Ketogenic Diet for Schizophrenia

Overseen By Juliette Kyner, B.A.

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Northern California Institute of Research and Education

Must be taking: 2nd generation antipsychotics

Must not be taking: Glucose-lowering drugs

Disqualifiers: Cancer, Axis 1 disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

70 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether a high-fat, low-carbohydrate ketogenic diet can improve brain function in people with schizophrenia and bipolar disorder. The diet aims to use fats instead of sugars for energy, which may help stabilize brain networks and reduce inflammation. The ketogenic diet has shown potential benefits in treating psychiatric conditions by restoring brain energy metabolism.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must be stable on a 2nd generation anti-psychotic for schizophrenia or schizoaffective disorder. You cannot participate if you are taking glucose-lowering drugs (other than metformin) or weight loss pills.

Is the ketogenic diet safe for humans, especially for those with schizophrenia?

The ketogenic diet, which is high in fat and low in carbohydrates, has been shown to improve metabolic and cardiovascular health markers in overweight or obese individuals. It may also provide neuroprotective benefits and improve brain function in people with schizophrenia. However, more controlled clinical trials are needed to confirm its safety and benefits in this population. ^{1 2 3 4 5}

How is the ketogenic diet treatment for schizophrenia different from other treatments?

The ketogenic diet is unique for schizophrenia because it shifts the body's energy source from glucose to ketones, which may help improve brain function by providing an alternative fuel source. This diet also eliminates gluten, which might play a role in reducing symptoms, and it addresses impaired glucose metabolism, a core issue in schizophrenia. ^{1 3 4 5 6}

What data supports the effectiveness of the ketogenic diet treatment for schizophrenia?

Research suggests that a ketogenic diet, which is high in fats and low in carbohydrates, may help improve symptoms of schizophrenia by providing an alternative energy source for the brain and improving metabolic and neural stability. Some studies have shown that this diet can normalize schizophrenia-like behaviors in animal models and improve brain function in people with serious mental illness. ^{1 2 3 4 5}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with schizophrenia or schizoaffective disorder stable on second-generation antipsychotics, or bipolar disorder. Participants must speak English, have internet access, and be able to heat up ketogenic meals. They should commit to a 4-week ketogenic diet. Exclusions include current cancer diagnosis, other major psychiatric disorders, pregnancy/breastfeeding, type 1 diabetes, history of weight loss surgery or significant weight changes.

Inclusion Criteria

Speak, read, comprehend English

I have been diagnosed with schizophrenia, schizoaffective disorder, or bipolar disorder and am stable on medication.

Exclusion Criteria

I have been diagnosed with a mental health disorder.

I have been diagnosed with cancer.

I have been diagnosed with type 1 Diabetes Mellitus.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either a ketogenic diet or diet as usual for 4 weeks to assess changes in neural network instability, metabolic, and inflammatory indices.

4 weeks

Baseline and posttreatment assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment, including changes in network stability, body composition, systemic inflammation, and insulin resistance.

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketogenic diet

Trial Overview The study tests if a very low carbohydrate ketogenic diet can improve cognitive deficits in individuals with schizophrenia or bipolar disorder by stabilizing neural networks. The diet consists of roughly 70% fat, 20% protein, and 10% carbohydrates and aims to shift the brain's energy source from glucose to ketones.

How Is the Trial Designed?

Group I: Ketogenic Diet Experimental Treatment 1 Intervention

The ketogenic diet is a normo-caloric diet composed of high-fat (70%), low-carbohydrate (10%), and adequate protein (20%) that induces fasting-like effects and the production of ketone bodies. Metabolic Meals will be delivered to KETO subjects' homes via courier, consisting of 3 meals a day plus snacks, targeting 70% fat, 20% protein, 10% carbohydrates.

Group II: Diet as usual Active Control 1 Intervention

The Diet As Usual (DAU) participants will be asked to maintain their current dietary habits and will be discouraged from starting new diets during the 4-week study.

Who Is Running the Clinical Trial?

Northern California Institute of Research and Education

Lead Sponsor

Trials

30

Recruited

10,400+

Published Research Related to This Trial

A low-carbohydrate, ketogenic diet led to the unexpected resolution of long-term symptoms in a patient with schizophrenia, suggesting a potential dietary intervention for managing this condition.

The improvement may be linked to metabolic changes from eliminating gluten and possible cellular-level modulation of schizophrenia, indicating a novel approach to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: a case report and review of the literature. Kraft, BD., Westman, EC.[2021]

Recent studies indicate that individuals with schizophrenia may experience dysfunction in glucose and energy metabolism, which could contribute to their symptoms, providing a rationale for the use of a ketogenic diet.

The ketogenic diet has shown promise in preclinical models and case studies, improving psychiatric symptoms and metabolic issues in patients with schizophrenia, suggesting it could be a novel therapeutic approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diet for schizophrenia: clinical implication. Sarnyai, Z., Kraeuter, AK., Palmer, CM.[2020]

Chronic administration of β-hydroxybutyrate (BHB) in mice replicated the therapeutic effects of a ketogenic diet, normalizing behaviors associated with schizophrenia in a model using NMDA receptor antagonism.

BHB treatment not only reduced hyperactivity and improved social interaction but also addressed disruptions in sensory processing, suggesting it could be a promising alternative treatment for schizophrenia by improving cerebral glucose metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of beta-hydroxybutyrate administration on MK-801-induced schizophrenia-like behaviour in mice. Kraeuter, AK., Mashavave, T., Suvarna, A., et al.[2020]

Individuals with schizophrenia, even those who are medication-naïve, show disrupted insulin and glucose metabolism, increasing their risk for Type 2 diabetes and cardiovascular diseases.

A ketogenic diet may offer significant benefits for people with schizophrenia by improving brain metabolism, cognitive function, and overall metabolic health, suggesting a need for further clinical trials to explore its efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Role of Ketogenic Metabolic Therapy on the Brain in Serious Mental Illness: A Review. Sethi, S., Ford, JM.[2022]

The ketogenic diet (KD), characterized by high fat and low carbohydrate intake, has shown promise in reducing symptoms of various psychiatric disorders based on a review of 14 studies.

While the results indicate a positive response for individuals adhering to the KD, further research is needed to clarify the specific benefits and mechanisms of action in psychiatric conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of the ketogenic diet in the treatment of psychiatric disorders. Tillery, EE., Ellis, KD., Threatt, TB., et al.[2023]

A 4-year-old girl with a rare FBXL4 gene mutation and severe lactic acidosis was successfully treated with a ketogenic diet (KD) after standard treatments failed, highlighting the KD's potential in managing mitochondrial disorders.

This case represents the first documented use of parenteral KD to effectively reduce lactic acidosis in a patient with mitochondrial depletion syndrome, suggesting a promising nonpharmacological intervention for similar conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The first case with FBXL4 mutation successfully treated with a parenteral ketogenic diet for lactic acidosis. İnci, A., Aktaş, E., Cengiz Ergin, FB., et al.[2022]

Citations

1. England pubmed.ncbi.nlm.nih.gov

Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: a case report and review of the literature. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Ketogenic diet for schizophrenia: clinical implication. [2020]

3. Germany pubmed.ncbi.nlm.nih.gov

Effects of beta-hydroxybutyrate administration on MK-801-induced schizophrenia-like behaviour in mice. [2020]

4. England pubmed.ncbi.nlm.nih.gov

The Role of Ketogenic Metabolic Therapy on the Brain in Serious Mental Illness: A Review. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

The use of the ketogenic diet in the treatment of psychiatric disorders. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

The first case with FBXL4 mutation successfully treated with a parenteral ketogenic diet for lactic acidosis. [2022]