The use of a low carbohydrate, ketogenic diet in bipolar disorder: systematic review

Abstract Background: Bipolar disorder is a neurodevelopmental illness characterized by severe biphasic changes in mood, energy, or thought. Key underlying metabolic pathologies thought to play a role include dysfunction in energy metabolism. The purpose of this article is to review the findings to date of the effects of a low carbohydrate ketogenic diet (KD) on mood symptoms in preclinical and clinical models of bipolar illness. The review highlights the underlying metabolic pathologies of bipolar disorder (BD) and potential therapeutic effects of the KD on these pathologies. The article also explores the potential effects of a KD on metabolic health in BD, including proposed mechanisms of action.Summary: Recent findings support the idea that bipolar disorder, along with other psychiatric disease, may have roots of metabolic dysfunction: cerebral glucose hypometabolism, oxidative stress, as well as mitochondrial and neurotransmitter dysfunction which has downstream effects on synapse connections. A KD provides alternative fuel to the brain aside from glucose and is believed to contain beneficial neuroprotective effects, including stabilization of brain networks, reduction of inflammation and oxidative stress. Several beneficial metabolic effects on insulin resistance, weight, and lipids have been shown. Based on its effectiveness in treating epilepsy, the KD has garnered recent interest in its application for mood disorders as it may imitate the pharmacological effects of mood stabilizers, commonly prescribed agents in the treatment of both BD and epilepsy. Additionally, it may improve metabolic dysfunction often seen in BD and repair deficits in energy metabolism. Limited case studies on KD treatment in BD have been reported; however, studies addressing the potential therapeutic effects of KD on metabolic abnormalities in mental illness are promising. Literature of plausible mechanisms and reports of improvements in psychosis, cognition and mood symptoms have been increasing.Conclusions: Preliminary findings support further testing of a low carbohydrate KD as a potential therapeutic tool in repairing energy metabolism in bipolar illness. Further research and clinical trials are needed to evaluate the efficacy of a KD as a supplemental or co-treatment of bipolar illness and the first open-label trial testing the diet in bipolar illness is currently underway at Stanford.