Metabolic disorders are conditions that disrupt the body's normal chemical processes, interfering with how the body converts food into energy. And it's estimated as many as one in three Americans suffer from metabolic syndrome -- raising their risk of cardiovascular disease, Type 2 diabetes and stroke.
For those with a serious mental illness, that likelihood is much, much higher.
Growing scientific evidence suggests that a high-fat, moderate-protein, low-carbohydrate ketogenic diet can help those patients manage their metabolic health and improve psychiatric symptoms and the weight-gaining side effects of their anti-psychotic medications.
In spring of 2024, Stanford psychiatrist and obesity specialist Shebani Sethi, MD, led a pilot study of 21 adults with bipolar disorder or schizophrenia who also had some kind of metabolic disorder and were prescribed antipsychotic medications. After four months on the ketogenic diet, most of the patients showed significant improvement in their psychiatric symptoms, a reduction in weight gain from their medications and relief from their metabolic disorders.
Sethi said more research is needed to conclusively demonstrate the efficacy of the dietary therapy and to detail the mechanisms underlying it. She is recruiting for a larger randomized control trial that will evaluate the effect of ketogenic therapy on the quality of life for people with schizophrenia, bipolar disorder and depression.
Several studies of the effects of the ketogenic nutritional therapy on Alzheimer's disease, attention deficit/hyperactivity disorder, bipolar disorder, anorexia nervosa and other neuropsychiatric disorders are also underway around the world.
But the results of Sethi's pilot study and others like it have already raised hopes for millions of patients suffering from serious mental illnesses, as well as from side effects of their medications and the metabolic disorders that often accompany them.
Here are five things Sethi wants you to know about where the science stands on ketogenic therapy:
Keto therapy has been used to treat neurological disorders for more than 100 years.
In 1921, long before modern anticonvulsant medications, endocrinologist Russell Wilder, MD, discovered that the ketogenic diet could mimic the metabolic effects of fasting, long known to reduce seizures. More than a dozen randomized controlled trials have since shown that ketogenic diets significantly and safely stabilize neuronal networks, quelling seizures in many patients with epilepsy.
A growing body of evidence that includes Sethi's research suggests the diet, or ketogenic metabolic therapy as she prefers to call it, can also help patients with serious mental illness such as depression, schizophrenia and bipolar disorder. The relatively new field of metabolic psychiatry, founded at Stanford Medicine by Sethi, focuses on addressing metabolic dysfunction with ketogenic and other metabolism-focused therapies to improve mental health outcomes.
Keto therapy stabilizes neurons and reduces inflammation in the brain.
Ketogenic therapy increases the ratio of gamma-aminobutyric acid to glutamate in neurons. Balancing these inhibitory and excitatory neurotransmitters helps suppress excessive neuronal firing that contributes to certain forms of mental illness.
"Bipolar mania involves fluctuations in energy states in which neuronal firing is more unstable," Sethi said, "and both anti-psychotic medications and ketogenic therapy can reduce that instability. We need neural network stability for mental health."
Ketogenic therapy significantly reduces inflammation in the brain -- which is strongly associated with depression, anxiety, schizophrenia and bipolar disorder -- by regulating immune signaling and reducing oxidative stress, among other probable mechanisms.
Many mental illnesses involve a significant metabolic component.
Mental and metabolic illnesses frequently occur together: More than 40% of people with severe mental illnesses also have metabolic syndrome. Metabolic dysfunction certainly exacerbates symptoms of mental illness, Sethi said, but evidence indicates it might often be an underlying cause as well. Metabolic syndrome and several forms of mental illness respond to many of the same medications. Similarly, they both also respond favorably to ketogenic therapy, Sethi's pilot study showed.
Pilot study shows ketogenic diet improves severe mental illness
Keto therapy can help with metabolic syndrome and insulin resistance.
Many patients suffering from mental illness also experience insulin resistance, which can lead to metabolic syndrome. The ketogenic diet reduces insulin resistance in addition to promoting weight loss and improving blood sugar, triglycerides and high-density lipoprotein, or HDL, cholesterol levels.
Keto therapy drastically reduces carbohydrate intake, causing the body to burn fat for fuel (ketosis), thereby stabilizing blood sugar levels and decreasing inflammation. By relying on fats as fuel instead of glucose, a brain in ketosis bypasses the need for glucose and insulin to enter the brain for energy production, which is a problem for many people with mental illness.
Keto therapy should be considered supplemental to primary mental health treatment.
Ketogenic therapy is a serious medical intervention, not to be confused with the related but much less rigorous weight-loss diet that is based on similar principles. Keto therapy can interact dangerously with some anti-psychotic medications, as well as with other health conditions, so an experienced physician and trained nutritionist should guide and monitor it.
Because there are also several versions of the diet, a professional should work with patients to choose the best one. Sethi said the objective in her clinic is "not to replace conventional treatments with ketogenic therapy, but to use the diet as one powerful therapeutic metabolic tool among many."
Illustration: Emily Moskal / Stanford Medicine
