Do GABA Supplements Work or Not? April 28, 2016

Gamma-aminobutyric acid, more commonly known as GABA, is an amino acid that behaves like a neurotransmitter for the central nervous system. Neurotransmitters are defined as endogenous (body-produced) messengers that modulate, enhance, or transmit signals from one neuron or cell to another, promoting some form of action in the target cell. GABA is essential for brain metabolism as well as optimal brain function.

GABA, also known as y-aminobutyric acid, is also considered an inhibitory neurotransmitter that regulates a number of psychological and physiological processes in the body. It has long been believed that GABA variations in the forebrain are associated with conditions such as anxiety and depression (1).
A component that has a big influence on emotional and stress responses, GABA is manufactured in the brain, and can help to balance neurons as well as emotional reactions to external stimulus like fear (adrenaline). It has an influence on our moods and sleep cycles. Low levels of GABA in the body have been associated with depressive states, anxiety disorders, extreme stress, and even irregular sleep cycles (2).

GABA 101

As one of the most prevalent neurotransmitters in the central nervous system (CNS), GABA is found predominantly in the cerebral cortex, where the brain interprets sensations and thinking processes. GABA is constructed from another major neurotransmitter, glutamate. Glutamate is an ‘excitatory’ neurotransmitter and encourages the transmission of nerve impulses. GABA’s function is just the opposite – inhibiting the firing or transmission of impulses. It slows down neuron activity as well as reduces stimulation of nerve cells common with anxiety disorders, panic attacks, and seizure disorders. Basically, GABA has a soothing effect on the body.

Decreased levels of GABA have been linked to conditions like chronic pain, anxiety, and/or mood disorders, as well as epilepsy. A number of animal studies have been conducted in regard to endogenous GABA and its effects on numerous aspects of physiological and psychological health and wellness, but very little research on GABA supplements has been conducted.

What Are GABA Supplements Supposed To Do?

GABA supplements have been widely used to boost sex drive because of its ability to act as a relaxant. (Less stress regarding sexual performance equates to more positive effects). A number of GABA supplement users today also rely on it to:

  • Improve sleep
  • Relieve anxiety
  • Improve mood
  • Treat ADHD
  • Relieve pain
  • Decrease blood pressure
  • Increase lean muscle mass
  • Burn fat
  • Increase tolerance, stamina, and endurance to exercise or physical activity

It is also believed to be beneficial in the treatment of enlarged prostate glands due to its function and role in the mechanisms that regulate sex hormone (testosterone) release. GABA is also perceived to promote secretions of the growth hormone.

GABA may also be effective in treating attention deficit disorders due to its mechanism of action on the brain receptors. Because of this action, it also has the potential of reducing cravings for alcohol and is also under review for its potential to treat alcohol dependence and abuse (3) .

What Is The Specific Function Of GABA In The Body?


  • Plays a role in inhibition, and reduces aggression and/or excitation
  • Has been shown to reduce anxiety
  • May play an important role in pain perception
  • Displays anticonvulsant and muscle relaxing properties

GABA and its association with mental health may decrease the number of conditions including anxiety disorders, schizophrenia, and Huntington’s chorea. In some situations, GABA has been used as an effective treatment of hypertension as well as epilepsy and epileptic-type conditions (4), (5).

Amino acid transmitters like GABA and neuropeptides endorphins, along with acetylcholine, play a major role in the development of a number of psychotropic drugs as well as monoamine transmitters (serotonin, dopamine, and norepinephrine). Any alteration of these chemical components may form a basis for psychiatric disease processes and can be the target for pharmacological-based treatments.

Such components like norepinephrine, dopamine, serotonin, glutamate, GABA, and CRH (corticotropin-releasing hormone) have been linked to mental activity. Changes in the release of transmitters and receptor responses can initiate a cause and consequence effect with regard to intercellular changes in neurons involved in such processes. For example, thought disorders such as schizophrenia are often associated with excessive transmission of the dopamine neurotransmitters, among other changes. GABA appears to play a specific role in the modulation of neuronal “excitability” as well as anxiety (6). A number of anti-anxiety drugs act by increasing effectiveness of GABA neurotransmitters, accomplished basically through the increase of receptor responsiveness.

GABA Mechanism Of Action

How exactly does GABA work? It basically has an effect on presynaptic inhibition in primary motor neuron afferent fibers, a component of the motor neuron system. Its function is to regulate “excitability” of its receptors, which are defined in three specific subunit categories:

  • Alpha
  • Beta
  • Gamma

Benzodiazepines have been shown to have an ability to bind with Alpha-1 subunits. Other benzodiazepines bind with other alpha subunits. GABA tends to mainly affect components of the endocrine system and has the potential to initiate increases in plasma growth hormone levels.

In high enough concentrations found in the pancreas islet cells, GABA has been studied for its ability to improve plasma levels through the reaction of immune hormones and components such as glucagon, insulin, and C-peptide without altering concentrations of glucose plasma. GABA is also an important aspect of endocrine disorder pathophysiology in conditions like diabetes mellitus and diseases of reproductive tracts and adrenal glands (7).

What About Biological Findings?

Neurons release chemicals known as neurotransmitters that convey messages along certain anatomic pathways (known as the limbic system) and provide structure for the transmission of electrical impulses that occur in the brain when anxiety-related responses are either sent or received. Neurochemicals that regulate anxiety include the above-mentioned dopamine, serotonin, GABA, norepinephrine, and epinephrine.

A number of theories abound regarding the basic cause of anxiety disorders. One is known as the GABA-benzodiazepine theory, which postulates that benzodiazepine receptors are linked to receptors that inhibit the activity of the GABA neurotransmitter. It causes a decline of GABA neural transmission, eliciting a calming effect. It is perceived that the binding action of benzodiazepine medications to benzodiazepine receptors can facilitate the behavior and action of GABA. This theory, therefore, proposes that benzodiazepine receptor abnormalities can lead to unregulated anxiety levels.

Does GABA Work For Anxiety?

Between 5% and 30% of the world’s population has prevalence of anxiety disorders, which are often associated with high comorbidity rates with additional psychiatric or medical conditions and disorders (8). Researchers have also determined that heredity and genetics can contribute to up to 30% prevalence that runs in families (9).
Drug treatments focus on increasing GABA concentrations are generally sought through the use of selective serotonin reuptake inhibitors (SSRIs). A report published in the American Journal of Psychiatry determined in one small study group that treatment with SSRIs increased cortical levels of GABA in patients diagnosed with depression (10).

GABA, when linked with other chemical components such as niacinamide and inositol, is believed to prevent anxiety or neural messages conveying stress from reaching the motor centers of the brain. These chemical components do this by occupying those receptor sites on cells.

In many ways, GABA can behave much like Valium (diazepam), Librium (chlordiazepoxide), and other types of prescription drug tranquilizers, although without the risk or fear of addiction. A number of studies have been performed in the capability of GABA to reduce anxiety. One study, “Association Study between GABA Receptor Genes and Anxiety Spectrum Disorders” determined that any malfunction or dysfunction of the GABA system itself can contribute to a number of neuropsychiatric conditions including depression, depressive disorders, as well as anxiety (11). This study focused on four GABA receptor genes for their possible link to genetic risk for anxiety disorders.

The study focused on twin populations exploring the potential for latent genetic risk factors associated with depressive and anxiety disorders. These GABA receptor genes included:

  • GABRA2
  • GABRA3
  • GABRA6
  • GABRG2

Ultimately, the study determined that variations in these four GABA receptor genes did not influence the potential for developing anxiety.

What About GABA For Weight Loss?

Studies regarding the efficacy of GABA supplements on weight loss are lacking. Endogenous GABA is something else. The neurotransmitter can contribute to the balance of energy in the body. A study performed at the Beth Israel Deaconess Medical Center determined that GABA does play a role in controlling energy balances in the body (12).
The Scientist published an online article defining the three major stages of weight maintenance by the body:

Stage 1 – The brain receives sensory information about leptin and ghrelin (hunger and satiety) hormones as well as fatty acid in glucose levels.

Stage 2 – The brain analyzes this information, accompanied by external cues and emotions.

Stage 3 – The brain adapts energy expenditure with food intake to maintain a balance of energy, which is designed to prevent excessive weight gain or obesity. Neuropeptides are involved, as are neurotransmitters. Another neuron (Agouti-related protein, known as AgRP) has a critical role in this process of regulation. It is also theorized that the release of GABA has the capability of mediating these AgRP neurons. Mice with disrupted GABA release were shown to exhibit “profound” metabolic changes. The end result determined that the engagement of GABA release from AgRP neurons were able to, at least in part, mediate the appetite stimulating action of the hormone ghrelin.

Other studies have sought to define the link between GABA, appetite, and weight loss. One study determined that taurine has the potential to activate glycine receptors (Gly-Rs) and perform as a weak agonist at GABA (A) receptors, reducing excitability of thalamocortical relay neurons (13). This potential was seen to activate extrasynaptic GABA (A)-Rs and Gly-Rs in mice. While not many of us are familiar with taurine, we are familiar with energy drinks like Red Bull.

The thalamus is located deep in the brain and plays a role in the control of behaviors. Taurine was shown to have a large impact on GABA receptors in the thalamus. The study determined that because GABA was vital in the formation of cellular-to-cellular connections in the developing brain, it may also play a role in neurological development in regard to hunger triggers.

Deficiencies In GABA

It’s been established that GABA plays numerous roles in a number of neurological as well as psychiatric disorders and conditions including anxiety, depression, and even insomnia. As a result, a number of drugs have been developed to stimulate GABA receptors, most especially in anti-anxiety as well as a sleep aid drugs. A number of medications include benzodiazepine:

  • Valium (diazepam)
  • Halcion (triazolam)
  • Xanax (alprazolam)
  • Ambien (zolpidem)
  • Doral (quazepam)

In addition, lack of GABA in the brain may have an impact on the olfactory senses (the smell perception) as well as taste perceptions.

What About Safety, Side Effects, And Contraindications Against Use?

Despite the numerous benefits often associated with GABA, too much of the amino acid in the bloodstream can cause the opposite of desired effects, resulting in increased anxiety. Other signs and symptoms of accelerated levels of GABA in the bloodstream include but are not limited to:

  • shortness of breath
  • a numb feeling around the mouth
  • tingling in the extremities

Serious side effects of GABA can include seizures, caused by an imbalance of message delivery signals and imbalances in the brain. When assessing the efficacy of any supplement, it’s also important to be aware of side effects, cautions, and contraindications against use. While GABA supplements may be popular, they can also pose a risk for some. Because of lack of information culled from clinical trials or research studies, it is unclear whether GABA supplements cause side effects or incur risks. However, it is recommended, due to this lack of information, that pregnant or nursing mothers do not use GABA or other supplements.

Currently, it is also unknown whether GABA supplements have the potential to interact with prescription or a number of over-the-counter drugs, herbal products, supplements, or foods.

Gathering information regarding side effects involves some research on user reviews. Some users of GABA supplements have noted periodic and throbbing heart rate. Others mention a change in their breath rate, while a few others comment about an odd tickling sensation on the skin of the face. However, such side effects are transitory in nature.

Individuals diagnosed with any medical conditions, including asthma, high blood pressure, anxiety, insomnia, or diabetes consult their physician before using GABA supplements.

Because GABA does promote a sense of relaxation, it can promote sedative effects in some individuals. Combining vitamin B6 with GABA can nullify the potential for drowsiness. But until a person is accustomed to their own reactions to GABA supplements, it is recommended that it be taken at night before bedtime.

Depending on the milligram strength and dosage recommendations (average 250 mg to 750 mg) two to three times daily, the most common side effects include a sensation of itching or tingling, increased heart rate, rapid or shortness of breath, as well as drowsiness.
Some users have complained of increased sense of anxiety when taking the supplements for over three months.

GABA injections (IV administration) can contribute to a number of other side effects including lightheadedness, increase blood pressure, heart rate, and dysphoria.

Cautions against use may also exist in conjunction with benzodiazepines, barbiturates, and alcohol. Individuals diagnosed with depressive disorders, including unipolar and bipolar disorders, should also use caution and discuss use with a physician before taking.

So, Do GABA Supplements Work Or Not?

GABA supplements are designed to calm the body. Supplements come in a variety of forms: capsules, pills, tablets, sprays, and topical creams. Any form of a supplement can have a positive or detrimental effect with regard to efficacy. The same applies to GABA supplements. Clinical trials and research regarding synthetic GABA are weak, and there is little evidence to support the belief that GABA in the supplement form can even reach the brain, resulting in nothing more than a placebo effect.

The issue with a number of oral supplements is that digestive processes can effectively destroy beneficial components of those supplements. Oral ingestion of GABA not only has to pass through the digestive system before it’s absorbed into the blood and even makes its way to your brain, but once there, it is unable to cross the blood-brain barrier.

The blood-brain barrier acts as a protective “interface” that separates the circulatory system from the brain itself. The blood-brain barrier (BBB) also protects the central nervous system from absorption of chemicals while at the same time regulating the transportation of molecules essential for health, and for maintaining a static or stable environment.

The blood-brain barrier is composed of endothelial, astrocyte, and pericyte cells. It acts much like the walls of a fortress to prevent dangerous chemicals and substances from entering the brain. This protection is provided against high levels of hormones, infection, and chemicals, but it’s not a membrane or covering. Rather, the blood-brain barrier is a mixture of components that are found in capillaries that feed the brain. In the body, capillaries are extremely permeable, which enables blood components to pass through their walls and into body tissues. However, the capillaries in the brain are extremely dense and allow only a few types of substances to be absorbed into the brain.

The bottom line is that the brain manufactures GABA by converting other components into GABA. However, GABA supplements cannot enter the brain. GABA supplements do not support the synthesis, support, or function of GABA concentrations in the brain.

GABA Precursor Supplements

However, GABA precursors can be used to help synthesize or boost the production of GABA in the brain. Green tea contains L-Theanine that is believed to provide a boost in the synthesis of GABA. Some formulations of GABA supplements, including GABA and niacin together, has the potential of passing through the blood-brain barrier and can increase the activation and function of GABA receptors (in animal studies).

The drug Picamilon, formed by combining synthetic niacin and GABA, was developed in the late 1960s in the Soviet Union and has been shown to penetrate through the blood-brain barrier (14). Another study (“Effect of nootropes on quantitative changes in the rat cerebral cortex GABA(A) receptor complexes under experimental hypokinesia conditions”) did show a tendency of picamilon injections to restore some active GABA(A) receptors (15).

GABA, unlike other amino acids, is not involved in the synthesis of proteins. A majority of amino acids provide a foundation for protein synthesis. But while it is considered, at least technically, as an amino acid, it’s produced from glutamate in the brain. Glutamate is a neurotransmitter and amino acid.

The bottom line is that GABA supplements may provide some benefits for some users, but individual results may vary depending on age, weight, health status, and nutrition and exercise levels.

However, as mentioned earlier, one supplement (Picamilon) may improve the synthesis of GABA in the body, and does have the ability to cross the blood-brain barrier. So does another relatively new supplement called Phenibut HCL. This nootropic is a derivative of the GABA neurotransmitter, and when stacked with other components, it can alleviate stress, improve mood, and for some, act as an antidepressant.


While studies continue to explore dietary, herbal, or natural supplements to improve numerous functions of neurotransmitters, hormones, and metabolism in the human body, studies in this area of GABA to treat depression, anxiety, weight loss, and so forth are lacking. Yes, some studies involving small animals have been conducted with promising results. But till date, large and placebo-controlled and double-blind studies have yet to definitively prove that GABA supplements work as well as they are marketed to.

When looking for any supplement, be aware of the ingredients, what those ingredients are supposed to do, and whether those ingredients are found in large enough quantities to do you any good, or if you’re just going to end up wasting your money.