ALL NATURAL GABA – Safe and Effective Dietary Ingredient for Relaxation

GABA is a widely accepted abbreviation for an amino acid called ?-aminobutyric acid. Unlike herbs and pharmaceuticals, GABA is a substance that is already a part of the normal brain chemistry. This makes GABA supplementation a type of intervention that we call orthomolecular. The term orthomolecular means that the compound used is already present in the body and is a part of its normal metabolism. Such molecules include amino acids, vitamins, fatty acids and their metabolites. For the same reason, herbs and pharmaceuticals are classified as xenobiotics, or substances inherently foreign to the body. GABA produced by fermentation is not only the same molecule already used in the brain, but is also synthesized via the same biochemical pathway as in the body (as discussed below). Thus, supplementation with orthomolecular type nutrients such as GABA is preferred by many as a gentler, less "invasive" option.

GABA is typically found in the CNS (Central Nervous System) where it acts as a neurotransmitter. Neurotransmitters are molecules that pass on or affect signal transmission between neurons or neurons and other cells in the body (i.e., transmission of signals between neurons and muscle cells, myocytes). More specifically, GABA is an inhibitory neurotransmitter in the brain cell junctions known as synapses. A pre-synaptic neuron releases GABA which then interacts with the GABA-receptors of the post-synaptic neuron. This results in a "calming" effect on the post-synaptic neuron which is achieved via a process called hyperpolarization and leads to decreasing neuron's excitability. This is an innate physiological mechanism which protects brain cells from getting "overwhelmed" from processing too many excitatory stimuli¹.

The immediate precursor of GABA in the body is glutamate, which is also a neurotransmitter, but an excitatory kind. Its effect is opposite to the inhibitory GABA influence. Glutamate is converted into ?-aminobutyric acid with the help of enzyme L-glutamic Acid Decorboxylase, or GAD. (4712). Enzyme GAD is found in many nerve endings in the brain. Neurons that secrete GABA are called GABAergic. Besides enzyme GAD, synthesis of GABA in GABAergic neurons also requires vitamin B6 as a co-factor².

GABA was discovered in the late 18th century as one of by-products of bacterial metabolism. It was not until the 1950s, however, when its role in the mammalian brain physiology was uncovered. Synthetic forms of GABA have been available for more than 30 years. Yet, its use has been largely limited by the lack of effectiveness of orally administered synthetic GABA on human brain physiology. Since then, GABA has made a full circle, when in 2006 a group of Japanese researchers demonstrated that oral administration of GABA obtained via bacterial fermentation produced measurable and statistically significant changes in the electromagnetic brainscape³.

All-natural GABA obtained by fermentation can be produced using a number of non-pathogenic microorganisms, including select strains of genus Lactobacillus^4,5. Many of the members of this genus of bacteria are considered to be beneficial, a.k.a. probiotics. Typically, they occupy the gastrointestinal tract, but are also found in a number of fermented foods, - both dairy and non-dairy (i.e. kim chi, sauerkraut, etc.). However, the ability of microorganisms to produce GABA is strain-specific. Out of 72 Lactobacillus strains found in various fermented foods only 3 were identified as GABA-synthesizers⁶. Microbial production of GABA involves the same enzyme GAD and vitamin B6 as a co-factor, but with more utilitarian purpose than in the brain. Glutamate is used as a preferred energy source resulting in production of ATP, CO2 and GABA as a by-product of bacterial metabolism^5,7.

The results of a clinical trial that studied the effect of orally administered "natural" GABA have recently become available³. The natural GABA employed in the study was obtained via microbial fermentation using Lactobacillus hilgardii K-3. This GABA-producing strain was originally isolated from kim chi, a traditional Korean fermented vegetable dish/condiment.

The trial was two-fold. In the first part, each subject was given 100mg of GABA or a placebo (distilled water) and their EEGs (electroencephalograms) were compared. An EEG is the method of recording electromagnetic activity of the brain, particularly brain waves. Among four types of waves are recognized on the EEG, there are two types of waves associated with sleep (d-waves and ?-waves) and two types observed during the state of arousal, or when the person is awake (a-waves and ß-waves). The a-waves occur during the state of relaxation, effortless alertness, while ß-waves are strongly associated with stress, difficult mental concentration, anxiety and unrest. Administration of GABA led to a significant increase of in a-waves and decrease of ß-waves. The achieved a/ß wave ratio is strongly correlated with a state of arousal with relaxation and without stress and anxiety.

Volunteers that participated in this study were also given 200 mg of L-theanine that produced a significantly less pronounced shift in electromagnetic brain activity. L-theanine is an amino acid present in tea leaves known for its relaxing properties. The mechanism of action of L-theanine, however, is related to its ability to influence serotonin metabolism in the brain^8,9. Serotonin is another neurotransmitter which effect is strongly associated with mood regulation.

In the second portion of the aforementioned study, healthy volunteers with a history of achrophobia (fear of heights) were offered to cross a 980 foot long, 175 foot high suspended bridge, putting them in a predictable stressful situation. Levels of immunoglobulin A (IgA) in the volunteers' saliva were chosen to evaluate psychosomatic effects of GABA during and after the stressful situation. The study showed that volunteers that took GABA before crossing the bridge did not have a decline in IgA levels, while subjects that took the placebo had a significant drop in the IgA concentration. Research suggests a strong link between stress and non-specific defense mechanisms, such as IgA production. Immunoglobulin A levels play a central role in mucosal resistance, particularly in the respiratory system and gastrointestinal track. This particular study establishes GABA's ability to attenuate stress-related IgA decline as one of the psychosomatic consequences of stress³.

While psychosomatics is a promising and important area of research, most of us on a daily basis deal with strictly psychological consequences of stress. Today, in our fast-paced society stress comes in all shapes and forms. More often than we realize, it leads to the feeling of anxiety, which, in turn, may provoke more serious psychological problems. Reducing the level of stress by removing yourself from a stressful situation is a desirable, but oftentimes not a viable option. Meditation, exercise, music, hobbies, etc., - all offer tools for coping with stress. Now, add GABA to this list as nature's own stress-fighting compound¹⁰.

Under no circumstances should one attempt to treat an anxiety disorder without consulting a physician. However, if you experience an occasional feeling of nervousness clearly related to a particular stressful situation, GABA supplementation might be the support you need. It takes about 30 minutes to reach the desired state of relaxation, so you may want to take it prior to a stress-related activity.

Researchers noticed a strong correlation between the levels of GABA (along with another neurotransmitter, serotonin) and complaints of irritability and overall discomfort in women, whose mood and well-being is affected by pre-menstrual syndrome (PMS). Most physicians now agree that, considering the strictly transitional nature of these complaints, and depending on the severity of such complaints, supplementation with GABA makes more sense than reaching for pharmaceutical-type solutions¹¹. The latter group should include not only synthetic drugs, but also natural herbal compounds.

Unlike herbs and pharmaceuticals, GABA is a substance that is already a part of the normal brain chemistry. This makes GABA supplementation a type of intervention that we call orthomolecular. The term orthomolecular means that the compound used is already present in the body and is a part of its normal metabolism. Such molecules include amino acids, vitamins, fatty acids and their metabolites. For the same reason, herbs and pharmaceuticals are classified as xenobiotics, or substances inherently foreign to the body. GABA produced by fermentation is not only the same molecule already used in the brain, but is also synthesized via the same biochemical pathway as in the body (as discussed previously). Thus, supplementation with orthomolecular type nutrients such as GABA is preferred by many as a gentler, less "invasive" option.

Finally, recent research points out that the calming effect of GABA also allows for better synchronization of large neuron clusters in the brain. These large neuron clusters working "in synch" are the very basis of our cohesive and sensory brain activity¹².

GABA is well tolerated and no side effects were observed during clinical trials.

Reference List

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3. Abdou AM, Higashiguchi S, Horie K, Kim M, Hatta H, Yokogoshi H. Relaxation and immunity enhancement effects of gamma-aminobutyric acid (GABA) administration in humans. Biofactors. 2006;26:201-208.
4. Yokoyama S, Hiramatsu J, Hayakawa K. Production of gamma-aminobutyric acid from alcohol distillery lees by Lactobacillus brevis IFO-12005. J Biosci Bioeng. 2002;93:95-97.
5. Park KB, Oh SH. Production of yogurt with enhanced levels of gamma-aminobutyric acid and valuable nutrients using lactic acid bacteria and germinated soybean extract. Bioresour Technol. 2006.
6. Komatsuzakia N, Shimaa J, Kawamotoa A, Momosed H, Kimura T. Production of g-aminobutyric acid (GABA) by Lactobacillus paracasei isolated from traditional fermented foods. Food Microbiology. 2005;22:497-504.
7. Higuchi T, Hayashi H, Abe K. Exchange of glutamate and gamma-aminobutyrate in a Lactobacillus strain. J Bacteriol. 1997;179:3362-3364.
8. Mason R. 200 mg of Zen L-Theanine Boosts Alpha Waves, Promotes Alert Relaxation. Alternative & Complementary Therapies. 2001;91-95.
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10. Kalueff AV, Nutt DJ. Role of GABA in anxiety and depression. Depress Anxiety. 2006;24:495-517.
11. Milewicz A, Jedrzejuk D. Premenstrual syndrome: From etiology to treatment. Maturitas. 2006.
12. Jeong HY, Gutkin B. Synchrony of neuronal oscillations controlled by GABAergic reversal potentials. Neural Comput. 2007;19:706-729.