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

Trial Summary

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 data supports the effectiveness of the treatment Ketogenic Therapy for bipolar disorder?

Some people with bipolar disorder have reported mood stabilization while on a ketogenic diet, which is traditionally used for epilepsy. The diet may help stabilize mood by affecting brain energy and reducing certain chemicals in the brain, similar to how some mood-stabilizing drugs work. ^{1 2 3 4 5}

Is the ketogenic diet safe for humans?

The ketogenic diet has been used safely in children, adolescents, and young adults with epilepsy, showing good safety profiles in multiple studies. While these studies focus on epilepsy, they provide some reassurance about the diet's general safety in humans. ^{2 3 6 7 8}

How is the ketogenic diet treatment different for bipolar disorder?

The ketogenic diet is unique for bipolar disorder because it alters the body's energy use, potentially stabilizing mood by reducing intracellular sodium and calcium, which is a common effect of mood stabilizers. Unlike traditional medications, it involves a low-carb diet that changes brain energy metabolism, which may help manage mood disorders. ^{1 3 4 5 9}

What is the purpose of this trial?

The present study is an open trial of ketogenic diets for adolescents and young adults (ages 12-21 yrs) in the depressive or mixed phases of bipolar disorder (BD). The investigators aim to determine whether combining standard of care pharmacological treatment for bipolar spectrum disorders with a 16-week ketogenic diet is well-tolerated and associated with improvements in depression, inflammatory and metabolic indicators, and executive functioning over the study period. The experimental treatment in this study is a 16-week full ketogenic diet. Four study sites (UCLA, U Cincinnati, U Colorado and U Pittsburgh) will recruit 80 total youth (20 each) from bipolar specialty clinics. All youth eligible for the ketogenic therapy will be provided with the ketogenic diet and standard of care pharmacological treatment. During the diet therapy youth will be seen by a study child/adolescent psychiatrist at least once a month (and more frequently when needed), with the psychiatrist recommending and providing side effects monitoring and pharmacotherapy as clinically indicated. The youth and caregivers will also meet with an expert dietitian who will coach all youth on maintaining the ketogenic diet (low carbs, high fats, medium protein) and making sure the child is tolerating the diet and getting enough liquid and nutrients, following the practice guidelines of the International Ketogenic Diet Study Group for treating youth. All youth and involved caregivers will also be provided will at least one motivational enhancement session to support them in goal setting and completion of the study elements. Throughout the study the investigators will assess metabolic (e.g., blood ketones, HOMA-IR) and inflammatory indicators (e.g., C-reactive protein), both for safety reasons and to assess correlates of symptomatic change. Independent evaluators will assess youth every month regarding their symptoms (depression, mania, anxiety, psychosis), psychosocial functioning, and quality of life. The investigators anticipate that the pilot will transpire over 24 months and be an important step toward establishing feasibility and acceptability of ketogenic therapy for this population, not only in terms of diet administration and compliance but also for obtaining symptomatic, metabolic and inflammatory measurements.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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 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]

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]

References

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

Ketosis and bipolar disorder: controlled analytic study of online reports. [2023]

2. England pubmed.ncbi.nlm.nih.gov

Pilot study of a ketogenic diet in bipolar disorder. [2023]

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

The ketogenic diet may have mood-stabilizing properties. [2008]

4. Switzerland pubmed.ncbi.nlm.nih.gov

The Current Status of the Ketogenic Diet in Psychiatry. [2020]

5. England pubmed.ncbi.nlm.nih.gov

The ketogenic diet for type II bipolar disorder. [2017]

6. Netherlands pubmed.ncbi.nlm.nih.gov

The ketogenic diet in children, adolescents and young adults with refractory epilepsy: an Italian multicentric experience. [2022]

7. England 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. [2022]

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

Efficacy and safety of the ketogenic diet for intractable childhood epilepsy: Korean multicentric experience. [2022]

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

Ketogenic diet as a metabolic therapy for mood disorders: Evidence and developments. [2019]