# GABA

Category: Hormones

Also known as: gamma-aminobutyric acid

GABA (gamma-aminobutyric acid) is a mediator of nervous inhibition whose heightened liberation occurs during sleep and near-sleep states, functioning as a core component of the body's protective anti-stress system. Peat argued that GABA is synthesized from glutamic acid by the…

10 passages · 2 authors · 1975–2023 · Most-cited: [Ray Peat](https://bioenergeticoracle.com/md/voices/ray-peat/index.md)

Canonical page: https://bioenergeticoracle.com/concepts/gaba

## Synthesis

**GABA (gamma-aminobutyric acid)** is a mediator of nervous inhibition whose heightened liberation occurs during sleep and near-sleep states, functioning as a core component of the body's protective anti-stress system. [Source 1, 3] Peat argued that GABA is synthesized from glutamic acid by the enzyme **glutamic acid decarboxylase (GAD)**, a process requiring *vitamin B6* as a coenzyme. [Source 1, 4] He noted that GAD is a peculiar enzyme inactivated by cold, suggesting it is relatively inactive in the *resting state* but becomes more active during brain activation or exhaustion, producing more GABA to promote rest and restoration. [Source 1, 4]

Peat situated GABA within a broad, holistic inhibitory network that opposes excitatory and catabolic processes. He observed that the protective steroids **progesterone** and **pregnenolone** act on the GABA receptor to reinforce its inhibitory effects, while *estrogen* has the opposite action, inhibiting GABA's function. [Source 9] This system extends structurally to other amino acids; Peat wrote that the similarity between the structures and actions of glycine and GABA suggests their receptors are similar, if not identical, and that both are opposed by the excitatory amino acid system activated by glutamic and aspartic acid. [Source 9] Dinkov has extended this by noting that many medium and short-chain saturated fatty acids are direct agonists of the GABA receptor, which explains the anti-epileptic mechanism of ketogenic diets. [Source 10]

The GABA system is central to tissue renewal and stress resistance without stimulating cell multiplication. Peat explained that GABA and progesterone improve regeneration by preventing premature cell death and promoting normal differentiation and maturation, countering the excitotoxic and mitochondrial-damaging effects of *polyunsaturated fatty acids* released during cellular excitation. [Source 2] He described GABA analogs as one of the most actively studied classes of adaptogens, with a wide range of stress-blocking actions including neural inhibition, progesterone promotion, and blood sugar regulation. [Source 3] Dinkov has argued that GABA agonists suppress the cortisol and estrogen pathways, leaving a hormonal profile of pregnenolone, progesterone, and DHEA that characterizes a youthful, anti-stress state. [Source 10]

Regarding practical application, Peat acknowledged that oral GABA supplementation normally does not cross the blood-brain barrier, but he cited research showing that stress can eliminate this barrier, allowing GABA to enter an exhausted brain and exert a beneficial inhibitory action. [Source 4, 6] He recommended supporting the GABA system with **magnesium**, **glucose**, **carbon dioxide**, and anti-inflammatory pro-GABA steroids rather than relying solely on direct supplementation. [Source 7] Dinkov has cited human studies showing that even 100 milligrams of oral GABA significantly lowers anxiety and depression scores, and that its effect synergizes with *L-theanine*. [Source 8] Peat also noted that the tropical fruit passionfruit contains compounds made along with GABA that help eliminate stressful over-excitation, and that even the sedative effects of cannabis can be protective against toxic over-stimulation by acting on this system. [Source 5]

## People also ask

### How does vitamin B6 relate to GABA production in the body?

Peat noted that the enzyme glutamic acid decarboxylase (GAD) synthesizes GABA from glutamic acid and requires vitamin B6 as a coenzyme to function.

### Why do progesterone and estrogen have opposite effects on the GABA system?

Peat observed that progesterone and pregnenolone act on the GABA receptor to reinforce its inhibitory effects, while estrogen inhibits GABA's function, creating opposing influences within the body's anti-stress network.

### Can oral GABA supplements actually reach the brain to have an effect?

Peat acknowledged that GABA normally does not cross the blood-brain barrier, but he cited research showing that stress can eliminate this barrier, allowing oral GABA to enter an exhausted brain and exert a beneficial inhibitory action.

## Related concepts

- [Migraine](https://bioenergeticoracle.com/md/concepts/migraine/index.md)
- [Arachidonic Acid](https://bioenergeticoracle.com/md/concepts/arachidonic-acid/index.md)
- [ATP (Adenosine Triphosphate)](https://bioenergeticoracle.com/md/concepts/atp-adenosine-triphosphate/index.md)
- [Beef](https://bioenergeticoracle.com/md/concepts/beef/index.md)
- [Beta oxidation](https://bioenergeticoracle.com/md/concepts/beta-oxidation/index.md)
- [Dopamine](https://bioenergeticoracle.com/md/concepts/dopamine/index.md)

## Cited passages

Passage numbers match the `[Source N]` markers in the synthesis above.

### Source 1 — Mind and Tissue: Russian Research Perspectives on the Human Brain

Ray Peat · Book · 1976

> **Ray Peat:** This type of receptor may be responsible for the trophic influences which maintain high polarization and which seem to be involved in such things as the "Bowditch staircase." Electrical stimulation may act on similar "receptors" in neurons. Vitamin B 6 is a coenzyme in carboxylation reactions and as such is involved in the synthesis of serotonin from 5- hydroxytryptophan, and also in the formation of GABA (gamma-aminobutyric acid) from glutamic acid. In the "resting" state, cell water seems to be more orderly, as if it had a lower "structural temperature." Some enzymes are inactivated by cold and presumably would be inactive in the resting state. GAD (glutamic acid decarboxylase) has been found to be among these peculiar enzymes, and this is the enzyme which decarboxylates glutamic acid, producing GABA. GABA has been shown to be a mediator of nervous inhibition on the basis of several criteria, including heightened GABA liberation in sleep and near-sleep (Sytinskiy, 1973). This would seem appropriate if the physical state of cell water is participating in brain regulation. During brain "activation" or exhaustion, this enzyme should become more active, producing more GABA and presumably thereby promoting rest and restoration. (Since hydroxylamine is an inhibitor of GABA degradation, it would be interesting to see what effect it has on psychoses, though it may be too toxic to be practical; the same might apply to hydrazine, which is used with considerable success in inoperable cancer, and often induces sleep as well as preventing cachexia.) The natural anesthetic steroids would probably be the first choice for a chemically induced state of sleep if they could be administered conveniently. Another enzyme that should be investigated from this point of view is NADase, since it too shows what may be a sensitivity to structure: In cell homogenates, it is sufficiently active to destroy NAD and thus stop glycolysis at the triose phosphate stage (Florey, 1966).

### Source 2 — The Gaba System Defenses and Tissue Renewal

Ray Peat · Article · 2007

> It can produce gliosis from excessive stimulation of cell division combined with a lack of the factors such as GABA needed for maturation into nerve cells, and it can kill nerve cells, by interrupting their energy production. The accumulation of this and related fatty acids with aging is a problem. The DHA and other polyunsaturated fatty acids released by cellular excitation cause mitochondrial damage and edema, but saturated fatty acids don't have those effects (Chan and Fishman, 1980, 1982; Chan, et al., 1988; Hillered and Chan, 1988, 1989).
>
> Alexis Carrel, with a famous experiment begun in 1912, showed that animal tissues kept in culture dishes with frequent (daily) changes of the growth medium didn't age, and he suggested that changes in the fats in the body accounted for aging. Lately the gene technology people have said fraud was involved in Carrel's experiments, but many other kinds of experiment produced similar results. For example, Hans Selye found that frequent changes of fluid prevented aging of tissue growing inside an implanted capsule. Polezhaev's discovery that mammalian tissues can be induced to regenerate by the presence of degenerating tissue (which releases the breakdown products of phospholipids and proteins) is consistent with the recent demonstrations that stem cell growth is activated by fatty acids and phospholipids.
>
> The saturated fats, rather than simply lacking the toxic and excitatory properties of the polyunsaturated fats, are being shown by many types of research to have protective, inhibitory, and restorative actions. The medium chain triglycerides (MCT, usually made from coconut oil) are easily oxidized by mitochondria, and are often used to produce ketosis, to prevent seizures. A high-fat diet has been used since about 1920 to control epilepsy, but there is no generally accepted explanation for its effect. A ketogenic diet produces acetone, acetoacetate, and beta-hydroxybutyrate ("ketone bodies") and these are protective against seizures (Rho, et al., 2002). Besides providing energy to mitochondria, hydroxybutyrate is structurally close to GABA.

### Source 3 — The Generality of Adaptogens

Ray Peat · Newsletter · 1991

> GABA analogs are now one of the most actively studied classes of adaptogens. GABA has a wide range of stress-blocking actions, including neural inhibition, progesterone promotion, and blood sugar regulation.
>
> The local anesthetics, which generally have a broad range of effects, are an important class of adaptogens. Procaine has been found to normalize almost every system studied.[One large study was done at Edgemoor Geriatric Hospital, Santee, California, in 1960.] Doses far too small to have an anesthetic effect have clear biological effects. Lidocaine is used to prevent heart arrhythmia, and acts partly by preventing excessive calcium uptake by the cells. The atropine family of drugs is structurally similar to the local anesthetics, and also have a long history of use in treating sickness and stress. Most of these chemicals have anti-histamine actions that are probably relevant to their value as adaptogens. These chemicals can protect microcirculation against spasms produced by exhaustion or overstimulation. Light can also have this effect.
>
> Promotion of synthesis and stabilization of the detoxifying enzymes is another function of some adaptogens. The catatoxic steroids do this, but since they also have an immediate protective effect (that could hardly involve the production of new enzymes), they probably have other mechanisms of action, such as improving the capacity for binding toxins of proteins such as albumin. Since even cholesterol has catatoxic action, I often advise people to eat more eggs for a variety of problems. The egg lipids (including phospholipids and cholesterol) enter the blood in microscopic particles, called chylomicrons. Synthetic liposomes are a pharmaceutical fad, promoted for their ability to transport various drugs, but the liposomes themselves (made from egg phosphatidylcholine and cholesterol) have anti-inflammatory and anti-bacterial actions. (Anti-inflammatory action of liposomes,) I think we have to include dietary eggs in our list of adaptogens.
>
> I have often described the thyroid hormone as the basic anti-stress hormone, because it is essential for respiratory energy production. The ATP produced under the influence of the thyroid hormone binds magnesium, and is relatively stable in its presence. ADP, the lower energy phosphate that results when ATP loses one phosphate group, happens to bind calcium.

### Source 4 — A Biophysical Approach to Altered Consciousness

Ray Peat · Newsletter · 1975

> High frequency (50006000) currents have been found to stimulate the brain.
>
> In embryonic muscle cells, when the depolarizing fast acetylcholine receptors are blocked by snake venom, then the cell's slow polarizing acetylcholine receptors are revealed This type of receptor may be responsible for the trophic influences which maintain high polarization and which seem to be involved in such things as the Bowditch staircase. Electrical stimulation may act on similar receptors in neurons.
>
> Vitamin B6 is a coenzyme in carboxyl-ation reactions and as such is involved in the synthesis of serotonin from 5-hy-droxy-tryptophan, and also in the formation of GABA (gamma-aminobutyric acid) from glutamic acid. In the resting state, cell water seems to be more orderly, as if it had a lower structural temperature. Some enzymes are inactivated by cold and presumably would be inactive in the resting state. GAD (glutamic acid decarboxylase) has been found to be among these peculiar enzymes, and this is the enzyme which decarboxylates glutamic acid, producing GABA. GABA has been shown to be a mediator of nervous inhibition on the basis of several criteria, including heightened GABA liberation in sleep and near-sleep.
>
> This would seem appropriate if the physical state of cell water is participating in brain regulation. During brain activation or exhaustion, this enzyme should become more active, producing more GABA and presumably thereby promoting rest and restoration. Since hydroxylamine is an inhibitor of GABA degradation, it would be interesting to see what effect it has on psychoses, though it may be too toxic to be practical; the same might apply to hydrazine, which is used with considerable success in inoperable cancer and often induces sleep as well as preventing cachexia. It raises the level of ATP systemic ally. Injected GABA is usually considered to enter only the fetal or infant brain, because of the blood brain barrier of the more mature organism. However, Nasonov and his students have shown that many kinds of stress will eliminate the barrier and that it can be interpreted as a physical state of the neuron, governing solubility. This suggests that GABA itself may be able to enter the brain and exert a beneficial inhibitory action if the brain is in a state of exhaustion from stress.

### Source 5 — So I just did this, would appreciate it someone would check, I couldn't identify one or two words.

Ray Peat · Interview · Mar 17, 2017 · https://www.youtube.com/watch?v=tJHU730SYHg

> **Andrew Murray:** Passionflower?
>
> **Ray Peat:** The tropical fruit, what’s it called –
>
> **Sarah Murray:** He was thinking you meant GABA.
>
> **Ray Peat:** Oh well it’s an activator, gamma hydroxybutyrate, yeah passionfruit, the word I was looking for.
>
> **Sarah Murray:** Granadilla, is another word for it.
>
> **Ray Peat:** It’s something we make along with GABA which helps to eliminate stressful over-excitation, the synuclein, which is one of the things that goes wrong and is damaged in Parkinson’s disease, it happens to have the same effects as rotenone, the toxic thing that has been seen to cause something exactly like Parkinson’s disease by blocking the Complex 1 of the mitochondrion.
>
> **Sarah Murray:** So, all of the herbs that act on GABA would be useful?
>
> **Ray Peat:** Yes. And even cannabis because of its sedative effects it can be protective against the toxic types of over-stimulation.
>
> **Sarah Murray:** And what about alcohol?
>
> **Ray Peat:** Yeah, I think that it’s anti-oxidant, can be anti-inflammatory and can be in the right circumstance it can be anti-Parkinson’s.
>
> **Andrew Murray:** And studies showing nicotine is protective in big studies that have been done?

### Source 6 — Ask the Herb Doctor: Viruses

Ray Peat · Interview · Mar 15, 2019

> ## Caller: Autoimmunity and GABA
>
> **Caller (Arizona):** Do you have any comments on people who have adverse childhood experiences and physical injuries? I had a head injury 20 years ago.
>
> **Ray Peat:** Those same things. The things that increase stability, energy production, and carbon dioxide production are constantly causing cells to be born and differentiate in the right direction.
>
> **Caller (Arizona):** Is there any use to GABA supplementation?
>
> **Ray Peat:** Normally it doesn't get into the brain because of the so-called blood-brain barrier. But when the brain is very injured, it is taken up because basically the brain needs it. But ordinarily, I think it's enough just to eat a pro-oxidative diet and avoid the excess of phosphate, lactic acid, iron, and so on.

### Source 7 — Ask the Herb Doctor: Viruses

Ray Peat · Interview · Mar 15, 2019

> ## Caller: Autoimmunity and GABA
>
> **Caller (Arizona):** Dr. Peat, your article on immunodeficiency mentions autoantibodies. Glutamate is an excitatory amino acid, and glutamate decarboxylase is the enzyme that turns glutamate into GABA, which is associated with relaxation. Some people have autoantibodies to this enzyme, associated with Type 1 diabetes and Stiff-Person Syndrome. How does the system work, and how do things like passion fruit juice influence the autoantibodies in GABA?
>
> **Ray Peat:** I think the energy system should be able to use the antibodies to clean out the defective enzymes and not continue to be produced. Supporting the GABA system with magnesium, glucose, carbon dioxide, anti-inflammatory things, the pro-GABA steroids derived from progesterone, and the anti-immune steroid DHEA helps to redirect the antibody production. Estrogen tends to make us overproduce antibodies but not be able to guide the correction process. Things that shift the whole physiology towards oxidation and the relaxed, highly energized state of the cell are the route out of all of those autoimmune diseases.

### Source 8 — What You Need to Know About Estrogen and Serotonin - Discussion Between Georgi Dinkov & Dr. Mercola

Georgi Dinkov · Interview · Oct 22, 2023

> **Georgi Dinkov:** So the proof, I mean, probably the official proof, even though there have been isolated studies, that oral GABA is bioavailable. Medicine claims it's not. And I think you could immediately realize why. If oral GABA is bioavailable, overnight, the entire industry of, at the very least, anti-anxiety medication goes away. They're all GABA agonists, right? So clearly, this is a big threat. Anyways, the study that actually, not the study, but the final confirmation that oral GABA is bioavailable is the company that I mentioned just a half an hour ago that's now selling the alcohol replacement. So the main effects of alcohol that most people like are because alcohol is a GABA agonist. GABA agonist, right. So the disinhibition, the calming, the chattiness, you know, the improved mood, all of these stem mostly from its effect as a GABA agonist. It has another one, NMDA antagonist, which is N-methyldeaspartate, another receptor, which is, that receptor is excitotoxic. So anything that inhibits it calms you down. Magnesium is perhaps the strongest natural NMDA antagonist, followed by ethanol. So this company looked and said, okay, we don't have to take alcohol because it has a lot of other bad effects. can we do the exact same effects with something else? And they said, GABA, let's just, you know, they don't disclose what the dosage is, but I've now, that I know that a human studies with it, even a hundred milligrams of oral GABA was enough to lower the assessments of patients with anxiety and depression disorders. to lower their score on whatever assessment worksheet it's being used. I think it's called the BEX depression scale is for depression. And there's another one for anxiety. Just 100 milligrams of GABA was sufficient to lower significantly the score on both scales. And combining with another GABA agonist amino acid known as L-theanine, which is found in tea, actually... drastically increase the effect. So they synergize.

### Source 9 — Gelatin, stress, longevity

Ray Peat · Article · 2009 · https://raypeat.com/articles/articles/gelatin.shtml

> The similarity between the structures and actions of glycine and GABA suggest that their “receptors” are similar, if not identical. For years, it has been known that progesterone and pregnenolone act on the GABA receptor, to reinforce the protective, inhibitory effects of GABA. Estrogen has the opposite effect, inhibiting GABA's action. Since GABA opposes estrogen and inhibits the growth of breast cancer, it wouldn't be surprising if glycine, alanine, etc., did the same. Recent research shows that progesterone and its metabolites also act on the “glycine receptor,” increasing inhibition, and that the “phytoestrogen,” genistein, antagonizes the inhibitory effect of glycine.
>
> The inhibitory systems are opposed by excitatory systems, especially by the excitatory amino acid system, activated by glutamic and aspartic acid. Progesterone and estrogen act on that system, too, decreasing and increasing excitation, respectively. I have previously discussed the arguments for viewing progesterone as a “cardinal adsorbent” (as in Ling and Fu, 1987, 1988, Ling, et al., 1984, a steroid alters glycine's influence on the cell's electrical behavior) which increases the lipophilic, fat-loving property of the cytoplasm, and estrogen as having the opposite action, increasing the water-loving hydrophilic quality of the cytoplasm. If we think of the proteins known as the GABA and glycine receptors as having some regions in which the basic amine of lysine associates with the acidic group of aspartic or glutamic acid, then the action of glycine, or other amino acids would be to introduce additional lipophilic carbon atoms into those regions (with the amino acids' polar ends pairing with their opposites on the protein), where the cardinal adsorbents exert their influence.
>
> Generally, biologists seem puzzled by such facts, because they don't fit into the “lock and key” model of molecular biology. But I think they make the organism easier to understand, since these constellations of facts illustrate simple and general physical principles. They suggest the idea that estrogen and progesterone and glycine, GABA, etc., will be active in any functioning cell, at a suitable concentration.

### Source 10 — Food Metabolism & Diets | Georgi Dinkov

Georgi Dinkov · Interview · Jul 24, 2023

> **Georgi Dinkov:** So GABA agonists will suppress the cortisol and testosterone pathway as well as the estrogen and estrogenic pathway. So you're going to be left with pregnenolone, progesterone, DHEA, and the androgens, but mostly in males, which is exactly the hormonal profile that we want to see in young people. In males, we want high levels of the sort of like the prometabolic anti-cortisol precursors like pregnenolone and DHEA and higher levels of androgens such as testosterone and even dihydrotestosterone. In women, we would like to see higher levels of pregnenolone, progesterone, DHEA. And if you look at the hormonal profiles of 20 to 25-year-old people, that's exactly what we see. But if you look at the hormonal profile of older people, especially over 45 or even 50, all of these so-called youth hormones, the precursors, the anti-cortisol, the anti-estrogenic hormones, they're all gone. They're all down by up to 80%. Neither the estrogen, nor the cortisol, nor the aldosterone declines. So really, the aging can be viewed as an endocrine problem where the brakes on stress have been removed, have disintegrated, and now the stress hormones rule unopposed. And basically, the body eventually catabolizes itself. So that, in a nutshell, is really basically what eating a so-called Western diet, which is really, for me, is a euphemism for a high PUVA, high CO diet, combined with also high carbs. But if you eat, if you go on a ketogenic diet, which is based primarily on saturated fats, you're going to be inhibiting a lot of these catabolic pro-inflammatory processes and returning the body towards a more youthful state in terms of hormonal balance, thyroid production, and general state of anti-stress.

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