Although the ketogenic diet has long been associated with the treatment of treatment-resistant epilepsy, interest in its potential advantages for mental illness is growing.
Could a seemingly intractable ailment like major depressive disorder, bipolar disorder, or schizophrenia really be improved by something as basic as a diet?
The available data is not as strong as it would be from gold-standard randomized controlled studies. However, additional research is being done, and medical professionals are eager to learn about accounts of individuals whose mental health disorders improved after following a ketogenic dietopens in a new tab or window.
However, there are obstacles that must be overcome in order for nutritional intervention trials to be successful, and it is unclear whether the medical profession as a whole will support them more broadly.
“There have to be randomized trials before we can make enthusiastic and evidence-based treatment recommendations,” Drew Ramsey, MD, a nutritional psychiatrist and member of the American Psychiatric Association, told MedPage Today. “That said, I’m hopeful and optimistic that patients are going to have more tools to treat their mental health disorders.”
What Is Said by the Evidence?
Ramsey pointed out that while the ketogenic diet is not particularly a food intervention, certain randomized controlled trials have demonstrated the potential benefits of diet on depression. For example, the AMMEND studyopens in a new tab or window revealed greater improvements in symptoms and quality of life for young men on the Mediterranean diet compared with controls, and the SMILES trialopens in a new tab or window showed better symptomatic improvement and remission rates with a dietary intervention compared with a control social support group.
Regarding the ketogenic diet in particular, the volume of evidence supporting its application in mental illnesses “is really starting to grow,” according to Georgia Ede, MD, a nutritional psychiatrist located in Massachusetts and spokesperson for MedPage Today.
Ede co-authored “The Ketogenic Diet for Refractory Mental Illness: A Retrospective Analysis of 31 Inpatients,” a French study that was published in Frontiers in Psychiatryopens in a new tab or window in 2022.
Admitted to a psychiatric hospital, patients with severe and protracted mental illness (major depressive disorder, bipolar disorder, and schizoaffective disorder) and poorly managed symptoms were started on a ketogenic diet as a supplement to traditional treatment.
Despite the fact that three patients were unable to stick to the diet for longer than 14 days, the researchers came to the conclusion that treating treatment-refractory mental illness with a ketogenic diet was “feasible, well-tolerated, and associated with significant and substantial improvements in depression and psychosis symptoms and multiple markers of metabolic health.”
According to Ede, over 40% of patients received remission from their diagnosis, and 64% of patients left the hospital with lower prescriptions for mental health issues.
A feasibility pilot study of the ketogenic diet in bipolar disorder was just finished in the United Kingdom, among other recent studies.
Twenty of the study’s twenty participants finished the six to eight-week ketogenic diet, according to study results that were published in BJPsych Openopens in a new tab or window in October of last year. Researchers discovered that most subjects adhered to the diet and achieved and maintained ketosis, and that most adverse events were manageable.
Which Research Projects Are Active?
An email from the National Institute of Mental Health (NIMH) directed MedPage Today to two trials—one headed by Maryland-based academics and the other by a Californian team—that the NIMH is funding to examine the impact of the ketogenic diet on mental illness.
An inpatient randomized controlled trial of a gluten-free diet is being supervised by Deanna Kelly, PharmD, of the Maryland Psychiatric Research Center, a collaborative venture between the University of Maryland School of Medicine and the state Department of Health. The experiment is focused on a subgroup of individuals with schizophrenia.
It was discovered that these patients had elevated IgG anti-gliadin antibody levels. The trial’s objective is to ascertain whether being gluten-free helps participants, as it is expected to lead to a decrease in gliadinopens in a new tab or window antibodies and symptoms of schizophrenia.
According to her, individuals have total choice over what they consume in the inpatient setting. The fact that the people giving the psychiatric ratings are blinded adds yet another level of rigor to the experiment.
Judith Ford, PhD, of the University of California, San Francisco, who also got funding from the NIMH, and her colleagues will investigate whether a ketogenic diet helps reduce neural network instability in individuals with schizophrenia. In particular, they are examining whether impaired glucose metabolism—at least partly mediated by insulin resistance—contributes to the disorder’s network instability, which may be the cause of patients’ accelerated aging and cognitive declineopens in a new tab or window.
“So far, it’s helping people’s overall intellectual function,” Ford said.
The National Institute on Mental and Health (NIMH) informed MedPage Today that while there aren’t any funding opportunities that “specifically focus on diet and mental health,” the organization will “consider relevant applications submitted under broader funding opportunity announcements.”
What Difficulties Still Await?
Many academics investigating the relationship between ketogenic diets and mental health have contacted a private foundation that supports this field of studyopens in a new tab or window.
According to Kelly, one of the challenges in obtaining federal funds is demonstrating targets of involvement. She clarified that even if there was a cure for depression, the researcher would still need to demonstrate how the brain contributes to the desired result—a reduction in depression.
“People have to spend their lives [in order to] understand the target,” Kelly stated “Not everybody can afford that. Sometimes, it’s not really even that clear.”
“That’s why we need other funding agencies to step up and take risks,” she added.
Additional expenses for hospital stays during clinical trials and the lack of pharmaceutical financing for food therapies are obstacles that researchers must overcome, according to Kelly.
The American Epilepsy Society member Mackenzie Cervenka, MD, medical director of the Adult Epilepsy Diet Center at Johns Hopkins Hospital in Baltimore, pointed out that the over a century-long history of using ketogenic diets for epilepsy patients is partly to blame for the potential interest in and promise of these diets for mental health.
Cervenka did add, though, that “it is important to be aware that there can be long-term side effects of the diet.”
According to her, individuals who stop going to their doctor for prescription drugs might not be checked for possible health issues like kidney stones, hyperlipidemia, and bone health.
Short-term research “may not be sufficient to indicate what the benefits could be in real-world applications,” according to Cervenka’s observation.For instance, “whether they are responders or not, in our experience, about 50% [of individuals] will stop the diet within 6 months,” the speaker stated.
According to her, this may be the result of issues with adherence or, in the case of epileptic patients, a failure to achieve enough seizure control, for example, in order to drive.
Furthermore, Ramsey emphasized the need to keep in mind that “not everything works for everybody.”
“We need more,” Ede concluded while speaking of randomized controlled trials. “Many clinicians will not feel comfortable until we have more.”
