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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how diet, specifically glucose and ketones, impacts brain function and behavior in people with bipolar disorder. Participants will undergo MRI scans and play money-winning games after consuming either glucose or ketones to observe different brain reactions. It suits those with a stable bipolar disorder diagnosis who haven't been hospitalized in the last four weeks. As an unphased study, this trial offers participants the opportunity to contribute to groundbreaking research on dietary impacts on mental health.

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 prior data suggests that this dietary protocol is safe for individuals with bipolar disorder?

Research has shown that ketogenic diets, which raise ketone levels in the body, are generally well-tolerated. Some studies have found that these diets can help reduce mental health symptoms, such as mood swings and sleep problems. For instance, one study found that 17% of participants on a ketogenic diet felt more satisfied with their lives, and 19% reported better sleep.

Another study noted improvements in mental health symptoms, suggesting the diet might help with conditions like bipolar disorder. While these results are encouraging, not everyone will experience the same benefits.

Overall, evidence suggests that ketosis could be a safe option for those with bipolar disorder, but consulting a healthcare provider before making major dietary changes is always best. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike current treatments for bipolar disorder that often involve medications like mood stabilizers and antipsychotics, the ketosis treatment being explored focuses on altering brain metabolism. By using ketone supplements, this approach targets brain energy use, which might influence mood regulation in a novel way. Researchers are excited because this metabolic shift could offer a new pathway for managing bipolar disorder, potentially with fewer side effects than traditional medications.

What evidence suggests that ketosis might be an effective treatment for bipolar disorder?

Research has shown that the ketogenic diet might help manage bipolar disorder. In one case, a person with bipolar disorder experienced significant improvement in depression after starting this diet. Another study found that 69% of people with bipolar disorder felt noticeably better when following the ketogenic diet. This trial will explore the effects of ketosis through a ketone supplement, allowing researchers to observe its impact on brain function. Ongoing clinical trials have reported a significant reduction in mood and metabolic symptoms with this approach. Overall, these findings suggest that ketosis could be a promising way to manage symptoms of bipolar disorder. ^{1 2 4 6 7}

Who Is on the Research Team?

Lilianne R Mujica-Parodi, Ph.D.

Principal Investigator

SUNY Stony Brook University

Are You a Good Fit for This Trial?

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.

My vision is 20/20 or can be corrected to 20/20 with contacts.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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) 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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11346312/

Retrospective case study: ketogenic metabolic therapy in ... In this case study, a ketogenic diet significantly improved treatment-resistant depressive symptoms in a patient with bipolar disorder. Both ...

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. psychiatrist.com psychiatrist.com/news/ketogenic-diet-shows-promise-for-bipolar-disorder/

Ketogenic Diet Shows Promise for Bipolar Disorder Clinical relevance: University of Edinburgh researchers suggest that a ketogenic diet could help better manage bipolar disorder.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11371693/

The effects of ketogenic metabolic therapy on mental health ... More recent data from open clinical trials have pointed toward a dramatic reduction in psychotic, affective, and metabolic symptoms in both ...

5. clinicaltrials.gov clinicaltrials.gov/study/NCT06920940

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

6. 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 ...

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

Impact of a Ketogenic Diet on Metabolic and Psychiatric ... Low-carbohydrate high-fat (LCHF) or ketogenic diets (KD) have been shown to reduce cardiovascular risk in those with insulin resistance.