What is the evidence base for the ketogenic diet in the treatment of schizophrenia, bipolar disorder, and schizoaffective disorder?

From the Guidelines

The ketogenic diet may be considered as an adjunctive treatment for schizophrenia, bipolar disorder, and schizoaffective disorder, but its use should be approached with caution and under medical supervision, as the current evidence is limited and inconclusive. The standard ketogenic diet consists of approximately 70-80% fat, 15-20% protein, and 5-10% carbohydrates, typically limiting carbs to 20-50g daily. Implementation should occur under medical supervision, particularly for patients on medications like valproate, lithium, or antipsychotics, as the diet may affect medication levels and metabolic parameters, as noted in the American Psychiatric Association's practice guideline for the treatment of patients with schizophrenia 1.

Key Considerations

• Gradual introduction over 2-4 weeks is recommended to minimize side effects like the "keto flu."
• Patients should be monitored for ketone levels (optimal range 1.5-3.0 mmol/L), medication interactions, and metabolic parameters.
• The diet's potential benefits stem from its ability to reduce neuroinflammation, stabilize glutamate levels, improve mitochondrial function, and increase GABA production, all of which may help regulate mood and reduce psychotic symptoms.
• Larger clinical trials are needed before the ketogenic diet can be broadly recommended as a standard treatment approach for these serious psychiatric conditions.

Limitations and Future Directions

• A recent systematic review with a meta-analysis of 41 RCTs assessed the effect of lifestyle interventions for weight management among people with severe mental disorders, including schizophrenia, schizoaffective disorder, or bipolar disorder, and found little support for implementing individualized lifestyle interventions to counteract weight gain in these populations 1.
• The generalizability of the findings is limited because people with severe symptoms of severe mental disorders, substance use disorders, or comorbid medical disorders were often excluded from studies.
• Further research could evaluate interventions designed to affect other causes of unhealthy lifestyle, such as loneliness and low socioeconomic status, or structural interventions facilitating healthy food and attractive possibilities for physical activity.

From the Research

Overview of Ketogenic Diet in Schizophrenia, Bipolar Disorder, and Schizoaffective Disorder

• The ketogenic diet has been explored as a potential therapeutic approach for schizophrenia, bipolar disorder, and schizoaffective disorder due to its effects on metabolic and psychiatric health 2, 3, 4, 5, 6.
• Studies have shown that the ketogenic diet may improve psychiatric symptoms, metabolic dysfunctions, and body composition in patients with these conditions 4, 5.

Mechanisms and Rationale

• The ketogenic diet provides an alternative fuel to glucose for bioenergetic processes in the brain, which may help normalize schizophrenia-like behaviors in animal models 4.
• The diet has been shown to alleviate inflammation and oxidative stress, modulate the gut microbiota community, and improve metabolic health markers, which may be beneficial for patients with serious mental illness 3.

Clinical Trials and Studies

• A randomized controlled clinical trial protocol has been developed to investigate the effects of a modified ketogenic diet on mental health and metabolic outcomes in schizophrenia and bipolar disorder 2.
• A pilot trial has shown improvements in metabolic health and psychiatric symptoms in individuals with schizophrenia or bipolar disorder who followed a ketogenic diet 5.
• Case studies and open trials have also reported positive effects of the ketogenic diet on psychiatric symptoms and metabolic outcomes in patients with these conditions 3, 4.

Limitations and Future Directions

• The number of clinical trials assessing the effect of the ketogenic diet on serious mental illness is still limited, and larger-scale studies are needed to confirm the findings 3, 6.
• The translation of basic research findings to clinical settings presents a complex issue, and more research is needed to examine the molecular mechanisms of the ketogenic diet against psychiatric diseases 6.
• Strict care and supervision by a physician and dietitian are recommended when initiating the ketogenic diet due to potential side effects and interactions with pharmacotherapy 3.