GABA stands for Gamma-aminobutyric acid (γ-Aminobutyric Acid) and is a nonessential protein amino acid.
The brain's major inhibitory neurotransmitter, GABA functions as the "off" switch in the brain. GABA is essential to limiting brain neuron excitation so that input signals are balanced and not overdone.
Appropriate levels of GABA prevent anxiety, improve mood, promote sleep, lower blood pressure, act as a muscle relaxant, aid in formation and storage of fear memories, increase insulin secretion and decrease blood glucose levels.
The inhibitory and excitatory balance between GABA and glutamate is very important for healthy brain function, and imbalance in these systems may contribute, in part, to the pathology of anxiety and depression, but we have yet to understand the mechanism.
In the brain, GABA is produced from glutamate in a single decarboxylation reaction. Isoforms of glutamic acid decarbocylase, the enzyme used for conversion, are expressed in tissues other than the brain, where they play a role in diseases of autoimmune character, including neurological disorders and insulin-dependent diabetes.
Neurotransmitters are the chemical messengers used by neurons to communicate with one another and with other types of cells. Every neurotransmitter behaves differently; inhibitory neurotransmitters tend to calm, while excitatory neurotransmitters tend stimulate the brain.
GABA’s primary function:
GABA’s primary function as the brain’s major inhibitory neurotransmitter is to prevent overstimulation. It does this by counteracting glutamate—the brain’s major excitatory neurotransmitter. When GABA binds to a receptor, it prevents stimulation by glutamate. When GABA levels are inadequate, overstimulation due to high levels of glutamate can occur and lead to symptoms of low GABA.
References:
- https://www.ncbi.nlm.nih.gov/pubmed/19058788
- https://www.ncbi.nlm.nih.gov/pubmed/21969419
- https://www.ncbi.nlm.nih.gov/pubmed/23861191
- https://www.ncbi.nlm.nih.gov/pubmed/23391588
- https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3327859/
- https://www.ncbi.nlm.nih.gov/pubmed/23853635
- https://www.ncbi.nlm.nih.gov/pubmed/22207903
- https://www.ncbi.nlm.nih.gov/pubmed/16952998
Research on urinary levels of GABA is scarce, however in individuals with anxiety and depression, GABA levels are low in the blood, in cerebrospinal fluid and in the brain (Mann, et. al. 2014; Goddard, 2016).
The neurodegenerative condition, Huntington’s disease, also manifests as lowered levels of GABA as neuron loss proceeds. Vitamin B6 deficiency impairs GABA formation, offering one option to help assist patients with inadequate GABA production.
Low GABA levels have been found in:
- panic anxiety
- depression
- alcoholism
- bipolar disorders
- Huntin
- also seen in patients with epileptic and Huntington disease.
Possible treatments:
With low GABA, supplementation with:
- GABA,
- L-theanine,
- cofactor support (e.g. B6),
- growth hormonereleasing hormone,
- Ginko biloba,
- Ashwagandha,
- Kava,
- Valerian root,
- Melissa off. (lemon balm),
- Scutellaria sinensis (skullcap),
- Gotu Cola,
- Magnolia and Phellodendron bark,
- and probiotics may be helpful
Additionally, yoga (Streeter et al., 2012) and meditation (Guglietti et al., 2013) increase brain GABA levels.
References:
- Alramadhan et al., 2012;
- Awad et al., 2007;
- Alexeev et al., 2012;
- Dhakal et al., 2012.
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High levels may reflect decreased ability to convert to succinate for use in the Krebs (citric acid) cycle for energy generation. Cofactors here are α-KG and vitamin B6.
GABA is elevated in sleep apnea, ovarian cancer, and is suspected in anxiety, foggy thinking, and lethargy.
High GABA levels in urine is seen in children diagnosed with infantile autism.
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2-Hydroxybutyric acid, 2-Hydroxyhippuric acid, 2-Hydroxyisocaproic acid, 2-Hydroxyisovaleric acid, 2-Hydroxyphenylacetic acid, 2-Oxo-4-methiolbutyric acid, 2-Oxoglutaric acid, 2-Oxoisocaproic acid, 2-Oxoisovaleric, 3-Hydroxy-3-methylglutaric, 3-Hydroxybutyric acid, 3-Hydroxyglutaric acid, 3-Indoleacetic acid (IAA), 3-Methyl-2-oxovaleric acid, 3-Methylglutaconic, 3-Methylglutaric acid, 3-Oxoglutaric acid, 4-Cresol, 4-Hydroxybenzoic acid, 4-Hydroxybutyric acid, 4-Hydroxyhippuric acid, 4-Hydroxyphenylacetic acid, 4-Hydroxyphenyllactic acid, 5-Hydroxyindoleacetic acid (5-HIAA), 5-Hydroxymethyl-furoic acid, Acetoacetic acid, Aconitic acid, Adipic acid, Arabinose, Ascorbic acid (Vitamin C), Carboxycitric acid, Citramalic acid, Citric acid, Creatinine, DHPPA (dihydroxyphenylpropionic acid), Dihydroxyphenylacetic acid (DOPAC), Ethylmalonic acid, Fumaric acid, Furan-2,5-dicarboxylic acid, Furancarbonylglycine, GABA, Glutaric acid (Vitamin B2), Glyceric acid, Glycolic acid, Hippuric acid, Homogentisic acid, Homovanillic acid (HVA), HPHPA (3-(3-hydroxyphenyl)-3-hydroxypropionic acid), HVA/DOPAC, HVA/DOPAC Ratio, Kynurenic acid, Lactic acid, Malic acid, Malonic acid, Mandelic acid, Methylcitric acid (Vitamin H), Methylmalonic acid (Vitamin B12), Methylsuccinic acid, N-Acetylaspartic acid, N-Acetylcysteine acid, Orotic acid, Oxalic acid, Pantothenic acid (Vitamin B5), Phenyllactic acid, Phenylpyruvic acid, Phosphoric acid, Pyridoxic acid (Vitamin B6), Pyroglutamic acid, Pyruvic acid, Quinolinic acid, Quinolinic acid/5-HIAA, Sebacic acid, Suberic acid, Succinic acid, Tartaric acid, Thymine, Tricarballyic acid, Uracil
