The Role of Ketogenic Metabolic Therapy on the Brain in Serious Mental Illness: A Review

Abstract

In search of interventions targeting brain dysfunction and underlying cognitive impairment in schizophrenia, we look at the brain and beyond to the potential role of dysfunctional systemic metabolism on neural network instability and insulin resistance in serious mental illness. We note that disrupted insulin and cerebral glucose metabolism are seen even in medication-naïve first-episode schizophrenia, suggesting that people with schizophrenia are at risk for Type 2 diabetes and cardiovascular disease, resulting in a shortened life span. Although glucose is the brain’s default fuel, ketones are a more efficient fuel for the brain. We highlight evidence that a ketogenic diet can improve both the metabolic and neural stability profiles. Specifically, a ketogenic diet improves mitochondrial metabolism, neurotransmitter function, oxidative stress/inflammation, while also increasing neural network stability and cognitive function. To reverse the neurodegenerative process, increasing the brain’s access to ketone bodies may be needed. We describe evidence that metabolic, neuroprotective, and neurochemical benefits of a ketogenic diet potentially provide symptomatic relief to people with schizophrenia while also improving their cardiovascular or metabolic health. We review evidence for KD side effects and note that although high in fat it improves various cardiovascular and metabolic risk markers in overweight/obese individuals. We conclude by calling for controlled clinical trials to confirm or refute the findings from anecdotal and case reports to address the potential beneficial effects of the ketogenic diet in people with serious mental illness.

Sleep, mood disorders, and the ketogenic diet: potential therapeutic targets for bipolar disorder and schizophrenia

“…Intracerebral ventricular injection of the ketone body, acetoacetate, in mice increases delta power during sleep ( 176 ). The ketogenic diet in both diabetics ( 177 ) and psychiatric ( 178 ) patients improved their subjective sleep quality measured by the Pittsburgh Sleep Quality Index. Narcoleptic patients on a ketogenic diet showed reduced narcolepsy symptoms ( 179 ).…”

Metabolic health: A new frontier

“…Many neurological diseases, including Alzheimer's and Parkinson's disease, major depressive disorder, bipolar disorder, schizophrenia and epilepsy, are characterised by impaired brain glucose utilisation, insulin resistance, neurotransmitter imbalances, mitochondrial dysfunction, oxidative stress and inflammation. 5 Traditionally, nutrition has not been considered a metabolic therapy affecting the structure and function of the brain. However, recent dietary advances in altering fuel provision to the brain and in high-dose micronutrient supplementation 6 show promise in influencing biological…”

From theory to practice: challenges and rewards of implementing ketogenic metabolic therapy in mental health

“…While much of the existing literature on Ketogenic Metabolic Therapy (KMT) for mental health is grounded in emerging research (1)(2)(3)(4), the perspective of a clinician, especially one with a background in clinical psychology, offers a distinctive viewpoint. Clinicians bridge the gap between theoretical research and its real-world application, providing valuable insights from their direct interactions with patients.…”