Effects of GABA food supplement on brain and behavior

Neurotransmitters as food supplements: the effects of GABA on brain and behavior – free full-text /PMC4594160/ – Front Psychol. Oct 2015

Finding this study in PubMed/PMC shows that such supplements are being taken seriously by scientists. To me, that sounds like an endorsement…

Gamma-aminobutyric acid (GABA) is the main inhibitory neurotransmitter in the human cortex. The food supplement version of GABA is widely available online.  …it is unclear whether these supplements confer benefits beyond a placebo effect.

There is some evidence in favor of a calming effect of GABA food supplements, but most of this evidence was reported by researchers with a potential conflict of interest.  

It has long been thought that GABA is unable to cross the blood–brain barrier (BBB), but the studies that have assessed this issue are often contradictory and range widely in their employed methods.

We suggest that any veridical [true] effects of GABA food supplements on brain and cognition might be exerted through BBB passage or, more indirectly, via an effect on the enteric nervous system.


Hundreds of people report that these supplements have helped them alleviate anxiety and/or improve sleep quality, in addition to other beneficial effects.

Interestingly, GABA has long been thought to be unable to cross the blood–brain barrier (BBB), which raises questions about the mechanisms of action behind such beneficial effects

The current paper aims to give a succinct overview of recent understanding of

  • GABA’s BBB permeability (Blood–Brain Barrier Permeability),
  • the role of GABA in treatment of diseases (GABA, Diseases, and Treatment),
  • its role as a food supplement (GABA as a Food Supplement), and
  • the possibility that this food supplement might affect the central nervous system through an effect on the enteric nervous system (Enteric Nervous System Effects of GABA).

GABA, Diseases, and Treatment

Increasing GABA in the brain has for years been the focus of drug development aiming to alleviate the severity of epileptic seizures

BBB permeability to GABA decreases with age

The GABA analog gabapentin [Neurontin] was developed as an anti-epileptic drug. Gabapentin functions by modulating enzymes involved in GABA synthesis.

One MRS study in humans has found that the administration of gabapentin increased brain GABA levels by 55.7%.

Nonetheless, a study exploring the effects of gabapentin in both rat and human neocortical slice preparations suggests that there might be a considerable difference between rodents and humans in the effects on GABA levels: gabapentin was found to increase GABA concentrations by 13% in human neocortical slices, while having no significant effect in rat neocortical slices

Here we are reminded that most studies of biological and even psychological processes are done in rodents. That gives us clues, but the effects found may not apply to humans at all.

Pain/opioid studies in rodents are completely senseless when pain is supposedly a bio-psycho-social disorder.

You can’t have it both ways:

  • if pain is a bio-psycho-social disorder, then rodent experiments are useless, but
  • if pain is mainly nociception, then rodent studies could be useful.

It angers me when the same people insisting that pain is a bio-psycho-social disorder use studies on rodents to “prove” their assumptions about pain.


In this paper we have discussed the conflicting evidence with regards to GABA’s BBB permeability. There are both a number of studies that were unable to show that GABA crosses the BBB and a number of studies that did show GABA’s ability to cross.

In view of the multitude of employed methods and species, in addition to the finding that GABA metabolism might differ between rodents and humans (Errante et al., 2002), it is not possible at this time to come to a definite conclusion with regards to GABA’s BBB permeability in humans.

Interestingly, in one of the discussed studies with rats, GABA by itself was found to increase brain GABA by 33%, but when GABA was administered together with L-arginine, brain GABA increased by 383.3%.

The authors suggest that this dramatic increase in brain GABA might be caused by an L-arginine-mediated increase in nitric oxide, which is thought to affect BBB permeability (Shukla et al., 1996). It would be interesting to see if this effect can be replicated in humans.

There is some evidence for the claims made by hundreds of consumers online concerning the calming effects of GABA food supplements, but evidence from independent studies is needed.

In addition, even if a calming effect of GABA can be reliably demonstrated, the mechanism through which these supplements work is unclear.

I really don’t care about the mechanism if the supplement works.

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