Brain Small Chain Fatty Acid Metabolism in Bipolar Disorder: Ketones

Small exploratory open-label pilot study to assess supplementation of a ketone ester (Juvenescence) combined with a 'ketogenic-mimicking diet' as a potential therapy for persons with bipolar disorder.

The overarching goal of this open-label, exploratory pilot study is to explore biomechanistic effects of exogenous ketone supplementation combined with a low glycemic diet (in effect, a 'ketogenic-mimicking diet') for patients with bipolar disorder. This represents a less restrictive metabolic intervention compared to a strict ketogenic diet while replicating two foundational elements of the ketogenic diet: low levels of glycemic/insulin signaling and high levels of circulating ketones. In addition to assessments of mood stability and global functioning, functional neuroimaging data will be obtained to better characterize the biomechanistic effects of this intervention.

Eligibility Criteria:
Inclusion Criteria:

* 18 and older
* Able to provide informed consent
* Diagnosis of bipolar disorder, type I or II as determined primarily via medical/psychiatric documentation provided from mental health provider with patient consent
* Regular access to smart phone capable of syncing biometric wearable data collection
* If taking psychiatric medications, on stable regimen as defined by no medication changes for mood stabilizers and/or antipsychotics in prior 4 weeks

Exclusion Criteria:

* Inability to adhere to dietary changes as specified in protocol (e.g., not in control of food selection)
* History of moderate-to-severe traumatic brain injury, e.g. loss of consciousness \> 10 min, neurologic sequela
* Evidence of large vessel stroke or mass lesion on previous MRI or MRI obtained during study
* History of significant GI disease (e.g., malabsorptive disorder, gastric cancer, intestinal resection)
* Pregnancy (as determined via urine pregnancy test at study initiation), if capable of becoming pregnant, or breastfeeding
* Unwilling to utilize birth control method during course of study (e.g., barrier contraception, oral contraceptive, IUD), if capable of becoming pregnant
* Currently receiving treatment with insulin (e.g., chronic pancreatitis, diabetes mellitus)
* History of mitochondrial disorder and/or significant uncontrolled metabolic/medical disorder
* Active/current illicit substance use (and/or consumption of \>1 alcoholic beverages per day) - defined as using psychoactive medications not as prescribed or using illicit substances (as determined via urine drug screen and screening interview)
* Use of marijuana or THC products more than once monthly on average
* Subjects with contra-indications to MR imaging, including pacemakers or severe claustrophobia, and/or size incompatible with scanner gantry, e. g., men over 6 feet tall that weigh more than 250 lbs, men under 6 feet tall that weigh over 220 lbs, women over 5'11" tall that weigh more than 220 lbs, or women under 5'10" tall that weigh more than 200 lbs. Subjects of these weights or greater typically have difficult fitting into the fMRI scanner properly.
* Suicidal thoughts with plans or intentions, as assessed by C-SSRS
* Any other condition or criteria that would preclude safe and meaningful participation in this study