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A Pilot Study of a Ketogenic Diet in Bipolar Disorder: Clinical, Metabolomic and Magnetic Resonance Spectroscopy Outcomes

doi: https://doi.org/10.1101/2023.10.23.23297391
This article is a preprint and has not been certified by peer review

Abstract

Background

Bipolar disorder and epilepsy are treated with anti-seizure medications. Preliminary evidence indicates that a ketogenic diet (a metabolic treatment for epilepsy) may be effective in the treatment of bipolar disorder.

Aims
To explore the impact of a ketogenic diet on clinical outcomes, and metabolomic and brain magnetic resonance spectroscopy biomarkers.

Methods
Euthymic individuals with bipolar disorder (N=27) were recruited to a 6-8 week single-arm trial of a modified ketogenic diet and a range of metabolic and clinical outcome measures were assessed.

Results
There was a positive correlation between daily ketone levels and ecological momentary assessments of mood (p < 0.001) and energy (p < 0.001) and an inverse correlation between ketone levels and impulsivity (p < 0.001) and anxiety (p < 0.001). Mean weight fell by 4.2kg (p < 0.001), mean BMI fell by 5.3% (p < 0.001) and mean systolic blood pressure was reduced by 7.4 mmHg (p < 0.041). Brain Glx (a putative marker of treatment response to anti-seizure medication) decreased by 13.1% in the posterior cingulate cortex (PCC) (p < 0.001) and by 9.2% in the anterior cingulate cortex ACC (p = 0.02). At the dietary cessation period, one third of participants, who reported reduced mood lability, opted to remain on a ketogenic diet.

Conclusion
The majority of participants had improved cardiometabolic risk parameters and approximately one third experienced improvement in psychiatric symptoms. The study findings are consistent with our a priori hypothesis of ketone bodies acting as an alternative metabolic substrate under conditions of impaired insulin signalling in a subgroup of patients with bipolar disorder.