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Researchers will test this nutritional therapy's ability to improve patients' mental and physical health. This project builds on a growing body of research suggesting the potential of metabolic therapies in treating serious mental illness.
Psychotic disorders carry a massive personal burden and are associated with a lower life expectancy. Psychosis does not develop immediately, but typically emerges following a period of early, subtle symptoms. Individuals in this stage, classified as CHR-P, represent a critical pre-symptomatic stage offering a window for preventive treatment. However, while diagnostic tools for detecting CHR-P are well-developed, treatment options remain limited. Currently, there is no specific, indicated treatment to reduce the rate of transition to full psychosis in CHR-P patients, underlining an urgent need for developing novel interventions.
This randomized controlled trial (RCT) will assign 50 CHR-P patients (aged 14-35) to either a 12-week modified ketogenic diet or a control diet. Symptom severity will be monitored throughout the trial using the Comprehensive Assessment of At-Risk Mental States (CAARMS) assessment tool, designed specifically to assess symptom severity in young people at high risk of developing psychosis. Participants will receive support from a registered dietitian and will use glucose/ketone meter kits to track adherence to the ketogenic diet. To evaluate efficacy and tolerability, the research team will assess symptom severity, cognitive function, sleep behavior, and physical health. The trial will also follow patients’ health status for up to three years after the intervention via electronic health records to evaluate the longer-term impact. Study lead and Associate Professor Amedeo Minichino, from the Department of Psychiatry, said:
We see promise in ketogenic therapy as a non-stigmatizing, accessible intervention for those navigating early signs of psychosis. If effective, the diet could represent a novel tool that will allow us to intervene before psychotic onset. We are hopeful that by studying the critical window that often precedes psychotic onset, we can change the long-term trajectory of mental well-being in our patients.
Since the majority of CHR-P patients do not receive antipsychotics, this will offer a unique opportunity to evaluate the clinical outcomes of ketogenic therapy as a stand-alone treatment, as well as to explore the biological mechanisms underlying both the disease and the intervention. New and growing evidence suggests that impaired brain energy metabolism, including mitochondrial dysfunction, may help us identify individuals with CHR-P who are more likely to later develop psychosis. In a subgroup of patients, the trial will measure brain energy directly using blood biomarkers and neuroimaging.
"This study is an important step forward in understanding the potential of ketogenic therapy on physical and mental health in this highly vulnerable patient group," said Jan Ellison Baszucki, co-founder and president of Baszucki Group. “This ambitious project represents a rare opportunity to gain a deeper understanding of how ketogenic therapy could fundamentally transform the trajectory of serious mental illness in a largely medication-naive population. We are thrilled to support the research team at Oxford in this first-of-its-kind trial.”
To learn more about Baszucki Group’s ongoing funded studies, visit the Metabolic Mind website.