Navigation
The effects of ketogenic metabolic therapy on mental health and metabolic outcomes in schizophrenia and bipolar disorder: a randomized controlled clinical trial protocol
Schizophrenia, schizoaffective disorder, and bipolar affective disorder are severe psychiatric conditions marked by chronic disruptions in emotional, behavioral, and cognitive functioning. These disorders share common features, including significant disturbances in affect, thought processes, and behavioral regulation. Epidemiologically, they are associated with a high prevalence of cardiovascular, metabolic, infectious, and respiratory comorbidities, leading to a reduced life expectancy of up to 25 years. Nutritional ketosis, an approach shown to be effective in treating various neurological disorders, has demonstrated promise in preclinical animal models of psychotic conditions. Recent open clinical trials suggest that nutritional ketosis can significantly reduce psychotic, affective, and metabolic symptoms in schizophrenia and bipolar disorder. The aim of this study was to explore the effects of nutritional ketosis through a modified ketogenic diet (MKD) over 14 weeks in stable, community-dwelling patients diagnosed with bipolar disorder, schizoaffective disorder, or schizophrenia. A randomized, placebo-controlled clinical trial involving 100 non-hospitalized adult participants with a diagnosis of bipolar disorder, schizoaffective disorder, or schizophrenia, all of whom were capable of providing consent and willing to modify their diet. Participants were either placed on a dietitian-guided, medically supervised ketogenic diet or a diet adhering to the Australian Guide to Healthy Eating, both for a duration of 14 weeks. Psychiatric and cognitive measures, including symptom improvement and functional changes, were assessed using the Positive and Negative Syndrome Scale (PANSS), Young Mania Rating Scale (YMRS), Beck Depression Inventory (BDI), WHO Disability Schedule, Affect Lability Scale, and the Cambridge Cognitive Battery. Metabolic outcomes were assessed by monitoring changes in body weight, blood pressure, liver and kidney function tests, lipid profiles, and markers of insulin resistance. Blood ketone and glucose levels were measured to explore potential correlations between primary and secondary outcomes. Additional optional assessments included hair cortisol analysis to examine long-term stress, and variations in fecal microbiome composition. Autonomic nervous system activity was monitored using wearable devices (OURA ring and EMBRACE wristband), tracking skin conductance, oximetry, continuous pulse monitoring, respiratory rate, movement, and sleep quality. Based on promising results from preclinical studies, other neurodevelopmental disorder research, and open trials in bipolar disorder and schizophrenia, we hypothesize that ketogenic metabolic therapy will be well-tolerated and lead to improvements in both psychiatric and metabolic outcomes, as well as overall social and community functioning. We also anticipate a potential correlation between the degree of ketosis achieved and improvements in metabolic, cognitive, and psychiatric outcomes in the intervention group.
Year: 2024
