A clinical trial just found that schizophrenia and bipolar patients who switched to a ketogenic diet showed significant reductions in depression and psychosis after four months. The drug doses did not change.
The treatment of schizophrenia and bipolar disorder has been built on pharmacology for more than half a century. Antipsychotic medications, mood stabilizers, and antidepressants form the backbone of care. Dietary intervention has never been part of the standard conversation, not because it has been tested and ruled out, but because it has rarely been tested at all in a rigorous way.
A new randomized controlled trial from the University of California San Francisco has now done that testing. The results, published today in Schizophrenia Bulletin, one of the most selective journals in psychiatric research, suggest that changing the brain’s primary energy source produces measurable psychiatric improvements that medication alone was not achieving, and does so in a population that clinicians have long assumed could not sustain a demanding dietary change.
The researchers recruited 58 adults who met diagnostic criteria for schizophrenia, schizoaffective disorder, or bipolar disorder with psychotic features. Participants were randomly assigned to either a ketogenic diet group or a diet-as-usual control group for one month. Crucially, psychiatric medication doses were not altered throughout the trial. Any symptom changes observed would reflect the dietary intervention, not a change in drug treatment.
The ketogenic diet restricts carbohydrates to roughly 10 percent of daily calories while increasing fat intake to around 70 percent. This restriction forces the body to break down fat into molecules called ketone bodies, which the brain can use as an alternative fuel source to glucose. Participants in the ketogenic group received 18 microwavable meals per week from a specialized delivery service and had access to a licensed dietitian throughout.
At the end of the first month, 83 percent of daily-tested participants in the ketogenic group had maintained nutritional ketosis. The most common assumption in psychiatric care is that patients with serious mental illness cannot adhere to a demanding nutritional protocol. This trial directly contradicted that assumption.
What changed in the body after one month
The first-month results were primarily metabolic. Compared to the diet-as-usual group, participants on the ketogenic diet showed significant reductions in body mass index, hemoglobin A1c (a marker of average blood sugar over several months), and insulin resistance. The control group showed essentially no change on any of these measures.
This matters beyond weight management. People diagnosed with psychotic disorders face dramatically elevated rates of metabolic syndrome, a cluster of conditions including high blood pressure, elevated blood sugar, and excess abdominal fat that substantially shortens life expectancy. The psychiatric medications most commonly prescribed for schizophrenia and bipolar disorder are themselves major contributors to this problem, driving weight gain, elevated glucose, and insulin resistance as side effects.
The ketogenic diet reversed these markers within a month without touching the medication doses. Cognitive performance and psychosis symptoms did not show statistically significant differences between the two groups at the one-month mark, though trends in the expected direction were present.
“We also showed that this diet is highly feasible in this population, with 83 percent of daily-tested participants maintaining ketosis in the one-month RCT portion of the study,” said lead researcher Judith Ford, a professor in the Department of Psychiatry and Behavioral Sciences at UCSF.
What changed in the brain after four months
Partway through the trial, additional funding allowed the researchers to offer all participants the option to continue on the ketogenic diet for four more months. Twenty-five individuals took up this offer. Because there was no control group for this extension phase, the researchers compared participants against their own baseline measurements rather than against a separate group.
After four months on the diet, the picture shifted considerably. Participants showed significant improvements in cognitive performance. Scores on validated measures of psychosis symptoms, including both the positive symptoms (hallucinations, delusions, disorganized thinking) and negative symptoms (emotional flatness, reduced motivation, social withdrawal) of schizophrenia, declined measurably. Depression scores dropped substantially.
The metabolic improvements from the first month were sustained. Body mass index and hemoglobin A1c remained lower than initial baseline levels throughout the extended phase. Adherence in this period was 94 percent, higher than the already surprising first-month figure.
“I don’t know if this surprised us, but we were really encouraged to see the high feasibility of this diet in an outpatient population of patients with schizophrenia-spectrum or bipolar-1 disorder,” Ford said. “A common assumption we hear is that the diet must be too difficult for participants with severe mental illness to adhere to, but 25 of the participants opted to continue on the diet beyond the one-month RCT.”
The finding that changes the interpretation
The most clinically significant result in the study was not the symptom improvement itself but what the improvement was tied to.
The researchers ran statistical tests to determine whether the psychiatric gains were driven by weight loss or by something specific to the metabolic state of ketosis. The answer was clear: higher blood ketone levels correlated directly with greater reductions in hemoglobin A1c and greater reductions in depressive symptoms. Changes in body weight did not correlate with these outcomes.
“We were gratified to find that the improvement in depressive symptoms and metabolic health was not related to weight loss but to ketone levels, even in the one-month RCT,” Ford said.
This distinction matters enormously for interpreting the mechanism. The improvement does not appear to be a general effect of eating less or losing weight. It appears to be specific to what happens when the brain switches from glucose to ketones as its primary fuel. Schizophrenia research has documented abnormalities in how the brain processes glucose for decades. Some researchers have proposed that ketone metabolism, which the brain handles through a different biochemical pathway, may bypass or compensate for this dysfunction.
The ketogenic diet was originally developed as a treatment for epilepsy, where it reduces seizures through effects on neuronal excitability. Its potential psychiatric applications are only beginning to be rigorously tested.
What the study cannot establish
The four-month extension phase is the limitation that the researchers emphasize most directly. Without a control group in that phase, the psychiatric improvements observed cannot be definitively attributed to the diet rather than to other factors, including the passage of time, the additional support from weekly check-ins with a dietitian, or the simple effect of receiving structured nutritional care.
“While we also saw significant improvements in depression, schizophrenia symptoms, and cognitive performance after four months on the ketogenic diet, we cannot attribute those effects to the specific diet, as it was offered to all participants at this stage,” Ford said.
The sample size of 58 participants is also small, preventing complex statistical modeling or the separation of outcomes by specific psychiatric diagnosis. The trial did not monitor cholesterol, detailed electrolyte balances, or adjustments to psychiatric medications, all of which would be important for evaluating long-term safety.
One further methodological caveat: the ketogenic group received 18 prepared meals per week while the control group did not, meaning some of the observed benefit in the ketogenic group might reflect the effect of having regular access to prepared, nutritious food rather than the metabolic state of ketosis specifically. The researchers acknowledge this and recommend that future studies control for this variable.
Where the research goes from here
The study is best understood as the most rigorous evidence yet that dietary intervention in serious psychiatric illness is feasible, produces metabolic benefits even in the short term, and warrants a larger, longer, properly controlled trial.
“Our results are really promising, indicating that a ketogenic diet is feasible and safe in patients with serious mental illness, and our single-arm extension findings also indicate that the ketogenic diet may be beneficial for alleviating depression and schizophrenia symptoms,” Ford said. “We hope to see more funding being made available for RCTs that follow larger groups of patients for longer periods of time to establish whether the ketogenic diet is an effective treatment strategy for serious mental illness.”
For the millions of people living with schizophrenia and bipolar disorder, many of whom experience partial responses to medication and significant metabolic side effects from treatment, the question of whether a dietary change could meaningfully supplement their care is not an academic one. This trial does not answer it definitively. But it produces the kind of controlled, peer-reviewed evidence that makes the question impossible to dismiss.
The study “Metabolic Improvements with a Ketogenic Diet Correlate with Symptom Improvement in Psychosis: A Randomized Controlled Trial” was authored by Samantha V. Abram, Juliette M. Kyner, An Vu, Zanib Naeem, Shebani Sethi, Michael S. Jacob, Susanna L. Fryer, Daniel H. Mathalon, and Judith M. Ford at the University of California San Francisco, and published August 8, 2026 in Schizophrenia Bulletin.
Source: University of California San Francisco. DOI: 10.1093/schbul/sbag082
