GABA and Ketogenic Diets

Estimated reading time: 5 minutes

We need to talk about the role of GABA in mental illness and neurological disorders. And then, I am going to explain to you why ketones can help regulate this neurotransmitter.

What is GABA?

GABA (gamma-aminobutyric acid) is the main inhibitory neurotransmitter in the brain, and it plays a critical role in regulating neuronal excitability and maintaining the balance between neuronal excitation and inhibition.

GABAergic dysfunction has been implicated in a wide range of psychiatric and neurological disorders, including anxiety disorders, depression, epilepsy, schizophrenia, and autism spectrum disorders.

Changes in GABA signaling can alter the balance between excitatory and inhibitory neurotransmission in the brain, leading to various symptoms depending on the affected brain regions and circuits.

What diagnoses see problems with GABA?

Lots.

Anxiety disorders and depression are often characterized by an imbalance between excitatory and inhibitory neurotransmission in brain regions such as the amygdala and prefrontal cortex. Reduced GABA signaling in these regions can lead to increased neuronal excitability and hyperarousal, which may contribute to anxiety and mood disorders.

Epilepsy is a neurological disorder characterized by recurrent seizures, and it is often associated with perturbations in GABA signaling. Reduced GABA signaling can lead to hyperexcitability and seizure activity, while increased GABA signaling can lead to sedation and anticonvulsant effects.

Schizophrenia is a complex psychiatric disorder that is associated with abnormalities in multiple neurotransmitter systems, including GABA. Reduced GABA signaling in the prefrontal cortex and other brain regions has been implicated in the cognitive deficits and positive symptoms (such as hallucinations and delusions) of schizophrenia.

Autism spectrum disorders are neurodevelopmental disorders that are characterized by impaired social communication and repetitive behaviors. GABAergic dysfunction has been implicated in the pathophysiology of autism, and alterations in GABA signaling have been observed in several brain regions in individuals with autism.

Ketones and GABA

What does all this have to do with a ketogenic diet? I am going to tell you. Because I want you to understand all the ways you can feel better. ⬇️

D-β-hydroxybutyrate (BHB; a ketone body) has been shown to enhance GABA signaling in the brain, which may have beneficial effects on cognitive function and neurological disorders.

Acetoacetate (another ketone body) has also been shown to modulate GABA signaling in the brain. We are still figuring out how, but the effect is absolutely there.

One proposed mechanism for acetoacetate’s effect on GABA signaling is that it may increase the availability of GABA by enhancing the activity of the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD).

GAD (enzyme) requires the cofactor pyridoxal 5′-phosphate (PLP) for its activity, and acetoacetate (a ketone body) has been shown to increase the availability of PLP in the brain. This may result in increased GABA synthesis and release, leading to enhanced GABA signaling. For those that don’t know, PLP is the active form of B6. Vitamin B6 is involved in the metabolism of amino acids, the synthesis of neurotransmitters such as serotonin and dopamine, and the regulation of gene expression.

Note: This is why I like to combine ketogenic diets with increased nutrient intake during healing. There are synergistic effects!

Another proposed mechanism is that acetoacetate may modulate GABA receptors, which are the proteins that mediate the effects of GABA on neuronal excitability.

Acetoacetate has been shown to enhance the activity of GABA-A receptors in the brain. GABA is a neurotransmitter in the brain that helps control brain activity. There are two types of receptors that GABA can bind to, called GABA-A and GABA-B receptors. GABA-A receptors act quickly to stop neurons from firing, while GABA-B receptors work more slowly to reduce activity in the brain. Both types of receptors are important for maintaining a balance between brain activity and relaxation.

Conclusion

So there you have it. Now you understand more about how a ketogenic diet helps balance the neurotransmitter GABA and the implications this has for the treatment of many neurological disorders and mental illnesses.

Go forth and make a better-informed decision in your recovery from mental illness and neurological disorder!

If you do a search on this blog (bottom of page) on your diagnosis, you will likely find an article that talks about disturbed GABA as it applies to your particular diagnosis. Here are some of those you might be interested in!

Obsessive-Compulsive Disorder (OCD)

Panic Disorder (PD)

Can keto treat my depression without medication?

And if you need help learning how to implement a ketogenic diet and personalizing your supplementation and lifestyle changes toward a better brain, you are welcome to check out my Brain Fog Recovery Program.

Brain Fog Recovery Program

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References

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Cahill, G. F. (2006). Fuel metabolism in starvation. Annual review of nutrition, 26, 1-22. DOI: 10.1146/annurev.nutr.26.061505.111258

D’Andrea Meira, I., Romão, T. T., Pires, D. O., da Silva-Maia, J. K., & de Oliveira, G. P. (2021). Ketogenic diet and epilepsy: what we know so far. Frontiers in neuroscience, 15, 684557. DOI: 10.3389/fnins.2021.684557

Lutas, A., & Yellen, G. (2021). The ketogenic diet: metabolic influences on brain excitability and epilepsy. Trends in neurosciences, 44(6), 383-394. DOI: 10.1016/j.tins.2021.02.004

Newman, J. C., & Verdin, E. (2014). Ketone bodies as signaling metabolites. Trends in endocrinology and metabolism, 25(1), 42-52. DOI: 10.1016/j.tem.2013.09.002

Sleiman, S. F., Henry, J., Al-Haddad, R., El Hayek, L., Abou Haidar, E., Stringer, T., … & Ninan, I. (2016). Exercise promotes the expression of brain derived neurotrophic factor (BDNF) through the action of the ketone body β-hydroxybutyrate. eLife, 5, e15092. DOI: 10.7554/eLife.15092

Yamanashi, T., Iwata, Y. T., & Shibata, M. (2017). Neurochemical basis underlying the enhancement of GABAergic transmission by β-hydroxybutyrate in the rat hippocampus. Neuroscience letters, 643, 35-40. DOI: 10.1016/j.neulet.2017.02.019

Yudkoff, M., Daikhin, Y., & Nissim, I. (2020). Heterogeneity in ketone body metabolism in the developing and mature brain. Journal of inherited metabolic disease, 43(1), 30-37. DOI: 10.1002/jimd.12156