABA or FMG diet respectively and this difference was maintained throughout the period of feeding. The time profile of blood-pressure change due to administration of FMG was similar to that of GABA. FMG did not inhibit angiotensin 1-converting enzyme. Furthermore, an FMG peptide-containing fraction from reverse-phase chromatography lacked a hypotensive effect in SHR/Izm rats. The present results suggest that low-dose oral GABA has a hypotensive effect in SHR/Izm and that the hypotensive effect of FMG is due to GABA.

Molecular structure and physiological functions of GABA (B) receptors.
Physiol Rev. 2004 Jul;84(3):835-67.
GABA (B) receptors are broadly expressed in the nervous system and have been implicated in a wide variety of neurological and psychiatric disorders. The cloning of the first GABA (B) receptor cDNAs in 1997 revived interest in these receptors and their potential as therapeutic targets. With the availability of molecular tools, rapid progress was made in our understanding of the GABA(B) system. This led to the surprising discovery that GABA (B) receptors need to assemble from distinct subunits to function and provided exciting new insights into the structure of G protein-coupled receptors (GPCRs) in general. As a consequence of this discovery, it is now widely accepted that GPCRs can exist as heterodimers. The cloning of GABA (B) receptors allowed some important questions in the field to be answered. It is now clear that molecular studies do not support the existence of pharmacologically distinct GABA (B) receptors, as predicted by work on native receptors. Advances were also made in clarifying the relationship between GABA (B) receptors and the receptors for gamma-hydroxybutyrate, an emerging drug of abuse. There are now the first indications linking GABA (B) receptor polymorphisms to epilepsy. Significantly, the cloning of GABA (B) receptors enabled identification of the first allosteric GABA (B) receptor compounds, which is expected to broaden the spectrum of therapeutic applications. Here we review current concepts on the molecular composition and function of GABA (B) receptors and discuss ongoing drug-discovery efforts.

Acupuncture-mediated inhibition of ethanol-induced dopamine release in the rat nucleus accumbens through the GABA B receptor.
Neurosci Lett. 2004 Oct 21;369(3):234-8.
Clinical trials are currently underway to determine the effectiveness of acupuncture in the treatment of drug abuse. However, there are still many unanswered questions about the basic mechanisms of acupuncture. Studies have shown that the GABA (B) receptor system may play a significant modulatory role in the mesolimbic system in drug abuse, including ethanol. The in vivo microdialysis study was designed to investigate the effect of acupuncture on acute ethanol-induced dopamine release in the nucleus accumbens and the potential role of the GABA (B) receptor system in acupuncture. Male Sprague-Dawley rats were administered with the highly selective GABA (B) antagonist SCH 50911 one hour prior to an intraperitoneal injection of ethanol. Immediately after ethanol treatment, acupuncture was given at bilateral Shenmen (HT7) points for 1min. Acupuncture at the specific acupoint HT7, but not at control points (PC6 or tail) significantly decreased dopamine release in the nucleus accumbens. Inhibition of dopamine release by acupuncture was completely prevented by SCH 50911. These results suggest that stimulation of specific acupoints inhibits ethanol-induced dopamine release by modulating GABA (B) activity and imply that acupuncture may be effective in blocking the reinforcing effects of ethanol.

GABA pharmacology-what prospects for the future?
Biochem Pharmacol. 2004 Oct 15;68(8):1537-40.
Following the recognition of GABA as an inhibitory neurotransmitter, the discovery of high affinity GABA uptake, and the characterisation of GABA receptors great progress has been made in developing GABA pharmacology. Tiagabide, the first marketed GABA uptake inhibitor may be followed by new and more selective uptake inhibitors. Knowledge of the molecular pharmacology of GABA-A receptors, both synaptic and non-synaptic, may lead to improved anti-anxiety / anticonvulsant agents devoid of the sedative and dependence liabilities of earlier compounds and new hypnotics. Gaboxadol (THIP) is an example of a novel hypnotic that acts on GABA-A receptors by a non-benzodiazepine mechanism. Exploiting neurosteroid interactions with GABAergic mechanisms also holds much future promise.

A role for GABA mechanisms in the motivational effects of alcohol.
Biochem Pharmacol. 2004 Oct 15;68(8):1515-25.
Low doses of ethanol have been hypothesized to act directly via proteins that form ligand-gated receptor channels, such as the gamma-aminobutyric acid (GABA) receptor complex, to allosterically alter function, particularly in specific brain areas such as those hypothesized to be involved in ethanol reinforcement. At the pharmacological level, one can antagonize the effects of ethanol with GABA antagonists, particularly its sedative, anxiolytic-like and acute reinforcing actions. Brain sites involved in the GABA ergic component of ethanol reinforcement include the ventral tegmental area, elements of the extended amygdala (including the central nucleus of the amygdala), and the globus pallidus. Chronic administration of ethanol sufficient to produce dependence and increased ethanol intake are associated with increased GABA release in the amygdala and increased sensitivity to GABA agonists. A hypothesis is proposed that GABA ergic interactions with the brain stress neurotransmitter corticotropin-releasing factor in specific elements of the extended amygdala may be an important component for the motivation for excessive drinking associated with the transition from social drinking to addiction.

Comparative study of the effect of picamilone and piracetam on learning in rats in a radial maze
Farmakol Toksikol. 1989 Jul-Aug;52(4):14-7.
During four weeks rats were learned to visit consequently 4 baited arms in the 8-armed radial maze. Picamilone ( nicotinoyl- GABA ) in a dose of 10 mg/kg daily accelerated rats to reach 80% level of learning (to 20-28 trials). After picamilone injections rats obtained the maximal level of short-term memory as just 3-5 trials. Piracetam in a dose of 200 mg/kg daily exerted no effects on long-term and short-term memory of rats in the radial maze.

GABA emails, questions and answers
Q. I bought some GABA earlier this year based on reading about burning fat.  I'm not sure that I've seen any results in that area.  I work our at Curves so I have been losing weight and toning.  The one thing I did notice is the relaxation that soothes me to sleep and stay asleep.  I had no idea that this was to be a benefit.  I struggle with sleeping all night.  I take 3 - 750mg capsules each night before bed.  When I am taking it and for several days after I sleep all night.  If I waken I am so relaxed I go right back to sleep. I just wanted to pass this to you.  After I noticed this benefit I searched the net for info and found some claims of this effect.  GABA has certainly been a blessing to me!

Q. I am a little concerned with some conflicting reports I have seen on GABA since I have started taking it. On the one hand a at first glance it sounded like a miracle supplement but the claims of increases in growth hormone I was slightly suspicious off, most adverts steal results and quotes from clinical drugs trials report "Increase HGH levels by 550%" etc When I read the more independent research on it, the doctors say, Yourself included (funnily enough this is not found in the commercial adverts) that GABA as a sport supplement, in powder form cannot transgress easily the brain/blood barrier so in reality, the GABA in your head, is the stuff your body produces naturally and nothing else. - Certainly amongst the guys I know taking it nobody taking it seemed to be turning into the hulk over night.

Q. I recently read an article on body building that claimed using Gaba in the amount of 5 grams daily will act to reduce body fat. This supplements was praised as the ultimate fat burner. During your research have you discovered it to have any body fat reducing capabilities?
   A. I have not come across this research with GABA and weight loss.

Q. I have found a significant amount of literature on the net saying that taking GABA between 2-5 grams per day leads to significant increases in HGH in the blood stream. I was wondering if this is true, and if so what the risks would be in taking it at such high levels.
   A. Long term risks of high dose gaba intake are unknown, and even if supplements of gaba raise hgh levels, we don't know for certain that raising hgh levels is beneficial or harmful in the long run.

Q. In one of the your books that I read I remember you writing that you didnt find the supplement gamma-aminobutyric acid (GABA) to be very effective for relieving anxiety by itself and that this was most likely because GABA does not cross the blood-brain barrier easily.  I agree that Kava Kava or 5-HTP are probably better for anxiety for most people but can you tell me whether at higher doses and/or more frequent dosing GABA could penetrate the blood-brain barrier and increase intracellular GABA levels significantly?
   A. Higher doses may lead to GABA crossing the blood brain barrier, but I have not personally tested this on myself or with patients.

Q. How long does it take for gaba to start working in you blood stream?
   A. GABA is readily and quickly absorbed into the bloodstream, but it has difficulty in crossing the blood-brain barrier and hence, at its present form sold over the counter, is not a reliable way to relieve anxiety.

Q. Are there any reasons to be cautious about using GABA as a sleep aid? Because it is an essential amino acid, I wonder if there are any potential negative effects of taking these supplements (I've seen them from 100-750mg).
   A. My clinical experience with GABA does not indicate this nutrient to have much of an effect on sleep since it doesn't seem that it crosses the blood brain barrier that well.

Q. I have read what you have to say about the supplement GABA and am wondering why you don't speak of Picamilone (I believe this is GABA bonded together with Niacin, in order to cross the blood-brain barrier). Is this not a natural supplement? I know very little about it except that it is said to be wonderful for reducing anxiety. I have tried all kinds of herbs and also GABA powder for my anxiety, but nothing has been too noticeable. Any comments on Picamilone?
   A. I found one study on GABA and picamilone as listed a few paragraphs above, besides this I know very little about it and have not had a chance to try it myself to see if it works.

Q. Can one use GABA for anxiety?
   A. I am not impressed with GABA for anxiety. Having said this, I have spoken to a few people who feel that GABA reduces anxiety. One user takes GABA in the morning and says it takes the edge off his anxiety, and the effects are noticed a few hours later. I have not personally noticed much of an effect from a GABA supplement, but I have not experimented with a GABA supplement for an extended time.

Q. Do you know of GABA side effects?
   A. I have not come across any noteworthy GABA side effects from a supplement.

Q. What is the right dosage?
   A. GABA dosage could vary between one to three pills of 250 mg each.

Q. I'm doing a paper in my psychology class in college and its on the effects of GABA and how it improves you focus and other thing s do you have anything manily about the focus effects of GABA.
   A. All the info we have about GABA is on our web page. Many other nutrients help focus much more than GABA, such as DMAE, acetylcarnitine, SAM-e, Mind Power Rx, etc.

Q. Is GABA helpful for weight loss?
   A. I seriously doubt if GABA helps weight loss.

Q. Please advice regarding increasing GABA binding. Is there is any good approach to increase GABA binding with out using benzodiazepines. I have
leaned that KAVA has some effect to increase GABA binding but in same time there is possible problem with liver. What about diet is there any diet approach to increase GABA binding.
   A. I am not aware of research with diet and the role of diet in influencing GABA receptors although I am certain that different foods will influence the binding or activity of various receptors.

Q. I have read your information page on GABA and was wondering if taking GABA sublingually might have a better chance of crossing the blood-brain barrier than regular pills/powder? Source Naturals makes a sublingual product called GABA Calm, which I have found helpful with anxiety. This sublingual pill also contains Glycine, N-Acetyly l-Tyrosine, Taurine and a small amount of magnesium. If it's unlikely that the mere 100mg of GABA in this product is getting to the brain, could the slight calming effect I feel could be due to the other ingredients? I'm sure there is the possibility that the immediacy of the sublingual form also increases the placebo effect, but I am curious as to your thoughts on this. Thank you and keep up the great work!
   A. I have not tried GABA Calm from Source Naturals so I do not know which of the ingredients is working to create calmness, perhaps the taurine? As to sublingual GABA, it still has to cress the blood brain barrier from the bloodstream, so I am not sure.

Q. I need to find out if I am on an anti-inflammatory, Asacol ( mesalamine ) and I have Crohn's disease, would it be safe to try GABA to see if it will help me relax. I have trouble sleeping unless I take sleeping tablets. I am also on Rivotril ( clonazepam ) at the moment to relaxation but do not feel much better for it.
   A. There's hardly any research done with the combination of drugs and supplements such as GABA, so we can't say. In most cases when the dosage of the supplement used is very low, it appears to be safe to take with medications, but there could be exceptions and unexpected reactions when drugs and supplements are combined. Ultimately you need to consult with your health care provider.

Q. I started taking GABA supplements several months ago when a promotion at work resulted in high stress and chronic insomnia. I had tried numerous other herbal sleep aids and nothing helped in the least, but, seemingly, the GABA worked miraculously when I started taking three 750 mg capsules right upon going to bed. And there was yet another dramatic positive effect of the GABA. I suffer from chronic and constant spasmodic cervical dystonia. After I started using the GABA the symptoms of the dystonia all but completely went away. Interestingly, I had been taking GABA every night for about four months and stopped suddenly about three weeks ago when I went on a backpacking trip. After I returned from the trip I did not begin taking the GABA again, within about a week my level of stress and anxiety had skyrocketed again and the dystonia symptoms returned unabated (though the symptom that led me to take the GABA in the first place, the insomnia, has not returned.
   A. Thanks for sharing this with us. What company brand were you using?
      Q. I've been using both "NOW" and "Source Naturals" GABA brands, buying whichever I could find for the cheapest price, and both seem to have been equally effective. I began taking four of the 750 mg GABA capsules about five days ago now (currently taking the "NOW" brand) and my anxiety level and dystonia symptoms have both calmed significantly once again.

Q. I started taking GABA supplements this past summer because I heard that it can help with stress and mild anxiety; it is also taken by bodybuilders because of the relationship between GABA and human growth hormone. I researched it and learned that there is great deal of doubt as to whether orally administered GABA can cross the blood-brain barrier, but I figured it was worth a try. It didn't work for anxiety AT ALL -- but it inexplicably cured what had become a VERY severe, chronic sleepwalking problem (severe to the point where I was sustaining injuries during the night). At the time, I had no idea why that would happen, but since then I've read up quite a bit on the chemistry of sleep. I already knew that sleepwalking occurred during slow-wave delta sleep, but I didn't know that the "chemical signature" of delta sleep was GABA, or that the brain produced human growth hormone during this sleep phase. It seems to me that these things are related, and that there could be some potential there for treatment or research. I'm wondering if you or one of your colleagues could make use of the idea? I have tried contacting some university faculty who specialize in sleep research, but no one seems particularly taken with the idea. I wonder if you could be on the forefront of marketing a sleepwalking cure? I would very much like to see this information help others who are in the same position that I was. By the way, I stopped taking the GABA last month, thinking maybe that I had "gotten over" sleepwalking. About a week later, I woke up with a bath towel inexplicably draped across the couch and a picture taken down off the wall. So I will definitely keep taking it!
   A. This is interesting and we will see if others with a sleep walking problem are helped by a GABA supplement or it just happened to be coincidence in your case. What what the GABA dosage and the brand?
      Q. It is called "GABA 750," GNC brand. It contains 750mg of gamma-aminobutyric acid per capsule. It has no other ingredients aside from gelatin. I usually take 2 a couple hours before bed (around 9:30), and another 2-3 about half an hour before bed. I sometimes take more on those rare occasions when I also take Ambien, a prescription sleep aid that greatly exacerbates my sleepwalking.

Q. Regarding GABA for anxiety treatment. Does this supplement taken orally, follow the same receptor sites that “Zanax or Valerian” does? I’ve been taking a formula that has 600mg of GABA in it with passion flower, magnesium and b-6, called “Nutrasleep” by Source Naturals. I’ve been taking it several times a week to treat anxiety and insomnia for recovering from 3rd stage Adrenal fatigue ( I have been on a strict protocol from my naturopathic doctor. I once was on Zanax about 8 years ago and had a very horrible time coming off this. Had to taper off very slowly over several weeks to a month. That is why I will never go on prescribed meds like this again. But, after taking the GABA periodically for over 4 months now, I’m having several nights a week, waking up sweating, anxiety, insomnia, and am wondering it I have built up a tolerance to the GABA and the receptor sites, causing withdrawal effects.
   A. It is difficult to say when a combination formula is taken that has GABA, passion flower, and other supplements which ingredient or combination is working or causing side effects. I am not familiar with Nutrasleep by Source Naturals. I am not impressed by GABA, alone in helping with anxiety. You may consider reading the information on anxiety and supplements helpful for this condition and discuss the options with your doctor. It is also a good idea to take occasional breaks from the regular use of supplements.

Q. Can GABA be addicting if taking a supplement for months?
   A. I am not sure but I doubt it since GABA supplements, by themselves, do not have a potent effect on brain chemistry.