Ketogenic Therapy in Serious Mental Illness: Emerging Evidence

Sarnyai, Zoltán; Palmer, Christopher M.

doi:10.1093/ijnp/pyaa036

Cited by 16 publications

(7 citation statements)

References 26 publications

(34 reference statements)

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“…Initial, evidence suggests that beta-hydroxybutyrate (BHB) (a primary ketone upregulated by the diet) can attenuate stress-induced behavioral and inflammatory responses via NLRP3 inhibition [ 92 ]. Positive impacts on mood, cognition, and weight loss have also been reported across several case studies in individuals with BD and schizophrenia [ 93 ]. Researchers at Stanford University have recently initiated the first open label trial to more rigorously investigate these findings in both disorders [94].…”

Section: Inflammasome Activationmentioning

confidence: 97%

Inflammatory signaling mechanisms in bipolar disorder

et al. 2021

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Bipolar disorder is a decidedly heterogeneous and multifactorial disease, with a high individual and societal burden. While not all patients display overt markers of elevated inflammation, significant evidence suggests that aberrant immune signaling contributes to all stages of the disease, and likely explains the elevated rates of comorbid inflammatory illnesses seen in this population. While individual systems have been intensely studied and targeted, a relative paucity of attention has been given to the interconnecting role of inflammatory signals therein. This review presents an updated overview of some of the most prominent pathophysiologic mechanisms in bipolar disorder, from mitochondrial, endoplasmic reticular, and calcium homeostasis, to purinergic, kynurenic, and hormonal/neurotransmitter signaling, showing inflammation to act as a powerful nexus between these systems. Several areas with a high degree of mechanistic convergence within this paradigm are highlighted to present promising future targets for therapeutic development and screening.

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Section: Inflammasome Activationmentioning

confidence: 97%

Inflammatory signaling mechanisms in bipolar disorder

et al. 2021

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“…However, as rigorous clinical trial evidence is not yet available in this field, it remains unclear to what extent serious mental illnesses may benefit from a metabolic approach. Therefore, to the isolated case reports of individuals with major depressive illness ( 19 ), bipolar illness ( 20 , 21 ), and psychotic illness ( 22 ) who have benefited from a KD, we add this case series of 31 patients with treatment-refractory mental illness treated with a KD in a semi-controlled hospital setting.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2022

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Background and HypothesisThe 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.Study DesignIn this retrospective analysis of clinical care, 31 adults with severe, persistent mental illness (major depressive disorder, bipolar disorder, and schizoaffective disorder) whose symptoms were poorly controlled despite intensive psychiatric management were admitted to a psychiatric hospital and placed on a ketogenic diet restricted to a maximum of 20 grams of carbohydrate per day as an adjunct to conventional inpatient care. The duration of the intervention ranged from 6 to 248 days.Study ResultsThree patients were unable to adhere to the diet for >14 days and were excluded from the final analysis. Among included participants, means and standard deviations (SDs) improved for the Hamilton Depression Rating Scale scores from 25.4 (6.3) to 7.7 (4.2), P < 0.001 and the Montgomery-Åsberg Depression Rating Scale from 29.6 (7.8) to 10.1 (6.5), P < 0.001. Among the 10 patients with schizoaffective illness, mean (SD) of the Positive and Negative Syndrome Scale (PANSS) scores improved from 91.4 (15.3) to 49.3 (6.9), P < 0.001. Significant improvements were also observed in metabolic health measures including weight, blood pressure, blood glucose, and triglycerides.ConclusionsThe 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.

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“…More thorough and long-term case surveys have been performed in diverse populations and have presented promising findings concerning symptoms’ management, safety, and feasibility [ 107 ]. Two individuals with established, therapy-tolerant schizoaffective disease adopted KD for body weight reduction [ 106 ].…”

Section: Resultsmentioning

confidence: 99%

The Relationship of Ketogenic Diet with Neurodegenerative and Psychiatric Diseases: A Scoping Review from Basic Research to Clinical Practice

et al. 2023

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Background: The ketogenic diet (KD) has become widespread for the therapy of epileptic pathology in childhood and adulthood. In the last few decades, the current re-emergence of its popularity has focused on the treatment of obesity and diabetes mellitus. KD also exerts anti-inflammatory and neuroprotective properties, which could be utilized for the therapy of neurodegenerative and psychiatric disorders. Purpose: This is a thorough, scoping review that aims to summarize and scrutinize the currently available basic research performed in in vitro and in vivo settings, as well as the clinical evidence of the potential beneficial effects of KD against neurodegenerative and psychiatric diseases. This review was conducted to systematically map the research performed in this area as well as identify gaps in knowledge. Methods: We thoroughly explored the most accurate scientific web databases, e.g., PubMed, Scopus, Web of Science, and Google Scholar, to obtain the most recent in vitro and in vivo data from animal studies as well as clinical human surveys from the last twenty years, applying effective and characteristic keywords. Results: Basic research has revealed multiple molecular mechanisms through which KD can exert neuroprotective effects, such as neuroinflammation inhibition, decreased reactive oxygen species (ROS) production, decreased amyloid plaque deposition and microglial activation, protection in dopaminergic neurons, tau hyper-phosphorylation suppression, stimulating mitochondrial biogenesis, enhancing gut microbial diversity, restoration of histone acetylation, and neuron repair promotion. On the other hand, clinical evidence remains scarce. Most existing clinical studies are modest, frequently uncontrolled, and merely assess the short-term impacts of KD. Moreover, several clinical studies had large dropout rates and a considerable lack of compliance assessment, as well as an increased level of heterogeneity in the study design and methodology. Conclusions: KD can exert substantial neuroprotective effects via multiple molecular mechanisms in various neurodegenerative and psychiatric pathological states. Large, long-term, randomized, double-blind, controlled clinical trials with a prospective design are strongly recommended to delineate whether KD may attenuate or even treat neurodegenerative and psychiatric disease development, progression, and symptomatology.

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Ketogenic Therapy in Serious Mental Illness: Emerging Evidence

Cited by 16 publications

References 26 publications

Inflammatory signaling mechanisms in bipolar disorder

Inflammatory signaling mechanisms in bipolar disorder

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

The Relationship of Ketogenic Diet with Neurodegenerative and Psychiatric Diseases: A Scoping Review from Basic Research to Clinical Practice

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