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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a ketogenic diet can improve cognitive issues, such as thinking and memory problems, in people with schizophrenia or bipolar disorder. The ketogenic diet, high in fats and low in carbohydrates, might stabilize brain energy use and enhance brain function. Participants will either follow this specific diet or continue their regular eating habits for four weeks. Individuals with schizophrenia or bipolar disorder who are stable on medication and willing to try a new diet or maintain their current one might be suitable for this study. As an unphased trial, this study offers a unique opportunity to contribute to understanding dietary impacts on mental health.

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.

What prior data suggests that the ketogenic diet is safe for people with schizophrenia and bipolar disorder?

Research has shown that ketogenic diets can be safe and well-tolerated for individuals with serious mental illnesses, such as schizophrenia. In some studies, participants with schizophrenia who followed a ketogenic diet experienced improvements in overall health, including the reversal of issues like metabolic syndrome, which involves high blood pressure and high blood sugar.

This diet is high in fats and low in carbohydrates, altering how the body obtains energy. Instead of using sugar, the body uses ketones, derived from fat. This shift can positively affect brain health.

However, like any dietary change, some individuals might experience side effects. These can include fatigue, headaches, or nausea, often referred to as the "keto flu." These symptoms are usually temporary as the body adjusts to the new diet.

Overall, the ketogenic diet has been studied for its potential benefits on brain health and is generally considered safe. It is important to consult a healthcare provider before making any dietary changes, especially for those with existing health conditions. ^{1 2 3 4 5}

Why are researchers excited about this trial?

The ketogenic diet is unique for treating schizophrenia because it shifts the body’s metabolism by emphasizing high-fat and low-carbohydrate intake, leading to the production of ketone bodies. Unlike traditional treatments like antipsychotic medications that target neurotransmitters, this diet induces a fasting-like state that may affect brain energy metabolism differently. Researchers are excited because this approach offers a non-pharmaceutical option that could potentially reduce symptoms without the side effects often associated with standard medications.

What evidence suggests that a ketogenic diet might be an effective treatment for schizophrenia?

Research suggests that the ketogenic diet, which participants in this trial may receive, might help individuals with schizophrenia and bipolar disorder. This diet is high in fats and low in carbohydrates. Studies have shown it can improve symptoms in those with serious mental health issues. For instance, a small study found that the ketogenic diet not only improved mental health but also reduced insulin resistance, a condition where the body doesn't use insulin properly. The diet may also boost brain energy by providing ketones, which can offer more energy than sugar. While more research is needed, early findings are promising for using the ketogenic diet to address thinking and memory problems in these conditions. ^{1 2 3 6 7}

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

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]

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]

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]

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]

Citations

1.

med.stanford.edu

med.stanford.edu/news/all-news/2024/04/keto-diet-mental-illness.html

Pilot study shows ketogenic diet improves severe mental illness

For people living with serious mental illness like schizophrenia or bipolar disorder, standard treatment with antipsychotic medications can be a ...

2.

sciencedirect.com

sciencedirect.com/science/article/pii/S0165178124001513

Ketogenic Diet Intervention on Metabolic and Psychiatric ...

Ketogenic diet therapy resulted in metabolic syndrome reversal in this cohort of serious mental illness ... low compared with high saturated fat intake: a ...

3.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7387764/

Ketogenic Therapy in Serious Mental Illness: Emerging ...

The ketogenic diet is typically a high-fat, moderate-protein, and very low–carbohydrate diet. Ratios of fats to protein and carbohydrate are ...

4.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10134254/

Efficacy of low carbohydrate and ketogenic diets in treating ...

Ketogenic diet, KD, Fat:carbohydrate:protein ratio calculated on an individual basis for children with epilepsy, High fat and very low carbohydrate: a ketogenic ...

5.

news.stanford.edu

news.stanford.edu/stories/2025/04/keto-diet-therapy-mental-illness-research

Stanford Medicine expert shares five key insights on keto ...

Growing scientific evidence suggests that a high-fat, moderate-protein, low ... Pilot study finds keto diet improves mental illness. A small ...

6.

clinicaltrials.gov

clinicaltrials.gov/study/NCT05705063?cond=bipolar%20ketogenic&rank=2

Impact of a Ketogenic Diet on Metabolic and Psychiatric ...

Low-carbohydrate high-fat (LCHF) or ketogenic diets (KD) have been shown to ... The Role of Ketogenic Metabolic Therapy on the Brain in Serious Mental Illness: A ...

7.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC8120987/

The use of the ketogenic diet in the treatment of psychiatric ...

The ketogenic diet (KD) is a high-fat, low-carbohydrate, and ... Schizophrenia, gluten, and low-carbohydrate, ketogenic diets: a case ...