Ketogenic Diet for Mental Illnesses

Overseen By Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Must not be taking: Clozapine

Disqualifiers: Pregnancy, Insulin dependence, Cardiovascular dysfunction, Substance abuse, others

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

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 determine how a ketogenic diet, low in carbs and high in fats, might improve the quality of life for individuals with serious mental illnesses such as schizophrenia, bipolar disorder, and major depressive disorder. Participants will either follow the LCHF Ketogenic Diet for 12 weeks or maintain their usual diet before switching to the ketogenic diet. It is suitable for individuals in the U.S. with bipolar disorder, major depressive disorder, or schizophrenia who are stable and not experiencing severe symptoms requiring hospitalization. The trial will monitor physical and mental health and provide coaching support. As an unphased trial, it offers participants the chance to explore a potentially life-enhancing dietary approach with supportive coaching.

Will I have to stop taking my current medications?

The trial allows participants to continue taking their current psychiatric medications if they are on a stable dose. You may need to switch medications before enrolling, but you should be stable enough to follow the study procedures.

What prior data suggests that the ketogenic diet is safe for mental illness treatment?

Research has shown that the ketogenic diet is generally well-tolerated by people with mental health conditions. One study found that patients with mental illnesses unresponsive to other treatments managed to follow a ketogenic diet successfully. Another study discovered that most patients experienced significant improvements in their mental health symptoms after adhering to the diet for four months.

Additionally, the diet helped some patients with serious mental illnesses improve health issues like diabetes and high cholesterol. These findings suggest that the ketogenic diet might be a safe option for people with conditions such as schizophrenia, bipolar disorder, and major depression. However, monitoring health while on the diet is important to ensure its suitability. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using a ketogenic diet for mental illnesses because it offers a fresh approach compared to traditional medications like antidepressants and mood stabilizers. This diet is low in carbohydrates and high in fats, which may help stabilize brain energy and reduce inflammation, potentially improving mental health symptoms. Additionally, the ketogenic diet emphasizes natural dietary changes rather than pharmaceutical interventions, which could mean fewer side effects and a more holistic method of managing mental health conditions.

What evidence suggests that the ketogenic diet might be an effective treatment for mental illnesses?

Research has shown that ketogenic diets might help people with serious mental health issues. A small study from Stanford Medicine found that these diets could help stabilize the brain. Another study found that symptoms of mental illnesses decreased by about 31% when patients followed a ketogenic diet. In this trial, participants in Arm 1 will follow a ketogenic diet for 12 weeks, while those in Arm 2 will first follow their usual diet for 12 weeks before switching to the ketogenic diet. Evidence also suggests that ketogenic diets might be helpful for conditions like bipolar disorder, schizoaffective disorder, and possibly depression and anxiety. These diets may work by balancing brain chemicals, stabilizing brain networks, and improving brain flexibility. ^{2 4 5 6 7}

Who Is on the Research Team?

Shebani Sethi, MD, ABOM

Principal Investigator

Stanford University

Michael Snyder, PhD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for U.S. residents with schizophrenia, bipolar disorder, or major depressive disorder who are clinically stable and not hospitalized in the past 3 months. They must have a moderate to severe condition score (PHQ-9 >10 or BPRS >40) and can be on stable psychiatric medication. Excluded are those with certain medical conditions, substance abuse issues, recent ketogenic dieting, or participation in other trials.

Inclusion Criteria

My depression is moderate to severe, stable, and I haven't been hospitalized recently.

I have bipolar disorder, not mild, stable, and no recent hospital visits.

Willing and able to give informed consent for participation in English

Exclusion Criteria

I have a family history of very high cholesterol.

I have not been in a clinical trial with investigational drugs that could affect this study in the last month.

I have severe kidney or liver problems.

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 for 12 weeks with monitoring of physical and psychological health and coaching support

12 weeks

Weekly visits (in-person or virtual)

Crossover Treatment

Participants initially on their usual diet crossover to a ketogenic diet for 12 weeks with monitoring and support

12 weeks

Weekly visits (in-person or virtual)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• LCHF Ketogenic Diet

Trial Overview The study compares the effects of a Low-Carbohydrate High-Fat (LCHF) Ketogenic Diet versus a standard Diet-as-Usual (DAU) on quality of life in patients with serious mental illnesses like schizophrenia and bipolar disorder. It's randomized to determine if this dietary intervention can improve health outcomes.

How Is the Trial Designed?

Group I: Arm 2: DAU- Ketogenic Diet Crossover Experimental Treatment 2 Interventions

Participants will follow 12 weeks of their usual diet (Diet-as-Usual, DAU). Then, participants will crossover and follow 12 weeks of the ketogenic diet. Monitoring of physical and psychological health and coaching support will occur throughout participation.

Group II: Arm 1: Ketogenic Diet Only Experimental Treatment 1 Intervention

Participants will follow 12 weeks of the ketogenic diet, with monitoring of physical and psychological health and coaching support.

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

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) is considered a relatively safe treatment for refractory childhood epilepsy, with severe adverse effects occurring in less than 0.5% of children, and no deaths attributed to the diet.

Common adverse effects include gastrointestinal disturbances and hyperlipidemia, but the main reason for discontinuation of the diet was lack of efficacy rather than safety concerns, highlighting the need for careful medical supervision during its implementation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and tolerability of the ketogenic diet used for the treatment of refractory childhood epilepsy: a systematic review of published prospective studies. Cai, QY., Zhou, ZJ., Luo, R., et al.[2018]

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]

The ketogenic diet (KD) has shown potential benefits in animal models for various mental disorders, including significant reductions in anxiety and depression-like behaviors, but results in human studies are mixed and not conclusive.

Currently, there is insufficient evidence to recommend KD as a treatment for mental disorders due to limitations in existing studies, such as reliance on animal models and lack of standardized measures like ketone levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Current Status of the Ketogenic Diet in Psychiatry. Bostock, EC., Kirkby, KC., Taylor, BV.[2020]

In a study of 31 adults with severe mental illnesses, a ketogenic diet significantly improved depression and psychosis symptoms, as shown by reductions in Hamilton Depression Rating Scale scores from 25.4 to 7.7 and PANSS scores from 91.4 to 49.3, all with P < 0.001.

The ketogenic diet was well-tolerated and also led to improvements in metabolic health markers, including weight, blood pressure, blood glucose, and triglycerides, indicating potential benefits beyond mental health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Ketogenic Diet for Refractory Mental Illness: A Retrospective Analysis of 31 Inpatients. Danan, A., Westman, EC., Saslow, LR., et al.[2022]

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/PMC10134254/

Efficacy of low carbohydrate and ketogenic diets in treating ... There was some evidence for efficacy of ketogenic diets in those with bipolar disorder, schizoaffective disorder and possibly unipolar depression/anxiety.

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

Ketogenic Diet Intervention on Metabolic and Psychiatric ... The psychiatric outcomes indicate that, on average, the severity of mental illness, as assessed by the Clinical Global Impressions scale, improved by 31 %.

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

Impact of a Ketogenic Diet on Metabolic and Psychiatric ... The purpose of this study is to evaluate both the metabolic and psychiatric outcomes with a KD diet in this psychiatric population. Official Title. Impact of A ...

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

The Ketogenic Diet for Refractory Mental Illness KDs also help rebalance neurotransmitter systems, (16) stabilize neural networks (60), improve neuroplasticity (61), and bridge the energy gap ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11122005/

The Potential Role of the Ketogenic Diet in Serious Mental ... Patients were admitted to a psychiatric hospital and put on a KD for up to 248 days. Symptoms were poorly controlled despite the intensification of psychiatric ...

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

Stanford Medicine expert shares five key insights on keto ... After four months on the ketogenic diet, most of the patients showed significant improvement in their psychiatric symptoms, a reduction in ...