For years, clinicians and researchers have asked an important question:
Can a ketogenic diet actually help people with serious mental illnesses like schizophrenia and bipolar disorder?
Until now, most of the evidence has come from case reports, pilot studies, and uncontrolled trials. I’m proud to have contributed to some of this literature. While these studies have been encouraging, they cannot establish efficacy with the same confidence as randomized controlled trials. Critics have rightly pointed out that stronger evidence is needed.
Now, we are beginning to get it.
Researchers from UCSF, the San Francisco VA, and Stanford have published the first randomized controlled trial of ketogenic therapy in people with schizophrenia-spectrum disorders and bipolar I disorder with psychosis. This is an important milestone for the field.
First, the good news
One of the biggest concerns people have raised over the years is whether individuals with serious mental illness could realistically follow a ketogenic diet.
This study provides reassuring evidence that many can.
Participants assigned to the ketogenic diet achieved nutritional ketosis within the first week and maintained ketone levels throughout the study. Only 3 of 18 participants randomized to the ketogenic diet in the first month had average ketone levels below the conventional nutritional ketosis threshold of 0.5 mmol/L, and only 1 of 18 participants in the four-month extension averaged below that threshold. That’s a much higher level of adherence than many skeptics anticipated and demonstrates that ketogenic therapy is feasible in an outpatient psychiatric population when appropriate support is provided.
The randomized portion of the trial also demonstrated meaningful improvements in metabolic health after just one month. Compared with participants eating their usual diet, those on the ketogenic diet experienced significant reductions in body weight, hemoglobin A1c, and insulin resistance. These changes occurred quickly and are particularly important because metabolic disease is one of the greatest contributors to premature mortality among people with serious mental illness.
What about psychiatric symptoms?
This is where the story becomes especially interesting.
The randomized, controlled portion of the study lasted only one month. During that month, psychiatric symptoms and cognition showed favorable trends, but the differences between groups were not statistically significant after correction for multiple comparisons.
However, the investigators later received additional funding that allowed participants to continue ketogenic therapy for a total of four months.
Importantly, this extension was no longer randomized or controlled. Everyone who continued received ketogenic therapy.
During those additional months, participants demonstrated significant improvements in positive symptoms, negative symptoms, depressive symptoms, and cognitive performance compared with their own baseline.
Because there was no control group during this extension, we cannot conclude with certainty that the ketogenic diet caused all of these improvements. Other factors, such as expectancy effects, the passage of time, or nonspecific aspects of study participation, could also have contributed. Nonetheless, there are few, if any, currently available treatments that have been shown to improve positive symptoms, negative symptoms, depressive symptoms, and cognition simultaneously. If these findings are replicated in future randomized trials, they could fundamentally change how we think about treating psychotic disorders.
One month may simply not be enough
One aspect of this study resonates strongly with my own clinical experience.
I’ve often observed that many patients begin experiencing metabolic improvements within weeks of starting ketogenic therapy, while psychiatric improvements frequently require substantially more time.
This trial lends support to this clinical observation.
The randomized phase showed early metabolic benefits after one month. The larger psychiatric and cognitive improvements reached statistical significance after four months of sustained treatment. That doesn’t prove that longer treatment is necessary, but it suggests that future clinical trials should not assume one month is sufficient to evaluate psychiatric outcomes. For patients and clinicians choosing to try ketogenic therapy, these findings also suggest the importance of setting realistic expectations. Based on the available evidence, meaningful psychiatric improvement may require three to four months of sustained treatment.
An intriguing clue about mechanism
Another intriguing finding was that improvements in depressive symptoms correlated with blood ketone levels, not with weight loss itself.
Participants who achieved higher levels of ketosis experienced greater improvements in depressive symptoms and glucose regulation, while weight loss alone did not explain these relationships. Although these analyses cannot establish causation, they support the hypothesis that ketosis itself, not simply losing weight, may contribute to some of the therapeutic effects.
Important limitations
Every study has limitations, and this one is no exception.
The sample size was relatively small. Participants in the control group did not receive meals, while those in the ketogenic group did, introducing potential differences beyond the diet itself. Medication changes were not systematically tracked. Most importantly, the psychiatric improvements occurred during the uncontrolled extension phase rather than during the randomized comparison.
These limitations mean we should interpret the findings with scientific caution.
The future looks bright
Perhaps the most exciting news is that this study won’t stand alone for long.
Several additional randomized controlled trials of ketogenic metabolic therapy for serious mental illness have recently been completed or are currently underway. As those studies report their results, we’ll have a much clearer picture of whether ketogenic therapy truly outperforms comparison diets for psychiatric symptoms, which patients benefit most, how long treatment should continue, and where ketogenic therapy fits within psychiatric practice.
For now, this trial provides something we have been waiting for: rigorous evidence that ketogenic therapy is feasible, improves metabolic health, and offers promising signals that sustained treatment may also improve psychiatric symptoms and cognition.
For those of us working to understand mental illness through the lens of brain metabolism, this study represents an important milestone. It doesn’t answer every question, but it marks important progress and provides exactly the kind of rigorous evidence needed to move the field forward.
Interested in Ketogenic Therapy for Serious Mental Illness?
MH² is among the world’s leading clinics dedicated to using ketogenic metabolic therapy for the treatment of serious mental illness. Our multidisciplinary team provides everything needed to implement this treatment safely and effectively, including psychiatric care, registered dietitians, health coaches, comprehensive laboratory monitoring, and DXA body composition scans. Whether you’re living with schizophrenia, bipolar disorder, or another complex psychiatric condition, we’re here to help you determine whether this approach is right for you.
Contact MH² today to learn more about our comprehensive programs.
Dr. Christopher Palmer is a Harvard psychiatrist and researcher working at the interface of metabolism and mental health. He is the Founder and Director of the Metabolic and Mental Health Program and the Director of the Department of Postgraduate and Continuing Education at McLean Hospital and an Assistant Professor of Psychiatry at Harvard Medical School. For almost 30 years, he has held administrative, educational, research, and clinical roles in psychiatry at McLean and Harvard. He has been pioneering the use of the medical ketogenic diet in the treatment of psychiatric disorders—conducting research in this area, treating patients, writing, and speaking around the world on this topic. Most recently, he has proposed that mental disorders can be understood as metabolic disorders affecting the brain, which has received widespread recognition in both national and international media outlets.
