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

Abstract

AbstractBackgroundBipolar 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.AimsTo explore the impact of a ketogenic diet on clinical outcomes, and metabolomic and brain magnetic resonance spectroscopy biomarkers.MethodsEuthymic 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.ResultsThere 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.ConclusionThe 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.Practitioner PointsA ketogenic diet may be effective in improving cardiometabolic risk factors and managing medication-induced weight gain. 95% of participants lost weight with a mean of 4.2kg (p< 0.001) over 8 weeks.Ketone level was correlated to improved daily ecological momentary assessments of mood (p< 0.001) and energy (p< 0.001) and decreased impulsivity (p< 0.001) and anxiety (p< 0.001).Participants who opted out of the dietary cessation period to remain on the diet, and who had reduced Affective Lability Scores, were characterised by more pronounced insulin resistance (HOMA-IR + 27.19%) and higher fasting insulin (+ 19.26%) at baseline.Study Registration Number: ISRCTN61613198