Ketogenic-Mimicking Diet as a Therapeutic Modality for Bipolar Disorder: Biomechanistic Rationale and Protocol for a Pilot Clinical Trial

There is growing interest in the investigation of ketogenic diets as a potential therapy for bipolar disorder. The overlapping pharmacotherapies utilized for both bipolar disorder and seizures suggest that a mechanistic overlap may exist between these conditions, with fasting and the ketogenic diet...

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Vydáno v:	Nutrients Ročník 15; číslo 13; s. 3068
Hlavní autoři:	Bohnen, Jeffrey, Wigstrom, Travis, Griggs, Alexis, Roytman, Stiven, Paalanen, Noah, Andrews, Hailemicael, Bohnen, Nicolaas, Franklin, Jacob, McInnis, Melvin
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Switzerland MDPI AG 07.07.2023 MDPI
Témata:	Bioenergetics biomarkers Bipolar disorder Bipolar Disorder - diet therapy Brain research Brain-derived neurotrophic factor Clinical medicine Clinical trials Convulsions & seizures Diet Diet, Ketogenic - methods Dietary supplements drug therapy emotions Epigenetics glucose Glycemic index Health aspects Humans Hypotheses insulin ketogenic diet Ketone Bodies Ketones Ketosis Medical research Medicine, Experimental Neural networks Nutrition research nutritional intervention Pathogenesis Patient compliance Pilot Projects Product development Protocol Seizures - prevention & control Sodium Michigan network stability ketosis mood mitochondria ketone ester metabolic psychiatry metabolism
ISSN:	2072-6643, 2072-6643
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Abstract	There is growing interest in the investigation of ketogenic diets as a potential therapy for bipolar disorder. The overlapping pharmacotherapies utilized for both bipolar disorder and seizures suggest that a mechanistic overlap may exist between these conditions, with fasting and the ketogenic diet representing the most time-proven therapies for seizure control. Recently, preliminary evidence has begun to emerge supporting a potential role for ketogenic diets in treating bipolar disorder. Notably, some patients may struggle to initiate a strict diet in the midst of a mood episode or significant life stressors. The key question addressed by this pilot clinical trial protocol is if benefits can be achieved with a less restrictive diet, as this would allow such an intervention to be accessible for more patients. Recent development of so-called ketone esters, that once ingested is converted to natural ketone bodies, combined with low glycemic index dietary changes has the potential to mimic two foundational components of therapeutic ketosis: high levels of ketones and minimal spiking of glucose/insulin. This pilot clinical trial protocol thus aims to investigate the effect of a ‘ketogenic-mimicking diet’ (combining supplementation of ketone esters with a low glycemic index dietary intervention) on neural network stability, mood, and biomarker outcomes in the setting of bipolar disorder. Positive findings obtained via this pilot clinical trial protocol may support future target engagement studies of ketogenic-mimicking diets or related ketogenic interventions. A lack of positive findings, in contrast, may justify a focus on more strict dietary interventions for future research.
AbstractList	There is growing interest in the investigation of ketogenic diets as a potential therapy for bipolar disorder. The overlapping pharmacotherapies utilized for both bipolar disorder and seizures suggest that a mechanistic overlap may exist between these conditions, with fasting and the ketogenic diet representing the most time-proven therapies for seizure control. Recently, preliminary evidence has begun to emerge supporting a potential role for ketogenic diets in treating bipolar disorder. Notably, some patients may struggle to initiate a strict diet in the midst of a mood episode or significant life stressors. The key question addressed by this pilot clinical trial protocol is if benefits can be achieved with a less restrictive diet, as this would allow such an intervention to be accessible for more patients. Recent development of so-called ketone esters, that once ingested is converted to natural ketone bodies, combined with low glycemic index dietary changes has the potential to mimic two foundational components of therapeutic ketosis: high levels of ketones and minimal spiking of glucose/insulin. This pilot clinical trial protocol thus aims to investigate the effect of a ‘ketogenic-mimicking diet’ (combining supplementation of ketone esters with a low glycemic index dietary intervention) on neural network stability, mood, and biomarker outcomes in the setting of bipolar disorder. Positive findings obtained via this pilot clinical trial protocol may support future target engagement studies of ketogenic-mimicking diets or related ketogenic interventions. A lack of positive findings, in contrast, may justify a focus on more strict dietary interventions for future research. There is growing interest in the investigation of ketogenic diets as a potential therapy for bipolar disorder. The overlapping pharmacotherapies utilized for both bipolar disorder and seizures suggest that a mechanistic overlap may exist between these conditions, with fasting and the ketogenic diet representing the most time-proven therapies for seizure control. Recently, preliminary evidence has begun to emerge supporting a potential role for ketogenic diets in treating bipolar disorder. Notably, some patients may struggle to initiate a strict diet in the midst of a mood episode or significant life stressors. The key question addressed by this pilot clinical trial protocol is if benefits can be achieved with a less restrictive diet, as this would allow such an intervention to be accessible for more patients. Recent development of so-called ketone esters, that once ingested is converted to natural ketone bodies, combined with low glycemic index dietary changes has the potential to mimic two foundational components of therapeutic ketosis: high levels of ketones and minimal spiking of glucose/insulin. This pilot clinical trial protocol thus aims to investigate the effect of a 'ketogenic-mimicking diet' (combining supplementation of ketone esters with a low glycemic index dietary intervention) on neural network stability, mood, and biomarker outcomes in the setting of bipolar disorder. Positive findings obtained via this pilot clinical trial protocol may support future target engagement studies of ketogenic-mimicking diets or related ketogenic interventions. A lack of positive findings, in contrast, may justify a focus on more strict dietary interventions for future research.There is growing interest in the investigation of ketogenic diets as a potential therapy for bipolar disorder. The overlapping pharmacotherapies utilized for both bipolar disorder and seizures suggest that a mechanistic overlap may exist between these conditions, with fasting and the ketogenic diet representing the most time-proven therapies for seizure control. Recently, preliminary evidence has begun to emerge supporting a potential role for ketogenic diets in treating bipolar disorder. Notably, some patients may struggle to initiate a strict diet in the midst of a mood episode or significant life stressors. The key question addressed by this pilot clinical trial protocol is if benefits can be achieved with a less restrictive diet, as this would allow such an intervention to be accessible for more patients. Recent development of so-called ketone esters, that once ingested is converted to natural ketone bodies, combined with low glycemic index dietary changes has the potential to mimic two foundational components of therapeutic ketosis: high levels of ketones and minimal spiking of glucose/insulin. This pilot clinical trial protocol thus aims to investigate the effect of a 'ketogenic-mimicking diet' (combining supplementation of ketone esters with a low glycemic index dietary intervention) on neural network stability, mood, and biomarker outcomes in the setting of bipolar disorder. Positive findings obtained via this pilot clinical trial protocol may support future target engagement studies of ketogenic-mimicking diets or related ketogenic interventions. A lack of positive findings, in contrast, may justify a focus on more strict dietary interventions for future research.
Audience	Academic
Author	Roytman, Stiven Paalanen, Noah McInnis, Melvin Andrews, Hailemicael Bohnen, Jeffrey Wigstrom, Travis Bohnen, Nicolaas Franklin, Jacob Griggs, Alexis
AuthorAffiliation	6 Department of Radiology, University of Michigan, Ann Arbor, MI 48109, USA 4 Morris K. Udall Center of Excellence for Parkinson’s Disease Research, University of Michigan, Ann Arbor, MI 48109, USA 2 University of Michigan Medical School, Ann Arbor, MI 48109, USA 8 Heinz C. Prechter Bipolar Research Program, University of Michigan, Ann Arbor, MI 48109, USA 7 Department of Psychiatry, University of Michigan, Ann Arbor, MI 48109, USA 1 Department of Neurology, University of Michigan, Ann Arbor, MI 48109, USA 5 Parkinson’s Foundation Research Center of Excellence, University of Michigan, Ann Arbor, MI 48109, USA 3 Neurology Service and GRECC, VA Ann Arbor Healthcare System, Ann Arbor, MI 48105, USA
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Snippet	There is growing interest in the investigation of ketogenic diets as a potential therapy for bipolar disorder. The overlapping pharmacotherapies utilized for...
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SubjectTerms	Bioenergetics biomarkers Bipolar disorder Bipolar Disorder - diet therapy Brain research Brain-derived neurotrophic factor Clinical medicine Clinical trials Convulsions & seizures Diet Diet, Ketogenic - methods Dietary supplements drug therapy emotions Epigenetics glucose Glycemic index Health aspects Humans Hypotheses insulin ketogenic diet Ketone Bodies Ketones Ketosis Medical research Medicine, Experimental Neural networks Nutrition research nutritional intervention Pathogenesis Patient compliance Pilot Projects Product development Protocol Seizures - prevention & control Sodium
Title	Ketogenic-Mimicking Diet as a Therapeutic Modality for Bipolar Disorder: Biomechanistic Rationale and Protocol for a Pilot Clinical Trial
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