Can Metabolism Shape Mental Health?

What New Research Suggests About the Ketogenic Diet and Schizophrenia

For more than a century, schizophrenia has been explained through the lens of neurotransmitters—especially dopamine. But an emerging wave of research is painting a different, and surprisingly empowering, picture: the brain’s energy supply may be one of the most important forces shaping mental health.

A new review published in the Journal of Inflammation Research (Hung et al., 2025) explores this idea through a fascinating question:

Could the ketogenic diet—originally used for epilepsy—help stabilize schizophrenia by restoring brain energy balance and reducing inflammation?

The answer, based on early clinical evidence and strong biological reasoning, is: possibly yes.

What This Review Found

The authors bring together clinical case reports, small pilot trials, animal studies, and molecular research.

Their thesis is clear:

Schizophrenia involves not just neurotransmitters, but deep disturbances in brain energy metabolism, inflammation, and mitochondrial function. The ketogenic diet appears to counteract several of these mechanisms at once.

This insight shifts the focus from “brain chemicals” to brain energy—a refreshing and more holistic way to understand mental health.

Early Clinical Evidence: Small Studies, Big Signals

Although research is still early, several case reports and pilot studies show promising results:

• 50% reduction in symptom severity in some patients

• Full remission in a handful of long-term cases

• Better sleep, cognition, and daily functioning

• Consistent weight loss and improved metabolic health

One of the most striking reports includes two patients who remained in full remission for 5 to 12 years while maintaining a ketogenic lifestyle.

These results are not definitive—but they are too compelling to ignore.

Why Might the Ketogenic Diet Help?

Three Key Mechanisms

1. It Calms Brain Inflammation

Schizophrenia is increasingly understood as a neuroinflammatory condition. Overactive microglial cells (the brain’s immune cells) prune synapses, generate oxidative stress, and disrupt neural circuits.

The ketogenic diet produces β-hydroxybutyrate (BHB), a natural anti-inflammatory molecule that:

• Inhibits the NLRP3 inflammasome

• Reduces IL-6, IL-1β, and TNF-α

• Protects synapses from excessive pruning

In short: it quiets a chronically inflamed brain.

2. It Supports Mitochondria—The Brain’s Power Stations

People with schizophrenia often show:

• impaired glucose metabolism

• reduced mitochondrial efficiency

• high oxidative stress

Ketones burn “cleaner” than glucose, producing:

• more ATP per molecule

• fewer reactive oxygen species

• a higher NAD⁺/NADH ratio (better redox control)

This lifts the brain out of an energy-deprived state and helps stabilize neural networks.

3. It Rebalances the Immune System

The ketogenic state suppresses Th17-driven inflammation and promotes regulatory T cells (Tregs), shifting the body from inflammatory mode to repair mode.

This is crucial because many schizophrenia pathways—including interneuron damage—are fueled by immune dysregulation.

Who Is Most Vulnerable to Brain Bioenergetic Insufficiency?

One of the most important ideas, often overlooked in psychiatry, is that not everyone begins with the same bioenergetic reserve.

Some people enter adulthood with a lower margin of safety. For example:

✔ Severe anemia

→ reduces oxygen delivery, lowering ATP availability in the brain.

✔ Thalassemia or chronic hemolytic disorders

→ cause chronic inflammation, oxidative stress, and mitochondrial strain.

✔ Nutritional deficiencies

→ lower mitochondrial function, antioxidant capacity, and neurotransmitter synthesis.

✔ Chronic illnesses or infections

→ compete for energy, leaving less available for the brain.

For individuals with these underlying stressors, the brain becomes more vulnerable. Even normal life challenges—sleep disruption, psychological stress, infections, poor diet—can tip an already fragile system into neuroinflammation, oxidative stress, and disrupted neural circuits.

This may help explain why some people are more susceptible to schizophrenia or other mental health disorders, while others exposed to the same life stressors are not.

The Deep Message: Mental Health Begins With Metabolic Health

This new line of research doesn’t claim that the ketogenic diet is a universal cure. It’s not. Larger trials are still needed, and KD is not appropriate for everyone.

But it does suggest:

• The brain is exquisitely sensitive to energy shortages.

• Restoring metabolic stability can improve psychiatric symptoms.

• Some mental illness may reflect a reversible state of bioenergetic maladaptation rather than permanent damage.

And this offers hope.

If part of schizophrenia’s biology is driven by low energy, chronic inflammation, and mitochondrial strain, then interventions that restore energy availability—including dietary therapies—may unlock new pathways to recovery.

Reference

Hung, A. A., Krycer, J. R., Sarnyai, Z., Palmer, C. M., & Navarro, S. (2025). The ketogenic diet: An anti-inflammatory treatment for schizophrenia? Journal of Inflammation Research, 18, 16761–16771. https://doi.org/10.2147/JIR.S540859