Ketogenic diet may aid mood, cognition in serious mental illness

Clinical takeaway: A ketogenic diet may be a feasible adjunct for the metabolic and mood burden of serious mental illness, with benefits that appear tied to ketosis rather than weight loss.

Antipsychotics quiet psychosis but rarely touch the depressive and cognitive symptoms that most affect daily life. The drugs also drive the weight gain and metabolic disease common in serious mental illness. A small trial now points to a ketogenic diet as a possible adjunct on both fronts. Patients on the diet for four months improved across psychiatric, cognitive, and metabolic measures. The symptom findings were uncontrolled, but the signal is worth watching.

Ketogenic diets have a long track record in drug-resistant epilepsy and a newer one in reversing metabolic syndrome. Small pilots hinted the same metabolic shift might ease psychiatric symptoms, but none could rule out weight loss, placebo response, or the other things that change when patients start a diet. This trial added a control arm and tracked blood ketones directly, so it could examine whether ketosis itself carries the benefit.

At one month, patients on the ketogenic diet lost more weight and had larger drops in HbA1c and insulin resistance than those on their usual diet. Higher ketone levels tracked with lower glucose and fewer depressive symptoms, and the link held after accounting for weight loss. Weight loss itself was unrelated to the gains, which points to ketosis as the active component.

The four-month results are more striking but rest on weaker ground. In the roughly two dozen patients who continued, psychiatric symptoms and cognition improved from baseline. But that extension had no control.

The trial randomized 58 outpatients with schizophrenia-spectrum or bipolar-1 disorder to a ketogenic diet or usual diet for one month, with an optional four-month extension on the diet. Adherence was high and no significant side effects were reported. The controlled comparison rested on the 47 participants who finished the first month.

The authors are clear on what should come next: larger and longer trials that keep the control arm in place to confirm whether the four-month psychiatric and cognitive gains hold up. The symptom improvements that matter most to patients are the ones this design left uncontrolled.

"The improvement we saw in cognitive and psychological symptoms is particularly important in people with psychotic disorders, because current medications that address their psychosis don't address their overall mental wellbeing, including cognitive or depressive symptoms, which can be debilitating," said Judith Ford, PhD, professor of psychiatry at the University of California, San Francisco.

Source: Abram SV, et al. (2026 Jul 8) Schizophr Bull. Metabolic improvements with a ketogenic diet correlate with symptom improvement in psychosis: a randomized controlled trial