Last Updated: September 28 2022

GABA is the 'downer' neurotransmitter that counters glutamate (upper), as the two mediate brain activation in a Yin-Yang manner. Highly important in the brain, oral ingestion of GABA is complex due to its difficulty in crossing the blood brain barrier.

GABA is most often used for

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GABA (Gamma-Aminobutyric Acid) is one of the more potent depressive neuroactive peptides in human brain tissue. It is involved in a wide range of suppressive and depressive activities intimate with the parasympathetic nervous system (PNS). It is synthesized directly from the excitatory neurotransmitter glutamate via the enzyme glutamate decarboxylase and can be reverse transformed to glutamate via the tricarboxylic acid cycle.[1]


GABA Regulation

It appears that changes in brain GABA concentrations and systemic GABA concentrations can be reflective of each other, and that changes in one of these markers induces changes in the other.[2]

Its uptake into the brain is high at nonphysiologically low levels[3] and has low uptake rates at higher nonphysiological concentrations. This phenomenon is caused by GABA being a self-inhibitor of its transport into the brain, able to block its own transport in doses above what is normal.[4] By this mechanism, neurological GABA levels stay constant.

Self-inhibition of GABA cannot stop all transport into the brain, and the highest recorded value of inhibition has been 80%.[4] Therefore superloading GABA might be able to overcome self-inhibition by passive diffusion.

In cases of supraphysiological GABA levels in the brain, the brain is able to eject excess GABA. The blood brain barrier's efflux rate for GABA is approximately 16 times as potent as the uptake rate, and is activated during periods of excessive GABA concentrations in neurological tissue as to prevent excessive depressive effects.[5]


GABA and the Blood Brain Barrier

In adults, GABA in systemic circulation seems to have very minimal uptake rates into brain tissue.[6] Youth seem to have greater blood brain barrier (BBB) permeability.[4] It appears to suppress its own entry across the blood brain barrier when in systemic excess, and shares this ability with beta-alanine, although GABA was more potent in this regard.[4]

Nitric oxide (NO) seems to be able to increase blood brain barrier permeability to GABA significantly.[7]


GABA and Growth Hormone

It was initially thought that GABA ingestion increases Growth Hormone secretion, although this is true to a degree earlier studies[8] have clarified 'Growth Hormone' into a more specific subset of analogues. Immunoreactive Growth hormone (irGH) and Immunofunctional Growth Hormone (ifGH) are two analogues which appear to be elevated in vivo after oral administration of GABA.

Despite GABAs inefficacy in passing the BBB, it appears to induce these changes via neurological means, more specifically a reaction which is mediated via dopamine release at a suprapituitary level.[9]

GABAs influence on GH secretion seems to be changed with resistance exercise. A greater overall area-under-curve and higher peak values are noted with the pairing.[10] Interestingly, the peak value with exercise occurs 30 minutes after ingestion yet 75 minutes during rest.[10] These augmenting effects may be due to exercise-induced NO potentiating GABA entry into the brain, as alluded to in the previous section.

Although it was not concluded in the previous study that the effects of GABA on growth hormone were direct (as hepatic biotransformation of GABA to other amines is a possibility), the researchers suspect it may be so.

It should be noted that Growth Hormone exists in over 100 different isoforms, and that irGH and ifGH may not exert the same benefits typically associated with the most common (22kDa) isoform of Growth Hormone.[11][12]

1.^Petroff OAGABA and glutamate in the human brainNeuroscientist.(2002 Dec)
7.^Shyamaladevi N, Jayakumar AR, Sujatha R, Paul V, Subramanian EHEvidence that nitric oxide production increases gamma-amino butyric acid permeability of blood-brain barrierBrain Res Bull.(2002 Jan 15)
8.^Cavagnini F, Invitti C, Pinto M, Maraschini C, Di Landro A, Dubini A, Marelli AEffect of acute and repeated administration of gamma aminobutyric acid (GABA) on growth hormone and prolactin secretion in manActa Endocrinol (Copenh).(1980 Feb)
9.^Cavagnini F, Benetti G, Invitti C, Ramella G, Pinto M, Lazza M, Dubini A, Marelli A, Müller EEEffect of gamma-aminobutyric acid on growth hormone and prolactin secretion in man: influence of pimozide and domperidoneJ Clin Endocrinol Metab.(1980 Oct)
10.^Powers ME, Yarrow JF, McCoy SC, Borst SEGrowth hormone isoform responses to GABA ingestion at rest and after exerciseMed Sci Sports Exerc.(2008 Jan)
11.^Nindl BC, Kraemer WJ, Marx JO, Tuckow AP, Hymer WCGrowth hormone molecular heterogeneity and exerciseExerc Sport Sci Rev.(2003 Oct)
12.^De Palo EF, Gatti R, Antonelli G, Spinella PGrowth hormone isoforms, segments/fragments: does a link exist with multifunctionalityClin Chim Acta.(2006 Feb)