Ketogenic Diet for Bipolar Disorder

(CBN Keto Trial)

Recruiting at 3 trial locations

Overseen By Danielle M Denenny, Ph.D.

Age: < 65

Sex: Any

Trial Phase: Academic

Sponsor: University of California, Los Angeles

Must not be taking: SGLT-2 inhibitors, Insulin, Antihypertensives, others

Disqualifiers: Pregnancy, Diabetes, Eating disorders, others

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

Compensation: Varies

Number of Visits: Unknown

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a ketogenic diet can improve symptoms of bipolar disorder in young people, focusing on those in depressive or mixed phases. Participants will follow a high-fat, low-carb diet for 16 weeks while continuing their usual medications. It suits adolescents and young adults with bipolar disorder who are stable enough for outpatient care and open to trying a new dietary approach. The goal is to determine if this diet can aid mood symptoms and overall health. As an unphased trial, this study provides a unique opportunity to investigate a novel dietary approach that could enhance well-being.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it does require that you do not take certain medications like SGLT-2 inhibitors, insulin, sulfonylureas, or certain antihypertensive medications. It's best to discuss your current medications with the study team to see if they are compatible with the trial.

What prior data suggests that this ketogenic diet is safe for adolescents and young adults with bipolar disorder?

Research suggests that the ketogenic diet might help people with bipolar disorder by improving mood and mental health. Although specific clinical trials for bipolar disorder have not yet been conducted, some reports indicate benefits such as increased life satisfaction and better sleep.

Information on safety is limited, but the ketogenic diet is already used for conditions like epilepsy in both children and adults, suggesting it might be safe. However, the diet involves consuming a lot of fats and very few carbs, which could be a significant change for some people.

The study will closely monitor any side effects, and participants will regularly meet with doctors and dietitians to ensure everything proceeds smoothly. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using a ketogenic diet for bipolar disorder because it represents a natural and holistic approach, contrasting with standard medications like mood stabilizers and antipsychotics. Unlike traditional treatments, which often target neurotransmitter imbalances, the ketogenic diet shifts the body's metabolism to use ketones for energy, potentially stabilizing mood through metabolic pathways. Additionally, this dietary intervention may offer fewer side effects compared to conventional drugs, appealing to those seeking alternative or supplementary options.

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

Research has shown that a ketogenic diet might help people with bipolar disorder. In some studies, 69% of participants with bipolar disorder experienced more than a one-point improvement in their overall mental health scores. Another study found that most patients on a ketogenic diet showed significant improvements in their mental health symptoms after four months. Although large clinical trials have not yet been conducted, these early findings suggest that a ketogenic diet could help manage symptoms of bipolar disorder. This trial will specifically evaluate the effects of ketogenic therapy on youth with bipolar spectrum disorders. ^{1 2 3 5 6}

Are You a Good Fit for This Trial?

This trial is for English-speaking adolescents and young adults aged 12-21 with bipolar disorder, who are stable enough for outpatient treatment. They must have experienced recent depressive or mixed symptoms but not be acutely psychotic, suicidal, or manic. Participants need to commit to monthly psychiatric evaluations and adhere to a ketogenic diet guided by a dietitian.

Inclusion Criteria

Youth must have a current BSD (bipolar I, II per DSM-5 criteria or other specified BSD by the University of Pittsburgh diagnostic criteria)

Participants must have had specific depression severity ratings in the 2 weeks prior to study intake

I (or my child) am willing to attend sessions with a psychiatrist and dietitian for the study.

Exclusion Criteria

Pregnancy or breastfeeding

Unstable respiratory condition

Current or history of anorexia nervosa

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

4 weeks

Initial phone screen and in-person visits for consent and assessments

Pre-Keto Preparation

Participants ramp up to the full keto diet with increasing keto meals each week

2-3 weeks

Weekly visits with dietitian for diet adjustment

Keto Therapy Trial

Participants follow a 16-week ketogenic diet with regular monitoring and support

16 weeks

Weekly visits with dietitian and monthly visits with psychiatrist

Post-Treatment Assessments

Post-treatment evaluation with symptom assessments and feedback

1 week

In-person visit for assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketogenic Therapy

Trial Overview The study tests if adding a strict 16-week ketogenic diet (low carbs, high fats) to standard medication improves depression and brain functioning in youth with bipolar disorder. It includes regular check-ups with psychiatrists and coaching from expert dietitians across four research sites.

How Is the Trial Designed?

Group I: Ketogenic Therapy for Bipolar Spectrum Disorders Experimental Treatment 1 Intervention

This is a pilot trial with one intervention arm. All youth meeting eligibility for the ketogenic therapy phase of this pilot trial will be invited to participate in the intervention and progress tracking.

Who Is Running the Clinical Trial?

University of California, Los Angeles

Lead Sponsor

Trials

1,594

Recruited

10,430,000+

University of Cincinnati

Collaborator

Trials

442

Recruited

639,000+

University of Pittsburgh

Collaborator

Trials

1,820

Recruited

16,360,000+

University of Colorado, Denver

Collaborator

Trials

1,842

Recruited

3,028,000+

Advanced Ketogenic Therapies

Collaborator

Baszucki Family Foundation

Collaborator

Trials

2

Recruited

100+

Published Research Related to This Trial

In a study of 16 pediatric patients with intractable epilepsy, 56% showed significant improvement in seizure control while on a ketogenic diet (KD), with three children becoming completely seizure-free.

The non-fasting ketogenic diet was found to be safe and effective, with most children gaining weight and only experiencing mild, reversible side effects such as hypoglycemia and vomiting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The efficacy of non-fasting ketogenic diet protocol in the management of intractable epilepsy in pediatric patients: a single center study from Saudi Arabia. Alameen Ali, H., Muthaffar, O., AlKarim, N., et al.[2022]

In a study of 199 patients with refractory epilepsy, the ketogenic diet (KD) demonstrated significant efficacy, with 58% of patients experiencing a reduction in seizure frequency of over 50% after 6 months, and 33% becoming seizure-free.

While the KD is generally safe and effective, with most complications being mild, there were five reported deaths, highlighting the need for careful monitoring of patients, especially those with symptomatic and partial epilepsies who may have a higher risk of relapse after discontinuation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of the ketogenic diet for intractable childhood epilepsy: Korean multicentric experience. Kang, HC., Kim, YJ., Kim, DW., et al.[2022]

The ketogenic diet may serve as a sustainable mood stabilizing treatment for individuals with type II bipolar disorder, as demonstrated by two women who maintained ketosis for 2 and 3 years, respectively, and experienced significant mood stabilization beyond that achieved with medication.

Both participants tolerated the diet well with no significant adverse effects, suggesting that the diet could be a safe alternative for mood management in bipolar disorder, potentially by reducing intracellular sodium and calcium levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ketogenic diet for type II bipolar disorder. Phelps, JR., Siemers, SV., El-Mallakh, RS.[2017]

In an analysis of comments from 274 individuals with bipolar disorder, 85.5% reported positive effects on mood stabilization from a ketogenic diet, with a significant number experiencing lasting improvements for months to years.

The ketogenic diet was associated with a higher rate of significant mood stabilization compared to other dietary interventions, suggesting it may have beneficial effects on mood, potentially linked to its impact on mitochondrial function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketosis and bipolar disorder: controlled analytic study of online reports. Campbell, IH., Campbell, H.[2023]

The ketogenic diet has shown significant efficacy in reducing seizure frequency in children with refractory epilepsy, with about two-thirds of patients experiencing a notable decrease and one-third becoming nearly seizure-free.

There is potential for the ketogenic diet to act as a mood stabilizer in bipolar disorder, as it may improve brain energy metabolism and reduce intracellular sodium levels, which are common mechanisms of effective mood stabilizers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ketogenic diet may have mood-stabilizing properties. El-Mallakh, RS., Paskitti, ME.[2008]

In a study of 56 young patients (ages 1-23) with refractory epilepsy, the classic 4:1 ketogenic diet as an add-on treatment led to over a 50% reduction in seizure frequency for 37.5% of patients after 3 months and 26.8% after 6 months, although effectiveness decreased by 12 months.

While 57.1% of patients experienced mild and transient side effects, the diet was particularly beneficial for 64% of patients with neuronal migration disorders, and some patients were able to reduce their antiepileptic medications after a few months on the diet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ketogenic diet in children, adolescents and young adults with refractory epilepsy: an Italian multicentric experience. Coppola, G., Veggiotti, P., Cusmai, R., et al.[2022]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10594182/

Pilot study of a ketogenic diet in bipolar disorder - PMC Recent evidence from case reports suggests that a ketogenic diet may be effective for bipolar disorder. However, no clinical trials have been conducted to date.

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

Ketogenic Diet Intervention on Metabolic and Psychiatric ... The percentage of participants with bipolar who showed >1 point improvement in clinical global impression was 69 %. Greater biomarker benefits observed with ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06920940

NCT06920940 | Child Bipolar Network Ketogenic Diet ... The investigators hypothesize that youth who complied with the 16-week keto diet therapy will show statistically significant reductions in bipolar mood ...

4. 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 ...

5. bmcpsychiatry.biomedcentral.com bmcpsychiatry.biomedcentral.com/articles/10.1186/s12888-025-06479-y

Pilot study of a ketogenic diet in bipolar disorder: a process ... This research aimed to explore the feasibility and acceptability of a ketogenic diet intervention for bipolar disorder, fidelity to its behavioural components

6. uc.edu uc.edu/news/articles/2025/02/researchers-explore-ketogenic-diets-effects-on-bipolar-disorder-among-teenagers-young-adults.html

Researchers explore ketogenic diet's effects on bipolar ... While preliminary research suggests ketogenic therapy has a beneficial impact on psychiatric and metabolic function in adults with bipolar ...