Ketogenic Diet for Bipolar Disorder

Overseen By Virginie-Anne Chouinard, MD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Mclean Hospital

Must not be taking: Propofol

Disqualifiers: Substance use disorder, Diabetes, Cancer, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

50 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a ketogenic diet (a very low carbohydrate, high-fat diet), combined with regular treatment, can enhance brain energy and reduce symptoms in individuals with bipolar disorder or schizoaffective disorder. Participants will either follow a ketogenic diet or adhere to the Dietary Guidelines for Americans, both alongside their usual medications. The trial seeks individuals diagnosed with bipolar I disorder or schizoaffective disorder within the last 7 years, who have a stable condition and have not recently changed their psychiatric medication. As an unphased trial, this study offers a unique opportunity to contribute to innovative research that could improve future treatment options.

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 have a stable psychiatric disorder with no change in psychiatric medications within the past 2 weeks before screening and should not need new psychiatric medications during the study.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the ketogenic diet, high in fats and low in carbohydrates, can improve metabolic health. This diet shifts the body's primary energy source from carbohydrates to fats. Some studies have found that individuals on a ketogenic diet might experience changes in blood fat levels, particularly if they are taking certain antipsychotic medications.

Other research suggests that most people can follow the diet without major issues. However, monitoring blood ketone levels is important, as the diet can affect them. In one study, overweight teenagers who followed a similar diet for 12 weeks lost more weight than those on a low-fat diet, without major safety concerns.

Overall, while the ketogenic diet appears promising, following medical advice and monitoring health indicators is crucial when starting this diet. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Most treatments for bipolar disorder rely on medications like mood stabilizers and antipsychotics. However, the ketogenic diet stands out because it focuses on altering metabolic processes in the body by switching the primary energy source from carbohydrates to fats, potentially impacting brain chemistry in a way that could stabilize mood. Researchers are excited about this approach because it offers a non-pharmacological option that might work alongside or even enhance the effects of traditional medications. Additionally, the diet involves daily ketone monitoring, providing real-time feedback on adherence, which could empower patients in managing their condition.

What evidence suggests that the ketogenic diet could be an effective treatment for bipolar disorder?

Research suggests that the ketogenic diet, high in fat and low in carbohydrates, might improve symptoms in people with bipolar disorder. Studies have found that this diet can lead to positive changes in the body, such as better weight control and improved insulin use, which might enhance mental health. In this trial, participants in the ketogenic diet arm will follow this diet for 12 weeks, while those in the Dietary Guidelines for Americans arm will adhere to standard dietary guidelines. A small study found that people with severe mental illness who tried the ketogenic diet reported feeling better. Although more research is needed, these early results suggest that the ketogenic diet could be a promising way to manage bipolar disorder. ^{6 7 8 9 10}

Who Is on the Research Team?

Virginie-Anne Chouinard, MD

Principal Investigator

Mclean Hospital

Are You a Good Fit for This Trial?

This trial is for individuals experiencing their first episode of bipolar disorder or schizoaffective disorder. Participants should be willing to follow specific dietary guidelines, including a ketogenic diet as part of the study.

Inclusion Criteria

I was diagnosed with bipolar I or schizoaffective disorder in the last 7 years.

My mental health condition is stable and my medications haven't changed in the last 2 weeks.

I don't expect to need new psychiatric medications for the next 12 weeks.

Exclusion Criteria

I have had weight loss surgery in the past.

I am currently diagnosed with cancer.

I have been diagnosed with type 1 or type 2 diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants follow either a ketogenic diet or the Dietary Guidelines for Americans for 12 weeks, with weekly diet counseling and daily blood ketone monitoring

12 weeks

Weekly visits (in-person or virtual) for diet counseling

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Open-label extension (optional)

Participants may opt into continuation of the ketogenic diet with daily blood ketone monitoring for an additional 12 weeks

12 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketogenic diet

Trial Overview

The study is testing how effective a ketogenic diet is when combined with standard treatments in improving brain energy metabolism and reducing psychiatric symptoms in new cases of bipolar and schizoaffective disorders.

How Is the Trial Designed?

Group I: Ketogenic diet arm Active Control 1 Intervention

Eligible participants assigned to the ketogenic diet arm will be asked to follow the ketogenic diet (KD) for 12 weeks in addition to any ongoing medications (e.g., mood stabilizers and/or second-generation antipsychotics). Participants will receive weekly and as needed diet counseling from a registered dietician. Participants will be asked to monitor and report their blood ketone levels each day via a finger-prick device provided by the study team. Participants have the ability to opt into an optional open label phase where they can continue on the ketogenic diet with the daily finger pricks for another 12 weeks after the 12-week main study.

Group II: Dietary Guidelines for Americans arm Active Control 1 Intervention

Eligible participants assigned to the Dietary Guidelines for Americans (DGA) arm will adhere to the Dietary Guidelines for Americans in addition to any ongoing medications (e.g., mood stabilizers and/or second-generation antipsychotics). Participants will receive weekly and as needed diet counseling from a registered dietician. Participants will be asked to monitor and report their blood ketone levels each day via a finger-prick device provided by the study team. Participants have the ability to opt into an optional open label phase where they can switch to the ketogenic diet with the daily finger pricks for 12 weeks after the 12-week main study.

Who Is Running the Clinical Trial?

Mclean Hospital

Lead Sponsor

Trials

221

Recruited

22,500+

Baszucki Family Foundation

Collaborator

Trials

2

Recruited

100+

Published Research Related to This Trial

The ketogenic diet, which is high in fat and low in carbohydrates, has been found to be more effective than many new antiepileptic drugs for treating refractory epilepsy.

There is a significant lack of awareness among pediatricians and neurologists regarding the ketogenic diet as a treatment option for epilepsy, highlighting the need for better education on this effective dietary intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ketogenic diet and other dietary treatments for refractory epilepsy in children. Sharma, S., Jain, P.[2021]

The ketogenic diet (KD) is an effective treatment for epilepsy, but it can lead to side effects due to its high fat and low carbohydrate composition, with short-term side effects being well-documented.

Recent studies have provided more data on long-term side effects of the KD, highlighting the need for improved monitoring practices in line with the International Ketogenic Diet Consensus Statement (IKDCS) from 2008.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term monitoring of the ketogenic diet: Do's and Don'ts. Bergqvist, AG.[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]

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]

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]

In a pilot study involving 12 adults with refractory epilepsy, the ketogenic diet (KD) led to a significant reduction in seizure frequency, with a 38.4% decrease in the first 4 months and a 44.1% decrease over the entire treatment period.

The diet was generally safe, with only mild adverse effects reported, and 56% of participants experienced a significant reduction in seizures, indicating that KD can be an effective adjunctive treatment for adults with epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diet treatment in adults with refractory epilepsy. Klein, P., Janousek, J., Barber, A., et al.[2017]

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]

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 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]

In a mouse model of malignant glioma, a ketogenic diet (KetoCal®) significantly increased survival by approximately 5 days compared to a standard diet, indicating its potential as a supportive treatment in cancer therapy.

The combination of the ketogenic diet and radiation therapy showed more than additive effects, with tumor growth significantly reduced in most mice on the ketogenic diet, suggesting that metabolic changes from the diet could enhance the effectiveness of conventional cancer treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ketogenic diet is an effective adjuvant to radiation therapy for the treatment of malignant glioma. Abdelwahab, MG., Fenton, KE., Preul, MC., et al.[2022]

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]

The ketogenic diet (KD) and modified Atkins diet (MAD) have shown significant efficacy in reducing seizure frequency in children and adolescents with refractory epilepsy, with 35-56.1% of participants achieving a reduction of 50% or more in seizures compared to only 6-18.2% in control groups.

Gastrointestinal side effects were the most common adverse effects reported, but no severe adverse effects were noted, suggesting that these dietary interventions are generally safe for young patients with epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diet for the treatment of pediatric epilepsy: review and meta-analysis. Sourbron, J., Klinkenberg, S., van Kuijk, SMJ., et al.[2021]

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