A McLean Hospital and Harvard trial of ketogenic and nutritional treatment in first-episode bipolar disorder is registered to report its main results by late 2027.
Virginie-Anne Chouinard, McLean Hospital and Harvard Medical School
Psychology & Behavioral Science Active Updated Jul 9, 2026
Metabolic interventions for mental illness
A randomized controlled trial from UCSF found a ketogenic diet reduced clinical symptoms of schizophrenia and bipolar disorder and improved daily cognitive performance, with effects that held after controlling for weight loss. The working hypothesis is that antipsychotic medications often disrupt the brain's ability to use glucose, and ketones produced when the body runs on fat may restore fuel to neural circuits standard drugs cannot reach. The arc spans nutrition science, metabolic biology, and psychiatry, and will run as larger trials test whether the mechanism holds and whether dietary interventions can work outside a research setting.
The story so far
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Jul 9, 2026 Latest
A UCSF randomized controlled trial published in Schizophrenia Bulletin found 83 percent of patients with schizophrenia or bipolar disorder maintained ketosis through a one-month primary phase, rising to 94 percent in a voluntary four-month extension, with no severe side effects reported. Psychiatric improvements held after researchers controlled for weight loss, and higher blood ketone levels correlated directly with sharper drops in both blood glucose and clinical depression scores, suggesting the effect is metabolic rather than a byproduct of slimming.
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Aug 21, 2024
An Australian-led group registered the field's first fully controlled test: 100 people with bipolar disorder, schizoaffective disorder or schizophrenia, randomly assigned, with a placebo comparison. Publishing the plan up front is how the field moves past small single-arm pilots.
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Mar 20, 2024
Shebani Sethi's team at Stanford ran the first US trial of a ketogenic diet for serious mental illness since 1965. Over four months, patients with schizophrenia saw their symptom scores drop by about a third on average, and none of the participants still met the criteria for metabolic syndrome by the end.
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Oct 10, 2023
Iain Campbell's team at the University of Edinburgh ran the first pilot of a ketogenic diet in bipolar disorder. Most of the 20 who finished stayed in ketosis, the diet proved manageable, and the researchers concluded a proper controlled trial was worth doing.
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Nov 15, 2022
Palmer laid out the bigger idea in a book, Brain Energy, arguing that mental illnesses are at root problems of brain metabolism and the mitochondria that power neurons. It is a popular book rather than a study, but it framed the question a wave of trials would go on to test.
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Feb 3, 2017
Harvard psychiatrist Chris Palmer published two cases of patients whose long-standing schizoaffective disorder eased on a ketogenic diet, the same diet used for a century to control epilepsy. Two patients is not proof, but it was an early clinical signal that helped get the field moving.
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