If your dog has epilepsy, you may have heard about the role of glutamate and GABA in managing seizures. These two neurotransmitters are the key players in brain chemistry, and their delicate balance determines whether the brain is calm or overstimulated. Understanding this relationship can help you make informed decisions about dietary and treatment options to help manage your dog’s epilepsy.
In this post, we’ll explore how glutamate and GABA interact in the brain, why this balance is so important for preventing seizures, and how changes in diet—especially a ketogenic diet—can support this balance.
What Are Glutamate and GABA?
Glutamate and GABA are neurotransmitters, which means they are chemicals that help brain cells communicate with one another. Think of them as the brain’s “on” and “off” switches:
Glutamate
Glutamate is the brain’s main excitatory neurotransmitter. It “excites” brain cells, helping them to fire signals and stay active. Glutamate is crucial for learning, memory, and everyday brain function, but too much of it can lead to overstimulation. In dogs with epilepsy, excessive glutamate activity can trigger seizures.
GABA
GABA (gamma-aminobutyric acid), on the other hand, is the brain’s main inhibitory neurotransmitter. It helps calm brain cells down by “inhibiting” their activity. You can think of GABA as the brain’s “brake pedal”, helping to slow down nerve activity and keep things under control. Low GABA levels or reduced GABA function can make the brain more prone to seizures.
The brain constantly works to keep these two chemicals in balance, ensuring there is just the right amount of excitatory and inhibitory activity. However, when this balance is tipped—especially with too much glutamate and not enough GABA—it can lead to seizures.
How Glutamate and GABA Imbalance Triggers Seizures
In a healthy brain, glutamate and GABA levels work in harmony to maintain stable brain function. But in dogs with epilepsy, this balance can be disrupted. Here’s what happens when there’s too much glutamate and not enough GABA:
Excessive Excitation: When there’s an overabundance of glutamate, it overstimulates the brain’s neurons, making them fire more rapidly than they should. This increased excitability can lead to the development of a seizure.
Reduced Inhibition: If GABA levels are too low, the brain’s natural inhibitory system is weakened. Without enough GABA to slow things down, the brain becomes more prone to runaway electrical activity, leading to seizures.
This imbalance between glutamate and GABA is one of the core issues in epilepsy. Research has shown that abnormal glutamate activity is strongly linked to seizure generation, while increasing GABA levels can help control seizures by calming overactive brain cells.
The Glutamate-GABA Cycle: Keeping the Brain in Balance
To understand how to manage this balance, it’s important to know about the glutamate-GABA cycle. This is the brain’s way of recycling these two neurotransmitters to ensure proper levels are maintained.
Here’s how it works:
Glutamate is released by neurons to excite other brain cells.
After it has done its job, glutamate is absorbed by special brain cells called astrocytes, which help prevent glutamate from building up in the brain.
The astrocytes then convert glutamate into glutamine, which is sent back to the neurons.
Neurons can use this glutamine to either make more glutamate or convert it into GABA.
This cycle is crucial for maintaining the right levels of both glutamate and GABA. However, in epilepsy, this cycle can become disrupted, leading to excessive glutamate and reduced GABA.
Have Questions About Canine Epilepsy?
Join our online community of epileptic pet owners who can help you through this journey. We know how stressful it can be caring for an epileptic dog, and we are here to help.
How the Ketogenic Diet Can Help Balance Glutamate and GABA
One of the most promising dietary interventions for epilepsy is the ketogenic diet. Originally developed to treat epilepsy in humans, the ketogenic diet has gained attention for its effectiveness in reducing seizures, including in dogs.
So, how does the ketogenic diet work when it comes to balancing glutamate and GABA?
Increasing GABA Production: The ketogenic diet encourages the brain to convert more glutamate into GABA. By providing an alternative energy source (ketones), the brain shifts its metabolic focus and begins to favour the production of GABA over glutamate. This increased GABA helps to calm the brain, reducing seizure activity.
Reducing Glutamate Levels: The ketogenic diet also helps by lowering glutamate levels in the brain. By reducing the amount of available glutamate, the brain becomes less excitable, decreasing the likelihood of seizures. This is particularly important in dogs with epilepsy, where glutamate excitotoxicity—a condition where too much glutamate causes damage to neurons—can worsen seizure activity.
Stabilising Brain Energy: The ketogenic diet changes the brain’s energy source from glucose (sugar) to ketones, which are produced from fat. This shift in energy metabolism not only reduces inflammation but also protects brain cells from the oxidative stress that can accompany seizures. By reducing stress on the brain and improving energy stability, the ketogenic diet helps maintain a more balanced brain environment, reducing seizure risk.
The Role of Diet in Managing Epilepsy
While medications remain the first line of treatment for epilepsy, dietary changes can play a powerful supportive role—particularly when it comes to balancing glutamate and GABA.
A high-fat, low-carbohydrate ketogenic diet helps to regulate brain chemistry by:
Reducing excitatory glutamate: By shifting the brain’s energy source, the ketogenic diet reduces the production of glutamate, lowering the brain’s overall excitability.
Increasing inhibitory GABA: The diet promotes the conversion of glutamate into GABA, boosting the brain’s ability to calm itself down and prevent seizures.
Improving brain metabolism: Ketones provide a more efficient energy source, protecting the brain from oxidative stress and inflammation that can worsen seizure activity.
In Summary: Keto Diets can Balance Brain Chemistry for Dogs with Seizures
The balance between glutamate and GABA is critical in managing epilepsy. Glutamate, as the brain’s excitatory neurotransmitter, plays an important role in brain activity but can become problematic when levels are too high. GABA, the inhibitory neurotransmitter, helps keep brain activity in check. When there’s too much glutamate and not enough GABA, the brain becomes overexcited, leading to seizures.
By making dietary changes—particularly through the ketogenic diet—you can help restore this balance. The ketogenic diet reduces glutamate levels and promotes the production of GABA, creating a more stable brain environment that is less prone to seizures. While every dog is different, and results may vary, understanding the interaction between these key neurotransmitters can empower you to make informed decisions about your dog’s epilepsy management.
Has Dogileptic Helped You and Your Epi Pup 🐶?
Running this site takes resources, and we rely on donations to keep information free and accessible. If our site has helped you, please consider giving back to support our mission.
Your donation means the world to us and to dogs we help 💕
References:
Yudkoff, Marc, et al. "Ketosis and brain handling of glutamate, glutamine, and GABA." Epilepsia 49 (2008): 73-75.
Barker-Haliski, Melissa, and H. Steve White. "Glutamatergic mechanisms associated with seizures and epilepsy." Cold Spring Harbor perspectives in medicine 5.8 (2015): a022863.
Chen, Tsang-Shan, et al. "The role of glutamate receptors in epilepsy." Biomedicines 11.3 (2023): 783.
Doherty, James, and Raymond Dingledine. "The roles of metabotropic glutamate receptors in seizures and epilepsy." Current Drug Targets-CNS & Neurological Disorders 1.3 (2002): 251-260.
Chapman, Astrid G. "Glutamate and epilepsy." The Journal of nutrition 130.4 (2000): 1043S-1045S.
Sarlo, Gabrielle L., Amy Kao, and Kathleen F. Holton. "Investigation of the low glutamate diet as an adjunct treatment for pediatric epilepsy: A pilot randomized controlled trial." Seizure: European Journal of Epilepsy 106 (2023): 138-147.
Yudkoff, Marc, et al. "The ketogenic diet and brain metabolism of amino acids: relationship to the anticonvulsant effect." Annu. Rev. Nutr. 27.1 (2007): 415-430.
Yudkoff, Marc, et al. "Ketogenic diet, brain glutamate metabolism and seizure control." Prostaglandins, leukotrienes and essential fatty acids 70.3 (2004): 277-285.
Zhang, Yifan, et al. "The anticonvulsant effects of ketogenic diet on epileptic seizures and potential mechanisms." Current neuropharmacology 16.1 (2018): 66-70.
Olson, Christine A., et al. "The gut microbiota mediates the anti-seizure effects of the ketogenic diet." Cell 173.7 (2018): 1728-1741.
Symes, John B. "Food intolerance, epilepsy, and" the GARD"[glutamate-aspartate restricted diet]." (2007): 66-68.
Symes, John B. "Idiopathic epilepsy-the dietary solution." (2008): 88-90.
Schmidt, Teresa, et al. "Urinary neurotransmitter patterns are altered in canine epilepsy." Frontiers in veterinary science 9 (2022): 893013.
Verdoodt, Fien, et al. "The role of nutrition in canine idiopathic epilepsy management: Fact or fiction?." The Veterinary Journal 290 (2022): 105917.
Schmidt, T., Meller, S., Meyerhoff, N., Twele, F., Zanghi, B., & Volk, H. A. (2023). STUDY PROTOCOL.
Vendramini, Thiago HA, et al. "Ketogenic diets: A systematic review of current scientific evidence and possible applicability in dogs and cats." Journal of Animal Physiology and Animal Nutrition 108.2 (2024): 541-556.
Peek, Saskia I., et al. "Epilepsy is more than a simple seizure disorder: Parallels between human and canine cognitive and behavioural comorbidities." The Veterinary Journal 303 (2024): 106060.
Coates, Joan R., and Robert L. Bergman. "Seizures in young dogs and cats: pathophysiology and diagnosis." seizure 5 (2005): 18.
Bough, K.J.; Gudi, K.; Han, F.T.; Rathod, A.H.; Eagles, D.A. An anticonvulsant profile of the ketogenic diet in the rat. Epilepsy Res., **2002**, 50(3), 313-325.
Melø, T.M., Nehlig, A., Sonnewald, U., 2006. Neuronal-glial interactions in rats fed a ketogenic diet. Neurochemistry International 48, 498-507.
Maalouf, M.; Sullivan, P.G.; Davis, L.; Kim, D.Y.; Rho, J.M. Ke- tones inhibit mitochondrial production of reactive oxygen species production following glutamate excitotoxicity by increasing NADH oxidation. Neuroscience, 2007, 145(1), 256-264.
Erecinska M, Nelson D, Daikhin Y, Yudkoff M. Regulation of GABA level in rat brain synaptosomes: fluxes through enzymes of the GABA shunt and effects of glutamate, calcium and ketone bodies. J Neurochem. 1996; 67:2325–34.
Juge, N., Gray, J.A., Omote, H., Miyaji, T., Inoue, T., Hara, C., Uneyama, H., Edwards, R.H., Nicoll, R.A., Moriyama, Y., 2010. Metabolic control of vesicular glutamate transport and release. Neuron 68, 99-112.
Comments