Ketogenic Diet Study Offers Hope for a New Treatment for Bipolar Disorder

A new paper has reported the clinical, neuroimaging and metabolic findings of an interventional trial that offers fresh insights into a ketogenic diet's impact on serious mental illnesses like bipolar disorder. Drs. Danny Smith, Iain Campbell, and their team from the University of Edinburgh published an analysis of their landmark European trial in BJPsych Open: “A Pilot Study of a Ketogenic Diet in Bipolar Disorder: Clinical, Metabolic, and Magnetic Resonance Spectroscopy Findings.” The paper points to mechanisms by which a ketogenic diet may impact brain metabolism to improve functioning, and establishes an important direction for future research.

Interest in the ketogenic diet is growing within the bipolar research community. As Dr. Campbell explains, “One of the most interesting properties of a ketogenic diet is that it’s an effective anti-seizure intervention in epilepsy, as evidenced by 13 randomized controlled trials and over a century of clinical use. Several anti-seizure medications are also used to treat bipolar disorder, so when we observe the effects of a ketogenic diet in bipolar disorder, it’s reasonable to explore whether there are shared mechanisms in the brain that would explain the diet’s effectiveness across brain-based disorders.”

Study Results

To test this hypothesis, 27 individuals with bipolar disorder in a stable state were enrolled in a six-to-eight-week pilot trial of a ketogenic diet. The researchers assessed clinical symptoms, metabolic markers, and brain metabolism. Twenty participants completed the trial.

This study was particularly unique because the researchers used advanced neuroimaging technology, magnetic resonance spectroscopy (MRS), to observe changes in brain metabolism. Through MRS, they observed reductions in Glx (a measure of glutamate and glutamine concentrations) in specific brain regions.

According to Dr. Campbell, “Among the most consistent observations in both bipolar disorder and epilepsy are elevated glutamate levels in brain imaging studies. Glutamate is an excitatory neurotransmitter, and several anti-seizure medications reduce brain glutamate levels. It was very interesting to see that brain glutamate levels were reduced over eight weeks of ketogenic diet treatment.”

Glutamate concentrations are often a therapeutic target for serious mental illnesses. In bipolar disorder, elevated glutamate can trigger manic episodes by overstimulating regions of the brain, contributing to mood instability, impulsivity, and anxiety. Depressive episodes often follow. This study's findings, showing reduced glutamate levels, offer a step forward in understanding how ketogenic metabolic therapy may improve mood stability and overall brain function.

Another strength of this study was the ketone testing. Impressively, 91% of ketone readings throughout the trial indicated ketosis, allowing researchers to examine how ketone levels correlated with brain metabolism and mental health improvements. The data revealed a relationship between higher ketone levels and improvements in mood and energy, along with reductions in impulsivity and anxiety.

The link between ketones and glutamate levels is also noteworthy. While researchers are still working to fully understand the role of glutamate and glutamine in mental illness, Dr. Campbell shares that “Glutamate, in addition to being a neurotransmitter, may also serve as a fuel source for the brain. When brain energy metabolism is impaired, as it often is in individuals with mental illness, the brain may increase glutamate levels for energy. In bipolar disorder, this can trigger manic symptoms. Providing ketones as an alternative fuel may reduce glutamate metabolism and excitatory activity.” More From Dr. Campbell.

Dr. Campbell’s journey into metabolic psychiatry is deeply personal, as he suffered decades of debilitating bipolar depression. Several years ago, he faced profound despair, feeling as if he were “suffocating” in a constant state of physical and mental pain. In a moment of crisis, he decided to focus on improving his physical health by losing weight, which led him to try a ketogenic diet. To his surprise, the diet brought significant relief to his depression symptoms, inspiring him to pursue the science behind it. Driven by personal experience and scientific curiosity, Dr. Campbell is now at the forefront of metabolic psychiatry research and a leader in the study of the mechanisms of ketogenic therapy in serious mental illness. Learn more about Dr. Campbell’s story.

Participants in this study shared powerful testimonials about their experiences. These stories highlight the significant improvements in quality of life that many experienced during the trial. In fact, more than a third of participants requested support to stay on the diet instead of following the trial’s protocol for ending the intervention.

“For the first time in years, I felt like my brain was finally running on the right fuel,” said one of the study participants.

“A ketogenic diet gave me a lifeline, restoring my energy and sense of hope,” said another study participant. “I felt like I was finally healing my mind, not just managing my bipolar symptoms. It opened me up to new possibilities and a brighter future.”

“Given the participants’ descriptions of improved physical and mental health, alongside the data showing changes in cardiometabolic, mental health, and brain imaging parameters, we believe it’s time to investigate this treatment in larger randomized controlled trials,” said Dr. Campbell.

The Future of Metabolic Psychiatry

Dr. Campbell continues: “There is an ongoing epidemic of metabolic dysfunction, affecting over 61 million people living with type 2 diabetes in Europe and over 400 million people worldwide. Many more have pre-diabetic conditions like insulin resistance and metabolic syndrome. The World Health Organization now recognizes this as a global health crisis. Metabolic dysfunction affects every major organ in the body, including the brain, which is one of the most metabolically active organs. Early research suggests that metabolic approaches, like a ketogenic diet, may be beneficial in treating psychiatric conditions. Through the Hub, we aim to pilot novel metabolic treatments and carry out large randomized controlled trials to explore their usefulness for people with psychiatric conditions.”

The “Hub” Dr. Campbell references is the UKRI Hub for Metabolic Psychiatry, a research organization focused on advancing research and clinical innovation in metabolic psychiatry. The Hub’s mission is to bridge the gap between physical and mental health, unifying two fields that have long been treated separately.

As Dr. Campbell explains, “Modern psychiatry has two great founders: Emil Kraepelin and Sigmund Freud. Kraepelin believed in finding a biological basis for mental illness, while Freud shifted his focus to psychoanalysis. This split has contributed to a divide between neuroscience and psychiatry—and between physical and mental health. Metabolic psychiatry is beginning to reunite these areas because, in both the underlying biology and in the lived experience of patients, no such distinctions exist.”

The Hub’s research integrates specialists from psychiatry, neuroscience, cardiovascular health, genetics, and even machine learning. This multidisciplinary approach, grounded in the real-life experiences of patients, is helping to usher in a new era in mental health treatment, where physical and mental health are treated as interconnected aspects of overall well-being.

A Step Forward

Dr. Campbell’s study is a significant step toward understanding how metabolic interventions could benefit individuals with serious mental illnesses like bipolar disorder. By combining personal experience with rigorous science, Dr. Campbell and his team are reshaping how we approach mental health treatment. As more research emerges, the link between metabolism and mental health could unlock other innovative approaches like ketogenic therapy, offering new hope to individuals and families affected by serious mental illness.

Written by Bret Scher