Exploring the role of ketone bodies in the diagnosis and treatment of psychiatric disorders

Abstract

In recent times, advances in the field of metabolomics have shed greater light on the role of metabolic disturbances in neuropsychiatric conditions. The following review explores the role of ketone bodies and ketosis in both the diagnosis and treatment of three major psychiatric disorders: major depressive disorder, anxiety disorders, and schizophrenia. Distinction is made between the potential therapeutic effects of the ketogenic diet and exogenous ketone preparations, as exogenous ketones in particular offer a standardized, reproducible manner for inducing ketosis. Compelling associations between symptoms of mental distress and dysregulation in central nervous system ketone metabolism have been demonstrated in preclinical studies with putative neuroprotective effects of ketone bodies being elucidated, including effects on inflammasomes and the promotion of neurogenesis in the central nervous system. Despite emerging pre-clinical data, clinical research on ketone body effectiveness as a treatment option for psychiatric disorders remains lacking. This gap in understanding warrants further investigating, especially considering that safe and acceptable ways of inducing ketosis are readily available.

Dose-Dependent Beneficial Effect of Ketone Supplement-Evoked Ketosis on Anxiety Level in Female WAG/Rij Rats: Sometimes Less Is More

“…It has also been demonstrated previously that exogenous ketone supplements, such as ketone salts (KSs) and ketone esters (KEs), not only increase the blood levels of ketone bodies (ketosis) but also effectively decrease anxiety levels in different preclinical rodent models [3,[9][10][11][12][13][14][15]. Moreover, the connection between the ketone supplement-evoked increase in blood ketone body β-hydroxybutyrate (βHB) levels and anxiolytic effects was also confirmed [3,9,12,14,16].…”

“…It has been demonstrated that up to one-third of the population can be affected by anxiety disorders during their lifetime [1][2][3]. However, our knowledge about the mechanism of action of anxiety disorders is far from complete [1,3].…”

“…It has been demonstrated that up to one-third of the population can be affected by anxiety disorders during their lifetime [1][2][3]. However, our knowledge about the mechanism of action of anxiety disorders is far from complete [1,3]. It has been demonstrated that changes, in particular GABA (gamma-aminobutyric acid)-ergic, serotonergic, glutamatergic, noradrenergic and adenosinergic systems in implicated brain areas, such as the hippocampus, prefrontal cortex and amygdala, may have a role in the pathological alterations resulting anxiety disorders [4][5][6][7].…”

Diabetes alters neuroeconomically dissociable forms of mental accounting

“…Indeed, diabetes in animals can impair novel spatial and object recognition as well as performance in Barnes, Morris watermaze, and active-avoidance foot-shock tasks, aspects of which may be correctable with glycemic control [42][43][44] . However, glucose is not the only fuel available to the brain; the brain can also utilize ketones as a fuel source, although this switch in metabolism requires mitochondrial adaptations, some of which have been linked to changes in motivated behavior 2,45,46 . More recent work has implicated glucose-independent roles of insulin function directly in the central nervous system [10][11][12][13][14] .…”

Diet and lifestyle impact the development and progression of Alzheimer’s dementia

“…It has been posited that the production of ketone bodies derived from a ketogenic diet may act as glutamate inhibitors in the NMDA extrasynaptic receptor, decreasing inflammation and oxidative stress ( 93 ). Nevertheless, more evidence-based research is needed before determining whether adherence to ketogenic diets reduces the risk of dementia ( 85 , 94 ) and psychiatric diseases ( 93 , 95 ).…”