Mood, Metabolism, and the GABA–Glutamate Balance
Why nutrition, insulin signaling, and inflammation matter more than we think
Anxiety and depression are often discussed as “chemical imbalances,” yet we rarely pause to ask a more foundational question:
What fuels the chemistry of the brain in the first place?
At the center of mood regulation are two primary neurotransmitters with opposing roles:
Glutamate – the brain’s main excitatory neurotransmitter
GABA (gamma-aminobutyric acid) – the brain’s primary inhibitory, calming neurotransmitter
Mental health depends on balance, not dominance.
A simple way to visualize this
Glucose-driven metabolism + inflammation → glutamate dominance
Ketone-supported metabolism + micronutrient sufficiency → GABA stability
Excess glutamate without adequate GABA creates a chronically “wired” brain.
The balance between GABA and glutamate functions like a neurological seesaw. When this system is well regulated, focus is clear, mood is stable, sleep is restorative, and stress responses are appropriately modulated. When the balance is disrupted and excitatory signaling outweighs inhibitory control, the nervous system shifts into a state of overactivation. Anxiety, panic, irritability, insomnia, and persistent rumination can emerge. Depression often presents alongside agitation or profound fatigue. Many individuals also experience heightened sensory sensitivity and a feeling of overwhelm, reflecting a brain that is no longer able to adequately dampen stimulation or restore calm.
Where insulin and blood sugar enter the picture
The brain is quite sensitive to fluctuations in glucose availability. Repeated blood sugar spikes drive increased insulin signaling, which over time can lead to hyperinsulinemia and a pro-inflammatory state within the nervous system. Neuroinflammation, in turn, impairs the brain’s ability to clear excess glutamate, resulting in excitotoxic stress on neurons. Clinically, this helps explain why many patients experience anxiety after carbohydrate-heavy meals, mood crashes during episodes of hypoglycemia, and worsening depressive symptoms in the context of metabolic syndrome or insulin resistance. Mood is not separate from metabolism—it is a direct reflection of it.
Benzodiazepines and the GABA problem
Benzodiazepines such as Xanax, Ativan, Klonopin, and Valium do not create or replenish GABA; instead, they bind to GABA-A receptors and amplify inhibitory signaling by forcing the system to respond more strongly. This process bypasses the brain’s own GABA production pathways, which over time can lead to downregulation of GABA receptors, reduced endogenous GABA synthesis, and the development of tolerance, dependence, and rebound anxiety. When these medications are reduced or withdrawn, excitatory glutamate signaling may dominate, leaving the nervous system in a heightened state of reactivity. This is not a moral failure or lack of willpower—it is biochemistry. Without adequate nutritional and metabolic support, the brain often struggles to re-establish balance on its own.
Nutrients essential for GABA production
GABA is synthesized from glutamate via the enzyme glutamate decarboxylase, which requires key cofactors:
Core nutrients
Vitamin B6 (P5P) – non-negotiable for GABA synthesis
Magnesium – stabilizes NMDA/glutamate receptors
Zinc – modulates GABA receptor function
Taurine – GABA-mimetic and membrane stabilizer
Glycine – inhibitory neurotransmitter, supports sleep
L-theanine – increases GABA and alpha-wave activity. In alpha state, sensory input is filtered more efficiently, reducing overwhelm.
Deficiencies here quietly push the brain toward excitability.
How to support GABA through daily diet
Food sources that matter
Vitamin B6
Wild-caught salmon
Pasture-raised poultry
Sunflower seeds
Pistachios
Magnesium
Pumpkin seeds
Almonds
Spinach
Dark leafy greens
Zinc
Oysters
Grass-fed beef
Pumpkin seeds
Taurine
Shellfish
Dark meat poultry
Glycine
Bone broth
Collagen
Gelatin-rich cuts
Sample GABA-supportive meals
Breakfast
Pasture-raised eggs cooked in olive oil with a side of sautéed spinach and some smoked wild caught salmon
Lunch
Bone broth–based soup with chicken and vegetables like carrots onions and zucchini with a side mixed greens salad with pumpkin seeds sprinkled on top
Dinner
Grass-fed beef or lamb with a side of roasted vegetables such as cauliflower and broccoli always with a generous drizzle of high polyphenol containing (Hypereleon) olive oil
These meals stabilize blood sugar and neurotransmitter balance.
Targeted supplements (when appropriate)
Clinical nutrition often requires more than food alone, especially when deficiencies are present.
Commonly used supports include:
Magnesium glycinate or threonate
Vitamin B6 as P5P
L-theanine
Taurine
Glycine
Zinc (balanced with copper when needed)
These should be individualized, especially in patients tapering medications or with trauma-sensitive nervous systems.
Where Ketogenic Metabolic Therapy fits in
Ketogenic Metabolic Therapy (KMT) shifts the brain’s primary fuel source from glucose to ketones, creating a fundamentally different metabolic environment for neural function. Ketones reduce neuroinflammatory signaling, improve mitochondrial efficiency, and lower glutamate-driven excitotoxicity while simultaneously enhancing GABAergic tone. By stabilizing insulin and cortisol rhythms, this metabolic shift supports a calmer, more resilient nervous system. This is why ketogenic approaches are increasingly being explored for anxiety disorders, treatment-resistant depression, bipolar spectrum conditions, PTSD, and other neuroinflammatory mood disorders. You can find more about this research at the Metabolic Mind website, some very brilliant minds at work there. This approach is not about restriction or deprivation—it is about fueling the brain in a way that better supports regulation, stability, and healing.
A closing thought
Depression and anxiety are not simply emotional experiences.
They are reflections of brain energy, inflammation, and nutrient availability.
When we address blood sugar regulation, insulin signaling, inflammation, micronutrient sufficiency, and neurotransmitter balance together, we begin to support the nervous system at its foundations. Rather than chasing symptoms, this integrated approach restores the biochemical conditions the brain needs to function optimally. In response, the nervous system often regains clarity, calm, and resilience, allowing mood, cognition, and stress tolerance to improve in a more sustained and physiologic way.
Call to Action
At Katallage Wellness, we support mental health through personalized nutrition and metabolic care, working alongside medical and therapeutic teams.
If you or your patients are struggling with anxiety, depression, or mood instability—and suspect metabolism may be part of the story—nutrition support can be a powerful starting point.
Learn more or schedule a nutrition consultation
www.KatallageWellness.com | Integrative & Functional Nutrition Care