The Ketogenic Diet for Refractory Mental Illness: A Retrospective Analysis of 31 Inpatients

By Albert Danan, Eric C. Westman, Laura R. Saslow, and Georgia Ede: For Complete Post, Click Here…

Background and Hypothesis: The robust evidence base supporting the therapeutic benefit of ketogenic diets in epilepsy and other neurological conditions suggests this same metabolic approach may also benefit psychiatric conditions.

Conclusions: The administration of a ketogenic diet in this semi-controlled setting to patients with treatment-refractory mental illness was feasible, well-tolerated, and associated with significant and substantial improvements in depression and psychosis symptoms and multiple markers of metabolic health.


Globally, an estimated 85 million people suffer from serious, persistent bipolar mood and psychotic illnesses (1), and at least 280 million (2) are thought to be afflicted with depressive illness. Yet even among those with access to modern professional care, meaningful improvement eludes many, and remission is rare. Nearly half of those receiving treatment for bipolar disorder continue to experience recurrent mood episodes (3). Across Europe, approximately 19% of those with depression are considered “treatment-resistant” (4). Worldwide, a mere 23% of those with schizophrenia respond well to antipsychotic medications (5), with symptom relief often coming at the expense of quality and length of life. Metabolic derangements such as hyperglycemia, hypertriglyceridemia, and weight gain are commonplace in those with bipolar disorder (6) as well as in those with schizophrenia (7), significantly increasing risk for obesity, type 2 diabetes, cardiovascular disease, and other chronic health conditions. Indeed, nearly two-thirds of patients initially hospitalized with acute psychosis develop obesity within 20 years of follow-up (8). Metabolic and other undesirable side effects drive approximately 74% of people to discontinue antipsychotic medicines within 18 months, contributing to high hospitalization and relapse rates (9).

These profound limitations of psychopharmacological treatments make the search for new approaches to mental illness of paramount importance. A compelling intervention attracting more attention in recent years is the ketogenic diet (KD), which restricts carbohydrate and induces lipolysis, generating circulating ketone bodies that serve as an adjunctive source of fuel for the brain, reducing its dependence on glucose (10).

Although the study of KDs for the treatment of psychiatric illnesses is in its infancy, the implementation of KDs in neurological illnesses dates back a century, when they first proved useful in the management of epilepsy (11). The now robust evidence base supporting the application of the KD to epilepsy and a growing number of other challenging neurological conditions (12) suggests this same metabolic approach may also benefit psychiatric conditions (13). For example, it is well established that epilepsy and bipolar illness share many neurochemical underpinnings, and this overlap is clinically supported by the fact that many of the same molecules prescribed to control seizures are also prescribed to stabilize mood (14). Indeed, the line separating brain illnesses considered neurological in nature from those considered psychiatric in nature may be more rhetorical than biological (15), as both categories of disease originate within the same organ and display many biochemical similarities, including dysregulation of neurotransmitter systems, destabilization of neural networks, neuroinflammation, excessive oxidative stress, impaired neuroplasticity, mitochondrial dysfunction, and disturbed cerebral glucose metabolism (1618).

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