Psychiatric Disorders

Metabolic Improvements with a Ketogenic Diet Correlate with Symptom Improvement in Psychosis: A Randomized Controlled Trial

People with schizophrenia-spectrum disorders and bipolar I disorder experience high rates of metabolic dysfunction, which may contribute to both poor physical health and persistent psychiatric symptoms. Because ketogenic diets can improve metabolic health and have shown promise in other neurological and psychiatric conditions, researchers conducted the first randomized controlled trial to evaluate their effects on metabolic health, psychiatric symptoms, and cognition in adults with psychotic disorders.

The study enrolled 58 outpatients with schizophrenia, schizoaffective disorder, or bipolar I disorder with psychotic features. Participants were randomized to either a ketogenic diet (KETO; n = 28) or diet as usual (DAU; n = 30) for one month. The ketogenic diet provided approximately 70–80% of calories from fat, 10–20% from protein, and no more than 10% from carbohydrate. Participants received 18 prepared ketogenic meals per week and weekly dietary support. Once home ketone monitoring became available partway through the study, a subset of participants measured daily blood β-hydroxybutyrate (BHB) levels, with nutritional ketosis defined as BHB ≥0.5 mmol/L.

After the randomized phase, participants in both groups were offered a four-month ketogenic diet extension, which 25 individuals completed. Metabolic markers, psychiatric symptoms, and cognitive performance were assessed throughout the study.

Key Findings

Feasibility and adherence:

• Twenty-five of 28 participants (89%) completed the one-month ketogenic intervention.
• Daily blood β-hydroxybutyrate (BHB) levels exceeded the nutritional ketosis threshold (≥0.5 mmol/L) within one week and averaged 1.28 mmol/L after one month and 1.26 mmol/L after four months.

Metabolic health:

• Compared with the diet-as-usual group, the ketogenic diet significantly reduced body weight, HbA1c, and insulin resistance after one month.
• Improvements in HbA1c remained significant after four months.

Psychiatric symptoms:

• Positive symptoms, negative symptoms, and depressive symptoms improved significantly after four months on the ketogenic diet.
• Greater increases in BHB were associated with larger reductions in depressive symptoms (P < 0.001).

Cognitive function:

• Overall cognitive performance improved significantly after four months on the ketogenic diet (P < 0.001).

Mechanistic findings:

• Higher BHB levels were associated with greater reductions in HbA1c (P < 0.001) and depressive symptoms, whereas weight loss was not associated with these improvements.
• The proportion of time spent in nutritional ketosis also correlated with reductions in depressive symptoms.

Safety and tolerability:

• No serious adverse events occurred.
• Reported side effects were generally mild, with headaches resolving following increased fluid and electrolyte intake.

Conclusion

The authors concluded that a ketogenic diet was feasible and well tolerated in outpatients with schizophrenia-spectrum disorders and bipolar I disorder with psychotic features. The intervention was associated with improvements in metabolic health, psychiatric symptoms, and cognitive performance, with benefits more closely related to nutritional ketosis than weight loss. However, because the randomized phase lasted only one month and the four-month extension lacked a control group, larger randomized controlled trials are needed to confirm these findings.