Ketosis for Bipolar Disorder

Recruiting at 2 trial locations

Overseen By Dost Ongur, MD PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: Stony Brook University

Must not be taking: Psychotropics, Insulin, Antidiabetics, others

Disqualifiers: Type 1 diabetes, Seizure disorders, Unstable medical illness, others

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

Compensation: Varies

Number of Visits: 3

Duration: 2 days

100 Participants Needed

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to test how specific components of diet affect brain function and behavior for individuals with bipolar. The main question it aims to answer is how glucose and ketones each affect the brain's response to risk and reward. Participants will be asked to provide blood (to assess baseline measures of how the body uses energy), and then to receive two MRI scan sessions, on separate days. During each MRI scan session, participants will play three games, from which they can win money, before and after drinking glucose (on one day) or ketones (on the other day). Investigators will compare individuals with and without bipolar to test whether the two groups differ in how their brains use energy, and to test how the brain's use of energy affects behavior.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that healthy volunteers should not be on psychotropic medication. If you are taking insulin or other antidiabetic medications, you may not be eligible to participate.

What data supports the effectiveness of the treatment Ketosis for Bipolar Disorder?

Research shows that the ketogenic diet, which induces ketosis, has helped stabilize mood in individuals with type II bipolar disorder, with some experiencing better results than with medication. Additionally, ketosis is known to provide an alternative energy source for the brain and may reduce inflammation and oxidative stress, which are linked to bipolar disorder. ^{1 2 3 4 5}

Is the ketogenic diet safe for humans?

Research shows that the ketogenic diet is generally safe for humans, with studies indicating no significant adverse effects in both short-term and long-term use. In a study with healthy adults, a novel ketone supplement was well-tolerated with no meaningful changes in safety measures, and in cases of bipolar disorder, the diet was well-tolerated with no significant adverse effects. ^{1 2 6 7 8}

How does the ketogenic diet treatment differ from other treatments for bipolar disorder?

The ketogenic diet is unique because it stabilizes mood by inducing ketosis, which reduces intracellular sodium and calcium levels, unlike traditional medications. This diet provides an alternative energy source for the brain, potentially improving mood stabilization without significant adverse effects. ^{1 2 3 4 6}

Research Team

Lilianne R Mujica-Parodi, Ph.D.

Principal Investigator

SUNY Stony Brook University

Eligibility Criteria

This trial is for individuals with bipolar disorder. Participants will need to provide blood samples and undergo two MRI scan sessions while playing money-winning games, after consuming glucose on one day and ketones on another.

Inclusion Criteria

I am able to understand and sign the consent form.

I have been diagnosed with bipolar disorder according to the DSM-V.

I am between 18 and 45 years old.

Exclusion Criteria

I have kidney disease.

I have had a condition where my lymphocytes multiply unusually.

I haven't had cancer in the last 5 years, except for skin cancer.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Baseline blood samples are taken to measure metabolic function variables

1 day

1 visit (in-person)

Treatment

Participants undergo two MRI scan sessions on separate days, playing games before and after consuming glucose or ketones

2 days

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Ketosis

Trial Overview The study investigates how diet components like glucose and ketones affect brain function in people with bipolar disorder. It compares the brain's energy use and behavioral responses during risk-reward tasks in an MRI setting.

Participant Groups

Group I: Ketone Supplement-MRI/MRS Experimental Treatment 2 Interventions

Participants (both the Bipolar Cohort and Healthy Comparison Cohort) will be tested twice, both times in an overnight fasting condition (8 hours no food, unrestricted water). Halfway through each of the two scan sessions, participants will be asked to drink either glucose (on one day) or ketones (on the other day). This within-subjects comparison will allow investigators to observe the effects of metabolism on brain function. Participants' glucose and ketone levels will also be measured, using a finger-prick blood measurement at three different times: 1) immediately before the scan session 2) 10 minutes after drinking the glucose or supplement 3) immediately following the scan session.

Who Is Running the Clinical Trial?

Stony Brook University

Lead Sponsor

Trials

225

Recruited

41,700+

Massachusetts General Hospital

Collaborator

Trials

3,066

Recruited

13,430,000+

Mclean Hospital

Collaborator

Trials

221

Recruited

22,500+

Findings from Research

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]

Oral administration of exogenous ketone supplements over 28 days effectively induced sustained nutritional ketosis in male rats, achieving ketone levels greater than 0.5 mM without the need for carbohydrate restriction.

The study showed that these supplements led to a rapid increase in β-hydroxybutyrate (βHB) levels and a decrease in blood glucose, while having minimal impact on lipid levels, indicating their potential safety and efficacy for therapeutic use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague-Dawley rats. Kesl, SL., Poff, AM., Ward, NP., et al.[2020]

The ketogenic diet and exogenous ketone supplements can effectively increase serum ketone levels, providing an alternative energy source for high-demand tissues like the brain and heart, which may enhance overall health.

Nutritional ketosis has shown potential therapeutic benefits for various conditions, including heart diseases, epilepsy, mitochondrial diseases, and neurodegenerative disorders, suggesting a growing interest in its application for precision nutrition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diets and Ketone suplementation: A strategy for therapeutic intervention. Saris, CGJ., Timmers, S.[2022]

Induced ketosis, through ketone body ingestion, provides an alternative energy source that can help alleviate symptoms of neuroprogressive disorders like schizophrenia, bipolar disorder, and major depressive disorder by reducing oxidative stress, mitochondrial dysfunction, and inflammation.

The review highlights that induced ketosis may also target abnormal signaling pathways and molecules associated with these disorders, suggesting a multifaceted mechanism of action, while also addressing the long-term safety of this approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induced Ketosis as a Treatment for Neuroprogressive Disorders: Food for Thought? Morris, G., Puri, BK., Carvalho, A., et al.[2021]

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 28-day study involving 59 healthy adults, the novel exogenous ketone diester bis-hexanoyl-(R)-1,3-butanediol (BH-BD) was found to be well-tolerated and safe, with no significant differences in tolerability scores compared to a placebo.

BH-BD effectively increased blood ketone levels one hour after consumption, indicating its potential for promoting nutritional ketosis without adverse effects on vital signs or laboratory measures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tolerability and Safety of a Novel Ketogenic Ester, Bis-Hexanoyl (R)-1,3-Butanediol: A Randomized Controlled Trial in Healthy Adults. Chen, O., Blonquist, TM., Mah, E., et al.[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]

References

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

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

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

Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague-Dawley rats. [2020]

3. Switzerland pubmed.ncbi.nlm.nih.gov

Ketogenic diets and Ketone suplementation: A strategy for therapeutic intervention. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Induced Ketosis as a Treatment for Neuroprogressive Disorders: Food for Thought? [2021]

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

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

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

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

7. Switzerland pubmed.ncbi.nlm.nih.gov

Tolerability and Safety of a Novel Ketogenic Ester, Bis-Hexanoyl (R)-1,3-Butanediol: A Randomized Controlled Trial in Healthy Adults. [2021]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Long-term monitoring of the ketogenic diet: Do's and Don'ts. [2017]