Farzad Hoque
Research Mentor: Jeffrey Bohnen
Mentor Department: Psychiatry, Medicine
Author(s): Farzad Hoque, Adelia Nasir, Lauren Gotting, Jeffrey Bohnen
Session: Session 3 (11:00 AM – 11:50 AM)
Presentation Type: Poster 27
Abstract
There is increasing interest in metabolic interventions as potential therapies for bipolar disorder, driven in part by converging evidence linking neuronal stability, mitochondrial function, and mood regulation to ketone metabolism. While ketogenic diets and fasting can induce robust elevations in circulating ketone bodies and associated metabolic changes implicated in neuronal excitability, their implementation may be challenging for many patients, particularly during periods of mood instability. Exogenous ketone ester supplementation represents a promising alternative approach to achieving key metabolic features of therapeutic ketosis; however, the metabolic handling of ketone esters in individuals with bipolar disorder has not yet been systematically characterized. This sub-study aims to conduct detailed metabolic mapping of ketone ester supplementation in individuals with bipolar disorder to address this critical knowledge gap. Using a crossover design, participants will consume one or two doses of a ketone ester supplement across two laboratory visits. Following ingestion, participants will be monitored for four hours, with serial blood and urine sampling to quantify levels of ketone bodies, glucose, insulin, and related metabolic biomarkers. These data will be used to construct pharmacokinetic profiles describing ketone synthesis, peak concentrations, and clearance in this population, for which no such data currently exist. In addition to metabolic outcomes, participants will undergo brief clinician-administered assessments and complete self-reported mood scales to allow for evaluation of clinical correlates. Ratios among key biomarkers may further inform optimal dosing strategies and target engagement for ongoing and future clinical trials investigating ketone ester-based or ketogenic-mimicking interventions in bipolar disorder. Collectively, this metabolic sub-study is intended to provide foundational data necessary for the rational design and interpretation of metabolic therapeutic trials in mood disorders.
