Summary: Researchers report that a ketogenic diet—which shifts the body from glucose toward fat-derived ketones for fuel—produced rapid metabolic benefits and notable improvements in persistent psychiatric symptoms. By bypassing impaired glucose pathways, the intervention restored brain energy availability and produced measurable gains in metabolic health, cognition, and mood without major adverse effects.
This randomized controlled trial supports the idea that targeted nutritional approaches can act as a metabolic psychiatry intervention, using ketone-based energy to stabilize neural function in people with serious mental illness.
Key Facts
- High adherence to ketosis: Contrary to concerns that restrictive diets are impractical for people with severe mental illness, participants achieved an 83% adherence rate to daily ketosis during the one-month randomized phase and a 94% adherence rate during the four-month extension, with no reports of serious side effects.
- Ketone levels linked to outcomes: In the randomized month, participants on the ketogenic diet showed large metabolic improvements versus diet-as-usual, and higher circulating ketone levels correlated with lower blood glucose and reduced depression scores.
- Benefits beyond weight loss: Statistical analyses showed that improvements in depressive symptoms were associated with ketosis itself rather than being explained solely by weight loss, suggesting the alternative fuel source in the brain is a key therapeutic mechanism.
- Longer-term cognitive and psychiatric gains: While metabolic markers improved within one month, participants who completed the optional four-month extension experienced sustained reductions in depression and core schizophrenia symptoms plus clear improvements in everyday cognitive performance.
- Medication gaps addressed: Standard antipsychotics often leave patients cognitively blunted and fatigued. The lead investigator emphasized that measurable cognitive and psychological improvements are clinically important because current medications usually fail to address these domains.
- Call for larger trials and public support: Funders and authors urge expanded public investment in larger, longer randomized trials to validate ketogenic and other metabolic therapies for serious mental illnesses and to develop standardized, brain-focused nutritional treatments within public healthcare.
Source: Stellate Communications
Published in Schizophrenia Bulletin, this first-of-its-kind randomized controlled trial from University of California, San Francisco (UCSF), partially funded by the National Institute of Mental Health (NIMH), examines whether a ketogenic diet can improve metabolism, psychiatric symptoms, and cognition in people with schizophrenia-spectrum and bipolar I disorder.
The trial enrolled 58 participants. Forty-seven completed the initial one-month randomized comparison between a ketogenic diet and diet-as-usual. Of those, 25 opted into a single-arm extension that continued the ketogenic diet for a total of four months.
During the one-month randomized phase, daily ketone readings among ketogenic-diet participants exceeded standard ketosis thresholds and were associated with meaningful reductions in weight, hemoglobin A1c, and insulin resistance compared with the control group. Importantly, higher ketone concentrations also correlated with reductions in depressive symptoms (measured by PHQ-9) and lower blood glucose, independent of weight loss.
Participants who completed the four-month extension sustained metabolic improvements and demonstrated significant decreases in depression and schizophrenia symptom scores alongside improved cognitive performance. Although the four-month results come from a smaller, single-arm group (n = 25), they provide a promising signal that prolonged ketosis may be necessary to capture the fuller psychiatric and cognitive benefits.
Lead author Judith M. Ford, PhD, Professor of Psychiatry at UCSF and the Weill Institute for Neurosciences, highlighted the clinical importance of these findings: current antipsychotic medications can control psychosis but often leave cognitive, mood, and functional deficits unaddressed. Demonstrating measurable improvements in these domains with a dietary intervention points to a potentially transformative adjunctive treatment.
Jan Ellison Baszucki, president of Baszucki Group and a study funder, said the trial adds to emerging clinical evidence supporting metabolic psychiatry and called for diverse, sustained investment to enable larger, longer trials that could integrate nutritional therapies into mainstream care.
Key Questions Answered:
A: Emerging evidence points to cerebral hypometabolism in serious psychiatric disorders: the brain’s ability to use glucose may be impaired, leaving neurons energy-starved and less stable. A ketogenic diet prompts the liver to produce ketones from fat. These ketones can bypass dysfunctional glucose pathways and provide a reliable, efficient fuel source that stabilizes neural networks and may reduce biological drivers of psychiatric distress.
A: The study’s analyses accounted for weight change and found that higher blood ketone levels predicted reductions in depressive symptoms even after adjusting for weight loss. This indicates that ketosis itself—not weight loss alone—likely contributes to the observed mental health benefits.
A: Although adherence and safety were excellent in this trial, it was conducted under clinical supervision. People with serious mental illness often take medications that affect metabolism and may require close monitoring. The research team recommends initiating and managing ketogenic therapy in partnership with qualified psychiatric and medical professionals to ensure safety and stability.
Editorial Notes:
- This article was edited by a Neuroscience News editor.
- The full journal paper was reviewed.
- Additional contextual details were added by editorial staff.
About this psychology and diet research news
Author: Clare Reynell
Source: Stellate Communications
Contact: Clare Reynell – Stellate Communications
Image: The image is credited to Neuroscience News
Original Research: Open access. “Metabolic improvements with a ketogenic diet correlate with symptom improvement in psychosis: A randomized controlled trial” by An Vu, Daniel H. Mathalon, Judith M. Ford, Juliette M. Kyner, Michael S. Jacob, Samantha V. Abram, Shebani Sethi, Susanna L. Fryer, Zanib Naeem. Schizophrenia Bulletin
DOI: 10.1093/schbul/sbag082
Abstract
Title: Metabolic improvements with a ketogenic diet correlate with symptom improvement in psychosis: A randomized controlled trial
Background and Hypothesis
Psychiatric medications often contribute to metabolic dysfunction in people with psychotic disorders. Ketogenic diets are known to improve components of metabolic syndrome and have anticonvulsant effects in epilepsy. Prior pilot studies suggested potential benefits in schizophrenia and bipolar disorder. This trial tested whether a ketogenic diet could improve metabolic health, psychiatric symptoms, and cognition in individuals with schizophrenia-spectrum and bipolar I disorders.
Study Methods
Participants were randomized to a ketogenic diet (KETO; n = 28) or diet-as-usual (DAU; n = 30) for one month. A KETO extension was then offered, and a subgroup completed four months on the diet (n = 25). Researchers assessed changes in metabolic markers, clinical symptoms, and cognitive function after one month (KETO versus DAU) and after four months (KETO versus baseline).
Study Results
KETO participants achieved daily ketone levels above standard ketosis thresholds. Compared with DAU, KETO participants experienced significant reductions in weight, hemoglobin A1c, and insulin resistance. After four months on KETO, clinical symptoms—including positive, negative, and depressive symptoms—and cognitive performance improved markedly. Higher ketone levels correlated with better pre-diabetic markers and lower depressive symptoms. Weight loss did not account for the metabolic and symptom improvements, implicating ketosis itself as a driving factor.
Conclusions
This trial demonstrates the feasibility of implementing a ketogenic diet in outpatients with schizophrenia and bipolar I disorder, with high adherence and no major adverse events reported. Participants showed improvements in metabolic health, cognitive function, and clinical symptoms. Improvements in depressive symptoms were associated with ketosis rather than weight loss, suggesting ketosis is a plausible therapeutic mechanism. Larger, longer, and fully controlled trials are needed to confirm these findings and to evaluate the safety and efficacy of ketogenic therapy as a treatment for serious mental illness.