GABA

GABA (gamma-aminobutyric acid) is the most important inhibitory neurotransmitter in the brain. It acts as a natural brake against overstimulation: it calms, relaxes, supports sleep and reduces anxiety. GABA is formed from glutamate via glutamate decarboxylase – an enzyme that depends on vitamin B6.

What GABA does in the body

Inhibitory nerve cells make GABA from glutamate; the enzyme glutamate decarboxylase (GAD) needs vitamin B6 for this. GABA is released at the contact points and binds to two receptor types: the GABA-A receptor is a chloride channel – when it opens, the downstream cell becomes harder to excite. Its effect is strengthened by the body's own neurosteroids such as allopregnanolone from progesterone and by substances such as benzodiazepines and alcohol. The GABA-B receptor dampens the cell more slowly via potassium channels. Afterwards GABA is taken back up and broken down with vitamin B6 to succinic acid, which enters energy metabolism. Outside the brain, the beta cells of the pancreas make GABA, and gut bacteria such as lactobacilli and bifidobacteria produce it in the gut. GABA hardly crosses the blood-brain barrier; values in blood or urine therefore mainly reflect production outside the brain and not directly the amount of GABA in the brain.

Low GABA – what happens in the body?

When little GABA acts in the brain, excitation predominates: neural networks react more readily and for longer, switching off and falling asleep become harder, muscle tension can rise, and with marked deficiency seizures can occur. Because GAD needs vitamin B6, less GABA is produced when vitamin B6 is lacking. Antibodies against GAD occur in type 1 diabetes and in the rare stiff person syndrome, in which the muscles are permanently tense. After long-term regular alcohol consumption the GABA-A receptors adapt, so that inhibition is lacking when alcohol is stopped. In studies using magnetic resonance spectroscopy, lower GABA values in the brain have been observed with depressed mood and anxiety disorders.

High GABA – what happens in the body?

When a lot of GABA acts in the brain, excitability is dampened: tiredness, drowsiness, slowed reactions and slacker muscles may follow. Very high values arise in the rare inherited deficiency of GABA transaminase, the breakdown enzyme, and with medications that specifically inhibit this enzyme. In severe liver disease, studies have observed an increased GABA effect in the brain. Raised values in blood or urine can also reflect increased production by gut bacteria or in the pancreas.

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