Abstract

(1) Background: The ketogenic diet (KD) was developed in the 1920s as a treatment for pediatric epilepsy and is emerging as a possible treatment option for certain mental health disorders. There is a link between certain mental health disorders and epilepsy, suggesting some commonality among underlying mechanisms. (2) Methods: The literature relating to mental disorders and the KD is sparse. The authors attempt to a narrative review of the existing literature to show that there may be validity to studying the KD as a treatment for certain mental health disorders. (3) Results: Various types of mitochondrial dysfunction and impaired oxidative metabolism have been identified in many mental health disorders (bipolar disorder, major depressive disorder, autism, schizophrenia, and others). Mitochondrial deficits may affect neuroplasticity and cause synaptic dysfunction, which could change brain structure and function in a way that might affect behavior. The KD has been associated with epigenetic changes in the genes associated with mitochondrial function. Chronic oxidative stress and inflammation have also been implicated in mental health disorders and may be reduced by the KD. The KD regulates glutamatergic transmission and may initiate extracellular changes as well, in a manner similar to pharmacological agents used to stabilize moods. The KD may be difficult for patient adherence and has been associated with many and potentially severe adverse effects. The role of the KD in addressing treatment-resistant pediatric epilepsy is established and epilepsy is comorbid with a number of mental health conditions. (4) Conclusions: There is a paucity of literature on this subject and there is no robust clinical evidence in support of the use of the KD for treating mental disorders but there are indications that the KD can reduce systemic inflammation, improve cerebral mitochondrial metabolism, and enhance endogenous antioxidation, all of which may be helpful in treating certain mental health conditions. The KD is also associated with serious health risks and clinicians must weigh risks versus benefits.

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