Ketogenic Diet for Schizophrenia

Overseen By Matthew Glassman, MS

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Maryland, Baltimore

Must be taking: Antipsychotics

Disqualifiers: Pregnancy, Diabetes, Heart failure, others

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore whether a ketogenic diet can improve symptoms of schizophrenia. Current treatments don't work well for everyone, and researchers are investigating if this high-fat, low-carb diet might offer another option. Participants will either follow a ketogenic diet or continue their regular diet to compare effects. Ideal candidates are those diagnosed with schizophrenia or schizoaffective disorder who haven't changed their antipsychotic medication dose in the last two weeks. As an unphased trial, this study provides a unique opportunity to contribute to groundbreaking research that could expand treatment options for schizophrenia.

Do I need to stop my current medications for this trial?

The trial does not specify if you need to stop your current medications. However, it requires that your antipsychotic medication dose has not changed in the last 14 days, suggesting you may continue your current regimen.

What prior data suggests that the ketogenic diet is safe for schizophrenia patients?

Research shows that the ketogenic diet might help people with schizophrenia. For example, one study found that patients who followed this diet experienced a noticeable decrease in their psychotic symptoms. Another study reported an average improvement of 32% in psychiatric symptoms for those on the diet.

Additionally, a small clinical trial suggested that the diet could help stabilize the brain, and other research has shown benefits for both mental health and metabolism. The ketogenic diet was also safe and well-tolerated by most patients in a hospital setting.

While these findings are promising, more thorough studies, like double-blind randomized controlled trials, are needed to confirm these results. Based on current evidence, the ketogenic diet appears to be a potentially safe option for managing schizophrenia symptoms. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for schizophrenia involve medications like antipsychotics that target neurotransmitters in the brain. But the ketogenic diet is different because it focuses on changing the body's energy source to ketones instead of glucose. This diet may help reduce inflammation and oxidative stress, which are thought to play a role in schizophrenia symptoms. Researchers are excited about this approach because it offers a potential new way to manage schizophrenia without relying on traditional medications, which can have significant side effects.

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

Research suggests that a ketogenic diet, which participants in this trial may receive, might help improve symptoms in people with schizophrenia. A small study found that this diet could help stabilize the brain. In another study, people with schizophrenia saw an average 32% improvement in their symptoms. Some reports also showed that patients on a ketogenic diet experienced significant improvement or even complete resolution of symptoms. Although these findings are promising, more research with larger groups is needed to confirm these results. Participants in this trial will follow either a ketogenic diet or a regular diet to compare their effects on schizophrenia symptoms. ^{2 3 4 6 7}

Who Is on the Research Team?

Deanna L Kelly, Pharm.D., BCPP

Principal Investigator

Study Principal Investigator

Are You a Good Fit for This Trial?

Adults aged 18-64 with schizophrenia or schizoaffective disorder, stable on antipsychotics for at least two weeks, and a BMI over 18.5 can join this trial. They must score sufficiently on tests to show they understand the consent process. Excluded are pregnant women, those with severe heart, kidney or liver issues, certain metabolic disorders, eating disorders or alcohol use disorder.

Inclusion Criteria

Minimum score of 45 on BPRS

I have been diagnosed with schizophrenia or schizoaffective disorder.

My antipsychotic medication dose has been stable for the last 14 days.

Exclusion Criteria

Refusal to eat intervention diet, food allergies or restrictions that the kitchen cannot accommodate, and/or dietary noncompliance with dietary energy needs

Corrected QT interval (QTc) prolongation greater than or equal to 500ms

I have a serious kidney condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants follow a ketogenic diet or a regular diet for 3 months

12 weeks

Weekly visits for assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketogenic Diet
• Regular Diet

Trial Overview This study is testing whether a ketogenic diet (high fat, low carb) helps improve symptoms of schizophrenia compared to a regular diet. It's designed as a double-blind controlled trial but hasn't been done before due to challenges in monitoring food intake in patients.

How Is the Trial Designed?

Group I: Ketogenic Diet Active Control 1 Intervention

Group II: Regular Diet Placebo Group 1 Intervention

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

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]

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 A small clinical trial led by Stanford Medicine found that the metabolic effects of a ketogenic diet may help stabilize the brain.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12237970/

Ketogenic therapy for schizophrenia: evidence, mechanisms ... During this time, PANSS scores showed modest improvements (female: 101 to 91; male: 82 to 75), and both experienced reductions in body fat.

3. sciencedirect.com sciencedirect.com/science/article/pii/S0165178124001513

Ketogenic Diet Intervention on Metabolic and Psychiatric ... Participants with schizophrenia showed an average of 32 % improvement according to the brief psychiatric rating scale. •. The percentage of participants with ...

4. frontiersin.org frontiersin.org/journals/nutrition/articles/10.3389/fnut.2025.1591937/full

Case Report: Remission of schizophrenia using a ... (15) reported that 10 patients with a primary diagnosis of schizophrenia who followed a ketogenic diet for two weeks exhibited improvement in ...

5. med.stanford.edu med.stanford.edu/news/insights/2025/04/keto-diet-ketogenic-therapy-mental-illness-bipolar.html

Five things to know about keto therapy and serious mental ... After four months on the ketogenic diet, most of the patients showed significant improvement in their psychiatric symptoms, a reduction in ...

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

Ketogenic Therapy in Serious Mental Illness: Emerging ... Within 2 months of starting the diet, both patients experienced significant reductions in psychotic symptoms as measured by the Positive and ...

7. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2022.951376/full

The Ketogenic Diet for Refractory Mental Illness This iteration of a KD was safe, feasible to administer in an inpatient setting, well tolerated by most patients, and associated with ...