Stanford’s Dr. Shebani Sethi’s Collaborative Paper on Metabolic Interventions Offers Hope for Schizophrenia, Bipolar Disorder, and Serious Depression
The Paper Emphasizes the Importance of Integrating Metabolic Approaches into Psychiatric Care and Explores the Relationship Between Systemic Metabolic Dysfunction and Mental Health
STANFORD, Calif.–(BUSINESS WIRE)–#BrainHealth–For decades, physicians have treated psychiatric conditions and physical conditions like diabetes or obesity as separate problems that happen to occur in the same patient. Today, Nature Mental Health published a paper that argues this view is outdated, and that metabolic dysfunction (or the inability of the body to process the food we eat in a healthy way) is not a side effect of psychiatric illness, but actually central to it.
Authored by Dr. Shebani Sethi, M.D., A.B.O.M., founder of Stanford Metabolic Psychiatry and Metabolic Psychiatry Labs, along with 16 other physicians, academics and scientists from the United States, Canada, the United Kingdom, Australia and Switzerland, the peer-reviewed article shows why people with some of the most serious mental illnesses – schizophrenia, bipolar disorder and major depressive disorder – also suffer from impaired energy metabolism.
The paper reviews 138 studies demonstrating the relationship between systemic and central metabolic dysfunction, such as abnormalities in processes like energy production and blood sugar regulation, and mental health outcomes across disorders. The research suggests these metabolic abnormalities can influence the brain and may be core drivers of serious mental illnesses.
One of the paper’s most actionable recommendations is that psychiatrists should routinely screen for metabolic dysfunction as a core part of understanding and treating mental illness. Tests include diabetes markers, lipid panels, inflammation markers, blood pressure, and BMI.
“The brain is only 2% of our body mass, but it consumes 20% of our energy,” said primary author Dr. Sethi. “We’re seeing irrefutable evidence that metabolic dysfunction affects how our brain functions, and that metabolic interventions have great potential to improve psychiatric symptoms.”
Suggested therapies include pharmacologic agents (such as metformin and GLP-1s); lifestyle strategies (like ketogenic diet, intermittent fasting, and exercise); and addressing theoretical models like allostatic load (chronic stress) and selfish brain (the brain prioritizing its own energy needs).
Founding of Metabolic Psychiatry Labs
As early as the 1920s, researchers reported metabolic abnormalities in patients with schizophrenia and bipolar disorder, including elevated lactate and reduced glutathione, a key antioxidant. Modern neuroimaging and biochemical studies have linked these changes to mitochondrial dysfunction and broader brain energy deficits.
“Between those observations a century ago and today, the field has focused largely on neurotransmitter and receptor models rather than bioenergetics,” Sethi commented. “Metabolic psychiatry is a return to those early roots, but now armed with modern technology, better imaging and deeper biological understanding.”
Sethi founded Metabolic Psychiatry Labs in 2024 in Palo Alto, Calif. The virtual clinic currently operates in five states: California, Florida, New York, Texas, and Virginia. Treating patients via telemedicine builds on decades of body/brain research and aims to identify the biomarkers and address the underlying metabolic factors that influence brain function and treatment response.
As a psychiatrist, a background in obesity medicine was not common, but Sethi’s initial patient experiences sparked her interest, exploration, and ultimately coined the term metabolic psychiatry in 2015 to describe the study of the connection between metabolism and mental health and to unify and equip researchers and clinicians across the globe with a common language. She wanted to explore why patients with metabolic abnormalities were also experiencing psychiatric conditions, and why ketogenic therapies and mitochondrial-targeted therapies were helping them recover.
Early in her training, she worked with a treatment-resistant schizophrenia patient whose condition improved through an obesity clinic, providing inspiration. She also observed how patients with conditions such as epilepsy or seizures could be treated successfully using ketogenic (high-fat, moderate protein, low-carb) therapies.
Her patients with insulin resistance often also exhibited severe depression. Her research uncovered how cerebral glucose hypometabolism – a condition where the brain cannot process glucose for energy correctly – was strongly linked to both conditions.
In 2024, Sethi published a 23-patient Stanford trial into the ketogenic diet’s effect on schizophrenia and bipolar disorder funded by the Obesity Treatment Foundation and the Baszucki Brain Foundation, and now has plans for a 120-patient expansion trial with a mechanistic, cognition, and quality of life focus.
“Many clinical trials are underway. This shift in treatment approaches may offer not just symptom management, but the possibility of addressing underlying biologically based energetic vulnerabilities of some of the most devastating conditions in human health,” Sethi added.
The paper “Metabolic psychiatry targeting metabolic dysregulation in mental health,” published March 30, 2026, in Nature Mental Health, is available here.
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About Metabolic Psychiatry Labs (MPL)
Founded by Shebani Sethi, M.D., A.B.O.M., the founder of Stanford Metabolic Psychiatry, Metabolic Psychiatry Labs (MPL) is a digital health telemedicine provider to patients with serious mental illness. It offers remote monitoring using individual care plans, hardware, software, a mobile app, and ongoing interactions with a clinical team. MPL focuses on prevention, halting progression, and treating mental illnesses, corroborating insights from the related fields of endocrinology, neuroscience, and immunology. Treatments unite nutrition, metabolism, and mental health care. More information is available at: www.metabolicpsychiatrylabs.com.
About Shebani Sethi, M.D., A.B.O.M.
Shebani Sethi is the founder of Metabolic Psychiatry Labs and the founding director of the first national flagship Metabolic Psychiatry clinical research program at Stanford. She is dual board-certified in psychiatry and obesity medicine. She completed her master’s in biotechnology at Johns Hopkins, M.D. certifications at Duke and the National University of Singapore, and her residency at Stanford. She is a member of the Obesity Medicine Association and the American Psychiatric Association. She founded Metabolic Psychiatry Labs in 2024 to treat patients with serious mental illnesses such as schizophrenia, bipolar disorder, and eating disorders using metabolic approaches, among other treatment options. She also conducts research studies in metabolism-based interventions in mental health, including nutrition studies measuring mitochondrial function. Upcoming medical trial collaborations include the Mayo Clinic and the University of Toronto. Learn more at: med.stanford.edu/profiles/shebani-sethi.
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