KORN KURATED RESEARCH

The Keto Diet, a Comprehensive Review, its Variants and Therapeutic Potential

While there is no right diet for everybody, emerging research underscores the benefits of the ketogenic diet, particularly in managing psychotic disorders and promoting overall mental health.

This week, I am focusing on the Keto diet. The ketogenic diet (70-90% fat in daily diet) was introduced in modern times by Dr. Russell Wilder at the Mayo Clinic in 1921 to treat intractable epilepsy. His goal was to mimic the effects of fasting, which led to ketogenesis, and his clinical work proved successful. 

While the controversy continues about which diet is best for us, the fact is there is no one right diet for everyone. It depends on who we are and what our brain, mind, and body need for nourishment. Nevertheless, there is compelling research on the keto diet, especially for epilepsy and psychotic disorders.  A grain free, low carb diet makes sense for this population since a significant percentage of people with a diagnosis of psychosis are highly reactive to the proteins found in gluten and have been found to have challenges with both brain glucose and phospholipid metabolism. And who doesn't benefit from a good supply of high-quality fats?

These papers provide a solid overview of what is known (and not) about how the Keto diet  works and provides descriptions of the four main variants: Classic KD (CKD), Modified Atkins Diet (MAD), Medium Chain Triglyceride Diet (MCT), and Low Glycemic Index Therapy (LGIT) 

These studies suggest the benefits and potential cautions associated with the keto diet. I always encourage my interested clients to try it for 3 months to see if they feel the benefits or if they feel better by adjusting the ratios of fats, proteins, and carbs. 

As I read these studies, I wondered what researchers are making the case against the keto diet. (I maintain every type of diet can work; it just needs to be the right match for the individual.) 

One recent paper I reviewed had fascinating findings, though the full implications are as yet unclear for our clinical practice. By comparing immune responses to the keto or vegan diet and switching from one diet to another, they showed changes to innate immunity versus adaptive immunity, as well as immediate changes in the microbiome. One outcome showed that a vegan diet enhanced the immune system's antiviral function, suggesting that under viral infection conditions, doing a “vegan cleanse” might be helpful. 

Tags: Keto diet, Ketogenic diet, mental health, metabolic psychiatry, metabolic therapy

Interested in Learning More?

• Course(s): Mental Health Disorders
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• Book(s): Nutrition Essentials For Mental Health

Referenced Research Publications

Psychiatry Research
2024, March 20
DOI: 10.1016/j.psychres.2024.115866

Ketogenic Diet Intervention on Metabolic and Psychiatric Health in Bipolar and Schizophrenia: A Pilot Trial

Abstract

The ketogenic diet (KD, also known as metabolic therapy) has been successful in the treatment of obesity, type 2 diabetes, and epilepsy. More recently, this treatment has shown promise in the treatment of psychiatric illness. We conducted a 4-month pilot study to investigate the effects of a KD on individuals with schizophrenia or bipolar disorder with existing metabolic abnormalities. Twenty-three participants were enrolled in a single-arm trial. Results showcased improvements in metabolic health, with no participants meeting metabolic syndrome criteria by study conclusion. Adherent individuals experienced significant reduction in weight (12 %), BMI (12 %), waist circumference (13 %), and visceral adipose tissue (36 %). Observed biomarker enhancements in this population include a 27 % decrease in HOMA-IR, and a 25 % drop in triglyceride levels. In psychiatric measurements, participants with schizophrenia showed a 32 % reduction in Brief Psychiatric Rating Scale scores. Overall Clinical Global Impression (CGI) severity improved by an average of 31 %, and the proportion of participants that started with elevated symptomatology improved at least 1-point on CGI (79 %). Psychiatric outcomes across the cohort encompassed increased life satisfaction (17 %) and enhanced sleep quality (19 %). This pilot trial underscores the potential advantages of adjunctive ketogenic dietary treatment in individuals grappling with serious mental illness.

Reference

Sethi, S., Wakeham, D., Ketter, T., Hooshmand, F., Bjornstad, J., Richards, B., Westman, E., Krauss, R. M., & Saslow, L. (2024). Ketogenic Diet Intervention on Metabolic and Psychiatric Health in Bipolar and Schizophrenia: A Pilot Trial. Psychiatry research, 335, 115866. https://doi.org/10.1016/j.psychres.2024.115866

Frontiers in Nutrition
2024, February 08
DOI: 10.3389/fnut.2024.1331181

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

Abstract

This perspective article delves into the implementation of Ketogenic Metabolic Therapy (KMT) by a mental health counselor who attempts to bridge the gap between emerging research and real-world clinical application. Grounded in the author's clinical experiences, the article communicates the potential of KMT in mental health care, highlighting both its therapeutic promise and the insights gained from hands-on patient interactions. While the adoption of KMT necessitates adjustments in societal, emotional, and dietary domains, especially within diverse mental health contexts, these challenges are surmountable with appropriate guidance and support. The article encourages the capture of qualitative data alongside quantitative measures and advocates for an approach that considers the broader implications of improved mental well-being on families and communities. As the field advances, interdisciplinary collaborations between researchers and clinicians will be pivotal in refining and expanding the application of KMT, ultimately enhancing patient outcomes and elevating the standard of mental health care.

Reference

Laurent N. (2024). From theory to practice: challenges and rewards of implementing ketogenic metabolic therapy in mental health. Frontiers in nutrition, 11, 1331181. https://doi.org/10.3389/fnut.2024.1331181

Signal Transduction and Targeted Therapy
2022, January 17
DOI: 10.1038/s41392-021-00831-w

Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations

Abstract

The ketogenic diet (KD) is a high-fat, adequate-protein, and very-low-carbohydrate diet regimen that mimics the metabolism of the fasting state to induce the production of ketone bodies. The KD has long been established as a remarkably successful dietary approach for the treatment of intractable epilepsy and has increasingly garnered research attention rapidly in the past decade, subject to emerging evidence of the promising therapeutic potential of the KD for various diseases, besides epilepsy, from obesity to malignancies. In this review, we summarize the experimental and/or clinical evidence of the efficacy and safety of the KD in different diseases, and discuss the possible mechanisms of action based on recent advances in understanding the influence of the KD at the cellular and molecular levels. We emphasize that the KD may function through multiple mechanisms, which remain to be further elucidated. The challenges and future directions for the clinical implementation of the KD in the treatment of a spectrum of diseases have been discussed. We suggest that, with encouraging evidence of therapeutic effects and increasing insights into the mechanisms of action, randomized controlled trials should be conducted to elucidate a foundation for the clinical use of the KD.

Reference

Zhu, H., Bi, D., Zhang, Y., Kong, C., Du, J., Wu, X., Wei, Q., & Qin, H. (2022). Ketogenic diet for human diseases: the underlying mechanisms and potential for clinical implementations. Signal transduction and targeted therapy, 7(1), 11. https://doi.org/10.1038/s41392-021-00831-w

Nature Medicine
2024, January 30
DOI: 10.1038/s41591-023-02761-2

Differential peripheral immune signatures elicited by vegan versus ketogenic diets in humans

Abstract

Nutrition has broad impacts on all physiological processes. However, how nutrition affects human immunity remains largely unknown. Here we explored the impact of a dietary intervention on both immunity and the microbiota by performing a post hoc analysis of a clinical trial in which each of the 20 participants sequentially consumed vegan or ketogenic diets for 2 weeks ( NCT03878108 ). Using a multiomics approach including multidimensional flow cytometry, transcriptomic, proteomic, metabolomic and metagenomic datasets, we assessed the impact of each diet, and dietary switch, on host immunity and the microbiota. Our data revealed that overall, a ketogenic diet was associated with a significant upregulation of pathways and enrichment in cells associated with the adaptive immune system. In contrast, a vegan diet had a significant impact on the innate immune system, including upregulation of pathways associated with antiviral immunity. Both diets significantly and differentially impacted the microbiome and host-associated amino acid metabolism, with a strong downregulation of most microbial pathways following ketogenic diet compared with baseline and vegan diet. Despite the diversity of participants, we also observed a tightly connected network between datasets driven by compounds associated with amino acids, lipids and the immune system. Collectively, this work demonstrates that in diverse participants 2 weeks of controlled dietary intervention is sufficient to significantly and divergently impact host immunity, which could have implications for precision nutritional interventions. ClinicalTrials.gov registration: NCT03878108.

Reference

Link, V. M., Subramanian, P., Cheung, F., Han, K. L., Stacy, A., Chi, L., Sellers, B. A., Koroleva, G., Courville, A. B., Mistry, S., Burns, A., Apps, R., Hall, K. D., & Belkaid, Y. (2024). Differential peripheral immune signatures elicited by vegan versus ketogenic diets in humans. Nature medicine, 30(2), 560–572. https://doi.org/10.1038/s41591-023-02761-2